
DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism.
Molecular psychiatry
Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations.
10.1038/s41380-024-02652-z
Trajectory patterns and predictors of cancer-related fatigue in postoperative lung cancer patients receiving chemotherapy.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:Cancer-related fatigue (CRF) is a chronic symptom that can affect the overall functioning of lung cancer patients throughout the course of the disease. However, there is limited research on the trajectory and predictors of CRF specifically in lung cancer patients. Furthermore, few studies have investigated the predictive role of positive psychological and social factors in relation to CRF. This study aimed to explore the trajectory of CRF and its predictors in postoperative chemotherapy patients with lung cancer. METHODS:A total of 202 lung cancer patients who underwent surgery and received adjuvant chemotherapy were recruited for this study. Baseline questionnaires were completed, covering sociodemographic information, disease details, CRF levels, personality traits, psychological resilience, and social support. CRF was assessed at three time points: first chemotherapy (T1), 3 months after chemotherapy (T2), and 6 months after chemotherapy (T3). Latent class growth modeling (LCGM) was used to identify distinct developmental trajectories of CRF. Logistic regression analysis was employed to examine predictors of CRF within different patient groups. RESULTS:The LCGM analysis revealed three distinct CRF trajectories: persistent high fatigue group (30.7%), rising fatigue group (30.7%), and no fatigue group (38.6%). Cancer stage (OR = 7.563, 95% CI = 2.468-23.182, P < 0.001), melancholic personality (OR = 6.901, 95% CI = 1.261-37.764, P = 0.026), and high psychological resilience (OR = 0.171, 95% CI = 0.041-0.706, P = 0.015) were associated with the CRF trajectory. On the other hand, sanguine personality (OR = 0.254, 95% CI = 0.071-0.916, P = 0.036) and high social support (OR = 0.168, 95% CI = 0.045-0.627, P = 0.008) were associated with the increasing fatigue trajectory. CONCLUSIONS:This study demonstrated that 60% of lung cancer patients experienced persistent fatigue throughout the assessment period. Moreover, it confirmed the heterogeneity of CRF trajectories among lung cancer patients. The severity of CRF was found to be higher in patients with advanced clinical stages, depressive personality traits, and lower psychological resilience.
10.1007/s00520-024-08715-9
Trajectories of depression and predictors in lung cancer patients undergoing chemotherapy: growth mixture model.
BMC psychiatry
BACKGROUND:Depression is prevalent among lung cancer patients undergoing chemotherapy, and the symptom cluster of fatigue-pain-insomnia may influence their depression. Identifying characteristics of patients with different depression trajectories can aid in developing more targeted interventions. This study aimed to identify the trajectories of depression and the fatigue-pain-insomnia symptom cluster, and to explore the predictive factors associated with the categories of depression trajectories. METHODS:In this longitudinal study, 187 lung cancer patients who were undergoing chemotherapy were recruited and assessed at the first (T1), second(T2), and fourth(T3) months using the Patient Health Questionnaire-9 (PHQ-9), the Brief Pain Inventory (BPI), the Brief Fatigue Inventory (BFI), and the Athens Insomnia Scale (AIS). Growth Mixture Model (GMM) and Latent Class Analysis (LCA) were used to identify the different trajectories of the fatigue-pain-insomnia symptom cluster and depression. Binary logistic regression was utilized to analyze the predictive factors of different depressive trajectories. RESULTS:GMM identified two depressive trajectories: a high decreasing depression trajectory (40.64%) and a low increasing depression trajectory (59.36%). LCA showed that 48.66% of patients were likely members of the high symptom cluster trajectory. Binary logistic regression analysis indicated that having a history of alcohol consumption, a higher symptom cluster burden, unemployed, and a lower monthly income predicted a high decreasing depression trajectory. CONCLUSIONS:Depression and fatigue-pain-insomnia symptom cluster in lung cancer chemotherapy patients exhibited two distinct trajectories. When managing depression in these patients, it is recommended to strengthen symptom management and pay particular attention to individuals with a history of alcohol consumption, unemployed, and a lower monthly income.
10.1186/s12888-024-06029-y
Cancer‑related fatigue during combined treatment of androgen deprivation therapy and radiotherapy is associated with mitochondrial dysfunction.
Feng Li Rebekah,Wolff Brian S,Liwang Josephine,Regan Jeniece M,Alshawi Sarah,Raheem Sumiyya,Saligan Leorey N
International journal of molecular medicine
Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non‑metastatic prostate cancer (NMPC). Despite the efficacy, treatment‑related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy‑Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants' whole blood. An ADT/RT‑induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel‑running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the ADT group was exacerbated during RT compared with the non‑ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non‑fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated the synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the CNS.
10.3892/ijmm.2019.4435
Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.
Fosså Alexander,Smeland Knut Halvor,Fluge Øystein,Tronstad Karl Johan,Loge Jon Håvard,Midttun Øivind,Ueland Per Magne,Kiserud Cecilie Essholt
PloS one
Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.
10.1371/journal.pone.0227384
Effects of the polysaccharides extracted from Chinese yam ( Thunb.) on cancer-related fatigue in mice.
Wang Yu,Liu Yuanxue,Zhang Yiqian,Huo Zhipeng,Wang Genbei,He Yi,Man Shuli,Gao Wenyuan
Food & function
The aim of this study was to investigate the anti-fatigue activity of Chinese Yam polysaccharides (CYPs). The structural characterization of CYPs was conducted using Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography-light scattering-refractive index, and ion chromatography. The weight-loaded swimming capability, behavior performance, tumor growth, content of adenosine triphosphate (ATP), and biochemical markers of CYP in a cancer-related fatigue mouse model were tested. The results showed that CYP is a mixture with an average of 75.57 kDa and is mainly composed of rhamnose, glucuronic acid, glucose, galactose, and arabinose with a molar ratio of 0.01 : 0.06 : 1.00 : 0.17 : 0.01. CYP increased the exhausting swimming time, which was decreased in the cisplatin (DDP) control group and the model group. CYP also increased the content of ATP in musculus gastrocnemius, which was down-regulated by DDP; the DDP had significantly enhanced the contents of interleukin-1β (IL-lβ), malondialdehyde (MDA), blood urea nitrogen (BUN) and lactic dehydrogenase (LDH) and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of CYP decreased the levels of IL-lβ, MDA, BUN and LDH, and up-regulated the SOD activity. The DDP + CYP group presented a decreased tumor volume and a lower tumor weight as compared with the model group. Moreover, the mice in the CYP or DDP + CYP groups had heavier body weights than the mice in the model group and DDP group. These results suggest that CYP should improve cancer-related fatigue the regulation of inflammatory responses, oxidative stress and increase in energy supplementation.
10.1039/d1fo00375e
Dynamic Analysis of Metabolic Response in Gastric Ulcer (GU) Rats with Electroacupuncture Treatment Using H NMR-Based Metabolomics.
Shen Jia-Cheng,Lian Lin-Yu,Zhang Yuan,He Qi-da,Chen Jiao-Long,Zhang Long-Bin,Huang Miao-Sen,Liu Mi,Qian Lin-Chao,Liu Cai-Chun,Yang Zong-Bao
Evidence-based complementary and alternative medicine : eCAM
Gastric ulcer (GU), a common digestive disease, has a high incidence and seriously endangers health of human. According to the previous studies, it has been proved that electroacupuncture at acupoints of stomach meridian had a good effect on GU. However, there are few published studies on metabolic response in gastric ulcer (GU) rats with electroacupuncture treatment. Herein, we observed the metabolic profiles in biological samples (stomach, liver, and kidney) of GU rats with electroacupuncture treatment by H NMR metabolomics combined with pathological examination. The male SD rats were induced by intragastric administration of 70% ethanol after fasting for 24 hours and treated by electroacupuncture at Zusanli (ST36) and Liangmen (ST21) for 1 day, 4 days, or 7 days, respectively. And the conventional histopathological examinations as well as metabolic pathways assays were also performed. We found that GU rats were basically cured after electroacupuncture treatment for 4 days and had a complete recovery after electroacupuncture treatment for 7 days by being modulated comprehensive metabolic changes, involved in the function of neurotransmitters, energy metabolism, cells metabolism, antioxidation, tissue repairing, and other metabolic pathways. These findings may be helpful to facilitate the mechanism elucidating of electroacupuncture treatment on GU.
10.1155/2019/1291427
Serum metabolomics reveals the effects of accompanying treatment on fatigue in patients with multiple myeloma.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS:This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS:The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION:The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.
10.1007/s00520-022-07526-0
Alteration of DNA Methylation in Gastric Cancer with Chemotherapy.
Choi Su Jin,Jung Seok Won,Huh Sora,Chung Yoon-Seok,Cho Hyosun,Kang Hyojeung
Journal of microbiology and biotechnology
Epigenetic alterations such as DNA methylation, histone acetylation, and chromatin remodeling can control gene expression by regulating gene transcription. DNA methylation is one of the frequent epigenetic events that play important roles in cancer development. Cancer cells can gain significant resistance to anticancer drugs and escape programmed cell death through major epigenetic changes, including DNA methylation. To date, several research groups have identified instances of both (i) hypermethylation of tumor suppressor genes, and (ii) global hypomethylation of oncogenes. These changes in DNA methylation status could be used as biomarkers for the diagnosis and prognosis of cancer patients undergoing chemotherapies or other clinical therapies. Herein, we describe genes for which methylation is dependent upon anticancer drug resistance in patients with gastric cancer; we then suggest a significant epigenetic target to focus on for overcoming anticancer drug resistance.
10.4014/jmb.1704.04035
Repeated Combined Chemotherapy with Cisplatin Lowers Carnitine Levels in Gastric Cancer Patients.
Kawai Akimasa,Matsumoto Hideo,Endou Youko,Honda Yui,Kubota Hisako,Higashida Masaharu,Hirai Toshihiro
Annals of nutrition & metabolism
BACKGROUND/AIMS:Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer. METHODS:Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected. RESULTS:The mean total carnitine level was 54.5 ± 13.7 μmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 μmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (p = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (p = 0.0218 and p = 0.0418). CONCLUSION:Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status.
10.1159/000485808
Enhanced Vasculogenic Capacity Induced by 5-Fluorouracil Chemoresistance in a Gastric Cancer Cell Line.
Peri Sara,Biagioni Alessio,Versienti Giampaolo,Andreucci Elena,Staderini Fabio,Barbato Giuseppe,Giovannelli Lisa,Coratti Francesco,Schiavone Nicola,Cianchi Fabio,Papucci Laura,Magnelli Lucia
International journal of molecular sciences
Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability.
10.3390/ijms22147698
LncRNA-CCAT5-mediated crosstalk between Wnt/β-Catenin and STAT3 signaling suggests novel therapeutic approaches for metastatic gastric cancer with high Wnt activity.
Cancer communications (London, England)
BACKGROUND:Although the constitutively activated Wnt/β-catenin signaling pathway plays vital roles in gastric cancer (GC) progression, few Wnt inhibitors are approved for clinical use. Additionally, the clinical significance of long non-coding RNAs (lncRNAs) in GC intraperitoneal dissemination (IPD) remains elusive. Here, we investigated the function and therapeutic potential of Wnt-transactivated lncRNA, colon cancer-associated transcript 5 (CCAT5), in GC metastasis. METHODS:LncRNA-sequencing assay was performed to document abundance changes of lncRNAs induced by Wnt family member 3A (Wnt3a) and degradation-resistant β-catenin (S33Y mutated) in ascites-derived GC cells with low Wnt activity. Luciferase reporter, Chromatin immunoprecipitation (ChIP)-re-ChIP assays were performed to determine how CCAT5 was transcribed. The clinical significance of CCAT5 was examined in 2 cohorts of GC patients. The biological function of CCAT5 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA-sequencing, mass spectrometry, and CRISPR/Cas9-knocknout system. The therapeutic potential of CCAT5 was examined through RNAi-based cell xenograft model and patient-derived xenograft (PDX) model of IPD. RESULTS:We identified a novel Wnt-regulated lncRNA, CCAT5, which was transactivated by the β-catenin/transcription factor 3 (TCF3) complex. CCAT5 was significantly upregulated in GC and predicted poor prognosis. Functional studies confirmed the promotive role of CCAT5 in GC growth and metastasis. Mechanistically, CCAT5 bound to the C-end domain of signal transducer and activator of transcription 3 (STAT3) and blocks Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1)-mediated STAT3 dephosphorylation, leading to STAT3 nuclear entry and transactivation, thus accelerating GC progression. Furthermore, we demonstrated that both Wnt3a and β-catenin acted as activator of STAT3 signaling pathway, and the interplay between CCAT5 and STAT3 was functionally essential for Wnt-drived STAT3 signaling and tumor evolution. Finally, we revealed in vivo si-CCAT5 selectively attenuated growth and metastasis of Wnt GC, but not Wnt GC. The combination of si-CCAT5 and oxaliplatin displayed obvious synergistic therapeutic effects on Wnt PDX mice. CONCLUSIONS:We identified a novel Wnt-transactivated lncRNA, CCAT5. Our study revealed a mechanism of STAT3 signaling regulation via canonical Wnt signaling and the functional significance of CCAT5 as critical mediator. We provided conceptual advance that lncRNAs serve as therapeutic targets reversing GC progression.
10.1002/cac2.12507
Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer.
International journal of molecular sciences
Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.
10.3390/ijms23116041
Body composition parameters for predicting the efficacy of neoadjuvant chemotherapy with immunotherapy for gastric cancer.
Frontiers in immunology
Background:Immune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported. Methods:The computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed. Results:Of the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm/m, p=0.042), SAI (from 34.7 to 32.9 cm/m, p=0.01) and VAI (from 32.4 to 26.8 cm/m, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm/m, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06-9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20-3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35-20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73-112.7, p=0.013). Conclusion:Low SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs.
10.3389/fimmu.2022.1061044
H3K27 acetylation activated-CD109 evokes 5-fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway.
Environmental toxicology
Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5-fluorouracil (5-FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5-FU-resistant GC cells. CD109 deficiency lessened the IC value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5-FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5-FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation-induced changes of IC values, cell viability, metastasis and apoptosis in NCI-N87/5-FU and SNU-1/5-FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated-CD109 enhanced 5-FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC.
10.1002/tox.23919
Marsdenia tenacissima (Roxb.) Moon injection exerts a potential anti-tumor effect in prostate cancer through inhibiting ErbB2-GSK3β-HIF1α signaling axis.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Marsdenia tenacissima injection (MTE), a traditional Chinese medical injection extracted from the rattan of Marsdenia tenacissima (Roxb.) Moon, has been approved for clinical use in China as an adjuvant therapeutic agent in multiple cancers, including esophageal cancer, gastric cancer, lung cancer, and liver cancer. However, the activity and mechanism of MTE on prostate cancer (PCa) remain to be defined. AIM OF THE STUDY:To investigate the activity and the underlying mechanism of MTE in the treatment of PCa. MATERIALS AND METHODS:The component characterization of MTE was analyzed by HPLC-CAD-QTOF-MS/MS technology. Cell Counting Kit-8 (CCK-8) assay was used to assess PCa cell proliferation. Colony formation assay was applied to detect the clonogenic ability of the cells. MetaboAnalyst5.0 database was employed to analyze the altered metabolites of PC3 cells treated with MTE obtained by UPLC-QTOF-MS/MS. Combined with metabolomics analysis and network pharmacology, we predicted the potential targets, which further were verified by Western Blot, RT-qPCR, and Immunohistochemistry assays. Finally, SeeSAR software was applied to predict the potential active components of MTE against PCa. RESULTS:A total of 21 components in MTE were confirmed by HPLC-CAD-QTOF-MS/MS analysis. MTE inhibited the proliferation and colony formation of PCa cells. A total of 20 metabolites closely related to glycerophospholipid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle were significantly changed in PC3 cells treated with MTE. The network pharmacology analysis revealed that MTE suppressed the growth of PC3 cells might by regulating the ErbB2-GSK3β-HIF1α signaling axis. Furthermore, we also confirmed that stimulation of MTE significantly inhibited the phosphorylation of ErbB2 at Tyr877 and the activities of its downstream signal transducers (GSK3β and HIF1α) in PCa, as well as the mRNA levels of critical factors (IDH2, LDHA, and HIF1A) in the tricarboxylic acid (TCA) cycle. Molecular docking further suggested that Tenacissimoside E, cryptochlorogenic acid, and scopoletin might be the active ingredients of MTE for PCa treatment. CONCLUSION:This study proposed that MTE exerts a potential anti-tumor effect in PCa through inhibiting ErbB2-GSK3β-HIF1α signaling axis, which may be related to the TCA cycle.
10.1016/j.jep.2022.115381
Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil.
Sasada Shinsuke,Miyata Yoshihiro,Tsutani Yasuhiro,Tsuyama Naohiro,Masujima Tsutomu,Hihara Jun,Okada Morihito
Oncology reports
Metabolomics has developed as an important new tool in cancer research. It is expected to lead to the discovery of biomarker candidates for cancer diagnosis and treatment. The current study aimed to perform a comprehensive metabolomic analysis of the intracellular dynamic responses of human gastric cancer cells to 5-fluorouracil (5-FU), referencing the mechanisms of drug action and drug resistance. Small metabolites in gastric cancer cells and 5-FU-resistant cells were measured by liquid chromatography-mass spectrometry. Candidates for drug targets were selected according to the presence or absence of resistance, before and after 5-FU treatment. In addition, the gene expression of each candidate was assessed by reverse transcription-polymerase chain reaction. The number of metabolites in cancer cells dramatically changed during short-term treatment with 5-FU. Particularly, proline was reduced to one-third of its original level and glutamate was increased by a factor of 3 after 3 h of treatment. The metabolic production of glutamate from proline proceeds by proline dehydrogenase (PRODH), producing superoxide. After 5-FU treatment, PRODH mRNA expression was upregulated 2-fold and production of superoxide was increased by a factor of 3. In 5-FU-resistant cells, proline and glutamate levels were less affected than in non-resistant cells, and PRODH mRNA expression and superoxide generation were not increased following treatment. In conclusion, the authors identified a candidate biomarker, PRODH, for drug effects using a meta-bolomic approach, a result that was confirmed by conventional methods. In the future, metabolomics will play an important role in the field of cancer research.
10.3892/or.2012.2182
Gypenoside inhibits gastric cancer proliferation by suppressing glycolysis via the Hippo pathway.
Scientific reports
Gastric cancer (GC) remains a global disease with a high mortality rate, the lack of effective treatments and the high toxicity of side effects are primary causes for its poor prognosis. Hence, urgent efforts are needed to find safe and effective therapeutic strategies. Gypenoside (Gyp) is a widely used natural product that regulates blood glucose to improve disease progression with few toxic side effects. Given the crucial role of abnormal glycometabolism in driving tumor malignancy, it is important to explore the association between Gyp and glycometabolism in GC and understand the mechanism of action by which Gyp influences glycometabolism. In this study, we demonstrated that Gyp suppresses GC proliferation and migration both in vitro and in vivo. We identified that Gyp suppresses the malignant progression of GC by inhibiting glycolysis using network pharmacology and metabolomics. Transcriptome analysis revealed that the Hippo pathway is a key regulator of glycolysis by Gyp in GC. Furthermore, Gyp induced upregulation of LATS1/2 proteins, leading to increased YAP phosphorylation and decreased TAZ protein expression. The YAP agonist XMU-MP-1 rescued the inhibitory effect of Gyp on GC proliferation by reversing glycolysis. These findings confirmed that Gyp inhibits GC proliferation by targeting glycolysis through the Hippo pathway. Our study examined the role of Gyp in the malignant progression of GC, explored its therapeutic prospects, elucidated a mechanism by which Gyp suppresses GC proliferation through interference with the glycolytic process, thus providing a potential novel therapeutic strategy for GC patients.
10.1038/s41598-024-69435-y
Lactic acid promotes macrophage polarization through MCT-HIF1α signaling in gastric cancer.
Zhang Lan,Li Shengmian
Experimental cell research
Reprogramming of energy metabolism and evading immune are two emerging hallmarks of cancers. Accumulating evidence suggest that reprogrammed energy metabolism contributes to a tumor-suppressive immune microenvironment in cancers. Macrophages are the most abundant immune cells in the tumor microenvironment and M2 macrophages are profoundly implicated in tumor initiation and progression. By gene set enrichment analysis, we found that glycolysis signature was closely associated with the M2 macrophage phenotype in gastric cancer. Enhanced glycolysis is characterized by significant production of lactate. Interestingly, we found that lactic acid is able to skew macrophage toward a M2-like state. Treatment of THP-1 cells or human monocytes with gastric cancer cell-derived conditioned media or lactic acid significantly increased expression of M2-related markers and faintly attenuated expression of M1-related markers. Moreover, knockdown of LDHA suppressed the ability of gastric cancer to skew macrophage toward M2 phenotype as revealed by reduced expression of M2-related markers and cytokines. Mechanistically, a-cyano-4-hydroxycinnamate (CHC), a monocarboxylate channel transporter (MCT) inhibitor, or HIF1α knockdown, significantly abrogated CD163 and ARG1 expression in THP-1 cells, suggesting that MCT-HIF1α signaling is responsible for macrophage polarization. Collectively, our findings identify the lactate-MCT-HIF1α axis as a critical signaling cascade that couples metabolic reprogramming to macrophage polarization in gastric cancer.
10.1016/j.yexcr.2020.111846
Are measures and related symptoms of cachexia recorded as outcomes in gastrointestinal cancer chemotherapy clinical trials?
Journal of cachexia, sarcopenia and muscle
BACKGROUND:Cachexia is prevalent in gastrointestinal cancers and worsens patient outcomes and chemotherapy compliance. We examined to what extent registered gastrointestinal cancer chemotherapy clinical trials record measures and related symptoms of cachexia as outcomes, and whether these were associated with trial characteristics. METHODS:Four public trial registries (2012-2022) were accessed for Phase II and/or III randomized controlled pancreatic, gastric, and colorectal cancer chemotherapy trial protocols. Trial outcome measures of overall survival and toxicity/side effects, and those related to cachexia [physical activity, weight/body mass index (BMI), dietary limitations, caloric intake, lean muscle mass] and symptoms (appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, and oral mucositis) were extracted, along with the number and types of performance status and patient-reported outcomes (PROs) tools. Data were summarized descriptively. Chi-square tests examined associations between outcomes and trial characteristics (cancer type, trial location, funding source, PROs tools, and commencement year). Statistical significance was set at P < 0.05. RESULTS:We included 540 trial protocols (pancreatic (35.2%), colorectal (33.3%) and gastric (31.5%)), with most trials from Europe (44.1%). Trial lead investigator was from academia (28.3%), industry (27.6%) and government (26.3%). Allied health professional involvement (26.9%) occurred at eligibility. Adjuvant therapy in trials was mainly treatment-related (68.1%). Additional medication included anti-nausea (2.2%) and analgesia (0.9%). Trial protocols mostly recorded overall survival (90.4%) and toxicity (78.9%), and the symptoms appetite loss (26.1%) and diarrhoea (19.1%), with the other symptoms recorded in <10% of the trials. Reporting of physical activity (P = 0.001), dietary limitations (P = 0.002), lean muscle mass (P = 0.027), appetite loss (P < 0.001), pain (P = 0.001), nausea (P = 0.012), and oral mucositis (P = 0.049) varied depending cancer type. Toxicity/side effects (P = 0.022), physical activity (P < 0.001), appetite loss, nausea, and vomiting (all P < 0.001), diarrhoea (P = 0.010), pain (P = 0.001), fatigue/insomnia (P = 0.001) varied depending on the trial location. Trial funding was predominantly from private/industry (34.3%) and influenced the reporting of overall survival (P = 0.049), weight/BMI (P = 0.005), caloric intake (P = 0.015), and pain (P = 0.031). Performance status and PROs tools were mentioned in 91.2% and 46.3% of the trials, respectively. Trials that incorporated PROs tools were more likely to report cachexia related outcomes, except for overall survival, lean muscle mass, and oral mucositis. The proportion of trials measuring weight/BMI increased with trial commencement year (P = 0.04). CONCLUSIONS:Cachexia-related outcomes were under-recorded in gastrointestinal cancer chemotherapy trials. As trial patients experience a high symptom burden, cachexia-relevant measures and symptoms should be assessed throughout the trial, and integrated with primary endpoints to support their progress.
10.1002/jcsm.13458
Efficacy of Modified Yiwei Shengyang Decoction in Combination with FOLFOX4 Chemotherapy for Advanced Gastric Cancer.
Alternative therapies in health and medicine
Objective:To explore the clinical efficacy of modified Yiwei Shengyang Decoction combined with FOLFOX4 chemotherapy regimen in patients with advanced gastric cancer. Methods:Ninety patients with advanced gastric cancer, admitted to Cangzhou Central Hospital from January 2021 to December 2022, were randomized 1:1 into control and study groups. The control group received FOLFOX4 chemotherapy alone, while the study group received additional modified Yiwei Shengyang Decoction. Chinese medicine (TCM) symptom scores (TCM symptoms refer to the signs and manifestations of imbalances or disharmony within the body according to the principles of Traditional Chinese Medicine. These symptoms are assessed and diagnosed based on a holistic understanding of the individual's physical, mental, and emotional state. TCM symptoms may include various indicators such as pulse characteristics, tongue appearance, body temperature, complexion, energy levels, sleep patterns, appetite, digestion, pain, and specific subjective experiences reported by the patient, such as fatigue, anxiety, or insomnia), gastric cancer biomarkers such as serum CEA and CA199 levels, immune function, clinical efficacy, and side effects were compared. Results:Before treatment, both groups had similar TCM symptom scores. Post-treatment, the study group showed significantly greater reductions in appetite, epigastric pain, nausea, vomiting, and diarrhea scores compared to the control group (P < .001). After treatment, CEA and CA199 levels decreased significantly in both groups, with the study group exhibiting significantly lower levels than the control group (P = .001, .001). Post-treatment, CD3+ and CD4+ levels were higher in the study group, while CD8+ levels were lower than in the control group (P < .001). Treatment efficiency was significantly higher in the study group (62.33%) than in the control group (37.78%) (P = .02). Conclusion:Modified Yiwei Shengyang Decoction combined with FOLFOX4 chemotherapy regimen is a promising option for patients with gastric cancer. It significantly improves immune indicators and appetite, reduces adverse symptoms including epigastric pain, nausea, vomiting, and diarrhea, and substantially enhances quality of life. Moreover, traditional Chinese medicine treatment is safe and merits promotion in clinics.
A Retrospective Cohort Study to Investigate the Incidence of Cachexia During Chemotherapy in Patients with Colorectal Cancer.
Shibata Masayuki,Fukahori Masaru,Kasamatsu Eiji,Machii Koji,Hamauchi Satoshi
Advances in therapy
INTRODUCTION:This retrospective study focused on cancer cachexia in clinical practice. We evaluated the incidence of cancer cachexia and the relationship between cancer cachexia and overall survival (OS) or toxicities in patients with advanced colorectal cancer after undergoing first-line systemic chemotherapy. METHODS:We examined 150 patients with colorectal cancer who underwent first-line systemic chemotherapy between February 1, 2010 and August 31, 2016 at Shizuoka Cancer Center Hospital and Kurume University Hospital. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m within the past 6 months according to the European Palliative Care Research Collaborative criteria. RESULTS:One hundred patients from Shizuoka Cancer Center and 50 from Kurume University Hospital were registered. Median age and body mass index were 65 years (range 29-85) and 21.7 kg/m (14.8-32.5), respectively. Cumulative incidence of cancer cachexia was 50.7% at 24 weeks, and reached 91.3% over the whole study period. OS was significantly different between patients with and without cancer cachexia within 24 weeks after starting first-line treatment, although the onset of cancer cachexia within 24 weeks could not be considered as an independent prognostic factor for OS. Severe appetite loss and fatigue tended to occur more frequently in patients with cancer cachexia within 24 weeks. CONCLUSION:Cancer cachexia appears to have an onset in approximately half of patients with advanced colorectal cancer within 24 weeks after starting first-line treatment. Although causal relationships were controversial, the onset of cancer cachexia within 24 weeks tends to be related to worse outcomes. Thus, it would be better to monitor weight loss leading to cachexia in patients with advanced colorectal cancer, especially within 24 weeks after starting first-line chemotherapy. TRIAL REGISTRATION:University Hospital Medical Information Network Clinical Trials Registry (UMIN000035002).
10.1007/s12325-020-01516-6
[Influence of combined therapy of guben yiliu III, moxibustion and chemotherapy on immune function and blood coagulation mechanism in patients with mid-late stage malignant tumor].
Liu Ju,Yu Ren-cun,Tang Wu-jun
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine
OBJECTIVE:To observe the supplementary effect of moxibustion and Guben Yiliu III (GBYL), a Chinese herbal compound preparation, in combination with chemotherapy. METHODS:Eighty-one patients of mid-late stage malignant tumor were randomly divided into 3 groups: 16 in Group A treated with chemotherapy and placebo; 35 in Group B treated with chemotherapy and GBYL and 30 in Group C treated with chemotherapy and GBYL plus moxibustion. The short-term effect of treatment, changes of blood picture, cell mediated immune function and blood coagulation in patients were observed. RESULTS:After chemotherapy, the lymphocyte count was significantly lowered in Group A and B (P < 0.01), but not in Group C (P > 0.05); lymphocyte subset T3 raised significantly in Group B; the average level of T-lymphocyte subsets was reduced in Group A while it increased in the other two groups; and a bi-directional regulation on plasma fibrinogen concentration was shown in Group C (P < 0.05). CONCLUSION:Moxibustion prevented dropping of lymphocyte count caused by chemotherapy. Combination of GBYL and moxibustion could prevent the lowering of T-lymphocyte subsets caused by chemotherapy, and moxibustion could regulate bi-directionally the patients' abnormality in part of blood coagulation mechanism.
Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer.
Redox biology
Chemotherapy is still one of the principal treatments for gastric cancer, but the clinical application of 5-FU is limited by drug resistance. Here, we demonstrate that ferroptosis triggered by STAT3 inhibition may provide a novel opportunity to explore a new effective therapeutic strategy for gastric cancer and chemotherapy resistance. We find that ferroptosis negative regulation (FNR) signatures are closely correlated with the progression and chemoresistance of gastric cancer. FNR associated genes (GPX4, SLC7A11, and FTH1) and STAT3 are upregulated in 5-FU resistant cells and xenografts. Further evidence demonstrates that STAT3 binds to consensus DNA response elements in the promoters of the FNR associated genes (GPX4, SLC7A11, and FTH1) and regulates their expression, thereby establishing a negative STAT3-ferroptosis regulatory axis in gastric cancer. Genetic inhibition of STAT3 activity triggers ferroptosis through lipid peroxidation and Fe accumulation in gastric cancer cells. We further develop a potent and selective STAT3 inhibitor, W1131, which demonstrates significant anti-tumor effects in gastric cancer cell xenograft model, organoids model, and patient-derived xenografts (PDX) model partly by inducing ferroptosis, thus providing a new candidate compound for advanced gastric cancer. Moreover, targeting the STAT3-ferroptosis circuit promotes ferroptosis and restores sensitivity to chemotherapy. Our finding reveals that STAT3 acts as a key negative regulator of ferroptosis in gastric cancer through a multi-pronged mechanism and provides a new therapeutic strategy for advanced gastric cancer and chemotherapy resistance.
10.1016/j.redox.2022.102317
Current Perspectives and Trend of Acupuncture in Breast Cancer-Related Symptoms: A Bibliometric Study.
Journal of pain research
Purpose:This bibliometric research aims to delineate global publication trends and emerging research interests in the use of acupuncture for breast cancer (BC)-related symptoms treatment over the past three decades. Furthermore, it identifies influential institutions, potential collaborative partners, and future research trends, thereby providing guidance for relevant, novel research directions. Methods:Scientific publications related to acupuncture for BC-related symptoms were gathered from the Web of Science Core Collection (WoSCC) from 1993 to 2023. Four software applications were principally used to analyze the resulting data: the "bibliometrix" package in the R environment (version 4.2.3), VOSviewer, CiteSpace6.1.R6, and the bibliometrics website. These applications were employed to evaluate different parameters. Results:A total of 621 papers on acupuncture in BC-related symptoms treatment were analyzed. The United States, China, and South Korea contributed the most, with Memorial Sloan Kettering Cancer Center, and Columbia University leading institutions. It is interesting to mention that Mao, Jun J. and Molassiotis, A. feature among the top 10 authors and co-cited authors. JAMA is the leading journal, with an ongoing focus on acupuncture's effectiveness. Keywords show that the initial research focus was mainly on "vasomotor symptoms", but in recent years there has been a gradual shift towards "pain", "chemotherapy-induced peripheral neuropathy (CIPN)", "electroacupuncture", and "non-specific effects". Conclusion:Acupuncture has demonstrated a unique value in the process of adjuvant treatment of BC-related symptoms, and has been shown to be effective in reducing pain, eliminating fatigue, and improving quality of life. The study of the mechanisms of acupuncture and the application of electroacupuncture are possible future research priorities in this field. This study offers a deep perspective on acupuncture for BC research, highlighting key points and future trends.
10.2147/JPR.S442151
ShenQi FuZheng Injection ameliorates fatigue-like behavior in mouse models of cancer-related fatigue.
Zhu Guodong,Zhang Bei,Jiang Funeng,Zhao Luqian,Liu Feng
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Cancer-related fatigue (CRF) not only has a negative impact on work, daily activities and social relationships, but also be a predictor of cancer patients' survival. And it has no FDA-approved therapy. ShenQi FuZheng Injection (SFI) is clinically used for adjuvant treatment of lung cancer and gastric cancer. And we found that SFI can improve the incidence of CRF in patients with gastric cancer. However, its efficacy against CRF remains to be elucidated. In the present study we established a tumor-bearing mouse fatigue model, conducted the forced swim test (FST) and grip strength measurements to evaluate the therapeutic effect of SFI. Additionally, we detected inflammation and immune indicators. The result showed that SFI administration could reduce depressive-like behaviors in tumor-bearing mice and inhibit tumor growth. In addition, SFI might improve fatigue symptoms by inhibiting pro-inflammatory cytokines produced by peripheral immune cells, restrain the dysfunction of exhausted T cells and improve the anti-tumor immunity through the targets of PDL1, TIM3 and FOXP3. These data suggested that SFI might be useful in alleviating CRF and provide further support to confirm SFI as a potential therapy for CRF in humans.
10.1016/j.biopha.2019.01.042
Treatment of postoperative gastric cancer with the Fuzheng Huoxue anticancer prescription.
Zhou A G,Huang D W,Ding Y X,Jiang H,Tang M L
World journal of gastroenterology
AIM:To study effects of the Fuzheng Huoxue anticancer prescription (Traditional Chinese Medicine) in treatment of gastric cancer. METHODS:Sixty-nine patients with histologically confirmed mid- or late-stage gastric cancer were assigned to two groups. The treatment group included 35 cases (26 males and 9 females; 2 patients aged 33-40 years, 18 patients aged 41-60 years, and 15 patients aged 61-75 years; mean group age = 58.4 years). The control group included 34 cases (23 males and 11 females; 4 patients aged 33-40 years, 16 patients aged 41-60 years, and 14 patients aged 61-75 years; mean group age = 56.8 years. The two groups were not significantly different in sex, age, their clinical and pathological stages of disease or operation mode. The two groups of patients were given similar treatments; however, patients in the treatment group were given the Fuzheng Huoxue anticancer prescription. In animal studies, SGC-7901 gastric cancers cells were inoculated into the backs of 30 nude mice under sterile conditions. After inoculation, the nude mice were randomly allocated to a control group, a traditional Chinese medicine group, and a chemotherapy group (n = 10 mice per group). The total weight of the 10 mice in each group was similar. Each nude mouse in the control group received 0.5 mL of saline solution each day. Mice in the traditional Chinese medicine group received 0.5 mL of the Fuzheng Huoxue anticancer prescription (containing 1.5 g crude drug) each day, while mice in the chemotherapy group were intraperitoneally injected with 1 mg of 5-Fu once a week for 8 wk. RESULTS:Prior to treatment, the mean OKT8 percentage among gastric patients in the treatment group was 45.94% ± 8.45%, the mean OKT4/OKT8 ratio was 0.89 ± 0.19, the mean AT-III concentration was 29.9 ± 7.9 mg/dL, the mean Fa value was 50.4% ± 24.4%, and the mean β-TG concentration was 91.0 ± 25.9 ng/dL. Prior to treatment, the mean percentage of OKT8 cells among patients in the control group was 49.21% ± 6.60%, the OKT4/OKT8 ratio was 0.94 ± 0.20, the AT-III concentration was 32.3 ± 7.2 mg/dL, the mean Fa value was 57.3% ± 24.6%, and the mean β-TG concentration was 87.5 ± 34.2 ng/dL. After treatment, the mean OKT8 percentage among patients in the treatment group was 33.52% ± 7.80%, the mean OKT4/OKT8 ratio was 1.47 ± 0.51, the mean AT-III concentration was 38.8 ± 5.5 mg/dL, the mean Fa value was 102.6% ± 31.6%, and the mean β-TG concentration was 62.3 ± 15.1 ng/dL. After treatment, the mean OKT8 percentage among patients in the control group was 42.22% ± 7.07%, the mean OKT4/OKT8 ratio was 1.12 ± 0.24, the mean AT-III concentration was 30.9 ± 8.0 mg/dL, the mean Fa value was 64.6% ± 26.9%, and the mean β-TG concentration was 67.0 ± 42.1 ng/dL. These data indicate that after treatment, the immunologic function of the T lymphocytes of gastric cancer patients in the treatment group was significantly improved (P < 0.01). Additionally, the hypercoagulability in the treatment group was also improved (P < 0.001), and the mean OKT4/OKT8 ratio, antithrombin III (AT-III) concentration, and fibrinolytic activity, etc. had all beome normalized. The one-year (86%), 3-year (69%), and 5-year (40%) survival rates in the treatment group were all higher than those in the control group (P < 0.05). The mean tumor weights in the control, traditional medicine, and chemotherapy groups were 0.895 ± 0.289 g, 0.433 ± 0.177 g, and 0.357 ± 0.142 g, respectively. The tumor-inhibition rates in the traditional Chinese medicine group and chemotherapeutic group (51.6% and 60.1%, respectively) were significantly better than that in the control group (P < 0.001). The mean tumor weight in the traditional Chinese medicine group (24.68 ± 1.93 g) was significantly higher than that in both the treatment group (22.96 ± 1.87 g) and control group (22.47 ± 2.18 g). CONCLUSION:The Fuzheng Huoxue anticancer prescription can not only replenish vital functions (Zhengqi), correct a hypercoagulatory state, improve immunologic function, and extend patient survival times, but may also directly inhibit gastric tumor growth without producing toxic side effects.
10.3748/wjg.v3.i3.189
M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by β-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of β-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.
10.1002/advs.202309298
The CXCR2 chemokine receptor: A new target for gastric cancer therapy.
Cytokine
Gastric cancer (GC) is one of the most common malignant tumors in the world, and current treatments are still based on surgery and drug therapy. However, due to the complexity of immunosuppression and drug resistance, the treatment of gastric cancer still faces great challenges. Chemokine receptor 2 (CXCR2) is one of the most common therapeutic targets in targeted therapy. As a G protein-coupled receptor, CXCR2 and its ligands play important roles in tumorigenesis and progression. The abnormal expression of these genes in cancer plays a decisive role in the recruitment and activation of white blood cells, angiogenesis, and cancer cell proliferation, and CXCR2 is involved in various stages of tumor development. Therefore, interfering with the interaction between CXCR2 and its ligands is considered a possible target for the treatment of various tumors, including gastric cancer.
10.1016/j.cyto.2024.156675
Facilitates Oncogenesis in Gastric Cancer Cells by Modulating miR-149 Expression.
Anticancer research
BACKGROUND/AIM:Circular RNA (circRNA) is related to gastric carcinogenesis and progression. This study explored the effects of circTCF25 on gastric cancer cell proliferation, migration, invasion, and cancer stem cell markers, as well as the potential network of circTCF25-miR and miR-149. MATERIALS AND METHODS:circTCF25 expression was detected in tissue specimens and cells by real-time quantitative reverse transcription polymerase chain reaction. Cell Counting Kit-8 and transwell assays were used to measure the effects of circTCF25 knockdown on proliferation, migration and invasion. The potential network of circTCF25 was analyzed using bioinformatic analysis. RESULTS:circTCF25 was overexpressed in human gastric cancer tissues, and a series of cancer cell lines, and was associated with shorter overall survival. Interfering with circTCF25 reduced gastric cancer cell proliferation, migration, invasion and expression of cancer stem cell markers. CircTCF25 reduced expression of miR-149, apparently by acting as a miR-149 sponge. A new circTCF25-miR-149 competitive endogenous RNA network in gastric cancer was constructed, and most core genes were associated with the malignant growth and metastatic behavior of gastric cancer. CONCLUSION:circTCF25 may have prognostic value and an oncogenic role in gastric cancer. A circTCF25-miR-149 RNA regulatory network was established which may provide novel biomarkers or potential therapeutic targets for treating gastric cancer.
10.21873/anticanres.16943
Sirt6-Mediated Cell Death Associated with Sirt1 Suppression in Gastric Cancer.
Cancers
BACKGROUND:Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. METHODS:After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. RESULTS:Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. CONCLUSION:We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer.
10.3390/cancers16020387
[Effect of moxibustion on IL-6/STAT3 signaling in frontal cortex of fatigue rats].
Li Chen,Li Tian-Ge,Wang Hong-Mei,Shui Ling,Lu Jun,Wu Ji-Hong,Chen Ying-Song
Zhen ci yan jiu = Acupuncture research
OBJECTIVE:To observe the effect of moxibustion on interleukin-6(IL-6)/signal transduction and transcriptional activator 3(STAT3) signaling pathway in the frontal cortex of fatigue rats, so as to reveal its mechanisms underlying alleviation of fatigue. METHODS:Twenty-one male SD rats were randomly divided into normal control, model, and moxibustion groups (=7 rats in each group). The fatigue model was established by forcing the rats to have an exhausted swim under load condition, once daily for 21 days. Moxibustion was applied to bilateral "Zusanli"(ST36) for about 15 min, once every other day for 21 days. The level of IL-6 in the frontal cortex was detected by ELISA, and the expression of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transduction and transcriptional activator 3(STAT3) and phosphorylated STAT3 (p-STAT3) proteins in the frontal cortex was detected by Western blot. RESULTS:After modeling, the levels of IL-6 content and p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly increased in the model group relevant to the normal control group (<0.01). Follo-wing moxibustion, the duration of load swimming on the 21 day was significantly prolonged (<0.01), content of IL-6 and levels of p-STAT3 protein expression and ratio of p-STAT3/STAT3 were significantly down-regulated in the moxibustion group compared with the model group (<0.05). No significant differences were found between the model and control, and between moxibustion and model groups in the expression levels of JAK2, p-JAK2, STAT3 and p-JAK2/JAK2 (>0.05). CONCLUSION:Moxibustion intervention can relieve fatigue in fatigue rats, which is associated with its function in inhibiting IL-6/STAT3 signaling pathway to reduce inflammatory injury.
10.13702/j.1000-0607.190618
Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.
Laboratory investigation; a journal of technical methods and pathology
Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.
10.1016/j.labinv.2024.102090
Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer.
Scientific reports
Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.
10.1038/s41598-024-63305-3
Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis.
Frontiers in molecular biosciences
Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer. Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters. Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered. This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.
10.3389/fmolb.2024.1399679
Interaction between intestinal flora and gastric cancer in tumor microenvironment.
Frontiers in oncology
Gastric Cancer (GC) is a prevalent malignancy globally and is the third leading cause of cancer-related deaths. Recent researches focused on the correlation between intestinal flora and GC. Studies indicate that bacteria can influence the development of gastrointestinal tumors by releasing bacterial extracellular vesicles (BEVs). The Tumor microenvironment (TME) plays an important role in tumor survival, with the interaction between intestinal flora, BEVs, and TME directly impacting tumor progression. Moreover, recent studies have demonstrated that intestinal microflora and BEVs can modify TME to enhance the effectiveness of antitumor drugs. This review article provides an overview and comparison of the biological targets through which the intestinal microbiome regulates TME, laying the groundwork for potential applications in tumor diagnosis, treatment, and prognosis.
10.3389/fonc.2024.1402483
Two-sample Mendelian randomization analysis of the relationship between periodontitis and risk of upper gastrointestinal cancers.
Postgraduate medical journal
PURPOSE:The aim of the present study is to explore the possible association between periodontitis and upper gastrointestinal (UGI) cancers, including esophageal and gastric cancers, utilizing the Mendelian randomization method. METHODS:In this research, we utilized the Mendelian randomization method to examine the causal association between periodontitis and UGI cancers. Genome-wide association studies data for periodontitis were obtained from the Gene-Lifestyle Interactions in Dental Endpoints consortium, while UGI cancers' data were accessed from FinnGen's Biobank. After rigorously screening instrumental variables for periodontitis, we analyzed them with UGI cancers primarily using the inverse variance weighted. Finally, to identify outliers, the results were subjected to a leave-one-out sensitivity analysis. RESULTS:Inverse variance weighted (fixed effect) results revealed that periodontitis is a risk factor for gastric cancer (OR = 1.7735, 95% CI: 1.1576 to 2.7170, P = 0.0085). As for esophageal cancer, no statistically significant correlation was observed. Furthermore, no outliers were detected in any of the results. CONCLUSION:Our two-sample Mendelian randomization study obviously demonstrates a significant positive association between periodontitis and gastric cancer, while no statistically significant correlation was found for esophageal cancer.
10.1093/postmj/qgae069
TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer.
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find effective therapeutic targets to enhance the sensitivity of GC to DDP. Studies have shown that Transmembrane protein 205 (TMEM205) is overexpressed in DDP-resistant human epidermoid carcinoma cells and correlates with drug resistance, and database analyses show that TMEM 205 is also overexpressed in GC, but its role in cisplatin-resistant gastric cancer remains unclear. In this study, we chose a variety of experiments in vivo and vitro, aiming to investigate the role of TMEM 205 in cisplatin resistance in gastric cancer. The results showed that TMEM 205 promoted proliferation, stemness, epithelial-mesenchymal transition (EMT), migration and angiogenesis of gastric cancer cells through activation of the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment.
10.1007/s10120-024-01517-2
Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis.
World journal of gastrointestinal oncology
BACKGROUND:The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates. AIM:To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC. METHODS:Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18. RESULTS:A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China ( = 1061), National Cancer Center ( = 138), and Shoichiro Tsugane ( = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: () infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models. CONCLUSION:In this study, we found that infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC infection, SNP, smoking, diet, and alcohol.
10.4251/wjgo.v16.i5.2200
Extracting big data from the internet to support the development of a new patient-reported outcome measure for breast implant illness: a proof of concept study.
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
PURPOSE:Individuals with health conditions often use online patient forums to share their experiences. These patient data are freely available and have rarely been used in patient-reported outcomes (PRO) research. Web scraping, the automated identification and coding of webpage data, can be employed to collect patient experiences for PRO research. The objective of this study was to assess the feasibility of using web scraping to support the development of a new PRO measure for breast implant illness (BII). METHODS:Nine publicly available BII-specific web forums were chosen post-consultation with two prominent BII advocacy leaders. The Python Selenium and Pandas packages were used to automate extraction of de-identified text from the individual posts/comments into a spreadsheet. Data were coded using a line-by-line approach and constant comparison was used to create top-level domains and sub-domains. RESULTS:6362 unique codes were identified and organized into four top-level domains of information needs, symptom experiences, life impact of BII, and care experiences. Information needs of women included seeking/sharing information pre-breast implant surgery, post-breast implant surgery, while contemplating explant surgery, and post-explant surgery. Symptoms commonly described by women included fatigue, brain fog, and musculoskeletal symptoms. Many comments described BII's impact on daily activities and psychosocial wellbeing. Lastly, some comments described negative care experiences and experiences related to advocating for themselves to providers. CONCLUSION:This proof-of-concept study demonstrated the feasibility of employing web scraping as a cost-effective, efficient method to understand the experiences of women with BII. These data will be used to inform the development of a BII-specific PROM.
10.1007/s11136-024-03672-6
Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY:This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS:This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS:The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS:Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.
10.1016/j.jep.2024.117791
Clinical Significance of Paraspinal Muscle Parameters as a prognostic factor for survival in Gastric Cancer Patients who underwent Curative Surgical Resection.
Eo Wankyu,Kwon Jungmi,An Soomin,Lee Sookyung,Kim Sehyun,Nam Dongwoo,Han Ga Young,Choi Sung Il,Chung Ho-Yeon
Journal of Cancer
The quantitative and qualitative skeletal muscle parameters have been proposed to predict the outcome of patients with gastric cancer. However, the evidence for their association with long-term survival is still conflicting. This study aimed to investigate the effect of paraspinal muscle parameters on overall survival (OS) and disease-free survival (DFS) in patients with gastric cancer who underwent curative resection. Patients with stages I or II gastric cancer who underwent curative resection between October 2006 and June 2016 were identified from electrical medical records. Paraspinal muscle area and attenuation were measured at the level of the third lumbar vertebra using computerized tomography images. For the analysis of OS and DFS, proportional hazards model was used, incorporating demographic, pathologic, laboratory, and radiologic variables. This study enrolled 296 patients (192 men and 104 women). In the multivariate proportional hazards model, total gastrectomy (hazard ratio [HR], 2.65; 95% Confidence interval [CI], 1.36-5.19; = 0.0044), neutrophil-lymphocyte ratio (NLR) (HR, 1.27; 95% CI, 1.06-1.51; = 0.0081), serum albumin level (HR, 0.16; 95% CI, 0.07-0.39; < 0.0001), paraspinal muscle area adjusted for body surface area (PMA) (HR, 3.06; 95% CI, 1.65-5.67; 0.0004), and mean attenuation in paraspinal muscle (PMMA) (HR, 3.38; 95% CI, 1.75-6.53; = 0.0003) were prognostic factors for OS. Similarly, total gastrectomy (HR, 2.11; 95% CI, 1.10-4.06; = 0.0243), NLR (HR, 1.25; 95% CI, 1.06-1.48; = 0.0071), serum albumin level (HR, 0.22; 95% CI, 0.10-0.51; = 0.0035), PMA (HR, 2.42; 95% CI, 1.34-4.37; 0.0035), and PMMA (HR, 3.19; 95% CI, 1.71-5.93; = 0.0003) were prognostic factors for DFS. The pretreatment paraspinal muscle parameters such as PMA and PMMA along with total gastrectomy, NLR, and serum albumin level could predict OS and DFS in patients with stages I or II gastric cancer who underwent curative surgical resection. Because PMA and PMMA are newly characterized parameters in gastric cancer, the relationship with the survival of these parameters requires further validation in further studies before they are subjected to clinical applications.
10.7150/jca.46637
Effect of acupuncture therapy for postoperative gastrointestinal dysfunction in gastric and colorectal cancers: an umbrella review.
Frontiers in oncology
Background:Gastrointestinal dysfunction is a prevalent postoperative complication in patients undergoing surgery for gastric cancer and colorectal cancer. Acupuncture holds promise as a great potential therapeutic intervention. The efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction has been assessed in some studies, however, the variability in results and study quality influences practical clinical application. Therefore, it is necessary to summarize and analyze the published clinical research data in this field. Objective:This study aimed to synthesize evidence from systematic reviews and meta-analyses in order to assess the efficacy of acupuncture therapy for postoperative gastrointestinal dysfunction in patients with gastric and colorectal cancer. Design:Umbrella review of systematic reviews and meta-analyses. Methods:We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Chinese biomedical literature service system (SinoMed), PubMed, Embase, Cochrane Library, and Web of Science for all systematic review/meta-analysis of acupuncture for postoperative gastrointestinal dysfunction in gastric and colorectal cancers. From the establishment of the database to July 8, 2023. Two independent reviewers conducted literature extraction and evaluation. The quality of included studies was assessed using The preferred reporting items for systematic reviews and meta-analysis statements 2020 (PRISMA2020), the quality of the methods was assessed using a measuring tool to assess systematic reviews 2 (AMSTAR 2), and the level of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The statistical analysis was conducted using RevMan 5.4, and the effect size was expressed as Odds Ratio (OR), Mean Difference (MD), and 95% confidence interval (CI) based on the extracted data type (test level α= 0.05). The heterogeneity was assessed using the statistic and Q-test (χ). The outcome indicators such as time to first defecation and time to first flatus were utilized as endpoints to assess the efficacy of different acupuncture therapies. Results:A total of six systematic reviews/meta-analyses were included in this study, involving 12 different acupuncture therapies. PRISMA 2020 indicated that the studies all scored between 13-20.5. There were deficiencies in protocol and registration, assessment of the quality of evidence for outcome indicators, risk of bias, and declaration of conflict of interest. The AMSTAR 2 evaluations showed that five studies were very low quality and one was low quality. The level of evidence for various acupuncture interventions varied from very low to moderate.For patients with gastrointestinal dysfunction after gastric cancer surgery, ear acupressure [MD=-11.92, 95% (-14.39,-9.44), <0.00001], moxibustion [MD=-19.16, 95% (-23.00,-16.22), <0.00001], warm needling [MD=-12.81, 95% (-17.61,-8.01), <0.00001], acupoint application [MD=-6.40, 95% (-10.26,-2.54), =0.001], manual acupuncture [MD=-18.32, 95% (-26.31,-10.39), <0.00001] and transcutaneous electrical acupoint stimulation (TEAS) [MD=-5.17, 95% (-9.59,-0.74), =0.02] could promote the recovery of gastrointestinal function after surgery.For postoperative colorectal cancer patients, electroacupuncture [MD=-15.17, 95% (-28.81,-1.54), <0.05], manual acupuncture [MD=-20.51, 95% (-39.19,-1.84), <0.05], warm needling [MD=-18.55, 95% (-23.86,-13.24), <0.05], ear acupressure [MD=-5.38, 95% (-9.80,-0.97), <0.05], acupoint application [MD=-26.30, 95% (-32.81,-19.79), <0.05], ear acupressure+acupressure [MD=-9.67, 95% (-13.58,-5.76), <0.05], ear acupressure+manual acupuncture [MD=-18.70, 95% (-21.01,-16.39), <0.05], ear acupressure+moxibustion [MD=-22.90, 95% (-30.10,-15.70), <0.05], moxibustion+acupressure [MD=-14.77, 95% (-20.59,-8.95), <0.05] improved postoperative gastrointestinal function. In addition, the efficacy of acupressure [MD=-12.00, 95% (-31.60,7.60), >0.05] needed to be further demonstrated. Conclusion:Acupuncture therapy has a positive therapeutic impact on postoperative gastrointestinal dysfunction in gastric and colorectal cancers, but this finding should still be taken with caution.
10.3389/fonc.2024.1291524
Interleukin 6-independent metabolic reprogramming as a driver of cancer-related fatigue.
Grossberg Aaron J,Vichaya Elisabeth G,Gross Phillip S,Ford Bianca G,Scott Kiersten A,Estrada Darlene,Vermeer Daniel W,Vermeer Paola,Dantzer Robert
Brain, behavior, and immunity
Fatigue is a common and debilitating symptom of cancer with few effective interventions. Cancer-related fatigue (CRF) is often associated with increases in inflammatory cytokines, however inflammation may not be requisite for this symptom, suggesting other biological mediators also play a role. Because tumors are highly metabolically active and can amplify their energetic toll via effects on distant organs, we sought to determine whether CRF could be explained by metabolic competition exacted by the tumor. We used a highly metabolically active murine E6/E7/hRas model of head and neck cancer for this purpose. Mice with or without tumors were submitted to metabolic constraints in the form of voluntary wheel running or acute overnight fasting and their adaptive behavioral (home cage activity and fasting-induced wheel running) and metabolic responses (blood glucose, ketones, and liver metabolic gene expression) were monitored. We found that the addition of running wheel was necessary to measure activity loss, used as a surrogate for fatigue in this study. Tumor-bearing mice engaged in wheel running showed a decrease in blood glucose levels and an increase in lactate accumulation in the skeletal muscle, consistent with inhibition of the Cori cycle. These changes were associated with gene expression changes in the livers consistent with increased glycolysis and suppressed gluconeogenesis. Fasting also decreased blood glucose in tumor-bearing mice, without impairing glucose or insulin tolerance. Fasting-induced increases in wheel running and ketogenesis were suppressed by tumors, which was again associated with a shift from gluconeogenic to glycolytic metabolism in the liver. Blockade of IL-6 signaling with a neutralizing antibody failed to recover any of the behavioral or metabolic outcomes. Taken together, these data indicate that metabolic competition between the tumor and the rest of the organism is an important component of fatigue and support the hypothesis of a central role for IL-6-independent hepatic metabolic reprogramming in the pathophysiology of CRF.
10.1016/j.bbi.2020.05.043
Hematocrit Is Associated with Cancer-Related Fatigue in Colorectal Cancer Survivors: A Longitudinal Analysis.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
BACKGROUND:Cancer-related fatigue (CRF) is a frequent symptom in colorectal cancer survivors. It is unknown to what extent anemia may contribute to CRF in colorectal cancer survivors. This study aimed to investigate the association between hematocrit, as marker for anemia, and CRF among colorectal cancer survivors from diagnosis until two years thereafter. METHODS:The study population included 1,506 newly diagnosed colorectal cancer survivors at any stage of disease from a prospective cohort study. Hematocrit and CRF (EORTC QLQ-C30) were assessed at diagnosis, six months, and two years after diagnosis. Multivariable logistic regression or multivariable linear mixed models were used to assess the associations of hematocrit with CRF prevalence, or CRF severity over time, respectively. RESULTS:A low hematocrit (levels <40% men/<36% women) was present in a third of the survivors at diagnosis and six months thereafter, and among 16% two years after diagnosis. The prevalence of CRF was 15% at diagnosis, peaked at 27% at six months, and was 14% two years after diagnosis. Hematocrit was associated with the prevalence of CRF at diagnosis [OR, 0.92; confidence interval (CI), 0.88-0.95], 6 months (OR, 0.89; 95% CI, 0.86-0.92), and 2 years (OR, 0.91; CI, 0.87-0.96) after diagnosis. Lower hematocrit was associated with higher severity of CRF over time (beta-coefficient = 1.3; CI, 1.5-1.1). CONCLUSIONS:Lower hematocrit levels were longitudinally associated with a higher prevalence and severity of CRF in colorectal cancer. IMPACT:Our findings emphasize the importance of long-term anemia monitoring and a potential role of anemia in CRF among colorectal cancer survivors.
10.1158/1055-9965.EPI-23-1048
Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.
American journal of respiratory and critical care medicine
Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. ) To identify and prioritize knowledge and research gaps and ) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. This statement identifies knowledge gaps in the ) detection and diagnostic evaluation of CRF in lung cancer survivors; ) timing, goals, and implementation of physical activity and rehabilitation; and ) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. This statement offers a prioritized research agenda to ) advance clinical and research efforts and ) increase awareness of CRF in lung cancer survivors.
10.1164/rccm.202210-1963ST
Inflammatory pathway genes associated with inter-individual variability in the trajectories of morning and evening fatigue in patients receiving chemotherapy.
Wright Fay,Hammer Marilyn,Paul Steven M,Aouizerat Bradley E,Kober Kord M,Conley Yvette P,Cooper Bruce A,Dunn Laura B,Levine Jon D,DEramo Melkus Gail,Miaskowski Christine
Cytokine
Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue. Patients completed the Lee Fatigue Scale to determine morning and evening fatigue severity a total of six times over two cycles of CTX. Using a whole exome array, 309 single nucleotide polymorphisms SNPs among the 64 candidate genes that passed all quality control filters were evaluated using hierarchical linear modeling (HLM). Based on the results of the HLM analyses, the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/signal transducers and activators of transcription (JAK/STAT, 10 genes); mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms in six genes from the cytokine (2 genes); inflammasome (2 genes); and NFkB (2 genes) pathways were associated with both morning and evening fatigue. Polymorphisms in six genes from the inflammasome (1 gene); JAK/STAT (1 gene); and NFkB (4 genes) pathways were associated with only morning fatigue. Polymorphisms in three genes from the inflammasome (2 genes) and the NFkB (1 gene) pathways were associated with only evening fatigue. Taken together, these findings add to the growing body of evidence that suggests that morning and evening fatigue are distinct symptoms.
10.1016/j.cyto.2016.12.023
Positive affect and fatigue as predictors of anti-inflammatory IL-10 concentrations among colorectal cancer patients during adjuvant chemotherapy.
Journal of psychosomatic research
OBJECTIVES:(1) To examine the relationships of positive and negative affect and symptoms of depression, anxiety, and fatigue at baseline with the anti-inflammatory cytokine IL-10 concentrations in serum at three points in colorectal cancer patients; and (2) to assess the relationship between these factors and disease recurrence or mortality after a median follow-up of 24 months. METHODS:In a prospective trial, 92 stage II or III colorectal cancer patients scheduled to receive standard chemotherapy were enrolled. Blood samples were collected prior to start of chemotherapy onset (T0), 3 months later (T1), and upon chemotherapy completion (T2). RESULTS:IL-10 concentrations were similar across the time points. Linear mixed-effects model analysis showed that controlling for confounders, higher positive affect and lower fatigue pretreatment (T0) predicted IL-10 concentrations across the time points (estimate = 0.18, SE = 0.08, 95% CI = 0.03, 0.34, p < .04 and estimate = -0.25, SE = 0.12, 95% CI = -0.50, 0.01, p < .04, respectively). Depression at T0 significantly predicted higher disease recurrence and mortality (estimate = 0.17, SE = 0.08, adjusted OR = 1.18, 95% CI = 1.02, 1.38, p = .03). CONCLUSIONS:We report on associations not previously assessed between positive affect and fatigue and the anti-inflammatory cytokine IL-10. Results add to previous findings suggesting that positive affect and fatigue could have a role in anti-inflammatory cytokine dysregulation.
10.1016/j.jpsychores.2023.111162
Diet quality indices and changes in cognition during chemotherapy.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:No evidence-based prevention strategies currently exist for cancer-related cognitive decline (CRCD). Although patients are often advised to engage in healthy lifestyle activities (e.g., nutritious diet), little is known about the impact of diet on preventing CRCD. This secondary analysis evaluated the association of pre-treatment diet quality indices on change in self-reported cognition during chemotherapy. METHODS:Study participants (n = 96) completed the Block Brief Food Frequency Questionnaire (FFQ) before receiving their first infusion and the PROMIS cognitive function and cognitive abilities questionnaires before infusion and again 5 days later (i.e., when symptoms were expected to be their worst). Diet quality indices included the Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet (aMED), and a low carbohydrate diet index and their components. Descriptive statistics were generated for demographic and clinical variables and diet indices. Residualized change models were computed to examine whether diet was associated with change in cognitive function and cognitive abilities, controlling for age, sex, cancer type, treatment type, depression, and fatigue. RESULTS:Study participants had a mean age of 59 ± 10.8 years and 69% were female. Although total diet index scores did not predict change in cognitive function or cognitive abilities, higher pre-treatment ratio of aMED monounsaturated/saturated fat was associated with less decline in cognitive function and cognitive abilities at 5-day post-infusion (P ≤ .001). CONCLUSIONS:Higher pre-treatment ratio of monounsaturated/saturated fat intake was associated with less CRCD early in chemotherapy. Results suggest greater monounsaturated fat and less saturated fat intake could be protective against CRCD during chemotherapy.
10.1007/s00520-022-07513-5
Association of plasma leptin, pro-inflammatory adipokines and cancer-related fatigue in early-stage breast cancer patients: A prospective cohort study.
Toh Yi Long,Tan Chia Jie,Yeo Angie Hui Ling,Shwe Maung,Ho Han Kiat,Gan Yan Xiang,Foo Koon Mian,Chu Pat,Olson Karin,Chan Alexandre
Journal of cellular and molecular medicine
Cancer-related fatigue (CRF) is subjective and has wide inter-individual variability. Given that leptin is commonly associated with fatigue syndrome, its use as a potential biomarker for CRF is being investigated. The primary objective of this study was to evaluate the association between leptin and CRF in early-stage breast cancer patients receiving chemotherapy. In a prospective cohort study, patients completed assessments at baseline (T1), during chemotherapy (T2) and after chemotherapy (T3). Levels of plasma leptin and adipokines were measured using a Luminex bead-immunoassay and CRF was measured using the Multi-Dimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Data were analysed longitudinally using a generalised estimating equation incorporating clinically relevant parameters and pro-inflammatory adipokines. The analysis included 136 patients (mean age ± SD = 51.5 ± 8.8 years; 69.1% receiving anthracycline-based chemotherapy). More patients experienced CRF at T3 (23.8%) than at T2 (13.8%) compared to baseline. An increase was observed in the median plasma leptin level at T2, followed by a decrease at T3 (T1: 4.07 ng/mL, T2: 4.95 ng/mL and T3: 3.96 ng/mL). In the multivariate model, the change in leptin levels over time was significantly associated with the total MFSI-SF score (β = -0.15, P = 0.003) after adjusting for the tumour necrosis factor-α (TNF-α) level, anxiety, depression, insomnia, age, menopausal status and type of chemotherapy. This is the first study to report leptin as a biomarker that predicts the onset of CRF over time. Future studies are required to validate the findings.
10.1111/jcmm.14319
Brain-derived neurotrophic factor polymorphism Val66Met protects against cancer-related fatigue.
Translational psychiatry
Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient's quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.
10.1038/s41398-020-00990-4
The GDF15-GFRAL axis mediates chemotherapy-induced fatigue in mice.
Brain, behavior, and immunity
Cancer-related fatigue is defined as a distressing persistent subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning. This form of fatigue is highly prevalent during cancer treatment and in some patients, it can persist for years after treatment has ended. An understanding of the mechanisms that drive cancer-related fatigue is still lacking, which hampers the identification of effective treatment options. Various chemotherapeutic agents including cisplatin are known to induce mitochondrial dysfunction and this effect is known to mediate chemotherapy-induced peripheral neuropathy and cognitive dysfunction. Mitochondrial dysfunction results in the release of mitokines that act locally and at distance to promote metabolic and behavioral adjustments to this form of cellular stress. One of these mitokines, growth differentiation factor 15 (GDF15) and its receptor, glial cell line-derived neurotrophic factor family receptor α-like (GFRAL), have received special attention in oncology as activation of GFRAL mediates the anorexic response that is responsible for cancer anorexia. The present study was initiated to determine whether GDF15 and GFRAL are involved in cisplatin-induced fatigue. We first tested the ability of cisplatin to increase circulating GDF15 in mice before assessing whether GDF15 can induce behavioral fatigue measured by decreased wheel running in healthy mice and increase behavioral fatigue induced by cisplatin. Mice administered a long acting form of GDF15, mGDF15-fc, decreased their voluntary wheel running activity. When the same treatment was administered to mice receiving cisplatin, it increased the amplitude and duration of cisplatin-induced decrease in wheel running. To determine whether endogenous GDF15 mediates the behavioral fatigue induced by cisplatin, we then administered a neutralizing monoclonal antibody to GFRAL to mice injected with cisplatin. The GFRAL neutralizing antibody mostly prevented cisplatin-induced decrease in wheel running and accelerated recovery. Taken together these findings demonstrate for the first time the role of the GDF15/GFRAL axis in cisplatin-induced behaviors and indicate that this axis could be a promising therapeutic target for the treatment of cancer-related fatigue.
10.1016/j.bbi.2022.11.008
Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group.
Kim J G,Sohn S K,Chae Y S,Song H S,Kwon K-Y,Do Y R,Kim M K,Lee K H,Hyun M S,Ryoo H M,Bae S H,Park K U,Lee W S,Baek J H,Chung H Y,Yu W
British journal of cancer
The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m(-2) plus oxaliplatin 120 mg m(-2) on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7-59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3-7.2) months and 9.9 (95% CI; 7.8-12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.
10.1038/sj.bjc.6604188
Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis.
Frontiers in endocrinology
Cancer-related fatigue (CRF) is the most common side effect of chemotherapy for breast cancer (BC). Acupuncture treatment has an anti-fatigue effect and can regulate gut microbiota disturbance in fatigue patients. Related studies have shown that the gut microbiota-gut-brain axis is closely related to the occurrence of CRF. In this study, we first investigated the alterations of acupuncture on fatigue-like behavior, gut microbiota, gut inflammation and neuroinflammation response, gut barriers, HPA axis, and serum metabolomics in CRF mice after BC chemotherapy. Then, the correlation analysis of gut microbiota and other indicators was discussed. Our results showed that acupuncture treatment could exert an anti-fatigue effect and ameliorate the gut barrier, gut inflammation, neuroinflammation, and dysfunction of the HPA axis in CRF mice after chemotherapy for BC. 16S rRNA sequencing showed that acupuncture treatment could enhance the abundance of , , and and decrease the abundances of , , and . Serum metabolomics analysis showed that acupuncture treatment could regulate the differential metabolites N-methylnicotinamide, beta-glycerophosphoric acid, geranyl acetoacetate, serotonin and phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine, and beta-alanine metabolic pathways. Correlation analysis indicated that there are certain correlations between gut microbiota and gut inflammation, neuroinflammation, gut barrier, HPA axis function and serum metabolites. In conclusion, our findings revealed that the anti-fatigue mechanism of acupuncture treatment may be closely related to the gut microbiota-gut-brain axis. This study also provided a new reference for basic and clinical research on CRF after breast cancer chemotherapy.
10.3389/fendo.2022.921119
Survival benefit from S-1 as compared to Fluorouracil in Asian patients with advanced gastrointestinal cancer: a meta-analysis.
Cancer science
Whether S-1 could replace 5-Fluorouracil (5-Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta-analysis was performed to compare the activity, efficacy and toxicity of S-1-based versus 5-Fu-based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S-1-based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09-2.70), but no significant progression-free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72-1.06). Subgroup analyses revealed that S-1-based chemotherapy significantly improved OS and ORR in subgroups of patients with non-platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S-1-based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S-1-based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S-1, and S-1-based chemotherapy could be considered to replace 5-Fu-based therapy for the treatment of advanced GI cancer in Asian patients.
10.1111/cas.12465
Platinum-induced muscle wasting in cancer chemotherapy: Mechanisms and potential targets for therapeutic intervention.
Moreira-Pais Alexandra,Ferreira Rita,Gil da Costa Rui
Life sciences
Platinum-based drugs are among the most effective anticancer therapies, integrating the standard of care for numerous human malignancies. However, platinum-based chemotherapy induces severe side-effects in cancer patients, such as cachexia. Weight loss, as well as fatigue and systemic inflammation are characteristics of this syndrome that adversely affects the survival and the quality of life of cancer patients. The signalling pathways involved in chemotherapy-induced cachexia are still to be fully understood, but the activity of several mediators associated with muscle wasting, such as myostatin and pro-inflammatory cytokines are increased by platinum-based drugs like cisplatin. Indeed, the molecular mechanisms behind chemotherapy-induced muscle wasting seem to be similar to the ones promoted by cancer in treatment-naive patients. Although some therapeutic agents are under investigation for treating muscle wasting in cancer patients, no effective treatment is yet available. Herein, we review the molecular mechanisms proposed to be involved in chemotherapy-related muscle wasting with a focus on the typical platinum-based drug cisplatin. Therapeutic strategies presently under investigation are also reviewed, providing an overview of the current efforts to preserve muscle mass and quality of life among cancer patients.
10.1016/j.lfs.2018.07.010
Platinum Accumulation and Cancer-Related Fatigue, Correlation With IL-8, TNF-α and Hemocytes.
Zhang Yuling,Huang Xiaoting,Feng Shanna,Chen Chen,Guo Dainian,Fang Ling
Frontiers in pharmacology
Platinum-based chemotherapy drugs cause platinum accumulation and result in cancer-related fatigue (CRF), which is related to immune response through still ambiguous mechanisms. We aimed to explore the correlation between platinum and CRF from the perspective of platinum accumulation. After allowing for complete metabolism of the administered platinum drugs, we collected blood samples from 135 patients who had at least two platinum chemotherapy rounds, correlated the platinum concentration (C-Pt), pro-inflammatory cytokines IL-8 and TNF-α, hematological index with therapeutic effect, adverse reactions and fatigue. The median platinum concentration was higher in patients treated with cisplatin than oxaliplatin (424.0 vs 211.3 μg/L), and the occurrence of fatigue was 64.4% in all subjects. Separately, the incidence and degree of fatigue were 74.1% and 9.5 in the patients with higher platinum concentration compared to 57.1% and 2.0 in the lower group. C-Pt, IL-8 and TNF-α were positively correlated with the degree of CRF, while erythrocyte count and hemoglobin were negatively correlated with the degree of CRF. Mediating effect analysis showed that increased IL-8 concentration mediated 57.4%, while decreased erythrocyte count mediated 24.1% of the C-Pt effect on CRF. Platinum accumulation may involve increasing IL-8, cause inflammation or aggravate anemia, which in combination lead to CRF.
10.3389/fphar.2021.658792
A retrospect study based on real-world data to observe metabolic function in cancer patients using albumin-bound paclitaxel.
Scientific reports
There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage.
10.1038/s41598-023-35992-x
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.
Lancet (London, England)
BACKGROUND:First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone. METHODS:In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116. FINDINGS:From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified. INTERPRETATION:Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients. FUNDING:Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.
10.1016/S0140-6736(21)00797-2
Oxaliplatin-Based Regimen is Superior to Cisplatin-Based Regimen in Tumour Remission as First-line Chemotherapy for Advanced Gastric Cancer: A Meta-Analysis.
Journal of Cancer
This study was initially designed to examine whether oxaliplatin-based regimen was superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced gastric cancer (GC). Literature in EMBASE, PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was searched. Only phase II or III randomized controlled trials (RCTs) comparing the effectiveness and safety between oxaliplatin-based and cisplatin-based regimens as first-line treatment for advanced GC were selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. The primary endpoints were complete remission rate (CRR), partial remission rate (PRR), objective response rate (ORR), and disease control rate (DCR). The second endpoint was the toxicity response. 2,140 patients from six phase II or III RCTs were included. Compared to cisplatin-based therapy, subjects who received oxaliplatin-based treatment had significantly higher PRR (OR: 1.25, 95%CI: 1.05-1.48, =0.01, I=0%), ORR (OR: 1.21, 95%CI: 1.02-1.44, =0.03, I=0%) and DCR (OR: 1.76, 95%CI: 1.31-2.38, =0.0002, I=25%), but not CRR (OR: 0.70, 95%CI: 0.37-1.31, =0.27, I=0%). In addition, oxaliplatin-based therapy significantly decreased all grades of leukopenia, neutropenia, anemia, febrile neutropenia, nausea, stomatitis, creatinine elevation and thromboembolism, as well as grades 3-4 of leukopenia, neutropenia, anemia and febrile neutropenia than cisplatin-based regimen. However, oxaliplatin-based treatment strikingly increased the risk of thrombocytopenia, sensory neuropathy, diarrhea, fatigue and liver dysfunction. Oxaliplatin-based regimen is superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced GC, and is associated with less toxicity and better tolerability.
10.7150/jca.28896
Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: A real-world data, non-inferiority analysis.
Visa Laura,Jiménez-Fonseca Paula,Martínez Elena Asensio,Hernández Raquel,Custodio Ana,Garrido Manuel,Viudez Antonio,Buxo Elvira,Echavarria Ignacio,Cano Juana María,Macias Ismael,Mangas Montserrat,de Castro Eva Martínez,García Teresa,Manceñido Felipe Álvarez,Montes Ana Fernández,Azkarate Aitor,Longo Federico,Serrano Asunción Díaz,López Carlos,Hurtado Alicia,Cerdá Paula,Serrano Raquel,Gil-Negrete Aitziber,Carnicero Alfonso Martín,Pimentel Paola,Ramchandani Avinash,Carmona-Bayonas Alberto,
Journal of geriatric oncology
OBJECTIVE:Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. MATERIALS AND METHODS:We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.<70years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. RESULTS:33% (n=489) of the cases analyzed were ≥70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3-4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91-1.14), P (non inferiority)=0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87-1.08), P(non-inferiority)=0.001. CONCLUSION:In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects.
10.1016/j.jgo.2017.11.008
The characteristics and related factors of insomnia among postoperative patients with gastric cancer: a cross-sectional survey.
Zhu Guang-Hui,Li Juan,Li Jie,Xu Bo-Wen,Wang He-Ping,Wang Xin-Miao,Hu Jia-Qi,Dai Ming-Hao
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PURPOSE:This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. METHODS:A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. RESULTS:① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was "poor". ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. CONCLUSION:Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.
10.1007/s00520-021-06295-6
The correlation of traditional chinese medicine deficiency syndromes, cancer related fatigue, and quality of life in breast cancer patients.
Chien Tsai-Ju,Song You-Lung,Lin Che-Pin,Hsu Chung-Hua
Journal of traditional and complementary medicine
BACKGROUND:To evaluate the correlation between the different traditional chinese medicine (TCM) deficiency syndromes, cancer related fatigue (CRF), and quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS:Ninety-five breast cancer patients were categorized into different qi ( qì), blood ( xuè), yin ( yin), and yang ( yáng) TCM deficiency syndrome groups (DSGs). We used the ICD-10 for diagnosing CRF. The QoL was assessed by the WHO-BREF and Short Form Health Survey (SF12) questionnaires. The major outcome was to compare the QoL scores between the different TCM DSGs. The second outcome was the intergroup analysis between the CRF and different TCM DSGs in breast cancer patients. RESULTS:The patients with qi deficiency ( qì xu) had a higher correlation with CRF (p=0.001) and poorer QoL both in the WHO-BREF and SF12 survey (p<0.001), whereas the patients with yin deficiency ( yin xu) had poorer QoL in the psychological (p=0.02) and social aspects (p=0.04). The qi deficiency ( qì xu) syndrome was closely associated with yin deficiency syndrome ( yin xu). (p=0.03). CONCLUSION:Our study confirmed the concept of Qi-deficiency ( qì xu) in TCM was associated with CRF as identified in cancer care in western medicine. The breast cancer patients with qi deficiency ( qì xu) have poorer QoL. Treatment of CRF and improving QoL by supplying qi ( qì) may warrant further investigation.
10.1016/s2225-4110(16)30101-8
The Therapeutic Effects of Acupuncture and Electroacupuncture on Cancer-related Symptoms and Side-Effects.
Journal of Cancer
In addition to cancer-related death, malignant progression also leads to a series of symptoms and side-effects, which would detrimentally affect cancer patients' the quality of life, adversely influence their adherence to treatments, and, therefore, negatively affect their long-term survival. Acupuncture and electroacupuncture (EA), as two classic treatment methods in traditional Chinese medicine, have been widely employed to cure various diseases. Recently, the clinical application of acupuncture and EA in cancer patients has received great attention. In this review, we summarized the clinical application of acupuncture and EA in alleviating the cancer symptoms, reducing the cancer treatment-related side-effects, and relieving the cancer pain. The symptoms and side-effects discussed in this review include fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), pain, xerostomia, and anxiety and depression. The underlying mechanisms of the therapeutic effects of acupuncture and EA might be related to the regulation of the mitochondrial function, coordination of the activity of the nervous system, adjustment of the production of neurotransmitters, and alleviation of the immune responses. In conclusion, acupuncture and EA have been proved to be beneficial for cancer patients. More research, however, is required to clarify the potential mechanisms behind acupuncture and EA for widespread adoption in clinical application.
10.7150/jca.55803
The fatigue paradox: Team perceptions of physician fatigue.
Field Emily,Lingard Lorelei,Cherry Richard,Van Koughnett Julie Ann,DeLuca Sandra,Taylor Taryn
Medical education
OBJECTIVES:Ongoing calls to implement fatigue risk management in residency education assume a shared understanding of physician fatigue as a workplace hazard, yet we lack empirical evidence that all health care team members maintain this assumption. Thus, this study seeks to explore how health care team members understand the role of physician fatigue in an effort to inform the implementation of fatigue risk management in residency training and medical practice. METHODS:This study uses constructivist grounded theory to explore perceptions of workplace fatigue and its impact on clinical practice. We conducted individual semi-structured interviews with physicians, nurses and senior residents across four hospitals in 8 different specialties for a total of 40 participants. Constant comparative analysis guided data analysis and led to the final grounded theory. RESULTS:While participants outlined multiple problematic manifestations of physician fatigue on clinical performance, they were reluctant to acknowledge any negative impact of fatigue on patient care. We refer to these contradictions as the fatigue paradox. Four key themes sustain the fatigue paradox: the indefatigable physician, blind spots, faith in safety nets and the minimisation of fatigue-related events. CONCLUSIONS:This study suggests that health care team members do not universally feel that physician fatigue is problematic for patient care, despite providing multiple examples to the contrary. This paradoxical understanding of fatigue likely exists because the system relies on fatigued physicians, particularly trainees, and provides few mechanisms to critically examine fatigue. Successful implementation of fatigue risk management in residency training may prove elusive if clinical supervisors are skeptical of the potentially negative impact of workplace fatigue.
10.1111/medu.14591
Serum leptin level and its association with fatigue in patients with chronic hepatitis C virus infection.
El-Gindy Eman M,Ali-Eldin Fatma A,Meguid Marwa A
Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology
BACKGROUND AND STUDY AIM:Fatigue is one of the most common presenting symptoms of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly investigated. Serum leptin levels are increased in cirrhosis and are suggested to have a role in the mediation of fatigue. This study was designed to assess possible association of serum leptin levels with fatigue and severity of liver disease in Egyptian patients with chronic hepatitis C infection. PATIENTS AND METHODS:Seventy patients and 20 control subjects participated in the study. They were subjected to clinical and laboratory assessment, the determination of serum leptin level by ELISA and the assessment of fatigue using the multidimensional assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue patterns for the past week. The MAF is a revision of the Piper Fatigue Scale. RESULTS:Fatigue was present in all patients (100%) and 13 subjects of the control group (65%). There was a highly significant statistical difference between cases and controls regarding the presence and severity of fatigue. Serum leptin level was significantly higher in cases (24.9±28) in comparison to the control subjects (14.8±8). Serum leptin was not related to severity of liver disease as assessed by the Child Pugh classification. Serum leptin levels were directly correlated to the severity of fatigue (p<0.01) in patients but not in the control subjects. CONCLUSION:Fatigue is highly prevalent in Egyptian patients with chronic HCV infection. Leptin might play a role in the mediation of fatigue in those patients drawing attention to biological basis of one of the most common symptoms facing clinician dealing with this problem.
10.1016/j.ajg.2012.05.001
Exosomal circKIAA1797 Regulates Cell Progression and Glycolysis by Targeting miR-4429/PBX3 Pathway in Gastric Cancer.
Biochemical genetics
In recent years, circular RNAs (circRNAs) are extensively studied in the progression of various types of cancer, while the mechanism of circKIAA1797 is rarely studied in gastric cancer (GC). Hence, this research aimed to investigate the expression of exosomal circKIAA1797 and its biological function in GC cells. Exosomes were extracted from the serum of GC patients and identified by transmission electron microscopy (TEM) and nanoparticle tracking analyzer (NTA). CD81, CD63, Bcl-2, Bax, and pre-leukemia transcription factor 3 (PBX3) protein levels were detected using western blot assay. circKIAA1797, microRNA-4429 (miR-4429), and PBX3 mRNA were determined by quantitative real-time PCR (RT-qPCR). Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and flow cytometry assay. Glucose consumption and lactate production levels were examined using glycolysis detection kits. The interaction between miR-4429 and circKIAA1797 or PBX3 was identified using dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. Xenograft mouse model assay was used to investigate the effect of exosomal circKIAA1797 in vivo. It was found that circKIAA1797 was up-regulated in GC tissues and cells, as well as in the exosomes derived from the serum of GC patients. Silencing of exosomal circKIAA1797 could hamper cell progression and glycolytic metabolism of GC. Mechanically, circKIAA1797 acted as a sponge of miR-4429 to regulate PBX3 expression. Moreover, the knockdown of exosomal circKIAA1797 repressed tumor growth in vivo. Our data demonstrated that knockdown of exosomal circKIAA1797 suppressed GC malignant phenotypes by regulating miR-4429/PBX3 axis, which might offer a promising therapeutic strategy for GC treatment.
10.1007/s10528-023-10529-z
Association between Interleukin-6 Levels and Perioperative Fatigue in Gastric Adenocarcinoma Patients.
Wu Jin-Ming,Yang Hui-Ting,Ho Te-Wei,Shun Shiow-Ching,Lin Ming-Tsan
Journal of clinical medicine
BACKGROUND:Gastric adenocarcinoma (GA), one of the most common gastrointestinal cancers worldwide, is often accompanied by cancer cachexia in the advanced stage owing to malnutrition and cancer-related symptoms. Although resection is the most effective curative procedure for GA patients, it may cause perioperative fatigue, worsening the extent of cancer cachexia. Although the relationship between cytokines and cancer fatigue has been evaluated, it is unclear which cytokines are associated with fatigue in GA patients. Therefore, this study aimed to investigate whether the changes in cytokine levels were associated with the perioperative changes in fatigue amongst GA patients. METHODS:We included GA patients undergoing gastric surgery in a single academic medical center between June 2017 and December 2018. Fatigue-related questionnaires, serum cytokine levels (interferon-gamma, interleukin (IL)-1, IL-2, IL-5, IL-6, IL-12 p70, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor), and biochemistry profiles (albumin, prealbumin, C-reactive protein, and white blood cell counts) were assessed at three time points (preoperative day 0 (POD 0), post-operative day 1 (POD 1), and postoperative day 7 (POD 7)). We used the Brief Fatigue Inventory-Taiwan Form to assess the extent of fatigue. The change in fatigue scores among the three time points, as an independent variable, was adjusted for clinicopathologic characteristics, malnutrition risk, and cancer stages. RESULTS:A total of 34 patients were included for analysis, including 12 female and 22 male patients. The mean age was 68.9 years. The mean score for fatigue on POD 0, POD 1, and POD 7 was 1.7, 6.2, and 3.6, respectively, with significant differences among the three time points ( < 0.001). Among the cytokines, only IL-6 was significantly elevated from POD 0 to POD 1. In the regression model, the change in IL-6 levels between POD 0 and POD 1 (coefficients = 0.01 for every 1 pg/mL increment; 95% confidence interval: 0.01-0.02; = 0.037) and high malnutrition risk (coefficients = 2.80; 95% confidence interval: 1.45-3.52; = 0.041) were significantly associated with changes in fatigue scores. CONCLUSIONS:The perioperative changes in plasma IL-6 levels are positively associated with changes in the fatigue scores of GA patients undergoing gastric surgery. Targeting the IL-6 signaling cascade or new fatigue-targeting medications may attenuate perioperative fatigue, and further clinical studies should be designed to validate this hypothesis.
10.3390/jcm8040543
Attitudes About Coping With Fatigue in Patients With Gastric Cancer: A Q-Methodology Study.
Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates
Cancer-related fatigue is the most common symptom in patients with cancer. Coping methods for cancer-related fatigue differ from those of patients without cancer, as the situations faced by patients with cancer are unique. This study aimed to identify subjectivity concerning coping with fatigue in Korean patients with gastric cancer. Q-methodology was used to examine subjective perceptions regarding coping with fatigue among Korean patients with gastric cancer. A convenience sample of 33 participants, who had been hospitalized in 2 university hospitals in South Korea, was recruited to participate in the study and 37 selected Q-samples were classified into a normal forced distribution using a 9-point bipolar grid. The obtained data were analyzed by using PC-QUANL for Windows. Three factors representing distinct attitudes about coping with fatigue emerged among Korean patients with gastric cancer: an optimistic mind, dependency on medicine, and exercise preference. The 3 factors explained 39.4% of the total variance (23.7%, 7.9%, and 7.8%, respectively). Based on the study findings, it is important to develop customized nursing interventions that consider the characteristics of each patient group with gastric cancer. Health professionals should assess the attitudes of patients with gastric cancer about coping with fatigue, explore their situation, and consider their lifestyle.
10.1097/SGA.0000000000000390
Symptom Clusters and Quality of Life in Gastric Cancer Patients Receiving Chemotherapy.
Fu Liang,Feng Xiuqin,Jin Yongyan,Lu Zhenqi,Li Rufang,Xu Wenxia,Chang Victor T,Hu Yan,Ye Xianghong
Journal of pain and symptom management
CONTEXT:Although gastric cancer is one of the most common tumors worldwide, there is little knowledge about symptom clusters and quality of life (QoL) in this population. OBJECTIVES:The objectives were to identify the symptom clusters in gastric cancer patients receiving chemotherapy, and explore their effects on QoL. METHODS:Gastric cancer patients receiving chemotherapy were recruited. Data were collected using the Memorial Symptom Assessment Scale Short Form, the Functional Assessment of Cancer Therapy-Gastric and the self-designed General Information Evaluation Form. The symptom clusters were extracted through the exploratory factor analysis. The influencing factors of symptom clusters and their effects on QoL were identified using multiple linear regression analysis. RESULTS:A total of 322 participants were enrolled from three medical centers. Five factors were identified in this exploratory factor analysis based on symptom prevalence, namely fatigue related symptom cluster, epithelial symptom cluster, neurologic symptom cluster, malnutrition related symptom cluster and psychological symptom cluster (χ = 31.470, P < 0.05). The affecting factors across symptom clusters and QoL subscales were relatively stable, but also different. Generally, fatigue related symptom cluster, malnutrition related symptom cluster and psychological symptom cluster demonstrated significantly negative effects on all aspects of QoL except social well being. CONCLUSION:Five symptom clusters were identified in gastric cancer patients receiving chemotherapy in mainland China. The symptom clusters negatively contributed to the variance in all aspects of QoL except social well being. Further studies should examine interventions for symptom clusters, their influencing factors, and their effects on improving QoL.
10.1016/j.jpainsymman.2021.09.003
MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia.
Marceca Gioacchino P,Nigita Giovanni,Calore Federica,Croce Carlo M
Frontiers in oncology
Cancer-associated cachexia is a heterogeneous, multifactorial syndrome characterized by systemic inflammation, unintentional weight loss, and profound alteration in body composition. The main feature of cancer cachexia is represented by the loss of skeletal muscle tissue, which may or may not be accompanied by significant adipose tissue wasting. Such phenotypic alteration occurs as the result of concomitant increased myofibril breakdown and reduced muscle protein synthesis, actively contributing to fatigue, worsening of quality of life, and refractoriness to chemotherapy. According to the classical view, this condition is primarily triggered by interactions between specific tumor-induced pro-inflammatory cytokines and their cognate receptors expressed on the myocyte membrane. This causes a shift in gene expression of muscle cells, eventually leading to a pronounced catabolic condition and cell death. More recent studies, however, have shown the involvement of regulatory non-coding RNAs in the outbreak of cancer cachexia. In particular, the role exerted by microRNAs is being widely addressed, and several mechanistic studies are in progress. In this review, we discuss the most recent findings concerning the role of microRNAs in triggering or exacerbating muscle wasting in cancer cachexia, while mentioning about possible roles played by long non-coding RNAs and ADAR-mediated miRNA modifications.
10.3389/fonc.2020.607196
Perceptions about traditional Chinese medicine use among Chinese breast cancer survivors: A qualitative study.
Cancer medicine
INTRODUCTION:An increasing number of breast cancer survivors (BCS) use traditional Chinese medicine (TCM) throughout their cancer journey. There is emerging evidence that TCM is effective in the reducing side effects of chemotherapy. However, qualitative patient-centric and culturally relevant research into TCM use is scant. This qualitative study aimed to explore the use and perceptions of Chinese Hong Kong BCS using TCM. METHODS:Participants were recruited from a university hospital and three breast cancer patient groups in Hong Kong. Questionnaires regarding the use of TCM were given to all participants, followed by individual semi-structured interviews on selected BCS to comprehensively understand TCM's use and perceptions. A greater emphasis was placed on the qualitative data. RESULTS:About half of the participants (n = 67, 48.9%) used TCM during their cancer treatment journey, among which almost all (n = 64, 95.5%) had improved symptoms. Sleeping disturbances (n = 58, 86.6%) and fatigue (n = 53, 79.1%) were the two most common symptoms that improved after TCM. Interview data revealed that participants used TCM to satisfy unmet needs that mainstream conventional Western medicine could not fulfil. They wished for a sense of control and better well-being. They expressed improvements in physical and psychological well-being after the use of TCM. Despite existing barriers, including high cost, long duration of treatment, and disapproval from oncologists, most would still recommend TCM to fellow survivors. CONCLUSIONS:Chinese Hong Kong BCS who used TCM reported positive experiences. Understanding how BCS perceive and use TCM is important to integrating TCM into survivorship care in this population.
10.1002/cam4.5046
Patient and caregiver perceptions of lymphoma care and research opportunities: A qualitative study.
Payne Jackelyn B,Dance Kaylin V,Farone Monique,Phan Anh,Ho Cathy D,Gutierrez Meghan,Chen Lillian,Flowers Christopher R
Cancer
BACKGROUND:Although the number of lymphoma survivors has increased, the needs and research priorities of survivors and their caregivers rarely are examined and addressed. Determining the needs and priorities for this population requires an assessment of the attitudes and experiences of patients and caregivers. The authors conducted a qualitative study with lymphoma survivors and their caregivers to determine care needs and research priorities. METHODS:In the first phase, 2 semistructured focus groups were conducted with 15 lymphoma survivors and their caregivers. In phase 2, a total of 19 individual semistructured telephone interviews were conducted with lymphoma survivors and their caregivers. In both phases, participants discussed cancer experiences and research priorities. All interviews were transcribed. MAXQDA software (version 18.0.8) was used for coding and identifying themes. RESULTS:The majority of participants felt disconnected from their clinical care team due to a lack of communication. Focus group participants noted a lack of information regarding diagnoses, treatment, research, and survivorship care. Participants coped with fear through strong social support and fostering relationships with their clinical care teams. Some caregivers felt completely ignored by clinicians. Participants expressed interest in research, but had difficulty finding relevant studies. Several interviewees desired holistic and survivorship-oriented research and more studies regarding quality of life and mental health. CONCLUSIONS:The results of the current study identified unmet needs in clinical care and patient-oriented research, including needs for a focus on quality of life after treatment, communication between patients and the scientific community, and emotional well-being. Health care professionals can use these data to provide care delivery, supportive services, and research that meets the needs of lymphoma survivors and their caregivers.
10.1002/cncr.32401
Profiles Combining Muscle Atrophy and Neutrophil-to-Lymphocyte Ratio Are Associated with Prognosis of Patients with Stage IV Gastric Cancer.
Shigeto Kota,Kawaguchi Takumi,Koya Shunji,Hirota Keisuke,Tanaka Toshimitsu,Nagasu Sachiko,Fukahori Masaru,Ushijima Tomoyuki,Matsuse Hiroo,Miwa Keisuke,Nagafuji Koji,Torimura Takuji
Nutrients
We aimed to investigate the impact of muscle atrophy and the neutrophil-to-lymphocyte ratio (NLR), a sub-clinical biomarker of inflammation and nutrition, on the prognosis of patients with unresectable advanced gastric cancer. We retrospectively enrolled 109 patients with stage IV gastric cancer (median age 69 years; female/male 22%/78%; median observational period 261 days). Independent factors and profiles for overall survival (OS) were determined by Cox regression analysis and decision-tree analysis, respectively. OS was calculated using the Kaplan-Meier method. The prevalence of muscle atrophy was 82.6% and the median NLR was 3.15. In Cox regression analysis, none of factors were identified as an independent factor for survival. The decision-tree analysis revealed that the most favorable prognostic profile was non-muscle atrophy (OS rate 36.8%). The most unfavorable prognostic profile was the combination of muscle atrophy and high NLR (OS rate 19.6%). The OS rate was significantly lower in patients with muscle atrophy and high NLR than in patients with non-muscle atrophy (1-year survival rate 28.5% vs. 54.7%; log-rank test = 0.0014). In conclusion, "muscle atrophy and high NLR" was a prognostic profile for patients with stage IV gastric cancer. Thus, the assessment of muscle mass, subclinical inflammation, and malnutrition may be important for the management of patients with stage IV gastric cancer.
10.3390/nu12061884
Long-Term Yogic Intervention Improves Symptomatic Scale and Quality of Life by Reducing Inflammatory Cytokines and Oxidative Stress in Breast Cancer Patients Undergoing Chemotherapy and/or Radiotherapy: A Randomized Control Study.
Cureus
INTRODUCTION:Inflammation has been associated with tumor proliferation and metastasis in breast cancer. Yoga is an ancient therapy that helps in reducing inflammation and improves the patient's quality of life (QoL) and fatigue. In the current study, we investigated the effects of long-term yogic intervention at different time points on the level of inflammatory cytokines and oxidative stress, along with the symptomatic scale and QoL in stage II/III breast cancer patients. METHODS:Ninety-six stage II/III breast cancer patients receiving chemotherapy and/or radiotherapy were enrolled and divided into two groups, non-yoga (Group I) and yoga (Group II). Participants in Group II practiced yoga five days per week for 48 weeks. The European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ30) was used to measure the QoL and symptomatic scale. Serum levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and granulocyte macrophage colony-stimulating factor (GM-CSF), and oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and nitric oxide (NO) were measured at baseline, 16, 32, and 48 weeks in both groups. RESULTS:Yoga significantly (p<0.05) reduced the level of IFN-γ, TNF-α, and MDA and improved QoL (p<0.001) and symptomatic scale (p<0.05) in Group II patients compared to Group I. NO was upregulated in Group I whereas in Group II, it was neither decreased nor increased. CONCLUSION:These findings suggest that yoga may reduce levels of inflammatory cytokines and improve QoL and symptomatic scale in breast cancer patients receiving chemotherapy and/or radiotherapy. Yoga can be an important additional therapy during cancer treatments to cope with treatment side effects including fatigue, depression, and immunological profile, which directly affects the patient's quality of life.
10.7759/cureus.33427
Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2.
Frontiers in immunology
can cause respiratory diseases, arthritis, genitourinary tract infections, and chronic fatigue syndrome and have been linked to the development of the human immunodeficiency virus. Because mycoplasma lacks a cell wall, its outer membrane lipoproteins are one of the main factors that induce inflammation in the organism and contribute to disease development. Macrophage-activating lipopeptide-2 (MALP-2) modulates the inflammatory response of monocytes/macrophages in a bidirectional fashion, indirectly enhances the cytotoxicity of NK cells, promotes oxidative bursts in neutrophils, upregulates surface markers on lymphocytes, enhances antigen presentation on dendritic cells and induces immune inflammatory responses in sebocytes and mesenchymal cells. MALP-2 is a promising vaccine adjuvant for this application. It also promotes vascular healing and regeneration, accelerates wound and bone healing, suppresses tumors and metastasis, and reduces lung infections and inflammation. MALP-2 has a simple structure, is easy to synthesize, and has promising prospects for clinical application. Therefore, this paper reviews the mechanisms of MALP-2 activation in immune cells, focusing on the application of MALP-2 in animals/humans to provide a basis for the study of pathogenesis in and the translation of MALP-2 into clinical applications.
10.3389/fimmu.2023.1113715
Targeting α7-nAChR by galantamine mitigates reserpine-induced fibromyalgia-like symptoms in rats: Involvement of cAMP/PKA, PI3K/AKT, and M1/M2 microglia polarization.
European journal of pharmacology
Fibromyalgia (FM) is a pain disorder marked by generalized musculoskeletal pain accompanied by depression, fatigue, and sleep disturbances. Galantamine (Gal) is a positive allosteric modulator of neuronal nicotinic acetylcholine receptors (nAChRs) and a reversible inhibitor of cholinesterase. The current study aimed to explore the therapeutic potential of Gal against reserpine (Res)-induced FM-like condition along with investigating the α7-nAChR's role in Gal-mediated effects. Rats were injected with Res (1 mg/kg/day; sc) for 3 successive days then Gal (5 mg/kg/day; ip) was given alone and with the α7-nAChR blocker methyllycaconitine (3 mg/kg/day; ip), for the subsequent 5 days. Galantamine alleviated Res-induced histopathological changes and monoamines depletion in rats' spinal cord. It also exerted analgesic effect along with ameliorating Res-induced depression and motor-incoordination as confirmed by behavioral tests. Moreover, Gal produced anti-inflammatory effect through modulating AKT1/AKT2 and shifting M1/M2 macrophage polarization. The neuroprotective effects of Gal were mediated through activating cAMP/PKA and PI3K/AKT pathways in α7-nAChR-dependent manner. Thus, Gal can ameliorate Res-induced FM-like symptoms and mitigate the associated monoamines depletion, neuroinflammation, oxidative stress, apoptosis, and neurodegeneration through α7-nAChR stimulation, with the involvement of cAMP/PKA, PI3K/AKT, and M1/M2 macrophage polarization.
10.1016/j.ejphar.2023.175810
Toll-like receptor 4 mediates the development of fatigue in the murine Lewis Lung Carcinoma model independently of activation of macrophages and microglia.
Vichaya Elisabeth G,Ford Bianca G,Quave Cana B,Rishi M Raafay,Grossberg Aaron J,Dantzer Robert
Psychoneuroendocrinology
Cancer-related fatigue at the time of tumor diagnosis is commonly attributed to inflammation associated with the disease process. However, we have previously demonstrated that running wheel deficits occur well before increased expression of proinflammatory cytokines in the liver and brain in a murine model of human papilloma virus-related head and neck cancer (mEER). Further, we have demonstrated that genetic deletion of type I interleukin-1 receptor and MyD88 has no effect. In the current investigation we sought to test the generality of this finding by assessing whether there is a role for toll-like receptor (TLR) 4-dependent inflammation in the fatigue-like behavior observed in mice with Lewis Lung Carcinoma (LLC) or mEER tumors. Genetic deletion of TLR4 attenuated tumor-induced elevations in liver pro-inflammatory cytokine expression in both models. However, it only abrogated wheel running deficits in LLC tumor bearing mice. To determine whether TLR4 signaling in the LLC model involves innate immune cells, mice were treated with the colony stimulating factor (CSF)-1 receptor antagonist PLX-5622 before and throughout tumor development to deplete microglia and peripheral macrophages. Administration of PLX-5622 had no protective effect on wheel running deficits in either mEER or LLC tumor models despite effective depletion of microglia and a down regulation of peripheral proinflammatory cytokine expression. These results indicate that the TLR4 signaling that mediates fatigue-like behavior in LLC mice is not dependent upon microglial or peripheral macrophage activation. Based on the literature and our data demonstrating attenuation of ubiquitin proteasome pathway activation in the gastrocnemius muscle of Tlr4 mice implanted with LLC cells, we interpret our current findings as indication that skeletal muscle TLR4 signaling may be involved. These results are important in that they add to the evidence that tumor-induced fatigue develops independently from classical neuroinflammation.
10.1016/j.psyneuen.2020.104874
[Mechanism of Cistanches Herba in treatment of cancer-related fatigue based on network pharmacology and experimental verification].
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 μg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.
10.19540/j.cnki.cjcmm.20221201.701
Molecular Replacement for Cancer Metabolic and Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Cancer Therapy.
Nicolson Garth L,Conklin Kenneth A
Cancer genomics & proteomics
During cancer treatment drug-induced oxidative stress can limit the effectiveness of therapy and cause a number of side effects such as fatigue, nausea, vomiting and diarrhea, as well as more serious adverse effects including cardiomyopathy, peripheral neuropathy, hepatotoxicity and pulmonary fibrosis. Many of these adverse effects are due to oxidative stress-mediated damage to normal tissues. Antioxidant administration and molecular replacement can mitigate the damage to normal tissues and reduce the adverse effects of cancer therapy without loss of therapeutic potential. For example, loss of efficiency in the electron transport chain caused by membrane peroxidation and reduction in coenzyme Q can occur during cytotoxic therapy. Molecular replacement of membrane lipids and enzymatic cofactors administered as nutritional supplements with antioxidants can prevent oxidative membrane damage and reduction of cofactors in normal tissues, restore mitochondrial and other cellular functions and reduce the adverse effects of cancer therapy. Recent clinical trials using cancer and non-cancer patients with chronic fatigue have shown the benefit of Molecular Replacement Therapy plus antioxidants in restoring mitochondrial electron transport function, reducing moderate to severe chronic fatigue and protecting mitochondrial and other cellular structures and enzymes from oxidative or other damage due to cytotoxic therapy.
Relationships between expression of , mitochondrial bioenergetics, and fatigue among patients with prostate cancer.
Hsiao Chao-Pin,Chen Mei-Kuang,Veigl Martina L,Ellis Rodney,Cooney Matthew,Daly Barbara,Hoppel Charles
Cancer management and research
Cancer-related fatigue (CRF) is the most debilitating symptom with the greatest adverse side effect on quality of life. The etiology of this symptom is still not understood. The purpose of this study was to examine the relationship between mitochondrial gene expression, mitochondrial oxidative phosphorylation, electron transport chain complex activity, and fatigue in prostate cancer patients undergoing radiotherapy (XRT), compared to patients on active surveillance (AS). The study used a matched case-control and repeated-measures research design. Fatigue was measured using the revised Piper Fatigue Scale from 52 patients with prostate cancer. Mitochondrial oxidative phosphorylation, electron-transport chain enzymatic activity, and gene expression were determined using patients' peripheral mononuclear cells. Data were collected at three time points and analyzed using repeated measures ANOVA. The fatigue score was significantly different over time between patients undergoing XRT and AS (<0.05). Patients undergoing XRT experienced significantly increased fatigue at day 21 and day 42 of XRT (<0.01). Downregulated mitochondrial gene (BC1, ubiquinol-cytochrome c reductase, synthesis-like, 0.05) expression, decreased OXPHOS-complex III oxidation (0.05), and reduced activity of complex III were observed over time in patients with XRT. Moreover, increased fatigue was significantly associated with downregulated and decreased complex III oxidation in patients undergoing XRT. Our results suggest that BCS1L and complex III in mitochondrial mononuclear cells are potential biomarkers and feasible therapeutic targets for acute XRT-induced fatigue in this clinical population.
10.2147/CMAR.S203317
Integrated mitochondrial function and cancer-related fatigue in men with prostate cancer undergoing radiation therapy.
Hsiao Chao-Pin,Chen Mei-Kuang,Daly Barbara,Hoppel Charles
Cancer management and research
INTRODUCTION:Fatigue experienced by cancer patients is one of the most common symptoms with the greatest adverse effect on quality of life, but arguably the least understood. The purpose of this study was to explore changes in integrated mitochondrial function and fatigue in non-metastatic prostate cancer patients receiving localized radiation therapy (XRT). MATERIALS AND METHODS:We proposed a mitochondrial bioenergetics mechanism of radiation-induced fatigue linking impaired oxidative phosphorylation (OXPHOS) through complex III and decreased adenosine triphosphate (ATP) production as consequences of XRT. Integrated mitochondrial function was measured as mitochondrial OXPHOS from patients' peripheral blood mononuclear cells. Fatigue was measured using the revised Piper Fatigue Scale. Data were collected before (day 0) and at day 21 of XRT. RESULTS:At day 21 of XRT, fatigue symptom intensified in 15 prostate cancer patients (<0.05). Mitochondrial OXPHOS complex III-linked and uncoupled complex III rates were significantly decreased in mononuclear cells at day 21 during XRT compared to that before XRT (<0.05). Additionally, increased fatigue appeared to be associated with decreased OXPHOS complex III-linked respiration in patients undergoing XRT. CONCLUSION:Fatigue was associated with OXPHOS complex III-linked oxidation and a defect in oxidation starting at complex III in mononuclear cell mitochondria was revealed at day 21 of XRT in 15 prostate cancer patients. Complex III is a potential target for pharmacological and, in particular, nutraceutical interventions, eg, Q10, for design of interventions for CRF.
10.2147/CMAR.S185706
Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma.
Grossberg Aaron J,Chu Linda C,Deig Christopher R,Fishman Eliot K,Hwang William L,Maitra Anirban,Marks Daniel L,Mehta Arnav,Nabavizadeh Nima,Simeone Diane M,Weekes Colin D,Thomas Charles R
CA: a cancer journal for clinicians
Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.
10.3322/caac.21626
Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:To provide guidance on exercise, diet, and weight management during active cancer treatment in adults. METHODS:A systematic review of the literature identified systematic reviews and randomized controlled trials evaluating the impact of aerobic and resistance exercise, specific diets and foods, and intentional weight loss and avoidance of weight gain in adults during cancer treatment, on quality of life, treatment toxicity, and cancer control. PubMed and the Cochrane Library were searched from January 2000 to May 2021. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS:The evidence base consisted of 52 systematic reviews (42 for exercise, nine for diet, and one for weight management), and an additional 23 randomized controlled trials. The most commonly studied types of cancer were breast, prostate, lung, and colorectal. Exercise during cancer treatment led to improvements in cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes. Preoperative exercise in patients with lung cancer led to a reduction in postoperative length of hospital stay and complications. Neutropenic diets did not decrease risk of infection during cancer treatment. RECOMMENDATIONS:Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. Evidence for other dietary and weight loss interventions during cancer treatment was very limited. The guideline discusses special considerations, such as exercise in individuals with advanced cancer, and highlights the critical need for more research in this area, particularly regarding diet and weight loss interventions during cancer treatment.Additional information is available at www.asco.org/supportive-care-guidelines.
10.1200/JCO.22.00687
Palliative Care and the Management of Common Distressing Symptoms in Advanced Cancer: Pain, Breathlessness, Nausea and Vomiting, and Fatigue.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Good symptom management in oncology is associated with improved patient and family quality of life, greater treatment compliance, and may even offer survival advantages. With population growth and aging, the proportion of patients with multiple symptoms-both related and unrelated to their cancer-is anticipated to increase, supporting calls for a more routine and integrated approach to symptom management. This article presents a summary of the literature for the use of symptom assessment tools and reviews the management of four common and distressing symptoms commonly experienced by people with advanced cancer: pain, breathlessness, nausea and vomiting, and fatigue. We also discuss the role of palliative care in supporting a holistic approach to symptom management throughout the cancer trajectory.
10.1200/JCO.19.00470
Acupuncture techniques and acupoints used in individuals under chemotherapy or radiotherapy treatment of cancer: A systematic review.
Journal of clinical nursing
AIMS AND OBJECTIVES:To describe the main acupuncture techniques and parameters that have been used in the most varied symptoms of different types of cancer. BACKGROUND:Clinical evidence about the potential effectiveness of acupuncture and related therapies to control signs and symptoms associated with cancer or its treatment has been in several studies. Currently, there is already evidence of the use of acupuncture for the treatment of nausea and vomiting, fatigue, dry mouth, anxiety, depression, insomnia and pain. However, many studies lack firm rights or reproducible guidelines for treatment. DESIGN:This study performs a systematic review of clinical trials related to the topic, based on the PRISMA protocol. Thus, a search was carried out in the Scopus, Pubmed and Web of Science databases, covering studies since January 2007. METHODS:Structured and organised according to PICO standards, using keywords ("cancer" OR "malignant tumour" OR "chemotherapy" OR "radiotherapy") AND ("acupuncture" OR "electroacupuncture") AND ("pain" OR "nausea" OR "vomit" OR "fatigue" OR "xerostomia" OR "insomnia" OR "depression" OR "neuropathy"). RESULTS:After the selection and evaluation phase, 23 studies were included and analysed. CONCLUSION:Based on this analysis, it is concluded that acupuncture is safe and there is evidence of the reduction of gastrointestinal symptoms, chemotherapy-induced peripheral neuropathy, pain, dry mouth, fatigue, insomnia, and improvement of cognitive capacity. RELEVANCE TO CLINICAL PRACTICE:Acupuncture treatments could act by minimising the side effects of conventional treatments and reducing symptoms induced by tumours. NO PATIENT OR PUBLIC CONTRIBUTION:The patients had no direct involvement with the study in question.
10.1111/jocn.16812
Research Status and Molecular Mechanism of the Traditional Chinese Medicine and Antitumor Therapy Combined Strategy Based on Tumor Microenvironment.
Frontiers in immunology
Treatment of malignant tumors encompasses multidisciplinary comprehensive diagnosis and treatment and reasonable combination and arrangement of multidisciplinary treatment, which is not a simple superimposition of multiple treatment methods, but a comprehensive consideration of the characteristics and specific conditions of the patients and the tumor. The mechanism of tumor elimination by restoring the body's immune ability is consistent with the concept of "nourishing positive accumulation and eliminating cancer by itself" in traditional Chinese medicine (TCM). The formation and dynamic changes in the tumor microenvironment (TME) involve many different types of cells and multiple signaling pathways. Those changes are similar to the multitarget and bidirectional regulation of immunity by TCM. Discussing the relationship and mutual influence of TCM and antitumor therapy on the TME is a current research hotspot. TCM has been applied in the treatment of more than 70% of cancer patients in China. Data have shown that TCM can significantly enhance the sensitivity to chemotherapeutic drugs, enhance tumor-suppressing effects, and significantly improve cancer-related fatigue, bone marrow suppression, and other adverse reactions. TCM treatments include the application of Chinese medicine monomers, extracts, classic traditional compound prescriptions, listed compound drugs, self-made compound prescriptions, as well as acupuncture and moxibustion. Studies have shown that the TCM functional mechanism related to the positive regulation of cytotoxic T cells, natural killer cells, dendritic cells, and interleukin-12, while negatively regulating of regulatory T cells, tumor-associated macrophages, myeloid-derived suppressive cells, PD-1/PD-L1, and other immune regulatory factors. However, the application of TCM in cancer therapy needs further study and confirmation. This article summarizes the existing research on the molecular mechanism of TCM regulation of the TME and provides a theoretical basis for further screening of the predominant population. Moreover, it predicts the effects of the combination of TCM and antitumor therapy and proposes further developments in clinical practice to optimize the combined strategy.
10.3389/fimmu.2020.609705
Acupuncture therapies for cancer-related fatigue: A Bayesian network meta-analysis and systematic review.
Frontiers in oncology
Background:Cancer-related fatigue (CRF) is one of the most commonly reported symptoms impacting cancer survivors. This study evaluated and compared the effectiveness and safety of acupuncture treatments for CRF. Methods:We searched PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine China National Knowledge Infrastructure, China Science and Technology Journal Database, and WanFang Database from inception to November 2022 to identify eligible randomized controlled trials (RCTs) comparing acupuncture treatments with sham interventions, waitlist (WL), or usual care (UC) for CRF treatment. The outcomes included the Cancer Fatigue Scale (CFS) and Pittsburgh Sleep Quality Index (PSQI), and pair-wise and Bayesian network meta-analyses were performed using STATA v17.0. Results:In total, 34 randomized controlled trials featuring 2632 participants were included. In the network meta-analysis, the primary analysis using CFS illustrated that point application (PA) + UC (standardized mean difference [SMD] = -1.33, 95% CI = -2.02, -0.63) had the highest probability of improving CFS, followed by manual acupuncture (MA) + PA (SMD = -1.21, 95% CI = -2.05, -0.38) and MA + UC (SMD = -0.80, 95% CI = -1.50, -0.09). Moreover, the adverse events of these interventions were acceptable. Conclusion:This study demonstrated that acupuncture was effective and safe on CRF treatment. However, further studies are still warranted by incorporating more large-scale and high-quality RCTs. Systematic review registration:https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022339769.
10.3389/fonc.2023.1071326
Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer.
Annals of surgical treatment and research
PURPOSE:We evaluated the changes in body composition (BC) and quality of life (QoL) in patients who underwent gastrectomy for advanced gastric cancer. METHODS:BC data using segmental multifrequency bioelectrical impedance analysis and QoL data from the EORTC (European Organisation for the Research and Treatment of Cancer) gathered via QLQ-C30 and QLQ-STO22 questionnaires were obtained from 300 patients preoperatively and at 1, 2, and 3 years after surgery. In total, 114 patients underwent total gastrectomy (TG group) and 186 underwent distal gastrectomy (DG group). RESULTS:According to BC analysis, at 3 years postoperatively, the average body weight (P = 0.002), protein mass (P = 0.028), body fat mass (P = 0.009), skeletal muscle mass (P = 0.037), and visceral fat area (P = 0.012) was significantly decreased in the TG group than in the DG group compared to the preoperative. In the QLQ-C30, physical functioning (P = 0.001), role functioning (P = 0.013), and fatigue (P = 0.005) showed significantly worse QoL in the TG group than in the DG group at 2 and 3 years postoperatively. In the QLQ-STO22, pain (P = 0.001), reflux symptoms (P = 0.009), eating restrictions (P = 0.001), anxiety (P = 0.008), taste (P = 0.011), and body image (P = 0.014) showed greater continuous deterioration postoperatively in the TG group than in the DG group. CONCLUSION:Persistent deterioration of BC and QoL is a serious concern following total gastrectomy. Long-term management of BC is required after gastrectomy and efforts should be made to improve the QoL in patients as soon as possible, postoperatively.
10.4174/astr.2020.98.5.262
Regulation and mechanism of action of miRNAs on insulin resistance in skeletal muscles.
Non-coding RNA research
The term "insulin resistance" is commonly understood as a decrease in the response of insulin-sensitive tissues to insulin at its sufficient concentration, leading to chronic compensatory hyperinsulinemia. Type 2 diabetes mellitus is based on mechanisms consisting in the development of resistance to insulin in target cells (hepatocytes, adipocytes, skeletal muscle cells), resulting in the termination of an adequate response of these tissues to interaction with insulin. Since in healthy people 75-80% of glucose is utilized by skeletal muscle, it is more likely that the main cause of insulin resistance is impaired insulin-stimulated glucose utilization by skeletal muscle. With insulin resistance, skeletal muscles do not respond to insulin at its normal concentration, thereby determining an increase in glucose levels and a compensatory increase in insulin production in response to this. Despite many years of studying diabetes mellitus (DM) and insulin resistance, the molecular genetic basis for the development of these pathological conditions is still the subject of numerous studies. Recent studies point to the involvement of microRNAs (miRNAs) as dynamic modifiers in the pathogenesis of various diseases. MiRNAs are a separate class of RNA molecules that play a key role in the post-transcriptional regulation of gene expression. Recent studies have shown that miRNAs dysregulation in DM is closely related to miRNAs regulatory abilities in skeletal muscle insulin resistance. This gave grounds to consider an increase or decrease in the expression of individual microRNAs in muscle tissue and consider them as new biomarkers for diagnosing and monitoring insulin resistance and promising directions for targeted therapy. This review presents the results of scientific studies examining the role of miRNAs in skeletal muscle insulin resistance.
10.1016/j.ncrna.2023.02.005
Prognostic role of pretreatment skeletal muscle index in gastric cancer patients: A meta-analysis.
Pathology oncology research : POR
The association between pretreatment skeletal muscle index (SMI) and long-term survival of gastric cancer patients remains unclear up to now. The aim of this meta-analysis was to identify the prognostic value of pretreatment SMI in gastric cancer. The PubMed, EMBASE and Web of Science electronic databases were searched up to 5 June 2022 for relevant studies. The primary outcome was overall survival (OS) and the second outcomes were disease-free survival (DFS) and cancer-specific survival (CSS). The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and survival of gastric cancer patients. All statistical analyses were conducted by STATA 15.0 software. A total of 31 retrospective studies involving 12,434 patients were enrolled in this meta-analysis. The pooled results demonstrated that lower pretreatment was significantly associated with poorer OS (HR = 1.53, < 0.001). Besides, lower pretreatment SMI was also related with worse DFS (HR = 1.39, < 0.001) and CSS (HR = 1.96, < 0.001). Pretreatment SMI was significantly associated with prognosis of gastric cancer patients and lower SMI predicted worse survival. However, more prospective high-quality studies are still needed to verify our findings.
10.3389/pore.2023.1611055
High intramuscular adipose tissue content was a favorable prognostic factor in patients with advanced gastric cancer treated with nivolumab monotherapy.
Journal of gastroenterology and hepatology
BACKGROUND:Nivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab. METHODS:We enrolled patients with AGC treated with nivolumab (n = 58, 67 years old, men/women 40/18). The subjects were classified into long-term or short-term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis. RESULTS:In decision tree analysis, immune-related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717 days (95% confidence interval [CI], 223 to not reached) in profile 1, 245 days (95% CI, 126 to 252) in profile 2, and 132 days (95% CI, 69 to 163) in profile 3. CONCLUSION:Immune-related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.
10.1111/jgh.16239
Low-level laser prevents doxorubicin-induced skeletal muscle atrophy by modulating AMPK/SIRT1/PCG-1α-mediated mitochondrial function, apoptosis and up-regulation of pro-inflammatory responses.
Ou Hsiu-Chung,Chu Pei-Ming,Huang Yu-Ting,Cheng Hui-Ching,Chou Wan-Ching,Yang Hsin-Lun,Chen Hsiu-I,Tsai Kun-Ling
Cell & bioscience
BACKGROUND:Doxorubicin (Dox) is a widely used anthracycline drug to treat cancer, yet numerous adverse effects influencing different organs may offset the treatment outcome, which in turn affects the patient's quality of life. Low-level lasers (LLLs) have resulted in several novel indications in addition to traditional orthopedic conditions, such as increased fatigue resistance and muscle strength. However, the mechanisms by which LLL irradiation exerts beneficial effects on muscle atrophy are still largely unknown. RESULTS:The present study aimed to test our hypothesis that LLL irradiation protects skeletal muscles against Dox-induced muscle wasting by using both animal and C2C12 myoblast cell models. We established SD rats treated with 4 consecutive Dox injections (12 mg/kg cumulative dose) and C2C12 myoblast cells incubated with 2 μM Dox to explore the protective effects of LLL irradiation. We found that LLL irradiation markedly alleviated Dox-induced muscle wasting in rats. Additionally, LLL irradiation inhibited Dox-induced mitochondrial dysfunction, apoptosis, and oxidative stress via the activation of AMPK and upregulation of SIRT1 with its downstream signaling PGC-1α. These aforementioned beneficial effects of LLL irradiation were reversed by knockdown AMPK, SIRT1, and PGC-1α in C2C12 cells transfected with siRNA and were negated by cotreatment with mitochondrial antioxidant and P38MAPK inhibitor. Therefore, AMPK/SIRT1/PGC-1α pathway activation may represent a new mechanism by which LLL irradiation exerts protection against Dox myotoxicity through preservation of mitochondrial homeostasis and alleviation of oxidative stress and apoptosis. CONCLUSION:Our findings may provide a novel adjuvant intervention that can potentially benefit cancer patients from Dox-induced muscle wasting.
10.1186/s13578-021-00719-w
Skeletal muscle mitochondrial dysfunction and muscle and whole body functional deficits in cancer patients with weight loss.
Journal of applied physiology (Bethesda, Md. : 1985)
Reductions in skeletal muscle mass and function are often reported in patients with cancer-associated weight loss and are associated with reduced quality of life, impaired treatment tolerance, and increased mortality. Although cellular changes, including altered mitochondrial function, have been reported in animals, such changes have been incompletely characterized in humans with cancer. Whole body and skeletal muscle physical function, skeletal muscle mitochondrial function, and whole body protein turnover were assessed in eight patients with cancer-associated weight loss (10.1 ± 4.2% body weight over 6-12 mo) and 19 age-, sex-, and body mass index (BMI)-matched healthy controls to characterize skeletal muscle changes at the whole body, muscle, and cellular level. Potential pathways involved in cancer-induced alterations in metabolism and mitochondrial function were explored by interrogating skeletal muscle and plasma metabolomes. Despite similar lean mass compared with control participants, patients with cancer exhibited reduced habitual physical activity (57% fewer daily steps), cardiorespiratory fitness [22% lower V̇o (mL/kg/min)] and leg strength (35% lower isokinetic knee extensor strength), and greater leg neuromuscular fatigue (36% greater decline in knee extensor torque). Concomitant with these functional declines, patients with cancer had lower mitochondrial oxidative capacity [25% lower O flux (pmol/s/mg tissue)] and ATP production [23% lower ATP production (pmol/s/mg tissue)] and alterations in phospholipid metabolite profiles indicative of mitochondrial abnormalities. Whole body protein turnover was unchanged. These findings demonstrate mitochondrial abnormalities concomitant with whole body and skeletal muscle functional derangements associated with human cancer, supporting future work studying the role of mitochondria in the muscle deficits associated with cancer. To our knowledge, this is the first study to suggest that skeletal muscle mitochondrial deficits are associated with cancer-associated weight loss in humans. Mitochondrial deficits were concurrent with reductions in whole body and skeletal muscle functional capacity. Whether mitochondrial deficits are causal or secondary to cancer-associated weight loss and functional deficits remains to be determined, but this study supports further exploration of mitochondria as a driver of cancer-associated losses in muscle mass and function.
10.1152/japplphysiol.00746.2021
(Pre)treatment risk factors for late fatigue and fatigue trajectories following radiotherapy for breast cancer.
International journal of cancer
Fatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (OR = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered.
10.1002/ijc.34640
Chinese Medicine in Cancer Treatment - How is it Practised in the East and the West?
So T-H,Chan S-K,Lee V H-F,Chen B-Z,Kong F-M,Lao L-X
Clinical oncology (Royal College of Radiologists (Great Britain))
Chinese medicine therapies in cancer treatment are very common in the East. Although it is usually classified as a form of complementary and alternative therapy in the West, Chinese medicine is an independent medical profession in Hong Kong and mainland China. It has a different perspective in understanding health and diseases compared with Western medicine. In oncology practice, whereas Western medicine focuses on direct tumour eradication by surgery, radiation therapy and systemic therapies, Chinese medicine focuses on restoring body balance and enhancing the body's defences (immunity), in addition to some cytotoxic herbal therapies. Most often patients, especially those in the East, receive both treatments. Chinese medicine is also commonly used to reduce side-effects from chemotherapy or radiation therapy, to aid recovery after an operation, to palliate symptoms and to address survivorship issues. However, this raises concerns of drug-herb interactions and toxicity in combination therapies. Commonly used Chinese medicine treatment modalities include acupuncture, moxibustion, diet therapy, prescribed Chinese medicine herbal decoction, single Chinese medicine herbs or supplements and tai chi. Although there is an increasing trend of Chinese medicine use in cancer patients in both the East and the West, the scientific evidence of safety and efficacy is often questioned by oncologists. This article reviews the current evidence in different Chinese medicine therapies in cancer management in both the East and the West.
10.1016/j.clon.2019.05.016
Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial.
Trials
BACKGROUND:Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. METHODS/DESIGN:This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. DISCUSSION:This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. TRIAL REGISTRATION:ClinicalTrials.gov NCT03607656 . Registered on 1 July 2018. The final protocol version is V1.1.
10.1186/s13063-022-06013-5
MOXIBUSTION ALLEVIATES GASTRIC PRECANCEROUS LESIONS IN RATS BY PROMOTING CELL APOPTOSIS AND INHIBITING PROLIFERATION-RELATED ONCOGENES.
Peng Li,Xie Yu-Feng,Wang Chen-Guang,Wu Huan-Gan,Liu Mi,Wang Ya-Dong,Ma Fu-Qiang,Chang Xiao-Rong,Yang Zong-Bao
African journal of traditional, complementary, and alternative medicines : AJTCAM
BACKGROUND:It is well known that gastric mucosa dysplasia and intestinal metaplasia are gastric precancerous lesions (GPL). Moxibustion treatment of (ST21) and (ST36) alleviated the inflammatory response and dysplasia of gastric mucosa in our previous study. The purpose of this study was to further examine the underlying mechanism of moxibustion treatment of ST21 and ST36 on GPL. MATERIALS AND METHODS:Sixty SD rats were divided into five groups and rats with GPL were treated with either moxibustion (ST), moxibustion (Sham), or vitacoenzyme. B-cell lymphoma 2 (bcl-2), tumor protein p53 (P53) and cellular Myc (C-MYC), which are related to cell apoptosis, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), argyrophilic nucleolar organizer region proteins (Ag-NORs), which are associated with cell proliferation, and cell signaling proteins, nuclear factor kappa B (NF-κB), epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal regulated kinase (p-ERK), were measured after moxibustion treatment. RESULTS:Compared with Control group, gastric mucosa in GPL group showed abnormal mucosal proliferation and pathological mitotic figure, the mRNA expression of bcl-2, P53 and C-MYC increased significantly ( < 0.01), the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κβ as well as EGFR/ERK signaling proteins also increased significantly ( < 0.01). Moxibustion treatment decreased gastric mucosal proliferation and pathological mitotic figure, down-regulated the mRNA expression of bcl-2, P53, C-MYC ( < 0.01), decreased the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κβ as well as EGFR/ERK signaling proteins significantly ( < 0.01). But moxibustion treatment of Sham didn't show the same effect on GPL. CONCLUSION:Moxibustion treatment inhibited cell apoptosis and reduced gastric mucosa dysplasia by inhibiting the expression of bcl-2, P53, C-MYC and decreased the activity of NF-κβ as well as EGFR/ERK signaling proteins.
10.21010/ajtcam.v14i2.16
Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.
Chen Kai-Bo,Wu Zhi-Wei,Wang Jun,Zhu Ling-Hua,Jin Xiao-Li,Chen Guo-Feng,Kang Mu-Xing,Huang Yi,Zhang Hang,Lin Le-Le,Shi Di-Ke,Wu Dan,Chen Jian-Feng,Chen Jian,Zhao Zhi-Qing
Trials
BACKGROUND:Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS:A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION:The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.
10.1186/s13063-022-06108-z
Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial.
Zhou Xin,Cao Shou-Gen,Tan Xiao-Jie,Liu Xiao-Dong,Li Ze-Qun,Kong Ling-Xin,Tian Yu-Long,Liu Dan,Shen Shuai,Sun Yu-Qi,Jiang Hai-Tao,Zhou Yan-Bing
Cancer management and research
Purpose:Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. Patients and Methods:We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1-3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. Results:Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1-5 (average: 2.55±0.21 vs 3.10±0.42, <0.001), and the use rate of opioids was lower (43.9 vs 75.0, =0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, <0.001) and defecation (72.20±16.24 vs 95.78±17.75, <0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, =0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, <0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. Conclusion:TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.
10.2147/CMAR.S292325
The feasibility and efficacy of perioperative auricular acupuncture technique via intradermal needle buried for postoperative movement-evoked pain after open radical gastrectomy: A randomized controlled pilot trial.
Wang Xiao-Qing,Xiao Lei,Duan Pei-Bei,Xu Qian,Yang Li-Hua,Wang A-Qin,Wang Yan
Explore (New York, N.Y.)
INTRODUCTION:Auricular acupuncture is widely used in the treatment of pain. Recently, the most commonly used method of auricular acupuncture is to embed an intradermal needle into the skin to enhance analgesia through continuous stimulation. We aimed to explore the efficacy and feasibility of this form of auricular acupuncture in the treatment of postoperative movement-evoked pain. METHODS:This single-blind randomized controlled pilot trial was conducted between 23/8/2019 and 10/1/2020. Forty patients were recruited and randomised to either the control group (n = 20) or the experimental group (n = 20). Patients in the control group received sham auricular acupuncture, while patients in the experimental group received auricular acupuncture. A standard routine analgesia was performed in both groups. The patients with NRS score≥4 were given rescue analgesia. Postoperative pain, use of opioids and other analgesics, postoperative recovery and patient's satisfaction were recorded. RESULTS:The credibility and feasibility of auricular acupuncture for postoperative pain were high in both groups. After auricular acupuncture, the scores of the postoperative movement-evoked pain had a tendency to decrease, but no significant difference was observed between two groups at any time point (P = 0.234∼0.888). The data on postoperative pain at rest confirmed that no significant difference was observed between two groups within 48 h of surgery (P = 0.134∼0.520), and the postoperative pain at rest scores decreased over time; however, from the third day, the pain at rest scores of the experimental group were decreased, and significant differences were observed between the two groups (P = 0.039∼0.047). As for use of rescue analgesic, total opioid consumption and the incidence of postoperative nausea and vomiting, there were no significant differences between the two groups (P = 0.311, P = 0.101, P = 0.661) . In terms of patients' satisfaction, the score of the experimental group was higher than that of the control group, and a significant difference was observed between the two groups (P = 0.000). As for adverse events, two participants reported pain and one patient reported discomfort at the insertion sites during the process of auricular acupuncture intervention, but they both were minor and tolerable. CONCLUSION:Auricular acupuncture may have a relief effect on mild postoperative pain at rest with pain score below 3, suggesting that it may be a feasible adjuvant method to relieve mild pain at rest. However, more multi-centre and large-sample studies are needed to verify this result.
10.1016/j.explore.2021.09.007
[Effect of grain-moxibustion on neutrophil to lymphocyte ratio and quality of life in patients with advanced gastric cancer].
Wang Li-Li,Wang Yan-Rong,Wang Jian-Wei,Guan Ling,Shu Man,Wang Tai-Zhong
Zhongguo zhen jiu = Chinese acupuncture & moxibustion
OBJECTIVE:To observe the effect of grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) on neutrophil to lymphocyte ratio (NLR) and quality of life (QOL) in patients with advanced gastric cancer. METHODS:Sixty patients with advanced gastric cancer were randomly divided into an observation group and a control group, 30 cases in each one. In the control group, conventional chemotherapy regimen combined with symptomatic treatment,such as antiemetic, acid-suppressive, liver-protecting drugs. On the basis of the treatment in the control group, grain-moxibustion was applied at Zusanli (ST 36) and Weishu (BL 21) in the observation group, 9 cones for each acupoint, once a day for a total of 90 days. The levels of NLR were observed before and after treatment, and the clinical efficacy and quality of life were evaluated in the two groups. RESULTS:After treatment, the value of NLR in the observation group was significantly lower than before treatment (<0.05), there was no significant difference before and after treatment in the control group (>0.05), and the descend range of observation group was larger than the control group (<0.05). The effective rates (RR) were 33.3% (10/30) in the observation group and 36.7% (11/30) in the control group, there was no significant difference between the two groups (>0.05). After treatment, the QOL in the observation group was improved in diarrhea, loss of appetite, fatigue, nausea and vomiting, general health states (<0.05), there was no significant difference in the control group before and after treatment in varions scores (>0.05), and the observation group was superior to the control group in fatigue, sleep disorder, loss of appetite, diarrhea and general health states after treatment (<0.05). CONCLUSION:Grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) can decrease NLR and improve QOL of patients with advanced gastric cancer.
10.13703/j.0255-2930.2019.11.009
Zusanli (ST36) Acupoint Injection with Neostigmine for Paralytic Postoperative Ileus following Radical Gastrectomy for Gastric Cancer: a Randomized Clinical Trial.
You Xiaolan,Wang Yuanjie,Wu Jian,Liu Qinghong,Liu Yanqing,Qian Yayun,Chen Jue,Tang Dong,Wang Daorong
Journal of Cancer
: The Zusanli (ST36) acupoint has been associated with treatment of various gastrointestinal conditions. There have been no studies of acupuncture therapy for paralytic postoperative ileus (PPOI). Patients with PPOI following gastrectomy for gastric cancer were randomized to receive ST36 acupoint injection with neostigmine, gluteal intramuscular injection with 1.0 mg neostigmine, ST36 acupuncture alone, or standard therapy. The main outcome was the effectiveness rate for recovery of peristalsis. Secondary outcomes were time to bowel sound recovery, time to first flatus, and time to first defecation. Tertiary outcomes were drug-related adverse events, including abdominal pain, diarrhea, nausea, vomiting, tearing, delirium, seizure, and anxiety. : ST36 acupoint injection with neostigmine and gluteal intramuscular injection of neostigmine gave a higher rate of peristalsis recovery, and the ST36 acupoint injection group showed significantly higher total effectiveness rate than that of the intramuscular injection group. These interventions gave significantly shorter times to bowel sound recovery, shorter times to first flatus and first defecation compared with ST36 acupuncture and standard post-operative therapy ( < 0.01). ST36 acupoint injection group gave shorter time to bowel sound recovery, shorter time to first flatus and first defecation than those of the intramuscular injection group ( < 0.01). Drug-related adverse events in the intramuscular injection group were more serious than in the ST36 acupoint injection group ( < 0.05). ST36 acupoint injection with neostigmine is safe and effective for treatment of PPOI.
10.7150/jca.24767
Effects of electroacupuncture on perioperative anxiety and stress response in patients undergoing surgery for gastric or colorectal cancer: Study protocol for a randomized controlled trial.
Frontiers in psychiatry
Background:Perioperative anxiety is one of the main psychological stresses experienced by patients who undergo cancer surgery. The surgery itself inevitably causes a stress response characterized by activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Both the perioperative anxiety and surgical stress response lead to increased levels of catecholamines and prostaglandins, which may be related to perioperative suppression of antimetastatic immunity and tumor-promoting alterations in the microenvironment. Hence, we designed this clinical trial to investigate the effect of electroacupuncture in reducing perioperative anxiety and surgical stress response. Methods:This is a randomized, single-center, parallel, and controlled clinical trial. Seventy-eight participants between the ages of 35 and 85 with gastric or colorectal cancer who plan to undergo tumorectomy will be randomly divided into an electroacupuncture group and a control group. The primary outcome will be the six-item short form of the State-Trait Anxiety Inventory score. The secondary outcomes will be the Amsterdam Preoperative Anxiety and Information Scale score; levels of plasma cortisol, adrenocorticotropic hormone, interleukin-6, and tumor necrosis factor-α; first exhaust time after surgery; postoperative quality of the recovery-15 score, numeric rating scale for pain score; and dosage of postoperative analgesics. Discussion:Cumulative studies revealed the efficacy of various types of acupuncture therapy with regard to reducing the anxiety and stress response caused by surgery. We expect that the results of this trial will provide high-quality clinical evidence for the choice of perioperative acupuncture for patients undergoing cancer surgery. Clinical trial registration:https://www.chictr.org.cn, identifier ChiCTR200003 7127.
10.3389/fpsyt.2023.1095650
Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: a pilot prospective cohort study.
Hsieh Yueh-Ling,Chou Li-Wei,Hong Shao-Fu,Chang Fei-Chi,Tseng Szu-Wen,Huang Chi-Chou,Yang Ching-Hsiang,Yang Chen-Chia,Chiu Wei-Feng
Acupuncture in medicine : journal of the British Medical Acupuncture Society
BACKGROUND:Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS:17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions. RESULTS:PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05). CONCLUSIONS:Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN.
10.1136/acupmed-2016-011112
Acupressure improves the postoperative comfort of gastric cancer patients: A randomised controlled trial.
Hsiung Wan-Ting,Chang Yi-Chuan,Yeh Mei-Ling,Chang Yung-Hsien
Complementary therapies in medicine
OBJECTIVE:This pilot study evaluated whether acupressure affected the postoperative comfort of gastric cancer patients following a subtotal gastrectomy. METHODS:A randomised controlled trial was conducted. Sixty patients were recruited from 141-bed general surgery ward at a 3000-bed medical centre in Northern Taiwan. Participants were randomly assigned to either a control group receiving regular postoperative care or to the experimental group receiving additional acupressure at acupoints of Neiquan (P6) and Zusanli (ST36) for 3 consecutive days. RESULTS:The similarities between two groups were in postoperative pain and the onset of postoperative nausea and vomiting (PONV) at the baseline. Following acupressure, significant differences were found in postoperative pain (P=.03) and time of first flatus (P=.04); but not PONV (P=.49), nor the time of first defecation (P=.34). CONCLUSIONS:Acupressure is a simple, noninvasive, safe, and economical procedure for improving the comfort of patients who undergo surgery for gastric cancer. Acupressure at the P6 and ST36 acupoints can improve postoperative comfort by alleviating pain and decreasing the time until first flatus. However, additional research is necessary to elucidate how acupressure can improve postoperative outcomes.
10.1016/j.ctim.2015.03.010
Chronic stress accelerates the process of gastric precancerous lesions in rats.
Zheng Jiayi,Cai Weiwu,Lu Xuen,He Wei,Li Ding,Zhong Haoyu,Yang Liangjun,Li Siyi,Li Haishan,Rafee Sereen,Zhao Ziming,Wang Qi,Pan Huafeng
Journal of Cancer
Gastrointestinal cancers account for 20% of all deaths worldwide. Gastric cancer (GC) patients are susceptible to psychological change, especially depression which is commonly induced by chronic stress. Gastric precancerous lesions (GPL) is an important prodromal stage in the occurrence of gastric cancer. Chronic stress influences the prognosis of GC and may influence the process of GPL as well. Sixty SD rats were randomly divided into a control group, GPL group, and GPL+CUMS group. In the GPL group, 200μg/mL N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) free drinking method combined with intermittent fasting was applied to establish the GPL animal model. Based on this, we combined the GPL rats with chronic unpredicted mild stress (CUMS) to establish a comprehensive model. We then evaluated their behavior by open field tests and sucrose preference tests. We tested the IL-6, IL-10, TNF-α, Ghrelin, Leptin and Somatostatin (SS) levels in serum and observed the expression of Ghrelin and Gastrokine 2(GKN2) in the gastric mucosa of rats with tumors by immunofluorescence. Our results showed that GPL and GPL+CUMS rats all displayed a significantly decreased total distance and mean velocity traveled in the open field test. The percentages of sucrose preference were significantly decreased in the GPL+CUMS group compared to the control group. In addition, IL-6 and TNF-α were significantly increased in both the GPL and GPL+CUMS groups. Furthermore, the GPL+CUMS group showed significantly increased TNF-α levels in serum compared to the GPL rats. Our results showed that the expression of NF-κB, p53, and BCL-2 were significantly increased while BAX was reduced in the GPL and GPL+CUMS groups. Moreover, Ghrelin and Leptin levels in serum were significantly decreased in the GPL and GPL+CUMS groups. SS levels in serum were significantly increased in the GPL+CUMS group. Additionally, we found that the GPL+CUMS rats with tumors not only had strong expression of GKN2 on the luminal side and the lamina propria of the gastric mucosa and tumor, but also had expression of Ghrelin on the luminal side of the gastric mucosa. The areas that showed strong expression of GKN2 and Ghrelin, are all located around the blood vessels in the tumor. GPL rats under chronic stress would aggravate the conditions of GPL, shorten the process of GPL, and increase the risk of tumorigenesis. In addition, the close monitoring of the mental health of cancer survivors and precancerous lesion patients is suggested to be of great significance in the prevention and treatment of cancer.
10.7150/jca.52658
Moxibustion for the side effects of surgical therapy and chemotherapy in patients with gastric cancer: A protocol for systematic review and meta-analysis.
Medicine
BACKGROUND:Side effects after surgical therapy and chemotherapy of gastric cancer substantially reduce patients' quality of life. This systematic review aims to investigate whether moxibustion, as a complementary treatment, is effective in alleviating side effects in patients with gastric cancer who underwent surgical therapy or chemotherapy. METHODS:We will systematically search nine English and Chinese electronic databases to find relevant randomized controlled trials (RCTs) that compare basic treatment with and without moxibustion for treating the side effects induced by surgical therapy or chemotherapy in patients with gastric cancer. The time frame of the search will be from inception to July 1, 2020, and the publication language will not be limited. The literature screening and data extraction will be completed independently by 2 reviewers. The Cochrane risk of bias tool will be used to assess the risk of bias. For the analyses of the side effects of both surgical therapy and chemotherapy, the primary outcomes are defined as the incidence of any side effect, response rate, and quality of life. For the analyses of the side effects of surgical therapy, the secondary outcomes include the incidence of each individual side effect, time to first flatus/defecation/bowel sounds, and length of in-hospital stay. For the analysis of the side effects of chemotherapy, the secondary outcomes include incidence of each individual side effect, white blood cell/red blood cell/platelets counts, and hemoglobin level. R v3.6.2 software will be used to perform the meta-analyses. The quality of evidence will be classified using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS:This study will provide the first systematic review evidence on the efficacy of moxibustion as adjuvant management for gastric cancer by rigorous quality assessment and appropriate data synthesis. The results will be submitted to a peer-reviewed journal for publication. CONCLUSION:The findings of this study will provide currently best evidence on moxibustion for patients with gastric cancer who underwent surgical therapy or chemotherapy and may impact clinical practice.PROSPERO registration number: CRD42020169511.
10.1097/MD.0000000000021087
Direct contact moxibustion promotes apoptosis of gastric cancer cells in rats by regulating intestinal flora.
Pan Li-Jia,Ma Shu-Ya,Wen Jing,Zhang Xiao-Qi,Xing Hai-Jiao,Jia Chun-Sheng
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan
OBJECTIVE:To examine whether direct contact moxibustion (DCM) can prevent and treat gastric cancer (GC) by regulating intestinal flora in rats. METHODS:Male Wistar rats were randomly divided into normal group, normal + DCM control group, model group, and model + DCM group. Gastric cancer rats were induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG, 20 mg/mL) by gavage. At the same time, the model rats and normal rats were given DCM at Zusanli (ST36), Weishu (BL21), and Zhongwan (CV12) for 16 weeks. After treatment, gastric tissues were collected to analyze the pathological changes and the apoptosis of gastric mucosa cells. In addition, the cecal stool was taken and analyzed by 16s rRNA sequencing. RESULTS:Gastric cancer-like pathological changes and different abundance of the intestinal flora were found in the model group. DCM promoted mucosa tissue apoptosis and regulated the abnormal changes of the intestinal microflora caused by MNNG; DCM also inhibited the growth of Ruminococcaceae and Prevotellaceae flora and promoted the growth of probiotic Akkermansia. Furthermore, DCM made the composition and abundance of intestinal microflora in the GC rats tending to the normal rats. CONCLUSION:DCM stimulating Zusanli (ST36), Weishu (BL21), and Zhongwan (CV12) promoted the apoptosis of gastric mucosa and delayed the progression of gastric cancer, possibly by decreasing Ruminococcaceae and Prevotellaceae bacteria (bacteria that produce short-chain fatty acids in the intestine) and promoting the growth of probiotic Akkermansia.
10.19852/j.cnki.jtcm.2021.06.011
Combined acupuncture and general anesthesia on immune and cognitive function in elderly patients following subtotal gastrectomy for gastric cancer.
Wang Ningke,Ou Yangwen,Qing Wenxiang
Oncology letters
This study investigated the effects of acupuncture combined with general anesthesia on postoperative immune and cognitive functions in elderly patients undergoing subtotal gastrectomy. We recruited 96 elderly patients who received anesthesia for subtotal gastrectomy and randomly divided them into control (n=48) and experimental (n=48) groups. The control group received general anesthesia and the experimental group received combined acupuncture and general anesthesia. We measured hemodynamic immediately before and after anesthesia induction, and immune observations before and after surgery. We found no significant differences in mean heart rate (HR), mean oxygen saturation (SpO2), and partial pressure of end-tidal carbon dioxide (PETCO2) in the perioperative period between the two groups. Mean arterial pressure (MAP) was lower in the experimental group than that in the control group (P<0.05). The levels of cluster of differentiation 3 (CD3), CD4 and CD4/CD8 in both groups were significantly lower after surgery in both groups (P<0.05). We also found some time-points in which the immune markers where significantly higher in the experimental group. In terms of adverse reactions, there were no differences in nausea, vomiting, and hypoxemia between the two groups (P>0.05), but the incidence of delayed recovery and postoperative agitation were significantly lower in the experimental group compared with those in the control group (P<0.05). One day after surgery, the experimental group showed better protection of cognitive function than the control group (P<0.05). Overall, combined acupuncture and general anesthesia in elderly gastric cancer patients receiving subtotal gastrectomy showed more stable hemodynamics and fewer stress responses during surgery. Thus, combined acupuncture and general anesthesia can shorten the recovery time from anesthesia, have less negative effects on immune function and decrease the incidence of postoperative cognitive impairment.
10.3892/ol.2017.7262
Long Noncoding RNA: Shining Stars in the Immune Microenvironment of Gastric Cancer.
Frontiers in oncology
Gastric cancer (GC) is a kind of malignant tumor disease that poses a serious threat to human health. The GC immune microenvironment (TIME) is a very complex tumor microenvironment, mainly composed of infiltrating immune cells, extracellular matrix, tumor-associated fibroblasts, cytokines and chemokines, all of which play a key role in inhibiting or promoting tumor development and affecting tumor prognosis. Long non-coding RNA (lncRNA) is a non-coding RNA with a transcript length is more than 200 nucleotides. LncRNAs are expressed in various infiltrating immune cells in TIME and are involved in innate and adaptive immune regulation, which is closely related to immune escape, migration and invasion of tumor cells. LncRNA-targeted therapeutic effect prediction for GC immunotherapy provides a new approach for clinical research on the disease.
10.3389/fonc.2022.862337
LncRNA and its role in gastric cancer immunotherapy.
Frontiers in cell and developmental biology
Gastric cancer (GC) is a potential dominant disease in tumor immunotherapy checkpoint inhibitors, and adoptive cell therapy have brought great hope to GC patients. However, only some patients with GC can benefit from immunotherapy, and some patients develop drug resistance. More and more studies have shown that long non-coding RNAs (lncRNAs) may be important in GC immunotherapy's prognosis and drug resistance. Here, we summarize the differential expression of lncRNAs in GC and their impact on the curative effect of GC immunotherapy, discuss potential mechanisms of activity in GC immunotherapy resistance regulated by lncRNAs. This paper reviews the differential expression of lncRNA in GC and its effect on immunotherapy efficacy in GC. In terms of genomic stability, inhibitory immune checkpoint molecular expression, the cross-talk between lncRNA and immune-related characteristics of GC was summarized, including tumor mutation burden (TMB), microsatellite instability (MSI), and Programmed death 1 (PD-1). At the same time, this paper reviewed the mechanism of tumor-induced antigen presentation and upregulation of immunosuppressive factors, as well as the association between Fas system and lncRNA, immune microenvironment (TIME) and lncRNA, and summarized the functional role of lncRNA in tumor immune evasion and immunotherapy resistance.
10.3389/fcell.2023.1052942
Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.
Journal of pain and symptom management
CONTEXT:Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES:This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS:In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS:Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION:EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.
10.1016/j.jpainsymman.2021.09.009
Treatment Alternative and High Safety Profile of Acupuncture Plus Chemotherapy for Advanced Gastric Cancer.
Evidence-based complementary and alternative medicine : eCAM
Objective:The aim of this study is to evaluate the safety and tumor marker level changes of acupuncture plus chemotherapy (FOLFOX4) for advanced gastric cancer. Methods:One hundred and twenty patients with advanced gastric cancer who were treated at our hospital between May 2019 and April 2021 were recruited for prospective analysis, and all patients were allocated to the control and experimental groups in a 1 : 1 ratio using the random number table method, with 60 patients in each group. They received either chemotherapy using the FOLFOX4 regimen (control group) or the FOLFOX4 chemotherapy plus acupuncture (experimental group). Outcome measures included tumor marker levels, quality of life, and adverse events. Results:Before treatment, the two groups showed similar tumor markers levels and the MOS 36-item short-form health survey (SF-36) scores ( > 0.05). FOLFOX4 chemotherapy plus acupuncture was associated with significantly lower levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 versus FOLFOX4 chemotherapy alone ( < 0.05). The patients who were given FOLFOX4 chemotherapy plus acupuncture showed significantly increased SF-36 scores versus monotherapy of the FOLFOX4 regimen ( < 0.05). The joint therapy resulted in a significantly lower incidence of adverse events versus the monotherapy ( < 0.05). Conclusion:Acupuncture plus chemotherapy using the FOLFOX4 regimen can effectively regulate the serum tumor marker levels of patients with advanced gastric cancer, with a high safety profile, which provides a viable treatment alternative.
10.1155/2022/8701779
Efficacy of Acupuncture and Moxibustion as a Subsequent Treatment after Second-Line Chemotherapy in Advanced Gastric Cancer.
Zhang Yong-Jie,Min Qi,Huang Ying,Liu Huai-Dong,Zhu Zi-Yuan,Jiang Fu-Jin,Hua Hai-Qing
Evidence-based complementary and alternative medicine : eCAM
Objective:To explore whether acupuncture and moxibustion can prevent disease progression of advanced gastric cancer patients completing second-line chemotherapy and, if so, the related mechanism. Method:Progression-free survival (PFS) and overall survival (OS) were main outcome measures. The real-time quantitative PCR was used to detect the expression of genes including T-bet, IFN-, GATA3, and IL-4 in peripheral blood mononuclear cells (PBMCs). IL-4, IL-6, Ca199, CRP, and IFN- in plasma levels were checked. Results:170 patients were randomly assigned in a 3 : 2 ratio to receive either acupuncture and moxibustion or sham acupuncture until progression. 135 patients were included in the primary analysis. Both PFS and OS in treatment group were proven to be better than control group. Acupuncture and moxibustion promoted typical Th1 cells drifting, as confirmed by increased T-bet/IFN- and decreased GATA3/IL-4 in mRNA levels from PBMCs, as well as upregulating IFN- and downregulating IL-4 in plasma levels. IL-6, Ca199, and CRP in plasma levels were also reduced by acupuncture and moxibustion. Conclusions:Acupuncture and moxibustion can prolong PFS and OS of advanced gastric cancer patients completing second-line chemotherapy by reversing Th1/Th2 shift and attenuating inflammatory responses.
10.1155/2020/8274021
EZH2: An Accomplice of Gastric Cancer.
Cancers
Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms. It has been found that EZH2 is overexpressed in the stomach, which promotes the progression of gastric cancer through multiple pathways. In addition, targeted inhibition of EZH2 expression can effectively delay the progression of gastric cancer and improve its resistance to chemotherapeutic agents. Given the many effects of EZH2 in gastric cancer, there are no studies to comprehensively describe this mechanism. Therefore, in this review, we first introduce EZH2 and clarify the mechanisms of abnormal expression of EZH2 in cancer. Secondly, we summarize the role of EZH2 in gastric cancer, which includes the association of the EZH2 gene with genetic susceptibility to GC, the correlation of the EZH2 gene with gastric carcinogenesis and invasive metastasis, the resistance to chemotherapeutic drugs of gastric cancer mediated by EZH2 and the high expression of EZH2 leading to poor prognosis of gastric cancer patients. Finally, we also clarify some of the current statuses of drug development regarding targeted inhibition of EZH2/PRC2 activity.
10.3390/cancers15020425
Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.
Oncogene
Gastric cancer (GC) is among the most lethal malignancies due to its poor early diagnosis and high metastasis rate, and new therapeutic targets are urgently needed to develop effective anti-GC drugs. Glutathione peroxidase-2 (GPx2) plays various roles in tumor progression and patient survival. Herein, we found that GPx2 was overexpressed and negatively correlated with poor prognosis by using clinical GC samples for validation. GPx2 knockdown suppressed GC proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo. In addition, proteomic analysis revealed that GPx2 expression regulated kynureninase (KYNU)-mediated metabolism. As one of the key proteins involved in tryptophan catabolism, KYNU can degrade the tryptophan metabolite kynurenine (kyn), which is an endogenous ligand for AhR. Next, we revealed that the activation of the reactive oxygen species (ROS)-mediated KYNU-kyn-AhR signaling pathway caused by GPx2 knockdown was involved in GC progression and metastasis. In conclusion, our results showed that GPx2 acted as an oncogene in GC and that GPx2 knockdown suppressed GC progression and metastasis by suppressing the KYNU-kyn-AhR signaling pathway, which was caused by the accumulation of ROS.
10.1038/s41388-023-02708-4
Interactions between gastric microbiota and metabolites in gastric cancer.
Dai Daofeng,Yang Yan,Yu Jieqing,Dang Tianfeng,Qin Wenjing,Teng Lisong,Ye Jing,Jiang Hongqun
Cell death & disease
The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.
10.1038/s41419-021-04396-y
Bone marrow microenvironment drives AML cell OXPHOS addiction and AMPK inhibition to resist chemotherapy.
Journal of leukocyte biology
The stromal niche plays a pivotal role in AML chemoresistance and energy metabolism reprogramming is a hallmark of a tumor. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor suppressing mammalian target of rapamycin complex 1 (mTORC1) activity. However, the role of AMPK-mTORC1 pathway on connecting AML cell energy metabolism reprogramming and chemoresistance induced by the bone marrow microenvironment (BMM) is not defined. Here, with a co-culture system that simulates the interaction between BMM and AML cells, it is shown that stromal contact led to a decreased sensitivity to chemotherapy accompanied by an increase of oxidative phosphorylation (OXPHOS) activity and mitochondrial ATP synthesis in AML cells. The increased OXPHOS activity and excessive ATP production promoted chemoresistance of AML cells through inhibiting AMPK activity and in turn activating mTORC1 activity. In an in vivo AML mouse model, depletion of AMPK activity with genetic targeting promoted AML progression and reduced their sensitivity to chemotherapeutic drugs. Collectively, AML cells' acquired increased OXPHOS activity as well as AMPK inhibition could be therapeutically exploited in an effort to overcome BMM-mediated chemoresistance.
10.1002/JLB.6A0821-409RR
Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer.
Seminars in cancer biology
Gastric cancer is a major source of global cancer mortality with limited treatment options and poor patient survival. As our molecular understanding of gastric cancer improves, we are now beginning to recognize that these cancers are a heterogeneous group of diseases with incredibly unique pathogeneses and active oncogenic pathways. It is this molecular diversity and oftentimes lack of common oncogenic driver mutations that bestow the poor treatment responses that oncologists often face when treating gastric cancer. In this review, we will examine the treatments for gastric cancer including up-to-date molecularly targeted therapies and immunotherapies. We will then review the molecular subtypes of gastric cancer to highlight the diversity seen in this disease. We will then shift our discussion to basic science and gastric cancer mouse models as tools to study gastric cancer molecular heterogeneity. Furthermore, we will elaborate on a molecular process termed paligenosis and the cyclical hit model as key events during gastric cancer initiation that impart nondividing mature differentiated cells the ability to re-enter the cell cycle and accumulate disparate genomic mutations during years of chronic inflammation and injury. As our basic science understanding of gastric cancer advances, so too must our translational and clinical efforts. We will end with a discussion regarding single-cell molecular analyses and cancer organoid technologies as future translational avenues to advance our understanding of gastric cancer heterogeneity and to design precision-based gastric cancer treatments. Elucidation of interpatient and intratumor heterogeneity is the only way to advance future cancer prevention, diagnoses and treatment.
10.1016/j.semcancer.2021.12.004
Current developments in gastric cancer: from molecular profiling to treatment strategy.
Nature reviews. Gastroenterology & hepatology
Gastric cancer and gastro-oesophageal junction cancer represent a global health-care challenge. Despite the efficacy of improved chemotherapy and surgical options, these patients still have a poor prognosis. In advanced disease, only trastuzumab and some immune checkpoint inhibitors, such as nivolumab and pembrolizumab in addition to chemotherapy, have demonstrated consistent and reliable efficacy in patients with HER2-positive and PDL1-positive tumours, respectively. In this Review, we discuss the intrinsic characteristics of gastric and gastro-oesophageal cancer from the molecular and clinical perspectives and provide a comprehensive review of previously reported and ongoing phase II and III clinical trials with targeted agents and immunotherapy in advanced and localized settings. Finally, we suggest alternative strategies to help overcome current challenges in precision medicine and to improve outcomes for these patients.
10.1038/s41575-022-00703-w