Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells.
Ferlazzo Guido,Tsang Ming L,Moretta Lorenzo,Melioli Giovanni,Steinman Ralph M,Münz Christian
The Journal of experimental medicine
During the innate response to many inflammatory and infectious stimuli, dendritic cells (DCs) undergo a differentiation process termed maturation. Mature DCs activate antigen-specific naive T cells. Here we show that both immature and mature DCs activate resting human natural killer (NK) cells. Within 1 wk the NK cells increase two-- to fourfold in numbers, start secreting interferon (IFN)-gamma, and acquire cytolytic activity against the classical NK target LCL721.221. The DC-activated NK cells then kill immature DCs efficiently, even though the latter express substantial levels of major histocompatibility complex (MHC) class I. Similar results are seen with interleukin (IL)-2--activated NK cell lines and clones, i.e., these NK cells kill and secrete IFN-gamma in response to immature DCs. Mature DCs are protected from activated NK lysis, but lysis takes place if the NK inhibitory signal is blocked by a human histocompatibility leukocyte antigen (HLA)-A,B,C--specific antibody. The NK activating signal mainly involves the NKp30 natural cytotoxicity receptor, and not the NKp46 or NKp44 receptor. However, both immature and mature DCs seem to use a NKp30 independent mechanism to act as potent stimulators for resting NK cells. We suggest that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.
10.1084/jem.20011149
Human NK Cells induce neutrophil apoptosis via an NKp46- and Fas-dependent mechanism.
Thorén Fredrik B,Riise Rebecca E,Ousbäck Jenny,Della Chiesa Mariella,Alsterholm Mikael,Marcenaro Emanuela,Pesce Silvia,Prato Carola,Cantoni Claudia,Bylund Johan,Moretta Lorenzo,Moretta Alessandro
Journal of immunology (Baltimore, Md. : 1950)
Polymorphonuclear neutrophils (PMN) are potent inflammatory effector cells essential to host defense, but at the same time they may cause significant tissue damage. Thus, timely induction of neutrophil apoptosis is crucial to avoid tissue damage and induce resolution of inflammation. NK cells have been reported to influence innate and adaptive immune responses by multiple mechanisms including cytotoxicity against other immune cells. In this study, we analyzed the effect of the interaction between NK cells and neutrophils. Coculture experiments revealed that human NK cells could trigger caspase-dependent neutrophil apoptosis in vitro. This event was dependent on cell-cell contact, and experiments using blocking Abs indicated that the effect was mediated by the activating NK cell receptor NKp46 and the Fas pathway. CD56-depleted lymphocytes had minimal effects on neutrophil survival, suggesting that the ability to induce neutrophil apoptosis is specific to NK cells. Our findings provide evidence that NK cells may accelerate neutrophil apoptosis, and that this interaction may be involved in the resolution of acute inflammation.
10.4049/jimmunol.1102002
Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma.
Barnig Cindy,Cernadas Manuela,Dutile Stefanie,Liu Xiaoli,Perrella Mark A,Kazani Shamsah,Wechsler Michael E,Israel Elliot,Levy Bruce D
Science translational medicine
Asthma is a prevalent disease of chronic inflammation in which endogenous counterregulatory signaling pathways are dysregulated. Recent evidence suggests that innate lymphoid cells (ILCs), including natural killer (NK) cells and type 2 ILCs (ILC2s), can participate in the regulation of allergic airway responses, in particular airway mucosal inflammation. We have identified both NK cells and ILC2s in human lung and peripheral blood in healthy and asthmatic subjects. NK cells were highly activated in severe asthma, were linked to eosinophilia, and interacted with autologous eosinophils to promote their apoptosis. ILC2s generated antigen-independent interleukin-13 (IL-13) in response to the mast cell product prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. Both NK cells and ILC2s expressed the pro-resolving ALX/FPR2 receptors. Lipoxin A4, a natural pro-resolving ligand for ALX/FPR2 receptors, significantly increased NK cell-mediated eosinophil apoptosis and decreased IL-13 release by ILC2s. Together, these findings indicate that ILCs are targets for lipoxin A4 to decrease airway inflammation and mediate the catabasis of eosinophilic inflammation. Because lipoxin A4 generation is decreased in severe asthma, these findings also implicate unrestrained ILC activation in asthma pathobiology.
10.1126/scitranslmed.3004812
Natural killer cells induce eosinophil activation and apoptosis.
Awad Ali,Yassine Hanane,Barrier Mathieu,Vorng Han,Marquillies Philippe,Tsicopoulos Anne,Duez Catherine
PloS one
Eosinophils are potent inflammatory cells with numerous immune functions, including antigen presentation and exacerbation of inflammatory responses through their capacity to release a range of largely preformed cytokines and lipid mediators. Thus, timely regulation of eosinophil activation and apoptosis is crucial to develop beneficial immune response and to avoid tissue damage and induce resolution of inflammation. Natural Killer (NK) cells have been reported to influence innate and adaptive immune responses by multiple mechanisms including cytotoxicity against other immune cells. In this study, we analyzed the effect of the interaction between NK cells and eosinophils. Co-culture experiments revealed that human NK cells could trigger autologous eosinophil activation, as shown by up-regulation of CD69 and down-regulation of CD62L, as well as degranulation, evidenced by increased CD63 surface expression, secretion of eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN). Moreover, NK cells significantly and dose dependently increased eosinophil apoptosis as shown by annexin V and propidium iodide (PI) staining. Direct contact was necessary for eosinophil degranulation and apoptosis. Increased expression of phosphorylated extracellular signal-regulated kinase (ERK) in cocultured eosinophils and inhibition of eosinophil CD63 expression by pharmacologic inhibitors suggest that MAPK and PI3K pathways are involved in NK cell-induced eosinophil degranulation. Finally, we showed that NK cells increased reactive oxygen species (ROS) expression by eosinophils in co-culture and that mitochondrial inhibitors (rotenone and antimycin) partially diminished NK cell-induced eosinophil apoptosis, suggesting the implication of mitochondrial ROS in NK cell-induced eosinophil apoptosis. Pan-caspase inhibitor (ZVAD-FMK) only slightly decreased eosinophil apoptosis in coculture. Altogether, our results suggest that NK cells regulate eosinophil functions by inducing their activation and their apoptosis.
10.1371/journal.pone.0094492
NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation.
Haworth Oliver,Cernadas Manuela,Levy Bruce D
Journal of immunology (Baltimore, Md. : 1950)
Immune responses are pathologically sustained in several common diseases, including asthma. To determine endogenous proresolving mechanisms for adaptive immune responses, we used a murine model of self-limited allergic airway inflammation. After cessation of allergen exposure, eosinophils and T cells were cleared concomitant with the appearance of increased numbers of NK cells in the lung and mediastinal lymph nodes. The mediastinal lymph node NK cells were activated, expressing CD27, CD11b, CD69, CD107a, and IFN-γ. NK cell depletion disrupted the endogenous resolution program, leading to delayed clearance of airway eosinophils and Ag-specific CD4(+) T cells. NK cell trafficking to inflamed tissues for resolution was dependent upon CXCR3 and CD62L. During resolution, eosinophils and Ag-specific CD4(+) T cells expressed NKG2D ligands, and a blocking Ab for the NKG2D receptor delayed clearance of these leukocytes. Of interest, NK cells expressed CMKLR1, a receptor for the proresolving mediator resolvin E1, and depletion of NK cells decreased resolvin E1-mediated resolution of allergic inflammation. Resolvin E1 regulated NK cell migration in vivo and NK cell cytotoxicity in vitro. Together, these findings indicate new functions in catabasis for NK cells that can also serve as targets for proresolving mediators in the resolution of adaptive immunity.
10.4049/jimmunol.1004007
Natural killer cells from patients with chronic rhinosinusitis have impaired effector functions.
Kim Ji Heui,Kim Gye Eun,Cho Gye Song,Kwon Hyung-Joon,Joo Chul Hyun,Kim Hun Sik,Jang Yong Ju
PloS one
Natural killer (NK) cells are multicompetent lymphocytes of the innate immune system that play a central role in host defense and immune regulation. Although increasing evidence suggests that innate immunity plays a key role in the pathogenesis of chronic rhinosinusitis (CRS), the role of NK cells in CRS has been poorly studied. This study aimed to characterize the peripheral blood NK cells from patients with CRS, and to compare the functions of these cells with those from non-CRS controls. The correlation between NK cell functional activity and prognosis was also assessed. Eighteen CRS patients and 19 healthy non-CRS controls were included. The patients with CRS were classified into two subgroups, namely a treatment-responsive group and recalcitrant group. NK cell degranulation was determined by measuring the cell surface expression of CD107a against 721.221 and K562 cells. Intracytoplasmic cytokine production was determined by flow cytometry. Compared to the controls, the NK cells of CRS group had an impaired ability to degranulate and to produce cytokines such as IFN-γ and TNF-α. The recalcitrant subgroup showed the most severe defects in NK cell effector functions. Moreover, the decreased NK cell functions in patients with CRS were associated with poor prognostic factors such as concomitant asthma and peripheral blood eosinophilia. NK cells, which were originally named for their ability to mediate spontaneous cytotoxicity towards diseased cells including infected cells, may play an important role in regulating the inflammatory process in CRS pathogenesis.
10.1371/journal.pone.0077177
Histological and immunological features of non-eosinophilic nasal polyps.
Kim Jeong-Whun,Hong Sung-Lyong,Kim Yoon-Keun,Lee Chul Hee,Min Yang-Gi,Rhee Chae-Seo
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
OBJECTIVE:The aim of this study was to investigate the histoimmunological features of non-eosinophilic nasal polyps (NPs). METHODS:Thirty patients with chronic rhinosinusitis and NPs were included in this study. NPs were grouped into eosinophilic and non-eosinophilic types according to the amount of eosinophils in the NPs. The amount of serum total IgE and peripheral blood eosinophils were measured. Basement membrane (BM) thickness was measured, along with the expression of chemokine receptor 5 (CCR5) and chemokine receptor 3 (CCR3) in NP lymphocytes. RESULTS:Non-eosinophilic NPs comprised 66.7% of the total NPs included in this study. The amount of eosinophils in NPs was related to eosinophilia of the peripheral blood, but not to elevated serum IgE. BM was significantly thinner in non-eosinophilic than in eosinophilic NPs. Lymphocytes expressing CCR5 or CCR3 were less frequently found in non-eosinophilic than in eosinophilic NPs. CONCLUSION:Histoimmunological characteristics of non-eosinophilic NPs differ from those of eosinophilic NPs; non-eosinophilic NPs may be featured by thinner BM and fewer CCR5- and CCR3-positive lymphocytes.
10.1016/j.otohns.2007.07.036
Clinical characteristics and surrogate markers of eosinophilic chronic rhinosinusitis in Southern China.
Zuo Kejun,Guo Jiebo,Chen Fenghong,Xu Rui,Xu Geng,Shi Jianbo,Li Huabin
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
The surrogate markers for subclassifying eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS remain elusive. We herein performed a cross-sectional study to assess the clinical implication of clinical symptoms, CT findings, blood eosinophil (EOS) examination based on histological examination of tissue eosinophilia in 105 adult CRS patients (including 72 with nasal polyps and 33 without nasal polyps) in southern China. We found the mean score of smell loss was significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05), whereas the average ethmoid osteitis index in non-ECRS subgroup was significantly higher than that in ECRS subgroup (p < 0.05). Moreover, we found both the mean blood EOS number and ratio were significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05). By applying receiver operating characteristic (ROC) curve analysis, we found blood EOS number had a sensitivity of 84.9 % and specificity of 84.4 % [area under the curve (AUC): 0.873] at the cutoff level of 0.16 × 10(9)/L, and blood EOS ratio had a sensitivity of 89.0 % and specificity of 84.4 % (AUC: 0.863) at the cutoff level of 2.05 % in this cohort. Our findings indicated that smell loss score, ethmoid osteitis index and blood EOS number and ratio may be used for the differential diagnosis of ECRS as the surrogate markers.
10.1007/s00405-014-2910-0
Chronic rhinosinusitis: risk factors for the recurrence of chronic rhinosinusitis based on 5-year follow-up after endoscopic sinus surgery.
Matsuwaki Yoshinori,Ookushi Tetsushi,Asaka Daiya,Mori Eri,Nakajima Tsuneya,Yoshida Takuto,Kojima Junya,Chiba Shintaro,Ootori Nobuyoshi,Moriyama Hiroshi
International archives of allergy and immunology
BACKGROUND:Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases in the US, and little is understood about its pathogenesis. This study was conducted to characterize, retrospectively, the clinical, objective and immunological parameters that accompany recurrence of CRS during long-term follow-up after surgery. METHODS:Fifty-six patients with CRS who had undergone endoscopic sinus surgery were followed up for 5 years after the surgery. The CRS parameters chosen were as follows: history of asthma and/or allergic rhinitis, peripheral eosinophilia of at least 520 cells/microl, peripheral eosinophil count, total IgE, presence of polyps, CT score, presence of fungi (positive fungal culture or stain), mucus or mucosal eosinophilia, mucosal eosinophil count, presence of acute infection after surgery, gender and age. Individual correlations and stepwise regression were performed. RESULTS:Patients with a total peripheral eosinophil count of 520/microl or more and those with asthma were likely to experience recurrence of CRS within 5 years after surgery. Furthermore, patients with mucus or mucosal eosinophilia who were diagnosed as having eosinophilic CRS (ECRS) showed a high incidence of recurrence within 5 years. The parameter of mucus or mucosal eosinophilia (diagnosis of ECRS) had a positive predictive value of 85.7%. CONCLUSIONS:Surgeons should always examine the inflammatory infiltrate of nasal polyps or the paranasal mucosa, and patients with ECRS require anti-inflammatory medications, such as steroids, for a long time after surgery. Long-term follow-up is also essential.
10.1159/000126066
Salt dual-fortified with iodine and micronized ground ferric pyrophosphate affects iron status but not hemoglobin in children in Cote d'Ivoire.
The Journal of nutrition
Deficiencies of iron and iodine are common in West Africa, and salt is one of very few food vehicles available for fortification. Salt dual-fortified with iodine and micronized ground ferric pyrophosphate (FePP) was tested for its efficacy in rural, tropical Côte d'Ivoire. First, salt and iron intakes, and iron bioavailability were estimated using 3-d weighed food records in 24 households. Local iodized salt was then fortified with 3 mg Fe/g salt as ground FePP (mean particle size = 2.5 mum), and stability, sensory and acceptability trials were done. The dual fortified salt (DFS) was distributed to households and its efficacy compared with that of iodized salt (IS) in a 6-mo, double-blind trial in 5- to 15-y-old iron-deficient children (n = 123). All children were dewormed at baseline. After 6 mo, serum ferritin (SF) and transferrin receptor (TfR) concentrations as well as body iron stores improved significantly in the DFS group but not in the IS GROUP (P < 0.05). Body iron increased from 4.6 +/- 2.7 to 5.9 +/- 2.7 mg/kg (mean +/- SD) in the DFS group; concentrations before and after treatment in the IS group were 5.5 +/- 2.9 and 5.6 +/- 3.1 mg/kg, respectively. The hemoglobin concentration and the prevalence of anemia did not change in either group. The prevalences of malaria, soil-transmitted helminths, and riboflavin deficiency were 55, 14, and 66%, respectively. In tropical West Africa, low-grade salt fortified with micronized ground FePP increased body iron stores but not hemoglobin in children. Iron utilization may have been impaired by the high prevalence of malaria and concurrent nutrient deficiencies.
10.1093/jn/136.7.1814
Dual fortification of salt with iodine and iron: a randomized, double-blind, controlled trial of micronized ferric pyrophosphate and encapsulated ferrous fumarate in southern India.
The American journal of clinical nutrition
BACKGROUND:Dual fortification of salt with iodine and iron could be a sustainable approach to combating iodine and iron deficiencies. OBJECTIVE:We compared the efficacy of dual-fortified salt (DFS) made by using 2 proposed contrasting formulas-one fortifying with iron as micronized ground ferric pyrophosphate (MGFePP) and the other with iron as encapsulated ferrous fumarate (EFF)-with the efficacy of iodized salt (IS) in schoolchildren in rural southern India. DESIGN:After stability and acceptability testing, a double-blind, household-based intervention was conducted in 5-15-y-old children (n = 458) randomly assigned into 3 groups to receive IS or DFS with iron as MGFePP or EFF, both at 2 mg/g salt. We measured hemoglobin, iron status, and urinary iodine at baseline, 5 mo, and 10 mo. RESULTS:Median serum ferritin and calculated median body iron improved significantly in the 2 groups receiving iron. After 10 mo, the prevalence of anemia decreased from 16.8% to 7.7% in the MGFePP group (P < 0.05) and from 15.1% to 5.0% in the EFF group (P < 0.01). The median urinary iodine concentration increased significantly in the IS and EFF groups (P < 0.001) but not in the MGFePP group. Losses of iodine in salt with 1.8% moisture were high for MGFePP, whereas the EFF segregated in salt with 0.5% moisture and caused color changes in some local foods. CONCLUSIONS:Both DFSs were efficacious in reducing the prevalence of anemia and iron deficiency in school-age children. Local salt characteristics should be taken into consideration when choosing an iron fortificant for DFS to achieve optimal iodine stability and color.
10.3945/ajcn.2008.26149
The influence of iron status on iodine utilization and thyroid function.
Zimmermann Michael B
Annual review of nutrition
Despite significant progress, deficiencies of iron and iodine remain major public health problems affecting > or =30% of the global population. These deficiencies often coexist in children. Recent studies have demonstrated that a high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodized salt programs. These findings argue strongly for improving iron status in areas of overlapping deficiency, not only to combat anemia but also to increase the efficacy of iodine prophylaxis. The dual fortification of salt with iodine and iron may prove to be an effective and sustainable method to accomplish these important goals.
10.1146/annurev.nutr.26.061505.111236
Purification and partial characterization of iodothyronine 5'-deiodinase from rat liver microsomes.
Goswami A,Rosenberg I N
Biochemical and biophysical research communications
We have isolated and purified iodothyronine 5'-deiodinase from rat liver microsomes to homogeneity as judged by PAGE and analytical HPLC. The enzyme progressively lost activity after solubilization, and specific activity enhancement was a modest 22-fold, but the final preparation still had substantial activity and was used for molecular characterization. The enzyme had an Mr of 56,000 with a single band in SDS-PAGE, suggesting absence of subunit structure. The high Km, and the GSH-responsive low Km, activities were co-purified, but the low Km enzyme lost GSH-responsiveness upon pretreatment with dithiothreitol (DTT) and urea. The enzyme was strongly inhibited by the iron chelator, alpha,alpha'-dipyridyl and showed a broad absorbance band at 410 nm. Spectral analysis with diethylpyrocarbonate (DEPC) revealed 5 histidine residues/mol enzyme, while enzyme activity was inhibited by DEPC in a pseudo-first order process with modification of 1 histidine residue/mol.
10.1016/s0006-291x(05)81013-7
Interaction of copper with iron, iodine, and thyroid hormone status in goitrous patients.
Kazi Tasneem Gul,Kandhro Ghulam Abbas,Afridi Hassan Imran,Kazi Naveed,Baig Jameel Ahmed,Arain Mohammad Balal,Shah Abdul Qadir,Syed Nasreen,Kumar Sham,Kolachi Nida Fatima,Khan Sumaira
Biological trace element research
In many developing countries, men and women are at high risk of goiter and iron deficiency. The aim of the recent study is to assess the interaction of (Cu), with iron (Fe), iodine/iodide (I), and thyroid hormones in goitrous patients. Sixty goitrous male (GMPs) and 72 female patients (GFPs) were evaluated for the Cu, Fe, I, and thyroid hormones status in biological samples (serum and urine), and compared to non-goitrous subjects of both genders (M = 106, F = 120). The biological samples were analyzed for Cu and Fe concentration using atomic absorption spectrometer, while I was measured by the potentiometric method, prior to microwave-assisted acid digestion (MD). Quality control for the method was established with certified samples. Significantly higher mean values of Cu in serum, and urine samples of GMPs and GFPs, while lower value of Fe and I were observed as compared to control subjects (p < 0.015), respectively. The mean values of free triiodothyronine (FT3) and free thyroxin (FT4) were found to be lower in goitrous patients of both genders than in the age-matched healthy controls (p < 0.006 and 0.002), respectively, in contrast high mean values of thyroid-stimulating hormone (TSH) were detected in patients (p < 0.009), as compared to non-goitrous subjects. It was observed that the deficiencies of Fe, I, and thyroid hormone in goitrous patients could be influenced by efficiency of Cu.
10.1007/s12011-009-8478-7
The role of iron deficiency in persistent goiter.
Dabbaghmanesh Mohammad-Hossein,Sadegholvaad Abdolsamad,Ejtehadi Fardad,Ranjbar-Omrani Gholamhossein
Archives of Iranian medicine
BACKGROUND:Iodine deficiency has been identified as a significant public health problem in Iran. The main strategy for controlling iodine deficiency was nationwide salt iodination. Over 10 years after starting this program, goiter is still endemic in school children. Iron deficiency may have interfered with the iodine intervention program. The objective of the present study was to evaluate the relationships between iron status, thyroid hormone profile, and the prevalence of goiter 11 years after implementation of the salt iodination program. METHODS:In this study which was conducted in Marvdasht, Shiraz, 1188 students aged eight to 13 years were enrolled. Goiter was graded according to the classification by the World Health Organization (WHO). Serum concentrations of thyroid hormones and thyroid stimulating hormone were determined using commercial kits. The urinary iodine level was measured using the digestion method. RESULTS:Goiter was endemic (39.6%); the majority of participants had grade 1 thyromegally. Despite the endemic status of goiter in southern Iran, the urine content of iodine reflected a normal iodine intake. The prevalence of iron deficiency was 16.4%. The iron-deficient patients had a significantly higher thyroid stimulating hormone level and lower free T4 concentrations than those with a normal serum ferritin level (P<0.001). CONCLUSION:Iron supplementation may improve thyroid metabolism in children but we still have to investigate the role of other goitrogens in this area.
08112/AIM.007
1,25-dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer.
Clinckspoor Isabelle,Verlinden Lieve,Overbergh Lutgart,Korch Christopher,Bouillon Roger,Mathieu Chantal,Verstuyf Annemieke,Decallonne Brigitte
The Journal of steroid biochemistry and molecular biology
Anaplastic thyroid cancer represents one of the most aggressive cancers. The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to have antiproliferative and/or redifferentiating properties in several malignancies, including thyroid cancer. The objective of this study was to investigate the effects of 1,25(OH)(2)D(3) and the superagonistic analog CD578 in anaplastic thyroid cancer, alone or in combination with paclitaxel, a taxane, and suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor with promising effects in undifferentiated thyroid cancer. Four human thyroid cancer cell lines (FTC-133, C643, 8505C and HTh74) were treated with 1,25(OH)(2)D(3) or CD578, alone or in combination with paclitaxel or SAHA. Effects on cell growth and differentiation were evaluated. Clear effects on growth arrest were observed in a clonogenic assay, and absolute cell counts demonstrated a 24-36% reduction in all cell lines after 72h treatment with 1,25(OH)(2)D(3) (10(-6)M) and a 60% inhibition after 120h in the most sensitive cell line HTh74. A similar growth inhibition was shown after treatment with a 1000-fold lower concentration of analog CD578. This growth arrest was explained by antiproliferative effects, further supported by an increased % of cells in the G(0)-G(1) phase of the cell cycle and by a decreased transcription factor E2F1 mRNA expression. Combination treatments of 1,25(OH)(2)D(3) or CD578 with paclitaxel or SAHA resulted in an additive and in some conditions a synergistic effect on the inhibition of proliferation. Redifferentiation analysis revealed only a modest increase in sodium iodide symporter and thyroglobulin mRNA expression after treatment with 1,25(OH)(2)D(3), without additive effect after combination treatment. No effects were observed on TSH-receptor or thyroid peroxidase mRNA expression. Our in vitro findings demonstrate that the superagonistic vitamin D analog CD578 holds promise as adjuvant antiproliferative therapy of anaplastic thyroid cancer, especially in combination with other drugs such as paclitaxel or SAHA.
10.1016/j.jsbmb.2010.12.008
Effects of manganese on thyroid hormone homeostasis: potential links.
Soldin O P,Aschner M
Neurotoxicology
Manganese (Mn) is an essential trace nutrient that is potentially toxic at high levels of exposure. As a constituent of numerous enzymes and a cofactor, manganese plays an important role in a number of physiologic processes in mammals. The manganese-containing enzyme, manganese superoxide dismutase (Mn-SOD), is the principal antioxidant enzyme which neutralizes the toxic effects of reactive oxygen species. Other manganese-containing enzymes include oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases and glutamine synthetase. Environmental or occupational exposure to high levels of manganese can cause a neuropathy resembling idiopathic Parkinson's disease, commonly referred to as manganism. Manganism and Parkinson's disease are both characterized by motor deficits and damage to nuclei of the basal ganglia, particularly the substantia nigra, with altered dopamine (and its metabolites) contributing to these disorders. Dopamine, a major neurotransmitter plays a crucial role in the modulation of the cognitive function, working memory and/or attention of the prefrontal cortex and the hippocampus. Dopamine is also a known inhibitory modulator of thyroid stimulating hormone (TSH) secretion. The involvement of dopamine and dopaminergic receptors in neurodevelopment, as well as TSH modulation, led us to hypothesize that excessive manganese exposure may lead to adverse neurodevelopmental outcomes due to the disruption of thyroid homeostasis via the loss of dopaminergic control of TSH regulation of thyroid hormones. This disruption may alter thyroid hormone levels, resulting in some of the deficits associated with gestational exposure to manganese. While the effects of manganese in adult populations are relatively well documented, comprehensive data on its neurodevelopmental effects are sparse. Given the importance of this topic, we review the potential participation of thyroid hormone dyshomeostasis in the neurodevelopmental effects of manganese positing the hypotheses that manganese may directly or indirectly affect thyroid function by injuring the thyroid gland or dysregulating dopaminergic modulation of thyroid hormone synthesis.
10.1016/j.neuro.2007.05.003
Increased lipid peroxidation and impaired enzymatic antioxidant defense mechanism in thyroid tissue with multinodular goiter and papillary carcinoma.
Erdamar Hüsamettin,Cimen Behzat,Gülcemal Harun,Saraymen Recep,Yerer Betül,Demirci Hüseyin
Clinical biochemistry
OBJECTIVES:We aimed to evaluate the oxidant/antioxidant status of thyroid tissue in patients with multinodular goiter, papillary carcinoma and to compare with their nonpathologic tissues. METHODS:We studied 41 patients with multinodular goiter who underwent surgical treatment. The patients were divided into three groups according to clinical diagnosis. Malondialdehyde, selenium, total superoxide dismutase and glutathione peroxidase of thyroid tissue samples were determined in 14 toxic multinodular goiters, 18 non-toxic multinodular goiters, and 9 papillary carcinomas. RESULT:Superoxide dismutase and glutathione peroxidase and selenium were found lower but malondialdehyde was higher in both nodule and cancerous tissues compared with those of control ones. The level of malondialdehyde in non-toxic multinodular goiters group was higher than toxic multinodular goiters group in nodule tissues. CONCLUSIONS:It can be stated that the lipid peroxidation is increased and enzymatic free radical defense system was significantly impaired in patients with both multinodular goiters and papillary carcinomas.
10.1016/j.clinbiochem.2010.02.005
Trace elements status in multinodular goiter.
Giray Belma,Arnaud Josiane,Sayek Iskender,Favier Alain,Hincal Filiz
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
Importance of iodine and selenium in thyroid metabolism is well known, but the roles of other essential trace elements including copper, zinc, manganese and iron on thyroid hormone homeostasis remain unclear. The aim of this study was to investigate the status of those trace elements in benign thyroid diseases and evaluate possible links between trace element concentrations and thyroid hormones. The study group was composed of 25 patients with multinodular goiter. Concentrations of thyroid hormones (plasma-free thyroxine, FT(4); free triiodothyronine, FT(3); and thyrotropin, TSH), selenium, copper, zinc, manganese and iron in plasma, and urinary iodine were determined. The results were compared with those of a healthy control group (n=20) with no thyroid disorder. A mild iodine deficiency was observed in the patients with multinodular goiter whereas urinary iodine levels were in the range of "normal" values in healthy controls. All patients were euthyroid, and their thyroid hormone concentrations were not significantly different from the control group. Plasma selenium, zinc and iron concentrations did not differ from controls, while copper and manganese levels were found to be significantly higher in the patients with multinodular goiter indicating links between these trace elements and thyroid function and possibly in development of goiter. Besides iodine, there was a significant correlation between plasma copper concentration and FT(3)/FT(4) ratio.
10.1016/j.jtemb.2009.11.003
Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.
Gärtner Roland,Gasnier Barbara C H,Dietrich Johannes W,Krebs Bjarne,Angstwurm Matthias W A
The Journal of clinical endocrinology and metabolism
In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.
10.1210/jcem.87.4.8421
Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis.
Mazokopakis Elias E,Papadakis John A,Papadomanolaki Maria G,Batistakis Antony G,Giannakopoulos Triantafillos G,Protopapadakis Eftichios E,Ganotakis Emmanuel S
Thyroid : official journal of the American Thyroid Association
OBJECTIVE:We studied the effects of selenium (Se) treatment on serum anti-thyroid peroxidase (TPO) levels in Greek patients with Hashimoto's thyroiditis (HT). DESIGN:We prospectively studied 80 women with HT, median age 37 (range 24-52) years, for 1 year. All patients received 200 microg Se in the form of l-selenomethionine orally for 6 months. At the end of the 6-month period, 40 patients continued taking 200 microg Se (Group A) and 40 patients stopped (Group B). Serum thyrotropin (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4)), anti-TPO, and anti-thyroglobulin (Tg) levels were measured at baseline and at the end of each 3-month period. MAIN OUTCOME:There was a significant reduction of serum anti-TPO levels during the first 6 months (by 5.6% and 9.9% at 3 and 6 months, respectively). An overall reduction of 21% (p < 0.0001) compared with the basal values was noted in Group A. In Group B, serum anti-TPO levels were increased by 4.8% (p < 0.0001) during the second 6-month period. CONCLUSIONS:Our study showed that in HT patients 6 months of Se treatment caused a significant decrease in serum anti-TPO levels, which was more profound in the second trimester. The extension of Se supplementation for 6 more months resulted in an additional 8% decrease, while the cessation caused a 4.8% increase, in the anti-TPO concentrations.
10.1089/thy.2007.0040
Thyroid disorders-assessments of trace elements, clinical, and laboratory parameters.
Przybylik-Mazurek Elwira,Zagrodzki Paweł,Kuźniarz-Rymarz Sylwia,Hubalewska-Dydejczyk Alicja
Biological trace element research
The trace elements studied in this work (Se, Cu, Zn) are the essential constituents or cofactors required to activate numerous enzymes and proteins, playing crucial role in various physiological processes. The disturbed levels of abovementioned elements may adversely affect the endocrine system, resulting in various thyroid disorders among other upsets. The aim of this study was to investigate possible associations between them and parameters of redox balance, thyroid function indices as well as clinical records (duration of disease and therapy, lag time between thyroid surgery and this study examination, LT4 dosage) in patients with different thyroid disorders, including malignant diseases of the gland. In the group of patients with papillary carcinoma, we found a statistically significant higher Cu concentration compared with controls and patients with Hashimoto disease. In the same groups, the parameter of Zn/Cu ratio demonstrated reciprocally arranged statistically significant differences. For the group of papillary cancer patients, there was a negative correlation between lag time since thyroid operation and GPX3 activity. Our data support hypothesis of indirect involvement of Zn and Cu in thyroid regulation. For selenium, lack of simple correlation between its serum level and thyroid indices implies the need for further research on other selenium status parameters more adequately depicting changes in endocrine system.
10.1007/s12011-010-8719-9
Selenium and thyroid.
Köhrle Josef,Gärtner Roland
Best practice & research. Clinical endocrinology & metabolism
Inadequate supply of the essential trace element selenium (Se) has been associated with predisposition for, or manifestation of, various human diseases such as Keshan and Kashin-Beck disease, cancer, impaired immune function, neurodegenerative and age-related disorders and disturbances of the thyroid hormone axis. Se deficiency in combination with inadequate iodine contributes to the pathogenesis of myxedematous cretinism. The recent identification of various distinct selenocysteine-containing proteins, encoded by 25 human genes, provides information on the molecular and biochemical basis of beneficial and possible adverse effects of this trace element. The thyroid gland is among the human tissues with the highest Se content per mass unit similar to other endocrine organs and the brain. Selenoproteins involved in cellular antioxidative defence systems and redox control, such as the glutathione peroxidase (GPx) and the thioredoxin reductase (TxnRd) family, are involved in protection of the thyroid gland from excess hydrogen peroxide and reactive oxygen species produced by the follicles for biosynthesis of thyroid hormones. In addition, the three key enzymes involved in activation and inactivation of thyroid hormones, the iodothyronine deiodinases (DIO1,2,3), are selenoproteins with development, cell- and pathology-related expression patterns. While nutritional Se supply is normally sufficient for adequate expression of functional Dio enzymes with exception of long-term parenteral nutrition and certain diseases impairing gastrointestinal absorption of Se compounds, the nutritional Se supply for the protection of the thyroid gland and synthesis of some more abundant selenoproteins of the GPx and the TrxR family might be limiting their proper expression under (patho-)physiological conditions.
10.1016/j.beem.2009.08.002
Selenium and the thyroid: a close-knit connection.
Duntas Leonidas H
The Journal of clinical endocrinology and metabolism
CONTEXT:The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease. EVIDENCE ACQUISITION:Clinical reports as well as a large number of biochemical articles linking selenium to thyroid have been considered. Interventional, prospective, randomized, controlled studies, including large observational studies, supplementing selenium in autoimmune thyroid disease, together with review articles published in Medline and Pubmed have undergone scrutiny. The methodological differences and variety of results emerging from these trials have been analyzed. EVIDENCE SYNTHESIS:Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination. However, considerable discord remains as to who should comprise target groups for selenium treatment, who will most benefit from such treatment, the precise impact of the basal antithyroid peroxidase level, and the effect of disease duration on the treatment outcome. Clearly, further in-depth studies and evaluation are required concerning the mechanism of action of selenium as well as the choice of supplements or dietary intake. CONCLUSIONS:Maintenance of "selenostasis" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease.
10.1210/jc.2010-0191
Selenium status, thyroid volume, and multiple nodule formation in an area with mild iodine deficiency.
Rasmussen Lone Banke,Schomburg Lutz,Köhrle Josef,Pedersen Inge Bülow,Hollenbach Birgit,Hög Antonia,Ovesen Lars,Perrild Hans,Laurberg Peter
European journal of endocrinology
OBJECTIVE:The objective was to study the associations between serum selenium concentration and thyroid volume, as well as the association between serum selenium concentration and risk for an enlarged thyroid gland in an area with mild iodine deficiency before and after iodine fortification was introduced. Another objective was to examine the association between serum selenium concentration and prevalence of thyroid nodules. DESIGN:Cross-sectional study. METHODS:We studied participants of two similar cross-sectional studies carried out before (1997-1998, n=405) and after (2004-2005, n=400) introduction of iodine fortification. Serum selenium concentration and urinary iodine were measured, and the thyroid gland was examined by ultrasonography in the same subjects. Associations between serum selenium concentration and thyroid parameters were examined in multiple linear regression models or logistic regression models. RESULTS:Serum selenium concentration was found to be significantly, negatively associated with thyroid volume (P=0.006), and a low selenium status significantly increased the risk for thyroid enlargement (P=0.007). Furthermore, low serum selenium status had a tendency to increase the risk for development of multiple nodules (P=0.087). CONCLUSIONS:Low serum selenium concentration was associated with a larger thyroid volume and a higher prevalence of thyroid enlargement.
10.1530/EJE-10-1026
[Changes of the spectrum on thyroid disease after the ten-year implementation of universal salt iodization in Guangxi Zhuang Autonomous Region].
Zhang Jia-yue,Li Song-ming,Leng Jin-li,Chen You-jiang,Pu Jian,Li Jin-ming,Pang Fei-xiong,Huang Yong-hong,Nong Jiang,Cen Yan-zeng,He Hui,Li Rui,Wei Li-ning,He Hong-yan
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
OBJECTIVE:To reveal the relationship between iodine nutrition and the change of spectrum on thyroid diseases through comparing the different iodine environments pre- and post- the universal salt iodization(USI)campaign. METHODS:To compare the urinary iodine concentration between 1000 normal people and 5998 patients with thyroid disease who had undergone surgical operations, from 4 major cities, including iodine deficient and rich areas of Guangxi Zhuang Autonomous Region. RESULTS:After USI was put into practice, the urinary iodine concentration of patients with thyroid appeared higher than those of normal people(324.3 µg/L vs. 238.5 µg/L, P < 0.05). The urinary iodine concentrations of nodular goiter,Graves disease, toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis were higher than those before the USI was taken(263.8 µg/L vs. 69.75 µg/L, 289.7 µg/L vs. 228.3 µg/L, 346.8 µg/L vs. 268.4 µg/L, 350.3 µg/L vs. 316.2 µg/L and 378.5 µg/L vs. 305.8 µg/L). The proportions of toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis appeared as 7.59% vs. 4.80%, 5.85% vs. 4.02% and 3.88% vs. 2.46%, all higher than those before the implementation of USI, except the nodular goiter which showed a reduction (63.56% vs. 69.75%). CONCLUSION:The spectrum of thyroid diseases appeared an obvious change in Guangxi within the last 10-year implementation of USI. However, the excessive intake of iodine might serve as a risk factor for toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis.
Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women.
The Journal of nutrition
Although the median urinary iodine concentration (UIC) is a good indicator of iodine status in populations, there is no established biomarker for individual iodine status. If the UIC were to be used to assess individuals, it is unclear how many repeat urine collections would be needed and if the collections should be spot samples or 24-h samples. In a prospective, longitudinal, 15-mo study, healthy Swiss women (n = 22) aged 52-77 y collected repeated 24-h urine samples (total n = 341) and corresponding fasting, second-void, morning spot urine samples (n = 177). From the UIC in spot samples, 24-h urinary iodine excretion (UIE) was extrapolated based on the age- and sex-adjusted iodine:creatinine ratio. Measured UIE in 24-h samples, estimated 24-h UIE, and UIC in spot samples were (geometric mean ± SD) 103 ± 28 μg/24 h, 86 ± 33 μg/24 h, and 68 ± 28 μg/L, respectively, with no seasonal differences. Intra-individual variation (mean CV) was comparable for measured UIE (32%) and estimated UIE (33%). The CV tended to be higher for the spot UIC (38%) than for the estimated 24-h UIE (33%) (P = 0.12). In this population, 10 spot urine samples or 24-h urine samples were needed to assess individual iodine status with 20% precision. Spot samples would likely be preferable because of their ease of collection. However, the large number of repeated urine samples needed to estimate individual iodine status is a major limitation and emphasizes the need for further investigation of more practical biomarkers of individual iodine status.
10.3945/jn.111.144071
A PRISMA-compliant systematic review and meta-analysis of the relationship between thyroid disease and different levels of iodine intake in mainland China.
Medicine
BACKGROUND:Low-iodine intake has historically been an issue in China, causing widespread iodine deficiency diseases (IDD). China started to introduce universal salt iodization in 1995, but reports of increased thyroid disease are a concern and appropriate levels of iodine intake must be considered. OBJECTIVE:To assess the prevalence of thyroid disease with different urinary iodine concentrations (UICs) in the general population of those residing in mainland China. Furthermore, we aimed to analyze the relationship between thyroid disease and UIC, to provide guidance in establishing effective health policies regarding iodine intake. METHODS:PubMed, Cochrane, Embase, CNKI, Wan fang, and CQVIP databases were searched for random community-based relevant studies with UIC published before January 2016 in mainland China. Two independent reviewers extracted data from eligible citations, and obtained prevalence of thyroid disease for different UICs, as well as the intergroup interaction P values. RESULTS:Forty-three articles were included. The prevalence of thyroid nodules was 22.3% (95% confidence interval [CI]: 20.6%-24.1%) for the low-iodine group, 25.4% (95% CI: 20.8%-28.8%) for the medium-iodine group, and 6.8% (95% CI: 2.8%-11.5%) for the high-iodine group. In the high-iodine group, the prevalence of thyroid nodules was lower than the other groups. The prevalence of 8.3% (95% CI: 3.8%-17.3%) for subclinical hypothyroidism in the high-iodine group was significantly higher than the low- and medium-iodine groups (P < .01). The prevalence of hypothyroidism in the medium-iodine group was 0.2% (95% CI: 0.1%-0.4%), and was lower than the prevalence of the other 2 groups (P < .01). There was no difference in prevalence of hyperthyroidism in each group. CONCLUSIONS:Thyroid nodules are the most easily detectable thyroid disease. These have a lower prevalence in the high-iodine group. The prevalence of most thyroid diseases is lowest for a UIC ranging from 100 to 299 μg/L. This serves as a reference for health policy-making with respect to iodine levels. Further studies on this topic should be carried out according to sufficient thyroid cancer data.
10.1097/MD.0000000000007279
Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases.
Kucharzewski M,Braziewicz J,Majewska U,Góźdź S
Biological trace element research
We investigated the possible differences between the concentrations of selenium in the whole blood and thyroid tissue of patients with thyroid disease. The study comprises 41 women with nodular goiter, 19 women and 2 men with thyroid cancer, 18 women with Graves' disease, and 7 women with thyroiditis. The concentration of selenium was determined by the TRXRF method. The lowest mean selenium level was achieved in the whole blood of women with Graves' disease and the highest in the whole blood of healthy people. In the thyroid cancer tissue, we found the lowest concentration of selenium and the highest in the thyroid gland of women with nodular goiter and Graves' disease. The low selenium levels in the thyroid tissue may increase thyroid cancer risk.
10.1385/BTER:88:1:25
Dietary iodine intake and urinary iodine excretion in patients with thyroid diseases.
Kim J Y,Kim K R
Yonsei medical journal
This study was conducted to examine the usual iodine intake in patients with thyroid diseases and to compare iodine status with normal subjects. The dietary iodine intake was assessed using a semi-quantitative food frequency questionnaire, and urinary iodine excretion was measured in 184 patients diagnosed with thyroid diseases and 207 normal subjects. The average usual iodine intake of patients with thyroid diseases was 673.8 +/- 794.9 ug/day and that of normal subjects was 468.9 +/- 481.9 ug/day. Among the patients with thyroid diseases, higher values were found in the patients with thyroid cancer (1460.6 +/- 1044.8 ug/day) and lower values were found in patients with simple goiter (443.5 +/- 470.4 ug/day). The urinary iodine excretions of patients and normal subjects were 4.33 +/- 5.70 mg/L and 2.11 +/- 0.69 mg/L, respectively. The iodine intake and urinary iodine excretion of patients with thyroid diseases were significantly higher than those of normal subjects (p < 0.05). The dietary iodine intake and urinary excretion of patients with thyroid cancer were significantly higher than other patients with thyroid diseases and normal subjects because of the use of seaweed or seaweed-containing dietary supplements (p < 0.01). This study suggests that the habitual ingestion of seaweed-containing dietary supplements in addition to dietary iodine intake will have adverse effects due to its excessive iodine intake.
10.3349/ymj.2000.41.1.22
Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy.
Martínez-Aguilar Juan,Clifton-Bligh Roderick,Molloy Mark P
Scientific reports
Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype.
10.1038/srep23660
High-resolution proteomics and metabolomics in thyroid cancer: Deciphering novel biomarkers.
Navas-Carrillo Diana,Rodriguez José Manuel,Montoro-García Silvia,Orenes-Piñero Esteban
Critical reviews in clinical laboratory sciences
The incidence of thyroid cancer (TC) - the most common endocrine malignancy - has been increasing sharply since the mid-1990s. The rate of TC incidence in both men and women has been faster than any other cancer. Both improved diagnoses (i.e. increased medical surveillance and more sensitive diagnostic tests, such as ultrasound and confirmation via fine-needle aspiration biopsy (FNAB)), and environmental factors detrimental to thyroid health are thought to account for the increased incidence. There are several histological types of thyroid carcinoma including papillary, follicular, medullary, and anaplastic. Determining the type of TC is crucial for prognosis and treatment selection. Unfortunately, approximately 20-30% of patients undergoing FNAB have inconclusive or indeterminate results, leading to unnecessary surgical intervention in 80% of patients with benign nodules. To resolve this diagnostic dilemma, new biomarkers of TC are needed. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, yet RNA levels are only indicative of protein synthesis. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in TC biomarker discovery, providing novel information on the molecular events associated with TC, and potentially leading to the identification of novel drug targets. This review thoroughly discusses the importance of novel proteomic and metabolomic approaches to identify new biomarkers for TC.
10.1080/10408363.2017.1394266
Cancer statistics in China, 2015.
CA: a cancer journal for clinicians
With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
10.3322/caac.21338