Human papillomavirus (HPV) in head and neck cancer.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
The term "head and neck cancer" has been widely adopted in the recent literature, to include the lesions at several anatomic sites: the lip, oral cavity, nose and para-nasal sinuses, naso-pharynx, oro-pharynx, hypo-pharynx, and larynx. In this communication, the data on human papillomavirus (HPV) involvement in oral, oro-pharyngeal, sino-nasal, and laryngeal carcinomas are reviewed. Our group was the first to present evidence on the involvement of HPV infections in both laryngeal and oral carcinogenesis, prompted by the discovery of morphological similarities between oral and cervical squamous cell lesions. The latest meta-analyses of the epidemiological studies as well as the multi-centre case-control studies have confirmed HPV as an independent risk factor for oral cancer, with a range of odds ratios (OR) between 3.7 and 5.4. Until 2002, 4768 oral carcinomas have been analysed for HPV DNA, and 22% were reported to contain HPV by any of the detection techniques. Of all non-genital cancers, tonsillar carcinomas appear to have the highest prevalence of HPV. By the end of 2002, 422 cases of tonsillar carcinoma have been analyzed for the presence of HPV DNA, with the overall detection rate of 51%. HPV 16 is the most prevalent HPV type found in 84% of HPV DNA-positive tumours. HPV seems to be mainly episomal in tonsillar carcinomas, but the significance of this observation is still obscure. Interestingly, patients with HPV 16-positive tumours seem to have a better overall- and disease-specific survival, as compared with the HPV-negative group. To date, 1041 sino-nasal papillomas have been analysed for HPV and 347 (33%) cases have been positive, whereas of the 322 sino-nasal carcinomas analysed so far, 70 (22%) have been positive for any HPV type. Laryngeal squamous cell papilloma and recurrent respiratory papillomatosis (RRP) are well-established HPV-induced tumours, whereas the role of HPV in laryngeal carcinomatosis remains controversial. The molecular mechanisms of HPV-associated carcinogenesis of the head and neck require further study.
HPV DNA genotyping, HPV E6*I mRNA detection, and p16/Ki-67 staining in Belgian head and neck cancer patient specimens, collected within the HPV-AHEAD study.
Simoens Cindy,Gorbaslieva Ivana,Gheit Tarik,Holzinger Dana,Lucas Eric,Ridder Ruediger,Rehm Susanne,Vermeulen Peter,Lammens Martin,Vanderveken Olivier M,Kumar Rekha Vijay,Gangane Nitin,Caniglia Alessandro,Maffini Fausto,Rubio Maria Belén Lloveras,Anantharaman Devasena,Chiocca Susanna,Brennan Paul,Pillai Madhavan Radhakrishna,Sankaranarayanan Rengaswamy,Bogers Johannes,Pawlita Michael,Tommasino Massimo,Arbyn Marc,
BACKGROUND:The main risk factors for head and neck cancer (HNC) are tobacco and alcohol use. However, an important fraction of oropharyngeal cancer (OPC) is caused by human papillomaviruses (HPV), a subgroup with increasing incidence in several western countries. METHODS:As part of the HPV-AHEAD study, we assessed the role of HPV infection in 772 archived tissue specimens of Belgian HNC patients: 455 laryngeal (LC), 106 oral cavity (OCC), 99 OPC, 76 hypopharyngeal (HC), and 36 unspecified parts of the head and neck. All specimens were tested for HPV DNA (21 genotypes); whereof all HPV DNA-positives, all HPV DNA-negative OPCs and a random subset of HPV DNA-negatives of the other HNC-sites were tested for the presence of type-specific HPV RNA and p16 over-expression. RESULTS:The highest HPV DNA prevalence was observed in OPC (36.4 %), and was significantly lower (p < 0.001) in the other HNCs (OCC:7.5 %, LC:6.6 %). HPV16 was the most common HPV-genotype in all HNCs. Approximately 83.0 % of the HPV DNA-positive OPCs tested HPV RNA or p16-positive, compared to about 37.5 % and 44.0 % in OCC and LC, respectively. Estimation of the attributable fraction of an HPV infection in HNC was very similar for HPV RNA or p16 in addition to DNA-positivity; with 30 % for OPC, and 3 % for OCC and LC. CONCLUSION:Our study confirms the heterogeneity of HPV DNA prevalence across anatomical sites in HNC, with a predominance of HPV16 in all sites. The estimated proportion of HPV-driven HNC in Belgium, during the period 1980-2014, was 10 times higher in OPC compared to OCC and LC.
Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine.
Zhang Feng-Ying,Hu Yi,Que Zhong-You,Wang Ping,Liu Yun-Hui,Wang Zhen-Hua,Xue Yi-Xue
International journal of molecular sciences
Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).
Liujunzi Tang, a famous traditional Chinese medicine, ameliorates cigarette smoke-induced mouse model of COPD.
Zhou Rui,Luo Fen,Lei Hui,Zhang Kai,Liu Jingyan,He He,Gao Jin,Chang Xiayun,He Ling,Ji Hui,Yan Tianhua,Chen Tong
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Liujunzi Tang is a traditional herbal medicine widely used in East Asia and clinically applied to treat Phlegm-Heat Syndrome. The purpose of the present study was to investigate the protective effects of Liujunzi Tang on cigarette smoke-induced (CS) mouse model of chronic obstructive pulmonary disease (COPD) and explore its potential molecular mechanism. MATERIALS AND METHODS:The mice received 1h of cigarette smoke for 8 weeks. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemical methods. Histopathological alteration was observed by hematoxylin-eosin (H&E) staining. Additionally, the expressions of nuclear transcription factor-κB (NF-κBp65) and (inhibitor of NF-κB)IκB-α were determined by western blot and immunohistochemistry analysis. RESULTS:Liujunzi Tang enhanced the activities of antioxidant enzymes and attenuated the levels of lipid oxidative production, meanwhile significantly inhibited the generations of inflammatory cytokines by inhibiting the phosphorylation of IκB-α and NF-κB. CONCLUSION:Our findings indicated that Liujunzi Tang exhibited the protective effect on cigarette smoke-induced COPD mice by anti-inflammatory and anti-oxidative properties through the inhibition of NF-κB activation.
[Research progress on anti-tumor effect of Chinese dragon's blood].
Tian Ying-Ying,Yang Ai-Lin,Chen Xiao-Nan,Li Jia-Qi,Tang Lei-Meng-Yuan,Huang Hui-Ming,Liu Ya-Xin,Qiu Hai-Ling,Ouyang Li-Shan,Li Jun,Tu Peng-Fei,Hu Zhong-Dong
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.
Anticancer efficacy of the ethyl acetate extract from the traditional Chinese medicine herb Celastrus orbiculatus against human gastric cancer.
Wang Haibo,Tao Lide,Ni Tengyang,Gu Hao,Jin Feng,Dai Xiaojun,Feng Jun,Ding Yanbing,Xiao Weiming,Guo Shiyu,Hisamitsu Tadashi,Qian Yayun,Liu Yanqing
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:The traditional Chinese medicine (TCM) herb Celastrus orbiculatus is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. The ethyl acetate extract of C. orbiculatus (C. orbiculatus extract, COE) was reported to show significant antitumor effects. However, no study in China or abroad has reported the effect and mechanism of COE in triggering apoptosis of gastric cancer (GC) cells. AIM OF STUDY:To further uncover the molecular mechanism underlying COE's apoptotic and anti-proliferative effects and lay a foundation for the development of novel, effective antitumor TCM agents. MATERIALS AND METHODS:The effect of COE on AGS and BGC-823 GC cell viability was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of AGS and BGC-823 cells induced by COE was analyzed using flow cytometry and a mitochondrial membrane potential assay kit (JC-1). The proliferating GC cells were identified and examined using a 5-bromo-2'-deoxyuridine (BrdU) staining kit and flow cytometric analysis. A western blot assay was used to detect the effect of COE on apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2), Bcl-extra-large (Bcl-xL), Bcl-2-like protein 12 (Bcl-L12), Bcl-2-associated X protein (Bax), and caspase as well as proliferation-related proteins, phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70s6k. Transmission electron microscopy (TEM) and an animal imaging technique were used to evaluate the microstructure of apoptotic GC cells and the effect of COE on tumor cell growth in vivo, respectively. RESULTS:The results indicate that COE significantly inhibited proliferation and induced apoptosis of GC AGS and BGC-823 cell lines both in vivo and in vitro. COE significantly decreased the cell mitochondrial membrane potential. Moreover, COE downregulated the levels of Bcl-2, Bcl-xL, and PI3K/Akt/mTOR/p70s6k while those of Bax and caspase were upregulated. More interestingly, COE altered the microstructure of the mitochondria. CONCLUSION:All these data collectively indicate that COE not only has significant antiproliferative effects but also has both in vivo and in vitro apoptotic effects. In addition, COE altered the structure and function of the mitochondria, which is another potential pathway for the antitumor activity of COE. These findings may provide a basis for the development of new anticancer TCM candidates.