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biomarkers in Head and neck cancers

Hidehito Horinouchi
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab...
October 17, 2016: Expert Opinion on Biological Therapy
Li Wang, Haihua Jiang, Wencai Li, Chuanliang Jia, Hua Zhang, Yan Sun, Xiumei Chen, Xicheng Song
OBJECTIVE: To investigate the functional mechanism of microRNA-182 (miR-182) in head and neck squamous cell carcinoma (HNSCC). DESIGN: HNSCC and normal samples were used to check both p53 and miR-182 expression. Two cancer cell lines with overexpression of miR-182 were used to check cell proliferation and migration. In vivo role of miR-182 was assessed using mouse xenograft tumor model. β-TrCP2 was found to be direct target of miR-182 by luciferase reporter assay...
September 30, 2016: Archives of Oral Biology
Kathrin Günther, Ronja Foraita, Juliane Friemel, Frauke Günther, Jörn Bullerdiek, Rolf Nimzyk, Dominique Nadine Markowski, Thomas Behrens, Wolfgang Ahrens
BACKGROUND: The transcription factor high-mobility AT-hook 2 (HMGA2) is involved in stem cell renewal and is expressed in many tumor tissues. Head and neck squamous cell carcinomas (HNSCC) comprise tumors of the upper aerodigestive tract and are characterized by high recurrence rates that represent a challenge to patient management. The study addresses the potential of HMGA2 as a molecular biomarker for HNSCC patient survival. METHODS: Patients with HNSCC of the larynx, pharynx, tonsils, or oral cavity were recruited in a hospital-based case-control study (n=202)...
October 14, 2016: Cancer Epidemiology, Biomarkers & Prevention
Yukinori Takenaka, Norihiko Takemoto, Toshimichi Yasui, Yoshifumi Yamamoto, Atsuhiko Uno, Haruka Miyabe, Naoki Ashida, Kotaro Shimizu, Susumu Nakahara, Atshushi Hanamoto, Takahito Fukusumi, Takahiro Michiba, Hironori Cho, Masashi Yamamoto, Hidenori Inohara
Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected...
2016: PloS One
Marlon C Rebelatto, Anita Midha, Amita Mistry, Constantine Sabalos, Nicole Schechter, Xia Li, Xiaoping Jin, Keith E Steele, Paul B Robbins, John A Blake-Haskins, Jill Walker
BACKGROUND: A high-quality programmed cell-death ligand 1 (PD-L1) diagnostic assay may help predict which patients are more likely to respond to anti-programmed cell death-1 (PD-1)/PD-L1 antibody-based cancer therapy. Here we describe a PD-L1 immunohistochemical (IHC) staining protocol developed by Ventana Medical Systems Inc. and key analytical parameters of its use in formalin-fixed, paraffin-embedded (FFPE) samples of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC)...
October 8, 2016: Diagnostic Pathology
Imran Petkar, Keith Rooney, Justin W G Roe, Joanne M Patterson, David Bernstein, Justine M Tyler, Marie A Emson, James P Morden, Kathrin Mertens, Elizabeth Miles, Matthew Beasley, Tom Roques, Shreerang A Bhide, Kate L Newbold, Kevin J Harrington, Emma Hall, Christopher M Nutting
BACKGROUND: Persistent dysphagia following primary chemoradiation (CRT) for head and neck cancers can have a devastating impact on patients' quality of life. Single arm studies have shown that the dosimetric sparing of critical swallowing structures such as the pharyngeal constrictor muscle and supraglottic larynx can translate to better functional outcomes. However, there are no current randomised studies to confirm the benefits of such swallow sparing strategies. The aim of Dysphagia/Aspiration at risk structures (DARS) trial is to determine whether reducing the dose to the pharyngeal constrictors with dysphagia-optimised intensity- modulated radiotherapy (Do-IMRT) will lead to an improvement in long- term swallowing function without having any detrimental impact on disease-specific survival outcomes...
October 6, 2016: BMC Cancer
Aditi Bhowmik, Sambuddha Das, Abhinandan Bhattacharjee, Biswadeep Choudhury, Momota Naiding, Sankar Kumar Ghosh, Yashmin Choudhury
We investigated the role of BRCA1, MDM2, and p53 in the pathogenesis of head and neck cancer (HNC) and evaluated their potential utility as blood-based predictive biomarkers of HNC. Immunostaining of tissue biopsies and whole blood lymphocytes (WBL) of 36 HNC patients were evaluated by immunohistochemistry (IHC) and immunocytochemistry (ICC), respectively. The staining intensities of BRCA1 and MDM2 in matched tissue and blood samples were significantly associated with cancer stage. Furthermore, the cellular levels of BRCA1, MDM2, and p53 were evaluated in peripheral blood lymphocytes (PBL) of 134 HNC patients and 126 controls by slot blotting...
October 6, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Dan Xu, Bing Zhang, Chongbing Liao, Wei Zhang, Weijia Wang, Ying Chang, Yongping Shao
Human beta-defensin 3 (hBD3), an antimicrobial peptide (AMP) expressed in epithelium in response to various stimulations including human papillomavirus infection, has recently been found to be overexpressed in head and neck cancers and exhibit tumorigenic activities. However, the role of hBD3 in cervical cancer remains to be investigated. In this study, we showed by immunohistochemistry that hBD3 expression was elevated in cervical cancer samples of different stages versus the normal tissue, and was positively correlated with the progression of the disease...
October 4, 2016: Oncotarget
Himalaya Parajuli, Muy-Teck Teh, Siren Abrahamsen, Ingrid Christoffersen, Evelyn Neppelberg, Stein Lybak, Tarig Osman, Anne Chr Johannessen, Donald Gullberg, Kathrine Skarstein, Daniela Elena Costea
BACKGROUND: Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin α11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker. AIM: To investigate integrin α11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (α-SMA), in HNSCC...
October 4, 2016: Journal of Oral Pathology & Medicine
Zubeyde Yalniz, Semra Demokan, Burak Karabulut, Murat Ulusan, Yusufhan Suoglu, Nejat Dalay
BACKGROUND: Sensitive and reliable new biomarkers are needed in head and neck cancer to predict the outcome and for therapy that is more effective. Copy number alterations are frequent and play a critical role in cancer. METHODS: Copy number alterations of 24 tumor suppressor genes in head and neck cancer were analyzed simultaneously in matched tumor and normal samples from 93 patients using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Chromosomes 3p and 9p displayed the most common alterations...
October 3, 2016: Head & Neck
Nicoleta Sinevici, Jeff O'sullivan
Oral Cancer (OC) is a subset of head and neck cancer (HNC) with an annual worldwide incidence of 275,000 cases. OC remains a significant burden worldwide in terms of diagnosis, treatment and prognosis. Despite desirable outcomes in early diagnosed OCs and treatment advances most OCs are detected in advanced stages. The 5-year survival rate of early-stage disease is ∼80% and that of late-stage disease is only ∼20%. Recurrence and chemoresistance from a treatment point of view and pain and disfiguration are important factors contributing to the high morbidity and mortality of OC...
October 2016: Oral Oncology
Henri Schmidt, Arutha Kulasinghe, Liz Kenny, Chamindie Punyadeera
Developing non-invasive diagnostic tools in the field of head and neck oncology has been a challenge. Analysis of circulating tumour derivatives in a patient's blood has been explored in other solid cancers. This includes analysis of circulating tumour DNA, intact circulating tumour cells (CTCs) and exosomes. These circulating tumour derivatives provide avenues of investigation which can be representative of a patient's primary tumour signature and can be assessed from a patient's blood sample. In advanced stage cancer patients, these tumour derivatives are found in higher amounts, attributed to higher cellular turnover (apoptosis, autophagy), lysed CTCs and sloughing from necrotic tumours...
October 2016: Oral Oncology
Kiyoshi Misawa, Daiki Mochizuki, Shiori Endo, Masato Mima, Yuki Misawa, Atsushi Imai, Kazuya Shinmura, Takeharu Kanazawa, Thomas E Carey, Hiroyuki Mineta
BACKGROUND: The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. METHODS: We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples...
September 29, 2016: Molecular Carcinogenesis
Xu Ji, Chao Guan, Xuejun Jiang, Hong Li
Abnormal methylation of certain cancer related genes strongly predicts a diagnosis of head and neck cancer (HNC), while the predictive power of methylation of other DNA markers for HNC remains unclear. To systemically assess the diagnostic value of DNA methylation patterns for HNC and the effect of methylation platform techniques and sample types, we performed a PubMed search for studies of the correlation between DNA methylation and HNC completed before July 2016, and extracted the sensitivity and specificity for methylated biomarkers...
September 23, 2016: Oncotarget
Damian T Rieke, Sebastian Ochsenreither, Konrad Klinghammer, Tanguy Y Seiwert, Frederick Klauschen, Inge Tinhofer, Ulrich Keilholz
Immune checkpoints are emerging treatment targets, but mechanisms underlying checkpoint expression are poorly understood. Since alterations in DNA repair genes have been connected to the efficacy of checkpoint inhibitors, we investigated associations between methylation of DNA repair genes and CTLA4 and CD274 (PD-L1) expression.A list of DNA repair genes (179 genes) was selected from the literature, methylation status and expression of inflammation-associated genes (The Cancer Genome Atlas data) was correlated in head and neck squamous cell carcinoma (HNSCC), cervical and lung squamous cell carcinoma...
September 23, 2016: Oncotarget
Jian Gao, Camilla H Ulekleiv, Trond S Halstensen
BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients...
September 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
Gregory S Alexander, Joshua D Palmer, Madalina Tuluc, Jianqing Lin, Adam P Dicker, Voichita Bar-Ad, Larry A Harshyne, Jennifer Louie, Colette M Shaw, D Craig Hooper, Bo Lu
BACKGROUND: Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1). Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient's own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20-40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment...
2016: Journal of Hematology & Oncology
Yenkai Lim, Yunxia Wan, Dimitrios Vagenas, Dmitry A Ovchinnikov, Chris F L Perry, Melissa J Davis, Chamindie Punyadeera
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumours with a typical 5 year survival rate of <40 %. DNA methylation in tumour-suppressor genes often occurs at an early stage of tumorigenesis, hence DNA methylation can be used as an early tumour biomarker. Saliva is an ideal diagnostic medium to detect early HNSCC tumour activities due to its proximity to tumour site, non-invasiveness and ease of sampling. We test the hypothesis that the surveillance of DNA methylation in five tumour-suppressor genes (RASSF1α, p16 (INK4a) , TIMP3, PCQAP/MED15) will allow us to diagnose HNSCC patients from a normal healthy control group as well as to discriminate between Human Papillomavirus (HPV)-positive and HPV-negative patients...
2016: BMC Cancer
Ayman Oweida, Shilpa Bhatia, Kellen Hirsch, Dylan Calame, Anastacia Griego, Steve Keysar, Todd Pitts, Jaspreet Sharma, Gail Eckhardt, Antonio Jimeno, Xiao Jing Wang, Gill Parkash, Joseph Califano, Sana Karam
Ephrin B2 is variably expressed on tumor cells and its blockade has been shown to inhibit angiogenesis in animal models of pancreatic, colorectal, lung and head and neck squamous cell carcinomas. However, the implications of ephrinB2 expression in cancer patients have remained elusive. In this study, we analyzed the cancer genome atlas (TCGA) for ephrinB2 expression. We report significant correlations between EFNB2 expression, overall survival and disease-free survival in head and neck squamous cell carcinoma (HNSCC, n = 519), pancreatic adenocarcinoma (n = 186) and bladder urothelial carcinoma (n = 410)...
September 20, 2016: Molecular Carcinogenesis
Turki Y Alhazzazi, Faisal T Alghamdi
BACKGROUND: Head and neck cancer (HNC) is the ninth most common cancer worldwide, and has a poor 5-year survival rate averaging 50%, which has not changed for decades. A high prevalence of HNC has been reported in the southwestern region of Saudi Arabia, as compared to other areas of the country. However, data in regards to HNC are scattered and not well documented. Thus, the aim of this systematic review was to gather all available and updated important information regarding HNC in Saudi Arabia, and highlight the gaps of knowledge in our country with regard to this disease...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
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