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Min Pan, Henrik Schinke, Elke Luxenburger, Gisela Kranz, Julius Shakhtour, Darko Libl, Yuanchi Huang, Aljaž Gaber, Miha Pavšič, Brigita Lenarčič, Julia Kitz, Mark Jakob, Sabina Schwenk-Zieger, Martin Canis, Julia Hess, Kristian Unger, Philipp Baumeister, Olivier Gires
Head and neck squamous cell carcinomas (HNSCCs) are characterized by outstanding molecular heterogeneity that results in severe therapy resistance and poor clinical outcome. Inter- and intratumoral heterogeneity in epithelial-mesenchymal transition (EMT) was recently revealed as a major parameter of poor clinical outcome. Here, we addressed the expression and function of the therapeutic target epidermal growth factor receptor (EGFR) and of the major determinant of epithelial differentiation epithelial cell adhesion molecule (EpCAM) in clinical samples and in vitro models of HNSCCs...
September 2018: PLoS Biology
Shanmei Du, Kui Liu, Peng Gao, Zhongyou Li, Jie Zheng
AIMS: Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) are caused by human papillomavirus (HPV) infection. The effect of arsenic trioxide (ATO) on HPV oncogene expression of HNSCC cells remains unknown. In this study, we investigated the anti-cancer activity and possible molecular pathways of ATO on the six HNSCC cell lines (three HPV-positive and three HPV-negative). METHODS: The effects of ATO on the cell proliferation, apoptosis, cell cycle of HNSCC cells were analyzed using CCK-8 assay, colony formation and flow cytometry...
September 20, 2018: Life Sciences
M-N Theodoraki, T K Hoffmann, E K Jackson, T L Whiteside
Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+ CD39+ regulatory T cells (Treg ) co-incubated with these exosomes...
October 2018: Clinical and Experimental Immunology
D Vicky de Boer, Arjen Brink, Marijke Buijze, Marijke Stigter-van Walsum, Keith D Hunter, Bauke Ylstra, Elisabeth Bloemena, C René Leemans, Ruud H Brakenhoff
Head and neck squamous cell carcinomas (HNSCCs) develop in fields of genetically altered cells. These fields are often dysplastic and a subset can be recognized as (erythro)leukoplakia, but most are macroscopically invisible. There is a lack of adequate treatment options to eradicate these fields, while they underlie the development of primary tumors as well as part of the local relapses. Unfortunately, there are almost no representative cellular models available to identify suitable treatment options. To this end, clinical biopsy specimens (n=98) were cultured from normal appearing mucosa of the surgical margins of patients with primary HNSCCs (n=32) to generate precancer cell culture models...
September 17, 2018: Molecular Cancer Research: MCR
Mohammad-Hossein Taziki, Abdolreza Fazel, Fatemeh Salamat, Seyed-Mehdi Sedaghat, Mohammad Ashaari, Hossein Poustchi, Ramin Shakeri, Reza Hoseinpoor, Susan Hasanpour-Heidari, Gholamreza Roshandel
BACKGROUND: Golestan province, in Northern Iran, is a high-risk area for esophageal squamous cell carcinoma (SCC). SCC is also the most common histological type of cancers of the head and neck region including cancers of oral cavity, oropharynx, hypopharynx and larynx. We aimed to present the incidence rate of head and neck SCC (HNSCC) in Golestan province during 2004 and 2013. METHODS: Data on HNSCC were obtained from Golestan population-based cancer registry (GPCR)...
September 1, 2018: Archives of Iranian Medicine
Dong Jin Lee, Young-Gyu Eun, Young Soo Rho, Eui Hyun Kim, Sun Young Yim, Sang Hee Kang, Bo Hwa Sohn, Gee Hwan Kwon, Ju-Seog Lee
OBJECTIVES: Heterogeneity of head and neck squamous cell carcinomas (HNSCCs) results in unpredictable outcomes for patients with similar stages of cancer. Beyond the role of human papilloma virus (HPV), no validated molecular marker of HNSCCs has been established. Thus, clinically relevant molecular subtypes are needed to optimize HNSCC therapy. The purpose of this study was to identify subtypes of HNSCC that have distinct biological characteristics associated with clinical outcomes and to characterize genomic alterations that best reflect the biological and clinical characteristics of each subtype...
October 2018: Oral Oncology
Alessandra Vidotto, Giovana M Polachini, Marina de Paula-Silva, Sonia M Oliani, Tiago Henrique, Rossana V M López, Patrícia M Cury, Fabio D Nunes, José F Góis-Filho, Marcos B de Carvalho, Andréia M Leopoldino, Eloiza H Tajara
BACKGROUND: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. METHODS: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC...
August 29, 2018: BMC Medical Genomics
Kazuhiro Kobayashi, Kenji Hisamatsu, Natsuko Suzui, Akira Hara, Hiroyuki Tomita, Tatsuhiko Miyazaki
Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes...
August 27, 2018: Journal of Clinical Medicine
N Raulf, P Lucarelli, S Thavaraj, S Brown, J M Vicencio, T Sauter, M Tavassoli
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer with approximately half a million cases diagnosed each year worldwide. HNSCC has a poor survival rate which has not improved for over 30 years. The molecular pathogenesis of HNSCCs remains largely unresolved; there is high prevalence of p53 mutations and EGFR overexpression; however, the contribution of these molecular changes to disease development and/or progression remains unknown. We have recently identified microRNA miR-196a to be highly overexpressed in HNSCC with poor prognosis...
October 2018: European Journal of Cancer
Matt Lechner, Ankur R Chakravarthy, Vonn Walter, Liam Masterson, Andrew Feber, Amrita Jay, Paul M Weinberger, Richard A McIndoe, Cillian T Forde, Kerry Chester, Nicholas Kalavrezos, Paul O'Flynn, Martin Forster, Terry M Jones, Francis M Vaz, D Neil Hayes, Tim R Fenton
OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project...
August 2018: Oral Oncology
Alexandra Iulia Irimie, Cornelia Braicu, Roxana Cojocneanu, Lorand Magdo, Anca Onaciu, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Smaranda Buduru, Ioana Berindan-Neagoe
Smoking is a well-known behavior that has an important negative impact on human health, and is considered to be a significant factor related to the development and progression of head and neck squamous cell carcinomas (HNSCCs). Use of high-dimensional datasets to discern novel HNSCC driver genes related to smoking represents an important challenge. The Cancer Genome Atlas (TCGA) analysis was performed in three co-existing groups of HNSCC in order to assess whether gene expression landscape is affected by tobacco smoking, having quit, or non-smoking status...
July 23, 2018: International Journal of Environmental Research and Public Health
Lixia Gao, Xiangdong Zhao, Liwei Lang, Chloe Shay, W Andrew Yeudall, Yong Teng
The functional relationship between apoptosis and autophagy in anticancer drug treatment is extremely complex, and the molecular machinery is obscure. This study aims to investigate the efficacy of CYT997, a novel microtubule-disrupting agent, in head and neck squamous cell carcinomas (HNSCCs) and complete the autophagy-apoptosis puzzle involved in drug action. We report here that CYT997 exhibits anticancer activity by triggering oxidative stress-associated apoptosis in HNSCC cells. Interestingly, upregulation of autophagy by mTOR-dependent pathways appears to have a cytoprotective role in preventing apoptosis by inhibiting CYT997-induced excessively high levels of reactive oxygen species (ROS)...
September 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
L van der Merwe, Y Wan, H J Cheong, C Perry, C Punyadeera
BACKGROUND: Early diagnosis of head and neck squamous cell carcinoma (HNSCCs) is an appealing way to increase survival rates in these patients as well as to improve quality of life post-surgery. Angiogenesis is a hallmark of tumor initiation and progression. We have investigated a panel of angiogenic factors in saliva samples collected from HNSCC patients and controls using the Bio-Plex ProTM assays. METHODS: We have identified a panel of five angiogenic proteins (sEGFR, HGF, sHER2, sIL-6Ra and PECAM-1) to be elevated in the saliva samples collected from HNSCC patients (n = 58) compared to a control cohort (n = 8 smokers and n = 30 non-smokers)...
July 13, 2018: BMC Cancer
Shilpa Bhatia, Anastacia Griego, Shelby Lennon, Ayman Oweida, Jaspreet Sharma, Christina Rohmer, Nomin Uyanga, Sanjana Bukkapatnam, Benjamin Van Court, David Raben, Christian Young, Lynn Heasley, Sana D Karam
Eph proteins have emerged as critical drivers affecting tumor growth and progression in human malignancies. Our The Cancer Genome Atlas (TCGA) data analysis showed that EphB3, a receptor tyrosine kinase, is frequently coamplified with PIK3CA in head and neck squamous cell carcinoma (HNSCC). We therefore hypothesized that EphB3 amplification plays a protumorigenic role in HNSCC and that EphB3 and PIK3CA are cooperating oncogenes that contribute toward its pathogenesis. This hypothesis was not experimentally supported, because EphB3 knockdown failed to alter HNSCC tumor cell growth in vitro or in vivo with an orthotopic model...
September 2018: Molecular Cancer Therapeutics
Natalia Saenz-Ponce, Rachael Pillay, Lilia Merida de Long, Trinayan Kashyap, Christian Argueta, Yosef Landesman, Mehlika Hazar-Rethinam, Samuel Boros, Benedict Panizza, Maarten Jacquemyn, Dirk Daelemans, Orla M Gannon, Nicholas A Saunders
Patient mortality rates have remained stubbornly high (40%) for the past 35 years in head and neck squamous cell carcinoma (HNSCC) due to inherent or acquired drug resistance. Thus, a critical issue in advanced SCC is to identify and target the mechanisms that contribute to therapy resistance. We report that the transcriptional inhibitor, E2F7, is mislocalized to the cytoplasm in >80% of human HNSCCs, whereas the transcriptional activator, E2F1, retains localization to the nucleus in SCC. This results in an imbalance in the control of E2F-dependent targets such as SPHK1 , which is derepressed and drives resistance to anthracyclines in HNSCC...
June 27, 2018: Science Translational Medicine
Ramona Gabriela Ursu, Mihai Danciu, Irene Alexandra Spiridon, Ruediger Ridder, Susanne Rehm, Fausto Maffini, Sandrine McKay-Chopin, Christine Carreira, Eric Lucas, Victor-Vlad Costan, Eugenia Popescu, Bogdan Cobzeanu, Nicolae Ghetu, Luminita Smaranda Iancu, Massimo Tommasino, Michael Pawlita, Dana Holzinger, Tarik Gheit
BACKGROUND: Limited information is available about the involvement of human papillomavirus (HPV) in head and neck squamous cell carcinomas (HNSCCs) in Romanian patients. OBJECTIVE: To evaluate the HPV-attributable fraction in HNSCCs collected in Northeastern Romania. MATERIALS AND METHODS: In total, 189 formalin-fixed paraffin-embedded tissue samples (99 oral cavity tumors, 28 oropharynx, 48 pharynx, and 14 larynx/hypopharynx) were analyzed for HPV DNA and RNA using Luminex-based assays, and for overexpression of p16INK4a (p16) by immunohistochemistry...
2018: PloS One
Esma Saada-Bouzid, Gérard Milano, Juliette Thariat
Squamous cell carcinomas are the most frequent subgroup among head and neck malignant tumors (HNSCC). Tobacco (±alcohol) and HPV infection, the two main risk factors, define two entities with distinct anatomo-clinical and genetic features. HPV-positive, non-tobacco-related HNSCCs are associated with a better prognosis, a rather simple genomic profile, frequent activating mutations of genes involved in pi3kinase-pathway, and the scarcity of mutations of tumor suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more complex, are characterized by almost mandatory inactivating mutations/deletions of tumor suppressor genes (TP53, CDKN2A) and the possible, but less frequent, activating mutations or amplifications of some oncogenes that encode for cell cycle proteins or receptors with tyrosine kinase activity...
September 2018: Bulletin du Cancer
A Picard, L Arowas, L Piroth, I Heard, T Ferry
OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors - especially oropharyngeal cancer - are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. METHODS: Retrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014...
June 7, 2018: Médecine et Maladies Infectieuses
Joanna K Strzelczyk, Łukasz Krakowczyk, Karolina Gołąbek, Aleksander J Owczarek
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are associated with an interplay between genetics and the environment; they account for 3% of all diagnosed malignant tumors in men and 2% of those in women. OBJECTIVES: The aim of the study was to analyze the significance of TIMP3, SFRP1, SFRP2, CDH1, RASSF1, RORA, and DAPK1 gene expression in head and neck squamous cell carcinoma tumors, and in matching surgical margin samples. We also analyzed the association between clinical parameters and the expression of the selected genes...
June 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Tomasz Szafarowski, Janusz Sierdzinski, Miroslaw J Szczepanski, Theresa L Whiteside, Nils Ludwig, Antoni Krzeski
PURPOSE: Microvessel density (MVD) corresponds to the intensity of neo-angiogenesis. MVD assessments are based on the expression levels of the vascular endothelium markers such as, e.g., CD34 or CD105. The goal of this study was to assess MVD among patients with head and neck squamous cell carcinoma (HNSCC), and to evaluate the predictive value of MVD in head and neck cancers. METHODS: The study included 49 patients treated for HNSCC and 11 patients with dysplasia of the upper respiratory tract epithelium...
July 2018: European Archives of Oto-rhino-laryngology
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