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https://www.readbyqxmd.com/read/28812223/prognostic-potential-of-klotho-and-sfrp1-promoter-methylation-in-head-and-neck-squamous-cell-carcinoma
#1
Abeer A Alsofyani, Rawiah A Alsiary, Alaa Samkari, Baraa T Alhaj-Hussain, Jalaluddin Azam Khan, Jaudah Al-Maghrabi, Aisha Elaimi, Mohammed H Al-Qahtani, Adel M Abuzenadah, Ashraf Dallol
Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues...
August 16, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28807520/egfr-amplification-plus-gene-expression-profiling-predicts-response-to-combined-radiotherapy-with-egfr-inhibition-a-preclinical-trial-in-10-hnscc-tumour-xenograft-models
#2
Lydia Koi, Steffen Löck, Annett Linge, Cedric Thurow, Sandra Hering, Michael Baumann, Mechthild Krause, Kristin Gurtner
BACKGROUND AND PURPOSE: Improvement of the results of radiotherapy by EGFR inhibitors is modest, suggesting significant intertumoural heterogeneity of response. To identify potential biomarkers, a preclinical trial was performed on ten different human squamous cell carcinoma xenografts of the head and neck (HNSCC) studying in vivo and ex vivo the effect of fractionated irradiation and EGFR inhibition. Local tumour control and tumour growth delay were correlated with potential biomarkers, e...
August 11, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28801876/tumor-dna-an-emerging-biomarker-in-head-and-neck-cancer
#3
Joseph A Bellairs, Rifat Hasina, Nishant Agrawal
Head and neck cancer (HNC) includes a diverse range of malignancies arising commonly from mucosal epithelia of the upper aerodigestive tract. Head and neck squamous cell carcinoma (HNSCC), the most common form of HNC, develops in the oral cavity, pharynx, and larynx and is associated with tobacco exposure, alcohol abuse, and infection with oncogenic viruses. Despite global advances in cancer care, HNSCC often presents with advanced disease and is associated with poor 5-year survival of ~50%. Genotyping tumor tissue to guide clinical decision-making is becoming commonplace in modern oncology, but in the management of HNSCC, tissue biopsies with cytopathology or histopathology remain the mainstay for diagnosis...
August 12, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28756882/cell-genomics-and-immunosuppressive-biomarker-expression-influence-pd-l1-immunotherapy-treatment-responses-in-hnscc-a-computational-study
#4
Amber M Bates, Emily A Lanzel, Fang Qian, Taher Abbasi, Shireen Vali, Kim A Brogden
OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is correlated with objective response rates to PD-1 and PD-L1 immunotherapies. However, both immunotherapies have only demonstrated 12%-24.8% objective response rates in patients with head and neck squamous cell carcinoma (HNSCC), demonstrating a need for a more accurate method to identify those who will respond before their therapy. Immunohistochemistry to detect PD-L1 reactivity in tumors can be challenging, and additional methods are needed to predict and confirm PD-L1 expression...
August 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28732368/meta-analysis-of-micrornas-expression-in-head-and-neck-cancer-uncovering-association-with-outcome-and-mechanisms
#5
Joshua Lubov, Mariana Maschietto, Iman Ibrahim, Alex Mlynarek, Michael Hier, Luiz Paulo Kowalski, Moulay A Alaoui-Jamali, Sabrina Daniela da Silva
Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#6
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28688683/predictive-and-prognostic-value-of-ct-based-radiomics-signature-in-locally-advanced-head-and-neck-cancers-patients-treated-with-concurrent-chemoradiotherapy-or-bioradiotherapy-and-its-added-value-to-human-papillomavirus-status
#7
Dan Ou, Pierre Blanchard, Silvia Rosellini, Antonin Levy, France Nguyen, Ralph T H Leijenaar, Ingrid Garberis, Philippe Gorphe, François Bidault, Charles Ferté, Charlotte Robert, Odile Casiraghi, Jean-Yves Scoazec, Philippe Lambin, Stephane Temam, Eric Deutsch, Yungan Tao
OBJECTIVES: To explore prognostic and predictive value of radiomics in patients with locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated with concurrent chemoradiotherapy (CRT) or bioradiotherapy (BRT). MATERIALS AND METHODS: Data of 120 patients (CRT vs. BRT matched 2:1) were retrospectively analyzed. A total of 544 radiomics features of the primary tumor were extracted from radiotherapy planning computed tomography scans. Cox proportional hazards models were used to examine the association between survival and radiomics features with false discovery rate correction...
August 2017: Oral Oncology
https://www.readbyqxmd.com/read/28679497/high-level-of-tobacco-carcinogen-derived-dna-damage-in-oral-cells-is-an-independent-predictor-of-oral-head-and-neck-cancer-risk-in-smokers
#8
Samir S Khariwala, Bin Ma, Chris Ruszczak, Steven G Carmella, Bruce R Lindgren, Dorothy K Hatsukami, Stephen S Hecht, Irina Stepanov
Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC).  We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared to cancer-free smokers.  In this study we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC...
July 5, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28645105/a-three-gene-immunohistochemical-panel-serves-as-an-adjunct-to-clinical-staging-of-patients-with-head-and-neck-cancer
#9
Chin-Ann J Ong, Nicholas B Shannon, Stefan Mueller, Sze Min Lek, Xuan Qiu, Fui Teen Chong, Ke Li, Kelvin K N Koh, Gerald C A Tay, Thakshayeni Skanthakumar, Jacqueline S G Hwang, Tony Kiat Hon Lim, Mei Kim Ang, Daniel S W Tan, Ngian-Chye Tan, Hiang Khoon Tan, Khee Chee Soo, N Gopalakrishna Iyer
BACKGROUND: Current management of head and neck squamous cell carcinoma (HNSCC) depends on tumor staging. Despite refinements in clinical staging algorithms, outcomes remain unchanged for the last two decades. In this study, we set out to identify a small, clinically applicable molecular panel to aid prognostication of patients with HNSCC. MATERIALS AND METHODS: Data from The Cancer Genome Atlas (TCGA) was used to derive copy number aberrations and expression changes to identify putative prognostic genes...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28640948/high-level-%C3%AE-iii-tubulin-overexpression-occurs-in-most-head-and-neck-cancers-but-is-unrelated-to-clinical-outcome
#10
Julie C Nienstedt, Alexander Gröbe, Till Clauditz, Ronald Simon, Adrian Muenscher, Rainald Knecht, Guido Sauter, Christoph Moebius, Marco Blessmann, Max Heiland, Christina Pflug
BACKGROUND: βIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, the present study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC...
June 22, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28638796/levels-of-neutrophil-gelatinase-assosciated-lipocalin-in-patients-with-head-and-neck-squamous-cell-carcinoma-in-indian-population-from-haryana-state
#11
Monica Verma, Kiran Dahiya, Abhishek Soni, Rakesh Dhankhar, Veena S Ghalaut, Aastha Bansal, Vivek Kaushal
AIM: To study the levels of neutrophil gelatinase associated lipocalin (NGAL) in head and neck squamous cell carcinoma (HNSCC). METHODS: This was a non randomized case control study conducted at Department of Biochemistry, in collaboration with Regional Cancer Center over a period of one year. The study population included 50 adult newly diagnosed HNSCC patients reporting in outpatient department at Regional Cancer Center and compared with 50 healthy controls. NGAL was estimated by ELISA technique...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#12
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629339/droplet-digital-pcr-for-detection-and-quantification-of-circulating-tumor-dna-in-plasma-of-head-and-neck-cancer-patients
#13
Joost H van Ginkel, Manon M H Huibers, Robert J J van Es, Remco de Bree, Stefan M Willems
BACKGROUND: During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biomarker for monitoring tumor burden during posttreatment surveillance of these patients. In this exploratory study, we investigated whether low level ctDNA in plasma of head and neck cancer patients can be detected using Droplet Digital PCR (ddPCR). METHODS: TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC)...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28617833/clinical-performance-validation-of-pitx2-dna-methylation-as-prognostic-biomarker-in-patients-with-head-and-neck-squamous-cell-carcinoma
#14
Verena Sailer, Heidrun Gevensleben, Joern Dietrich, Diane Goltz, Glen Kristiansen, Friedrich Bootz, Dimo Dietrich
BACKGROUND: Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc...
2017: PloS One
https://www.readbyqxmd.com/read/28616099/epigenetic-silencing-of-sall3-is-an-independent-predictor-of-poor-survival-in-head-and-neck-cancer
#15
Kiyoshi Misawa, Daiki Mochizuki, Atsushi Imai, Yuki Misawa, Shiori Endo, Masato Mima, Hideya Kawasaki, Thomas E Carey, Takeharu Kanazawa
BACKGROUND: This study examined Sal-like protein (SALL)3 methylation profiles of head and neck cancer (HNSCC) patients at diagnosis and follow-up and evaluated their prognostic significance and value as a biomarker. SALL3 expression was examined in a panel of cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the SALL3 promoter was examined by quantitative methylation-specific PCR. RESULTS: SALL3 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 64...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28608777/tumor-metabolism-in-the-microenvironment-of-nodal-metastasis-in-oral-squamous-cell-carcinoma
#16
Joseph Curry, Patrick Tassone, Kurren Gill, Madalina Tuluc, Voichita BarAd, Mehri Mollaee, Diana Whitaker-Menezes, Ulrich Rodeck, Adam Luginbuhl, David Cognetti, William Keane, Ubaldo Martinez-Outschoorn
Objective In many cancers, including head and neck squamous cell carcinoma (HNSCC), different regions within a tumor have different metabolic phenotypes. Transfer of metabolites between compartments promotes tumor growth and aggressive behavior. Metabolic compartmentalization in HNSCC nodal metastases has not been studied, nor has its impact on extracapsular extension or clinical outcomes been determined. Study Design Retrospective analysis based on immunohistochemistry staining. Setting Tertiary care center...
June 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28592616/multicenter-phase-ii-study-of-panitumumab-in-platinum-pretreated-advanced-head-and-neck-squamous-cell-cancer
#17
Marco Siano, Francesca Molinari, Vittoria Martin, Nicolas Mach, Martin Früh, Stefania Freguia, Irene Corradino, Michele Ghielmini, Milo Frattini, Vittoria Espeli
LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies...
July 2017: Oncologist
https://www.readbyqxmd.com/read/28560858/basal-subtype-is-predictive-for-response-to-cetuximab-treatment-in-patient-derived-xenografts-of-squamous-cell-head-and-neck-cancer
#18
Konrad Klinghammer, Raik Otto, Jan-Dirk Raguse, Andreas E Albers, Ingeborg Tinhofer, Iduna Fichtner, Ulf Leser, Ulrich Keilholz, Jens Hoffmann
Cetuximab is the single targeted therapy approved for the treatment of head and neck cancer (HNSCC). Predictive biomarkers have not been established and patient stratification based on molecular tumor profiles has not been possible. Since EGFR pathway activation is pronounced in basal subtype, we hypothesized this activation could be a predictive signature for an EGFR directed treatment. From our patient-derived xenograft platform of HNSCC, 28 models were subjected to Affymetrix gene expression studies on HG U133+ 2...
May 30, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28559019/il6-is-associated-with-response-to-dasatinib-and-cetuximab-phase-ii-clinical-trial-with-mechanistic-correlatives-in-cetuximab-resistant-head-and-neck-cancer
#19
L P Stabile, A M Egloff, M K Gibson, W E Gooding, J Ohr, P Zhou, N J Rothenberger, L Wang, J L Geiger, J T Flaherty, J R Grandis, J E Bauman
OBJECTIVE: Src family kinase (SFK) activation circumvents epidermal growth factor receptor (EGFR) targeting in head and neck squamous cell carcinoma (HNSCC); dual SFK-EGFR targeting could overcome cetuximab resistance. PATIENTS AND METHODS: We conducted a Simon two-stage, phase II trial of the SFK inhibitor, dasatinib, and cetuximab in biomarker-unselected patients with cetuximab-resistant, recurrent/metastatic HNSCC. Pre- and post-treatment serum levels of interleukin-6 (IL6) were measured by ELISA...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28552844/pd-l1-a-novel-prognostic-biomarker-in-head-and-neck-squamous-cell-carcinoma
#20
Tim Müller, Martin Braun, Dimo Dietrich, Seher Aktekin, Simon Höft, Glen Kristiansen, Friederike Göke, Andreas Schröck, Johannes Brägelmann, Stefanie A E Held, Friedrich Bootz, Peter Brossart
BACKGROUND: The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking...
May 2, 2017: Oncotarget
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