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biomarkers hnscc

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https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#1
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515105/free-circulating-methylated-dna-in-blood-for-diagnosis-staging-prognosis-and-monitoring-of-head-and-neck-squamous-cell-carcinoma-patients-an-observational-prospective-cohort-study
#2
Andreas Schröck, Annette Leisse, Luka de Vos, Heidrun Gevensleben, Freya Dröge, Alina Franzen, Malin Wachendörfer, Friederike Schröck, Joerg Ellinger, Marcus Teschke, Timo Wilhelm-Buchstab, Jennifer Landsberg, Stefan Holdenrieder, Gunther Hartmann, John K Field, Friedrich Bootz, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCC) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox 2 (SHOX2) and septin 9 (SEPT9) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance...
May 17, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28507307/a-novel-indication-for-panobinostat-as-a-senolytic-drug-in-nsclc-and-hnscc
#3
Leleesha Samaraweera, Alfred Adomako, Alicia Rodriguez-Gabin, Hayley M McDaid
Panobinostat (pano) is an FDA-approved histone deacetylase inhibitor. There is interest in evaluating alternate dosing schedules and novel combinations of pano for the treatment of upper aerodigestive and lung malignancies; thus we evaluated it in combination with Taxol, a chemotherapeutic with activity in both diseases. Dose-dependent synergy was observed in Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines and was due to senescence rather than potentiation of cell death...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490889/identification-of-potential-biomarkers-and-analysis-of-prognostic-values-in-head-and-neck-squamous-cell-carcinoma-by-bioinformatics-analysis
#4
Bo Yang, Zhifeng Chen, Yu Huang, Guoxu Han, Weizhong Li
The purpose of this study was to find disease-associated genes and potential mechanisms in head and neck squamous cell carcinoma (HNSCC) with deoxyribonucleic acid microarrays. The gene expression profiles of GSE6791 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were obtained with packages in R language and STRING constructed protein-protein interaction (PPI) network of the DEGs with combined score >0.8. Subsequently, module analysis of the PPI network was performed by Molecular Complex Detection plugin and functions and pathways of the hub gene in subnetwork were studied...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28487502/pdcd1-pd-1-promoter-methylation-predicts-outcome-in-head-and-neck-squamous-cell-carcinoma-patients
#5
Diane Goltz, Heidrun Gevensleben, Joern Dietrich, Friederike Schroeck, Luka de Vos, Freya Droege, Glen Kristiansen, Andreas Schroeck, Jennifer Landsberg, Friedrich Bootz, Dimo Dietrich
BACKGROUND: Biomarkers that facilitate the prediction of disease recurrence in head and neck squamous cell carcinoma (HNSCC) may enable physicians to personalize treatment. In the current study, DNA promoter methylation of programmed cell death 1 (PDCD1, PD-1) was evaluated as a prognostic biomarker in HNSCC patients. RESULTS: High PDCD1 methylation (mPDCD1) was associated with a significantly shorter overall survival after surgical resection in both the discovery (HR = 2...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446642/co-targeting-mtorc-and-egfr-signaling-as-a-therapeutic-strategy-in-hnscc
#6
Adam D Swick, Prashanth J Prabakaran, Margot C Miller, Amal M Javaid, Michael M Fisher, Emmanuel Sampene, Irene M Ong, Rong Hu, Mari Iida, Kwangok P Nickel, Justine Y Bruce, Deric L Wheeler, Randall J Kimple
Head and neck squamous cell carcinomas (HNSCCs) are frequently altered along the PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, the use of compounds targeting this pathway as monotherapy has been underwhelming in initial clinical trials and identification of predictive biomarkers remains challenging. To investigate mTORC specific inhibition we tested catalytic mTORC (AZD8055) and PI3K/mTORC (NVP-BEZ-235) inhibitors +/- cetuximab in a panel of HNSCC cell lines and patient derived xenografts (PDX)...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28440978/methylation-status-of-p16ink4a-in-human-papillomavirus-associated-cancer-of-oral-cavity-and-oropharynx-in-northeastern-thailand
#7
Piyawut Swangphon, Chamsai Pientong, Ati Burassakarn, Patravoot Vatanasapt, Pilaiwan Kleebkaow, Natcha Patarapadungkit, Thanabut Treebupachatsakul, Supannee Promthet, Bunkerd Kongyingyoes, Tipaya Ekalaksananan
Background: Over-expression of p16INK4a protein is a biomarker for human papillomavirus (HPV)-associated cervical cancer. However, absence of p16INK4a protein expression in HPV-associated cancer of the oral cavity and oropharynx has been reported. Among a number of possible reasons for this is methylation, which is frequently noted in the promoter region of p16INK4a and is associated with silencing of the gene and disease severity. Methods: We investigated the relationships between p16INK4a protein expression, HPV infection and methylation status of the p16INK4a promoter in cancers of the oral cavity and oropharynx...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlate-with-response-in-head-and-neck-cancer-patients
#8
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8(+) tumor-infiltrating lymphocytes (TIL) and compared them with those of peripheral blood T lymphocytes (PBL) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28352657/randomized-placebo-controlled-window-trial-of-egfr-src-or-combined-blockade-in-head-and-neck-cancer
#9
Julie E Bauman, Umamaheswar Duvvuri, William E Gooding, Tanya J Rath, Neil D Gross, John Song, Antonio Jimeno, Wendell G Yarbrough, Faye M Johnson, Lin Wang, Simion Chiosea, Malabika Sen, Jason Kass, Jonas T Johnson, Robert L Ferris, Seungwon Kim, Fred R Hirsch, Kimberly Ellison, John T Flaherty, Gordon B Mills, Jennifer R Grandis
BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28351564/role-of-cancer-stem-cell-marker-doublecortin-like-kinase-1-in-head-and-neck-squamous-cell-carcinoma
#10
Lorenz Kadletz, Dietmar Thurnher, Robert Wiebringhaus, Boban M Erovic, Ulana Kotowski, Sven Schneider, Rainer Schmid, Lukas Kenner, Gregor Heiduschka
BACKGROUND: So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro. METHODS: We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28347920/mir-200b-and-mir-155-as-predictive-biomarkers-for-the-efficacy-of-chemoradiation-in-locally-advanced-head-and-neck-squamous-cell-carcinoma
#11
Anne-Katrin Hess, Annika Müer, Fabian Dominik Mairinger, Wilko Weichert, Albrecht Stenzinger, Michael Hummel, Volker Budach, Ingeborg Tinhofer
BACKGROUND: The predictive value of microRNAs (miRNAs) in tumour cells and infiltrating immune cells for the efficacy of chemoradiation (CRTX) in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated. METHODS: Formalin-fixed, paraffin-embedded tumour material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin (CDDP-CRTX) or 5-fluorouracil/mitomycin C (MMC-CRTX)...
March 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28285707/intratumoural-heterogeneity-measured-using-fdg-pet-and-mri-is-associated-with-tumour-stroma-ratio-and-clinical-outcome-in-head-and-neck-squamous-cell-carcinoma
#12
J W Choi, D Lee, S H Hyun, M Han, J-H Kim, S J Lee
AIM: To evaluate the association between the tumour-stroma ratio and intratumoural heterogeneity measured using 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) and magnetic resonance imaging (MRI), and further investigate the prognostic significance of imaging biomarkers in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Textural-based imaging parameters of the primary tumour were extracted in 44 patients. In addition, the difference between the minimum and maximum apparent diffusion coefficient (ADC) values (ADCdiff) was calculated on MRI...
March 9, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28261333/surveilling-the-potential-for-precision-medicine-driven-pd-1-pd-l1-targeted-therapy-in-hnscc
#13
REVIEW
J E Mann, R Hoesli, N L Michmerhuizen, S N Devenport, M L Ludwig, T R Vandenberg, C Matovina, N Jawad, M Mierzwa, A G Shuman, M E Spector, J C Brenner
Immunotherapy is becoming an accepted treatment modality for many patients with cancer and is now approved for use in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Despite these successes, a minority of patients with HNSCC receiving immunotherapy respond to treatment, and few undergo a complete response. Thus, there is a critical need to identify mechanisms regulating immune checkpoints in HNSCC such that one can predict who will benefit, and so novel combination strategies can be developed for non-responders...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#14
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174607/pitx3-dna-methylation-is-an-independent-predictor-of-overall-survival-in-patients-with-head-and-neck-squamous-cell-carcinoma
#15
Verena Sailer, Emily Eva Holmes, Heidrun Gevensleben, Diane Goltz, Freya Dröge, Alina Franzen, Jörn Dietrich, Glen Kristiansen, Friedrich Bootz, Andreas Schröck, Dimo Dietrich
BACKGROUND: Molecular biomarkers assisting risk-group assignment and subsequent treatment stratification are urgently needed for patients with squamous cell cancer of the head and neck region (HNSCC). Aberrant methylation is a frequent event in cancer and, therefore, a promising source for potential biomarkers. Here, the methylation status of the paired-like homeodomain transcription factor 3 (PITX3) was evaluated in HNSCC. METHODS: Using a quantitative real-time PCR, PITX3 methylation was assessed in a cohort of 326 HNSCC patients treated for localized or locally advanced disease (training cohort)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28174235/an-integrated-approach-identifies-mediators-of-local-recurrence-in-head-neck-squamous-carcinoma
#16
Francesca Citron, Joshua Armenia, Giovanni Franchin, Jerry Polesel, Renato Talamini, Sara D'Andrea, Sandro Sulfaro, Carlo M Croce, William Klement, Dave Otasek, Chiara Pastrello, Tomas Tokar, Igor Jurisica, Deborah French, Riccardo Bomben, Emanuela Vaccher, Diego Serraino, Barbara Belletti, Andrea Vecchione, Luigi Barzan, Gustavo Baldassarre
PURPOSE: Head and Neck Squamous Cell Carcinomas (HNSCC) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected microRNAs (miRs) could be used as biomarkers of recurrence in HNSCC. EXPERIMENTAL DESIGN: A Nanostring array was used to identify miRs associated with locoregional recurrence in 44 HNSCC patients...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28160562/the-tumor-suppressor-capability-of-p53-is-dependent-on-non-muscle-myosin-iia-function-in-head-and-neck-cancer
#17
Sonya D Coaxum, Jessica Tiedeken, Elizabeth Garrett-Mayer, Jeffrey Myers, Steven A Rosenzweig, David M Neskey
Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53). Our recent work has identified an approach to stratify patients with tumors harboring high or low risk TP53 mutations. Non-muscle Myosin IIA (NMIIA) was recently identified as a tumor suppressor in HNSCC. We now demonstrate that low MYH9 expression is associated with decreased survival in patients with head and neck cancer harboring low-risk mutp53 but not high-risk mutp53...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28126323/mutations-of-the-lim-protein-ajuba-mediate-sensitivity-of-head-and-neck-squamous-cell-carcinoma-to-treatment-with-cell-cycle-inhibitors
#18
Ming Zhang, Ratnakar Singh, Shaohua Peng, Tuhina Mazumdar, Vaishnavi Sambandam, Li Shen, Pan Tong, Lerong Li, Nene N Kalu, Curtis R Pickering, Mitchell Frederick, Jeffrey N Myers, Jing Wang, Faye M Johnson
The genomic alterations identified in head and neck squamous cell carcinoma (HNSCC) tumors have not resulted in any changes in clinical care, making the development of biomarker-driven targeted therapy for HNSCC a major translational gap in knowledge. To fill this gap, we used 59 molecularly characterized HNSCC cell lines and found that mutations of AJUBA, SMAD4 and RAS predicted sensitivity and resistance to treatment with inhibitors of polo-like kinase 1 (PLK1), checkpoint kinases 1 and 2, and WEE1. Inhibition or knockdown of PLK1 led to cell-cycle arrest at the G2/M transition and apoptosis in sensitive cell lines and decreased tumor growth in an orthotopic AJUBA-mutant HNSCC mouse model...
April 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28109476/a-three-lncrna-signature-derived-from-the-atlas-of-ncrna-in-cancer-tanric-database-predicts-the-survival-of-patients-with-head-and-neck-squamous-cell-carcinoma
#19
Wei Cao, Jian-Nan Liu, Zeqi Liu, Xu Wang, Ze-Guang Han, Tong Ji, Wan-Tao Chen, Xin Zou
OBJECTIVE: Long non-coding RNAs (lncRNAs) have important biological functions and can be used as prognostic biomarkers in cancer. To identify a lncRNA prognostic signature for head and neck squamous cell carcinoma (HNSCC). METHOD: We analysed RNA-seq data derived from the TANRIC database to identify a lncRNA prognostic signature model using the orthogonal partial least squares discrimination analysis (OPLS-DA) and 1.5-fold expression change criterion methods. The prognosis prediction model based on the lncRNA signatures and clinical parameters were evaluated using the 5-fold cross validation method...
February 2017: Oral Oncology
https://www.readbyqxmd.com/read/28098902/downregulation-of-leucine%C3%A2-rich%C3%A2-%C3%AE-%C3%A2-2%C3%A2-glycoprotein%C3%A2-1-expression-is-associated-with-the-tumorigenesis-of-head-and-neck-squamous-cell-carcinoma
#20
COMPARATIVE STUDY
Yongping Wang, Chen Chen, Qingquan Hua, Lei Wang, Fen Li, Man Li, Zhidan Mei, Tao Zhou, Bokui Xiao, Zezhang Tao
Leucine-rich-α-2-glycoprotein 1 (LRG1) is considered as a potential biomarker as it is aberrantly expressed in various malignancies. However, there is limited information regarding its role in head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to explore the expression pattern of LRG1 in HNSCC and its clinicopathological significance. We first analyzed LRG1 gene expression in HNSCC by investigating data obtained from the Gene Expression Omnibus (GEO) database. The results showed that LRG1 was downregulated in HNSCC tissues and its expression level was negatively related to tumor T and N stages and degree of malignancy...
March 2017: Oncology Reports
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