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https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#1
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+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
January 23, 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
#12
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
#13
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...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098823/integrative-mirna-gene-expression-analysis-enables-refinement-of-associated-biology-and-prediction-of-response-to-cetuximab-in-head-and-neck-squamous-cell-cancer
#14
Loris De Cecco, Marco Giannoccaro, Edoardo Marchesi, Paolo Bossi, Federica Favales, Laura D Locati, Lisa Licitra, Silvana Pilotti, Silvana Canevari
This paper documents the process by which we, through gene and miRNA expression profiling of the same samples of head and neck squamous cell carcinomas (HNSCC) and an integrative miRNA-mRNA expression analysis, were able to identify candidate biomarkers of progression-free survival (PFS) in patients treated with cetuximab-based approaches. Through sparse partial least square-discriminant analysis (sPLS-DA) and supervised analysis, 36 miRNAs were identified in two components that clearly separated long- and short-PFS patients...
January 14, 2017: Genes
https://www.readbyqxmd.com/read/28053877/metabolomic-analysis-identifies-differentially-produced-oral-metabolites-including-the-oncometabolite-2-hydroxyglutarate-in-patients-with-head-and-neck-squamous-cell-carcinoma
#15
Pranab K Mukherjee, Pauline Funchain, Mauricio Retuerto, Richard J Jurevic, Nicole Fowler, Brian Burkey, Charis Eng, Mahmoud A Ghannoum
BACKGROUND: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. METHODS: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28042706/do-cdk4-6-inhibitors-have-potential-as-targeted-therapeutics-for-squamous-cell-cancers
#16
REVIEW
Nene N Kalu, Faye M Johnson
Introduction Dysregulation of cell cycle progression has an established link to neoplasia and cancer progression. Components of the cyclin D-CDK4/6-INK4-Rb pathway are frequently altered in squamous cell carcinomas (SCCs) by diverse mechanisms, including viral oncogene-induced degradation, mutation, deletion, and amplification. Activation of the CDK4/6 pathway may predict response to CDK4/6 inhibitors and provide clinical biomarkers. Recently, the CDK4/6 inhibitor palbociclib showed clinical efficacy in combination with cetuximab in HNSCC patients...
February 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28039483/mir-21-as-prognostic-biomarker-in-head-and-neck-squamous-cell-carcinoma-patients-undergoing-an-organ-preservation-protocol
#17
Lidia Maria Rebolho Batista Arantes, Ana Carolina Laus, Matias Eliseo Melendez, Ana Carolina de Carvalho, Bruna Pereira Sorroche, Pedro Rafael Martins De Marchi, Adriane Feijó Evangelista, Cristovam Scapulatempo-Neto, Luciano de Souza Viana, André Lopes Carvalho
Despite progress in the treatment of head and neck squamous cell carcinoma (HNSCC) in recent decades, including new surgical techniques, radiotherapy advances and chemotherapy schedules, the prognosis for the affected patients has not improved at the same pace, and still, most HNSCC patients are diagnosed in advanced stages. To increase their survival, the development of better screening methods for early detection is required and appropriate tailored therapeutic interventions are desired. The aim of the present study was to evaluate miRNAs as prognostic biomarkers in patients undergoing organ preservation protocol for locally advanced HNSCC...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28036101/cetuximab-sensitivity-of-head-and-neck-squamous-cell-carcinoma-xenografts-is-associated-with-treatment-induced-reduction-in-egfr-pegfr-and-psrc
#18
Adam Jedlinski, Stina Garvin, Ann-Charlotte Johansson, Per-Henrik Edqvist, Fredrik Ponten, Karin Roberg
BACKGROUND: The aims of this study were to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC) cell lines in an in vivo xenograft model and to identify treatment-induced changes in the epidermal growth factor receptor (EGFR) signaling pathway that could be used as markers for cetuximab treatment response. MATERIALS AND METHODS: The in vitro and in vivo cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UT-SCC-45, was assessed using a crystal violet assay and xenografts in nude mice, respectively...
December 30, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28031227/cetuximab-resistance-in-head-and-neck-cancer-is-mediated-by-egfr-k521-polymorphism
#19
Friederike Braig, Malte Kriegs, Minna Voigtlaender, Beate Habel, Tobias Grob, Karina Biskup, Veronique Blanchard, Markus Sack, Anja Thalhammer, Isabel Ben Batalla, Ingke Braren, Simon Laban, Antje Danielczyk, Steffen Goletz, Elzbieta Jakubowicz, Bruno Märkl, Martin Trepel, Rainald Knecht, Kristoffer Riecken, Boris Fehse, Sonja Loges, Carsten Bokemeyer, Mascha Binder
Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K521 (K-allele), which is expressed in >40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation...
December 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/28024726/defining-the-boundaries-and-expanding-the-utility-of-head-and-neck-cancer-patient-derived-xenografts
#20
Adam D Swick, Andrew P Stein, Timothy M McCulloch, Gregory K Hartig, Irene M Ong, Emmanuel Sampene, Prashanth J Prabakaran, Cheng Z Liu, Randall J Kimple
BACKGROUND: Patient derived xenografts (PDXs) represent an essential tool in oncologic research, and we sought to further expand our repertoire of head and neck squamous cell carcinoma (HNSCC) while determining potential boundaries for this system. METHODS: We consented new patients for PDX development and determined if a 24-h time delay from tumor excision to xenograft implantation affected PDX establishment. We developed a tissue microarray (TMA) from formalin fixed, paraffin embedded PDXs and their subsequent passages and carried out quantitative immunohistochemistry for EGFR, pEGFR, pAkt, pERK and ERCC1...
January 2017: Oral Oncology
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