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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
#1
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
#2
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...
January 1, 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
#3
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...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036101/cetuximab-sensitivity-of-head-and-neck-squamous-cell-carcinoma-xenografts-is-associated-with-treatment-induced-reduction-of-egfr-pegfr-and-psrc
#4
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
#5
Friederike Braig, Malte Kriegs, Beate Habel, Minna Voigtlaender, Tobias Grob, Karina Biskup, Véronique 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
#6
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
https://www.readbyqxmd.com/read/28006059/the-kras-variant-and-cetuximab-response-in-head-and-neck-squamous-cell-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#7
Joanne B Weidhaas, Jonathan Harris, Dörthe Schaue, Allen M Chen, Robert Chin, Rita Axelrod, Adel K El-Naggar, Anurag K Singh, Thomas J Galloway, David Raben, Dian Wang, Chance Matthiesen, Vilija N Avizonis, Rafael R Manon, Omar Yumen, Phuc Felix Nguyen-Tan, Andy Trotti, Heath Skinner, Qiang Zhang, Robert L Ferris, David Sidransky, Christine H Chung
Importance: There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment. Objectives: To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based transforming growth factor β1 (TGF-β1)...
December 22, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/28002801/effect-of-3q-oncogenes-sec62-and-sox2-on-lymphatic-metastasis-and-clinical-outcome-of-head-and-neck-squamous-cell-carcinomas
#8
Florian Bochen, Hana Adisurya, Silke Wemmert, Cornelia Lerner, Markus Greiner, Richard Zimmermann, Andrea Hasenfus, Mathias Wagner, Sigrun Smola, Thorsten Pfuhl, Alessandro Bozzato, Basel Al Kadah, Bernhard Schick, Maximilian Linxweiler
Chromosome 3q26 amplification represents a frequent alteration in head and neck squamous cell carcinomas (HNSCCs). Overexpression of 3q26 encoded genes SEC62 and SOX2 was detected in various cancers, including HNSCCs, indicating their potential function as oncogenes. In our study, we elucidated the function of SEC62 and SOX2 in HNSCC patients, with a main focus on their effect on lymphatic metastasis and patient survival. We analyzed SEC62 and SOX2 expression in tissue specimens from 65 HNSCC patients and 29 patients with cervical cancer of unknown primary (CUP); a higher SEC62 and lower SOX2 expression was observed in the lymph node metastases from HNSCC patients compared with the respective primary tumor...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994655/alteration-status-and-prognostic-value-of-met-in-head-and-neck-squamous-cell-carcinoma
#9
Yoon Ah Cho, Eun Kyung Kim, Su Jin Heo, Byoung Chul Cho, Hye Ryun Kim, Ji Myung Chung, Sun Och Yoon
The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of the MET copy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC)...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27980104/the-fa-brca-pathway-identified-as-the-major-predictor-of-cisplatin-response-in-head-and-neck-cancer-by-functional-genomics
#10
Sanne R Martens-de Kemp, Arjen Brink, Ida H van der Meulen, Renee X De Menezes, Dennis E Te Beest, C Rene Leemans, Victor W van Beusechem, Boudewijn J M Braakhuis, Ruud H Brakenhoff
Patients with advanced stage head and neck squamous cell carcinoma (HNSCC) are often treated with cisplatin-containing chemoradiation protocols. Although cisplatin is an effective radiation sensitizer, it causes severe toxicity and not all patients benefit from the combination treatment. HNSCCs expectantly not responding to cisplatin may better be treated with surgery and postoperative radiation or cetuximab and radiation, but biomarkers to personalize chemoradiotherapy, are not available. We performed an unbiased genome-wide functional genetic screen in vitro to identify genes that influence the response to cisplatin in HNSCC cells...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27977878/effects-of-potentially-functional-polymorphisms-in-suppressor-of-cytokine-signaling-3-socs3-on-the-risk-of-head-and-neck-squamous-cancer
#11
Dong Hang, Yin Yin, Lihua Wang, Hua Yuan, Jiangbo Du, Meng Zhu, Juncheng Dai, Ning Chen, Zhibin Hu, Hongbing Shen, Hongxia Ma
BACKGROUND: Suppressor of cytokine signaling 3 (SOCS3) has been identified as an inhibitor of JAK/STAT pathway that plays a significant role in carcinogenesis. SOCS3 and JAK2 polymorphisms may influence the gene expression or function, contributing to the disease susceptibility; however, such effect has not been evaluated in head and neck squamous cell carcinoma (HNSCC). METHODS: A case-control study was performed to test the associations of SOCS3 and JAK2 polymorphisms with risk of HNSCC in 576 cases and 1552 cancer-free controls from China...
December 15, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27938998/epidermal-growth-factor-receptor-egfr-pathway-polymorphisms-as-predictive-markers-of-cetuximab-toxicity-in-locally-advanced-head-and-neck-squamous-cell-carcinoma-hnscc-in-a-spanish-population
#12
J Fernández-Mateos, R Seijas-Tamayo, R Mesía, M Taberna, M Pastor Borgoñón, E Pérez-Ruiz, J C Adansa Klain, S Vázquez Fernández, E Del Barco Morillo, A Lozano, R González Sarmiento, J J Cruz-Hernández
OBJECTIVES: To examine the relationship between polymorphisms of the epidermal growth factor receptor (EGFR) pathway and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with cetuximab. MATERIAL AND METHODS: Multicenter, retrospective, observational pilot study which included 110 patients with histologically-confirmed human papillomavirus (HPV) negative HNSCC in locally advanced stages (III-IVA-B) and who were treated with chemotherapy and radiotherapy plus cetuximab between 2003 and 2013...
December 2016: Oral Oncology
https://www.readbyqxmd.com/read/27913709/hpv-positive-oropharyngeal-cancer-via-p16-immunohistochemistry-in-japan
#13
Julia Toman, Scott Von Larson, Hirohito Umeno, Takashi Kurita, Tohru Furusaka, Hisashi Hasegawa, Manju L Prasad, Clarence T Sasaki
OBJECTIVES: Human papillomavirus (HPV) has emerged as a driving cause of head and neck cancer, but investigations outside the West are limited. A p16 immunohistochemistry is a commonly used biomarker for HPV cancers. We sought to investigate the pathology and rates of HPV head and neck oropharyngeal cancer in Japan via p16 immunohistochemistry at 2 institutions in Japan. METHODS: Fifty-nine oropharyngeal specimens from 2 university hospitals in Japan were examined for morphology and p16 immunohistochemistry...
February 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#14
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
December 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27906454/immunotherapy-of-head-and-neck-cancer-emerging-clinical-trials-from-a-national-cancer-institute-head-and-neck-cancer-steering-committee-planning-meeting
#15
Julie E Bauman, Ezra Cohen, Robert L Ferris, David J Adelstein, David M Brizel, John A Ridge, Brian O'Sullivan, Barbara A Burtness, Lisa H Butterfield, William E Carson, Mary L Disis, Bernard A Fox, Thomas F Gajewski, Maura L Gillison, James W Hodge, Quynh-Thu Le, David Raben, Scott E Strome, Jean Lynn, Shakun Malik
Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. The goals of the meeting were to consider phase 2 or 3 trial designs primarily in 3 different patient populations: those with previously untreated, human papillomavirus-initiated oropharyngeal cancers; those with previously untreated, human papillomavirus-negative HNSCC; and those with recurrent/metastatic HNSCC...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27899422/high-risk-hpv-biomarkers-and-outcome-in-matched-cohorts-of-head-and-neck-cancer-patients-positive-and-negative-for-hiv
#16
Heather M Walline, Thomas E Carey, Christine M Goudsmit, Emily L Bellile, Gypsyamber D'souza, Lisa A Peterson, Jonathan B McHugh, Sara I Pai, J Jack Lee, Dong M Shin, Robert L Ferris
: In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR and In Situ Hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27889751/targeted-therapy-of-head-and-neck-cancer
#17
Damian T Rieke, Konrad Klinghammer, Ulrich Keilholz
Head and neck squamous cell carcinoma (HNSCC) is one of the most common solid cancers worldwide. It is mainly caused by exposure to tobacco smoke and alcohol as well as infection with the human papilloma virus (HPV). The prognosis is poor, especially once it recurs or metastasizes. Current therapeutic options include surgery, radio- and chemotherapy. Epidermal growth factor receptor (EGFR) inhibitors are so far the only targeted agents that have been approved in head and neck cancer. Primary or secondary resistance is frequent or will eventually develop...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#18
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27865373/extracapsular-spread-in-head-and-neck-squamous-cell-carcinoma-a-systematic-review-and-meta-analysis
#19
REVIEW
Maxime Mermod, Genrich Tolstonog, Christian Simon, Yan Monnier
Extracapsular spread (ECS) is one of the most important prognostic factors in head and neck squamous cell carcinoma (HNSCC). However, despite its major clinical relevance, there are still a number of important remaining issues regarding this condition. Indeed, standardized diagnostic and grading criteria of ECS are still lacking. The imaging modality of choice for its diagnosis is a matter of debate. Current research looking at the identification of specific biomarkers is ongoing. Recent findings demonstrate a direct correlation between the level of extension of ECS and a poor prognosis...
November 2016: Oral Oncology
https://www.readbyqxmd.com/read/27865368/effect-of-hpv-on-head-and-neck-cancer-patient-survival-by-region-and-tumor-site-a-comparison-of-1362-cases-across-three-continents
#20
Gypsyamber D'Souza, Devasena Anantharaman, Tarik Gheit, Behnoush Abedi-Ardekani, Daniel C Beachler, David I Conway, Andrew F Olshan, Victor Wunsch-Filho, Tatiana N Toporcov, Wolfgang Ahrens, Kathy Wisniewski, Franco Merletti, Stefania Boccia, Eloiza H Tajara, Jose P Zevallos, José Eduardo Levi, Mark C Weissler, Sylvia Wright, Ghislaine Scelo, Angela L Mazul, Massimo Tommasino, Paul Brennan, Gabriella Cadoni
OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16(INK4a) and HPV16 DNA (by PCR)...
November 2016: Oral Oncology
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