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oral oncogenes

Samantha Raymond, Bian Liu, Emanuela Taioli
BACKGROUND: The purpose of this study was to describe the prevalence of oral human papillomavirus (HPV) types according to race and to examine risk factors for oral HPV infection in United States adults. METHODS: Using 2009-2014 data from the National Health and Nutrition Examination Survey, 13 981 subjects were examined. Prevalence of oral HPV and individual oncogenic HPV types were described according to race. Multivariable logistic and linear regressions were used to examine the risk factors for infection and coinfection...
May 13, 2018: Head & Neck
K Kalinsky, J A Sparano, X Zhong, E Andreopoulou, B Taback, L Wiechmann, S M Feldman, P Ananthakrishnan, A Ahmad, S Cremers, A N Sireci, J R Cross, D K Marks, P Mundi, E Connolly, K D Crew, M A Maurer, H Hibshoosh, S Lee, D L Hershman
INTRODUCTION: The PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III BC. MATERIALS AND METHODS: Two doses of weekly oral MK2206 were administered at days - 9 and - 2 before surgery. The primary endpoint was reduction of pAktSer473 in breast tumor tissue from diagnostic biopsy to surgery. Secondary endpoints included changes in PI3K/AKT pathway tumor markers, tumor proliferation (ki-67), insulin growth factor pathway blood markers, pharmacokinetics (PK), genomics, and MK-2206 tolerability...
May 7, 2018: Clinical & Translational Oncology
Lu Dai, Jing Qiao, Luis Del Valle, Zhiqiang Qin
High-risk human papillomavirus (HPV) infection is the etiological agent of cervical, oral and oropharyngeal cancers. Another oncogenic virus, Kaposi sarcoma-associated herpesvirus (KSHV) can cause several human cancers arising in those immunocompromised patients. KSHV DNA has been detected in the oral cavity and the female genital tract, although its detection rate in cervical samples is relatively low. Therefore, it remains unclear about the role of KSHV co-infection in the development of HPV-related neoplasia...
2018: American Journal of Cancer Research
Akhilesh Krishna, Shraddha Singh, Vineeta Singh, Vijay Kumar, Uma Shankar Singh, Satya Narayan Sankhwar
Background: Harvey-Ras (H-Ras) is an important guanosine triphosphatase protein for the regulation of cellular growth and survival. Altered Ras signaling has been observed in different types of cancer either by gene amplification and/or mutation. The H-Ras oncogene mutations are well reported, but expression of the H-Ras gene is still unknown. Objective: This study aimed to examine both protein and messenger-RNA (mRNA) expressions of H-Ras in oral squamous cell carcinoma (OSCC) and analyzed the association with risk habits and the clinicopathological profile of cases...
January 2018: Journal of Oral and Maxillofacial Pathology: JOMFP
Mohd Younis Bhat, Jayshree Advani, Pavithra Rajagopalan, Krishna Patel, Vishalakshi Nanjappa, Hitendra S Solanki, Arun H Patil, Firdous A Bhat, Premendu P Mathur, Bipin Nair, T S Keshava Prasad, Joseph A Califano, David Sidransky, Harsha Gowda, Aditi Chatterjee
Carcinogenic effect of tobacco in oral cancer is through chewing and/or smoking. Significant differences exist in development of oral cancer between tobacco users and non-users. However, molecular alterations induced by different forms of tobacco are yet to be fully elucidated. We developed cellular models of chronic exposure to chewing tobacco and cigarette smoke using immortalized oral keratinocytes. Chronic exposure to tobacco resulted in increased cell scattering and invasiveness in immortalized oral keratinocytes...
May 4, 2018: Scientific Reports
Pavithra Rajagopalan, Krishna Patel, Ankit P Jain, Vishalakshi Nanjappa, Keshava K Datta, Tejaswini Subbannayya, Kiran K Mangalaparthi, Anjali Kumari, Malini Manoharan, Coral Karunakaran, Sakthivel Murugan, Bipin Nair, T S Keshava Prasad, Premendu P Mathur, Ravi Gupta, Rohit Gupta, Arati Khanna-Gupta, Joseph Califano, David Sidransky, Harsha Gowda, Aditi Chatterjee
(250 words) Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months...
May 3, 2018: Cancer Biology & Therapy
Daniela Vargas-Robles, Magda Magris, Natalia Morales, Maurits N C de Koning, Iveth Rodríguez, Tahidid Nieves, Filipa Godoy-Vitorino, Gloria I Sánchez, Luis David Alcaraz, Larry J Forney, María-Eglée Pérez, Luis García-Briceño, Leen-Jan van Doorn, María Gloria Domínguez-Bello
Human papillomavirus (HPV), an etiological agent of cervical cancer (CC), has infected humans since ancient times. Amerindians are the furthest migrants out of Africa, and they reached the Americas more than 14,000 years ago. Some groups still remain isolated, and some migrate to towns, forming a gradient spanning urbanization. We hypothesized that, by virtue of their history, lifestyle, and isolation from the global society, remote Amerindian women have lower HPV diversity than do urban women (Amerindian or mestizo)...
June 27, 2018: MSphere
Scott M Schuetze, Vanessa Bolejack, Dafydd G Thomas, Margaret von Mehren, Shreyaskumar Patel, Brian Samuels, Edwin Choy, Gina D'Amato, Arthur P Staddon, Kristen N Ganjoo, Warren A Chow, Daniel A Rushing, Charles A Forscher, Dennis A Priebat, David M Loeb, Rashmi Chugh, Scott Okuno, Denise K Reinke, Laurence H Baker
Importance: Gastrointestinal stromal tumors (GISTs) are life-threatening when metastatic or not amenable to surgical removal. In a few patients with advanced GISTs refractory to imatinib mesylate, treatment with sunitinib malate followed by regorafenib provides tumor control; however, additional active treatments are needed for most patients. Objective: To evaluate the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates in patients with GISTs treated with dasatinib...
April 26, 2018: JAMA Oncology
Yuan-Hua Wu, Wun-Syuan Wu, Li-Ching Lin, Chiang-Shin Liu, Sheng-Yow Ho, Bour-Jr Wang, Bu-Miin Huang, Ya-Ling Yeh, Hui-Wen Chiu, Wei-Lei Yang, Ying-Jan Wang
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a malignant tumor that may occur anywhere within the oral cavity. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. We investigated the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in OSCC cells treated with bortezomib (a proteasome inhibitor) combined with irradiation (IR) treatment. METHODS: The effects of combined treatment in OSCC cells were investigated using assays of cell viability, autophagy, apoptosis, western blotting, and immunofluorescence staining...
April 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yi-Yen Lee, Aliaksandr A Yarmishyn, Mong-Lien Wang, Hsiao-Yun Chen, Shih-Hwa Chiou, Yi-Ping Yang, Chun-Fu Lin, Pin-I Huang, Yi-Wei Chen, Hsin-I Ma, Ming-Teh Chen
Background: Glioblastoma multiforme (GBM) is the most malignant brain tumor, and there is no effective treatment strategy. Patients with GBM have a median overall survival of only 14.6 months. Current treatment consists of safe and maximal surgical excision, followed by concurrent chemoradiotherapy and maintenance chemotherapy. There are several obstacles that hinder the effectiveness of this aggressive treatment. Temozolomide (TMZ) is an oral alkylating drug that acts through alkylating the O 6 position of guanine in DNA that leads to cell death...
2018: Cancer Management and Research
Anji Anura, Anees Kazi, Mousumi Pal, Ranjan Rashmi Paul, Sanghamitra Sengupta, Jyotirmoy Chatterjee
Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework...
April 23, 2018: Histochemistry and Cell Biology
Antoine Italiano, Jean-Charles Soria, Maud Toulmonde, Jean-Marie Michot, Carlo Lucchesi, Andrea Varga, Jean-Michel Coindre, Stephen J Blakemore, Alicia Clawson, Benjamin Suttle, Alice A McDonald, Mark Woodruff, Scott Ribich, Eric Hedrick, Heike Keilhack, Blythe Thomson, Takashi Owa, Robert A Copeland, Peter T C Ho, Vincent Ribrag
BACKGROUND: Activating enhancer of zeste homolog 2 (EZH2) mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg, mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity. In this first-in-human study, we aimed to investigate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a first-in-class selective inhibitor of EZH2...
April 9, 2018: Lancet Oncology
Xu Ding, Yang Zheng, Zhao Wang, Wei Zhang, Yibo Dong, Wantao Chen, Jiang Li, Weiming Chu, Wei Zhang, Yi Zhong, Li Mao, Xiaomeng Song, Yunong Wu
Notch1 signaling is essential for tissue development and tumor progression. This signaling pathway has also been implicated in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). However, the role of Notch1 expression in OL and its malignant transformation is unknown. This study aimed to examine the Notch1 expression patterns by immunohistochemistry (IHC) in a cohort of 78 Chinese patients with OL and to analyze the relationship between the patterns and progression of OL to OSCC. Strong Notch1 staining was observed in 10 (13%) of the 78 OL patients, but it was not associated with any of the clinicopathological parameters...
March 27, 2018: Oncology Reports
Rebecca Ronsley, S Rod Rassekh, Yaoqing Shen, Anna F Lee, Colleen Jantzen, Jessica Halparin, Catherine Albert, Douglas S Hawkins, Shazhan Amed, Ralph Rothstein, Andrew J Mungall, David Dix, Geoffrey Blair, Helen Nadel, Steven J M Jones, Janessa Laskin, Marco A Marra, Rebecca J Deyell
Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding...
April 2018: Cold Spring Harbor Molecular Case Studies
Yi-Long Wu, James Chih-Hsin Yang, Dong-Wan Kim, Shun Lu, Jianying Zhou, Takashi Seto, Jin-Ji Yang, Noboru Yamamoto, Myung-Ju Ahn, Toshiaki Takahashi, Takeharu Yamanaka, Allison Kemner, Debasish Roychowdhury, Jolanda Paolini, Tiziana Usari, Keith D Wilner, Koichi Goto
Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies...
March 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Akhilesh Krishna, Madan Lal Brahma Bhatt, Vineeta Singh, Shraddha Singh, Pravin Kumar Gangwar, Uma Shankar Singh, Vijay Kumar, Divya Mehrotra
Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form the transcription factor AP-1 complex which participates in signal transduction and regulation of normal cellular processes. In tumorigenesis, c-Fos promotes invasive growth through down-regulation of tumor suppressor genes but its role in oral carcinogenesis is not clear. Objectives: This study concerned c-fos gene expression in normal and malignant tissues of the oral cavity, with attention to associations between expression status and clinico-pathological profiles of OSCC patients...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Chih-Yu Peng, Tung-Yuan Wang, Shiuan-Shinn Lee, Pei-Ling Hsieh, Yi-Wen Liao, Lo-Lin Tsai, Chih-Yuan Fang, Cheng-Chia Yu, Ching-Shui Hsieh
BACKGROUND: The let-7 family of microRNAs have been considered as tumor suppressors in various cancers, however, the role of let-7c in oral squamous cell carcinoma has not been determined yet. METHODS: In this study, phenotypical behaviors and the radio/chemoresistance were examined subsequent to overexpression of let-7c. In addition, the expression of let-7c in cancer stem cells was evaluated and the effect of let-7c on stemness characteristics were assessed. Also, luciferase activity assays was performed to test whether interleukin (IL)-8 was a putative target of let-7c...
March 27, 2018: Journal of Oral Pathology & Medicine
Bruce W Konicek, Andrew R Capen, Kelly M Credille, Philip J Ebert, Beverly L Falcon, Gary L Heady, Bharvin K R Patel, Victoria L Peek, Jennifer R Stephens, Julie A Stewart, Stephanie L Stout, David E Timm, Suzane L Um, Melinda D Willard, Isabella H Wulur, Yi Zeng, Yong Wang, Richard A Walgren, Sau-Chi Betty Yan
Merestinib is an oral multi-kinase inhibitor targeting a limited number of oncokinases including MET, AXL, RON and MKNK1/2. Here, we report that merestinib inhibits neurotrophic receptor tyrosine kinases NTRK1/2/3 which are oncogenic drivers in tumors bearing NTRK fusion resulting from chromosomal rearrangements. Merestinib is shown to be a type II NTRK1 kinase inhibitor as determined by x-ray crystallography. In KM-12 cells harboring TPM3-NTRK1 fusion, merestinib exhibits potent p-NTRK1 inhibition in vitro by western blot and elicits an anti-proliferative response in two- and three-dimensional growth...
March 2, 2018: Oncotarget
I Gkouveris, N Nikitakis, A Sklavounou
p38 protein belongs to Mitogen-activated protein kinases family that link extracellular stimuli with intracellular responses participating in numerous of fundamental cell processes. Persistent activation of STAT3 has been associated with cell proliferation, differentiation and apoptosis in oral squamous cell carcinoma (OSCC). This study examines the effects of p38 modulation on STAT3 signaling and cellular activities in OSCC cells and investigates possible correlation of p38 expression with tumor degree of differentiation...
March 21, 2018: Pathology Oncology Research: POR
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem in the United States with an estimated 50,260 deaths in 2017. Over the past two decades, several agents have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic CRC (mCRC). Regorafenib (BAY 73-4506) is a small-molecule multikinase inhibitor that was approved for the treatment of mCRC in 2012. This agent is a novel oral diphenylurea-based multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases (RTKs; VEGFR-1, VEGFR-2, VEGFR-3, TIE-2), oncogenic RTKs (c-KIT, RET), stromal RTKs (PDGFR-B, FGFR-1), and intracellular signaling kinases (c-RAF/RAF-1, BRAF, BRAFV600E )...
2018: Cancer Management and Research
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