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oral oncogenes

Yemarshet K Gebreyohannes, Patrick Schöffski, Thomas Van Looy, Jasmien Wellens, Lise Vreys, Jasmien Cornillie, Ulla Vanleeuw, Dana T Aftab, Maria Debiec-Rychter, Raf Sciot, Agnieszka Wozniak
In the majority of gastrointestinal stromal tumors (GIST) oncogenic signaling is driven by KIT mutations. Advanced GIST is treated with tyrosine kinase inhibitors (TKI) such as imatinib. Acquired resistance to TKI is mainly caused by secondary KIT mutations, but can also be attributed to a switch of KIT dependency to another receptor tyrosine kinase (RTK). We tested the efficacy of cabozantinib, a novel TKI targeting KIT, MET, AXL, and vascular endothelial growth factor receptors (VEGFR), in patient-derived xenograft (PDX) models of GIST, carrying different KIT mutations...
October 24, 2016: Molecular Cancer Therapeutics
Gennaro Altamura, Annunziata Corteggio, Giuseppe Borzacchiello
A possible causative role of Felis catus papillomavirus type 2 (FcaPV2) in the development of feline oral and cutaneous squamous cell carcinomas (SCC) has been recently suggested by demonstrating viral gene expression in vivo and transforming properties by its putative oncogenes E6 and E7 in vitro. The activated molecules MEK (pMEK), ERK (pERK) and Akt (pAkt) are signaling transduction effectors regulating cell proliferation and inhibition of apoptosis, which are critical steps towards tumour formation. Here, we show by Western blotting (WB) that expression of FcaPV2 E6 in feline epithelial cells enhances pMEK, pERK and pAkt levels compared to control cells...
November 15, 2016: Veterinary Microbiology
K K Dey, R Bharti, G Dey, I Pal, Y Rajesh, S Chavan, S Das, C K Das, B C Jena, P Halder, J G Ray, I Kulavi, M Mandal
Oral cancer consists of squamous cell carcinoma within the oral cavity or on the lip. The clinical prognosis of this cancer is mostly poor owing to delayed diagnosis and a lack of appropriate early detection biomarkers to identify the disease. In the current study, we investigated the role of the S100A7 calcium-binding protein in oral squamous cell carcinoma as an activator of the p38/MAPK and RAB2A signaling pathway. The aim of the present study was to determine whether S100A7 and RAB2A have a role in tumor progression and to assess their potential as early detection biomarkers for oral cancer...
October 21, 2016: Cancer Gene Therapy
Huei-Tzu Chien, Sou-De Cheng, Wen-Yu Chuang, Chun-Ta Liao, Hung-Ming Wang, Shiang-Fu Huang
Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, including FADD (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs...
2016: PloS One
Dom-Gene Tu, Wei-Ting Lin, Cheng-Chia Yu, Shiuan-Shinn Lee, Chih-Yu Peng, Taichen Lin, Chuan-Hang Yu
BACKGROUND/PURPOSE: Previously, we successfully identified oral cancer stem cells (OCSC) displaying enhanced stemness and tumorigenic potentials. In the study, we investigated the chemotherapeutic effect of the flavonoid luteolin, commonly found in fruits and vegetables, on targeting OCSC. METHODS: Oralspheres was applied to isolate OCSC. aldehyde dehydrogenase 1 activity and CD44 positivity of OCSC with luteolin treatment were assessed by flow cytometry analysis...
October 11, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
P Morbini, M Benazzo
Human papillomavirus (HPV)-associated squamous cell carcinoma of the oropharynx is a well-defined entity mostly affecting young to middle-aged male non-smokers. It is generally associated with a favourable outcome, and for this reason a less intensive therapeutic approach has been proposed for this subset of patients. The incidence of HPV-associated oropharyngeal cancers is rapidly increasing in most Western countries, but detailed epidemiological data are not available for the Italian population. Furthermore, among other head and neck regions, a smaller proportion of oral high-grade dysplasia and cancers seems to depend on HPV infection, whereas its role in laryngeal cancer is recognised as less relevant...
August 2016: Acta Otorhinolaryngologica Italica
Carolin Götz, Enken Drecoll, Melanie Straub, Oliver Bissinger, Klaus-Dietrich Wolff, Andreas Kolk
BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. RESULTS: HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5...
October 6, 2016: Oncotarget
Sarron Randall-Demllo, Ruchira Fernando, Terry Brain, Sukhwinder Singh Sohal, Anthony L Cook, Nuri Guven, Dale Kunde, Kevin Spring, Rajaraman Eri
AIM: To determine if exacerbation of pre-existing chronic colitis in Winnie (Muc2 mutant) mice induces colonic dysplasia. METHODS: Winnie mice and C57BL6 as a genotype control, were administered 1% w/v dextran sulphate sodium (DSS) orally, followed by drinking water alone in week-long cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon...
October 7, 2016: World Journal of Gastroenterology: WJG
Khadega A Abuelgasim, Saeed Alshieban, Nada A Almubayi, Ayman Alhejazi, Abdulrahman R Jazieh
We describe the case of a young man with therapy-naive chronic myeloid leukemia who did not initially have any peripheral blood or bone marrow excess blasts but presented with extramedullary myeloid blast crises involving the central nervous system and multiple lymph nodes. Conventional cytogenetic tests were positive for t(9;22)(q34:q11) as well as for trisomy 8, 14 and 21 and del(16q). The patient's peripheral blood and bone marrow were positive for the BCR-ABL oncogene when analyzed by fluorescence in situ hybridization and polymerase chain reaction...
May 2016: Case Reports in Oncology
Jipei Du, Yufang Wang, Degao Chen, Guangyu Ji, Qizhao Ma, Shiping Liao, Yanjiang Zheng, Ji Zhang, Yiping Hou
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known for its ability to preferentially induce apoptosis in malignant cells without causing damage to most normal cells. However, inherent and acquired resistance of tumor to TRAIL-induced apoptosis limits its therapeutic applicability. Here we show that the orally available tyrosine kinase inhibitor, BAY61-3606, enhances the sensitivity of human colon cancer cells, especially those harboring active mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene, to TRAIL-induced apoptosis in vitro and in vivo...
October 6, 2016: Cancer Letters
Amani M Harrandah, Sarah G Fitzpatrick, Molly H Smith, Dunrui Wang, Donald M Cohen, Edward K L Chan
OBJECTIVE: Malignant transformation of oral premalignant lesions is the key process in the progression to oral squamous cell carcinoma (OSCC). Previously, we identified miR-7 and miR-21 as candidate oncogenes and miR-375 and miR-494 as candidate tumor suppressors in OSCC. We aim to evaluate these microRNAs as biomarkers of malignant transformation in oral premalignant lesions. STUDY DESIGN: Formalin-fixed, paraffin-embedded samples from progressive premalignant lesions and paired sequential OSCC tumors at the same site were obtained from same patients (n = 31)...
August 6, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Chandrika Gowda, Mansi Sachdev, Sunil Muthisami, Malika Kapadia, Lidija Petrovic-Dovat, Melanie Hartman, Yali Ding, Chunhua Song, Jonathon L Payne, Bi-Hua Tan, Sinisa Dovat
BACKGROUND: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective...
October 6, 2016: Current Pharmaceutical Design
Tomonori Sasahira, Miyako Kurihara, Yukiko Nishiguchi, Chie Nakashima, Tadaaki Kirita, Hiroki Kuniyasu
AIMS: Pancreatic adenocarcinoma upregulated factor (PAUF) is a novel secretory protein, which promotes tumor progression, metastasis, and poor prognosis in pancreatic, cervical, and colorectal carcinoma. It is also associated with gemcitabine resistance in pancreatic cancer cells. However, the expression and function of PAUF in oral squamous cell carcinoma (OSCC) remain unknown. METHODS AND RESULTS: We performed an immunohistochemical analysis of PAUF in 222 clinicopathologically characterized cases of OSCC...
October 5, 2016: Histopathology
Emma D Deeks
Ceritinib (Zykadia™) is an oral, selective inhibitor of the anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase which, after genetic rearrangement, acts as an oncogenic driver in a proportion of non-small cell lung cancers (NSCLCs). The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country). Approval was based on its clinical benefit in this setting in the phase I and II trials known as ASCEND-1 and -2...
October 2016: Targeted Oncology
Angel M Mayor, Eduardo J Santiago-Rodriguez, Eddy Rios-Olivares, Guillermo Tortolero-Luna, Robert F Hunter-Mellado
BACKGROUND: The study describes the cancer trends in a Puerto Rican Hispanic HIV/AIDS cohort for three different time periods as defined by the availability of combination antiretroviral therapy (cART) in the Island: pre (1992-1995), early (1996-2002, and recent (2003-2009). METHODS: AIDS and non-AIDS related malignancies risk, standardized incidence rate and one year mortality was evaluated in the cohort before and after cART. RESULTS: Of the 281 malignancies found in 265 persons; 72% were in men, 38% in injecting drug users and 42...
2016: International Journal of Cancer Research
Mei Sze Tan, Jing Wei Tan, Siow-Wee Chang, Hwa Jen Yap, Sameem Abdul Kareem, Rosnah Binti Zain
BACKGROUND: The potential of genetic programming (GP) on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis. METHOD: GP is applied on an oral cancer dataset that contains 31 cases collected from the Malaysia Oral Cancer Database and Tissue Bank System (MOCDTBS)...
2016: PeerJ
Nicoleta Sinevici, Jeff O'sullivan
Oral Cancer (OC) is a subset of head and neck cancer (HNC) with an annual worldwide incidence of 275,000 cases. OC remains a significant burden worldwide in terms of diagnosis, treatment and prognosis. Despite desirable outcomes in early diagnosed OCs and treatment advances most OCs are detected in advanced stages. The 5-year survival rate of early-stage disease is ∼80% and that of late-stage disease is only ∼20%. Recurrence and chemoresistance from a treatment point of view and pain and disfiguration are important factors contributing to the high morbidity and mortality of OC...
October 2016: Oral Oncology
Brittany Knick Ragon, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi, Jorge Cortes, Gautam Borthakur, LaKiesha DeBose, Zhihong Zeng, Heather Schneider, Naveen Pemmaraju, Guillermo Garcia-Manero, Steven Kornblau, William Wierda, Jan Burger, Courtney D DiNardo, Michael Andreeff, Marina Konopleva, Naval Daver
Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day...
September 27, 2016: American Journal of Hematology
Seong M Kim, Saurabh G Roy, Bin Chen, Tiffany M Nguyen, Ryan J McMonigle, Alison N McCracken, Yanling Zhang, Satoshi Kofuji, Jue Hou, Elizabeth Selwan, Brendan T Finicle, Tricia T Nguyen, Archna Ravi, Manuel U Ramirez, Tim Wiher, Garret G Guenther, Mari Kono, Atsuo T Sasaki, Lois S Weisman, Eric O Potma, Bruce J Tromberg, Robert A Edwards, Stephen Hanessian, Aimee L Edinger
Oncogenic mutations drive anabolic metabolism, creating a dependency on nutrient influx through transporters, receptors, and macropinocytosis. While sphingolipids suppress tumor growth by downregulating nutrient transporters, macropinocytosis and autophagy still provide cancer cells with fuel. Therapeutics that simultaneously disrupt these parallel nutrient access pathways have potential as powerful starvation agents. Here, we describe a water-soluble, orally bioavailable synthetic sphingolipid, SH-BC-893, that triggers nutrient transporter internalization and also blocks lysosome-dependent nutrient generation pathways...
September 26, 2016: Journal of Clinical Investigation
Shaleen Multani, Dhananjaya Saranath
Globocan 2012 reports the global oral cancer incidence of 300,373 new oral cancer cases annually, contributing to 2.1 % of the world cancer burden. The major well-established risk factors for oral cancer include tobacco, betel/areca nut, alcohol and high-risk oncogenic human papilloma virus (HPV) 16/18. However, only 5-10 % of individuals with high-risk lifestyle develop oral cancer. Thus, genomic variants in individuals represented as single nucleotide polymorphisms (SNPs) influence susceptibility to oral cancer...
September 20, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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