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oral oncogenes

Marie C Matrka, Katherine A Cimperman, Sarah R Haas, Geraldine Guasch, Lisa A Ehrman, Ronald R Waclaw, Kakajan Komurov, Adam Lane, Kathryn A Wikenheiser-Brokamp, Susanne I Wells
Esophageal cancer occurs as either squamous cell carcinoma (ESCC) or adenocarcinoma. ESCCs comprise almost 90% of cases worldwide, and recur with a less than 15% five-year survival rate despite available treatments. The identification of new ESCC drivers and therapeutic targets is critical for improving outcomes. Here we report that expression of the human DEK oncogene is strongly upregulated in esophageal SCC based on data in the cancer genome atlas (TCGA). DEK is a chromatin-associated protein with important roles in several nuclear processes including gene transcription, epigenetics, and DNA repair...
March 14, 2018: PLoS Genetics
Yousef Zakharia, Arup Bhattacharya, Youcef M Rustum
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent...
February 13, 2018: Oncotarget
Yu Wang, Wenyu Guo, Zhaoqing Li, Yansheng Wu, Chao Jing, Yu Ren, Minghui Zhao, Lingping Kong, Chao Zhang, Jiabin Dong, Yu Shuang, Shanshan Sun, Jinliang Chen, Chuanqiang Wu, Yu Qiao, Xin Qu, Xudong Wang, Lun Zhang, Rui Jin, Xuan Zhou
Abnormal activation of signal transducer and activator of transcription 3 (STAT3) serves a pivotal role in oral squamous cell carcinoma (OSCC) tumor cell invasion into normal tissues or distant organs. However the downstream regulatory network of STAT3 signaling remains unclear. The present study aimed to investigate the potential mechanism underlying how STAT3 triggers enhancer of zeste homolog 2 (EZH2) expression and inhibits microRNA (miR)-200a/b/429 expression in SCC25 and SCC15 cells in vitro and in vivo...
April 2018: International Journal of Oncology
Jun-Ichi Kawada, Shotaro Ando, Yuka Torii, Takahiro Watanabe, Yoshitaka Sato, Yoshinori Ito, Hiroshi Kimura
Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in EBV-associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV-associated lymphoma cell lines...
March 9, 2018: Cancer Medicine
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
March 8, 2018: Oncology Reports
Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M Qaiser Fatmi
Oral Squamous Cell Carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use as an early diagnostic marker. Dysregulated expression of miRNAs is known to affect cell growth, and these may function as tumor suppressors or oncogenes in various cancers. The main objective of this study was to characterize the extracellular miRNAs involved in oral cancer (OC) that can potentially be used as biomarkers of OC...
2018: BioMed Research International
David E Gerber, Mark A Socinski, Joel W Neal, Heather A Wakelee, Keisuke Shirai, Lecia V Sequist, Rachel P Rosovsky, Rogerio C Lilenbaum, Bruno R Bastos, Chao Huang, Melissa L Johnson, Paul J Hesketh, Deepa S Subramaniam, Martin F Dietrich, Feng Chai, Yunxia Wang, Julia Kazakin, Brian Schwartz, Joan H Schiller, Julie R Brahmer, Ronan J Kelly
BACKGROUND: KRAS mutations are identified in approximately 25% of non-small cell lung cancer (NSCLC) cases and are associated with resistance to currently available targeted therapies. The MET oncogene may be implicated in malignant progression of KRAS-mutant tumors. In a pre-specified subset analysis of KRAS mutant cancers in an earlier phase 2 study of erlotinib plus the oral MET inhibitor tivantinib, combination therapy was associated with substantial clinical benefit compared to erlotinib alone (progression-free survival [PFS] HR 0...
March 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
David R Calabrese, Katherine Zlotkowski, Stephanie Alden, William M Hewitt, Colleen M Connelly, Robert M Wilson, Snehal Gaikwad, Lu Chen, Rajarshi Guha, Craig J Thomas, Beverly A Mock, John S Schneekloth
Approaches to characterize the nucleic acid-binding properties of drugs and druglike small molecules are crucial to understanding the behavior of these compounds in cellular systems. Here, we use a Small Molecule Microarray (SMM) profiling approach to identify the preferential interaction between chlorhexidine, a widely used oral antiseptic, and the G-quadruplex (G4) structure in the KRAS oncogene promoter. The interaction of chlorhexidine and related drugs to the KRAS G4 is evaluated using multiple biophysical methods, including thermal melt, fluorescence titration and surface plasmon resonance (SPR) assays...
February 22, 2018: Nucleic Acids Research
P Ramos-García, M Bravo, L González-Ruiz, M Á González-Moles
OBJECTIVES: To examine cytoplasmic cyclin D1 expression levels in oral carcinogenesis and evaluate their possible oncogenic significance and their clinicopathological and prognostic implications. MATERIALS AND METHODS: Immunohistochemical analysis of 69 oral squamous cell carcinomas (OSCCs) was performed, revealing 23 with cytoplasmic cyclin D1 expression. We analyzed the association of the percentage of cyclin D1-positive cells and the intensity of expression with TNM classification, tumor stage, differentiation degree, cell morphology, and Ki-67 expression...
March 2018: Oral Diseases
Pavithra Rajagopalan, Vishalakshi Nanjappa, Krishna Patel, Ankit P Jain, Kiran K Mangalaparthi, Arun H Patil, Bipin Nair, Premendu P Mathur, T S Keshava Prasad, Joseph A Califano, David Sidransky, Harsha Gowda, Aditi Chatterjee
Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months. Chronic exposure to cigarette smoke resulted in increased cellular proliferation and invasive ability of oral keratinocytes...
February 26, 2018: Journal of Cell Communication and Signaling
Simar Pal Singh, Floris Dammeijer, Rudi W Hendriks
Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies...
February 19, 2018: Molecular Cancer
Hideki Ueno, Shunsuke Kondo, Shusuke Yoshikawa, Koichi Inoue, Valérie Andre, Masaomi Tajimi, Haruyasu Murakami
Background This phase I dose-escalation study investigated the safety of the Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors. Methods Patients received taladegib orally once daily for 28-day cycles, using a 3 + 3 dose-escalation method. The primary objective was the safety and tolerability of taladegib at doses up to the global recommended dose (400 mg). Secondary objectives included pharmacokinetics, changes in skin glioma-associated oncogene homolog 1 (Gli1) transcript levels, and antitumor activity...
February 17, 2018: Investigational New Drugs
Jacques Cadranel, Alexis B Cortot, Hervé Lena, Bertrand Mennecier, Pascal Do, Eric Dansin, Julien Mazieres, Christos Chouaid, Maurice Perol, Fabrice Barlesi, Gilles Robinet, Sylvie Friard, Luc Thiberville, Clarisse Audigier-Valette, Alain Vergnenegre, Virginie Westeel, Khemaies Slimane, Alexandru Buturuga, Denis Moro-Sibilot, Benjamin Besse
Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase ( ALK ) positive ( ALK + ) non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU study included crizotinib-pretreated patients with advanced ALK + or ROS proto-oncogene 1 positive ( ROS1 + ) tumours. Patients received oral ceritinib (750 mg·day -1 as a starting dose) and best tumour response (as evaluated by the investigator) and safety were reported every 3 months...
January 2018: ERJ Open Research
Deep Dutta, Raghuvansh Kumar Pandey, Rakhee Gogoi, Nagender Solanki, Renu Madan, Anupam Mondal, Shruti Dogra, Pradeep Thapa
BACKGROUND: Tumor induced osteomalacia (TIO) are extremely rare paraneoplastic syndrome with less than 300 reported cases. This report highlights the pitfalls and challenges in diagnosing and localizing TIO in patients with refractory and resistant osteomalacia. PATIENT AND METHODS: 41- year gentleman with 4-year history of musculoskeletal weakness and pathologic fractures presented in wheelchair bound incapacitated state of 1-year duration. Investigations were significant for severe hypophosphatemia, severe phosphaturia, normal serum calcium, reduced 1,25-dihydroxy vitamin-D, elevated ALP, elevated intact parathyroid hormone (iPTH), and pseudo-fractures involving pelvis and bilateral femur...
February 14, 2018: Endokrynologia Polska
Randy S Schrecengost, Cecelia L Green, Yan Zhuang, Staci N Keller, Ryan A Smith, Lynn W Maines, Charles D Smith
Glycogen synthase kinase-3s (GSK3α and GSK3β) are constitutively active protein kinases that target over 100 substrates, incorporate into numerous protein complexes, and regulate vital cellular functions such as proliferation, apoptosis and inflammation. Cyclin-dependent kinase 9 (CDK9) regulates RNA production as a component of positive transcription elongation factor b and promotes expression of oncogenic and inflammatory genes. Simultaneous inhibition of these signaling nodes is a promising approach for drug discovery, although previous compounds exhibit limited selectivity and clinical efficacy...
February 6, 2018: Journal of Pharmacology and Experimental Therapeutics
Richa Tiwari, Indrajit Sahu, Bihari Lal Soni, Gajanan J Sathe, Pankaj Thapa, Pavan Patel, Shruti Sinha, Chella Krishna Vadivel, Shweta Patel, Sayli Nitin Jamghare, Swapnil Oak, Rahul Thorat, Harsha Gowda, Milind M Vaidya
Keratin 8/18 the predominant keratin pair of simple epithelia is often aberrantly expressed in various squamous cell carcinomas (SCCs) including skin-SCC. Its aberrant expression is correlated with increased invasiveness and poor prognosis of the same, although the underlying mechanism is still unclear. A previous report from our laboratory has shown K8 mediated regulation of α6β4 integrin signaling and thereby tumorigenic potential of oral-SCC derived cells. Another study on transgenic mouse model has shown that during skin carcinogenesis, K8 favors conversion of papillomas towards malignancy...
February 10, 2018: FEBS Journal
Minako Ikoma, Soren Gantt, Corey Casper, Yuko Ogata, Qing Zhang, Ryan Basom, Michael R Dyen, Timothy M Rose, Serge Barcy
Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). Both KSHV and HIV infections are endemic in Uganda, where KS is among the most common cancers in HIV-infected individuals. Recent studies examined the use of small RNAs as biomarkers of disease, including microRNAs (miRNAs), with viral and tumor-derived miRNAs being detected in exosomes from individuals with KSHV-associated malignancies. In the current study, the host and viral extracellular mature miRNA expression profiles were analyzed in blood of KS-negative individuals in Uganda, comparing those with or without KSHV detectable from the oropharynx...
2018: PloS One
V Sgroi, M Bassanelli, M Roberto, E Iannicelli, R Porrini, P Pellegrini, A Tafuri, P Marchetti
Background: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer...
2018: Experimental Hematology & Oncology
Xiyan Chen, Weiting Gu, Qi Wang, Xucheng Fu, Ying Wang, Xin Xu, Yong Wen
Transcriptional co-activator Yes-associated protein (YAP) is a key oncogene in mammalian cells. The present understanding of YAP in oral squamous cells carcinoma (OSCC) remains unclear. The purpose of this study is to investigate the effects of YAP on proliferation and apoptosis in OSCC and the molecular mechanism. The results showed the expression level of YAP was higher in OSCC tissues than that in adjacent normal tissues. Knockdown of YAP in CAL27 cell lines prohibited cell proliferation while augmented apoptosis...
January 2, 2018: Oncotarget
Paul A VanderLaan, Deepa Rangachari, Adnan Majid, Mihir S Parikh, Sidharta P Gangadharan, Michael S Kent, Danielle C McDonald, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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