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oral oncogenes

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https://www.readbyqxmd.com/read/28193778/ag-221-a-first-in-class-therapy-targeting-acute-myeloid-leukemia-harboring-oncogenic-idh2-mutations
#1
Katharine Yen, Jeremy Travins, Fang Wang, Muriel D David, Erin Artin, Kim Straley, Anil Padyana, Stefan Gross, Byron DeLaBarre, Erica Tobin, Yue Chen, Raj Nagaraja, Sung Choe, Lei Jin, Zenon Konteatis, Giovanni Cianchetta, Jeffrey O Saunders, Francesco G Salituro, Cyril Quivoron, Paule Opolon, Olivia Bawa, Véronique Saada, Angelo Paci, Sophie Broutin, Olivier A Bernard, Stéphane de Botton, Benoît S Marteyn, Monika Pilichowska, YingXia Xu, Cheng Fang, Fan Jiang, Wentao Wei, Shengfang Jin, Lee Silverman, Wei Liu, Hua Yang, Lenny Dang, Marion Dorsch, Virginie Penard-Lacronique, Scott A Biller, Shin-San Michael Su
Somatic gain-of-function mutations in isocitrate dehydrogenase (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite, (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the Tet family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28178115/prevalence-of-and-risk-factors-for-oral-human-papillomavirus-infection-with-multiple-genotypes-in-the-united-states
#2
Thanh Cong Bui, Ly Thi-Hai Tran, Thuy Nhu Thai, Sanjay S Shete, Damon J Vidrine, Erich M Sturgis
BACKGROUND: This study investigated the prevalence of and risk factors for oral human papillomavirus (HPV) infection with multiple genotypes in the United States. METHODS: Data were from the nationally representative 2009-2012 National Health and Nutrition Examination Survey. This analysis comprised 9257 participants for whom data on oral HPV (37 genotypes) and associated risk factors were available. RESULTS: The weighted prevalence of multitype (2-6 types) oral HPV infection was 1...
March 2017: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/28167449/curcumin-and-treatment-of-melanoma-the-potential-role-of-micrornas
#3
REVIEW
Diana Lelli, Claudio Pedone, Amirhosssein Sahebkar
Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle...
February 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28118606/protein-s-drives-oral-squamous-cell-carcinoma-tumorigenicity-through-regulation-of-axl
#4
Ghada Abboud-Jarrous, Shivam Priya, Avi Maimon, Stuart Fischman, Mayan Cohen-Elisha, Rakefet Czerninski, Tal Burstyn-Cohen
The TAM family of proto-oncogenic receptor protein tyrosine kinases, comprising of TYRO3, AXL, and MERTK, is implicated in many human cancers. Their activation leads to cancer cell proliferation, enhanced migration, invasion, and drug resistance; however how TAMs are activated in cancers is less understood. We previously showed that Protein S (PROS1) is a ligand of the TAM receptors. Here we identify PROS1 as a mediator of Oral Squamous Cell Carcinoma (OSCC) in proliferation, cell survival and migration. We demonstrate that excess PROS1 induces OSCC proliferation and migration...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107185/hyaluronan-synthase-3-mediated-oncogenic-action-through-forming-inter-regulation-loop-with-tumor-necrosis-factor-alpha-in-oral-cancer
#5
Yi-Zih Kuo, Wei-Yu Fang, Cheng-Chih Huang, Sen-Tien Tsai, Yi-Ching Wang, Chih-Li Yang, Li-Wha Wu
Hyaluronan (HA) is a major extracellular matrix component. However, its role and mediation in oral cancer remains elusive. Hyaluronan synthase 3 (HAS3), involved in pro-inflammatory short chain HA synthesis, was the predominant synthase in oral cancer cells and tissues. HAS3 overexpression significantly increased oral cancer cell migration, invasion and xenograft tumorigenesis accompanied with the increased expression of tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1). Conversely, HAS3 depletion abrogated HAS3-mediated stimulation...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28101204/downregulation-of-mir-221-222-by-a-microrna-sponge-promotes-apoptosis-in-oral-squamous-cell-carcinoma-cells-through-upregulation-of-pten
#6
Lijie Zhou, Fangfang Jiang, Xijuan Chen, Zifeng Liu, Ying Ouyang, Wei Zhao, Dongsheng Yu
MicroRNA-221 and microRNA-222 (miR-221/222) have been identified as oncogenes and confirmed to be overexpressed in various types of cancer. However, the regulation mechanism of miR-221/222 in oral squamous cell carcinoma (OSCC) remains to be fully elucidated. Previously, an miR-221/222 sponge was successfully constructed and its effect on the downregulation of miR-221/222 expression was investigated. In the present study, the dual luciferase reporter assay revealed a phosphatase and tensin homolog (PTEN) deletion on chromosome 10 to be a target gene of miR-221/222...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096095/functional-role-and-therapeutic-targeting-of-p21-associated-kinase-4-pak4-in-multiple-myeloma
#7
Mariateresa Fulciniti, Joaquin Martinez-Lopez, William Senapedis, Stefania Oliva, Rajya Lakshmi Bandi, Nicola Amodio, Yan Xu, Raphael L Szalat, Annamaria Gulla, Mehmet K Samur, Aldo Roccaro, Maria Linares, Michele Cea, Erkan Baloglu, Christian Argueta, Yosef Landesman, Sharon Shacham, Siyuan Liu, Monica Schenone, Shiaw-Lin Wu, Barry Karger, Rao Prabhala, Kenneth C Anderson, Nikhil C Munshi
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28093311/long-non-coding-rna-fth1p3-facilitates-oral-squamous-cell-carcinoma-progression-by-acting-as-a-molecular-sponge-of-mir-224-5p-to-modulate-fizzled-5-expression
#8
Chen-Zheng Zhang
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) during tumorigenesis. In this study, the qRT-PCR results revealed that the lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) was over-expressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. Ectopic expression of FTH1P3 facilitates cell proliferation and colony formation in OSCC cells. Moreover, FTH1P3 acted as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-224-5p and thereby modulating the expression of fizzled 5...
April 5, 2017: Gene
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#9
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088212/ultrasensitive-detection-of-oncogenic-human-papillomavirus-in-oropharyngeal-tissue-swabs
#10
Andre Isaac, Morris Kostiuk, Han Zhang, Cameron Lindsay, Fawaz Makki, Daniel A O'Connell, Jeffrey R Harris, David W J Cote, Hadi Seikaly, Vincent L Biron
BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR...
January 14, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28081185/upregulated-expression-of-transient-receptor-potential-cation-channel-subfamily-v-receptors-in-mucosae-of-patients-with-oral-squamous-cell-carcinoma-and-patients-with-a-history-of-alcohol-consumption-or-smoking
#11
Akiko Sakakibara, Shunsuke Sakakibara, Junya Kusumoto, Daisuke Takeda, Takumi Hasegawa, Masaya Akashi, Tsutomu Minamikawa, Kazunobu Hashikawa, Hiroto Terashi, Takahide Komori
OBJECTIVES: Transient receptor potential cation channel (subfamily V, members 1-4) (TRPV1-4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1-4 receptors...
2017: PloS One
https://www.readbyqxmd.com/read/28030842/loss-of-runx3-expression-inhibits-bone-invasion-of-oral-squamous-cell-carcinoma
#12
Junhee Park, Hyun-Jeong Kim, Ki Rim Kim, Sun Kyoung Lee, Hyungkeun Kim, Kwang-Kyun Park, Won-Yoon Chung
High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012149/endoplasmic-reticulum-stress-and-apoptosis-triggered-by-sub-chronic-lead-exposure-in-mice-spleen-a-histopathological-study
#13
Giovanni Corsetti, Claudia Romano, Alessandra Stacchiotti, Evasio Pasini, Francesco S Dioguardi
Lead (Pb) is an environmental oncogenic metal that induces immunotoxicity and anaemia. Emerging evidence has linked Pb toxicity with endoplasmic reticulum-driven apoptosis and autophagy. Glucose-regulated protein of 78 kDa (Grp78 or binding immunoglobulin protein (BiP)), a master endoplasmic reticulum chaperone, drives macrophage activation and regulates protein folding and calcium flux in response to heavy metals. The spleen may be involved in Pb poisoning due to its crucial role in erythrocatheresis and immune response, although there are no data to support this theory...
December 24, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/27999209/s4s8-rpa-phosphorylation-as-an-indicator-of-cancer-progression-in-oral-squamous-cell-carcinomas
#14
Jeff Rector, Sasha Kapil, Kelly J Treude, Phyllis Kumm, Jason G Glanzer, Brendan M Byrne, Shengqin Liu, Lynette M Smith, Dominick J DiMaio, Peter Giannini, Russell B Smith, Greg G Oakley
Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27973759/an-update-on-the-implications-of-cyclin-d1-in-oral-carcinogenesis
#15
REVIEW
Pablo Ramos-García, José Antonio Gil-Montoya, Crispian Scully, Ángela Ayén, Lucía González-Ruiz, Francisco-José Navarro-Triviño, Miguel Ángel González-Moles
Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1-S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including: cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma...
December 14, 2016: Oral Diseases
https://www.readbyqxmd.com/read/27941877/repression-of-caspase-3-and-rna-binding-protein-hur-cleavage-by-cyclooxygenase-2-promotes-drug-resistance-in-oral-squamous-cell-carcinoma
#16
H Janakiraman, R P House, S Talwar, S M Courtney, E S Hazard, G Hardiman, S Mehrotra, P H Howe, V Gangaraju, V Palanisamy
A well-studied RNA-binding protein Hu Antigen-R (HuR), controls post-transcriptional gene regulation and undergoes stress-activated caspase-3 dependent cleavage in cancer cells. The cleavage products of HuR are known to promote cell death; however, the underlying molecular mechanisms facilitating caspase-3 activation and HuR cleavage remains unknown. Here, we show that HuR cleavage associated with active caspase-3 in oral cancer cells treated with ionizing radiation and chemotherapeutic drug, paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of caspase-3 and HuR, which reduced the rate of cell death in paclitaxel resistant oral cancer cells...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27935063/human-papillomavirus-hpv-infection-in-a-case-control-study-of-oral-squamous-cell-carcinoma-and-its-increasing-trend-in-northeastern-thailand
#17
Pensiri Phusingha, Tipaya Ekalaksananan, Patravoot Vatanasapt, Kulchaya Loyha, Supannee Promthet, Bunkerd Kongyingyoes, Natcha Patarapadungkit, Jureeporn Chuerduangphui, Chamsai Pientong
Human papillomavirus (HPV) is an independent risk factor for development of oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of HPV infection and the trend in percentage of HPV-associated OSCC over a 5-year period in northeastern Thailand. In this case-control study, 91 exfoliated oral cell samples and 80 lesion cell samples from OSCC cases and exfoliated oral cells from 100 age/gender-matched controls were collected. HPV infection was investigated by PCR using GP5+/GP6+ primers followed by HPV genotyping using reverse line blot hybridization...
December 9, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27930766/differences-in-the-prevalence-of-human-papillomavirus-hpv-in-head-and-neck-squamous-cell-cancers-by-sex-race-anatomic-tumor-site-and-hpv-detection-method
#18
Gypsyamber D'Souza, William H Westra, Steven J Wang, Annemieke van Zante, Alicia Wentz, Nicole Kluz, Eleni Rettig, William R Ryan, Patrick K Ha, Hyunseok Kang, Justin Bishop, Harry Quon, Ana P Kiess, Jeremy D Richmon, David W Eisele, Carole Fakhry
Importance: Human papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear. Objective: To explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC). Design, Setting, and Participants: Retrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females...
December 8, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27929118/exosomal-microrna-mir-1246-induces-cell-motility-and-invasion-through-the-regulation-of-dennd2d-in-oral-squamous-cell-carcinoma
#19
Sujata Sakha, Tomoki Muramatsu, Koji Ueda, Johji Inazawa
Metastasis is associated with poor prognosis in cancers. Exosomes, which are packed with RNA and proteins and are released in all biological fluids, are emerging as an important mediator of intercellular communication. However, the function of exosomes remains poorly understood in cancer metastasis. Here, we demonstrate that exosomes isolated by size-exclusion chromatography from a highly metastatic human oral cancer cell line, HOC313-LM, induced cell growth through the activation of ERK and AKT as well as promoted cell motility of the poorly metastatic cancer cell line HOC313-P...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926533/andrographolide-impedes-cancer-stemness-and-enhances-radio-sensitivity-in-oral-carcinomas-via-mir-218-activation
#20
Po-Yu Yang, Pei-Ling Hsieh, Tong Hong Wang, Cheng-Chia Yu, Ming-Yi Lu, Yi-Wen Liao, Tzu-Hsin Lee, Chih-Yu Peng
Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it...
December 1, 2016: Oncotarget
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