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https://www.readbyqxmd.com/read/27932243/inhibition-of-mtor-eif4e-by-anti-viral-drug-ribavirin-effectively-enhances-the-effects-of-paclitaxel-in-oral-tongue-squamous-cell-carcinoma
#1
Dehua Dai, Hujie Chen, Jing Tang, Yi Tang
Upregulation of eIF4E is associated with poor clinical outcome in many human cancers and represents a potential therapeutic target. However, the function of eIF4E remains unknown in oral tongue squamous cell carcinoma (OTSCC). In this work, we show that ribavirin, an anti-viral drug, effectively augments sensitivity of OTSCC cells to paclitaxel via inhibiting mTOR/eIF4E signaling pathway. Ribavirin dose-dependently inhibits proliferation and induces apoptosis in SCC-9 and CAL27 cells. Combination of ribavirin and paclitaxel are more effectively in inhibiting proliferation and inducing apoptosis in OTSCC cells...
December 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27930667/protein-phosphatase-6-protects-prophase-i-arrested-oocytes-by-safeguarding-genomic-integrity
#2
Meng-Wen Hu, Tie-Gang Meng, Zong-Zhe Jiang, Ming-Zhe Dong, Heide Schatten, Xingzhi Xu, Zhen-Bo Wang, Qing-Yuan Sun
Mammalian oocytes are arrested at prophase of the first meiotic division in the primordial follicle pool for months, even years, after birth depending on species, and only a limited number of oocytes resume meiosis, complete maturation, and ovulate with each reproductive cycle. We recently reported that protein phosphatase 6 (PP6), a member of the PP2A-like subfamily, which accounts for cellular serine/threonine phosphatase activity, functions in completing the second meiosis. Here, we generated mutant mice with a specific deletion of Ppp6c in oocytes from the primordial follicle stage by crossing Ppp6cF/F mice with Gdf9-Cre mice and found that Ppp6cF/F; GCre+ mice are infertile...
December 8, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#3
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27913532/t-cell-acute-lymphoblastic-leukemia
#4
Elizabeth A Raetz, David T Teachey
T-cell acute lymphoblastic leukemia (T-ALL) is biologically distinct from its B lymphoblastic (B-ALL) counterpart and shows different kinetic patterns of disease response. Although very similar regimens are used to treat T-ALL and B-ALL, distinctions in response to different elements of therapy have been observed. Similar to B-ALL, the key prognostic determinant in T-ALL is minimal residual disease (MRD) response. Unlike B-ALL, other factors including age, white blood cell count at diagnosis, and genetics of the ALL blasts are not independently prognostic when MRD response is included...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27905484/independent-control-of-natural-killer-cell-responsiveness-and-homeostasis-at-steady-state-by-cd11c-dendritic-cells
#5
Thuy Thanh Luu, Sridharan Ganesan, Arnika Kathleen Wagner, Dhifaf Sarhan, Stephan Meinke, Natalio Garbi, Günter Hämmerling, Evren Alici, Klas Kärre, Benedict J Chambers, Petter Höglund, Nadir Kadri
During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27902464/expression-of-rab1a-is-upregulated-in-human-lung-cancer-and-associated-with-tumor-size-and-t-stage
#6
Xinxin Wang, Feng Liu, Xiaoyu Qin, Tinglei Huang, Bo Huang, Yanjie Zhang, Bin Jiang
Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined...
November 29, 2016: Aging
https://www.readbyqxmd.com/read/27873319/lung-neuroendocrine-tumours-deep-sequencing-of-the-four-who-histotypes-reveals-chromatin-remodelling-genes-as-major-players-and-a-prognostic-role-for-tert-rb1-men1-and-kmt2d
#7
Michele Simbolo, Andrea Mafficini, Katarzyna O Sikora, Matteo Fassan, Stefano Barbi, Vincenzo Corbo, Luca Mastracci, Borislav Rusev, Federica Grillo, Caterina Vicentini, Roberto Ferrara, Sara Pilotto, Federico Davini, Giuseppe Pelosi, Rita T Lawlor, Marco Chilosi, Giampaolo Tortora, Emilio Bria, Gabriella Fontanini, Marco Volante, Aldo Scarpa
Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNET) comprising the 4 WHO classification categories: 53 typical carcinoid (TC), 35 atypical carcinoid (AC), 27 large cell neuroendocrine carcinoma (LCNEC), and 33 small cell lung carcinoma (SCLC). A discovery screen was conducted on 46 samples using whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen and validated on additional 102 LNET by targeted NGS, and their prevalence was evaluated on the whole series...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27863423/cancer-cell-ccl5-mediates-bone-marrow-independent-angiogenesis-in-breast-cancer
#8
Michael John Sax, Christin Gasch, Vineel Rag Athota, Ruth Freeman, Parisa Rasighaemi, David Elton Westcott, Christopher John Day, Iva Nikolic, Benjamin Elsworth, Ming Wei, Kelly Rogers, Alexander Swarbrick, Vivek Mittal, Normand Pouliot, Albert Sleiman Mellick
It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849011/intrinsic-cellular-signaling-mechanisms-determine-the-sensitivity-of-cancer-cells-to-virus-induced-apoptosis
#9
Yunfei Wang, Dawei Li, Jian Luo, Guimei Tian, Lisa Y Zhao, Daiqing Liao
Cancer cells of epithelial and mesenchymal phenotypes exhibit different sensitivities to apoptosis stimuli, but the mechanisms underlying this phenomenon remain partly understood. We constructed a novel recombinant adenovirus expressing Ad12 E1A (Ad-E1A12) that can strongly induce apoptosis. Ad-E1A12 infection of epithelial cancer cells displayed dramatic detachment and apoptosis, whereas cancer cells of mesenchymal phenotypes with metastatic propensity were markedly more resistant to this virus. Notably, forced detachment of epithelial cells did not further sensitize them to Ad-E1A12-induced apoptosis, suggesting that cell detachment is a consequence rather than the cause of Ad-E1A12-induced apoptosis...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815218/oxyresveratrol-activates-parallel-apoptotic-and-autophagic-cell-death-pathways-in-neuroblastoma-cells
#10
Md Ataur Rahman, Kausik Bishayee, Ali Sadra, Sung-Oh Huh
BACKGROUND: Drug resistance from apoptosis is a challenging issue with different cancer types, and there is an interest in identifying other means of inducing cytotoxicity. Here, treatment of neuroblastoma cells with oxyresveratrol (OXYRES), a natural antioxidant, led to dose-dependent cell death and increased autophagic flux along with activation of caspase-dependent apoptosis. METHODS: For cell viability, we performed the CCK-8 assay. Protein expression changes were with Western blot and immunocytochemistry...
November 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27811956/probing-the-pi3k-akt-mtor-pathway-using-31-p-nmr-spectroscopy-routes-to-glycogen-synthase-kinase-3
#11
Su M Phyu, Chih-Chung Tseng, Ian N Fleming, Tim A D Smith
Akt is an intracellular signalling pathway that serves as an essential link between cell surface receptors and cellular processes including proliferation, development and survival. The pathway has many downstream targets including glycogen synthase kinase3 which is a major regulatory kinase for cell cycle transit as well as controlling glycogen synthase activity. The Akt pathway is frequently up-regulated in cancer due to overexpression of receptors such as the epidermal growth factor receptor, or mutation of signalling pathway kinases resulting in inappropriate survival and proliferation...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27805285/survivin-inhibitor-ym155-induces-mitochondrial-dysfunction-autophagy-dna-damage-and-apoptosis-in-bcl-xl-silenced-glioma-cell-lines
#12
Esther P Jane, Daniel R Premkumar, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
Because the anti-apoptotic protein Bcl-xL is overexpressed in glioma, one might expect that inhibiting or silencing this gene would promote tumor cell killing. However, our studies have shown that this approach has limited independent activity, but may tip the balance in favor of apoptosis induction in response to other therapeutic interventions. To address this issue, we performed a pharmacological screen using a panel of signaling inhibitors and chemotherapeutic agents in Bcl-xL silenced cells. Although limited apoptosis induction was observed with a series of inhibitors for receptor tyrosine kinases, PKC inhibitors, Src family members, JAK/STAT, histone deacetylase, the PI3K/Akt/mTOR pathway, MAP kinase, CDK, heat shock proteins, proteasomal processing, and various conventional chemotherapeutic agents, we observed a dramatic potentiation of apoptosis in Bcl-xL silenced cells with the survivin inhibitor, YM155...
November 2, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27793898/targeting-the-pi3k-pten-akt-mtor-pathway-in-treatment-of-sarcoma-cell-lines
#13
Hui Jun Lim, Xiaochun Wang, Philip Crowe, David Goldstein, Jia-Lin Yang
BACKGROUND/AIM: Sarcoma carries a poor prognosis prompting the need for targeted therapies aimed at deregulated signaling pathways. These include the PI3K/Akt/mTOR pathway commonly up-regulated in malignancies attributed to loss of PTEN expression. However, PTEN status and activation state of PI3K/Akt/mTOR pathway have not been comprehensively studied in sarcoma. The aims of this study were to characterise PTEN and Akt expression in a panel of sarcoma cell lines and then to examine mTOR inhibition using ridaforolimus...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27779100/hmgb1-inhibits-klotho-expression-and-malignant-phenotype-in-melanoma-cells-by-activating-nf-%C3%AE%C2%BAb
#14
Biao Xie, Ke Cao, Jinjin Li, Jia Chen, Jintian Tang, Xiang Chen, Kun Xia, Xiao Zhou, Yan Cheng, Jianda Zhou, Huiqing Xie
The molecular and cellular mechanisms behind the involvement of inflammation in melanoma have not been fully elucidated. In this study, knockdown of Hmgb1 expression increased apoptosis, reduced invasion and p-NF-κB expression, but increased Klotho protein level in melanoma tumor cells. The effect of Hmgb1 knockdown was overcome by LPS. Introduction of exogenous Hmgb1 significantly decreased apoptosis, increased invasion, elevated p-NF-κB, but lowered Klotho protein level in melanoma cells. The effect of exogenous Hmgb1 was agonized by NF-κB inhibitor CAPE...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27771251/anthelmintic-drug-ivermectin-inhibits-angiogenesis-growth-and-survival-of-glioblastoma-through-inducing-mitochondrial-dysfunction-and-oxidative-stress
#15
Yingying Liu, Shanshan Fang, Qiushi Sun, Bo Liu
Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner...
October 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27761114/prolonged-calorie-restriction-downregulates-skeletal-muscle-mtorc1-signaling-independent-of-dietary-protein-intake-and-associated-microrna-expression
#16
Lee M Margolis, Donato A Rivas, Maria Berrone, Yassine Ezzyat, Andrew J Young, James P McClung, Roger A Fielding, Stefan M Pasiakos
Short-term (5-10 days) calorie restriction (CR) downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1), however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR)...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27729611/pict-1-triggers-a-pro-death-autophagy-through-inhibiting-rrna-transcription-and-akt-mtor-p70s6k-signaling-pathway
#17
Chen Hongbo, Duo Yanhong, Hu Bo, Wang Zhiwei, Zhang Fang, Tsai Hsiangi, Zhang Jianping, Zhou Lanzhen, Wang Lijun, Wang Xinyu, Huang Laiqiang
PICT-1 was originally identified as a tumor suppressor. Here, we found that PICT-1 overexpression triggered pro-death autophagy without nucleolar disruption or p53 accumulation in U251 and MCF7 cells. Truncated PICT-1 fragments 181-346 and 1-346, which partly or totally lack nucleolar localization, showed weaker autophagy-inducing effects than full-length PICT-1 and a well-defined nucleolar mutant (181-479). Furthermore, PICT-1 partly localizes to the nucleolar fibrillar center (FC) and directly binds to ribosomal DNA (rDNA) gene loci, where it interacts with upstream binding factor (UBF)...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27729429/mtor-activity-and-its-prognostic-significance-in-human-colorectal-carcinoma-depending-on-c1-and-c2-complex-related-protein-expression
#18
Tamás Sticz, Anna Molnár, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Gyula Végső, Tamás Micsik, László Kopper, Anna Sebestyén
AIMS: Tumour heterogeneity and altered activation of signalling pathways play important roles in therapy resistance. The PI3K/Akt/mTOR signalling network is a well-known regulator of several functions that contribute to tumour growth. mTOR exists in two functionally different multiprotein complexes. We aimed to determine mTOR activity-related proteins in clinically followed, conventionally treated colon carcinomas and to analyse the correlation between clinical data and mTORC1 and mTORC2 activity...
October 11, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27686868/pan-raf-co-operates-with-pi3k-dependent-signalling-and-critically-contributes-to-myeloma-cell-survival-independently-of-mutated-ras
#19
E Müller, S Bauer, T Stühmer, A Mottok, C-J Scholz, T Steinbrunn, D Brünnert, A Brandl, H Schraud, S Kreßmann, A Beilhack, A Rosenwald, R C Bargou, M Chatterjee
Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in MM cell lines, primary MM cells in vitro, and in a syngeneic MM mouse model in vivo...
September 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27680680/microrna-21-protects-against-cardiac-hypoxia-reoxygenation-injury-by-inhibiting-excessive-autophagy-in-h9c2-cells-via-the-akt-mtor-pathway
#20
Zhouqing Huang, Shengjie Wu, Fanqi Kong, Xueli Cai, Bozhi Ye, Peiren Shan, Weijian Huang
MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)-induced injury. Here, we investigated the function of miR-21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR-21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR-21+ H/R) group, (miR-21-negative control + H/R) group, (BEZ235+ H/R) group and (miR-21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs...
September 29, 2016: Journal of Cellular and Molecular Medicine
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