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https://www.readbyqxmd.com/read/27919956/expression-patterns-of-growth-and-survival-genes-with-prognostic-implications-in-advanced-pancreatic-cancer
#1
Dimitrios Pectasides, Vasiliki Kotoula, George Papaxoinis, Zoi Alexopoulou, Christos Dervenis, Epaminontas Samantas, Kleo Papaparaskeva, Elpida Charalambous, Chrysoula Gkakou, Christos Agalianos, Konstantine T Kalogeras, George Pentheroudakis, George Fountzilas
AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919448/fx11-inhibits-aerobic-glycolysis-and-growth-of-neuroblastoma-cells
#2
Eric J Rellinger, Brian T Craig, Alexandra L Alvarez, Haley L Dusek, Kwang W Kim, Jingbo Qiao, Dai H Chung
BACKGROUND: The MYC family of proteins promotes neuroblastoma tumorigenesis at least in part through the induction of aerobic glycolysis by promoting the transcription of key glycolytic enzymes, such as LDHA. FX11 is a selective inhibitor of LDHA that has demonstrated preclinical efficacy in adult cancers. Herein, we hypothesized that FX11 would inhibit aerobic glycolysis and block growth of neuroblastoma cells. METHODS: We surveyed 3 MYCN-single copy and 5 MYCN-amplified neuroblastoma cell lines to correlate C-MYC/N-MYC protein levels with LDHA expression...
December 2, 2016: Surgery
https://www.readbyqxmd.com/read/27918060/effect-of-small-molecules-on-cell-reprogramming
#3
REVIEW
M Baranek, A Belter, M Z Naskręt-Barciszewska, M Stobiecki, W T Markiewicz, J Barciszewski
The essential idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are able to indefinitely self-renew and differentiate into all cell types of the body which makes them a potent substantial player in regenerative medicine. The easily accessible source of induced pluripotent stem cells may allow obtaining and cultivating tissues in vitro. Reprogramming refers to regression of mature cells to its initial pluripotent state. One of the approaches affecting pluripotency is the usage of low molecular mass compounds that can modulate enzymes and receptors leading to the formation of pluripotent stem cells (iPSCs)...
December 5, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27917784/suppression-of-bromodomain-containing-protein-4-by-shrna-a-new-approach-for-cancer-treatment
#4
Turan Kaya, Berke Kahraman, Nurgeldi Bazarov, Alperen S Toker, Ayse Celik, Sadik Cigdem, Esra Gunduz
PURPOSE: MYC is a transcription factor coding gene that is believed to control 15% of the genes in the entire human genome. The central role of c-MYC in cancer pathogenesis makes it a major therapeutic target in field of anticancer agent development. METHODS: We targeted the acetyl-lysine binding modules or bromodomains, which are associated with c-MYC transcriptional activation. RESULTS: Sequence specific inhibition of BET bromodomains with small hairpin RNAs (shRNAs) resulted in cessation of cellular proliferation in different cancer cell lines...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27916586/selaginella-uncinata-flavonoids-ameliorated-ovalbumin-induced-airway-inflammation-in-a-rat-model-of-asthma
#5
Bing Yu, Wei Cai, Huan-Huan Zhang, Yu-Sen Zhong, Jie Fang, Wen-You Zhang, Li Mo, Lu-Chen Wang, Chen-Huan Yu
ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao" is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries. AIM OF THE STUDY: This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma...
December 1, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27913676/translational-control-by-mtor-independent-routes-how-eif6-organizes-metabolism
#6
REVIEW
Annarita Miluzio, Sara Ricciardi, Nicola Manfrini, Roberta Alfieri, Stefania Oliveto, Daniela Brina, Stefano Biffo
Over the past few years, there has been a growing interest in the interconnection between translation and metabolism. Important oncogenic pathways, like those elicited by c-Myc transcription factor and mTOR kinase, couple the activation of the translational machinery with glycolysis and fatty acid synthesis. Eukaryotic initiation factor 6 (eIF6) is a factor necessary for 60S ribosome maturation. eIF6 acts also as a cytoplasmic translation initiation factor, downstream of growth factor stimulation. eIF6 is up-regulated in several tumor types...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913503/diffuse-large-b-cell-lymphoma-r-chop-failure-what-to-do
#7
Bertrand Coiffier, Clémentine Sarkozy
Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913436/erk-and-p38-mapk-activities-determine-sensitivity-to-pi3k-mtor-inhibition-via-regulation-of-myc-and-yap
#8
Taru Muranen, Laura M Selfors, Julie Hwang, Lisa L Gallegos, Jonathan L Coloff, Carson C Thoreen, Seong A Kang, David M Sabatini, Gordon B Mills, Joan S Brugge
Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell-targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27911270/saha-and-or-mg132-reverse-the-aggressive-phenotypes-of-glioma-cells-an-in-vitro-and-vivo-study
#9
Xue-Feng Yang, Zhi-Juan Zhao, Jia-Jie Liu, Xiang-Hong Yang, Yang Gao, Shuang Zhao, Shuai Shi, Ke-Qiang Huang, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27908660/targeting-of-multiple-senescence-promoting-genes-and-signaling-pathways-by-triptonide-induces-complete-senescence-of-acute-myeloid-leukemia-cells
#10
Yanyan Pan, Mei Meng, Nana Zheng, Zhifei Cao, Ping Yang, Xiaodong Xi, Quansheng Zhou
Leukemia cells aberrantly overexpress senescence-suppression telomerase reverse transcriptase (TERT) and down-regulate key senescence-promoting genes to escape complete senescence, resulting in immortalization and malignant progression. Accordingly, induction of complete senescence is a sensible strategy for anti-leukemia therapy. However, effective senescence-based anti-leukemia drugs with low toxicity are currently lacking. In this study, we found that triptonide (chemical name diterpene triepoxide), a small molecule derived from the herb Tripterygium wilfordii Hook, strongly induced complete senescence in cultured acute myeloid leukemia (AML) cell lines, and potently inhibited growth and colony formation of U937 and HL-60 AML cell line with IC50 values of 7...
November 28, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#11
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27907214/derivation-of-induced-trophoblast-cell-lines-in-cattle-by-doxycycline-inducible-piggybac-vectors
#12
Takamasa Kawaguchi, Dooseon Cho, Masafumi Hayashi, Tomoyuki Tsukiyama, Koji Kimura, Shuichi Matsuyama, Naojiro Minami, Masayasu Yamada, Hiroshi Imai
Trophectoderm lineage specification is one of the earliest differentiation events in mammalian development. The trophoblast lineage, which is derived from the trophectoderm, mediates implantation and placental formation. However, the processes involved in trophoblastic differentiation and placental formation in cattle remain unclear due to interspecies differences when compared with other model systems and the small repertoire of available trophoblast cell lines. Here, we describe the generation of trophoblast cell lines (biTBCs) from bovine amnion-derived cells (bADCs) using an induced pluripotent stem cell technique...
2016: PloS One
https://www.readbyqxmd.com/read/27907212/diffuse-large-b-cell-lymphoma-cell-line-u-2946-model-for-mcl1-inhibitor-testing
#13
Hilmar Quentmeier, Hans G Drexler, Vivien Hauer, Roderick A F MacLeod, Claudia Pommerenke, Cord C Uphoff, Margarete Zaborski, Mattias Berglund, Gunilla Enblad, Rose-Marie Amini
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n)...
2016: PloS One
https://www.readbyqxmd.com/read/27906180/mir-148a-3p-represses-proliferation-and-emt-by-establishing-regulatory-circuits-between-erbb3-akt2-c-myc-and-dnmt1-in-bladder-cancer
#14
Xiao Wang, Zhen Liang, Xin Xu, Jiangfeng Li, Yi Zhu, Shuai Meng, Shiqi Li, Song Wang, Bo Xie, Alin Ji, Ben Liu, Xiangyi Zheng, Liping Xie
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27904699/generation-of-induced-pluripotent-stem-cells-with-high-efficiency-from-human-embryonic-renal-cortical-cells
#15
Ling Yao, Ruifang Chen, Pu Wang, Qi Zhang, Hailiang Tang, Huaping Sun
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904658/circulating-microparticles-enhanced-rat-vascular-wall-remodeling-following-endothelial-denudation
#16
Fan-Yen Lee, Hung-I Lu, Han-Tan Chai, Jiunn-Jye Sheu, Yi-Ling Chen, Tein-Hung Huang, Gour-Shenq Kao, Sheng-Yi Chen, Sheng-Ying Chung, Pei-Hsun Sung, Hsueh-Wen Chang, Mel S Lee, Hon-Kan Yip
This study tested the hypothesis that circulating microparticles (MPs) exacerbated vascular wall (VW) remodeling after endothelial denudation by 0.014 wire in a rat model. Adult male Sprague Dawley rats (n = 40) were equally categorized into group 1 [sham-control (SC); 3.0 mL saline intravenous injection], group 2 [SC + intravenous MPs (1.0 × 10(7)) derived from patients with carotid artery stenosis (CAS)], group 3 [femoral arterial endothelial denudation (FAED)], group 4 (FAED + MPs derived from healthy subjects), and group 5 (FAED + CAS-derived MPs)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903915/max-is-an-epigenetic-sensor-of-5-carboxylcytosine-and-is-altered-in-multiple-myeloma
#17
Dongxue Wang, Hideharu Hashimoto, Xing Zhang, Benjamin G Barwick, Sagar Lonial, Lawrence H Boise, Paula M Vertino, Xiaodong Cheng
The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5'-CACGTG-3'. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903752/hexim1-as-a-robust-pharmacodynamic-marker-for-monitoring-target-engagement-of-bet-family-bromodomain-inhibitors-in-tumors-and-surrogate-tissues
#18
Xiaoyu Lin, Xiaoli Huang, Tamar Uziel, Paul Hessler, Daniel H Albert, Lisa A Roberts-Rapp, Keith F McDaniel, Warren M Kati, Yu Shen
An increasing number of BET family protein inhibitors have recently entered clinical trials. It has been reported that attempts of monitoring target engagement of the BET bromodomain inhibitor OTX015 using literature-described putative pharmacodynamic (PD) markers such as c-Myc, BRD2, etc. failed to detect PD marker responses in AML patients treated at active dose and those with clinical responses. Here we report the identification and characterization of HEXIM1 and other genes as robust PD markers for BET inhibitors...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903583/aspirin-therapy-reduces-the-ability-of-platelets-to-promote-colon-and-pancreatic-cancer-cell-proliferation-implications-for-the-oncoprotein-c-myc
#19
Annachiara Mitrugno, Joanna L Sylman, Anh T P Ngo, Jiaqing Pang, Rosalie C Sears, Craig Williams, Owen J T McCarty
Aspirin, an anti-inflammatory and anti-thrombotic drug, has become the focus of intense research as a potential anti-cancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anti-cancer effect of aspirin when used in low, anti-platelet doses. However, the mechanism(s) through which low dose aspirin works is poorly understood. In this study we aimed to determine the effect of aspirin on the crosstalk between platelets and cancer cells...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#20
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
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