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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
Rizhen Yu, Ji-An Chen, Jing Xu, Jin Cao, Yanlin Wang, Sandhya S Thomas, Zhaoyong Hu
BACKGROUND: Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF-1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation. METHODS: Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone...
November 17, 2016: Journal of Cachexia, Sarcopenia and Muscle
April D Lake, Alexandria L Chaput, Petr Novak, Nathan J Cherrington, Catharine L Smith
The molecular mechanisms behind the transition from simple steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) are not clearly understood. This hinders development of effective therapies for treatment and prevention of NASH. In this study expression profiling data from normal, steatosis, and NASH human livers were used to predict transcription factors that are misregulated as mechanistic features of NAFLD progression. Previously-published human NAFLD gene expression profiling data from normal, steatosis, and NASH livers were subjected to transcription factor binding site enrichment analysis...
December 15, 2016: Biochemical Pharmacology
Shenshen Wu, Shizhi Wang, You Fu, Weiyan Tang, Hua Jin, Qingtao Meng, Chengcheng Zhang, Mengjing Cui, Xiaoli Cao, Xiaobo Li, Zhengdong Zhang, Rui Chen
Recently, several studies have showed that FAS (rs2234767, rs1800682) and FASL (rs763110) functional single nucleotide polymorphisms (SNPs) were associated with the risk of various cancers. However, the association between cervical cancer risk and the three SNPs above remained inconclusive. In this work, we performed a two-stage case-control study on 1155 cervical cancer patients and 1252 matched healthy controls to determine the roles of the mentioned SNPs in cervical cancer susceptibility. We genotyped the FAS rs2234767, rs1800682, and FASL rs763110 polymorphisms by using PCR-TaqMan assays...
October 28, 2016: International Journal of Cancer. Journal International du Cancer
Ryan Pekson, Vladimir Poltoratsky, Samir Gorasiya, Sruthi Sundaram, Charles R Ashby, Ivana Vancurova, Sandra E Reznik
Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits LPS-induced increases in placental pro-inflammatory cytokines and up-regulates the anti-inflammatory cytokine Interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study we investigate how DMA produces its anti-inflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264...
October 24, 2016: Molecular Medicine
Valeria Hansberg-Pastor, Aliesha González-Arenas, Ignacio Camacho-Arroyo
Many progesterone (P4) actions are mediated by its intracellular receptor (PR), which has two isoforms (PR-A and PR-B) differentially transcribed from separate promoters of a single gene. In glioblastomas, the most frequent and aggressive brain tumors, PR-B is the predominant isoform. In an in silico analysis we showed putative CCAAT/Enhancer Binding Protein (C/EBP) binding sites at PR-B promoter. We evaluated the role of C/EBPβ in PR-B expression regulation in glioblastoma cell lines, which expressed different ratios of PR and C/EBPβ isoforms (LAP1, LAP2, and LIP)...
September 20, 2016: Molecular and Cellular Endocrinology
Prerana Bhandari, Firoz Ahmad, Swarna Mandava, Bibhu Ranjan Das
BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted specic polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most significantly associated with risk of developing childhood B-lineage ALL...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Masaki Mogi, Katsuhiko Kohara, Hirotomo Nakaoka, Harumi Kan-No, Kana Tsukuda, Xiao-Li Wang, Toshiyuki Chisaka, Hui-Yu Bai, Bao-Shuai Shan, Masayoshi Kukida, Jun Iwanami, Tetsuro Miki, Masatsugu Horiuchi
BACKGROUND: Sarcopenic obesity, age-related muscle loss, which is compensated by an increase in fat mass, impairs quality of life in elderly people. Although the increase in intramuscular fat is associated with decreased insulin sensitivity and increased metabolic risk factors, the origin of diabetes-associated intramuscular fat has not been elucidated. Here, we investigated intramuscular fat deposition using a muscle injury model in type 2 diabetic mice. METHODS: Male 8-week-old C57BL/6 and 8-week-old and 26-week-old KKAy underwent intramuscular injection of cardiotoxin (Ctx) (100 μL/10 μM) into the tibialis anterior (TA) muscles...
May 2016: Journal of Cachexia, Sarcopenia and Muscle
Amit J Sabnis, Christopher J Guerriero, Victor Olivas, Anin Sayana, Jonathan Shue, Jennifer Flanagan, Saurabh Asthana, Adrienne W Paton, James C Paton, Jason E Gestwicki, Peter Walter, Jonathan S Weissman, Peter Wipf, Jeffrey L Brodsky, Trever G Bivona
Cytosolic and organelle-based heat-shock protein (HSP) chaperones ensure proper folding and function of nascent and injured polypeptides to support cell growth. Under conditions of cellular stress, including oncogenic transformation, proteostasis components maintain homeostasis and prevent apoptosis. Although this cancer-relevant function has provided a rationale for therapeutically targeting proteostasis regulators (e.g., HSP90), cancer-subtype dependencies upon particular proteostasis components are relatively undefined...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
X M Guo, X P Liu, G B Chang, L Xu, Y L Bi, H Z Wang, Y Zhang, P F Zhu, Y Wu, G H Chen
NLRC5 plays an important role in the innate immunity and cellular immunity in many species, but the regulatory mechanism of NLRC5 expression in chickens remains unclear. In this study, a series of deletion fragments of the NLRC5 promoter region were constructed and dual-luciferase assay was performed. Then, we detected the SNP in the core region and its function. Important transcriptional regulatory elements were predicted and identified. Methylation of CpG islands was measured. The results revealed that the two core regions of -4372 to -3756 and -2925 to -2265 in the NLRC5 promoter were essential for NLRC5 mRNA expression in which a SNP (A/G), located at -2470, was found to have an effect on the transcriptional activity...
October 2016: Animal Genetics
Junpeng Liu, Weifeng Han, Lei Chen, Kanglai Tang
The aim of the present study was to assess the expression of sirtuin (Sirt)1 in tendon stem cells (TSCs) and to elucidate its association with osteogenic and adipogenic differentiation of TSCs. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were performed to detect Sirt1 mRNA and protein levels in TSCs, respectively. TSCs were positive for Sirt1 expression, which was elevated by Sirt1 activator SRT1720 in a time- and concentration- dependent manner, and decreased by Sirt1 inhibitor EX527...
August 2016: Molecular Medicine Reports
Krishnakumar Malu, Rahul Garhwal, Margery G H Pelletier, Deepali Gotur, Stephanie Halene, Monika Zwerger, Zhong-Fa Yang, Alan G Rosmarin, Peter Gaines
Nuclear segmentation is a hallmark feature of mammalian neutrophil differentiation, but the mechanisms that control this process are poorly understood. Gene expression in maturing neutrophils requires combinatorial actions of lineage-restricted and more widely expressed transcriptional regulators. Examples include interactions of the widely expressed ETS transcription factor, GA-binding protein (GABP), with the relatively lineage-restricted E-twenty-six (ETS) factor, PU.1, and with CCAAT enhancer binding proteins, C/EBPα and C/EBPε...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Madara Kreile, Linda Piekuse, Dmitrijs Rots, Zane Dobele, Zhanna Kovalova, Baiba Lace
INTRODUCTION: Childhood acute lymphoblastic leukaemia (ALL) is a complex disease caused by a combination of genetic susceptibility and environmental exposure. Previous genome-wide association studies have reported several single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. Several variations in genes encoding enzymes involved in carcinogenesis are suggested as being associated with an increased risk of ALL development. MATERIAL AND METHODS: We enrolled 77 paediatric ALL patients and 122 healthy controls, and in addition parental DNA was also available for 45 probands...
June 1, 2016: Archives of Medical Science: AMS
Ting-Yu Chang, Hsin-An Chen, Ching-Feng Chiu, Yi-Wen Chang, Tsang-Chih Kuo, Po-Chun Tseng, Weu Wang, Mien-Chie Hung, Jen-Liang Su
Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensitization and reduce cancer stem-like cell properties in this setting. Elevating Dicer expression increased levels of the AXL kinase targeting miRNA miR-494, thereby repressing AXL expression to increase paclitaxel sensitivity...
July 1, 2016: Cancer Research
Rebekah H Nagler, Cabral A Bigman, Shoba Ramanadhan, Divya Ramamurthi, K Viswanath
BACKGROUND: Americans remain under-informed about cancer and other health disparities and the social determinants of health (SDH). The news media may be contributing to this knowledge deficit, whether by discussing these issues narrowly or ignoring them altogether. Because local media are particularly important in influencing public opinion and support for public policies, this study examines the prevalence and framing of disparities/SDH in local mainstream and ethnic print news. METHODS: We conducted a multi-method content analysis of local mainstream (English language) and ethnic (Spanish language) print news in two lower income cities in New England with substantial racial/ethnic minority populations...
April 2016: Cancer Epidemiology, Biomarkers & Prevention
Electra D Paskett, Jessica L Krok-Schoen, Michael L Pennell, Cathy M Tatum, Paul L Reiter, Juan Peng, Brittany M Bernardo, Rory C Weier, Morgan S Richardson, Mira L Katz
BACKGROUND: Uptake of the human papillomavirus (HPV) vaccine is low in Appalachian Ohio and areas with high cervical cancer rates. METHODS: We conducted a group-randomized trial among 12 counties in Appalachian Ohio randomized to receive either an HPV vaccine (intervention counties) or influenza vaccine (comparison counties) multilevel intervention (MLI). Parents (n = 337) who had a daughter aged 9 to 17 years who had not received the HPV vaccine were recruited from commercial lists...
April 2016: Cancer Epidemiology, Biomarkers & Prevention
Gloria D Coronado, Shirley A A Beresford, Dale McLerran, Ricardo Jimenez, Donald L Patrick, India Ornelas, Sonia Bishop, John R Scheel, Beti Thompson
BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women in the United States, and Latinas have relatively low rates of screening participation. The Multilevel Intervention to Increase Latina Participation in Mammography Screening study (¡Fortaleza Latina!) sought to assess the efficacy of a clinic- and patient-level program to increase breast cancer screening among Latinas in Western Washington who seek care at a safety net health center. METHODS: The study enrolled 536 Latinas ages 42 to 74 who had a primary care clinic visit in the previous 5 years and had not obtained a mammogram in the previous 2 years...
April 2016: Cancer Epidemiology, Biomarkers & Prevention
Damali N Martin, Tram Kim Lam, Katy Brignole, Kimlin T Ashing, William J Blot, Linda Burhansstipanov, Jarvis T Chen, Mark Dignan, Scarlett Lin Gomez, Maria Elena Martinez, Alicia Matthews, Julie R Palmer, Eliseo J Perez-Stable, Mario Schootman, Hugo Vilchis, Alexander Vu, Shobha Srinivasan
Medically underserved populations in the United States continue to experience higher cancer burdens of incidence, mortality, and other cancer-related outcomes. It is imperative to understand how health inequities experienced by diverse population groups may contribute to our increasing unequal cancer burdens and disparate outcomes. The National Cancer Institute convened a diverse group of scientists to discuss research challenges and opportunities for cancer epidemiology in medically underserved and understudied populations...
April 2016: Cancer Epidemiology, Biomarkers & Prevention
Hanene Gharbi, Islem Ben Hassine, Ismail Soltani, Ines Safra, Slah Ouerhani, Hind Bel Haj Othmen, Mouheb Teber, Ahlem Farah, Hassiba Amouri, Nourel Houda Toumi, Salima Abdennebi, Salem Abbes, Samia Menif
Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL. These studies have been conducted in European and Thai populations, and it is unclear whether these observations generalize to other populations with a lower incidence of pediatric ALL...
April 2016: Pediatric Hematology and Oncology
Gaëlle Palierne, Aurélie Fabre, Romain Solinhac, Christine Le Péron, Stéphane Avner, Françoise Lenfant, Coralie Fontaine, Gilles Salbert, Gilles Flouriot, Jean-François Arnal, Raphaël Métivier
Transcriptional regulation by the estrogen receptor-α (ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17β-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis...
July 2016: Molecular Endocrinology
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