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https://www.readbyqxmd.com/read/28069727/the-obesity-paradox-in-cancer-moving-beyond-bmi
#1
EDITORIAL
Shlomit Strulov Shachar, Grant R Williams
Body mass index (BMI) and simple counts of weight are easy and available tools in the clinic and in research. Recent studies have shown that cancer patients with a low normal BMI (or those with weight loss) have worse outcomes than obese patients. These results suggest that obesity has a protective effect and has been termed the "obesity paradox." In this commentary, we discuss hypothetical explanations and take a step beyond BMI or simple weights alone to present other useful and more specific body composition metrics, such as muscle tissue mass, visceral fat mass, and subcutaneous fat mass...
January 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28062363/governing-roles-for-trib3-pseudokinase-during-stress-erythropoiesis
#2
Arvind Dev, Ruth Asch, Edward Jachimowicz, Nicole Rainville, Ashley Johnson, Emily Greenfest-Allen, Don M Wojchowski
In response to anemia, the heightened production of erythropoietin (EPO) can sharply promote erythroid progenitor cell (EPC) formation. Specific mediators of such EPO- accelerated erythropoiesis, however, are not well understood. Presently, we first report that the expression of Trib3 in adult bone marrow EPCs in vivo is nominal at steady state, but strongly activated upon EPO challenge. In a knockout mouse model, Trib3 disruption modestly decreased steady-state erythrocyte numbers, and increased mean corpuscular volume...
January 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28031014/cebp-epigenetic-dysregulation-as-a-drug-target-for-the-treatment-of-hematologic-and-gynecologic-malignancies
#3
Chengming Sun, Ping Duan, Caifu Luan
The CCAAT/enhancer binding proteins (C/EBPs) form a family of transcription factors regulating many genes' expression in a variety of cells/tissues/organs at different developmental stages. With their capability of binding to a loosely defined consensus DNA sequence and through extensive protein-protein interactions, C/EBPs modulate diverse functions including cell differentiation, metabolism, and immune response, under both physiological and pathological conditions such as the establishment of hematological lineages, the maintenance of normal reproductive function, and the development of malignant disease...
December 28, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27986655/association-between-body-mass-index-and-cancer-survival-in-a-pooled-analysis-of-22-clinical-trials
#4
EDITORIAL
Heather Greenlee, Joseph M Unger, Michael LeBlanc, Scott Ramsey, Dawn L Hershman
BACKGROUND: Data are inconsistent on the association between body mass index (BMI) at time of cancer diagnosis and prognosis. We used data from 22 clinical treatment trials to examine the association between BMI and survival across multiple cancer types and stages. METHODS: Trials with ≥5 years of follow-up were selected. Patients with BMI < 18.5 kg/m(2) were excluded. Within a disease, analyses were limited to patients on similar treatment regimens. Variable cutpoint analysis identified a BMI cutpoint that maximized differences in survival...
December 16, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27986654/association-of-weight-change-after-colorectal-cancer-diagnosis-and-outcomes-in-the-kaiser-permanente-northern-california-population
#5
EDITORIAL
Jeffrey A Meyerhardt, Candyce H Kroenke, Carla M Prado, Marilyn L Kwan, Adrienne Castillo, Erin Weltzien, Elizabeth M Cespedes Feliciano, Jingjie Xiao, Bette J Caan
BACKGROUND: Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown. METHODS: We identified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I-III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis...
January 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27927209/coordinated-inhibition-of-c-ebp-by-tribbles-in-multiple-tissues-is-essential-for-caenorhabditis-elegans-development
#6
Kyung Won Kim, Nishant Thakur, Christopher A Piggott, Shizue Omi, Jolanta Polanowska, Yishi Jin, Nathalie Pujol
BACKGROUND: Tribbles proteins are conserved pseudokinases that function to control kinase signalling and transcription in diverse biological processes. Abnormal function in human Tribbles has been implicated in a number of diseases including leukaemia, metabolic syndromes and cardiovascular diseases. Caenorhabditis elegans Tribbles NIPI-3 was previously shown to activate host defense upon infection by promoting the conserved PMK-1/p38 mitogen-activated protein kinase (MAPK) signalling pathway...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27927200/tribbles-ortholog-nipi-3-and-bzip-transcription-factor-cebp-1-regulate-a-caenorhabditis-elegans-intestinal-immune-surveillance-pathway
#7
Deborah L McEwan, Rhonda L Feinbaum, Nicholas Stroustrup, Wilhelm Haas, Annie L Conery, Anthony Anselmo, Ruslan Sadreyev, Frederick M Ausubel
BACKGROUND: Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. RESULTS: We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27913676/translational-control-by-mtor-independent-routes-how-eif6-organizes-metabolism
#8
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/27897418/suppression-of-muscle-wasting-by-the-plant-derived-compound-ursolic-acid-in-a-model-of-chronic-kidney-disease
#9
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
https://www.readbyqxmd.com/read/27836672/transcription-factor-binding-site-enrichment-analysis-predicts-drivers-of-altered-gene-expression-in-nonalcoholic-steatohepatitis
#10
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
https://www.readbyqxmd.com/read/27790710/a-novel-mechanism-of-rs763110-polymorphism-contributing-to-cervical-cancer-risk-by-affecting-the-binding-affinity-of-c-ebp%C3%AE-and-oct1-complex-to-chromatin
#11
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 using PCR-TaqMan assays...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27782292/n-n-dimethylacetamide-significantly-attenuates-lps-and-tnf%C3%AE-induced-proinflammatory-responses-via-inhibition-of-the-nuclear-factor-kappa-b-pathway
#12
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
https://www.readbyqxmd.com/read/27663075/ccaat-enhancer-binding-protein-%C3%AE-negatively-regulates-progesterone-receptor-expression-in-human-glioblastoma-cells
#13
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
https://www.readbyqxmd.com/read/27644650/association-of-genetic-variants-in-arid5b-ikzf1-and-cebpe-with-risk-of-childhood-de-novo-b-lineage-acute-lymphoblastic-leukemia-in-india
#14
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
https://www.readbyqxmd.com/read/27493874/diabetic-mice-exhibited-a-peculiar-alteration-in-body-composition-with-exaggerated-ectopic-fat-deposition-after-muscle-injury-due-to-anomalous-cell-differentiation
#15
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
https://www.readbyqxmd.com/read/27450084/combined-chemical-genetic-approach-identifies-cytosolic-hsp70-dependence-in-rhabdomyosarcoma
#16
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
https://www.readbyqxmd.com/read/27429394/characterization-of-the-nlrc5-promoter-in-chicken-snps-regulatory-elements-and-cpg-islands
#17
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
https://www.readbyqxmd.com/read/27357961/mechanism-of-osteogenic-and-adipogenic-differentiation-of-tendon-stem-cells-induced-by-sirtuin%C3%A2-1
#18
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
https://www.readbyqxmd.com/read/27342846/cooperative-activity-of-gabp-with-pu-1-or-c-ebp%C3%AE%C2%B5-regulates-lamin-b-receptor-gene-expression-implicating-their-roles-in-granulocyte-nuclear-maturation
#19
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
https://www.readbyqxmd.com/read/27279837/analysis-of-possible-genetic-risk-factors-contributing-to-development-of-childhood-acute-lymphoblastic-leukaemia-in-the-latvian-population
#20
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
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