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https://www.readbyqxmd.com/read/28644137/analyses-of-germline-variants-associated-with-ovarian-cancer-survival-identify-functional-candidates-at-the-1q22-and-19p12-outcome-loci
#1
Dylan M Glubb, Sharon E Johnatty, Michael C J Quinn, Tracy A O'Mara, Jonathan P Tyrer, Bo Gao, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Ignace Vergote, Digna R Velez Edwards, Alicia Beeghly-Fadiel, Javier Benitez, Maria J Garcia, Marc T Goodman, Pamela J Thompson, Thilo Dörk, Matthias Dürst, Francesmary Modungo, Kirsten Moysich, Florian Heitz, Andreas du Bois, Jacobus Pfisterer, Peter Hillemanns, Beth Y Karlan, Jenny Lester, Ellen L Goode, Julie M Cunningham, Stacey J Winham, Melissa C Larson, Bryan M McCauley, Susanne Krüger Kjær, Allan Jensen, Joellen M Schildkraut, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Helga B Salvesen, Line Bjorge, Penny M Webb, Peter Grant, Tanja Pejovic, Melissa Moffitt, Claus K Hogdall, Estrid Hogdall, James Paul, Rosalind Glasspool, Marcus Bernardini, Alicia Tone, David Huntsman, Michelle Woo, Aocs Group, Anna deFazio, Catherine J Kennedy, Paul D P Pharoah, Stuart MacGregor, Georgia Chenevix-Trench
We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498474/effect-of-mir-1244-on-cisplatin-treated-non-small-cell-lung-cancer-via-mef2d-expression
#2
Guang-Jian Li, Guang-Qiang Zhao, Jia-Peng Yang, Yong-Chun Zhou, Kai-Yun Yang, Yu-Jie Lei, Yun-Chao Huang
The aim of this study was to investigate the function of miR-1244 in cisplatin-treated non-small cell lung cancer (NSCLC). The results of quantitative PCR analysis revealed that the expression levels of miR-1244 in cisplatin‑treated A549 and NCI-H522 human lung cancer cell lines were lower than those in untreated A549 and NCI-H522 cells. Similarly, the expression level of miR-1244 in NSCLC tissue samples from cisplatin-treated patients was also lower than that in non-cisplatin-treated NSCLC patients. Notably, the overall survival times of cisplatin-treated NSCLC patients with high miR-1244 expression were superior to those patients with low miR-1244 expression...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28480592/slow-myofiber-commitment-by-semaphorin-3a-secreted-from-myogenic-stem-cells
#3
Ryuichi Tatsumi, Takahiro Suzuki, Mai-Khoi Q Do, Yuki Ohya, Judy E Anderson, Ayumi Shibata, Mai Kawaguchi, Shunpei Ohya, Hideaki Ohtsubo, Wataru Mizunoya, Shoko Sawano, Yusuke Komiya, Riho Ichitsubo, Koichi Ojima, Shin-Ichiro Nishimatsu, Tsutomu Nohno, Yutaka Ohsawa, Yoshihide Sunada, Mako Nakamura, Mitsuhiro Furuse, Yoshihide Ikeuchi, Takanori Nishimura, Takeshi Yagi, Ronald E Allen
Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) → myogenin-myocyte enhancer factor 2D → slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression...
May 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28473466/antagonistic-regulation-of-cell-cycle-and-differentiation-gene-programs-in-neonatal-cardiomyocytes-by-homologous-mef2-transcription-factors
#4
Cody A Desjardins, Francisco J Naya
Cardiomyocytes acquire their primary specialized function (contraction) before exiting the cell cycle. In this regard, proliferation and differentiation must be precisely coordinated for proper cardiac morphogenesis. Here, we have investigated the complex transcriptional mechanisms employed by cardiomyocytes to coordinate antagonistic cell-cycle and differentiation gene programs through the molecular dissection of the core cardiac transcription factor, MEF2. Knockdown of individual MEF2 proteins, MEF2A, -C, and -D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular homeostasis and gene regulation...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28469958/mir-421-inhibits-the-malignant-phenotype-in-glioma-by-directly-targeting-mef2d
#5
Liang Liu, Sitong Cui, Rui Zhang, Yan Shi, Liangsheng Luo
MicroRNA-421 (miRNA-421) dysregulation has been found in various human tumors, however, the biological function and molecular mechanism of miR-421 in glioma remain unclear. In this study, we investigated the potential biological roles of miR-421 in glioma cell lines. First, we demonstrated that compared with that of low grade gliomas (LGG), miR-421 expression is much lower in high grade gliomas (HGG) within the CGGA (Chinese Glioma Genome Atlas) database. MiR-421 expression in 5 normal brain tissues and 20 glioma tissues were in agreement with the result in the CGGA...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28461502/mef2d-haploinsufficiency-downregulates-the-nrf2-pathway-and-renders-photoreceptors-susceptible-to-light-induced-oxidative-stress
#6
Saumya Nagar, Sarah M Noveral, Dorit Trudler, Kevin M Lopez, Scott R McKercher, Xuemei Han, John R Yates, Juan C Piña-Crespo, Nobuki Nakanishi, Takumi Satoh, Shu-Ichi Okamoto, Stuart A Lipton
Gaining mechanistic insight into interaction between causative factors of complex multifactorial diseases involving photoreceptor damage might aid in devising effective therapies. Oxidative stress is one of the potential unifying mechanisms for interplay between genetic and environmental factors that contribute to photoreceptor pathology. Interestingly, the transcription factor myocyte enhancer factor 2d (MEF2D) is known to be important in photoreceptor survival, as knockout of this transcription factor results in loss of photoreceptors in mice...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28457811/methylene-blue-attenuates-neuroinflammation-after-subarachnoid-hemorrhage-in-rats-through-the-akt-gsk-3%C3%AE-mef2d-signaling-pathway
#7
Hangzhe Xu, Jianru Li, Zhijiang Wang, Majing Feng, Yongfeng Shen, Shenglong Cao, Tao Li, Yucong Peng, Linfeng Fan, Jingyin Chen, Chi Gu, Feng Yan, Lin Wang, Gao Chen
Subarachnoid hemorrhage (SAH) is a serious medical problem with few effective pharmacotherapies available, and neuroinflammation has been identified as an important pathological process in early brain injury (EBI) after SAH. Methylene blue (MB) is an older drug that has been recently proven to exert extraordinary neuroprotective effects in several brain insults. However, no study has reported the beneficial effects of MB in SAH. In the current investigation, we studied the neuroprotective effects of MB in EBI after SAH and focused on its anti-inflammatory role...
April 27, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28340574/myocyte-enhancer-factor-2d-provides-a-cross-talk-between-chronic-inflammation-and-lung-cancer
#8
Hai-Xing Zhu, Lin Shi, Yong Zhang, Yi-Chun Zhu, Chun-Xue Bai, Xiang-Dong Wang, Jie-Bai Zhou
BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. METHODS: We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition...
March 24, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28298358/identification-of-%C3%AE-catenin-interacting-proteins-in-nuclear-fractions-of-native-rat-collecting-duct-cells
#9
Jacqueline R Hwang, Chung-Lin Chou, Barbara Medvar, Mark A Knepper, Hyun Jun Jung
The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser(552)) of β-catenin, a multifunctional protein that acts as a transcriptional coregulator in the nucleus. The purpose of this study was to identify β-catenin-interacting proteins that might be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells, using experimental and computational approaches...
July 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28271248/network-reconstruction-reveals-that-valproic-acid-activates-neurogenic-transcriptional-programs-in-adult-brain-following-traumatic-injury
#10
Gerald A Higgins, Patrick Georgoff, Vahagn Nikolian, Ari Allyn-Feuer, Brian Pauls, Richard Higgins, Brian D Athey, Hasan E Alam
OBJECTIVES: To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). METHODS: Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. RESULTS: The transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis...
March 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#11
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B Ballak, Charles A Dinarello, Bas Heinhuis, Leo A B Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling
BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals...
February 22, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28063919/proteomic-analysis-of-the-protective-effects-of-aqueous-bark-extract-of-terminalia-arjuna-roxb-on-isoproterenol-induced-cardiac-hypertrophy-in-rats
#12
Santosh Kumar, Md Jahangir Alam, Pankaj Prabhakar, Sayeed Ahmad, Subir K Maulik, Manish Sharma, Shyamal K Goswami
ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous bark extract of Terminalia arjuna (TA) has been in use as an ethnomedicine for cardiovascular ailments in the Indian subcontinent for centuries. Studies using hemodynamic, ROS scavenging and anti-inflammatory parameters in animal models have shown its anti-atherogenic, hypotensive, inotropic, anti-inflammatory effects. However, details analysis on its effects on established molecular and cell biological markers are a prerequisite for its wider acceptance to the medical community...
January 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28058730/multilocus-analysis-reveals-three-candidate-genes-for-chinese-migraine-susceptibility
#13
X-K An, J Fang, Z-Z Yu, Q Lin, C-X Lu, H-L Qu, Q-L Ma
Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform...
January 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27977899/individual-evaluation-of-cardiac-marker-expression-and-self-beating-during-cardiac-differentiation-of-p19cl6-cells-on-different-culture-substrates
#14
Tetsuji Yamaoka, Mitsuhi Hirata, Takaaki Dan, Atsushi Yamashita, Akihisa Otaka, Takahiko Nakaoki, Azizi Miskon, Sachiro Kakinoki, Atsushi Mahara
Cell-based therapies using self-beating cardiomyocytes have been attracting great attention for use in cardiac regeneration, although an effective procedure to improve cardiac differentiation and self-beating induction is required. The purpose of this study is to clarify the effect of the culture substrate on cardiac maturation by separately evaluating the cardiac differentiation step and the beating induction step in vitro. To this end, the well-studied cardiomyocyte-like progenitor cell line P19CL6 and neonatal cardiomyocytes (NCMs) were selected and cultured on substrates coated with collagen type I (Col-I), gelatin (Gel), fibronectin (FN), or poly-l-lysine (PLL)...
April 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27827316/brm-promoter-polymorphisms-and-survival-of-advanced-non-small-cell-lung-cancer-patients-in-the-princess-margaret-cohort-and-cctg-br-24-trial
#15
Geoffrey Liu, Sinead Cuffe, Shermi Liang, Abul Kalam Azad, Lu Cheng, Yonathan Brhane, Xin Qiu, David W Cescon, Jeffrey Bruce, Zhuo Chen, Dangxiao Cheng, Devalben Patel, Brandon C Tse, Scott A Laurie, Glenwood Goss, Natasha B Leighl, Rayjean Hung, Penelope A Bradbury, Lesley Seymour, Frances A Shepherd, Ming Sound Tsao, Bingshu E Chen, Wei Xu, David N Reisman
Introduction: BRM, a key catalytic subunit of the SWI/SNF chromatin remodeling complex, is a putative tumor susceptibility gene that is silenced in 15% of non-small cell lung cancer (NSCLC). Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) are associated with reversible epigenetic silencing of BRM protein expression.Experimental Design: Advanced NSCLC patients from the Princess Margaret (PM) cohort study and from the CCTG BR.24 clinical trial were genotyped for BRM promoter polymorphisms. Associations of BRM variants with survival were assessed using log-rank tests, the method of Kaplan and Meier, and Cox proportional hazards models...
May 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27824051/genomic-analyses-identify-recurrent-mef2d-fusions-in-acute-lymphoblastic-leukaemia
#16
Zhaohui Gu, Michelle Churchman, Kathryn Roberts, Yongjin Li, Yu Liu, Richard C Harvey, Kelly McCastlain, Shalini C Reshmi, Debbie Payne-Turner, Ilaria Iacobucci, Ying Shao, I-Ming Chen, Marcus Valentine, Deqing Pei, Karen L Mungall, Andrew J Mungall, Yussanne Ma, Richard Moore, Marco Marra, Eileen Stonerock, Julie M Gastier-Foster, Meenakshi Devidas, Yunfeng Dai, Brent Wood, Michael Borowitz, Eric E Larsen, Kelly Maloney, Leonard A Mattano, Anne Angiolillo, Wanda L Salzer, Michael J Burke, Francesca Gianni, Orietta Spinelli, Jerald P Radich, Mark D Minden, Anthony V Moorman, Bella Patel, Adele K Fielding, Jacob M Rowe, Selina M Luger, Ravi Bhatia, Ibrahim Aldoss, Stephen J Forman, Jessica Kohlschmidt, Krzysztof Mrózek, Guido Marcucci, Clara D Bloomfield, Wendy Stock, Steven Kornblau, Hagop M Kantarjian, Marina Konopleva, Elisabeth Paietta, Cheryl L Willman, Mignon L Loh, Stephen P Hunger, Charles G Mullighan
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27698762/tfp5-prevents-1-methyl-4-phenyl-pyridine-ion-induced-neurotoxicity-in-mouse-cortical-neurons
#17
Qi-Shan Zhang, Yuan-Gao Liao, Zhong Ji, Yong Gu, Hai-Shan Jiang, Zuo-Shan Xie, Su-Yue Pan, Ya-Fang Hu
The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP(+))-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP(+) was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP(+)), scrambled peptide (Scb) (Scb + MPP(+)) and TFP5 (TFP5 + MPP(+)) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27507882/mef2d-bcl9-fusion-gene-is-associated-with-high-risk-acute-b-cell-precursor-lymphoblastic-leukemia-in-adolescents
#18
Kyogo Suzuki, Yusuke Okuno, Nozomu Kawashima, Hideki Muramatsu, Tatsuya Okuno, Xinan Wang, Shinsuke Kataoka, Yuko Sekiya, Motoharu Hamada, Norihiro Murakami, Daiei Kojima, Kotaro Narita, Atsushi Narita, Hirotoshi Sakaguchi, Kimiyoshi Sakaguchi, Nao Yoshida, Nobuhiro Nishio, Asahito Hama, Yoshiyuki Takahashi, Kazuko Kudo, Koji Kato, Seiji Kojima
PURPOSE: Acute lymphoblastic leukemia (ALL) makes up a significant proportion of all pediatric cancers, and relapsed ALL is a leading cause of cancer-associated deaths in children. Identification of risk factors and druggable molecular targets in ALL can lead to a better stratification of treatments and subsequent improvement in prognosis. PATIENTS AND METHODS: We enrolled 59 children with relapsed or primary refractory ALL who were treated in our institutions. We primarily performed RNA sequencing (RNA-seq) using patients' leukemic cells to comprehensively detect gene fusions and analyze gene expression profiles...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27499645/first-in-human-phase-1-trial-of-agarose-beads-containing-murine-renca-cells-in-advanced-solid-tumors
#19
Barry H Smith, Tapan Parikh, Zoe P Andrada, Thomas J Fahey, Nathaniel Berman, Madeline Wiles, Angelica Nazarian, Joanne Thomas, Anna Arreglado, Eugene Akahoho, David J Wolf, Daniel M Levine, Thomas S Parker, Lawrence S Gazda, Allyson J Ocean
PURPOSE: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective...
2016: Cancer Growth and Metastasis
https://www.readbyqxmd.com/read/27487558/brm-polymorphisms-pancreatic-cancer-risk-and-survival
#20
Maja Segedi, Laura N Anderson, Osvaldo Espin-Garcia, Ayelet Borgida, Teresa Bianco, Dangxiao Cheng, Zhuo Chen, Devalben Patel, M Catherine Brown, Wei Xu, David Reisman, Steven Gallinger, Michelle Cotterchio, Rayjean Hung, Geoffrey Liu, Sean P Cleary
Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM-1321), create MEF2D transcription binding sites that lead to epigenetic silencing of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex. BRM suppression can be reversed pharmacologically.(1) Our group and others have reported associations with lung, head and neck, hepatocellular cancer risk,(1-3) and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077). Herein, we assessed risk and survival associations with pancreatic cancer...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
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