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https://www.readbyqxmd.com/read/28104508/exposure-to-high-levels-of-fumarate-and-succinate-leads-to-apoptotic-cytotoxicity-and-altered-global-dna-methylation-profiles-in-vitro
#1
Johannes F Wentzel, Angélique Lewies, Abel J Bronkhorst, Etresia van Dyk, Lissinda H du Plessis, Piet J Pretorius
In the Krebs cycle, succinate is oxidized to fumarate by succinate dehydrogenase (SDH), followed by the conversion of fumarate to malate by fumarate hydratase (FH). In cells with defective SDH and FH, the Krebs cycle is congested, respiration impaired and fumarate and succinate accumulates. Several studies have indicated that the accumulation of these substrates are associated with cytotoxicity and oncogenesis. High levels of succinate and fumarate induce hypoxia inducible factor (HIF1A) hydroxylases, leading to the activation of oncogenic HIF pathways...
January 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28092369/context-dependent-role-for-chromatin-remodeling-component-pbrm1-baf180-in-clear-cell-renal-cell-carcinoma
#2
A Murakami, L Wang, S Kalhorn, P Schraml, W K Rathmell, A C Tan, R Nemenoff, K Stenmark, B-H Jiang, M E Reyland, L Heasley, C-J Hu
A subset of clear cell renal cell carcinoma (ccRCC) tumors exhibit a HIF1A gene mutation, yielding two ccRCC tumor types, H1H2 type expressing both HIF1α and HIF2α, and H2 type expressing HIF2α, but not functional HIF1α protein. However, it is unclear how the H1H2 type ccRCC tumors escape HIF1's tumor-suppressive activity. The polybromo-1 (PBRM1) gene coding for the BAF180 protein, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, is inactivated in 40% ccRCCs, the function and mechanism of BAF180 mutation is unknown...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28088462/activation-of-the-hypoxia-inducible-factor-1-alpha-subunit-pathway-in-steatotic-liver-contributes-to-formation-of-cholesterol-gallstones
#3
Yoichiro Asai, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Masamitsu Maekawa, Midori Honma, Masanori Ikeda, Keigo Murakami, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Takashi Sugisawa, Yumiko Chiba, Yasuteru Kondo, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Yasuhiro Nakamura, Hiroaki Yamaguchi, Kozo Tanaka, Hironobu Sasano, Nariyasu Mano, Yoshiyuki Ueno, Tooru Shimosegawa, Hideki Katagiri
BACKGROUND AND AIMS: Hypoxia inducible factor 1 alpha subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with non-alcoholic fatty liver disease (NAFLD). NAFLD increases risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. METHODS: We performed studies with mice with inducible disruption of Hif1a in hepatocytes, via a Cre adenoviral vector (iH-HIFKO mice), and mice without disruption of Hif1a (control mice)...
January 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28077088/integrated-rna-seq-and-dnase-seq-analyses-identify-phenotype-specific-bmp4-signaling-in-breast-cancer
#4
M Ampuja, T Rantapero, A Rodriguez-Martinez, M Palmroth, E L Alarmo, M Nykter, A Kallioniemi
BACKGROUND: Bone morphogenetic protein 4 (BMP4) plays an important role in cancer pathogenesis. In breast cancer, it reduces proliferation and increases migration in a cell line-dependent manner. To characterize the transcriptional mediators of these phenotypes, we performed RNA-seq and DNase-seq analyses after BMP4 treatment in MDA-MB-231 and T-47D breast cancer cells that respond to BMP4 with enhanced migration and decreased cell growth, respectively. RESULTS: The RNA-seq data revealed gene expression changes that were consistent with the in vitro phenotypes of the cell lines, particularly in MDA-MB-231, where migration-related processes were enriched...
January 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28074863/herb-pair-danggui-honghua-mechanisms-underlying-blood-stasis-syndrome-by-system-pharmacology-approach
#5
Shi-Jun Yue, Lan-Ting Xin, Ya-Chu Fan, Shu-Jiao Li, Yu-Ping Tang, Jin-Ao Duan, Hua-Shi Guan, Chang-Yun Wang
Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28055967/cycling-hypoxia-affects-cell-invasion-and-proliferation-through-direct-regulation-of-claudin1-claudin7-expression-and-indirect-regulation-of-p18-through-claudin7
#6
Hong Liu, Feifei Jiang, Xinshan Jia, Jing Lan, Hao Guo, Erran Li, Aihui Yan, Yan Wang
Claudins (CLDNs), the major integral membrane proteins at tight junction, play critical roles in apical cell-to-cell adhesion, maintenance of epithelial polarity, and formation of impermeable barriers between epithelial cells.We investigated in this study the expression of CLDNs- Claudin1 (CLDN1) and Claudin7 (CLDN7), and their relation to tumor progression in nasopharyngeal cancer (NPC). CLDN7, rather than CLDN1, showed higher expression in both undifferentiated tumor tissue and the poorly differentiated CNE2 cells, compared with differentiated tissue and the highly differentiated CNE1 cells...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038356/mrna-overexpression-of-the-hypoxia-inducible-factor-1-alpha-subunit-gene-hif1a-an-independent-predictor-of-poor-overall-survival-in-chronic-lymphocytic-leukemia
#7
Christos K Kontos, Sotirios G Papageorgiou, Marios A Diamantopoulos, Andreas Scorilas, Efthimia Bazani, Diamantina Vasilatou, Konstantinos Gkontopoulos, Eirini Glezou, Georgia Stavroulaki, George Dimitriadis, Vasiliki Pappa
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28036268/role-of-vhl-hif1a-and-sdh-on-the-expression-of-mir-210-implications-for-tumoral-pseudo-hypoxic-fate
#8
Anna Merlo, Cristóbal Bernardo-Castiñeira, Inés Sáenz-de-Santa-María, Ana S Pitiot, Milagros Balbín, Aurora Astudillo, Nuria Valdés, Bartolomé Scola, Raquel Del Toro, Simón Méndez-Ferrer, José I Piruat, Carlos Suarez, María-Dolores Chiara
The hypoxia-inducible factor 1α (HIF-1α) and its microRNA target, miR-210, are candidate tumor-drivers of metabolic reprogramming in cancer. Neuroendocrine neoplasms such as paragangliomas (PGLs) are particularly appealing for understanding the cancer metabolic adjustments because of their associations with deregulations of metabolic enzymes, such as succinate dehydrogenase (SDH), and the von Hippel Lindau (VHL) gene involved in HIF-1α stabilization. However, the role of miR-210 in the pathogenesis of SDH-related tumors remains an unmet challenge...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031235/htp-nutraceutical-screening-for-histone-deacetylase-inhibitors-and-effects-of-hdacis-on-tumor-suppressing-mirnas-by-trichostatin-a-and-grapeseed-vitis-vinifera-in-hela-cells
#9
Elizabeth A Mazzio, Karam F A Soliman
BACKGROUND/AIM: Aggressive tumor malignancies are a consequence of delayed diagnosis, epigenetic/phenotype changes and chemo-radiation resistance. Histone deacetylases (HDACs) are a major epigenetic regulator of transcriptional repression, which are highly overexpressed in advanced malignancy. While original chemotherapy drugs were modeled after phytochemicals elucidated by botanical screenings, HDAC inhibitors (HDACi) such as apicidin, trichostatin A (TSA) and butyrate were discovered as products of fungus and microbes, in particular, gut microbiota...
2, 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28030564/poorly-differentiated-medullary-phenotype-predicts-poor-survival-in-early-lymph-node-negative-gastro-esophageal-adenocarcinomas
#10
Christoph Treese, Pedro Sanchez, Patricia Grabowski, Erika Berg, Hendrik Bläker, Martin Kruschewski, Oliver Haase, Michael Hummel, Severin Daum
BACKGROUND: 5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0). METHODS: Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival...
2016: PloS One
https://www.readbyqxmd.com/read/28030556/hepatocyte-hypoxia-inducible-factor-1-mediates-the-development-of-liver-fibrosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#11
Omar A Mesarwi, Mi-Kyung Shin, Shannon Bevans-Fonti, Christina Schlesinger, Janet Shaw, Vsevolod Y Polotsky
BACKGROUND: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis...
2016: PloS One
https://www.readbyqxmd.com/read/27994516/genes-involved-in-angiogenesis-and-mtor-pathways-are-frequently-mutated-in-asian-patients-with-pancreatic-neuroendocrine-tumors
#12
Wen-Chi Chou, Po-Han Lin, Yi-Chen Yeh, Yi-Ming Shyr, Wen-Liang Fang, Shin-E Wang, Chun-Yu Liu, Peter Mu-Hsin Chang, Ming-Han Chen, Yi-Ping Hung, Chung-Pin Li, Yee Chao, Ming-Huang Chen
Introduction: To address the issue of limited data on and inconsistent findings for genetic alterations in pancreatic neuroendocrine tumors (pNETs), we analyzed sequences of known pNET-associated genes for their impact on clinical outcomes in a Taiwanese cohort. Methods: Tissue samples from 40 patients with sporadic pNETs were sequenced using a customized sequencing panel that analyzed 43 genes with either an established or potential association with pNETs. Genetic mutations and clinical outcomes were analyzed for potential associations...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27989982/meta-analysis-of-microarray-based-expression-profiles-to-identify-differentially-expressed-genes-in-intracranial-aneurysms
#13
Zhe Xu, Hao Li, Jiangman Song, Bing Han, Zheng Wang, Yong Cao, Shuo Wang, Jizong Zhao
OBJECTIVE: To gain comprehensive insight into the molecular mechanism of formation and rupture of intracranial aneurysms (IAs). METHODS: All publicly accessible microarray-based whole-genome gene expression profiles on IAs were retrieved. The significance analysis of microarrays method was applied to identify differentially expressed genes (DEGs). Functional annotation was performed using gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses...
January 2017: World Neurosurgery
https://www.readbyqxmd.com/read/27981753/association-between-genetic-polymorphisms-involved-in-the-hypoxia-inducible-factor-pathway-and-lung-cancer-risk-a-case-control-study-in-japan
#14
Yuzo Yamamoto, Chikako Kiyohara, Saiko Ogata-Suetsugu, Naoki Hamada, Yoichi Nakanishi
AIM: Hypoxia-inducible factor (HIF) contributes to the adaptation of tumor cells to hypoxic conditions, so genetic polymorphisms involved in this pathway may affect cellular response to hypoxia and be associated with cancer risk. Thus, we examined the association between the lung cancer risk and genetic polymorphisms involved in the HIF pathway. METHODS: This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of HIF1A rs11549467, HIF1A rs11549465, HIF1A rs2057482, HIF2A rs13419896 and vascular endothelial growth factor A (VEGFA) rs833061 on the risk of lung cancer using TaqMan real-time PCR assay...
December 16, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27965712/targeted-inhibition-of-the-mir-199a-214-cluster-by-crispr-interference-augments-the-tumor-tropism-of-human-induced-pluripotent-stem-cell-derived-neural-stem-cells-under-hypoxic-condition
#15
Yumei Luo, Xuehu Xu, Xiuli An, Xiaofang Sun, Shu Wang, Detu Zhu
The human induced pluripotent stem cell (hiPSC) provides a breakthrough approach that helps overcoming ethical and allergenic challenges posed in application of neural stem cells (NSCs) in targeted cancer gene therapy. However, the tumor-tropic capacity of hiPSC-derived NSCs (hiPS-NSCs) still has much room to improve. Here we attempted to promote the tumor tropism of hiPS-NSCs by manipulating the activity of endogenous miR-199a/214 cluster that is involved in regulation of hypoxia-stimulated cell migration...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27902480/down-regulation-of-rna-binding-motif-single-stranded-interacting-protein-3-along-with-up-regulation-of-nuclear-hif1a-correlates-with-poor-prognosis-in-patients-with-gastric-cancer
#16
Youliang Wu, Dapeng Yun, Yingjie Zhao, Yuqi Wang, Ruochuan Sun, Qiang Yan, Shangxin Zhang, Mingdian Lu, Zhen Zhang, Daru Lu, Yongxiang Li
Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear.To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885528/a-network-biology-approach-to-understanding-the-importance-of-chameleon-proteins-in-human-physiology-and-pathology
#17
Golnaz Bahramali, Bahram Goliaei, Zarrin Minuchehr, Sayed-Amir Marashi
Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein...
November 24, 2016: Amino Acids
https://www.readbyqxmd.com/read/27862406/expression-pattern-of-hif1alpha-and-vasohibins-during-follicle-maturation-and-corpus-luteum-function-in-the-bovine-ovary
#18
B Berisha, D Schams, D Rodler, F Sinowatz, M W Pfaffl
The aim of this study was to characterize expression patterns of hypoxia-inducible factor-1alpha (HIF1A) and vasohibin family members (VASH1 and VASH2) during different stages of ovarian function in cow. Experiment 1: Antral follicle classification occurred by follicle size and estradiol-17beta (E2) concentration in the follicular fluid into 5 groups (<0.5, 0.5-5, 5-40, 40-180 and >180 E2 ng/ml). Experiment 2: Corpora lutea (CL) were assigned to the following stages: days 1-2, 3-4, 5-7, 8-12, 13-16 and >18 (after regression) of oestrous cycle and of pregnancy (months 1-2, 3-4, 6-7, >8)...
November 11, 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27818937/depot-specific-differences-in-angiogenic-capacity-of-adipose-tissue-in-differential-susceptibility-to-diet-induced-obesity
#19
Mun-Gyu Song, Hye-Jin Lee, Bo-Yeong Jin, Ruth Gutierrez-Aguilar, Kyung-Ho Shin, Sang-Hyun Choi, Sung Hee Um, Dong-Hoon Kim
OBJECTIVE: Adipose tissue (AT) expansion requires AT remodeling, which depends on AT angiogenesis. Modulation of AT angiogenesis could have therapeutic promise for the treatment of obesity. However, it is unclear how the capacity of angiogenesis in each adipose depot is affected by over-nutrition. Therefore, we investigated the angiogenic capacity (AC) of subcutaneous and visceral fats in lean and obese mice. METHODS: We compared the AC of epididymal fat (EF) and inguinal fat (IF) using an angiogenesis assay in diet-induced obese (DIO) mice and diet-resistant (DR) mice fed a high-fat diet (HFD)...
November 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27805868/ovariectomy-alters-gene-expression-of-the-hippocampal-formation-in-middle-aged-rats
#20
Miklós Sárvári, Imre Kalló, Erik Hrabovszky, Norbert Solymosi, Zsolt Liposits
Ovarian hormones regulate the transcriptome of the hippocampus and modulate its functions. During menopause this complex signaling declines, leading to impaired learning and memory. This study was undertaken to clarify the effects of long-term, surgical ovariectomy (OVX) on the rat hippocampal transcriptome. At age of 13 months, intact control and ovariectomized groups were formed. All animals were sacrificed 5 weeks after gonadectomy, hippocampal formations were dissected and processed for transcriptome analysis...
November 2, 2016: Endocrinology
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