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https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#1
Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28300471/decoupling-of-dna-methylation-and-activity-of-intergenic-line-1-promoters-in-colorectal-cancer
#2
Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund, Cristina Tufarelli
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased towards young and transpositionally active elements. Here, we investigate the relationship between methylation of two intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression...
March 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28286086/hyper-methylation-of-the-upstream-cpg-island-shore-is-a-likely-mechanism-of-gper1-silencing-in-breast-cancer-cells
#3
Mohan C Manjegowda, Paridhi Singhal Gupta, Anil M Limaye
GPER1, also known as GPR30, is a novel seven-transmembrane G-protein coupled estrogen receptor that mediates both short-term (non-genomic) and long-term (genomic) effects of estrogen in target cells and tissues. A substantial body of work over the last two decades has highlighted its therapeutic or prognostic utility. However, the clinical data on the expression of GPER1 in breast tissue is ambiguous. Analysis of TCGA RNAseq data revealed significantly lower mean expression of GPER1 mRNA in primary breast tumors compared to that in normal breast tissues...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28278702/kr%C3%A3-ppel-like-factor-4-contributes-to-the-pathogenesis-of-mantle-cell-lymphoma
#4
Xin-Yu Li, Ling-Yun Geng, Xiang-Xiang Zhou, Na Wei, Xiao-Sheng Fang, Ying Li, Xin Wang
Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. Krüppel-like factor 4 (KLF4) has been reported as a bi-regulator in malignancies, but little is known about its role in MCL. Here, we showed that KLF4 was downregulated in three MCL cell lines and lymph nodes from MCL patients, which resulted in a negative prognosis. We also found that the regulation of KLF4 could inhibit the proliferation and induce apoptosis of Jeko-1 cells. The lentivirally over-expressed KLF4 protein was found bind to β-catenin and could inhibit downstream molecules such as cyclinD1 and c-Myc...
February 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28259927/autophagy-induction-in-the-skeletal-myogenic-differentiation-of-human-tonsil-derived-mesenchymal-stem-cells
#5
Saeyoung Park, Yoonyoung Choi, Namhee Jung, Jieun Kim, Seiyoon Oh, Yeonsil Yu, Jung-Hyuck Ahn, Inho Jo, Byung-Ok Choi, Sung-Chul Jung
Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation and are thus a valuable source for the replacement of diseased or damaged organs. Previously, we reported that the tonsils can be an excellent reservoir of MSCs for the regeneration of skeletal muscle (SKM) damage. However, the mechanisms involved in the differentiation from tonsil-derived MSCs (T-MSCs) to myocytes via myoblasts remain unclear. To clarify these mechanisms, we analyzed gene expression profiles of T-MSCs during differentiation into myocytes compared with human skeletal muscle cells (hSKMCs)...
February 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28240298/glucocorticoid-receptor-positively-regulates-transcription-of-fndc5-in-the-liver
#6
Hyoung Kyu Kim, Yu Jeong Jeong, In-Sung Song, Yeon Hee Noh, Kyo Won Seo, Min Kim, Jin Han
Irisin is secreted by skeletal muscle during exercise and influences energy and metabolic homeostasis. This hormone is a cleaved and secreted fragment of fibronectin type III domain-containing 5 (FNDC5). Elucidation of the FNDC5 gene regulation mechanism is necessary to clarify the function of irisin as a potential therapeutic target in human metabolic diseases. Thus, we investigated the genetic and epigenetic mechanisms that regulate expression of the FNDC5 gene. FNDC5 mRNA was strong expressed in major energy-dependent human tissues, including heart, brain, liver, and skeletal muscle...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230826/modifying-effects-of-5-azacytidine-on-metal-containing-proteins-profile-in-guerin-carcinoma-with-different-sensitivity-to-cytostatics
#7
V F Chekhun, Y V Lozovska, L A Naleskina, T V Borikun, A P Burlaka, I N Todor, D V Demash, T M Yalovenko, T V Zadvornyi, A O Pavlova, D M Storchay, N Yu Lukianova
AIM: To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. MATERIALS AND METHODS: The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment...
December 2016: Experimental Oncology
https://www.readbyqxmd.com/read/28217822/how-to-diagnose-early-5-azacytidine-induced-pneumonitis-a-case-report
#8
Srimanta Chandra Misra, Laurence Gabriel, Eric Nacoulma, Gérard Dine, Valentina Guarino
Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m(2) for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid...
December 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/28216553/an-improved-syringe-agroinfiltration-protocol-to-enhance-transformation-efficiency-by-combinative-use-of-5-azacytidine-ascorbate-acid-and-tween-20
#9
Huimin Zhao, Zilong Tan, Xuejing Wen, Yucheng Wang
Syringe infiltration is an important transient transformation method that is widely used in many molecular studies. Owing to the wide use of syringe agroinfiltration, it is important and necessary to improve its transformation efficiency. Here, we studied the factors influencing the transformation efficiency of syringe agroinfiltration. The pCAMBIA1301 was transformed into Nicotiana benthamiana leaves for investigation. The effects of 5-azacytidine (AzaC), Ascorbate acid (ASC) and Tween-20 on transformation were studied...
February 14, 2017: Plants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#10
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28207785/dna-methylation-of-the-fthl17-5-upstream-region-regulates-differential-fthl17-expression-in-lung-cancer-cells-and-germline-stem-cells
#11
Nana Aoki, Kentaro Mochizuki, Yasuhisa Matsui
The Ferritin heavy polypeptide-like 17 (Fthl17) gene is a member of the cancer/testis antigen gene family, and is preferentially expressed in cancer cells and in testis. Although DNA methylation has been linked to the regulation of human FTHL17 gene expression, detailed epigenetic regulation of its expression has not been investigated. To address this, we assessed the epigenetic regulation of murine Fthl17 gene expression in cancer cells and germ cells. Fthl17 was more highly expressed in testis, a murine lung cancer cell line, KLN205, and in germline stem cells (GSCs) than in normal lung tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#12
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28131982/use-of-5-azacitidine-for-therapy-related-myeloid-neoplasms-in-patients-with-concomitant-active-neoplastic-disease
#13
M Annereau, C Willekens, L El Halabi, C Chahine, V Saada, N Auger, A Danu, E Bermudez, J Lazarovici, D Ghez, A Leary, B Pistilli, F Lemare, E Solary, S de Botton, R-P Desmaris, J-B Micol
BACKGROUND: Patients diagnosed with therapy-related myeloid neoplasms (TRMN) with concomitant active neoplastic disorder (CAND) are usually proposed for best supportive care (BSC). We evaluated the feasibility of using 5-azacytidine (AZA) in this setting. METHODS: All patients referred to Gustave Roussy between 2010 and 2015 for TRMN diagnosis (less than 30% blast) and eligible for AZA treatment were included. Patients with CAND proposed for BSC were also described...
January 20, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28100780/a-novel-microrna-located-in-trkc-gene-regulates-wnt-signaling-pathway-and-is-differentially-expressed-in-colorectal-cancer-specimens
#14
Sadat Dokanehiifard, Atena Yasari, Hadi Najafi, Meisam Jafarzadeh, Maryam Nikkhah, Seyed Javad Mowla, Bahram M Soltani
Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis, differentiation and tumorigenesis. TrkC diverse functions might be attributed to the hypothetical non-coding RNAs, embedded within the gene. Using bioinformatics approaches, a novel miRNA named TrkC-miR2 was predicted within TrkC gene, capable of regulating Wnt pathway. For experimental verification of this miRNA, predicted TrkC-premir2 sequence was overexpressed in SW480 cells, which led to the detection of two mature TrkC-miR2 isomiRs, and their endogenous forms were detected in human cell lines as well...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100624/azacytidine-treatment-inhibits-the-progression-of-herpes-stromal-keratitis-by-enhancing-regulatory-t-cell-function
#15
Siva Karthik Varanasi, Pradeep B J Reddy, Siddheshvar Bhela, Ujjaldeep Jaggi, Fernanda Gimenez, Barry T Rouse
Ocular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28063323/genetic-and-epigenetic-regulation-on-the-transcription-of-gabrb2-genotype-dependent-hydroxymethylation-and-methylation-alterations-in-schizophrenia
#16
Lu Zong, Lin Zhou, Yu Hou, Lulu Zhang, Wei Jiang, Wenwei Zhang, Lijuan Wang, Xia Luo, Shiqing Wang, Cong Deng, Zhizhen Peng, Shufen Li, Jiming Hu, Hu Zhao, Cunyou Zhao
To improve our understanding of the abnormalities and non-Mendelian inheritance characteristics of schizophrenia, this study examined DNA methylation (5mC) and hydroxymethylation (5hmC) in the schizophrenia-associated GABRB2 gene encoding the type A γ-aminobutyric acid receptor β2 subunit. DNAs from the peripheral white blood cells of 279 schizophrenic patients and 256 controls from the Chinese Han population were examined to reveal that the GABRB2 promoter P1-5mC level which was correlated with olanzapine administration, P2-5mC/5hmC level, and Alu-5mC level which was correlated with administration of ziprasidone or oxcarbazepine, were increased in schizophrenic patients...
December 28, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28062506/wnt-signaling-pathway-inhibitor-sclerostin-inhibits-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis
#17
Smriti Murali Krishna, Sai-Wang Seto, Roby J Jose, Jiaze Li, Susan K Morton, Erik Biros, Yutang Wang, Vianne Nsengiyumva, Jan H N Lindeman, Gabriela G Loots, Catherine M Rush, Jeffrey M Craig, Jonathan Golledge
OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOST(Tg)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28061437/keap1-nrf2-pathway-in-kidney-cancer-frequent-methylation-of-keap1-gene-promoter-in-clear-renal-cell-carcinoma
#18
Federico Pio Fabrizio, Manuela Costantini, Massimiliano Copetti, Annamaria la Torre, Angelo Sparaneo, Andrea Fontana, Luana Poeta, Michele Gallucci, Steno Sentinelli, Paolo Graziano, Paola Parente, Vincenzo Pompeo, Laura De Salvo, Giuseppe Simone, Rocco Papalia, Francesco Picardo, Teresa Balsamo, Gerardo Paolo Flammia, Domenico Trombetta, Angela Pantalone, Klaas Kok, Ferronika Paranita, Lucia Anna Muscarella, Vito Michele Fazio
The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma)...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28035374/activation-of-oncogenic-pathways-in-classical-hodgkin-lymphoma-by-decitabine-a-rationale-for-combination-with-small-molecular-weight-inhibitors
#19
Tatjana Maria Swerev, Thomas Wirth, Alexey Ushmorov
DNA methylation is an epigenetic control mechanism that contributes to the specific phenotype and to the oncogenic program of virtually all tumor entities. Although efficacy of demethylating agents in classical Hodgkin lymphoma (cHL) was not specifically tested, a case of regression of relapsed metastatic cHL was described as a fortunate side‑effect of the demethylating agent 5‑azacytidine in a patient with myelodysplastic syndrome. We investigated molecular mechanisms of decitabine (5‑Aza‑dC) antitumor activity in cHL using gene expression profiling followed by gene set enrichment analysis...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27998022/the-effects-of-the-dna-methyltranfserases-inhibitor-5-azacitidine-on-ageing-oxidative-stress-and-dna-methylation-of-adipose-derived-stem-cells
#20
Katarzyna Kornicka, Krzysztof Marycz, Monika Marędziak, Krzysztof A Tomaszewski, Jakub Nicpoń
Human adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self-renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients' age. Age-related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction...
February 2017: Journal of Cellular and Molecular Medicine
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