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https://www.readbyqxmd.com/read/29321553/prediction-of-co-expression-genes-and-integrative-analysis-of-gene-microarray-and-proteomics-profile-of-keshan-disease
#1
Sen Wang, Rui Yan, Bin Wang, Peiru Du, Wuhong Tan, Mikko J Lammi, Xiong Guo
Keshan disease (KD) is a kind of endemic cardiomyopathy which has a high mortality. However, molecular mechanism in the pathogenesis of KD remains poorly understood. Serum samples were collected from 112 KD patients and 112 normal controls. Gene microarray was used to screen differently expressed genes. Genevestigator was applied to forecast co-expression genes of significant gene. iTRAQ proteomics analysis was used to verify significant genes and their co-expression genes. GO, COG, IPA and STRING were applied to undertake function categorization, pathway and network analysis separately...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312565/dissect-new-mechanistic-insights-for-geniposide-efficacy-on-the-hepatoprotection-using-multiomics-approach
#2
Shi Qiu, Aihua Zhang, Tianlei Zhang, Hui Sun, Yu Guan, Guangli Yan, Xijun Wang
A multi-omics approach could yield in-depth mechanistic insights. Here, we performed an integrated analysis of miRNAome, proteome and metabolome, aimed to investigate the underlying mechanism of active product geniposide in ethanol-induced apoptosis. We found that integrative meta-analysis identified 28 miRNAs, 20 proteins and 7 metabolites significantly differentially expressed, respectively. Further analysis identified geniposide extensively regulated multiple metabolism pathways and the most important related pathway was citrate cycle (TCA cycle)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306105/distinct-gene-alterations-with-a-high-percentage-of-myeloperoxidase-positive-leukemic-blasts-in-de-novo-acute-myeloid-leukemia
#3
Rena Kamijo, Hidehiro Itonaga, Rika Kihara, Yasunobu Nagata, Tomoko Hata, Norio Asou, Shigeki Ohtake, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Tomoki Naoe, Hitoshi Kiyoi, Yasushi Miyazaki
The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ≤50% MPO-positive blasts, (MPO-low group), respectively...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29291002/mutations-in-the-dna-methylation-pathway-and-number-of-driver-mutations-predict-response-to-azacitidine-in-myelodysplastic-syndromes
#4
M Teresa Cedena, Inmaculada Rapado, Alejandro Santos-Lozano, Rosa Ayala, Esther Onecha, María Abaigar, Esperanza Such, Fernando Ramos, José Cervera, María Díez-Campelo, Guillermo Sanz, Jesús Hernández Rivas, Alejandro Lucía, Joaquin Martínez-López
We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290954/wee1-epigenetically-modulates-5-hmc-levels-by-py37-h2b-dependent-regulation-of-idh2-gene-expression
#5
Nupam P Mahajan, Pavani Malla, Shambhavi Bhagwat, Vasundhara Sharma, Amod Sarnaik, Jongphil Kim, Shari Pilon-Thomas, Jeffery Weber, Kiran Mahajan
Epigenetic signaling networks dynamically regulate gene expression to maintain cellular homeostasis. Previously, we uncovered that WEE1 phosphorylates histone H2B at tyrosine 37 (pY37-H2B) to negatively regulate global histone transcriptional output. Although pY37-H2B is readily detected in cancer cells, its functional role in pathogenesis is not known. Herein, we show that WEE1 deposits the pY37-H2B marks within the tumor suppressor gene, isocitrate dehydrogenase 2 (IDH2), to repress transcription in multiple cancer cells, including glioblastoma multiforme (GBMs), melanoma and prostate cancer...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287594/comprehensive-molecular-biomarker-identification-in-breast-cancer-brain-metastases
#6
Hans-Juergen Schulten, Mohammed Bangash, Sajjad Karim, Ashraf Dallol, Deema Hussein, Adnan Merdad, Fatma K Al-Thoubaity, Jaudah Al-Maghrabi, Awatif Jamal, Fahad Al-Ghamdi, Hani Choudhry, Saleh S Baeesa, Adeel G Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Breast cancer brain metastases (BCBM) develop in about 20-30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. METHODS: We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p < 0...
December 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29279549/recent-progress-in-the-understanding-of-angioimmunoblastic-t-cell-lymphoma
#7
Manabu Fujisawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) has been classified as a subtype of mature T-cell neoplasms. The recent revision of the WHO classification proposed a new category of nodal T-cell lymphoma with follicular helper T (TFH)-cell phenotype, which was classified into three diseases: AITL, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with TFH phenotype. These lymphomas are defined by the expression of TFH-related antigens, CD279/PD-1, CD10, BCL6, CXCL13, ICOS, SAP, and CXCR5. Although recurrent mutations in TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene fusions, such as ITK-SYK and CTLA4-CD28, were not diagnostic criteria, they may be considered as novel criteria in the near future...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29274134/a-distinct-immunophenotype-identifies-a-subset-of-npm1-mutated-aml-with-tet2-or-idh1-2-mutations-and-improved-outcome
#8
Emily F Mason, Frank C Kuo, Robert P Hasserjian, Adam C Seegmiller, Olga Pozdnyakova
Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in acute myeloid leukemia (AML). NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings...
December 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29243965/enasidenib-a-targeted-inhibitor-of-mutant-idh2-proteins-for-treatment-of-relapsed-or-refractory-acute-myeloid-leukemia
#9
Eytan M Stein
Mutations in IDH2 genes (mIDH2) occur in approximately 12% of patients with acute myeloid leukemia. Enasidenib is an oral, small-molecule inhibitor of mIDH2 proteins. Enasidenib is shown to suppress the oncometabolite, 2-hydroxyglutarate, and promote differentiation of leukemic bone marrow blasts. In a Phase I dose-escalation and expansion study, 40.3% of patients with relapsed/refractory acute myeloid leukemia responded to enasidenib monotherapy, including 19.3% who achieved complete remission and 11% who proceeded to transplant...
January 2018: Future Oncology
https://www.readbyqxmd.com/read/29238464/curcumin-enhances-liver-sirt3-expression-in-the-rat-model-of-cirrhosis
#10
Sara Chenari, Fatemeh Safari, Ali Moradi
Objectives: Bill duct ligation (BDL) is a representative model of biliary cholestasis in animals. Curcumin has a protective effect on the liver; however, its underlying mechanisms are not completely known. This study explored the hepatoprotective activity of curcumin on hepatic damage via measuring the expression of sirtuin3 (SIRT3), AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase 1A (CPT-1A), isocitrate dehydrogenase2 (IDH2) and manganese superoxide dismutase (MnSOD) as well as the level of serum lipid profile in the BDL fibrotic rat model...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29193057/prognostic-utility-of-six-mutated-genes-for-older-patients-with-acute-myeloid-leukemia
#11
Jinghan Wang, Zhixin Ma, Qinrong Wang, Qi Guo, Jiansong Huang, Wenjuan Yu, Huanping Wang, Jingwen Huang, Yang Washington Shao, Suning Chen, Jie Jin
Approximately 50% of older patients with acute myeloid leukemia (AML) do not obtain chromosomal abnormalities as an effective risk-stratification, and present cytogenetically normal AML (CN-AML). In order to develop a reliable prediction model for stratifying the risk of these elderly patients, we conducted a study with a discovery and validation design. As a result, we found the top 6 mutated genes in the discovery cohort of 26 case by the whole exome sequencing, and verified as recurrent mutations in the large cohort of 329 patients by sanger sequencing...
November 29, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29184081/allosteric-inhibitor-remotely-modulates-the-conformation-of-the-orthestric-pockets-in-mutant-idh2-r140q
#12
Jiao Chen, Jie Yang, Xianqiang Sun, Zhongming Wang, Xiaolan Cheng, Wuguang Lu, Xueting Cai, Chunping Hu, Xu Shen, Peng Cao
Neomorphic mutation R140Q in the metabolic enzyme isocitrate dehydrogenase 2 (IDH2) is found to be a driver mutation in cancers. Recent studies revealed that allosteric inhibitors could selectively inhibit IDH2/R140Q and induce differentiation of TF-1 erythroleukemia and primary human AML cells. However, the allosteric inhibition mechanism is not very clear. Here, we report the results from computational studies that AGI-6780 binds tightly with the divalent cation binding helices at the homodimer interface and prevents the transition of IDH2/R140Q homodimer to a closed conformation that is required for catalysis, resulting in the decrease of the binding free energy of NADPHs...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180699/mutant-idh1-dependent-chromatin-state-reprogramming-reversibility-and-persistence
#13
Sevin Turcan, Vladimir Makarov, Julian Taranda, Yuxiang Wang, Armida W M Fabius, Wei Wu, Yupeng Zheng, Nour El-Amine, Sara Haddock, Gouri Nanjangud, H Carl LeKaye, Cameron Brennan, Justin Cross, Jason T Huse, Neil L Kelleher, Pavel Osten, Craig B Thompson, Timothy A Chan
Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation...
November 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29172136/idh1-and-idh2-mutations-in-postoperative-diffuse-glioma-associated-epilepsy
#14
Andrew Neal, Patrick Kwan, Terence John O'Brien, Michael E Buckland, Michael Gonzales, Andrew Morokoff
OBJECTIVE: Isocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II-IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency. METHODS: This was a retrospective study. Patients with grades II-IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included...
November 21, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29170066/glioma-epigenetics-from-subclassification-to-novel-treatment-options
#15
REVIEW
Olga Gusyatiner, Monika E Hegi
Gliomas are the most common malignant primary brain tumors, of which glioblastoma is the most malignant form (WHO grade IV), and notorious for treatment resistance. Over the last decade mutations in epigenetic regulator genes have been identified as key drivers of subtypes of gliomas with distinct clinical features. Most characteristic are mutations in IDH1 or IDH2 in lower grade gliomas, and histone 3 mutations in pediatric high grade gliomas that are also associated with characteristic DNA methylation patterns...
November 20, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29166738/-expression-characteristics-and-prognosis-significance-of-mirna-181a-in-acute-myeloid-leukemia-with-normal-karyotype
#16
X X Zhuang, Q L Ma, H P Wang, M X Yu, X Li, H T Meng, W J Yu, C J Jin, L S You, J Jin
Objective: To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance. Methods: The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29164635/influence-of-genetic-variants-of-idh1-idh2-tet2-and-dnmt3a-on-cytarabine-cytotoxicity-in-different-populations
#17
Y Wang, J K Lamba
WHAT IS KNOWN AND OBJECTIVE: Cytarabine (ara-C) is the mainstay of treatment for acute myeloid leukaemia. Resistance and toxicity are common reasons for its treatment failure. Genetic variants of susceptibility genes may be involved in resistance and toxicity to ara-C. This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. METHODS: HapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara-C at different concentrations (1, 5, 40 and 80 μmol/L)...
November 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29162772/functional-alteration-of-canine-isocitrate-dehydrogenase-2-idh2-via-an-r174k-mutation
#18
Shota Kawakami, Kazuhiko Ochiai, Yuiko Kato, Masaki Michishita, Hinako Hirama, Ryo Obara, Daigo Azakami, Masami Watanabe, Toshinori Omi
Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional, or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K)...
November 21, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29156201/which-new-agents-will-be-incorporated-into-frontline-therapy-in-acute-myeloid-leukemia
#19
REVIEW
Richard M Stone
For 4 decades, new agents had not been permanently approved for use in treating acute myeloid leukemia (AML). The long dry spell was broken in 2017, however, with the approval of several agents: midostaurin for addition to chemotherapy in mutant FLT3 patients undergoing intensive chemotherapy, enasidenib in advanced mutant IDH2 patients, CPX-351 in secondary AML patients, and gemtuzumab ozogamicin in conjunction with standard chemotherapy in AML. This review surveys the use of tyrosine kinase inhibitors to treat patients with mutant FLT3 AML, mutant KIT AML, as well as IDH inhibitors and explores some questions regarding their integration into the treatment armamentarium for AML...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#20
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
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