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https://www.readbyqxmd.com/read/27909741/the-role-of-epigenetic-modifiers-in-extended-cultures-of-functional-hepatocyte-like-cells-derived-from-human-neonatal-mesenchymal-stem-cells
#1
M Cipriano, J C Correia, S P Camões, N G Oliveira, P Cruz, H Cruz, M Castro, J L Ruas, J M Santos, J P Miranda
The development of predictive in vitro stem cell-derived hepatic models for toxicological drug screening is an increasingly important topic. Herein, umbilical cord tissue-derived mesenchymal stem cells (hnMSCs) underwent hepatic differentiation using an optimized three-step core protocol of 24 days that mimicked liver embryogenesis with further exposure to epigenetic markers, namely the histone deacetylase inhibitor trichostatin A (TSA), the cytidine analogue 5-azacytidine (5-AZA) and dimethyl sulfoxide (DMSO)...
December 1, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27899806/preleukemia-one-name-many-meanings
#2
REVIEW
H P Koeffler, G Leong
Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia which nearly always progress to AML. More recently investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations which were also present at diagnosis of AML...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899775/-leukemia
#3
Minenori Eguchi-Ishimae, Mariko Eguchi
Leukemia is derived from hematopoietic stem/progenitor cells that have acquired genetic abnormalities, leading to malignant transformation. The basis of therapyfor leukemia is a combination of anti-cancer drugs based on risk stratification. The overall 5-year survival rate in leukemia patients of all ages is still 40%, although it has improved in pediatric patients. Leuke- mia itself is a heterogeneous disease that includes various entities/subtypes with different pathogenic gene aberrations. Selection of the treatment strategylargelydepends on risk stratification, and this in turn is mainlybased on specific recurrent chromosome aberrations...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27877211/the-three-gene-signature-in-urinary-extracellular-vesicles-from-patients-with-clear-cell-renal-cell-carcinoma
#4
Giuseppe De Palma, Fabio Sallustio, Claudia Curci, Vanessa Galleggiante, Monica Rutigliano, Grazia Serino, Pasquale Ditonno, Michele Battaglia, Francesco P Schena
Renal cell carcinoma (RCC) accounts for more than 2% of neoplasias in humans worldwide. Renal biopsy is the gold standard among the diagnostic procedures, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for RCC are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, appears to be a common feature of neoplasia. Consistently, cancer-derived EVs are increased in blood and urine. Therefore, urinary samples may be a non-invasive approach for discovering new diagnostic biomarkers...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#5
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27829312/cudc-907-promotes-bone-marrow-adipocytic-differentiation-through-inhibition-of-histone-deacetylase-and-regulation-of-cell-cycle
#6
Dalia Ali, Hassan Alshammari, Radhakrishnan Vishnubalaji, Elna Paul Chalisserry, Rimi Hamam, Musaed Alfayez, Moustapha Kassem, Abdullah Aldahmash, Nehad M Alajez
The role of bone marrow adipocytes (BMA) in overall energy metabolism and their effects on bone mass is currently an area of intensive investigation. BMA differentiate from bone marrow stromal cells (BMSCs), however, the molecular mechanisms regulating BMA differentiation are not fully understood. Herein, we investigated the effect of CUDC-907, identified by screening an epigenetics small-molecule library, on adipocytic differentiation of human BMSCs, and determined its molecular mechanism of action. hMSCs exposed to CUDC-907 (500 nM) exhibited enhanced adipocytic differentiation (~2...
November 9, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27819178/myelodysplastic-syndromes-and-acute-leukemia-with-genetic-predispositions-a-new-challenge-for-hematologists
#7
Nicolas Duployez, Sophie Lejeune, Aline Renneville, Claude Preudhomme
The determination of an underlying genetic predisposition is not automatically part of the diagnosis of hematological malignancies (HM) in routine practice. However, it is assumed that genetic predispositions to HM are currently underestimated due to great variations in disease phenotype, variable latency and incomplete penetrance. Most of patients do not display any biological or clinical signs besides the overt hematological disease and many of them have a lack of personal or family history of malignancies...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27812248/prevalence-and-prognostic-impact-of-cebpa-gene-mutation-simplified-assay-technique-in-egyptian-acute-myeloid-leukemia-patients-with-normal-cytogenetics
#8
Samy B Said, Samir A El-Masry, Dalia A Salem, Mona M Taalab, Amr S Al-Posttany
Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), especially in those with a normal cytogenetics. However, few studies were done on Egyptian AML patients and none of them look for easier and less expensive method for CEBPA mutation screening. This study is aimed to investigate the prevalence of CEBPA mutations and its clinical and prognostic impact in Egyptian patients with cytogenetically normal AML (CN-AML)...
December 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27736291/clinical-significance-of-galectin-3-in-patients-with-adult-acute-myeloid-leukemia-a-retrospective-cohort-study-with-long-term-follow-up-and-formulation-of-risk-scoring-system
#9
Na Gao, Wen-Zheng Yu, Nong-Jian Guo, Xue-Xia Wang, Jian-Rong Sun
Galectin-3 plays an increasingly important role in development and progression of tumor. However, little is known about the clinical impact of galectin-3 in non-acute promyelocytic leukemia (non-M3 AML). Peripheral blood of 298 patients with primary non-M3 AML and 30 normal donors was collected for measurement of galectin-3. Galectin-3 levels were significantly higher compared with the control group (p < .001). Patients with higher galectin-3 levels had lower CR rates (p = .001) and 1-year overall survival (OS) rates (p = ...
October 13, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27694926/nup98-is-rearranged-in-3-8-of-pediatric-aml-forming-a-clinical-and-molecular-homogenous-group-with-a-poor-prognosis
#10
S Struski, S Lagarde, P Bories, C Puiseux, N Prade, W Cuccuini, M-P Pages, A Bidet, C Gervais, M Lafage-Pochitaloff, C Roche-Lestienne, C Barin, D Penther, N Nadal, I Radford-Weiss, M-A Collonge-Rame, B Gaillard, F Mugneret, C Lefebvre, A Petit, G Leverger, C Broccardo, I Luquet, M Pasquet, E Delabesse
Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 (NUP98) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, since the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3...
October 3, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27646892/-characterization-of-mutational-pattern-in-patients-with-ph-negative-myeloproliferative-neoplasms
#11
F Xing, Y N Lin, Q Sun, L Qin, Y J Jia, D L Zhang, K Ru
Objective: To characterize the molecular profile in patients with Ph negative myeloproliferative neoplasms (MPN) by exploring 49 gene mutations. Methods: Targeted gene sequencing were performed to analyze 49 MPN-associated genes in 51 patients with Ph negative MPN, of which CARL (exon 9), NPM1 (exon 12) and CEBPA (TAD, BZIP domains) were investigated by using Sanger sequencing simultaneously, while FLT3-ITD was assessed by PCR method. Results: Mutations were detected in 73.5% (36/49) of genes, and the mutational rates of JAK2-V617F, CALR (exon 9) and MPL were 60...
September 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/27645901/loss-of-dro1-ccdc80-results-in-obesity-and-promotes-adipocyte-differentiation
#12
Jessica I Grill, Jens Neumann, Andreas Herbst, Andrea Ofner, Felix Hiltwein, Maximilian K Marschall, Heike Zierahn, Eckhard Wolf, Marlon R Schneider, Frank T Kolligs
To investigate the role of DRO1 in obesity and adipogenesis in vivo, we generated a constitutive Dro1 knockout mouse model and analyzed the effect of DRO1 loss on body growth under standard and high fat diet feeding conditions. Loss of DRO1 resulted in a significant increase in body weight which was accompanied by a substantial expansion of white adipose tissue depots. The obese phenotype could be further enhanced by a high fat dietary challenge which also resulted in impaired glucose metabolism and the development of hepatosteatosis in Dro1 knockout mice...
September 16, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27626217/persistent-dnmt3a-mutation-burden-in-dnmt3a-mutated-adult-cytogenetically-normal-acute-myeloid-leukemia-patients-in-long-term-remission
#13
Yanjun Sun, Hongjie Shen, Ting Xu, Zhen Yang, Huiying Qiu, Aining Sun, Suning Chen, Depei Wu, Yang Xu
DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia (CN-AML) patients and can be present many years before the disease develops. However, the clinical significance of DNMT3A mutation burden in CN-AML remains unclear. In this study, 81 DNMT3A mutated adult CN-AML patients in their first complete remission (CR) were enrolled at our center from March 2005 to May 2015. All patients were identified as having DNMT3A exon 23 mutations, and R882H was the most frequent variant (n=49, 60.49%)...
October 2016: Leukemia Research
https://www.readbyqxmd.com/read/27602952/the-significance-of-c-690g-t-polymorphism-rs34529039-and-expression-of-the-cebpa-gene-in-ovarian-cancer-outcome
#14
Bozena Konopka, Lukasz Michal Szafron, Ewa Kwiatkowska, Agnieszka Podgorska, Aleksandra Zolocinska, Barbara Pienkowska-Grela, Agnieszka Dansonka-Mieszkowska, Anna Balcerak, Martyna Lukasik, Anna Stachurska, Agnieszka Timorek, Beata Spiewankiewicz, Mona El-Bahrawy, Jolanta Kupryjanczyk
The CEBPA gene is known to be mutated or abnormally expressed in several cancers. This is the first study assessing the clinical impact of CEBPA gene status and expression on the ovarian cancer outcome. The CEBPA gene sequence was analyzed in 118 ovarian cancer patients (44 platinum/cyclophosphamide (PC)-treated and 74 taxane/platinum (TP)-treated), both in tumors and blood samples, and in blood from 236 healthy women, using PCR-Sanger sequencing and Real-Time quantitative PCR (qPCR)-based genotyping methods, respectively...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27566578/long-non-coding-rna-hoxa-as3-interacts-with-ezh2-to-regulate-lineage-commitment-of-mesenchymal-stem-cells
#15
Xin-Xing Zhu, Ya-Wei Yan, Demeng Chen, Chun-Zhi Ai, Xifeng Lu, Shan-Shan Xu, Shan Jiang, Gen-Shen Zhong, Dong-Bao Chen, Yi-Zhou Jiang
Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27553254/differentiation-potential-of-rabbit-cd90-positive-cells-sorted-from-adipose-derived-stem-cells-in-vitro
#16
Xinghui Song, Chaoyang Hong, Qingqing Zheng, Hailan Zhao, Kangping Song, Zhe Liu, Jiang Shen, Yanwei Li, Jiajia Wang, Ting Shen
To investigate the differentiation potential of purified CD90(+) cells sorted from adipose-derived stem cells (ADSCs), CD90(+) cells were sorted from rabbit ADSCs using flow cytometry. Then, cell expansion of CD90(+) cells and unsorted ADSCs was observed using an inverted microscope. Furthermore, cell surface markers including CD40, CD105, and CD90 on CD90(+) cells and unsorted ADSCs were quantified using flow cytometry. Additionally, multi-lineage differentiation ability between CD90(+) cells and unsorted ADSCs was compared, and expression of adipocyte-related genes PPAR-r and CEBPA as well as stem cell-related gene SOX2 in CD90(+) cells and unsorted ADSCs was determined using real-time quantitative PCR...
August 23, 2016: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27470916/whole-exome-sequencing-reveals-the-spectrum-of-gene-mutations-and-the-clonal-evolution-patterns-in-paediatric-acute-myeloid-leukaemia
#17
Norio Shiba, Kenichi Yoshida, Yuichi Shiraishi, Yusuke Okuno, Genki Yamato, Yusuke Hara, Yasunobu Nagata, Kenichi Chiba, Hiroko Tanaka, Kiminori Terui, Motohiro Kato, Myoung-Ja Park, Kentaro Ohki, Akira Shimada, Junko Takita, Daisuke Tomizawa, Kazuko Kudo, Hirokazu Arakawa, Souichi Adachi, Takashi Taga, Akio Tawa, Etsuro Ito, Keizo Horibe, Masashi Sanada, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations...
July 29, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27462403/adipocyte-nuclei-captured-from-vat-and-sat
#18
Suresh Ambati, Ping Yu, Elizabeth C McKinney, Muthugapatti K Kandasamy, Diane Hartzell, Clifton A Baile, Richard B Meagher
BACKGROUND: Obesity-related comorbidities are thought to result from the reprogramming of the epigenome in numerous tissues and cell types, and in particular, mature adipocytes within visceral and subcutaneous adipose tissue, VAT and SAT. The cell-type specific chromatin remodeling of mature adipocytes within VAT and SAT is poorly understood, in part, because of the difficulties of isolating and manipulating large fragile mature adipocyte cells from adipose tissues. METHODS: We constructed MA-INTACT (Mature Adipocyte-Isolation of Nuclei TAgged in specific Cell Types) mice using the adiponectin (ADIPOQ) promoter (ADNp) to tag the surface of mature adipocyte nuclei with a reporter protein...
2016: BMC Obesity
https://www.readbyqxmd.com/read/27439608/epigenetic-role-of-nuclear-s6k1-in-early-adipogenesis
#19
Sang Ah Yi, Jihoon Han, Jeung-Whan Han
S6K1 is a key regulator of cell growth, cell size, and metabolism. Although the role of cytosolic S6K1 in cellular processes is well established, the function of S6K1 in the nucleus remains poorly understood. Our recent study has revealed that S6K1 is translocated into the nucleus upon adipogenic stimulus where it directly binds to and phosphorylates H2B at serine 36. Such phosphorylation promotes EZH2 recruitment and subsequent histone H3K27 trimethylation on the promoter of its target genes including Wnt6, Wnt10a, and Wnt10b, leading to repression of their expression...
August 2016: BMB Reports
https://www.readbyqxmd.com/read/27436336/npm1-flt3-and-cebpa-mutations-in-pediatric-patients-with-aml-from-argentina-incidence-and-prognostic-value
#20
Patricia Rubio, B Campos, J A Digiorge, M S Gallego, A Medina, J G Rossi, M S Felice, C N Alonso
Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10...
July 19, 2016: International Journal of Hematology
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