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Ye Liu, Di Huang, Zhaoyang Wang, Chao Wu, Zhao Zhang, Dan Wang, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
The proto-oncogene LIM-domain only 2 (lmo2) was traditionally considered to be a pivotal transcriptional regulator in hematopoiesis and leukemia. Recently, the cytosolic localization of LMO2 was revealed in multiple epithelial tissues and a variety of solid tumors. However, the function of LMO2 in these epithelia and solid tumors remains largely unclear. The Wnt signaling pathway is a crucial determinant of development, and abnormalities in several key segments of this pathway contribute to oncogenesis. The current study demonstrated that LMO2 participates in the regulation of canonical Wnt signaling in the cytoplasm by binding to Dishevelled-1/2 (DVL-1/2) proteins...
October 25, 2016: Scientific Reports
Yeguang Hu, Zhihong Zhang, Mariko Kashiwagi, Toshimi Yoshida, Ila Joshi, Nilamani Jena, Rajesh Somasundaram, Akinola Olumide Emmanuel, Mikael Sigvardsson, Julien Fitamant, Nabeel El-Bardeesy, Fotini Gounari, Richard A Van Etten, Katia Georgopoulos
IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors...
September 1, 2016: Genes & Development
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
Xi Wang, Ying Liu, Lingling Dai, Qi Liu, Liuqun Jia, Huan Wang, Lin An, Xiaogang Jing, Meng Liu, Pengfei Li, Zhe Cheng
Forkhead box P3 (Foxp3) is a member of forkhead box transcription factor family and it was identified as a tumor suppressor in various solid tumors. This study evaluated the expression of Foxp3 in non-small cell lung cancer (NSCLC) and investigated its role in epithelial‑mesenchymal transition (EMT) of cancer cells. qRT-PCR and western blot analysis were used for examining the expression of Foxp3 in NSCLC tissues and the non-tumor tissues. A tissue microarray was constructed and scored for evaluating the clinical significance of Foxp3 expression in NSCLC tissues...
October 2016: Oncology Reports
Chao Wu, Ye Liu, Xiangxiang Gu, Tianhui Zhu, Shuang Yang, Wei Sun
In eukaryotic cells, the post-translational modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is the most common trigger for protein degradation and is involved in the regulation of a wide range of biological processes. FAT10 (HLA-F-adjacent transcript 10), which belongs to the UBL family, is activated specifically through the UBA6-USE1 cascade and targets substrates covalently for 26S proteasomal degradation. LMO2 is a well-recognized transcriptional regulator in hematopoietic and endothelial systems; however, it is predominantly located in the cytoplasm of epithelium-derived cells...
September 23, 2016: Biochemical and Biophysical Research Communications
Kvetoslava Peckova, Michael Michal, Ladislav Hadravsky, Saul Suster, Ivan Damjanov, Marketa Miesbauerova, Dmitry V Kazakov, Zdenka Vernerova, Michal Michal
BACKGROUND: Littoral cell angioma (LCA) is a rare primary splenic tumor frequently associated with internal malignancies. Immunohistochemistry (IHC) can prove a distinct hybrid endothelial/histiocytic phenotype of littoral cells and is a helpful adjunct to render the correct diagnosis. We present a series of 25 LCA with an emphasis on the frequent association of the neoplasm with visceral malignancies and provide a detailed immunohistochemical analysis by employing new markers. DESIGN: All 25 cases with available tissue blocks were immunohistochemically stained for endothelial and histiocytic markers...
July 4, 2016: Histopathology
Anna-Sophia Wiekmeijer, Karin Pike-Overzet, Martijn H Brugman, Marja C J A van Eggermond, Martijn Cordes, Edwin F E de Haas, Yunlei Li, Edwin Oole, Wilfred F J van IJcken, R Maarten Egeler, Jules P Meijerink, Frank J T Staal
Overexpression of LMO2 is known to be one of the causes of T-cell acute lymphoblastic leukemia (T-ALL) development; however, the mechanisms behind its oncogenic activity are incompletely understood. LMO2-overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as the main preleukemic event. The effects of LMO2 overexpression on human T-cell development in vivo are unknown. Here, we report studies of a humanized mouse model transplanted with LMO2-transduced human hematopoietic stem/progenitor cells...
September 2016: Experimental Hematology
Sandra Capellera-Garcia, Julian Pulecio, Kishori Dhulipala, Kavitha Siva, Violeta Rayon-Estrada, Sofie Singbrant, Mikael N E Sommarin, Carl R Walkley, Shamit Soneji, Göran Karlsson, Ángel Raya, Vijay G Sankaran, Johan Flygare
Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs...
June 14, 2016: Cell Reports
K Ruggero, O Al-Assar, J S Chambers, R Codrington, T Brend, T H Rabbitts
No abstract text is available yet for this article.
September 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tina M Green, Andreas K Jensen, René Holst, Steffen Falgreen, Martin Bøgsted, Karin de Stricker, Torben Plesner, Torben Mourits-Andersen, Mikael Frederiksen, Hans E Johnsen, Lars M Pedersen, Michael B Møller
We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Including International Prognostic Index (IPI) as a variable in a penalized Cox regression, we investigated the association with disease progression for single genes or gene combinations in four models...
September 2016: British Journal of Haematology
T Hoang, J A Lambert, R Martin
SCL, a transcription factor of the basic helix-loop-helix family, is a master regulator of hematopoiesis. Scl specifies lateral plate mesoderm to a hematopoietic fate and establishes boundaries by inhibiting the cardiac lineage. A combinatorial interaction between Scl and Vegfa/Flk1 sets in motion the first wave of primitive hematopoiesis. Subsequently, definitive hematopoietic stem cells (HSCs) emerge from the embryo proper via an endothelial-to-hematopoietic transition controlled by Runx1, acting with Scl and Gata2...
2016: Current Topics in Developmental Biology
K J Hewitt, K D Johnson, X Gao, S Keles, E H Bresnick
Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies...
2016: Current Topics in Developmental Biology
C S Tremblay, F C Brown, M Collett, J Saw, S K Chiu, S E Sonderegger, S E Lucas, R Alserihi, N Chau, M L Toribio, M P McCormack, M Chircop, P J Robinson, S M Jane, D J Curtis
Mutations in the DYNAMIN2 (DNM2) gene are frequently detected in human acute T-cell lymphoblastic leukemia (T-ALL), although the mechanisms linking these mutations to disease pathogenesis remain unknown. Using an ENU-based forward genetic screen for mice with erythroid phenotypes, we identified a heterozygous mouse line carrying a mutation in the GTPase domain of Dnm2 (Dnm2(V265G)) that induced a microcytic anemia. In vitro assays using the V265G mutant demonstrated loss of GTPase activity and impaired endocytosis that was comparable to other DNM2 mutants identified in human T-ALL...
April 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Chen-Yi Jiang, Jun-Jie Yu, Yuan Ruan, Xiao-Hai Wang, Wei Zhao, Xing-Jie Wang, Yi-Ping Zhu, Yuan Gao, Kui-Yuan Hao, Lei Chen, Bang-Min Han, Shu-Jie Xia, Fu-Jun Zhao
Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland possesses a stronger inclination for PCa than transition zone. We previously found a variety of genes that differently expressed among different prostate stromal cells, including LIM domain only 2 (LMO2) which highly expressed in peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts (CAFs) compared to transition zone derived stromal cells (TZSCs)...
May 3, 2016: Oncotarget
Susan C Pitt, Roland A Hernandez, Matthew A Nehs, Atul A Gawande, Francis D Moore, Daniel T Ruan, Nancy L Cho
BACKGROUND: Thyroid cancer patients frequently have favorable outcomes. However, a small subset develops aggressive disease refractory to traditional treatments. Therefore, we sought to characterize oncogenic mutations in thyroid cancers to identify novel therapeutic targets that may benefit patients with advanced, refractory disease. STUDY DESIGN: Data on 239 thyroid cancer specimens collected between January 2009 and September 2014 were obtained from the Dana Farber/Brigham and Women's Cancer Center...
June 2016: Journal of the American College of Surgeons
Rabab M Aly, Mona M Taalab, Eman M Abdsalam, Omar H Elyamany, Omar E Hasan
The LIM domain only protein 2 (LMO2) is a key regulator of hematopoietic stem cell development. Expression of LMO2 has been evaluated in B-cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia; however, information concerning its role in breakpoint cluster region/Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) negative B-cell acute lymphoblastic leukemia (B-ALL) remains limited. The present study investigated LMO2 expression using quantitative polymerase chain reaction in 85 adult patients with BCR/ABL negative B-ALL, and associated the expression of LMO2 with established prognostic factors...
March 2016: Oncology Letters
Sheng Zhou, Soghra Fatima, Zhijun Ma, Yong-Dong Wang, Taihe Lu, Laura J Janke, Yang Du, Brian P Sorrentino
Insertional oncogenesis due to retroviral (RV) vector integration has caused recurrent leukemia in multiple gene therapy trials, predominantly due to vector integration effects at the LMO2 locus. While currently available preclinical safety models have been used for evaluating vector safety, none have predicted or reproduced the recurrent LMO2 integrations seen in previous X-linked severe combined immunodeficiency (X-SCID) and Wiskott-Aldrich clinical gene therapy trials. We now describe a new assay for assessing vector safety that recapitulates naturally occurring insertions into Lmo2 and other T-cell proto-oncogenes leading to a preleukemic developmental arrest in primary murine thymocytes cultured in vitro...
June 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Carolina A Braghini, Flavia C Costa, Halyna Fedosyuk, Renee Y Neades, Lesya V Novikova, Matthew P Parker, Robert D Winefield, Kenneth R Peterson
Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin)...
April 2016: Experimental Biology and Medicine
Fen Zhang, Donglan Luo, Xinlan Luo, Yu Chen, Jie Xu, Jie Chen, Hengguo Zhuang, Yanhui Liu
OBJECTIVE: To evaluate the diagnostic value of HGAL and LMO2 expression and compare with CD10 and bcl-6 in follicular lymphoma (FL). METHODS: 63 cases of FL were collected from Guangdong General Hospital. The expression of HGAL, LMO2, CD10 and bcl-6 was assessed by immunohistochemistry. RESULTS: The expression rates of HGAL, LMO2, CD10 and bcl-6 were 98.4% (62/63), 82.5% (52/63), 82.5% (52/63) and 87.3% (55/63), respectively. The expression rate of HGAL was higher than those of LMO2, CD10 and bcl-6, but the differences were not significant (P>0...
February 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Shuangtao Zhao, Xiaoli Dong, Wenzhi Shen, Zhen Ye, Rong Xiang
Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets...
May 2016: Cancer Medicine
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