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https://www.readbyqxmd.com/read/27880729/lmo2-promotes-tumor-cell-invasion-and-metastasis-in-basal-type-breast-cancer-by-altering-actin-cytoskeleton-remodeling
#1
Ye Liu, Zhaoyang Wang, Di Huang, Chao Wu, Huihui Li, Xin Zhang, Bin Meng, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
LMO2 is traditionally recognized as a pivotal transcriptional regulator during embryonic hematopoiesis and angionenesis, and its ectopic expression in T lymphocyte progenitors is closely correlated to the onset of acute T lymphocytic leukemia. However, recently studies revealed complicated expression features and dual functions of LMO2 on tumor behaviors in a variety of cancer types, including breast cancers. Basal-type breast cancer is one of the breast cancer subtypes and a prognostically unfavorable subtype among all breast cancers...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27869129/reprogramming-mouse-fibroblasts-into-engraftable-myeloerythroid-and-lymphoid-progenitors
#2
Hui Cheng, Heather Yin-Kuan Ang, Chadi A El Farran, Pin Li, Hai Tong Fang, Tong Ming Liu, Say Li Kong, Michael Lingzi Chin, Wei Yin Ling, Edwin Kok Hao Lim, Hu Li, Tara Huber, Kyle M Loh, Yuin-Han Loh, Bing Lim
Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase(+) megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27851970/the-hematopoietic-transcription-factors-runx1-and-erg-prevent-aml1-eto-oncogene-overexpression-and-onset-of-the-apoptosis-program-in-t-8-21-amls
#3
Amit Mandoli, Abhishek A Singh, Koen H M Prange, Esther Tijchon, Marjolein Oerlemans, Rene Dirks, Menno Ter Huurne, Albertus T J Wierenga, Eva M Janssen-Megens, Kim Berentsen, Nilofar Sharifi, Bowon Kim, Filomena Matarese, Luan N Nguyen, Nina C Hubner, Nagesha A Rao, Emile van den Akker, Lucia Altucci, Edo Vellenga, Hendrik G Stunnenberg, Joost H A Martens
The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27825111/protocol-for-qrt-pcr-analysis-from-formalin-fixed-paraffin-embedded-tissue-sections-from-diffuse-large-b-cell-lymphoma-validation-of-the-six-gene-predictor-score
#4
Nilgun Tekin, Nader Omidvar, Tim Peter Morris, Paulette Conget, Flavia Bruna, Botond Timar, Eva Gagyi, Ranjan Basak, Omkar Naik, Chirayu Auewarakul, Narongrit Sritana, Debora Levy, Juliano Julio Cerci, Sergio Paulo Bydlowski, Juliana Pereira, Mark Pierre Dimamay, Filipinas Natividad, June-Key Chung, Nevin Belder, Isinsu Kuzu, Diana Paez, Maurizio Dondi, Robert Carr, Hilal Ozdag, Rose Ann Padua
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27792641/lim-domain-only-2-regulates-endothelial-proliferation-angiogenesis-and-tissue-regeneration
#5
Shu Meng, Gianfranco Matrone, Jie Lv, Kaifu Chen, Wing Tak Wong, John P Cooke
BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation...
October 6, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27779255/lmo2-attenuates-tumor-growth-by-targeting-the-wnt-signaling-pathway-in-breast-and-colorectal-cancer
#6
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
https://www.readbyqxmd.com/read/27664237/superenhancer-reprogramming-drives-a-b-cell-epithelial-transition-and-high-risk-leukemia
#7
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
https://www.readbyqxmd.com/read/27579918/meta-analysis-of-transcriptome-regulation-during-induction-to-cardiac-myocyte-fate-from-mouse-and-human-fibroblasts
#8
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
https://www.readbyqxmd.com/read/27574108/foxp3-downregulation-in-nsclc-mediates-epithelial-mesenchymal-transition-via-nf-%C3%AE%C2%BAb-signaling
#9
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
https://www.readbyqxmd.com/read/27569286/lmo2-blocks-the-uba6-use1-interaction-and-downstream-fat10ylation-by-targeting-the-ubiquitin-fold-domain-of-uba6
#10
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
https://www.readbyqxmd.com/read/27374010/littoral-cell-angioma-of-the-spleen-a-study-of-25-cases-with-confirmation-of-frequent-association-with-visceral-malignancies
#11
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
https://www.readbyqxmd.com/read/27302866/overexpression-of-lmo2-causes-aberrant-human-t-cell-development-in%C3%A2-vivo-by-three-potentially-distinct-cellular-mechanisms
#12
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
https://www.readbyqxmd.com/read/27264182/defining-the-minimal-factors-required-for-erythropoiesis-through-direct-lineage-conversion
#13
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
https://www.readbyqxmd.com/read/27256700/lmo2-and-il2rg-synergize-in-thymocytes-to-mimic-the-evolution-of-scid-x1-gene-therapy-associated-t-cell-leukaemia
#14
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
https://www.readbyqxmd.com/read/27196819/multiplex-polymerase-chain-reaction-based-prognostic-models-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#15
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
https://www.readbyqxmd.com/read/27137657/scl-tal1-in-hematopoiesis-and-cellular-reprogramming
#16
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
https://www.readbyqxmd.com/read/27137654/the-hematopoietic-stem-and-progenitor-cell-cistrome-gata-factor-dependent-cis-regulatory-mechanisms
#17
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
https://www.readbyqxmd.com/read/27118408/loss-of-function-mutations-of-dynamin-2-promote-t-all-by-enhancing-il-7-signalling
#18
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
https://www.readbyqxmd.com/read/27028859/lim-domain-only-2-over-expression-in-prostate-stromal-cells-facilitates-prostate-cancer-progression-through-paracrine-of-interleukin-11
#19
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
https://www.readbyqxmd.com/read/27010584/identification-of-novel-oncogenic-mutations-in%C3%A2-thyroid-cancer
#20
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
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