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https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#1
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28159972/role-of-id-proteins-in-bmp4-inhibition-of-profibrotic-effects-of-tgf-%C3%AE-2-in-human-tm-cells
#2
Avani A Mody, Robert J Wordinger, Abbot F Clark
Purpose: Increased expression of TGF-β2 in primary open-angle glaucoma (POAG) aqueous humor (AH) and trabecular meshwork (TM) causes deposition of extracellular matrix (ECM) in the TM and elevated IOP. Bone morphogenetic proteins (BMPs) regulate TGF-β2-induced ECM production. The underlying mechanism for BMP4 inhibition of TGF-β2-induced fibrosis remains undetermined. Bone morphogenic protein 4 induces inhibitor of DNA binding proteins (ID1, ID3), which suppress transcription factor activities to regulate gene expression...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28131394/novel-adenovirus-encoded-virus-like-particles-displaying-the-placental-malaria-associated-var2csa-antigen
#3
Anne-Marie C Andersson, Mafalda Resende, Ali Salanti, Morten A Nielsen, Peter J Holst
The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria and the CSA binding region of VAR2CSA has been identified as a promising vaccine target against placental malaria. Here we designed adenovirus encoded virus-like particles (VLP) by co-encoding Simian Immunodeficiency Virus (SIV) gag and VAR2CSA...
January 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28036274/comprehensive-tissue-specific-gene-set-enrichment-analysis-and-transcription-factor-analysis-of-breast-cancer-by-integrating-14-gene-expression-datasets
#4
Wen-Xing Li, Kan He, Ling Tang, Shao-Xing Dai, Gong-Hua Li, Wen-Wen Lv, Yi-Cheng Guo, San-Qi An, Guo-Ying Wu, Dahai Liu, Jing-Fei Huang
Breast cancer is the most commonly diagnosed malignancy in women. Several key genes and pathways have been proven to correlate with breast cancer pathology. This study sought to explore the differences in key transcription factors (TFs), transcriptional regulation networks and dysregulated pathways in different tissues in breast cancer. We employed 14 breast cancer datasets from NCBI-GEO and performed an integrated analysis in three different tissues including breast, blood and saliva. The results showed that there were eight genes (CEBPD, EGR1, EGR2, EGR3, FOS, FOSB, ID1 and NFIL3) down-regulated in breast tissue but up-regulated in blood tissue...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28035402/transforming-growth-factor-%C3%AE-1-suppresses-bone-morphogenetic-protein-2-induced-mesenchymal-epithelial-transition-in-hsc-4-human-oral-squamous-cell-carcinoma-cells-via-smad1-5-9-pathway-suppression
#5
Takahiro Chiba, Akira Ishisaki, Seiko Kyakumoto, Toshiyuki Shibata, Hiroyuki Yamada, Masaharu Kamo
Squamous cell carcinoma is the most common cancer in the oral cavity. We previously demonstrated that transforming growth factor-β1 (TGF-β1) promotes the epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (hOSCC) cells; however, it remains to be clarified whether the TGF-β superfamily member bone morphogenetic protein (BMP) affects this process in hOSCC cells. Here, we examined the independent and collective effects of TGF-β1 and BMP-2 on EMT and mesenchymal‑epithelial transition (MET) in a panel of four hOSCC cell lines...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#6
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28012775/comparison-of-functional-assays-used-in-the-clinical-development-of-a-placental-malaria-vaccine
#7
Caroline Pehrson, Kristine K Heno, Yvonne Adams, Mafalda Resende, Line Mathiesen, Max Soegaard, Willem A de Jongh, Thor G Theander, Ali Salanti, Morten A Nielsen
BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/28011860/reprogramming-derived-gene-cocktail-increases-cardiomyocyte-proliferation-for-heart-regeneration
#8
Yuan-Yuan Cheng, Yu-Ting Yan, David J Lundy, Annie Ha Lo, Yu-Ping Wang, Shu-Chian Ruan, Po-Ju Lin, Patrick Ch Hsieh
Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction...
February 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28003475/single-cell-transcriptomics-reveals-unanticipated-features-of-early-hematopoietic-precursors
#9
Jennifer Yang, Yoshiaki Tanaka, Montrell Seay, Zhen Li, Jiaqi Jin, Lana Xia Garmire, Xun Zhu, Ashley Taylor, Weidong Li, Ghia Euskirchen, Stephanie Halene, Yuval Kluger, Michael P Snyder, In-Hyun Park, Xinghua Pan, Sherman Morton Weissman
Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes...
December 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27998768/low-grade-inflammation-inhibits-vegf-induced-huvecs-migration-in-p53-dependent-manner
#10
Sushil Panta, Munekazu Yamakuchi, Toshiaki Shimizu, Kazunori Takenouchi, Yoko Oyama, Toyoyasu Koriyama, Tsuyoshi Kojo, Teruto Hashiguchi
In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs)...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27995357/bone-morphogenetic-protein-modulator-bmper-regulates-endothelial-barrier-function
#11
Thomas Helbing, Gwendoline Wiltgen, Alexandra Hornstein, Elena Z Brauers, Linus Arnold, Adrian Bauer, Jennifer S Esser, Philipp Diehl, Sebastian Grundmann, Katrin Fink, Cam Patterson, Christoph Bode, Martin Moser
The endothelium serves as a selective barrier and controls the exchange of nutrients, hormones, and leukocytes between blood and tissues. Molecular mechanisms contributing to the pathogenesis of endothelial barrier dysfunction remain incompletely understood. Accumulating evidence implicates bone morphogenetic protein (BMP)-modulator BMPER as a key regulator in endothelial biology. Herein, we analyze the impact of BMPER in the control of endothelial barrier function. To assess the role of BMPER in vascular barrier function in mice, we measured the leakage of Evans blue dye from blood into interstitial lung tissue...
December 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27978873/-relationship-between-id1-and-egfr-tki-resistance-%C3%A2-in-non-small-cell-lung-cancer
#12
Yuchen Bao, Yinmin Zhao, Bin Chen, Jie Luo, Qinfang Deng, Hui Sun, Boxiong Xie, Songwen Zhou
BACKGROUND: Non-small cell lung cancer (NSCLC) presents the highest morbidity and mortality among malignant tumors worldwide. The overall effective rate of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is 30% to 40%, and PFS (progression-free sruvival) is 12 months. However, EGFR-TKI resistance is typical in clinical observations, and this phenomenon significantly affects tumor suppression. To overcome this resistance, a new prognostic factor associated with lung cancer drug resistance should be discovered...
December 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27959431/bmp-signaling-pathways-affect-differently-migration-and-invasion-of-esophageal-squamous-cancer-cells
#13
Min Hu, Facai Cui, Fengzhen Liu, Jinlin Wang, Xiaoxia Wei, Yi Li
Bone morphogenetic proteins (BMPs) are broadly involved in normal embryo development and abnormal pathological process such as cancer. The complexity and diversity of BMPs and their signaling pathways impose quite different or even conflicting effects on clinical traits of tumors. The aim of the present study was to investigate whether different BMPs, including BMP2, BMP4, BMP6 and BMP7, influence esophageal squamous cancer cell (ESCC) growth, invasion and metastasis. BMP6 and type I receptor ALK2 and type II receptor BMPRII, ActRIIA and ActRIIB were expressed in all ESCC cell lines...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27900085/id1-upregulation-and-foxo3a-downregulation-by-epstein-barr-virus-encoded-lmp1-in-hodgkin-s-lymphoma
#14
Jun-Ichiro Ikeda, Naoki Wada, Satoshi Nojima, Shinichiro Tahara, Yoko Tsuruta, Kaori Oya, Eiichi Morii
Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27864336/bmp4-promotes-mouse-ips-cell-differentiation-to-male-germ-cells-via-smad1-5-gata4-id1-and-id2
#15
Shi Yang, Qingqing Yuan, Minghui Niu, Jingmei Hou, Zijue Zhu, Min Sun, Zheng Li, Zuping He
Generation of male germ cells from pluripotent cells could provide male gametes for treating male infertility and offer an ideal model for unveiling molecular mechanisms of spermatogenesis. However, the influence and exact molecular mechanisms, especially downstream effectors of BMP4 signaling pathways, in male germ cell differentiation of the induce pluripotent stem (iPS) cells, remain unknown. This study was designed to explore the role and mechanism of BMP4 signaling in the differentiation of mouse iPS cells to male germ cells...
February 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27855784/smad4-restricts-differentiation-to-promote-expansion-of-satellite-cell-derived-progenitors-during-skeletal-muscle-regeneration
#16
Nicole D Paris, Andrew Soroka, Alanna Klose, Wenxuan Liu, Joe V Chakkalakal
Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4, the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration...
November 18, 2016: ELife
https://www.readbyqxmd.com/read/27817024/expression-of-senescence-associated-genes-in-multipotent-mesenchymal-stromal-cells-during-long-term-cultivation-at-various-hypoxic-levels
#17
M V Lobanova, A Y Ratushnyy, L B Buravkova
The expression of several genes which functions are associated with cellular senescence was analyzed in multipotent mesenchymal stromal cells during long-term cultivation at different oxygen levels (20, 5, and 1%) using the RT² Profiler™ PCR Array Human Cellular Senescence system (Qiagen, United States). It was established that replicative senescence processes develop most actively in the cells cultured under the standard conditions (20% O2). The most significant changes were observed in the expression of CCND1, ID1, IGF1, PIK3CA, and SERPINE1 genes...
September 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27814765/antibody-responses-to-the-full-length-var2csa-and-its-dbl-domains-in-cameroonian-children-and-teenagers
#18
Barriere A Y Fodjo, Njika Atemnkeng, Livo Esemu, Emile K Yuosembom, Isabella A Quakyi, Viviane H M Tchinda, Joseph Smith, Ali Salanti, Jude Bigoga, Diane W Taylor, Rose G F Leke, Anna Babakhanyan
BACKGROUND: Antigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta...
November 4, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27793834/early-molecular-events-during-retinoic-acid-induced-differentiation-of-neuromesodermal-progenitors
#19
Thomas J Cunningham, Alexandre Colas, Gregg Duester
Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis...
December 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27793034/therapeutic-efficacy-of-the-bromodomain-inhibitor-otx015-mk-8628-in-alk-positive-anaplastic-large-cell-lymphoma-an-alternative-modality-to-overcome-resistant-phenotypes
#20
Michela Boi, Maria Todaro, Valentina Vurchio, Shao Ning Yang, John Moon, Ivo Kwee, Andrea Rinaldi, Heng Pan, Ramona Crescenzo, Mangeng Cheng, Leandro Cerchietti, Olivier Elemento, Maria E Riveiro, Esteban Cvitkovic, Francesco Bertoni, Giorgio Inghirami
Anaplastic large cell lymphomas (ALCL) represent a peripheral T-cell lymphoma subgroup, stratified based on the presence or absence of anaplastic lymphoma kinase (ALK) chimeras. Although ALK-positive ALCLs have a more favorable outcome than ALK-negative ALCL, refractory and/or relapsed forms are common and novel treatments are needed. Here we investigated the therapeutic potential of a novel bromodomain inhibitor, OTX015/MK-8628 in ALK-positive ALCLs.The effects of OTX015 on a panel of ALK+ ALCL cell lines was evaluated in terms of proliferation, cell cycle and downstream signaling, including gene expression profiling analyses...
October 25, 2016: Oncotarget
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