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https://www.readbyqxmd.com/read/28435517/inhibition-of-the-platelet-derived-growth-factor-receptor-beta-pdgfrb-using-gene-silencing-crenolanib-besylate-or-imatinib-mesylate-hampers-the-malignant-phenotype-of-mesothelioma-cell-lines
#1
Ombretta Melaiu, Calogerina Catalano, Chiara De Santi, Monica Cipollini, Gisella Figlioli, Lucia Pellè, Elisa Barone, Monica Evangelista, Alice Guazzelli, Laura Boldrini, Elisa Sensi, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Luciano Mutti, Gabriella Fontanini, Federica Gemignani, Stefano Landi
Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25)...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28426709/pdgfrb-is-a-direct-regulatory-target-of-tgf%C3%AE-signaling-in-atrioventricular-cushion-mesenchymal-cells
#2
Yin Peng, Shun Yan, Dongquan Chen, Xiangqin Cui, Kai Jiao
Cushion formation is the initial step for the development of valvuloseptal structures in mammalian hearts. TGFβ signaling plays critical roles in multiple steps of cushion morphogenesis. We used a newly developed conditional immortal atrioventricular cushion mesenchymal cell line, tsA58-AVM, to identify the TGFβ regulatory target genes through microarray analysis. Expression of ~1350 genes was significantly altered by TGFβ1 treatment. Subsequent bioinformatic analysis of TGFβ activated genes revealed that PDGF-BB signaling is the top hit as the potential upstream regulator...
2017: PloS One
https://www.readbyqxmd.com/read/28417142/heterozygous-pdgfrb-mutation-in-a-three-generation-family-with-autosomal-dominant-infantile-myofibromatosis
#3
Clemence Lepelletier, Yasser Al-Sarraj, Christine Bodemer, Hibbah Shaath, Sylvie Fraitag, Marios Kambouris, Dominique Hamel-Teillac, Hatem El Shanti, Smail Hadj-Rabia
is missing (Short communication).
April 18, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28412213/acute-mast-cell-leukemia-associated-with-t-4-5-q21-q33
#4
Ren Ching Wang, David Ward, Philip Dunn, Chung-Che Chang
To the best of our knowledge, this manuscript describes clinical, and pathologic findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33), compatible with fusion of PDGFRB gene to a rare partner, PRKG2. Translocation involving PDGFRB gene is confirmed by FISH study. This case presented a relatively fulminant clinical course with acute mast cell leukemia and "C" findings (cytopenia, hepatosplenomegaly and weight loss), mast cell sarcoma and severe basophilia. Despite aggressive presentation initially, the patient responded well to TKI treatment and is currently in complete remission, 33months after diagnosis...
April 13, 2017: Human Pathology
https://www.readbyqxmd.com/read/28408464/targetable-kinase-gene-fusions-in-high-risk-b-all-a-study-from-the-children-s-oncology-group
#5
Shalini C Reshmi, Richard C Harvey, Kathryn G Roberts, Eileen Stonerock, Amy Smith, Heather Jenkins, I-Ming Chen, Marc Valentine, Yu Liu, Yongjin Li, Ying Shao, John Easton, Debbie Payne-Turner, Zhaohui Gu, Thai Hoa Tran, Jonathan V Nguyen, Meenakshi Devidas, Yunfeng Dai, Nyla A Heerema, Andrew J Carroll, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Anne L Angiolillo, Michael J Burke, Wanda L Salzer, Patrick A Zweidler-McKay, Karen R Rabin, William L Carroll, Jinghui Zhang, Mignon L Loh, Charles G Mullighan, Cheryl L Willman, Julie M Gastier-Foster, Stephen P Hunger
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed childhood B-ALL patients with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of which were excluded from additional analysis because of the presence of BCR-ABL1 (n=46) or ETV6-RUNX1 (n=11)...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28393601/genetic-analysis-of-non-syndromic-familial-multiple-supernumerary-premolars
#6
Doo Hwan Bae, Ji Hyun Lee, Je Seon Song, Han-Sung Jung, Hyung Jun Choi, Ji Hun Kim
OBJECTIVE: Supernumerary teeth, a term describing a condition where patients have an abnormally large number of teeth, can be associated with non-syndromic or syndromic phenotypes. PDGFRs are cell surface tyrosine kinase receptors, and are involved in several aspects of tooth development. The purpose of this study was to identify causative genes of familial supernumerary teeth and the molecular pathogenesis of tooth number abnormalities through genetic analysis of a family that showed supernumerary premolars in two successive generations...
April 10, 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/28376302/multimodal-recognition-of-diverse-peptides-by-the-c-terminal-sh2-domain-of-phospholipase-c-%C3%AE-1-protein
#7
Marissa A McKercher, Xiaoyang Guan, Zhongping Tan, Deborah S Wuttke
SH2 domains recognize phosphotyrosine (pY)-containing peptide ligands and play key roles in the regulation of receptor tyrosine kinase pathways. Each SH2 domain has individualized specificity, encoded in the amino acids neighboring the pY, for defined targets that convey their distinct functions. The C-terminal SH2 domain (PLCC) of the phospholipase C-γ1 full-length protein (PLCγ1) typically binds peptides containing small and hydrophobic amino acids adjacent to the pY, including a peptide derived from platelet-derived growth factor receptor B (PDGFRB) and an intraprotein recognition site (Y783 of PLCγ1) involved in the regulation of the protein's lipase activity...
April 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/28376187/a-novel-diagnostic-tool-for-selecting-patients-with-mesenchymal-type-colon-cancer-reveals-intratumor-subtype-heterogeneity
#8
Inge Ubink, Sjoerd G Elias, Cathy B Moelans, Miangela M Laclé, Wilhelmina M U van Grevenstein, Paul J van Diest, Inne H M Borel Rinkes, Onno Kranenburg
Background: Consensus molecular subtype 4 (CMS4) is a recently identified aggressive colon cancer subtype for which platelet-derived growth factor receptors (PDGFRs) and KIT are potential therapeutic targets. We aimed to develop a clinically applicable CMS4 reverse transcription polymerase chain reaction (RT-qPCR) test to select patients for PDGFR/KIT-targeted therapy. Methods: We used logistic regression to develop a CMS4 prediction rule based on microarray expression values of PDGFRA , PDGFRB , PDGFC , and KIT (566 training and 1259 test samples, using the 273-gene random forest classifier as CMS4 reference standard)...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28339066/microrna%C3%A2-499-rs3746444-a-g-polymorphism-functions-as-a-biomarker-to-predict-recurrence-following-endoscopic-submucosal-dissection-in-primary-early-gastric-cancer
#9
Huiyong Shi, Xiangshan Yang, Yanan Zhen, Shoujun Huo, Ruixue Xiao, Zhongfa Xu
The aim of the present study was to investigate the molecular mechanism, including the potential regulatory and signaling pathways, of platelet‑derived growth factor receptor β (PDGFRB), which underlies the recurrence of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD). Online microRNA (miRNA) target prediction tools were used, which identified PDGFRB as the candidate target gene of miR‑499a in gastric cancer cells, and PFGRBR was then confirmed as the direct gene using a luciferase reporter assay system...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28334876/pdgfrb-gain-of-function-mutations-in-sporadic-infantile-myofibromatosis
#10
Florence A Arts, Raf Sciot, Bénédicte Brichard, Marleen Renard, Audrey de Rocca Serra, Guillaume Dachy, Laura A Noël, Amélie I Velghe, Christine Galant, Maria Debiec-Rychter, An Van Damme, Miikka Vikkula, Raphaël Helaers, Nisha Limaye, Hélène A Poirel, Jean-Baptiste Demoulin
Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28327445/nine-differentially-expressed-genes-from-a-post-mortem-study-and-their-association-with-suicidal-status-in-a-sample-of-suicide-completers-attempters-and-controls
#11
Martina Balestri, Concetta Crisafulli, Luigi Donato, Ina Giegling, Raffaella Calati, Niki Antypa, Barbara Schneider, Dragan Marusic, Maria Eugenia Tarozzi, Dorjan Marusic, Metka Paragi, Annette M Hartmann, Bettina Konte, Agnese Marsano, Alessandro Serretti, Dan Rujescu
Several lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its aetiology. We focused on nine genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) which we previously detected as differentially expressed in the cortex of suicide victims compared to controls. We investigated 84 variants within these genes in 495 suicidal subjects (299 completers and 196 attempters) and 1513 controls (109 post-mortem and 1404 healthy). We evaluated associations with: 1) suicidal phenotype; 2) possible endophenotypes for suicidal behaviour...
March 10, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28315338/lymphatic-and-vascular-markers-in-an-optic-nerve-crush-model-in-rat
#12
A Trost, D Bruckner, A Kaser-Eichberger, K Motloch, B Bogner, C Runge, C Strohmaier, S Couillard-Despres, H A Reitsamer, F Schroedl
Only few tissues lack lymphatic supply, such as the CNS or the inner eye. However, if the scleral border is compromised due to trauma or tumor, lymphatics are detected in the eye. Since the situation in the optic nerve (ON), part of the CNS, is not clear, the aim of this study is to screen for the presence of lymphatic markers in the healthy and lesioned ON. Brown Norway rats received an unilateral optic nerve crush (ONC) with defined force, leaving the dura intact. Lesioned ONs and unlesioned contralateral controls were analyzed 7 days (n = 5) and 14 days (n = 5) after ONC, with the following markers: PDGFRb (pericyte), Iba1 (microglia), CD68 (macrophages), RECA (endothelial cell), GFAP (astrocyte) as well as LYVE-1 and podoplanin (PDPN; lymphatic markers)...
March 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28303467/mir-9-5p-down-regulates-pit2-but-not-pit1-in-human-embryonic-kidney-293-cells
#13
D P Paiva, M Keasey, J R M Oliveira
Inorganic phosphate (Pi) is an essential component for structure and metabolism. PiT1 (SLC20A1) and PiT2 (SLC20A2) are members of the mammalian type-III inorganic phosphate transporters. SLC20A2 missense variants are associated with primary brain calcification. MicroRNAs (miRNAs) are endogenous noncoding regulatory RNAs, which play important roles in post-transcriptional gene regulation. MicroRNA-9 (miR-9) acts at different stages of neurogenesis, is deeply rooted in gene networks controlling the regulation of neural progenitor proliferation, and is also linked with cancers outside the nervous system...
March 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28300161/foxo-transcription-factors-protect-against-the-diet-induced-fatty-liver-disease
#14
Xiaoyan Pan, Yang Zhang, Hyeong-Geug Kim, Suthat Liangpunsakul, X Charlie Dong
Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298627/novel-mutations-of-pdgfrb-cause-primary-familial-brain-calcification-in-chinese-families
#15
Chong Wang, Xiang-Ping Yao, Hai-Ting Chen, Jing-Hui Lai, Xin-Xin Guo, Hui-Zhen Su, En-Lin Dong, Qi-Jie Zhang, Ning Wang, Wan-Jin Chen
Four causative genes, including solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor b (PDGFRB), platelet-derived growth factor b (PDGFB)and xenotropic and polytropic retrovirus receptor 1 (XPR1), have been identified to cause primary familial brain calcification (PFBC). However, PDGFRB mutations seem to be quite rare and no PDGFRB mutations have been reported in Chinese PFBC patients. A total of 146 PFBC patients including 12 families and 134 sporadic patients were recruited in this study...
March 16, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28298363/mutual-interaction-between-endothelial-cells-and-mural-cells-enhances-bmp9-signaling-in-endothelial-cells
#16
Yuki Tachida, Nanae Izumi, Toyo Sakurai, Hideki Kobayashi
Hereditary hemorrhagic telangiectasia is characterized by the formation of abnormal vascular networks and caused by the mutation of genes involved in BMP9 signaling. It is also known that the interaction between endothelial cells (ECs) and mural cells (MCs) is critical to maintain vessel integrity. However, it has not yet fully been uncovered whether the EC-MC interaction affects BMP9 signaling or not. To elucidate this point, we analyzed BMP9 signaling in a co-culture of several types of human primary culture ECs and MCs...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28281307/integrated-expression-analysis-identifies-transcription-networks-in-mouse-and-human-gastric-neoplasia
#17
Zheng Chen, Mohammed Soutto, Bushra Rahman, Muhammad W Fazili, DunFa Peng, Maria Blanca Piazuelo, Heidi Chen, M Kay Washington, Yu Shyr, Wael El-Rifai
Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach [Tff1-KO (LGD) and Tff1 wild-type (normal)] and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P < ...
March 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28276839/visualization-of-vascular-mural-cells-in-developing-brain-using-genetically-labeled-transgenic-reporter-mice
#18
Bongnam Jung, Thomas D Arnold, Elisabeth Raschperger, Konstantin Gaengel, Christer Betsholtz
The establishment of a fully functional blood vascular system requires elaborate angiogenic and vascular maturation events in order to fulfill organ-specific anatomical and physiological needs. Although vascular mural cells, i.e. pericytes and vascular smooth muscle cells, are known to play fundamental roles during these processes, their characteristics during vascular development remain incompletely understood. In this report, we utilized transgenic reporter mice in which mural cells are genetically labeled to examine developing vascular mural cells in the central nervous system (CNS)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28263720/simvastatin-down-regulates-differential-genetic-profiles-produced-by-organochlorine-mixtures-in-primary-breast-cell-hmec
#19
LETTER
Javier Rivero, Luis Alberto Henríquez-Hernández, Luis D Boada, Jose Pestano, Octavio P Luzardo, María Camacho, Manuel Zumbado, Pilar F Valerón
Women all over the world are exposed to an unavoidable contamination by organochlorine pesticides and other chemical pollutants. Many of them are considered as xenoestrogens and have been associated with the development and progression of breast cancer. We have demonstrated that the most prevalent pesticide mixtures found in healthy women and in women diagnosed with breast cancer modulates the gene expression in human epithelial mammary cells. Statins are well-known cholesterol-depleting agents acting as inhibitors of cholesterol synthesis...
April 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28261327/multiple-myo18a-pdgfrb-fusion-transcripts-in-a-myeloproliferative-neoplasm-patient-with-t-5-17-q32-q11
#20
Guangying Sheng, Zhao Zeng, Jinlan Pan, Linbing Kou, Qinrong Wang, Hong Yao, Lijun Wen, Liang Ma, Depei Wu, Huiying Qiu, Suning Chen
BACKGROUND: Myeloproliferative neoplasms (MPNs), typically defined by myeloid proliferation and eosinophilia, and are only rarely caused by platelet-derived growth factor receptor beta (PDGFRB) gene rearrangements. CASE PRESENTATION: Here, we report a unique case of MPN that is negative for eosinophilia and characterized by a novel PDGFRB rearrangement. After cytogenetic analysis revealed a karyotype of t(5;17) (q32;q11), we used fluorescence in situ hybridization to specifically identify the PDGFRB gene at 5q31-q33 as the gene that had been translocated...
2017: Molecular Cytogenetics
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