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https://www.readbyqxmd.com/read/28521628/cd36-positive-b-lymphoblasts-predict-poor-outcome-in-children-with-b-lymphoblastic-leukemia
#1
Joanna G Newton, John T Horan, Scott Newman, Michael R Rossi, Rhett P Ketterling, Sunita I Park
Objective We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36+ B-LL compared to patients with CD36- B-LL. Methods We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28509585/identification-of-a-novel-fusion-tbl1xr1-pdgfrb-in-a-patient-with-acute-myeloid-leukemia-harboring-the-dek-nup214-fusion-and-clinical-response-to-dasatinib
#2
Paulo Vidal Campregher, Nathalia da Silva Halley, Gabriela Amaral Vieira, Juliana Folloni Fernandes, Elvira Deolinda Rodrigues Pereira Velloso, Siraj Ali, Tariq Mughal, Vincent Miller, Cristovão Luis Pitangueira Mangueira, Vicente Odone, Nelson Hamerschlak
No abstract text is available yet for this article.
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#3
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28505006/myopericytomatosis-clinicopathologic-analysis-of-11-cases-with-molecular-identification-of-recurrent-pdgfrb-alterations-in-myopericytomatosis-and-myopericytoma
#4
Yin P Hung, Christopher D M Fletcher
Myopericytoma is a benign tumor of concentrically distributed perivascular myoid cells. Its molecular basis and relationship with myofibroma/myofibromatosis and other pericytic tumors are not fully understood. In our consultation/surgical files of over 1000 myopericytic lesions, we identified 11 cases with diffuse dermal/subcutaneous involvement by microscopic myopericytomatous nodules, a phenomenon we have termed myopericytomatosis. Myopericytomatosis affected mostly adults (female:male=8:3; median age, 37 y; range, 9 to 63 y) in the lower extremities (foot/ankle, 5; calf, 3; knee, 1; thigh, 1; neck, 1) over months to 25 years, ranging from 1...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28496993/successful-application-of-whole-genome-sequencing-in-a-medical-genetics-clinic
#5
David Bick, Pamela C Fraser, Michael F Gutzeit, Jeremy M Harris, Tina M Hambuch, Daniel C Helbling, Howard J Jacob, Juliet N Kersten, Steven R Leuthner, Thomas May, Paula E North, Sasha Z Prisco, Bryce A Schuler, Mary Shimoyama, Kimberly A Strong, Scott K Van Why, Regan Veith, James Verbsky, Arthur M Weborg, Brandon M Wilk, Rodney E Willoughby, Elizabeth A Worthey, David P Dimmock
A pilot program was initiated using whole genome sequencing (WGS) to diagnose suspected genetic disorders in the Genetics Clinic at Children's Hospital of Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis, this increased to 36% (8/22). Disease causing variants were identified in SKIV2L, CECR1, DGKE, PYCR2, RYR1, PDGFRB, EFTUD2, and BCS1L. In 75% (6/8) of diagnosed cases, the diagnosis affected treatment and/or medical surveillance...
June 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28464908/a-phase-i-study-of-lapatinib-in-combination-with-foretinib-a-c-met-axl-and-vascular-endothelial-growth-factor-receptor-inhibitor-in-human-epidermal-growth-factor-receptor-2-her-2-positive-metastatic-breast-cancer
#6
Stephen K Chia, Susan L Ellard, Mihaela Mates, Stephen Welch, Catalin Mihalcioiu, Wilson H Miller, Karen Gelmon, Caroline Lohrisch, Vikaash Kumar, Sara Taylor, Linda Hagerman, Rachel Goodwin, Tao Wang, Shingo Sakashita, Ming S Tsao, Elizabeth Eisenhauer, Penelope Bradbury
BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC)...
May 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28449810/novel-t-5-11-q32-q13-4-with-numa1-pdgfrb-fusion-in-a-myeloid-neoplasm-with-eosinophilia-with-response-to-imatinib-mesylate
#7
Ying S Zou, Nicole L Hoppman, Zeba N Singh, Sameer Sawhney, Sandy D Kotiah, Maria R Baer
We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13...
April 2017: Cancer Genetics
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
#8
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
#9
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
#10
Clemence Lepelletier, Yasser Al-Sarraj, Christine Bodemer, Hibbah Shaath, Sylvie Fraitag, Marios Kambouris, Dominique Hamel-Teillac, Hatem El Shanti, Smail Hadj-Rabia
No abstract text is available yet for this article.
April 18, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28412213/acute-mast-cell-leukemia-associated-with-t-4-5-q21-q33
#11
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
#12
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
#13
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
#14
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 25, 2017: Biochemistry
https://www.readbyqxmd.com/read/28376187/a-novel-diagnostic-tool-for-selecting-patients-with-mesenchymal-type-colon-cancer-reveals-intratumor-subtype-heterogeneity
#15
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
#16
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
#17
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...
May 15, 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
#18
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
#19
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
#20
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
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