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PDGFRβ

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https://www.readbyqxmd.com/read/27885822/from-type%C3%A2-i-to-type%C3%A2-ii-design-synthesis-and-characterization-of-potent-pyrazin-2-ones-as-dfg-out-inhibitors-of-pdgfr%C3%AE
#1
Eugen Bethke, Boris Pinchuk, Christian Renn, Lydia Witt, Joachim Schlosser, Christian Peifer
Reversible protein kinase inhibitors that bind in the ATP cleft can be classified as type I or type II binders. Of these, type I inhibitors address the active form, whereas type II inhibitors typically lock the kinase in an inactive form. At the molecular level, the conformation of the flexible activation loop holding the key DFG motif controls access to the ATP site, thereby determining an active or inactive kinase state. Accordingly, type I and type II kinase inhibitors bind to so-called DFG-in or DFG-out conformations, respectively...
November 25, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27881889/expression-of-caf-related-proteins-is-associated-with-histologic-grade-of-breast-phyllodes-tumor
#2
Hye Min Kim, Yu Kyung Lee, Ja Seung Koo
Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0...
2016: Disease Markers
https://www.readbyqxmd.com/read/27856617/pdgfr%C3%AE-regulates-craniofacial-development-through-homodimers-and-functional-heterodimers-with-pdgfr%C3%AE
#3
Katherine A Fantauzzo, Philippe Soriano
Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor α (PDGFRα) has well-documented functions in this process, the role of PDGFRβ in murine craniofacial development is not well established. We demonstrate that PDGFRα and PDGFRβ are coexpressed in the craniofacial mesenchyme of mid-gestation mouse embryos and that ablation of Pdgfrb in the neural crest lineage results in increased nasal septum width, delayed palatal shelf development, and subepidermal blebbing...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27821319/a-phase-ii-study-of-sorafenib-in-recurrent-and-or-metastatic-salivary-gland-carcinomas-translational-analyses-and-clinical-impact
#4
L D Locati, F Perrone, B Cortelazzi, C Bergamini, P Bossi, E Civelli, C Morosi, S Lo Vullo, M Imbimbo, P Quattrone, G P Dagrada, R Granata, C Resteghini, A Mirabile, S Alfieri, E Orlandi, L Mariani, G Saibene, S Pilotti, L Licitra
BACKGROUND: Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT)...
November 4, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27803296/homocysteine-deteriorates-intrahepatic-derangement-and-portal-systemic-collaterals-in-cirrhotic-rats
#5
Hung-Chun Tung, Shao-Jung Hsu, Ming-Hung Tsai, Te-Yueh Lin, I-Fang Hsin, Teh-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Hsin-Ling Ho, Han-Chieh Lin, Shou-Dong Lee
In liver cirrhosis, the altered levels of vasoactive substances, especially endothelin-1 (ET-1) and nitric oxide (NO) leads to elevated intrahepatic resistance, increased portal-systemic collaterals, and abnormal intra- and extra-hepatic vascular responsiveness. These derangements aggravate portal hypertension-related complications such as gastroesophageal variceal bleeding. Homocysteine, a substance implicated in cardiovascular diseases, has been found with influences on vasoresponsiveness and angiogenesis...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27793148/pdgfr%C3%AE-c-kit-pulp-cells-are-odontoblastic-progenitors-capable-of-producing-dentin-like-structure-in-vitro-and-in-vivo
#6
Shiwei Cai, Wenjian Zhang, Wei Chen
BACKGROUND: Successful pulp regeneration depends on identification of pulp stem cells capable of differentiation under odontoblastic lineage and producing pulp-dentinal like structure. Recent studies demonstrate that platelet-derived growth factor (PDGF) plays an important role in damage repair and tissue regeneration. The aim of this study was to identify a subpopulation of dental pulp cells responsive to PDGF and with dentin regeneration potential. METHODS: Pulp tissues were isolated from 12 freshly extracted human impacted third molars...
October 28, 2016: BMC Oral Health
https://www.readbyqxmd.com/read/27779900/ablation-of-pericyte-like-cells-in-lungs-by-oropharyngeal-aspiration-of-diphtheria-toxin
#7
Chi F Hung, Yu-Hua Chow, W Conrad Liles, William A Altemeier, Lynn M Schnapp
: We previously demonstrated that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablate FoxD1-derived cells. METHOD: We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) where FoxD1-derived cells heritably express iDTR and are sensitive to DT...
October 25, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27778377/dynamics-of-pdgfr%C3%AE-expression-in-different-cell-types-after-brain-injury
#8
Jenni Kyyriäinen, Xavier Ekolle Ndode-Ekane, Asla Pitkänen
Platelet-derived growth factor receptor β (PDGFRβ) is upregulated after brain injury and its depletion results in the blood-brain barrier (BBB) damage. We investigated the time-window and localization of PDGFRβ expression in mice with intrahippocampal kainic acid-induced status epilepticus (SE) and in rats with lateral fluid-percussion-induced traumatic brain injury (TBI). Tissue immunohistochemistry was evaluated at several time-points after SE and TBI. The distribution of PDGFRβ was analyzed, and its cell type-specific expression was verified with double/triple-labeling of astrocytes (GFAP), NG2 cells, and endothelial cells (RECA-1)...
October 25, 2016: Glia
https://www.readbyqxmd.com/read/27764516/characteristics-of-the-expression-of-kai1-cd82-and-pdgfr%C3%AE-and-their-impact-on-glioma-progression
#9
M Paradowski, M Bilinska, J Bar
The biological features of glioma cells may define their clinical outcome. Little is known about the interactions between KAI1/CD82 metastatic suppressor protein and PDGFR in gliomas. The aim of the study was to examine KAI1/CD82 and PDGFR expression in gliomas in order to find the impact of these proteins on progression of the tumors. PDGFR, KAI1/CD82 protein expression and mRNA of genes were evaluated on eighty four paraffin-embedded tissue of gliomas using immunohistochemical staining and RT-PCR analysis...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27751871/hif1%C3%AE-induced-pdgfr%C3%AE-signaling-promotes-developmental-hsc-production-via-il-6-activation
#10
Sung-Eun Lim, Virginie Esain, Wanda Kwan, Lindsay N Theodore, Mauricio Cortes, Isaura M Frost, Sarah Y Liu, Trista E North
Hematopoietic stem cells (HSCs) have the ability to both self-renew and differentiate into all of the mature blood cell lineages and thereby reconstitute the entire blood system. Therefore, HSCs are therapeutically valuable for treatment of hematological malignances and bone marrow failure. We showed recently that transient glucose elevation elicited dose-dependent effects on HSCs through elevated metabolic activity and subsequent reactive oxygen species-mediated induction of Hypoxia-Inducible Factor 1α (Hif1α)...
October 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27742657/chromoplectic-tpm3-alk-rearrangement-in-a-patient-with-inflammatory-myofibroblastic-tumor-who-responded-to-ceritinib-after-progression-on-crizotinib
#11
A S Mansfield, S J Murphy, F R Harris, S I Robinson, R S Marks, S H Johnson, J B Smadbeck, G C Halling, E S Yi, D Wigle, G Vasmatzis, J Jen
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy...
October 14, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27737004/tyrosine-kinase-inhibitors-regulate-opg-through-inhibition-of-pdgfr%C3%AE
#12
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
https://www.readbyqxmd.com/read/27736501/validation-of-cross-species-reactivity-of-the-vegf-a-pdgfr%C3%AE-bifunctional-antibody-pf-06653157
#13
Roshan Ashoor, Dong Lee, Alvan Cheng, Bart Jessen, Wenhu Huang
PURPOSE: PF-06653157 is a bifunctional antagonist monoclonal antibody (mAb) that targets human VEGF-A ligand and PDGF-Rβ. With the advent of PF-06653157 as an angiogenesis inhibitor and potential treatment for angiogenesis deregulation diseases, a relevant toxicology species is needed for toxicity and efficacy studies. Investigative studies were conducted to validate the mAb dual antagonist properties in a human system and determine its cross-reactive pharmacology in nonhuman cells. METHODS: Sequence alignment was used to determine percent sequence identity of VEGF and PDGF receptors and ligands; qualitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the presence of PDGF-Rβ on cells of interest...
October 13, 2016: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27698080/tyrosine-kinase-receptor-expression-in-canine-liposarcoma
#14
G Avallone, V Pellegrino, P Roccabianca, E Lepri, L Crippa, G Beha, L De Tolla, G Sarli
The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP...
October 3, 2016: Veterinary Pathology
https://www.readbyqxmd.com/read/27198239/thrombin-stimulated-platelet-derived-exosomes-inhibit-platelet-derived-growth-factor-receptor-beta-expression-in-vascular-smooth-muscle-cells
#15
Ming Tan, Hong-Bing Yan, Jian-Nan Li, Wen-Ke Li, Yuan-Yuan Fu, Wen Chen, Zhou Zhou
BACKGROUND/AIMS: It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs. METHODS: Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27138650/laminin-regulates-pdgfr%C3%AE-cell-stemness-and-muscle-development
#16
Yao Yao, Erin H Norris, Christopher E Mason, Sidney Strickland
Muscle-resident PDGFRβ(+) cells, which include pericytes and PW1(+) interstitial cells (PICs), play a dual role in muscular dystrophy. They can either undergo myogenesis to promote muscle regeneration or differentiate into adipocytes and other cells to compromise regeneration. How the differentiation and fate determination of PDGFRβ(+) cells are regulated, however, remains unclear. Here, by utilizing a conditional knockout mouse line, we report that PDGFRβ(+) cell-derived laminin inhibits their proliferation and adipogenesis, but is indispensable for their myogenesis...
2016: Nature Communications
https://www.readbyqxmd.com/read/27128408/pdgfr%C3%AE-is-a-novel-marker-of-stromal-activation-in-oral-squamous-cell-carcinomas
#17
Vinay K Kartha, Lukasz Stawski, Rong Han, Paul Haines, George Gallagher, Vikki Noonan, Maria Kukuruzinska, Stefano Monti, Maria Trojanowska
Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contributing to their activation remain poorly characterized, in part due to fibroblast heterogeneity and the scarcity of reliable fibroblast surface markers. To search for such markers in oral squamous cell carcinoma (OSCC), we applied a novel approach that uses RNA-sequencing data derived from the cancer genome atlas (TCGA)...
2016: PloS One
https://www.readbyqxmd.com/read/27127135/the-involvement-of-pdgf-b-pdgfr%C3%AE-axis-in-the-resistance-to-antiangiogenic-and-antivascular-therapy-in-renal-cancer
#18
Alin Adrian Cumpănas, Anca Maria Cimpean, Ovidiu Ferician, Raluca Amalia Ceausu, Simona Sarb, Vlad Barbos, Alice Dema, Marius Raica
BACKGROUND/AIM: Studies developed in the field of platelet-derived growth factors/platelet-derived growth factor receptors (PDGFs/PDGFRs) inhibition have focused on the therapeutic effects on tumor cells, neglecting their potential effects on tumor blood vessels. We herein propose a differential and critic assessment of platelet-derived growth factor B (PDGF-B) and platelet-derived growth factor receptor β (PDGFRβ) in renal cell carcinoma, correlated with the four main vascular patterns previously reported by our team...
May 2016: Anticancer Research
https://www.readbyqxmd.com/read/27102439/the-transcription-factor-runx2-regulates-receptor-tyrosine-kinase-expression-in-melanoma
#19
Rajeev K Boregowda, Daniel J Medina, Elke Markert, Michael A Bryan, Wenjin Chen, Suzie Chen, Anna Rabkin, Michael J Vido, Samuel I Gunderson, Marina Chekmareva, David J Foran, Ahmed Lasfar, James S Goydos, Karine A Cohen-Solal
Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase (RTK) expression in melanoma. We have demonstrated that RUNX2-deficient melanoma cells display a significant decrease in three receptor tyrosine kinases, EGFR, IGF-1R and PDGFRβ...
May 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27093993/-the-study-of-4-cases-of-myeloid-neoplasm-with-t-5-12-q33-p13-and-the-literatures-review
#20
REVIEW
Linbing Kou, Jinlan Pan, Huiying Qiu, Suning Chen, Jiannong Cen, Jun Zhang, Shuxiao Bai, Chunxiao Wu, Yafang Wu, Yanlei Gong, Juan Shen
OBJECTIVE: To report clinical and laboratory features of 4 cases of myeloid neoplasm with t (5;12) (q33;p13). METHODS: Cytogenetic examination of bone marrow cells obtained from patients was performed by 24 h culture method. R banding technical was used for karyotype analysis. PDGFRβ gene rearrangement was detected by FISH using dual color break apart PDGFRβ probe. ETV6-PDGFRβ fusion genes were detected by multiple-reverse transcription polymerase chain reaction (RT-PCR)...
April 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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