OBJECTIVE To investigate the relationship between gene mutations and protein expressions of PDGFR α and C-kit in gastrointestinal stromal tumors (GIST) and its significance in tumorigenesis. METHODS Single strand conformation polymorphism-polymerase chain reaction (PCR-SSCP), immunohistochemistry and Western blot were used to detect the gene mutations in PDGFR α and C-kit and their protein ex...

BACKGROUND The majority of chordomas show activation of the platelet-derived growth factor receptor (PDGFR). Based on in vitro intertumoral variation in response to recombinant PDGF protein and PDGFR inhibition, and variable tumor response to imatinib, we hypothesized that chordomas resistant to PDGFR inhibition may possess downstream activation of the pathway. METHODS Molecular profiling was...

Hypertension increases mechanical force on the arterial wall by as much as 30%, resulting in marked alterations in signal transductions and gene expression in vascular smooth muscle cells (VSMCs) that contribute to matrix protein synthesis, cell proliferation, and differentiation. How the mechanical stimuli are converted into a biological signal in cells has yet to be studied. We investigated t...

Expression of PDGF B-chain and the PDGF receptor beta-subunit (PDGFR beta) is detected immunocytochemically during the development of glomeruli in human kidneys of 54 to 105 days gestational age. During the early stages (vesicular, comma-shape and S-shape) of glomerulogenesis, PDGF B-chain is localized to differentiating epithelium of the glomerular vesicle, while PDGFR beta is expressed in the...

Rationale: c-myb null (knockout) embryonic stem cells (ESC) can differentiate into cardiomyocytes but not contractile smooth muscle cells (SMC) in embryoid bodies (EB). Objective: To define the role of c-Myb in SMC differentiation from ESC. Methods and Results: In wild-type (WT) EB, high c-Myb levels on days 0–2 of differentiation undergo ubiquitin-mediated proteosomal degradation on days 2.5–3...

PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II-stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. In the present study, we demonstrate that the inhibition of PI3K in VSMCs by expression of a dominant-negative p85alpha mutant lacking the p110-binding domain (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated PAI-1 (pla...

Paralleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell...

Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2 participa...

BACKGROUND The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively ...