Search results for "Platelet"

CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphoc…

2009

AbstractCD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors…

PDGFRβ and FGFR2 mediate endothelial cell differentiation capability of triple negative breast carcinoma cells

2014

Triple negative breast cancer (TNBC) is a very aggressive subgroup of breast carcinoma, still lacking specific markers for an effective targeted therapy and with a poorer prognosis compared to other breast cancer subtypes. In this study we investigated the possibility that TNBC cells contribute to the establishment of tumor vascular network by the process known as vasculogenic mimicry, through endothelial cell differentiation. Vascular-like functional properties of breast cancer cell lines were investigated in vitro by tube formation assay and in vivo by confocal microscopy, immunofluorescence or immunohistochemistry on frozen tumor sections. TNBCs express endothelial markers and acquire th…

Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.

2008

This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expressi…

PDGFRa/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy

2008

As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRalp…

Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.

2014

Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found…

Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors.

2011

c-Kit tyrosine kinase receptor and its ligand stem cell factor have multiple functions during development, whereas in adulthood they are mostly needed for stem cell (SC) maintenance and mast cell (MC) biology. c-Kit plays an essential tumor-cell-intrinsic role in many types of cancer, either providing the tumorigenic force when aberrantly activated or conferring stem-like features characterizing the most aggressive variants. A tumor-cell-extrinsic role occurs through c-Kit-dependent accessory cells (such as MCs) that infiltrate tumors and deeply influence their progression. c-Kit-targeted therapy with tyrosine kinase inhibitors (TKIs) may ideally work against both tumor and stromal cells. H…

Results from a phase III trial (GRID) evaluating regorafenib (REG) in metastatic gastrointestinal stromal tumour (GIST): Subgroup analysis of outcome…

2013

10551 Background: REG, an oral receptor kinase inhibitor with activity against KIT, PDGFR, VEGFR, FGFRs, and other oncologic targets, demonstrated significant improvement in progression-free survival (PFS) over placebo (PL) in a phase III study (GRID) of patients (pts) with advanced GIST following failure of at least imatinib (IM) and sunitinib (SU). To understand the impact of pts’ baseline characteristics on outcome, we performed an exploratory analysis of REG effects across pt subgroups based on sex, age, and mitotic index of primary GIST tissue, as well as duration and number of lines of previous therapies. Methods: Adult pts with metastatic GIST (n=199) progressing after at least IM a…

Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 3 LEA…

2019

TPS4152 Background: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor) as second-line treatment of advanced HCC, pembro showed meaningful clinical efficacy in pts previously treated with sorafenib, with median PFS 4.9 mo, median OS 12.9 mo, and a manageable safety profile. In results from the pha…

2021

AIMS Platelet indices have been associated with traditional cardiovascular risk factors, cardiovascular diseases and all-cause mortality. This study aimed to investigate the role of platelet count, mean platelet volume (MPV) and platelet-to-leukocyte ratio, including platelet-to-monocyte and platelet-to-lymphocyte ratio with cardiac function, heart failure (HF) phenotypes and clinical outcome, worsening of HF. METHODS AND RESULTS Univariate and multivariable linear and Cox regression analyses were used to investigate the associations between platelet indices, cardiac function and worsening of HF in 3250 subjects enrolled in the MyoVasc study. Higher MPV, lower platelet count, lower platelet…

Management of Patients with Asymptomatic and Symptomatic Carotid Artery Disease: Update on Anti-Thrombotic Therapy

2019

AbstractThe most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (< 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60%…