1,721,065 research outputs found
Manipulating intracellular Ca2+ signals to stimulate therapeutic angiogenesis in cardiovascular disorders
No full textEndothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy
No full textElevated plasma EDA fibronectin in primary myelofibrosis is determined by high allele burden of JAK2V617F mutation and strongly predicts splenomegaly progression
No full textIn primary myelofibrosis, extra-domain A fibronectin (EDA-FN), the result of alternative splicing of FN gene, sustains megakaryocyte proliferation and confers a pro-inflammatory phenotype to bone marrow cell niches. In this work we assessed the levels of circulating EDA-FN in plasma samples of 122 patients with primary myelofibrosis. Patients with a homozygous JAK2V617F genotype displayed the higher level of plasma EDA-FN. Increased EDA-FN levels were associated with anemia, elevated high-sensitivity C-reactive protein, bone marrow fibrosis and splanchnic vein thrombosis at diagnosis. While no correlation was observed with CD34+ hematopoietic stem cell mobilization, elevated blood level of EDA-FN at diagnosis was a predictor of large splenomegaly (over 10 cm from the left costal margin) outcome. Thus, EDA-FN expression in primary myelofibrosis may represent the first marker of disease progression, and a novel target to treat splenomegaly
VEGF induces human endothelial progenitor cells proliferation by triggering oscillations in [Ca2+]i
No full textEndothelial progenitor cells (EPCs) traffi c from the bone marrow to the site of tissue
regeneration and sustain neo-vascularization after acute vascular injury and upon
the angiogenic switch in solid tumors. Therefore, they represent a suitable tool for
cell-based therapy in regenerative medicine and provide a novel promising target in
the fi ght against cancer. The main stimulus responsible for EPC egression from the
bone marrow and engraftment within neovessels is vascular endothelial growth factor
(VEGF). Intracellular Ca2+ signals regulate numerous endothelial functions, such
as proliferation, migration, and diff erentiation, and underpin VEGF eff ect on mature
endothelium. We have recently shown that EPC growth is governed by a storedependent
Ca2+ entry (SOCE) pathway on the plasma membrane, which is activated
by depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pools1. The
present study aimed at investigating the nature and the role of VEGF-elicited Ca2+
signals in EPCs. All the putative SOCE mediators (i.e. TRPC1, TRPC4, Orai1 and
Stim1) were present in EPCs. VEGF induced long lasting Ca2+ oscillations, however,
removal of external Ca2+ (0Ca2+) and SOCE inhibition with BTP-2 reduced the number
of Ca2+ spikes. Blockade of phospholipase C-? (PLC-?) with U73122 and emptying
the InsP3-sensitive Ca2+ pools with cyclopiazonic acid (CPA) prevented the Ca2+
response to VEGF. Accordingly, the Ca2+ response to VEGF was inhibited by superfusing
CPA during the ongoing oscillations. Notably, VEGF induced EPC was abrogated
by SOCE inhibition with BTP-2. Similarly, VEGF promoted NF-kB translocation
into the nucleus in a BTP-2-sensitive manner. Thus, VEGF causes an initial InsP3-
dependent Ca2+ discharge followed by SOCE-mediated Ca2+ entry in cEPCs. SOCE,
in turn, controls store refi lling and induces cell proliferation by recruiting NF-kB
Characterization of Ca2+ signals in Endothelial Progenitor Cells from Human Peripheral Blood and Umbilical Cord Blood
No full textNon-invasive optical imaging procedures for the in vivo evaluation of cell populations and molecular processes
No full textCanonical transient receptor potential channel 3 as a novel target for cell-based therapy in endothelial colony forming cells
No full textVEGF induces human endothelial progenitor cells to proliferate by eliciting oscillations in intracellular Ca2+ concentration
No full textVEGF-induced Ca2+ oscillations in umbilical cord blood-derived endothelial colony forming cells
No full textThe role of endothelial colony forming cells in kidney cancer's pathogenesis, and in resistance to anti-VEGFR agents and mTOR inhibitors: A speculative review
Full text linkRenal cell carcinoma (RCC) is highly dependent on angiogenesis, due to the overactivation of the VHL/HIF/VEGF/VEGFRs axis; this justifies the marked sensitivity of this neoplasm to antiangiogenic agents which, however, ultimately fail to control tumor growth. RCC also frequently shows alterations in the mTOR signaling pathway, and mTOR inhibitors have shown a similar pattern of initial activity/late failure as pure antiangiogenic agents. Understanding mechanisms of resistance to these agents would be key to improve the outcome of our patients. Circulating endothelial cells are a family of mainly bone marrow-derived progenitors, which have been postulated to be responsible of the reactivation of angiogenesis in different tumors. In this review, we shall discuss the complex nature and function of these cells, the evidence pro and contra their contribution to tumor vascularization, especially as far as RCC is concerned, and their possible role in determining resistance to presently available treatment
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