1,820 research outputs found
Mammalian tumor xenografts induce neovascularization in zebrafish embryos.
The zebrafish (Danio rerio)/tumor xenograft model represents
a powerful new model system in cancer. Here, we describe a
novel exploitation of the zebrafish model to investigate tumor
angiogenesis, a pivotal step in cancer progression and target
for antitumor therapies. Human and murine tumor cell lines
that express the angiogenic fibroblast growth factor (FGF) 2
and/or vascular endothelial growth factor (VEGF) induce the
rapid formation of a new microvasculature when grafted close
to the developing subintestinal vessels of zebrafish embryos at
48 h postfertilization. Instead, no angiogenic response was
exerted by related cell clones defective in the production of
these angiogenic growth factors. The newly formed blood
vessels sprout from the subintestinal plexus of the zebrafish
embryo, penetrate the tumor graft, and express the transcripts
for the zebrafish orthologues of the early endothelial markers
Fli-1, VEGF receptor-2 (VEGFR2/KDR), and VE-cadherin.
Accordingly, green fluorescent protein–positive neovessels
infiltrate the graft when tumor cells are injected in transgenic
VEGFR2:G-RCFP zebrafish embryos that express green fluorescent
protein under the control of the VEGFR2/KDR
promoter. Systemic exposure of zebrafish embryos immediately
after tumor cell injection to prototypic antiangiogenic
inhibitors, including the FGF receptor tyrosine kinase inhibitor
SU5402 and the VEGFR2/KDR tyrosine kinase inhibitor
SU5416, suppresses tumor-induced angiogenesis without
affecting normal blood vessel development. Accordingly,
VE-cadherin gene inactivation by antisense morpholino
oligonucleotide injection inhibits tumor neovascularization
without affecting the development of intersegmental and
subintestinal vessels. These data show that the zebrafish/
tumor xenograft model represents a novel tool for investigating
the neovascularization process exploitable for drug
discovery and gene targeting in tumor angiogenesis
Erythropoietin/erythropoietin-receptor system is involved in angiogenesis in human hepatocellular carcinoma
Ribatti D, Marzullo A, Gentile A, Longo V, Nico B, Vacca A & Dammacco F (2007) Histopathology 50, 591–596 Erythropoietin/erythropoietin-receptor system is involved in angiogenesis in human hepatocellular carcinom
Nutraceuticals and their role in tumor angiogenesis
Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis (angioprevention). Nutraceuticals, such as omega-3 fatty acids, amino acids, proteins, vitamins, minerals, fibers, and phenolic compounds, improve health benefits as they are a source of bioactive compounds that, among other effects, can regulate angiogenesis. The literature concerning the pro-angiogenic and/or anti-angiogenic nutraceuticals and the possible activated pathways in cancer and other non-neoplastic diseases by in vivo and in vitro experiments are reviewed
Angiogenesis and Progression in Human Melanoma
In tumor growth, angiogenesis, the process of new-formation of blood vessels from pre-existing ones, is uncontrolled and unlimited in time. The vascular phase is characterized by the new-formation of vascular channels that enhances tumor cell proliferation, local invasion and hematogenous metastasis. Human malignant melanoma is a highly metastatic tumor with poor prognosis, and high resistance to treatment. Parallel with progression, melanoma acquires a rich vascular network, whereas an increasing number of tumor cells express the laminin receptor, which enables their adhesion to the vascular wall, favouring tumor cell extravasation and metastases. Melanoma neovascularization has been correlated with poor prognosis, overall survival, ulceration and increased rate of relapse. Secretion of various angiogenic cytokines, i.e. VEGF-A, FGF-2, PGF-1 and -2, IL-8, and TGF-1 by melanoma cells promote the angiogenic switch and has been correlated to transition from the radial to the vertical growth phase, and to the metastatic phase. Moreover, melanoma cells overexpress αvβ3, αvβ5, α2β1 and α5β1 integrins and release, together with stromal cells, higher amount of metalloproteases that increasing their invasive potential and angiogenesis. Basing on these observations, different molecular targets of antiangiogenic molecules has be recognized and various antiangiogenic agents are currently in preclinical and clinical trials for melanoma
Different spatial distribution of inflammatory cells in the tumor microenvironment of ABC and GBC subgroups of diffuse large B cell lymphoma
Diffuse Large B-Cell Lymphoma (DLBCL) presents a high clinical and biological heterogeneity, and the tumor microenvironment chracteristics are important in its progression. The aim of this study was to evaluate tumor T, B cells, macrophages and mast cells distribution in GBC and ABC DLBCL subgroups through a set of morphometric parameters allowing to provide a quantitative evaluation of the morphological features of the spatial patterns generated by these inflammatory cells. Histological ABC and GCB samples were immunostained for CD4, CD8, CD68, CD 163, and tryptase in order to determine both percentage and position of positive cells in the tissue characterizing their spatial distribution. The results evidenced that cell patterns generated by CD4-, CD8-, CD68-, CD163- and tryptase-positive cell profiles exhibited a significantly higher uniformity index in ABC than in GCB subgroup. The positive-cell distributions appeared clustered in tissues from GCB, while in tissues from ABC such a feature was lower or absent. The combinations of spatial statistics-derived parameters can lead to better predictions of tumor cell infiltration than any classical morphometric method providing a more accurate description of the functional status of the tumor, useful for patient prognosis
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