Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that prostanoids are essential for local inflammation including cell proliferation and apoptosis. Accordingly, prostaglandin E2 (PGE(2)) is a critical factor in wound healing, tumor invasiveness and progression. Therefore, the aim of the present work was to evaluate effects by PGE(2) on tumor vascular density at early onset of tumor growth where hypoxia is limited. Wild-type mice (C57Bl, C3H/HeN) bearing either MCG-101 tumors or a malignant melanoma (K1735-M2) with either high or insignificant PGE(2) production and subsequently different in sensitivity to cyclooxygenase (COX) inhibition were used. Tumor angiogenesis was estimated by intravital microscopy and immune histochemical analysis in wild type and EP(1) or EP(3) subtype receptor knockout mice (C57Bl). Both MCG-101 and K1735-M2 tumor cells stimulated early outgrowth of tumor vessels in proportion to intrinsic growth rate of tumor cells. Indomethacin had no effects on tumor growth or tumor related vascular area in K1735-M2 bearing mice. By contrast, indomethacin decreased tumor cell proliferation and increased apoptosis in MCG-101 tumors with subsequent adaptation in tumor vascular density. Effects of indomethacin on early growth of MCG-101 tumors were not related to tumor content of bFGF protein, while our earlier studies on long-term tumor growth have shown decreased mRNA levels of bFGF during indomethacin treatment. Early onset of tumor growth was significantly promoted in EP(3)- but not in EP(1)-knockouts, although long-term tumor growth is attenuated in EP(1)-knockouts as reported elsewhere. Our results demonstrate that tumor production of PGE(2) promotes primarily net growth of tumor cells with subsequent adaptations in development of the tumor vasculature. Therefore, it is likely that angiogenesis is not a limiting step at the early onset of tumor growth.
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PMID:Cyclooxygenase inhibition in early onset of tumor growth and related angiogenesis evaluated in EP1 and EP3 knockout tumor-bearing mice. 1640 May 21

Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells.
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PMID:Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia. 2155 80