Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1965, Kerr described a type of death, apoptosis, with different characteristics from necrosis. Apoptosis has an important role in the development and cell homeostasis. Excessive or insufficient apoptosis contributes to the pathogenesis of pathology like ischemia, neurodegeneration, autoimmunity, viral infection, and tumor growth or regression. Apoptosis is subdivided into four sequential phases: order of death; death of cell; phagocytosis of apoptotic bodies and degradation of apoptotic bodies. Death programs converge on sequential activation of a proteases family, caspases. Some aspects of graft rejection can be interpreted as failure of apoptosis in host immunity cells; sometimes rejection involves induction of apoptosis. Apoptotic-type lesions were found in early vascular occlusions, one of the cause of graft failure. Then, an augmented apoptosis in hepatic graft biopsy can be used like a signal of early vascular occlusion. In hepatic transplantation, apoptosis is followed by a proteolytic cascade, which causes sequential activation of caspases. Synthetic inhibitor of caspases can be used, then, in the prevention and/or treatment of pathologies with implication of apoptosis due to ischemia-reperfusion. These inhibitors are not enough for prevention of hepatic lesions, even if caspases inhibitor can be a strategy for treatment of hepatic graft rejection.
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PMID:[The role of apoptosis in hepatic graft rejection]. 1237 Jun 60

Kallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth.
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PMID:Kallistatin is a new inhibitor of angiogenesis and tumor growth. 1238 24

Using a model with external ligation of the thigh, the effect of ischemia-reperfusion injury on tumor growth and the activity of lung metastasis was investigated in mice inoculated a spontaneous murine osteosarcoma cell line (POS-1) in vivo. POS-1 cell suspension was inoculated into the right hind footpad of 70 mice. Four weeks after inoculation, the ipsilateral thigh was ligated for 3 h in 15 mice and the contralateral thigh in 15 mice. Another ten mice were inoculated with POS-1 without ligating the thigh. The number of metastatic foci on the lung surface 6 weeks after inoculation was 2.29+/-0.98 (mean+/-SE) foci/lungs in mice with ipsilateral ligation and 6.25+/-2.41 in mice with contralateral ligation, which were significantly lower than control (13.40+/-1.42 in mice no ligation) (P<0.01). The number of metastatic foci on the lung surface in mice with intraperitoneal injection of superoxide dismutase (SOD) and catalase was 3.25+/-0.65 (mean+/-SE) foci/lungs in mice with ligation which was significantly greater than that in mice without SOD and catalase injection 1.29+/-0.97 (P=0.04). Cell viability was 9.12+/-4.07% with 100 microM H(2)O(2) in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. It revealed that at concentrations of 100 microM H(2)O(2) or higher was cytotoxic to POS-1. In cell invasion assay, the number of invading cells with 10 microM H(2)O(2) was 2.80+/-0.53 cells/field, which was significantly lower than control (5.93+/-0.18) (mean+/-SE), indicating that low-dose H(2)O(2) suppressed invasion of POS-1. These results suggested that reperfusion injury had selective cytotoxicity to POS-1 through producing reactive oxygen species. Activated oxygen was considered to inhibit the regional growth and the ability of lung metastasis of POS-1 cells.
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PMID:Inhibition of lung metastasis of osteosarcoma cell line POS-1 transplanted into mice by thigh ligation. 1240 67

The term bland arterial embolization refers to catheter-directed delivery of particulate material for the purpose of embolizing selected arteries. This technique is used in humans to treat a number of conditions, including arteriovenous malformations, uterine fibroids, and epistaxis. The term chemoembolization refers to selective intra-arterial delivery of chemotherapeutic agents in conjunction with particulate material for the purpose of embolizing arteries supplying blood to a tumor. Compared with traditional modes of drug delivery, chemoembolization increases local concentration and dwell time of the chemotherapeutic agent, augments tumor ischemia, and minimizes systemic toxic effects. In humans, the technique has shown encouraging results in the treatment of a variety of nonresectable tumors. The present report describes techniques for percutaneous bland arterial embolization and chemoembolization in dogs and goats and results of these techniques in 3 dogs and a goat. Bland arterial embolization was performed in 2 dogs and the goat. The goals of treatment included pain palliation, reduction of tumor growth, and control of hemorrhage, and each animal was considered to have benefited from the procedure on the basis of the preprocedural goals. Chemoembolization was performed in 1 dog for treatment of a nonresectable hepatocellular carcinoma. Unfortunately, this dog did not live long enough to identify any response to treatment. Results for animals studied illustrate the feasibility of bland arterial embolization and chemoembolization in veterinary patients and suggest that embolization may provide an alternative method of treatment for animals with inoperable lesions.
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PMID:Percutaneous arterial embolization and chemoembolization for treatment of benign and malignant tumors in three dogs and a goat. 1245 12

Chemokines, a large family of inflammatory cytokines, have been shown to play a critical role in the regulation of angiogenesis during several pathophysiologic processes, such as tumor growth, wound healing and ischemia. Semiquantitative or quantitative angiogenesis assays are commonly utilized to screen the angiogenic or angiostatic activity of chemokines. These include in vitro endothelial cell activation assays and ex vivo or in vivo models of neovascularization. Chemokines may exert their regulatory activity on angiogenesis directly or as a consequence of leukocyte infiltration and/or the induction of growth factor expression. The effect of chemokines on endothelium can be assessed by performing in vitro assays on purified endothelial cell populations or by in vivo assays. Nevertheless, each model used to evaluate the angiogenic or angiostatic activity of a discrete factor has advantages and limitations. Thus, in order to avoid under- or overestimating the regulatory effect of chemokines on angiogenesis and to evaluate all aspects of the angiogenic process, multiple assays are usually performed. This review summarizes past and recent studies on chemokines as modulators of angiogenesis with particular emphasis on the methods currently used for the assessment of chemokine-mediated angiogenic or angiostatic responses.
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PMID:Analysis of the role of chemokines in angiogenesis. 1253

Angiogenesis, the development of new capillaries form pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate in response to growth factors to form functional vessels. Therapeutic angiogenesis is proposed to restore tissue integrity and function following damage and ischemia, while strategies aimed to block or suppress the neovascular growth are designed as adjuvant therapies for cancer treatment. Different experimental and clinical observations support the existence of a molecular/biochemical link between vasodilation, nitric oxide (NO) production and angiogenesis. NO significantly contributes to the prosurvival/proangiogenic program of capillary endothelium by triggering cell growth and differentiation via endothelial-constitutive NO synthase (ecNOS) activation, and cyclic GMP (cGMP) dependent gene transcription. Re-establishment of a balanced NO production in the cardiovascular system results in a reduction of cell damage during inflammatory and vascular diseases. Elevation of NOS activity in correlation with angiogenesis and tumor growth and aggressiveness has been extensively reported in experimental and human tumors. On these bases, the nitric oxide pathway appears to be a promising target for the development of pro- and anti-angiogenic therapeutic strategies. In particular, the use of NOS inhibitors or NO scavengers seems appropriate to reduce edema, block angiogenesis and facilitate antitumor drug delivery.
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PMID:Role of nitric oxide in the modulation of angiogenesis. 1257 Aug

Adenosine is released during tissue injury, ischemia and tumor growth, and promotes angiogenesis. Because mast cells accumulate in the proximity of new blood vessel development, we examined if they may contribute to adenosine-induced angiogenesis. We found that HMC-1 human mast cells express A2A, A2B, and A3 adenosine receptors. The adenosine agonist NECA (100 micromol/L) increased interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and angiopoietin-2 mRNA expression. NECA-induced secretion of IL-8 and VEGF was verified by ELISA. A2B receptors mediate VEGF and IL-8 secretion because neither CGS21680 (selective A2A agonist) nor IB-MECA (selective A3 agonist) produced this effect, and it was inhibited by the selective A2B antagonist IPDX but not by the selective A2A antagonist SCH58261 or the selective A3 antagonist MRS1191. In contrast, the selective A3 agonist IB-MECA (EC50 1 nmol/L) stimulated angiopoietin-2 expression. Conditioned media from NECA-activated HMC-1 stimulated human umbilical vein endothelial cell proliferation and migration, and induced capillary tube formation. Capillary formation induced by mast cell-conditioned media was maximal if both HMC-1 A2B and A3 receptors were activated, whereas activation of A2B receptor alone was less effective. Thus, adenosine A2B and A3 receptors act in a functional cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from human mast cells.
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PMID:Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors. 1260 Aug 79

Nitric oxide (NO) is an important signaling molecule for ischemia, inflammation, angiogenesis, immune response, and cell growth and differentiation. It has recently been shown that increased production of NO within various human cancers may contribute to tumor angiogenesis, tumor growth and metastasis, and tumor-related immune suppression. NO can be produced by several NO synthases (NOS), including inducible synthase (iNOS), which is expressed during cell activation and produces NO in larger quantity and for a longer period of time than non-inducible NOSs. In this study, we examined the expression levels of iNOS mRNA and protein in prostate adenocarcinoma using a paired nonneoplastic and neoplastic primary prostate cell culture system and related prostatectomy specimens. Six pairs of neoplastic and nonneoplastic primary prostate cell cultures were established from radical prostatectomy specimens based on homogeneity of the originating tumor and the nonneoplastic tissue. Radioactive reverse transcriptase polymerase chain reaction and subsequent quantitative analysis of iNOS mRNA were performed on the cultures using beta-actin as an internal control. Immunohistochemical studies with an anti-iNOS monoclonal antibody were performed on the corresponding formalin-fixed paraffin-embedded prostatectomy tissue sections. We observed marked patient-to-patient variation in "normal" levels of iNOS mRNA. However, all six neoplastic cultures showed moderately to markedly higher mRNA levels than did their paired nonneoplastic cultures. In addition, iNOS protein levels were significantly higher in paraffin-embedded prostate cancer tissue sections than in adjacent nonneoplastic tissue. Overexpression of iNOS mRNA and protein levels is present in moderately differentiated prostate adenocarcinoma and may contribute to prostate cancer angiogenesis, tumor growth, and tumor-related immunosuppression.
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PMID:Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. 1285 39

Bone marrow-Derived cells have been proposed to form new vessels or at least incorporate into growing vessels in adult organisms under certain physiological and pathological conditions. We investigated whether bone marrow-Derived cells incorporate into vessels using mouse models of hindlimb ischemia (arteriogenesis and angiogenesis) and tumor growth. C57BL/6 wild-type mice were lethally irradiated and transplanted with bone marrow cells from littermates expressing enhanced green fluorescent protein (GFP). At least 6 weeks after bone marrow transplantation, the animals underwent unilateral femoral artery occlusions with or without pretreatment with vascular endothelial growth factor or were subcutaneously implanted with methylcholanthrene-induced fibrosarcoma (BFS-1) cells. Seven and 21 days after surgery, proximal hindlimb muscles with growing collateral arteries and ischemic gastrocnemius muscles as well as grown tumors and various organs were excised for histological analysis. We failed to colocalize GFP signals with endothelial or smooth muscle cell markers. Occasionally, the use of high-power laser scanning confocal microscopy uncovered false-positive results because of overlap of different fluorescent signals from adjacent cells. Nevertheless, we observed accumulations of GFP-positive cells around growing collateral arteries (3-fold increase versus nonoccluded side, P<0.001) and in ischemic distal hindlimbs. These cells were identified as fibroblasts, pericytes, and primarily leukocytes that stained positive for several growth factors and chemokines. Our findings suggest that in the adult organism, bone marrow-Derived cells do not promote vascular growth by incorporating into vessel walls but may function as supporting cells.
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PMID:Bone marrow-derived cells do not incorporate into the adult growing vasculature. 1511 31

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.
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PMID:Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis. 1516 78


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