Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydralazine has been used widely to reduce tumor blood flow and thereby to induce hypoxia and to reduce extracellular pH (pHe) in tumors. Here we have investigated and compared the effects of the vasodilating drugs hydralazine, captopril, nifedipine, prazosin, sodium nitroprusside, and labetalol to reduce pHe in EMT-6 and KHT tumors of mice and to cause antitumor effects. After a single injection, captopril was most effective in reducing pHe in EMT-6 tumors with a decrease in mean pHe from 6.93 to 6.67 at 2 h after injection, while nifedipine was most effective for KHT tumors with a decrease in mean pHe from 6.96 to 6.75 at 1 h after injection. During 72 h of chronic administration into mice bearing tumors, nifedipine was ineffective in reducing pHe, but both captopril and hydralazine caused a small but significant reduction of pHe. Captopril caused significant delay in growth of the tumors, but had only a small effect on clonogenic cell survival. Captopril appears to be the most effective vasodilating drug to enhance tumor acidity.
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PMID:The effects of vasodilating drugs on pH in tumors. 1056 16

Angiotensin I-converting enzyme (ACE), a common element of renin-angiotensin system (RAS) and kallikrein-kinin system (KKS), is involved in myelopoiesis modulation, mainly by cleaving the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Based on this finding and in our results showing B1 and B2 kinin receptors expression in murine bone marrow (BM) cells, we evaluated the ACE influence on myelopoiesis of kinin B1 receptor knockout mice (B1KO) using long-term bone marrow cultures (LTBMCs). Captopril and AcSDKP were used as controls. Enhanced ACE activity, expressed by non-hematopoietic cells (Ter-199(-) and CD45(-)), was observed in B1KO LTBMCs when compared to wild-type (WT) cells. ACE hyperfunction in B1KO cells was maintained when LTBMCs from B1KO mice were treated with captopril (1.0microM) or AcSDKP (1.0nM). Although no alterations were observed in ACE mRNA and protein levels under these culture conditions, 3.0nM of AcSDKP increased ACE mRNA levels in WT LTBMCs. No alteration in the number of GM-CFC was seen in B1KO mice compared to WT animals, even when the former were treated with AcSDKP (10microg/kg) or captopril (100mg/kg) for 4 consecutive days. Hematological data also revealed no differences between WT and B1KO mice under basal conditions. When the animals received 4 doses of lipopolysaccharide (LPS), a decreased number of blood cells was detected in B1KO mice in relation to WT. We also found a decreased percentage of Gr1(+)/Mac-1(+), Ter119(+), B220(+), CD3(+), and Lin(-)Sca1(+)c-Kit(+) (LSK) cells in the BM of B1KO mice compared to WT animals. Low AcSDKP levels were observed in BM cultures from B1KO in comparison to WT cultures. We conclude that ACE hyperfunction in B1KO mice resulted in faster hydrolysis of AcSDKP peptide, which in turn decreased in BM tissues allowing HSC to enter the S stage of the cell cycle.
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PMID:Myelopoiesis modulation by ACE hyperfunction in kinin B(1) receptor knockout mice: relationship with AcSDKP levels. 2009 76