Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of sodium borocaptate (BSH), a drug that has been used clinically for boron neutron capture therapy (BNCT) of malignant brain tumors, have been characterized by measuring boron concentrations by direct current plasma-atomic emission spectroscopy (DCP-AES) in a group of 23 patients with high-grade gliomas. The disposition of BSH following intravenous (i.v.) infusion, which was determined by measuring plasma boron concentrations by DCP-AES, was consistent with a three-compartment open model with zero-order input and first-order elimination from the central compartment. Boron disposition was linear over the dose range of 26.5-88.2 mg BSH/kg body weight (b.w.), corresponding to 15-50 mg boron/kg b.w. Mean total body boron plasma clearance was 14.4 +/- 3.5 ml/min and the harmonic mean half-lives (range) were 0.6 (0.3-3.7), 6.5 (4.8-10.1) and 77.8 (49.6-172.0) h for the alpha, beta, and gamma disposition phases, respectively. Using an empirically determined plasma: blood boron concentration ratio of 1.3 +/- 0.2, the calculated total body boron blood clearance was 18.5 +/- 4.5 ml/min. In order to develop a model for selecting the optimum dosing paradigm, a pharmacokinetic correlation was established between the boron content of normal brain, solid tumor, and infiltrating tumor to the shallow tissue pharmacokinetic compartment (C2). Based on our model, it was concluded that although multiple i.v. infusions of BSH might increase absolute tumor boron concentrations, they will not improve the tumor: plasma boron concentration ratios over those attainable by a single i.v. infusion. The results from our study are confirmatory of those previously reported by others when blood sampling has been carried out for a sufficient period of time to adequately characterize the pharmacokinetics.
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PMID:Pharmacokinetics of sodium borocaptate: a critical assessment of dosing paradigms for boron neutron capture therapy. 1274 11

Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p<0.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p<0.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p<0.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.
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PMID:The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity. 2450 93

The novel function of the renin-angiotensin system (RAS) is cardiovascular homeostasis. While the major active mediator angiotensin II (ANG II) produces most of the physiologic responses via angiotensin II type I receptor (AT1R), recent insights have looked at the implications of ANG II and its impact on solid tumor formation. Preclinical studies have demonstrated the direct effect of ANG II on the stimulation of angiogenesis via VEGF and other proliferative mediators. RAS components have thus been identified in numerous malignant tissues. Inhibition of the AT1R via angiotensin-converting enzyme inhibitors (ACE-Is) has demonstrated a decrease in solid tumor development and metastasis. Numerous retrospective analyses have demonstrated a reduction in colorectal cancer incidence, polyp formation, and distant metastasis in patients taking inhibitors of the RAS. The use of commonly prescribed anti-hypertensive medications as a chemo-preventative medication may have a remarkable impact in the colorectal cancer community. Further investigation and prospective clinical trials may provide further insight into the potentially beneficial use of ACE-Is and their impact on colorectal cancer.
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PMID:Interactions of the renin-angiotensin system in colorectal cancer and metastasis. 2559 47

Solid tumor has unique vascular architecture, excessive production of vascular mediators, and extravasation of macromolecules from blood vessels into the tumor tissue interstitium. These features comprise the phenomenon named the EPR effect of solid tumors, described in 1986. Our investigations on the EPR revealed that many mediators, such as bradykinin, NO, and prostaglandins, are involved in the EPR effect, which is now believed to be the most important element for cancer-selective drug delivery. However, tumors in vivo manifest great diversity, and some demonstrate a poor EPR effect, for example, because of impaired vascular flow involving thrombosis, with poor drug delivery and therapeutic failure. Another important element of this effect is that it operates in metastatic cancers. Because few drugs are currently effective against metastases, the EPR effect offers a great advantage in nanomedicine therapy. The EPR effect can also be augmented two to three times via nitroglycerin, ACE inhibitors, and angiotensin II-induced hypertension. The delivery of nanomedicines to tumors can thereby be enhanced. In traditional PDT, most PSs had low MW and little tumor-selective accumulation. Our hydroxypropylmetacrylamide-polymer-conjugated-PS, zinc protoporphyrin (apparent MW >50 kDa) showed tumor-selective accumulation, as revealed by fluorescent imaging of autochthonous cancers. After one i.v. injection of polymeric PS followed by two or three xenon light irradiation/treatments, most tumors regressed. Thus, nanoprobes with the EPR effect seem to have remarkable effects. Enhancing the EPR effect by using vascular modulators will aid innovations in PDT for greater tumor-targeted drug delivery.
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PMID:A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next-Generation Chemotherapeutics and Photodynamic Therapy--Problems, Solutions, and Prospects. 2623 91

Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. There is a document that angiotensin (AT) which is found to be involved in the progression of CRC. Furthermore, Angiotensin receptor inhibitors (ARIs) and angiotensin-converting enzyme Inhibitors (ACE-Is) demonstrate activity in CRC by their inhibition of both Insulin-like growth factor 1 (IGF-1) and Vascular endothelial growth factor (VEGF), and therefore present a potentially novel therapeutic strategy in colorectal cancer, which have summarized in the current review. Preclinical studies have illustrated the direct effect of major active mediator angiotensin II (ATII) on the promotion of angiogenesis through VEGF and other proliferative mediators. Suppression of the angiotensin II type I receptor (AT1R) via ACE-Is has shown a reduction in the development of solid tumor and metastasis, particularly CRC incidence, polyp formation, and distant metastasis. MicroRNAs (miRs) are a family of small nucleotides without coding that plays an important role after transcribing hundreds to thousands of non-coding and coding gene. Against this background, the application of anti-hypertensive medications such as losartan might have a therapeutic impact, although further preclinical and clinical studies might provide novel insight into the potentially beneficial effect of ACE-Is in the treatment of colorectal cancer patients.
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PMID:The Therapeutic Potential of Angiotensin-converting Enzyme and Angiotensin Receptor Inhibitors in the Treatment of Colorectal Cancer: Rational Strategies and Recent Progress. 3063 92