Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin converting enzyme inhibitors (ACEi) prescribed for cardiovascular and renal disease since 1980 are widely atoxic and several experimental studies and one epidemiological study have demonstrated an effect of ACEi on cancer. ACEi has the effect of modifying gene expression; inhibiting proliferation and invasion of cancer cells; reducing endothelial cell migration and angiogenesis in vitro, whereas tumour growth and metastasis were inhibited in vivo. Several mechanisms of action are possible but inhibition of matrix metalloprotease activity, reduced expression of vascular endothelial growth factor and interference with the renin-angiotensin system were demonstrated by the experimental studies. In this paper we review the laboratory investigations and epidemiological studies on the anti-cancer actions of ACEi and present a summary of the evidence regarding the potential use of ACEi in cancer treatment.
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PMID:Angiotensin converting enzyme inhibitors for cancer treatment? 1516 62

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide hormone of the renin-angiotensin system with vasodilator and anti-proliferative properties. Human adenocarcinoma SK-LU-1 and A549 cells as well as non-small lung cancer SK-MES-1 cells were treated with serum in the presence and absence of Ang-(1-7), to determine whether Ang-(1-7) inhibits the growth of lung cancer cells. Ang-(1-7) caused a significant reduction in serum-stimulated growth in all three lung cancer cell lines. Treatment with Ang-(1-7) resulted in both a dose- and time-dependent reduction in serum-stimulated DNA synthesis in all three cell lines, with IC(50)'s in the sub-nanomolar range. The Ang-(1-7) receptor antagonist [D-Ala(7)]-Ang-(1-7) blocked the attenuation of the serum-stimulated DNA synthesis of SK-LU-1 cells by Ang-(1-7), while neither AT(1) nor AT(2) angiotensin receptor subtype antagonists prevented the response to the heptapeptide. MAS mRNA and protein, a receptor for Ang-(1-7), was detected in the three lung cancer cell lines, suggesting that the anti-proliferative effect of Ang-(1-7) in the cancer cells may be mediated by the non-AT(1), non-AT(2), AT((1-7)) receptor MAS. Other angiotensin peptides [Ang I, Ang II, Ang-(2-8), Ang-(3-8) and Ang-(3-7)] did not attenuate mitogen-stimulated DNA synthesis of SK-LU-1 cells, demonstrating that Ang-(1-7) selectively inhibits SK-LU-1 cancer cell growth. Pre-treatment of SK-LU-1 cells with 10 nM Ang-(1-7) reduced serum-stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2, indicating that the anti-proliferative effects may occur, at least in part, through inhibition of the ERK signal transduction pathway. The results of this study suggest that Ang-(1-7) inhibits lung cancer cell growth through the activation of an angiotensin peptide receptor and may represent a novel chemotherapeutic and chemopreventive treatment for lung cancer.
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PMID:Inhibition of human lung cancer cell growth by angiotensin-(1-7). 1528 77

Hypokalemic paralysis is a medical emergency due to the risks of cardiac arrhythmia, respiratory failure, and rhabdomyolysis. Besides supplementing patients with KCl to hasten recovery, the astute physician must search for the underlying cause to avoid missing a treatable and curable disorder. We report on an elderly Korean man who presented with marked limb paralysis, myalgias, and mild hypertension. He had prostate cancer treated with orchiectomy and hormone therapy 2 years previously. The major biochemical abnormalities were hypokalemia (K+: 1.7 mmol/l) associated with high renal K+ wasting and metabolic alkalosis (HCO3-: 42.6 mmol/l). Low plasma renin activity, low aldosterone concentration, and normal cortisol concentration pointed to a state of pseudohyperaldosteronism. While reviewing his drug history, the patient revealed he had been consuming eight packs (100 ml/pack) of a Korean herbal tonic daily to treat his prostate cancer for the past 2 months. A significant amount of glycyrrhizic acid (0.23 mg/ml), an active ingredient of licorice, was detected in the tonic. Discontinuation of the herbal tonic along with KCl supplementation achieved recovery in 2 weeks. As many complementary/alternative medicines for cancer contain licorice, this must be kept in mind as a cause of hypokalemia in cancer patients.
Support Care Cancer 2004 Nov
PMID:A hidden cause of hypokalemic paralysis in a patient with prostate cancer. 1535 80

Survival in patients with heart failure remains very poor, and is worse than that for most common cancers, including bowel cancer in men and breast cancer in women. The renin-angiotensin-aldosterone system (RAAS) is not completely blocked by angiotensin-converting enzyme (ACE) inhibition. Blockade of the RAAS at the AT1-receptor has the theoretical benefit of more effective blockade of the actions of angiotensin II. ACE inhibitors (ACE-Is) prevent the breakdown of bradykinin: this has been blamed for some of the unwanted effects of ACE-Is although bradykinin may have advantageous effects in heart failure. Consequently, ACE-Is and ARBs might be complementary or even additive treatments; recent trials have tested these hypotheses. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme compared the angiotensin receptor blocker (ARB) candesartan (target dose 32 mg once daily) to placebo in three distinct but complementary populations of patients with symptomatic heart failure. These were: patients with reduced left ventricular ejection fraction (LVEF) who were ACE-I-intolerant (CHARM-Alternative); patients with reduced LVEF who were being treated with ACE-Is (CHARM-Added); and patients with preserved left ventricular systolic function (CHARM-Preserved). There were substantial and statistically significant reductions in the primary composite end point (risk of cardiovascular death or hospital admission for heart failure) in CHARM-Alternative. This was also the case in CHARM-Added, supporting and extending the findings of Val-HeFT. In CHARM-Preserved, the effect of candesartan on the primary end point did not reach conventional statistical significance though hospital admission for heart failure was reduced significantly with candesartan. In the CHARM-Overall programme there was a statistically borderline reduction in all-cause mortality with a clear reduction in cardiovascular mortality. All-cause mortality was reduced by 12% in the two CHARM trials in patients with low LVEF. CHARM succeeded in answering a number of questions about the safety and efficacy of ARB use in heart failure. It showed evidence for a clinical benefit of candesartan both additive to and independent of ACE-I use. The benefits in terms of clinical outcomes were seen irrespective of beta-blocker usage. Benefits in patients with preserved LVEF were shown in the proportion of patients hospitalised with worsening heart failure and in overall number of admissions for heart failure. Candesartan had expected effects on blood pressure and renal function, emphasising the need for careful patient monitoring.
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PMID:Angiotensin inhibition in heart failure. 1552 37

Endometrial carcinoma is one of the most common gynecological malignancies. Most cases are diagnosed in older patients with diabetes, hypertension, or obesity. The renin-angiotensin system (RAS) has a central role controlling blood pressure and sodium homeostasis. RAS polymorphisms have been reported as genetic determinants of essential hypertension. The objective of this study was to analyze angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. The presence of an angiotensin converting enzyme (ACE) polymorphism was analyzed by polymerase chain reaction in DNA isolated from peripheral blood samples of 171 women: 70 cases with endometrial cancer (age, 63.6 +/- 9.5 years) and 101 normal control women (age, 61.3 +/- 6.4 years). We detected DD genotype in 47.5%, ID genotype in 44.3%, and II genotype in 8.2% of cases. The allele frequency was 0.69 for D allele and 0.30 for I allele. In normotensives, we found that the presence of I allele (genotypes ID and II) is significantly associated to an earlier age (56.0 +/- 10.1 versus 65.8 +/- 9.9) of onset of endometrial carcinoma (P=0.029). We observed that normotensive women carriers of an allele I have a higher risk of development of endometrial cancer under the age of 63 years (odds ratio=3.60, 95% confidence interval=1.03-12.56; P=0.037). Our findings suggest that ACE polymorphism may be associated with the development of endometrial carcinoma and with the onset of this tumor in younger women. The definition of a pharmacogenomic profile of human neoplasia may help to identify targets for the development of therapeutic or chemoprevention strategies.
Cancer Genet Cytogenet 2004 Nov
PMID:Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. 1552 1

Angiotensin-I converting enzyme inhibitors (ACE-Is) are commonly used as safe antihypertensive agents, and it has recently been suggested that they decrease the risk of cancer development. Recent studies have revealed that the renin-angiotensin system (RAS) is involved in the development of many types of tumor. Angiotensin-II (AT-II) has many biological effects, including neo-vascularization, which plays a pivotal role in tumor development. AT-II induces a potent angiogenic factor, namely the vascular endothelial growth factor (VEGF). Some studies have proven that several ACE-Is are potent inhibitors of experimental tumor development and angiogenesis at clinically comparable doses. VEGF expression in tumors is also significantly suppressed by ACE-Is. When used in combination with the conventional anti-cancer drugs, ACE-Is exert more potent anti-tumor activities as compared with either single agent, in addition to suppression of the intra-tumoral angiogenesis. Furthermore, ACE-Is reportedly not only suppress tumor growth but also attenuate the carcinogenesis process in which angiogenesis is involved. Since ACE-Is are already in widespread clinical case without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention.
Curr Cancer Drug Targets 2004 Nov
PMID:Angiotensin-I converting enzyme inhibitors as potential anti-angiogenic agents for cancer therapy. 1557 13

Our previous study demonstrated that Angiotensin II (Ang-II) which is well known to be a main peptide of the renin-angiotensin system could activate the cell proliferation of prostate cancer as well as EGF, and an Ang-II receptor blocker(ARB) could inhibit it through the suppression of phosphorylation of MAPK and STAT3. Also, ARB exerted an antiproliferative effect on prostate cancer through paracrine factors from stromal cells. We believe that ARBs have the novel ability to suppress the development or progression of prostate cancer. Furthermore, based on the idea that inhibition of G protein-coupled receptor signaling in cancer and stromal cells could suppress prostate cancer growth, a novel treatment such as molecular targeting therapy to overcome this devastating disease could be possible in the future.
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PMID:[Novel molecular targeting therapeutics for prostate cancer]. 1571 89

Improvements in abdominal imaging techniques have increased the detection of clinically inapparent adrenal masses, or incidentalomas (AI), the appropriate diagnosis and management of which have become a common clinical problem for health care professionals. Once an adrenal mass has been detected, the clinician needs to address two questions: 1) is the tumor hormonally active? and 2) is there any chance of the mass being malignant? The majority of AI is non-hypersecretory cortical adenomas, but an endocrine evaluation can lead to the identification of subtle hormone excess. An overnight low-dose dexamethasone suppression test, fractionated urinary or plasma metanephrine assay and, in hypertensive patients, establishing the upright plasma aldosterone/plasma renin activity ratio are recommended as preliminary screening steps. Masses greater than 4 cm are at greater risk of malignancy. Morphological imaging features may be helpful in the distinction between benign and malignant forms. Fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients to establish any metastatic disease. Adrenalectomy is indicated by evidence of a functional adrenal mass, or a suspected malignant form. We advocate adrenalectomy of subtle hypercortisolism, especially in the presence of hypertension, obesity, diabetes or osteoporosis potentially aggravated by glucocorticoid excess. A close follow-up is needed, particularly in the first year after diagnosis.
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PMID:A comprehensive approach to adrenal incidentalomas. 1576 28

Angiotensin II (Ang II) is a main effector peptide in the renin-angiotensin system and participates in the regulation of vascular tone. It also has a role in the expression of growth factors that induce neovascularisation which is closely associated to the growth of malignant gliomas. We have shown that the selective blockage of the AT1 receptor of angiotensin inhibits tumour growth, cell proliferation and angiogenesis of C6 rat glioma. The aim of this study was to study the effects of the blockage of AT1 receptor on the synthesis of growth factors, and in the genesis of apoptosis in cultured C6 glioma cells and in rats with C6 glioma. Administration of losartan at doses of 40 or 80 mg kg(-1) to rats with C6 glioma significantly decreased tumoral volume and production of platelet-derived growth factor, vascular endothelial growth factor and basic fibroblast growth factor. It also induced apoptosis in a dose-dependent manner. Administration of Ang II increased cell proliferation of cultured C6 cells which decreased by the administration of losartan. Our results suggest that the selective blockage of AT1 diminishes tumoral growth through inhibition of growth factors and promotion of apoptosis.
Br J Cancer 2005 Apr 11
PMID:Blockage of angiotensin II type I receptor decreases the synthesis of growth factors and induces apoptosis in C6 cultured cells and C6 rat glioma. 1578 46

Aldosterone-producing adrenocortical carcinoma (APAC) is a rare cause of hypertension often diagnosed late because of paucity of information. Thus, we delineated its clinical course and survival rates based on two cases referred to us that featured diverging clinical courses, and on a scrutiny of the literature since 1955 when the first case of APAC was identified. Data on demography, imaging results, hormonal assessment, histology, and clinical course were extracted independently by the investigators. We included in our database 58 cases, most presenting with Conn's syndrome. Plasma aldosterone levels were on average increased 14-fold; plasma renin activity was suppressed in 55% of cases. The tumor showed extremely variable size and weight, and no gender or side preference. Metastases were present in 10% of all cases at initial diagnosis and in an additional 48% of cases at follow-up. Median survival was 546 days (95% confidence interval (CI): 240-851); median time to either recurrence or death was 212 days (95% CI: 29-395). No clinical or histological signs predicted survival with Cox regression analysis. We concluded that, although an ominous course with a poor survival rate is common, no sign accurately predicts the course of APAC. Thus, molecular studies to identify diagnostic markers of survival are mandatory.
Endocr Relat Cancer 2005 Mar
PMID:Aldosterone-producing adrenocortical carcinoma: an unusual cause of Conn's syndrome with an ominous clinical course. 1578 46


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