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

In this study we have analyzed 84 patients (58 women, 26 men, mean age 57 +/- 1.1 year) hospitalized in the Department of Nephrology, Endocrinology and Metabolic Diseases of the Medical University of Silesia in Katowice from 01.01.1999 to 30.04.2003 because of incidentally discovered adrenal tumors (incidentaloma). The diameter of the tumors ranged from 8 to 86 mm (mean size 35.4 +/- 1.8 mm). Unilateral tumors were found in 74 patients and bilateral ones in 10 patients. In all patients circadian rhythm of plasma cortisol concentration and urinary cortisol excretion were measured. In 73 patients with a history of hypertension plasma renin activity was estimated in basal conditions and after stimulation by sodium restriction and upright position. Aldosteronemia and urinary metoxycatecholamines excretion were also determined. 45 patients with tumors >4 cm and/or with suspicion of malignancy or hormonal hypersecretion were qualified for surgical treatment. Thirty two patients out of the selected 45 have been operated so far. In two patients histopathological examination confirmed malignancy (adrenocortical carcinoma in one patient and metastatic cancer in the other one). The remaining 30 patients were operated because of size of the adrenal mass (16 patients) or biochemical suspicion of pheochromocytoma (12 patients, 5 of them with the mass size >4 cm) or primary aldosteronism (2 patients). The histological examination confirmed Conn syndrome in two patients and pheochromocytoma in one patient.
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PMID:[Clinical, biochemical and hormonal characteristics of 84 patients with incidentally found adrenal tumor (incidentaloma)]. 1596 10

We previously demonstrated that pleiotrophin (PTN the protein, Ptn the gene) highly regulates the levels of expression of the genes encoding the proteins of the renin-angiotensin pathway in mouse aorta. We now demonstrate that the levels of expression of these same genes are significantly regulated in mouse aorta by the PTN family member midkine (MK the protein, Mk the gene); a 3-fold increase in expression of renin, an 82-fold increase in angiotensinogen, a 6-fold decrease in the angiotensin converting enzyme, and a 6.5-fold increase in the angiotensin II type 1 and a 9-fold increase in the angiotensin II type 2 receptor mRNAs were found in Mk-/- mouse aorta in comparison with the wild type (WT, +/+). The results in Mk-/- mice are remarkably similar to those previously reported in Ptn-/- mouse aorta, with the single exception of that the levels of the angiotensinogen gene expression in Ptn-/- mice are equal to those in WT+/+ mouse aorta, and thus, in contrast to Mk gene expression unaffected by levels of Ptn gene expression. The data indicate that MK and PTN share striking but not complete functional redundancy. These data support potentially high levels importance of MK and the MK/PTN developmental gene family in downstream signals initiated by angiotensin II either in development or in the many pathological conditions in which MK expression levels are increased, such as atherosclerosis and many human neoplasms that acquire constitutive endogenous Mk gene expression by mutation during tumor progression and potentially provide a target through the renin-angiotensin pathway to treat advanced malignancies.
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PMID:Midkine, a newly discovered regulator of the renin-angiotensin pathway in mouse aorta: significance of the pleiotrophin/midkine developmental gene family in angiotensin II signaling. 1597 60

The Eighth European Meeting on Hypertension, held in Milan, Italy, was attended by approximately 4000 people. The programme consisted of 120 presentations, 337 poster sessions, 6 invited lectures/debates (endothelin antagonists; cardiac renin-angiotensin system; cancer and hypertension; adducin; angiotensin converting enzyme (ACE) gene polymorphism; pulse pressure) and 2 plenary sessions on 'sleep apnea and hypertension' and 'treatment of hypertension in the elderly'.
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PMID:Eighth European meeting on hypertension. 1598 69

In patients with chronic renal failure, cancer incidence is increased. This may be related to an elevated level of genomic damage, which has been demonstrated by micronuclei formation as well as by comet assay analysis. Advanced glycation end products (AGEs) are markedly elevated in renal failure. In the comet assay, the model AGEs methylglyoxal- and carboxy(methyl)lysine-modified bovine serum albumin (BSA) induced significant DNA damage in colon, kidney, and liver cells. The addition of antioxidants prevented AGE-induced DNA damage, suggesting enhanced formation of reactive oxygen species (ROS). The coincubation with dimethylfumarate (DMF), an inhibitor of NF-kappaB translocation, reduced the genotoxic effect, thereby underscoring the key role of NF-kappaB in this process. One of the genes induced by NF-kappaB is angiotensinogen. The ensuing proteolytic activity yields angiotensin II, which evokes oxidative stress as well as proinflammatory responses. A modulator of the renin-angiotensin system (RAS), the angiotensin II (Ang II) receptor 1 antagonist, candesartan, yielded a reduction of the AGE-induced DNA damage, connecting the two signal pathways, RAS and AGE signaling. We were able to identify important participants in AGE-induced DNA damage: ROS, NF-kappaB, and Ang II, as well as modulators to prevent this DNA damage: antioxidants, DMF, and AT1 antagonists.
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PMID:Genotoxicity of advanced glycation end products: involvement of oxidative stress and of angiotensin II type 1 receptors. 1603 94

An apparent low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors is reported; however, the molecular mechanisms have not been elucidated. Angiotensin-II (Ang-II) is well known to be associated with hypertension, as a main peptide of the renin-angiotensin system, and its detailed molecular mechanisms have recently been elucidated. For instance, Ang-II directly activates the mitogenic signal transduction pathway through the angiotensin-II type-1 (AT1) receptor in smooth muscle cells and cardiac myocytes. Ang-II receptor blockers (ARBs), a class of antihypertensive agent, suppress signal transduction pathways mediated by growth factors such as epidermal growth factor (EGF), through the AT1 receptor. Our studies demonstrated that an ARB had the potential for antiproliferative effects and inhibition of angiogenesis in prostate cancer cells. The AT1 receptor is categorized in the guanosine phosphate binding protein-coupled receptors (GPCRs), which are viewed as critical regulators of the interactions between epithelial and stromal cells. Hence, we consider that in overcoming prostate cancer, it is very important to inhibit GPCR signaling in cancer cells by ARBs. It is unclear how prostate cancer growth changes from being hormone dependent to independent, and no effective therapy has therefore been developed. Our clinical data revealed that ARB administration decreased prostate specific antigen (PSA) and improved performance status in patients with hormone-refractory prostate cancer. This review provides an insight into the key role of Ang-II and the possibility of ARBs for molecular targeting of mitogenesis and angiogenesis in prostate cancer.
Curr Cancer Drug Targets 2005 Aug
PMID:Antiproliferative efficacy of angiotensin II receptor blockers in prostate cancer. 1610 80

The mechanism behind iodinated radiocontrast nephropathy remains elusive. Direct oxidative damage is the prevailing hypothesis, but the apparent protective effect of iodine against oxidation contradicts this view. We propose that autonomic dysfunction participates in the pathogenesis of radiocontrast nephropathy and may account for other contrast-associated reactions previously attributed to allergy. Iodine, through its effects on thyroid function and chemoreceptor response to metabolic acidosis, may induce hyperadrenergia and consequently diminish renovascular flow and urine output. The renal response to adrenergia likely served an adaptive function during prehistoric evolution when trauma was a dominant source of hypovolemia and adrenergia, but the response may behave maladaptively today as evolutionarily nai ve triggers for adrenergia have emerged. Autonomic dysfunction can further impair renal function by deranging renovascular autoregulation and inducing oxidative reperfusion injury as a secondary phenomenon. Many other causes of acute renal failure such as drug toxicity, surgery, hospitalization, and diabetes may operate through hyperadrenergia, impaired renovascular autoregulation, and oxidative reperfusion injury. Dialysis, a volume reduction therapy for renal failure, can counterintuitively worsen renal dysfunction by exacerbating adrenergia, which may explain its association with accelerated atherosclerosis, inflammation, and cancer. Other examples of vicious cycles that perpetuate renal dysfunction may include renal artery stenosis, carotid stenosis, and atherosclerosis as well as the cardio-renal, hepato-renal, and pulmonary-renal syndromes. The benefits of hydration and bicarbonate in protecting renal function may operate in part through baroreceptor- and chemoreceptor-mediated reduction of sympathovagal ratio, respectively. New treatment paradigms for renal failure including pharmacologic and electro-mechanical therapies are envisioned based on autonomic remodeling, reduced sympathovagal ratio, and neuromodulation of pathways typically associated with trauma such as renin, angiotensin, vasopressin, and aldosterone.
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PMID:Contrast nephropathy may be partly mediated by autonomic dysfunction: renal failure considered as a modern maladaptation of the prehistoric trauma response. 1633 Jan 57

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.
Br J Cancer 2006 Feb 27
PMID:Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival. 1643 90

Angiotensin II (Ang II), a main effector peptide in the renin-angiotensin system (RAS), plays a fundamental role as a vasoconstrictor in controlling cardiovascular function and renal homeostasis. Ang II also acts as a growth promoter or angiogenic factor via type 1 angiotensin II receptors (AT1Rs) in certain tumour cell lines. Recent studies have shown the activation of the local RAS in various tumour tissues, including the abundant generation of Ang II by angiotensin-converting enzyme (ACE) and the upregulation of AT1R expression. Thus, considerable attention has been paid to the role of the RAS in cancer and its blockade as a new approach to the treatment of cancer. There is increasing evidence that the Ang II-AT1R system is involved in tumour growth, angiogenesis and metastasis in experimental models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker, both of which have been used as antihypertensive drugs. In addition, specific Ang II-degrading enzymes are expressed in tumours and play a regulatory role in cell proliferation and invasion. This review focuses on the role of the Ang II-AT1R system in solid tumours, particularly in the progression of gynaecological cancer, and presents the clinical potential of manipulating the angiotensin system as a novel and promising strategy for cancer treatment.
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PMID:Manipulating the angiotensin system--new approaches to the treatment of solid tumours. 1650 34

Angiotensin II has mitogenic and angiogenic effects and its receptors are widespread, particularly in epithelial tissue. Tissue renin angiotensin systems (tRASs) may be a local source of angiotensin II that has specific paracrine functions. To investigate the presence of a tRAS in normal human breast and tumours. Immunocytochemistry, and quantitative RT-PCR was used to establish: (i) the presence and localisation of RAS components, (ii) the possibility of their involvement in cancer. (1) mRNA coding for angiotensinogen, prorenin, angiotensin converting enzyme (ACE), and both AT1 and AT2 receptors was demonstrated in normal and diseased breast tissues. (2) (pro)renin was identified in epithelial cells in both normal and diseased tissue, but in invasive carcinoma, its distribution was mostly confined to fibroblasts or could not be detected at all. (3) Angiotensin converting enzyme was shown in epithelial cells in both normal and malignant tissue. The results are consistent with the hypothesis that a tRAS is present in the breast, and is disrupted in invasive cancer.
Br J Cancer 2006 Jul 03
PMID:Localisation of renin-angiotensin system (RAS) components in breast. 1675 91

Cathepsin B is an abundant and ubiquitously expressed cysteine peptidase of the papain family. It is involved in many physiological processes, such as remodeling of the extracellular matrix (wound healing), apoptosis, and activation of thyroxine and renin. In addition to its physiological roles, cathepsin B is important in many pathological processes, such as inflammation, parasite infection and cancer, where it is highly up-regulated. In cancer patients, elevated cathepsin B activity correlates to poor therapy outcome. Therefore, it is not surprising that the use of cathepsin B inhibitors reduces both tumor cell motility and invasiveness in vitro. This review summarizes recent developments in cathepsin B inhibition. To date, numerous protein inhibitors of cathepsin B have been described, some of which are of endogenous origin and function as regulators of cathepsin B activity in the cell, such as the cystatins. In addition, some exogenous protein inhibitors of cathepsin B have been isolated from various natural sources, and the use of X-ray crystal structures of cathepsin B complexed with such protein inhibitors has resulted in the design and synthesis of many new small-molecular-weight compounds as inhibitors of cathepsin B. These synthetic compounds generally contain an electrophilic functionality that reacts with cathepsin B. In the present review, these inhibitors are divided according to their mechanisms of action, as reversible and irreversible, and then further subdivided into groups for their full descriptions.
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PMID:Inhibitors of cathepsin B. 1691 57


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