Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective alpha(1)-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G(0)-G(1) cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to alpha-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the alpha-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory kappaB (IkappaB)-alpha expression, and nuclear factor-kappaB transcription and decreased basal and TNFalpha-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective alpha(1)-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its alpha-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-kappaB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
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PMID:Alpha1-adrenergic receptor antagonists: novel therapy for pituitary adenomas. 1602 Apr 84

Diabetes is one of the most common chronic diseases in the United States. An estimated 18.2 million people in the US (6.3%) have diabetes; among them 2.8 million are African Americans (AAs). On average, AAs are twice as likely to have diabetes as European Americans (EAs) of similar age. AAs disproportionately suffer from various diseases in the US. Many of these diseases include hypertension, cardiovascular disease (CVD), diabetes mellitus (DM-beta predominantly Type II), and cancers of the prostate and pancreas. A number of risk factors such as smoking, a high fat diet, little physical activity, stress, and meager access to health care have been the subject of numerous investigations. However, the factor of the interaction between genetics and the environment has received very little attention in the scientific community. Of note, the content of zinc in pancreatic beta gells is among the highest in the body; however, very little is known about the uptake and storage of zinc inside these cells. We hypothesize that one of the major reason AAs disproportionally suffer from DM (as well as some other illnesses like prostate cancer, CVD and hypertension) is due to their inherent inability to transport appropriate amount of zinc in the crucial cell types that require relatively higher amount of zinc than the other cell types. In this article, we will explore in detail the possible genetic and environmental link between human zinc transporters (hZIPs) and their differential expressions in the islet beta cells from AAs as compared to other racial groups, particularly EAs, in both normal healthy individuals and diabetic patients. We hypothesize that the hZIPs play an important role in the development of diabetes, and the main reason AAs disproportionately suffer from DM (as well as other illnesses like prostate and pancreatic cancers, hypertension, and CVD) as compared to EAs may be due the low degree of expressions of the critical zinc transporters in the beta cells. Understanding the molecular events in the pathogenesis of DM with regards to regulation of zinc uptake would be critical to the evaluation of the natural history of diabetes in humans and especially in various racial groups. If a direct link between zinc transport and diabetes can be established, then a special nutritional formula, medication or other intervention might be especially designed to test the ability to decrease the incidence of this disease in DM susceptible groups, particularly in AAs.
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PMID:Role of zinc and zinc transporters in the molecular pathogenesis of diabetes mellitus. 1604 3

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.
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PMID:Antiproliferative efficacy of angiotensin II receptor blockers in prostate cancer. 1610 80

Garlic has been used throughout the world to treat coughs, toothache, earache, dandruff, hypertension, hysteria, diarrhoea, dysentery, diptheria, vaginitis and many other conditions. Garlic contains a complex mixture of oil and water-soluble organosulfur compounds. Diallyl disulfide (DADS), an oil-soluble constituent of garlic seems to be effective in reducing tumour cells originating from colon, lung and skin. Hence our present study focuses on the dose-dependent effect of DADS on an androgen-dependent prostate cancer cell line. Various concentrations of DADS ranging from 25 to 100 microM were given to LNCaP cells and the activity of lactate dehydrogenase (LDH) prostatic acid phosphatase (PAcP) and the level of prostate specific antigen were studied. DADS reduced the secretory activity of LNCaP cells with the gradual increase in dosage. DADS was found to act as a good antiproliferative agent, which was confirmed by proliferation assay. DADS also induced apoptosis and nuclear segmentation in the higher doses.
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PMID:Antiproliferative effect of diallyl disulfide (DADS) on prostate cancer cell line LNCaP. 1614 93

Lycopene is a carotenoid found predominantly in tomatoes and tomato products. In contrast to beta-carotene it is not a precursor of vitamin A in humans. Lycopene is not destroyed during food processing, moreover its bioavailability improves. Lycopene is the most powerful antioxidant amongst carotenoids. Beside the antioxidant effect it influences the expression of various proteins (enzymes of biotransformation, cyclin D1, connexins). According to epidemiologic studies tomato lycopene may reduce the risk of prostate cancer and cardiovascular diseases. Positive effects are also hypothesized in case of other diseases such as osteoporosis, neurodegenerative diseases and hypertension. Neither adverse effects upon lycopene supplementation nor lycopene toxicity have been reported. Therefore, several arguments support the consumption of natural lycopene, whilst there are no contraindications according to the present knowledge.
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PMID:[Lycopene--a natural antioxidant]. 1615 10

The case of a 57-year-old male with a history significant for myeloproliferative disease, chronic renal failure, hypertension, and prostate cancer is described. His complete blood count was remarkable for neutrophilia and, notably, eosinophilia. Subsequent to two syncopal episodes, a transthoracic echocardiogram was performed as part of the workup, which showed an unusual calcified mass in the left ventricular apical region but separate from the apical myocardium, with normal left ventricular systolic function. A transesophageal echocardiogram and computed tomography of the chest confirmed the presence of extensive calcification in the left ventricle of unusual location and shape. This patient probably had Loeffler endocarditis related to myeloproliferative disorder, complicated by calcification of the endocardial sclerotic lesions.
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PMID:Left ventricular endocardial calcification in a patient with myeloproliferative disease. 1621 93

Previous studies have suggested that hyperinsulinaemia and other components of metabolic syndrome are risk factors for clinical prostate cancer. This prospective study tested the hypothesis that hyperinsulinaemia and other components of metabolic syndrome are risk factors for lethal clinical prostate cancer. The clinical, haemodynamic, anthropometric, metabolic and insulin profile at baseline in men who had died from clinical prostate cancer during follow-up was compared with the profile of men who were still alive at follow-up. If the hypothesis is true, men with an unfavourable prognosis would have a higher profile at baseline than those with a favourable prognosis. A total of 320 patients in whom clinical prostate cancer, stages T2-3, had been diagnosed were consecutively included in the study during 1995-2003. Height, body weight, waist measurement, hip measurement and blood pressure were determined. Body mass index and waist/hip ratio (WHR) were calculated. Blood samples were collected to determine triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, uric acid, alanine aminotransferase and fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual benign prostatic hyperplasia (BPH) growth rate was calculated. The diagnosis of prostate cancer was established using transrectal ultrasound-guided automatic needle biopsy of the prostate gland. All patients with clinical prostate cancer were followed up until their death or until the study was terminated on 31 December 2003. At follow-up, 54 patients had died from prostate cancer and 219 were still alive. The results showed that the men who died of clinical prostate cancer during the follow-up period were older (P < 0.001), had a larger prostate gland volume (P < 0.001), a faster BPH growth rate (P < 0.001), a higher prevalence of type 2 diabetes (P < 0.035) and treated hypertension (P < 0.023), a higher stage (P < 0.001) and grade (P = 0.028) of clinical prostate cancer, a higher prostate-specific antigen (PSA) level (P < 0.001) and a higher PSA density (P < 0.001) at baseline than men still alive with clinical prostate cancer at follow-up. These men also had a lower HDL-cholesterol level (P = 0.027), a higher fasting plasma insulin level (P = 0.004), a higher WHR (P = 0.097) of borderline significance and a higher uric acid level (P = 0.079) of borderline significance. Eliminating the effect on mortality of higher stage and grade of the clinical prostate cancer and PSA at baseline, the following statistically significant correlations remained: a higher fasting plasma insulin level (P = 0.010) and a lower HDL-cholesterol level of borderline significance (P = 0.065). In conclusion, hyperinsulinaemia and five other previously established components of metabolic syndrome are shown to be prospective risk factors for deaths that can be ascribed to prostate cancer. These findings confirm previous study, which indicate that prostate cancer is a component of metabolic syndrome. Moreover, these data indicate that hyperinsulinaemia and other metabolic disorders precede deaths caused by prostate cancer. Thus, our data support the hypothesis that hyperinsulinaemia is a promoter of clinical prostate cancer. Furthermore, our data suggest that the insulin level could be used as a marker of prostate cancer prognosis and tumour aggressiveness, regardless of the patient's prostate cancer stage, cancer grade and PSA level.
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PMID:Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. 1624 13

Immune thrombocytopenic purpura (ITP) occurs in 2-3% of chronic lymphocytic leukemia (CLL) patients, whereas autoimmune thrombocytopenia is very rare before the diagnosis of lymphoma. A 67-year-old patient, was admitted to our Department because of purpura on his inferior limbs. Family history revealed arterial hypertension, a previous presence of hepatitis C virus (HCV) antibodies, with no sign of liver damage. Physical examination showed purpura of inferior limbs. Laboratory analysis revealed: marked thrombocytopenia (platelet count 5000/microL); hypogammaglobulinemia (9%, immunoglobulin-IgG 634 mg/dL); presence of HCV antibody (negative HCV-RNA); low-titer anti-nuclear antibody and anti-smooth muscle antibody (1:80); positive cryoglobulin (polycolonal, IgG-IgM, cryocrit 0.5%). Abdomen ultrasound revealed a mild liver steatosis and bone marrow aspirate megakaryocytic hyperplasia. Platelet kinetics study showed a markedly reduced platelet half-life (<1 day) with evident splenic uptake. The patient was treated with steroids, intravenous Ig and immunosuppressive agent (cyclophosphamide) with only temporary effect; a splenectomy was therefore performed with a subsequent durable increase in the platelet count. Two years later, the patient underwent a prostatectomy for prostate cancer and within the pelvic nodal screening the histological examination unexpectedly revealed features of B-cell non-Hodgkin's lymphoma, type CCL/small lymphocytic lymphoma; a bone marrow aspirate showed a monotypic CD5+, CD19+, CD23+ B-cell proliferation confirming the diagnosis of CLL. Six months later, a computed tomography scan revealed multiple pathological node enlargements (1.5-3 cm), compatible with a malignant lymphoma. The marked thrombocytopenia may have been an early expression of the lymphoproliferative disease. Otherwise, the association between CLL and ITP might reflect the underlying role of HCV infection causing an immune dysregulation responsible for both pathologies.
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PMID:Association between immune thrombocytopenic purpura and chronic lymphocytic leukemia in a patient carrier of anti-hepatitis C virus antibodies. 1625 Jan 87

Erectile dysfunction (ED) is a highly prevalent condition in aging men with significant interpersonal and psychosocial consequences. Large-scale epidemiologic studies have demonstrated a consistent age-related loss of erectile function in men from different geographic and ethnic backgrounds, with approximately half of men over 70 years of age reporting moderate to severe symptoms. ED is associated strongly with specific comor-bidities, such as cardiovascular disease and hypertension, diabetes mellitus, lower urinary tract symptoms, prostate cancer, and depression. Lifestyle factors, including obesity and exercise frequency, also have been implicated in recent studies.
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PMID:Epidemiology of erectile dysfunction: the role of medical comorbidities and lifestyle factors. 1629 Oct 33

Since the mid-1980s, permanent prostate brachytherapy has been utilized increasingly as a potentially curative treatment for patients of all ages with clinically localized prostate cancer To determine the 8-year biochemical progression-free survival rate for patients who had undergone monotherapeutic brachytherapy for clinically organ-confined prostate cancer, we conducted a study of 202 patients at Schiffler Cancer Center at Wheeling Hospital in Wheeling, W.Va. These patients had undergone brachytherapy without supplemental external beam radiation therapy or androgen deprivation therapy for clinical T1b-T2c NxM0 (2002 AJCC) prostate cancer from April 1995 through May 2001. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 5.2 years. All patients underwent brachytherapy more than 3 years prior to analysis. Biochemical success was defined as a PSA < 0.4 ng/mL after a nadir. Clinical, treatment and dosimetric parameters evaluated for biochemical progression-free survival included patient age, clinical T-stage, Gleason score, pretreatment PSA, risk group, percent positive biopsies, isotope, prostate volume, brachytherapy planning volume, V100/150/200, D90, tobacco status, hypertension and diabetes. For the entire group, 8-year biochemical progression-free survival was 97.4% for Pd-103 and 93.3% for I-125. The median post-treatment PSA for the entire group was < 0.1 ng/mL. In multivariate analysis, only pretreatment PSA predicted biochemical outcome with a trend for better outcome with younger patient age and lesser percent positive biopsies. The results of our study indicate that permanent interstitial brachytherapy as a monotherapeutic approach for patients with clinically organ-confined disease results in a high probability of 8-year biochemical progression-free survival with a median PSA < 0.1 ng/mL. Generous periprostatic treatment margins with documented high quality day 0 postoperative dosimetry are mandatory for such outcomes.
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PMID:Monotherapeutic brachytherapy for clinically organ-confined prostate cancer. 1629 98


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