Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

16 patients with advanced carcinoma of the prostate were studied in a prospective trial during treatment with oestrogens. Changes in plasma levels of gonadotropins (LH and FSH) and testosterone as well as salt-water balance, antithrombin III, fibrinolytic activity, plasma lipoproteins known to influence the risk of cardiovascular complications, were recorded during the initial 2 months. The plasma testosterone, LH and FSH concentrations were suppressed. The plasma volume was increased and the plasma albumin concentration was decreased. The antithrombin III concentration and the tissue fibrinolytic activity were decreased. The low density lipoprotein (LDL) level decreased and the high density lipoprotein (HDL) level increased. The recorded changes of cardiovascular risk factors indicate that the risk of water retention and thereby congestive heart failure and the risk for thromboembolic disease are increased during oestrogen treatment. The changes in lipoproteins with a marked elevation of the HDL/LDL ratio are thought to retard the development of atherosclerosis.
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PMID:[Effects of oestrogens on cardiovascular risk factors in patients with carcinoma of the prostate (author's transl)]. 680 22

The purpose of the present study was to perform a BPH risk factor analysis in men, relating the prostate gland volume to components of the metabolic syndrome and to identify clues to the etiology of BPH. Our material comprised a consecutive series of 158 patients with lower urinary tract symptoms with or without manifestations of the metabolic syndrome. In this group, the measured volume of the prostate was related consecutively to potential risk factors. The diagnoses atherosclerosis, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained from the patient's medical history. Data on blood pressure, waist and hip measure, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, cholesterol, triglycerides, HDL and LDL-cholesterol, uric acid and ALAT. The prostate gland volume was determined using ultrasound. Our results show that there was a larger prostate gland in men with NIDDM (P=0.0058), treated hypertension (P=0.0317), obesity (P<0.0001), low HDL-cholesterol levels (P=0.0132) and high insulin levels (P<0.0001) than in men without these conditions. The prostate gland volume correlated positively with the systolic blood pressure (r(s)=0.17; P=0.03), obesity (r(s)=0.34; P<0.0001) and fasting insulin (r(s)=0.38; P<0.0001) and negatively with HDL-cholesterol (r(s)=-0.22; P=0.009). On the basis of our findings, we concluded that NIDDM, treated hypertension, obesity, low HDL-cholesterol levels and high insulin levels constitute risk factors for the development of BPH. The results suggest that BPH is a facet of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinemia as patients with the metabolic syndrome. The findings generate a hypothesis of a causal relationship between high insulin levels and the development of BPH. In a clinical setting, the findings of the present report suggest that, in any patient presenting with BPH, the possible presence of NIDDM, hypertension, obesity, high insulin and low HDL-cholesterol levels should be considered. Conversely, in patients suffering from these conditions, the possibility of a clinically important BPH should be kept in mind.
Prostate Cancer Prostatic Dis 1998 Mar
PMID:Components of the metabolic syndrome-risk factors for the development of benign prostatic hyperplasia. 1249 10

To review the current literature regarding the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), and the role of phosphodiesterase-5 (PDE5) inhibitors for the treatment of LUTS. Review of recently published (1990-2009) data regarding epidemiologic and pathophysiologic mechanisms are involved in LUTS-ED, focusing on PDE5 inhibitors particularly evidenced from level 1 clinical trials. Search terms included phosphodiesterase inhibitors, nitric oxide, autonomic hyperactivity, Rho-kinase, atherosclerosis, LUTS, benign prostatic hypertrophy, and ED. Results of several epidemiologic studies show a possible causal relationship between LUTS and ED. Four possible mechanisms have been proposed to explain this association. Multiple large clinical trials have shown a benefit in LUTS after PDE5-inhibitors treatment. PDE5 inhibitors show promise as a future treatment for LUTS, either in conjunction with existing therapies or as a primary treatment.
Prostate Cancer Prostatic Dis 2009
PMID:PDE5 inhibitors for LUTS. 1968 1

A mounting body of evidence suggests that increased production of reactive oxygen species (ROS) is linked to aging processes and to the etiopathogenesis of aging-related diseases, such as cancer, diabetes, atherosclerosis and degenerative diseases like Parkinson's and Alzheimer's. Excess ROS are deleterious to normal cells, while in cancer cells, they can lead to accelerated tumorigenesis. In prostate cancer (PC), oxidative stress, an innate key event characterized by supraphysiological ROS concentrations, has been identified as one of the hallmarks of the aggressive disease phenotype. Specifically, oxidative stress is associated with PC development, progression and the response to therapy. Nevertheless, a thorough understanding of the relationships between oxidative stress, redox homeostasis and the activation of proliferation and survival pathways in healthy and malignant prostate remains elusive. Moreover, the failure of chemoprevention strategies targeting oxidative stress reduced the level of interest in the field after the recent negative results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial. Therefore, a revisit of the concept is warranted and several key issues need to be addressed: The consequences of changes in ROS levels with respect to altered redox homeostasis and redox-regulated processes in PC need to be established. Similarly, the key molecular events that cause changes in the generation of ROS in PC and the role for therapeutic strategies aimed at ameliorating oxidative stress need to be identified. Moreover, the issues whether genetic/epigenetic susceptibility for oxidative stress-induced prostatic carcinogenesis is an individual phenomenon and what measurements adequately quantify prostatic oxidative stress are also crucial. Addressing these matters will provide a more rational basis to improve the design of redox-related clinical trials in PC. This review summarizes accepted concepts and principles in redox research, and explores their implications and limitations in PC.
Prostate Cancer Prostatic Dis 2013 Sep
PMID:Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics. 2367 Feb 56

High mobility group box 1 (HMGB1) was originally discovered as a chromatin-binding protein several decades ago. It is now increasingly evident that HMGB1 plays a major role in several disease conditions such as atherosclerosis, diabetes, arthritis, sepsis, and cancer. It is intriguing how deregulation of HMGB1 can result in a myriad of disease conditions. Interestingly, HMGB1 is involved in cell proliferation, angiogenesis, and metastasis during cancer progression. Furthermore, HMGB1 has been demonstrated to exert intracellular and extracellular functions, activating key oncogenic signaling pathways. This paper focuses on the role of HMGB1 in prostate cancer development and highlights the potential of HMGB1 to serve as a key target for prostate cancer treatment.
Prostate Cancer 2013
PMID:HMGB1: A Promising Therapeutic Target for Prostate Cancer. 2376 11

The genetic risk for prostate cancer has been governed by a few rare variants with high penetrance and over 150 commonly occurring variants with lower impact on risk; however, most of these variants have been identified in studies containing exclusively European individuals. People of non-European ancestries make up less than 15% of prostate cancer GWAS subjects. Across the globe, incidence of prostate cancer varies with population due to environmental and genetic factors. The discrepancy between disease incidence and representation in genetics highlights the need for more studies of the genetic risk for prostate cancer across diverse populations. To better understand the genetic risk for prostate cancer across diverse populations, we performed PrediXcan and GWAS in a case-control study of 4,769 self-identified African American (2,463 cases and 2,306 controls), 2,199 Japanese American (1,106 cases and 1,093 controls), and 2,147 Latin American (1,081 cases and 1,066 controls) individuals from the Multiethnic Genome-wide Scan of Prostate Cancer. We used prediction models from 46 tissues in GTEx version 8 and five models from monocyte transcriptomes in the Multi-Ethnic Study of Atherosclerosis. Across the three populations, we predicted 19 gene-tissue pairs, including five unique genes, to be significantly (lfsr < 0.05) associated with prostate cancer. One of these genes, NKX3-1, replicated in a larger European study. At the SNP level, 110 SNPs met genome-wide significance in the African American study while 123 SNPs met significance in the Japanese American study. Fine mapping revealed three significant independent loci in the African American study and two significant independent loci in the Japanese American study. These identified loci confirm findings from previous GWAS of prostate cancer in diverse populations while PrediXcan-identified genes suggest potential new directions for prostate cancer research in populations across the globe.
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PMID:Multi-ethnic transcriptome-wide association study of prostate cancer. 3298 14