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)

Obesity is currently reaching epidemic levels worldwide and is a major predisposing factor for a variety of life-threatening diseases including diabetes, hypertension and cardiovascular diseases. Recently, it has also been suggested to be linked with cancer. Epidemiological studies have shown that obesity increases the risk of colon cancer by 1.5-2 fold with obesity-associated colon cancer accounting for 14-35% of total incidence. Several factors, altered in obesity, may be important in cancer development including increased levels of blood insulin, insulin-like growth factor I, leptin, TNF-alpha, IL-6 as well as decreased adiponectin. A unifying characteristic of all these factors is that they increase the activity of the PI3K/Akt signal pathway. The PI3K/Akt signal pathway in turn activates signals for cell survival, cell growth and cell cycle leading to carcinogenesis. Here we review the evidence that PI3K/Akt and its downstream targets are important in obesity-associated colon cancer and thus, that targeted inhibition of this pathway could be employed for the prevention of obesity-associated colon cancer and incorporated into the therapy regime for those with irremovable colon cancers.
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PMID:Obesity, the PI3K/Akt signal pathway and colon cancer. 1952 47

Oral squamous cell carcinoma (OSCC), a common malignancy worldwide, is an important contributor to the overall international cancer burden. Squamous cell carcinomas (SCCs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in the HBP reiterate many of the features observed in human OSCCs. The major risk factors associated with human oral cancer such as tobacco, betel quid and alcohol promote HBP carcinogenesis. SCCs induced by DMBA in the cheek pouch of Syrian hamsters are morphologically and histologically similar to human OSCC. Like human oral carcinogenesis, HBP carcinogenesis is a multistep process that involves sequential progression from hyperplasia to invasive carcinoma through varying degrees of dysplasia. In addition, HBP tumours express several biochemical and molecular markers that are also expressed in human OSCC. Multiple signaling pathways are dysfunctional in both human and hamster OSCCs. In particular, cell proliferation, apoptosis and angiogenesis are intricately interlinked in malignant transformation of the HBP mucosa by DMBA. The HBP carcinogenesis model is the best-known animal system for intervention by chemopreventive agents because of easy accessibility for examination, and follow-up of lesions. A number of synthetic and natural products have been documented to exhibit chemopreventive efficacy in the HBP model. Chemoprevention studies in the HBP model can serve as a crucial link in the potential efficacy assessment of candidate agents for oral cancer prevention and therapy.
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PMID:Of humans and hamsters: the hamster buccal pouch carcinogenesis model as a paradigm for oral oncogenesis and chemoprevention. 1953 66

Smoking, one of the avoidable causes of mortality, is considered a major risk factor for cardiovascular diseases, chronic obstructive pulmonary diseases, and bronchopulmonary cancer. Many studies suggest that nicotine induces vasoconstriction, not only in coronary arteries but also in peripheral vessels, hypertension, pro-atherogenic effects, due to increase of platelet activation and fatty acids concentration, alterations of endothelial-cell shapes, as well as endothelial-cell proliferation. The main affected vascular biochemical parameters are: endothelin-1, cholesterol, triglycerides, lipoproteins, C-reactive protein, nitric oxide, fibrinogen, and uric acid. Cigarette smoke induces inflammation in respiratory epithelium, through local irritation due to release of oxidants, aldehydes, acids, ammonium; impaired ciliar function, and retention of mucus and toxins, followed by infection; carcinogenesis due to oncogene-expression induced by oxidants, aromatic hydrocarbons, and nitrosamines. These effects are induced by alterations of endothelin-1, nitric oxide, IL1, IL6, TNF, and the CYP Enzyme System. Saliva is the first biological fluid encountered by the cigarette smoke. In vitro and in vivo salivary exposure to cigarette smoke has been shown to determine changes of concentrations of lactate dehydrogenase, amylase, and uric acid, in saliva--important factors of the antioxidant salivary system. Such changes may promote occurrence of upper digestive cancers.
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PMID:[The role of smoking in changing essential parameters in body homeostasis]. 1963 60

Hypertension is a known risk factor for renal cell carcinoma (RCC), although the underlying biological mechanisms of its action are unknown. To clarify the role of hypertension in RCC, we examined the risk of RCC in relation to 142 single-nucleotide polymorphisms (SNPs) in eight genes having a role in blood pressure control. We analyzed 777 incident and histologically confirmed RCC cases and 1035 controls who completed an in-person interview as part of a multi-center, hospital-based case-control study in Central Europe. Genotyping was conducted with an Illumina GoldenGate Oligo Pool All assay using germ line DNA. Of the eight genes examined, AGT (angiotensinogen) was most strongly associated with RCC (minimum P-value permutation test = 0.02). Of the 17 AGT tagging SNPs considered, associations were strongest for rs1326889 [odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.15-1.58] and rs2493137 (OR = 1.31, 95% CI = 1.12-1.54), which are located in the promoter. Stratified analysis revealed that the effects of the AGT SNPs were statistically significant in participants with hypertension or high body mass index (BMI) (> or =25 kg/m(2)), but not in subjects without hypertension and with a normal BMI (<25 kg/m(2)). Also, haplotypes with risk-conferring alleles of markers located in the promoter and intron 1 regions of AGT were significantly associated with RCC compared with the common haplotype in subjects with hypertension or high BMI (global P = 0.003). Our findings suggest that common genetic variants of AGT, particularly those in the promoter, increase RCC risk among subjects who are hypertensive or overweight.
Carcinogenesis 2010 Apr
PMID:Variants in blood pressure genes and the risk of renal cell carcinoma. 2004 54

Oct-4 is a transcription factor considered to be one of the defining pluripotency markers in embryonic stem cells. Its expression has also been demonstrated in adult stem cells, tumorigenic cells, and, most recently and controversially, in somatic cells. Oct-4 pseudogenes also contribute to carcinogenesis. Oct-4 may be involved in the excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) in patients with idiopathic pulmonary arterial hypertension (IPAH), contributing to the pathogenesis of IPAH. In this study, we show that Oct-4 isoforms are upregulated in IPAH-PASMC. Human embryonic stem cells (H9 line) and human PASMC from normotensive subjects were used throughout the investigation as positive and negative controls. In addition to significant upregulation of Oct-4 in a population of IPAH-PASMC, HIF-2alpha, a hypoxia-inducible transcription factor that has been shown to bind to the Oct-4 promoter and induces its expression and transcriptional activity, was also increased. Interestingly, a substantial upregulation of Oct-4 isoforms and HIF-2alpha was also observed in normal PASMC exposed to chronic hypoxia. In conclusion, the data suggest that both Oct-4 isoforms are upregulated and potentially have a significant role in the development of vascular abnormalities associated with the pathogenesis of IPAH and in pulmonary hypertension triggered by chronic hypoxia.
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PMID:Upregulation of Oct-4 isoforms in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension. 2013 78

Vanadium, a dietary micronutrient, is yet to be established as an essential part of the human diet. Over the past century, several biological effects of vanadium, such as insulin-mimetic action as well as amelioration of hyperlipidemia and hypertension, have been discovered. This transition element is known to influence a battery of enzymatic systems, namely phosphatases, ATPases, peroxidases, ribonucleases, protein kinases and oxidoreductases. Multiple biochemical and molecular actions of vanadium have been implicated in its inhibitory effects on various tumor cells of human origin. Successful in vitro studies over the past few decades have advanced the anticancer research on vanadium into the preclinical stage. Vanadium in several animal cancer models provides protection against all stages of carcinogenesis--initiation, promotion, and progression. This review focuses on the current advances in cancer prevention and treatment as well as early detection by vanadium compounds in preclinical animal models while pointing to possible mechanisms of such diverse beneficial effects. Clinical pharmacokinetic and potential toxicity studies on vanadium are also highlighted in this review. Supporting and challenging evidence as well as future directions of vanadium research exploring the possibility of using this dietary agent for detection, prevention and treatment of human cancers are critically discussed.
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PMID:Vanadium in the detection, prevention and treatment of cancer: the in vivo evidence. 2020 39

After more than two decades of rising rates, in recent years the total kidney cancer incidence worldwide has shown signs of stabilizing, or even decreasing. In adults, kidney cancer consists of renal cell carcinoma (RCC), the predominant form, and renal transitional cell carcinoma (RTCC); these types primarily arise in the renal parenchyma and renal pelvis, respectively. Although temporal trends by kidney cancer type are not well established worldwide, incidence of RCC in the US has continued to rise, mainly for early-stage tumors, while that of RTCC has declined, and total kidney cancer mortality rates have leveled. Stabilization of kidney cancer mortality rates has also been reported in Europe. These trends are consistent with reports of increasing incidental diagnoses and a downward shift in tumor stage and size in clinical series. The changing prevalence of known risk factors for RCC, including cigarette smoking, obesity, and hypertension, is also likely to affect incidence trends, although their relative impact may differ between populations. Accumulating evidence suggests an etiologic role in RCC for physical activity, alcohol consumption, occupational exposure to trichloroethylene, and high parity among women, but further research is needed into the potential causal effects of these factors. Genetic factors and their interaction with environmental exposures are believed to influence risk of developing RCC, but a limited number of studies using candidate-gene approaches have not produced conclusive results. Large consortium efforts employing genome-wide scanning technology are underway, which hold promise for novel discoveries in renal carcinogenesis.
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PMID:Epidemiology and risk factors for kidney cancer. 2044 58

Agents that are safe, affordable, and efficacious are urgently needed for the prevention of chronic diseases such as cancer. Sesamin, a lipid-soluble lignan, is one such agent that belongs to a class of phytoestrogens, isolated from sesame (Sesamum indicum), and has been linked with prevention of hyperlipidemia, hypertension, and carcinogenesis through an unknown mechanism. Because the transcription factor NF-kappaB has been associated with inflammation, carcinogenesis, tumor cell survival, proliferation, invasion, and angiogenesis of cancer, we postulated that sesamin might mediate its effect through the modulation of the NF-kappaB pathway. We found that sesamin inhibited the proliferation of a wide variety of tumor cells including leukemia, multiple myeloma, and cancers of the colon, prostate, breast, pancreas, and lung. Sesamin also potentiated tumor necrosis factor-alpha-induced apoptosis and this correlated with the suppression of gene products linked to cell survival (e.g., Bcl-2 and survivin), proliferation (e.g., cyclin D1), inflammation (e.g., cyclooxygenase-2), invasion (e.g., matrix metalloproteinase-9, intercellular adhesion molecule 1), and angiogenesis (e.g., vascular endothelial growth factor). Sesamin downregulated constitutive and inducible NF-kappaB activation induced by various inflammatory stimuli and carcinogens, and inhibited the degradation of IkappaBalpha, the inhibitor of NF-kappaB, through the suppression of phosphorylation of IkappaBalpha and inhibition of activation of IkappaBalpha protein kinase, thus resulting in the suppression of p65 phosphorylation and nuclear translocation, and NF-kappaB-mediated reporter gene transcription. The inhibition of IkappaBalpha protein kinase activation was found to be mediated through the inhibition of TAK1 kinase. Overall, our results showed that sesamin may have potential against cancer and other chronic diseases through the suppression of a pathway linked to the NF-kappaB signaling.
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PMID:Sesamin manifests chemopreventive effects through the suppression of NF-kappa B-regulated cell survival, proliferation, invasion, and angiogenic gene products. 2046 Apr 1

Oesophageal squamous cell carcinoma (OSCC) remains a public health problem in many countries, especially in emerging and developing countries. Epidemiology of OSCC is characterized by marked differences in prevalence between countries/regions/ethnical groups. The highest incidence in the world is reached by populations living in specific areas of northwestern Xinjiang, China where age-adjusted mortality may reach 150 of 100 000. In fact, there are also marked differences among the various geographical areas and the various ethnic groups within the region, which suggests specific risk factors. Behavioural factors include those factors which are common to all 'high-risk populations', such as tobacco smoking and alcohol drinking. However, the very unusual sex ratio (1.2 : 1.0) and young age range of OSCC occurrence suggests the involvement of additional early risk factors shared by males and females, and which are different from those studied in other 'high-risk' areas of the world, including China, such as LinXian area. These include drinking very hot and salted tea, boiled with milk; a diet rich in meat, especially salted, dry and/or smoked meat, and dairy products; and a diet poor in fresh fruit and vegetables. The combination of hot drinks (such as milk, tea and soups) and high-degree spirit drinks, and hard food (bread, meat and cheese), together with poor oral hygiene and tooth loss, is likely to add mechanical injury of the oesophagus to other factors linked to climate characteristics of the area (drought) and dietary habits, which promote a sodium and nitrosamine-rich diet. Association of early and severe hypertension in the same populations at high risk of OSCC might likely raise more attention. Human papilloma virus (HPV) infection, and especially HPV 16/18 E6/E7, with gene mutations and association with p53 overexpression, may contribute to the extremely high incidence of OSCC observed in Xinjiang, and could be accessible to prevention. Infection may especially be a crucial additional factor in the Uygur population in which not only HPV infection but also infection with other oncogenic viruses, such as HHV8, are highly prevalent. Genetic polymorphism might interact with viruses and/or viral products to promote carcinogenesis. These observations in northwestern China suggest that usually neglected factors, such as sodium excess and viral infection, could be taken into more account when studying OSCC risk factors in other parts of the world, especially Europe.
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PMID:Northwestern China: a place to learn more on oesophageal cancer. Part one: behavioural and environmental risk factors. 2052 May 61

The aim of this study is to investigate the relationships between hypertension, hypertension medication and bladder cancer risk in a population-based case-control study conducted in Los Angeles. Non-Asians between the ages of 25 and 64 years with histologically confirmed bladder cancers diagnosed between 1987 and 1996 were identified through the Los Angeles County Cancer Surveillance Program. A total of 1585 cases and their age-, gender- and race-matched neighborhood controls were included in the analyses. Conditional logistic regression models were used to examine the relationship between history of hypertension, medication use and bladder cancer risk. A history of hypertension was not related to bladder cancer; however, among hypertensive individuals, there was a significant difference in bladder cancer risk related to the use of diuretics or antihypertensive drugs (P for heterogeneity = 0.004). Compared with individuals without hypertension, hypertensive individuals who regularly used diuretics/antihypertensives had a similar risk [odds ratio (OR) 1.06; 95% confidence interval (CI) 0.86-1.30], whereas untreated hypertensive subjects had a 35% reduction in risk (OR: 0.65; 95% CI: 0.48-0.88). A greater reduction in bladder cancer risk was observed among current-smokers (OR: 0.43; 95% CI: 0.27-0.71) and carriers of GSTM1-null (homozygous absence) genotypes (OR: 0.43; 95% CI: 0.22-0.85). Similarly, among smokers with GSTM1-null genotype, levels of 4-aminobiphenyl-hemoglobin adducts were significantly lower among untreated hypertensive individuals (45.7 pg/g Hb) compared with individuals without hypertension (79.8 pg/g Hb) (P = 0.009). In conclusion, untreated hypertension was associated with a reduced risk of bladder cancer.
Carcinogenesis 2010 Nov
PMID:Hypertension, diuretics and antihypertensives in relation to bladder cancer. 2073 8


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