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Lipid-lowering Drug (lipid-lowering + drug)
Selected AbstractsStatins, stem cells, and cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Kalamegam Gauthaman Abstract The statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) were proven to be effective antilipid agents against cardiovascular disease. Recent reports demonstrate an anticancer effect induced by the statins through inhibition of cell proliferation, induction of apoptosis, or inhibition of angiogenesis. These effects are due to suppression of the mevalonate pathway leading to depletion of various downstream products that play an essential role in cell cycle progression, cell signaling, and membrane integrity. Recent evidence suggests a shared genomic fingerprint between embryonic stem cells, cancer cells, and cancer stem cells. Activation targets of NANOG, OCT4, SOX2, and c-MYC are more frequently overexpressed in certain tumors. In the absence of bona fide cancer stem cell lines, human embryonic stem cells, which have similar properties to cancer and cancer stem cells, have been an excellent model throwing light on the anticancer affects of various putative anticancer agents. It was shown that key cellular functions in karyotypically abnormal colorectal and ovarian cancer cells and human embryonic stem cells are inhibited by the statins and this is mediated via a suppression of this stemness pathway. The strategy for treatment of cancers may thus be the targeting of a putative cancer stem cell within the tumor with specific agents such as the statins with or without chemotherapy. The statins may thus play a dual prophylactic role as a lipid-lowering drug for the prevention of heart disease and as an anticancer agent to prevent certain cancers. This review examines the relationship between the statins, stem cells, and certain cancers. J. Cell. Biochem. 106: 975,983, 2009. © 2009 Wiley-Liss, Inc. [source] Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemiaJOURNAL OF INTERNAL MEDICINE, Issue 2 2003P. R. W. De Sauvage Nolting Abstract., de Sauvage Nolting PRW, Defesche JC, Buirma RJA, Hutten BA, Lansberg PJ, Kastelein JJP (Academic Medical Center, Amsterdam; Clinical Research, Haarlem; Slotervaart Hospital, Amsterdam; the Netherlands). Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia. J Intern Med 2003; 253: 161,168. Objective., Patients with familial hypercholesterolaemia (FH) vary widely in terms of onset of cardiovascular disease (CVD). Design., The association between cardiovascular risk factors and prevalent CVD was examined in a cross-sectional study in order to elucidate their contribution to atherogenesis. Setting and subjects., Patients were recruited from 37 Dutch Lipid Clinics. The diagnosis of FH was based on a uniform diagnostic protocol, confirmed by DNA analysis in 62% of the cases. All patients were investigated free from any lipid-lowering drug for at least 6 weeks. Main outcome measures., Differences in lipids, lipoproteins and other risk factors for CVD were analysed in FH patients with and without CVD. Results., A total of 526 patients were assessed and more than 37% had a history of CVD with a mean age of onset of 46.8 years. Mean LDL cholesterol (LDL-C) levels were severely elevated (8.38 ± 2.13 mmol L,1). In univariate analysis, age, presence of hypertension or diabetes, body mass index, triglycerides (TG) and low HDL cholesterol (HDL-C) were all significantly associated with CVD. Also in multivariate analysis, all these risk factors, except TG and diabetes, were significantly linked to CVD. Conclusion., A high CVD risk in this large well-documented characterized sample of FH patients is not only conferred by elevated LDL-C but also by low HDL-C. [source] Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an antidiabetic and lipid-lowering drug, after oral administration of its hydroxypropyl-,-cyclodextrin complex to bile duct-cannulated ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2006Takumi Hara Abstract The effect of bile acids on bioavailability of FPFS-410 (2-(N -Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine) after oral administration of the drug and its 2-hydroxypropyl-,-cyclodextrin (HP-,-CyD) complex was investigated. The complexation with HP-,-CyD increased the oral bioavailability of FPFS-410 in normal rats in a HP-,-CyD concentration-dependent manner, compared with that of drug alone. In bile duct-cannulated rats, bile acid concentrations in pylic serum and biliary were decreased to 18% and 14% of sham-operated rats, respectively. After oral administration of the HP-,-CyD complex, the plasma levels of FPFS-410 were lower in bile duct-cannulated rats than in sham-operated rats up to 1 h, however, this order reversed from 2 to 12 h. The plasma levels of M1, a dominant metabolite of FPFS-410 in rats, significantly decreased until 2 h after administration of the complex in bile duct-cannulated rats, compared with in sham-operated rats. Bioconversion of FPFS-410 to M1 and CYP3A2 expression in the liver was markedly lowered by bile duct-cannulation. Bile duct-cannulation did not, however, affect the serum levels of estradiol. These results suggest that bile acids have a pivotal role for bioavailability of FPFS-410 after oral administration of the FPFS-410 complex with HP-,-CyD through CYP3A2 activity in liver of rats. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1771,1782, 2006 [source] Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR)DIABETIC MEDICINE, Issue 1 2009S. Gudbjörnsdottir Abstract Aims Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. Methods This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). Results In patients with CHD 1,2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA1c < 7%, 47%/54% (P < 0.01); blood pressure , 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) , 25 kg/m2], 86%/85%; obesity (BMI , 30 kg/m2), 41%/42%; smokers in age group < 65 years, 16,23%/18,19%; as well as waist circumference , 102 cm (men) or , 88 cm (women), 68% in 2005. Conclusions Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients. [source] Association of low cholesterol with primary intracerebral haemorrhage: a case control studyACTA NEUROLOGICA SCANDINAVICA, Issue 3 2009D. N. Orken Objectives,,, Epidemiological studies have shown that the incidence of intracerebral haemorrhage (ICH) is high in patients with low cholesterol levels. The aim of this study was to investigate the correlation between ICH and low cholesterol in cases of primary ICH. Material and methods,,, Two hundred and fifty-nine patients with primary intracerebral haemorrhage and 137 healthy individuals were included in this study. Patients with prior cerebrovascular accident, secondary ICH, hereditary lipid metabolism disorders, thyroid diseases and those using lipid-lowering drugs were excluded. In all subjects, cholesterol levels were measured after 12 h of fasting. Results,,, Mean cholesterol levels were 205.8 ± 51.4 mg/dl in the ICH group and 230.2 ± 38.9 mg/dl in the control group. Mean cholesterol levels of patients were significantly lower than the controls (P < 0.000). In ICH group, the frequency of patients who had very low cholesterol levels was significantly higher than the control group (P < 0.000). Conclusions,,, Individuals with lower cholesterol levels have an increased risk of ICH. Therefore, before treatment with statins, clinicians must be aware of the possible ICH risk. [source] Simvastatin inactivates ,1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cellsCANCER SCIENCE, Issue 6 2007Ikuko Takeda The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, also called statins, are commonly used as lipid-lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell,extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose-dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. The expression of ,1-integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up-regulation of cell cycle regulators and apoptosis-inducing factors and the down-regulation of integrin-associated molecules and cell proliferation markers. Of down-regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells. (Cancer Sci 2007; 98: 890,899) [source] | ||||||||||