Biomedical subjects

Vangelis G Manolopoulos

Publications and source records attributed to Vangelis G Manolopoulos.

4 recordsLinked to original sources

PubMed2006

Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer.

BACKGROUND AND AIMS: D2 gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. PATIENTS AND METHODS: Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. RESULTS: The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50+/-8 and 62+/-10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). CONCLUSION: Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.

Aged↗

PubMed2006

Pharmacological characterization in vitro of EP2306 and EP2302, potent inhibitors of squalene synthase and lipid biosynthesis.

We investigated the effects of EP2306 and EP2302, two novel 2-biphenylmorpholine derivatives, on squalene synthase activity in rabbit and human liver microsomes, lipid biosynthesis, low-density lipoprotein (LDL) receptor expression and LDL protein uptake as well as apoB secretion in HepG2 cells. Both EP2306 and EP2302 inhibited squalene synthase activity dose-dependently. In rabbit liver microsomes, the IC50 values were 33 microM for EP2306 and 0.6 microM for EP2302 whereas in human liver microsomes, they were 63 microM for EP2306 and 1 microM for EP2302. Both EP2300 compounds inhibited cholesterol production by HepG2 cells dose dependently with IC50 values of 13.3 microM for EP2306 and 3 microM for EP2302. Furthermore, both EP2300 compounds and simvastatin significantly reduced triglyceride synthesis and apoB secretion and increased LDL receptor expression and LDL uptake in HepG2 cells. In summary, we have shown that EP2300 compounds are potent inhibitors of squalene synthase activity in rabbit and human liver microsomes and also they are effective inhibitors of cholesterol and triglyceride biosynthesis in HepG2 cells. These results suggest that EP2306 and EP2302 might prove to be useful for lipid-lowering and treatment of atherosclerosis in vivo.

Animals↗

PubMed2004

Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) in vitro and in vivo.

The oxidation of low-density lipoprotein (LDL) is an important event in the development of atherosclerosis. In the present study, the antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2302) were studied. Both compounds inhibited dose-dependently the in vitro oxidation of LDL induced by copper ions. EP2306 and EP2302 increased significantly the lag phase of the oxidation reaction at 0.1 and 10 microM, respectively, whereas they reduced the rate of the reaction at 1 and 10 microM, respectively. This inhibitory effect was not due to a free radical scavenging or copper-chelating activity of EP2300 compounds. Moreover, EP2306 and EP2302 inhibited 12-lipoxygenase activity dose-dependently with IC50 values of 454 and 318 microM, respectively, but had no effect on 15-lipoxygenase activity. In hyperlipidaemic rabbits treated with EP2306 for 4 weeks, there was a decrease in thiobarbituric acid-reactive substance (TBARS) levels and a significant increase in total peroxyl radical-trapping potential (TRAP) levels as compared to control animals. The present data suggest that EP2300 compounds are effective inhibitors of copper-mediated LDL oxidation in vitro. Moreover, EP2306 acts as an antioxidant in hyperlipidaemic rabbits, a property which could be beneficial in reducing atherosclerosis.

Animals↗

PubMed2004

Atorvastatin and simvastatin decrease the uptake of acetylated low-density lipoprotein by human monocytes.

Several lines of evidence indicate that HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin-converting enzyme inhibitors exert anti-atherogenic effects in vitro and in vivo. In the present study, we determined the effect of members of the above classes of drugs on the uptake of modified low-density lipoprotein (LDL) by U937 cells (human monocytic cell line), a key event in the progression of atherosclerosis. U937 cells were treated with drugs and subsequently the uptake of fluorescent acetylated LDL was assessed by flow cytometry. The HMG-CoA reductase inhibitors, atorvastatin and simvastatin (1-30 mumol/l), but not calcium channel blockers or angiotensin-converting enzyme inhibitors, inhibited the uptake of modified LDL by monocytes. Therefore, atorvastatin and simvastatin may slow down the progression of atherosclerosis by inhibiting the formation of foam cells.

Angiotensin-Converting Enzyme Inhibitors↗