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This study consists of the bioassay-guided fractionation of the dichloromethane extract from Eudistoma vannamei and the pharmacological characterization of the active fractions. The dried hydromethanolic extract dissolved in aqueous methanol was partitioned with dichloromethane and chromatographed on a silica gel flash column. The anti-proliferative effect was monitored by the MTT assay. Four of the latest fractions, numbered 14 to 17, which held many chemical similarities amongst each other, were found to be the most active. The selected fractions were tested for viability, proliferation and death induction on cultures of HL-60 promyeloblastic leukemia cells. The results suggested that the observed cytotoxicity is related to apoptosis induction.

Chemical investigation of the methanolic extract of the ascidian Didemnum psammatodes has led to the identification of fourteen known compounds: three methyl esters (methyl myristate, methyl palmitate and methyl stearate), four steroids (cholesterol, campesterol, stigmasterol and beta-sitosterol), two fatty acids (palmitic acid and stearic acid), three glyceryl ethers {(1,2-propanediol, 3-(heptadecyloxy), batyl alcohol and 1,2-propanediol, 3-[(methyloctadecyl)oxy]} and two nucleosides (thymidine and 2'-deoxyguanosine). Their structures were proposed by NMR and comparison with literature data and GC analysis in comparison with authentic sample. The cytotoxic activity of these compounds was evaluated against human leukemia cell line panel using the MTT assay. The mixture of the three methyl esters was the most active group of compounds, showing antiproliferative and cytotoxic effects. Further studies on their mode of action suggest that these activities are connected with inhibition of DNA synthesis and induction of both necrosis and apoptosis.

Objective: We evaluated the effects of l-arginine-enriched total enteral nutrition (LATEN) on tumor-free and right kidney tumor-bearing rats through the determination of in vivo concentrations of metabolites to better understand intermediary metabolism in this model., Methods: Rats were individually housed in wire cages within a controlled environment (25 degrees C and 50% relative humidity) and exposed to a 12-h light-and-dark cycle. Rats comprised the following groups: tumor-free on enteral nutrition plus l-amino acid (n = 8); tumor-free on enteral nutrition plus l-arginine (n = 8); tumor bearing on enteral nutrition plus l-amino acids (n = 8); and tumor bearing on enteral nutrition plus l-arginine (n = 8). Rats had their right kidneys inoculated with saline or tumor cells and were subjected to laparotomy or gastrostomy on day 1 and received chow diet for the next 2 days. Gastrostomy with enteral nutrition was performed on days 3 to 9. On day 9, body weight gain, tumor growth as volume, in vivo blood (microM/mL), and tissue (microM/g) metabolite concentrations were determined. The Mann-Whitney U test was used to test significance., Results: LATEN in tumor-free rats decreased liver (0.25 +/- 0.03 versus 0.13 +/- 0.03 micromol/g, P < 0.05) and right kidney (0.13 +/- 0.1 versus 0.04 +/- 0.00 micromol/g, P < 0.05) ketone body concentrations. LATEN in tumor-bearing rats decreased blood pyruvate (0.17 +/- 0.01 versus 0.10 +/- 0.008 microM/mL, P < 0.005), lactate (5.2 +/- 0.3 versus 2.9 +/- 0.28 microM/mL, P < 0.01), and glucose (6.4 +/- 0.8 versus 3.7 +/- 0.5 microM/mL, P < 0.05). Glucose concentrations decreased in liver (13.9 +/- 2.0 versus 4.89 +/- 0.6 microM/g, P < 0.005) and tumor (3.5 +/- 0.8 versus 1.41 +/- 0.3 microM/g, P < 0.05). There were no changes in body weight gain (21 +/- 2.0 versus 30.3 +/- 3.6 g) or tumor growth (1.53 +/- 0.1 versus 1.26 +/- 0.01 cm(3))., Conclusions: LATEN decreased ketone body concentrations in liver and kidney in tumor-free rats, possibly due to lower ketogenesis and decreased kidney uptake. In tumor-bearing rats, LATEN decreased lacticemia and glycemia and pyruvate blood concentrations. LATEN also reduced liver and tumor glucose concentrations in tumor-bearing animals. The possibility of LATEN-induced insulin and insulin-like growth factor-1 liberation signaling these changes is discussed.