Biomedical subjects

G Bocci

Publications and source records attributed to G Bocci.

30 records · Page 2Linked to original sources

PubMed1997

Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201-995).

The present study investigates the effect of the somatostatin analogue octreotide acetate (SMS 201-995) on experimental angiogenesis in vitro and in vivo. Octreotide reduced the proliferation of human HUV-EC-C endothelial cells (mean, -45.8% versus controls at 10(-9) M; P < 0.05) as well as the density of the vascular network of the chick chorioallantoic membrane (mean, -35.7% versus controls at 50 microgram; P < 0.05). Furthermore, octreotide significantly inhibited chick chorioallantoic membrane neovascularization by the human MCF-10Aint-2 mammary cells secreting the angiogenic protein FGF-3. The proliferation of endothelial and smooth muscle cells from rat aorta explants on fibronectin was reduced by octreotide 10(-8) M (mean, -32.6% versus controls; P < 0.05), and a similar effect was produced on cells sprouting from explants cultured in fibrin (mean, -52.9% versus controls; P < 0.05). Topical administration of octreotide 10 microgram/day for 6 days inhibited rat cornea neovascularization induced by AgNO3/KNO3 (mean, -50.6% versus controls; P < 0.05). Octreotide 40 microgram/day i.p was tested on angiogenesis in rat mesentery obtained by i.p. injections of compound 48/80, a mast cell degranulating agent, or conditioned medium from MCF-10Aint-2 cells and was able to reduce the extent of neovascularization (mean, -45.6 and -64.1%, respectively, versus controls; P < 0.05). These data provide evidence that octreotide is an inhibitor of experimental angiogenesis in vitro and in vivo.

Animals↗

PubMed1996

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine and methotrexate.

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine (6-MP) and methotrexate (MTX) was investigated in patients as well as in rats and in HL-60 human leukemic cells. Ten children affected by acute lymphoblastic leukemia (ALL) in remission received daily doses of 6-MP given at 25 mg/m2 and i.v. infusion of high-dose MTX at 2 or 5 g/m2 once every other week. When 6-MP was given alone, the mean peak plasma concentration (Cmax) and area under the curve (AUC) of 6-MP were 72.5 ng/ml and 225.3 h ng ml(-1). Concurrent treatment with MTX at 2 or 5 g/m2 resulted in a mean increase of 108% and 121% in the Cmax and of 69% and 93% in the AUC, respectively. In rats treated with an oral dose of 6-MP at 75 mg/m2, MTX given i.p. at 5 g/m2 produced mean increases of 110% and 230% in the Cmax and AUC of 6-MP, respectively. In HL-60 human leukemic cells incubated with 6-MP at 250 ng/ml, the cumulative intracellular concentration of 6-thioguanine and 6-MP nucleotides was not significantly modified by treatment with 20 micrograms/ml of MTX. The present findings indicate that high-dose MTX enhances the bioavailability of 6-MP as evidenced by the observed increases in the plasma Cmax and AUC of 6-MP in humans and animals.

Adolescent↗

PubMed1995

Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the proliferation of human colon adenocarcinoma cell lines.

The activity of the synthetic somatostatin analogue SMS 201-995 was investigated in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines. The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/- 1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8 M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480 cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also evaluated. The treatment produced a synergistic antiproliferative effect against SW620 cells as compared to untreated cultures, with growth inhibition being -20.2 +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU ml-1, respectively, but did not increase the activity of SMS 201-995 against the SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells.

Adenocarcinoma↗

PubMed1995

Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice.

The pharmacokinetics of single intraperitoneal doses of paclitaxel (18 and 36 mg/kg) in mice were investigated in the present study. The analysis of drug concentrations by HPLC indicated that the plasma Cmax (13.0 +/- 3.1 and 25.7 +/- 2.8 micrograms/ml, respectively) were reached at the 2nd hr. The values of CL were low (0.06 and 0.1 ml/min, respectively), and t1/2 beta values of 3.0 and 3.7 hr were found, after 18 and 36 mg/kg, respectively. The highest tissue concentrations were observed in the liver (50.2 +/- 3.1 and 92.0 +/- 9.5 micrograms/g respectively), followed by the pancreas (39.3 +/- 9.9 micrograms/g) and the ovary (53.4 +/- 5.6 micrograms/g) after 18 and 36 mg/kg, respectively. In the case of the colic tissue, paclitaxel Cmax were 14.4 +/- 0.8 and 32.8 +/- 3.5 micrograms/g at the 3rd hr, respectively, with sustained drug levels still detectable 24 hr after treatment. Paclitaxel Cmax values of 12.7 +/- 3.0 and 53.4 +/- 5.6 micrograms/g were detected in the ovary after 18 and 36 mg/kg, respectively. The overall results provide evidence that, after intraperitoneal administration, paclitaxel concentrates in peritoneal organs; however, the intraperitoneal route does not prevent systemic drug exposure, allowing high and sustained levels of paclitaxel also in several extraperitoneal tissues.

Animals↗

PubMed1970