W S Hong — Page 4 | PubMed Health

PubMedDate not supplied

Pharmacokinetics of platinum following the administration of cis-(glycolato-O,O')[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane]platinum(II) in dogs.

The pharmacokinetic study on cis-(glycolato-O,O') [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]-platinum(II) (SKI 2034R, NSC D642489) was performed in beagle dogs. A single dose of 2.0 mg/kg of SKI 2034R was given by i.v. bolus to three beagle dogs. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for SKI 2034R declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0-->infinity) determined for ultrafiltrable platinum derived from SKI 2034R, as an active component, was 2.76 +/- 0.13 micrograms.h/ml (mean +/- S.D.), with an initial half-life of 0.15 +/- 0.09 hour, a terminal half-life of 0.96 +/- 0.12 hour, a total clearance of 12.07 +/- 0.67 ml/min/kg, and a steady-state volume of distribution of 0.82 +/- 0.06 1/kg.

Animals↗

PubMedDate not supplied

Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines.

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.

Adenoma↗