Hisao Ekimoto

composition-dependent in vivo antitumor activity of adriamycin-conjugated polymeric micelle against murine colon adenocarcinoma 26

AbstractMicelle-forming block copolymer–drug conjugates, Adriamycin-conjugated polyethylene glycol–poly(aspartic acid) block copolymers (PEG-P[Asp(ADR)]), were synthesized in eight compositions with varying chain lengths of the segments constituting the block co-polymer. The antitumor activity of this micelle-forming polymeric anticancer drug against murine colon adenocarcinoma 26 (C 26) was evaluated by injection into the tail vein. The in vivo activity of the micelle-forming polymeric anticancer drug was revealed to be strongly dependent on the composition, while the in vitro cytotoxic activity was found to be in the same range regard-less of the composition. One composition of PEG–P[Asp(ADR)] was observed to significantly suppress tumor growth and to prolong survival of the treated mice in a wide dose range. These results indicated that selective delivery of the micelle-forming polymeric anti-cancer drug to the tumor was achieved by the appropriate composition of the block copolymer–drug conjugates.

Human ovarian cancer cell lines resistant to cisplatin, doxorubicin, and l-phenylalanine mustard are sensitive to Δ7-prostaglandin Δ1 and Δ12-prostaglandin J2

Abstract The antitumor activity of Δ 7 -prostaglandin A 1 (Δ 7 -PGA 1 ) or Δ 12 -prostaglandin J 2 (Δ 7 -PGJ 2 ) on human ovarian cancer cell lines resistant to cisplatin (CDDP), doxorubicin (ADR), and l-phenylalanine mustard (1-PAM) was studied in vitro . A2780 AD , A2780 (parent cells of A2780 AD ), 2008DDP, and 2008 cells (parent cells of 2008DDP) were used. The antitumor activities of the drugs were defined with 50% inhibitory concentration (IC50) estimated from growth inhibition curves, which were obtained by an indirect colorimetric method. Drug-resistance ratios obtained from IC50 values, by comparing A2780 AD and A2780 cells, were 62.5 for ADR, 4.6 for CDDP, 4.9 for 1-PAM, 1.5 for Δ 7 -PGA 1 , and 1.8 for Δ 7 -PGJ 2 . Those obtained by comparing 2008DDP and 2008 cells were 1.1 for ADR, 16.0 for CDDP, 2.9 for 1-PAM, 2.3 for Δ 7 -PGA 1 , and 3.2 for Δ 7 -PGJ 2 . Thus some human ovarian cancer cells resistant to ADR, CDDP, and 1-PAM remain sensitive to antitumor PGs.

Antagonists of platelet activating factor from Swietenia mahogani (L.) JACQ

Abstract The structures of swietemahonin A (1), E (2), and 3-acetylswietenolide (3), isolated as antagonists of platelet activating factor from the ether extract of Swietenia mahogani (L.) Jacq., were determined based on the 2-D NMR spectroscopy.

Micelle Forming Polymeric Anticancer Drug Containing Chemically Bound and Physically Incorporated Adriamycin

Micelle forming polymeric drug(MFPD) containing chemically bound and physically incorporated adriamycin(ADR) was designed. Three MFPD samples containing various contents of physically incorporated ADR were prepared and their antitumor activities were evaluated with murine tumor cell C26 in vivo. The activities seemed to depend on a dose of physically incorporated ADR rather than a dose of total ADR. Therefore, it is presumed that the major part of the activity of MFPD depends on physically incorporated ADR. This MFPD with both chemically bound and physically incorporated ADR is promissing for a highly active antitumor agent against solid tumors.