著者

Kosuke Shimizu Miki Takada Tomohiro Asai Kenji Irimura Kazuhiko Baba Naoto Oku

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.6, pp.783-786, 2002 (Released:2002-06-01)

参考文献数

19

被引用文献数

10 13

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To enhance the therapeutic efficacy as well as to reduce the side effect, we attempted to liposomalize 4β-aminoalkyl-4′-O-demethyl-4-desoxypodophyllotoxin (TOP-53), a novel and effective topoisomerase II inhibitor. More than 90% of TOP-53 was efficiently incorporated into the liposomes composed of dipalmitoylphosphatidylcholine and cholesterol by remote-loading method. Anti-tumor activity of liposomal TOP-53 against solid tumor was examined in vivo using colon26 NL-17 carcinoma model mice. Three doses of liposomal TOP-53 (12 mg/kg/dose) showed significant tumor growth suppression (97.5% reduction determined at day 25) and the increase in life span (33%) of tumor-bearing mice. Furthermore, one mouse out of 5 was completely cured after treatment. Since similar efficacy was observed in the free TOP-53 treated group, liposomalization does not contribute much to the enhancement of therapeutic efficacy. However, a slight but measurable damage at the injection site was observed when free TOP-53 was injected, and the damage was diminished by the liposomalization. Taken together, liposomalization reduces the side effect rather than enhancing the therapeutic efficacy when TOP-53 is used.

著者

Kazuo Hakoi Taiji Hayashi Kenji Irimura Shuji Hayashi Satoshi Suzuki Shuji Yamaguchi Noboru Konishi Shoji Fukushima

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.14, no.1, pp.13, 2001 (Released:2001-06-01)

参考文献数

35

被引用文献数

1 1

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DHG, a glycosaminoglycan extracted from the sea cucumber is known to show antithrombotic effects in animals and be a possible therapeutic agent for prevention of disseminated intravascular coagulation. In toxicology study, however, dose-dependent intracellular deposition of eosinophilic or basophilic droplets, and crystalloid substances were observed in the proximal tubular epithelial cells of the kidneys when male Sprague-Dawley rats were administered DHG daily for two weeks at the doses of 10, 100, and 200 mg/kg. In contrast to heparin, a glycosaminoglycan that has been reported to induced similar deposits which were identified to be composed of a hemoglobin-like substance using the alizarin red staining. The inclusions observed in rats given DHG were immunohistochemically positive for α2u-globulin. Moreover, the droplets showed metachromasia in toluidine blue staining, and negative for Hall's, Gmelin's, Schmol's tests, and alizarin red staining, but the crystalloids were positive for alizarin red staining. These results suggested that DHG-induced degeneration of proximal tubular epithelial cells in male rats is related to α2u-globulin accumulation.