Biomedical subjects

Yasuo Mizumura

Publications and source records attributed to Yasuo Mizumura.

3 recordsLinked to original sources

PubMed2006

[Spicamycin derivative].

Spicamycin, induced differentiation of human myeloid leukemia cells (HL-60), is found to show a potent antitumor activity by inhibiting protein synthesis. Among the various semisynthetic derivatives of spicamycin, KRN5500 showed a marked efficacy in human tumor xenograft model. KRN5500 itself has, however, only minor inhibitory effects on protein synthesis in cell free system. A metabolite, SAN-Gly, which is thought to be generated through metabolism of KRN5500 by a cytosomal enzyme, exhibited a marked inhibitory effect. KRN5500 is expected to be useful even for treatment of refractory solid tumors because of its unique antitumor mechanism. A phase I clinical trials underwent at the National Cancer Center Hospital in Tokyo and at the National Cancer Institute in the USA. Unfortunately, the drug toxicities in addition to grade 4 pulmonary disorders were occurred, partly caused by the organic solvents and chemical essential for its dissolution. To overcome such a severe adverse effects, we conducted to examine whether incorporation of KRN5500 into polymeric micelles (KRN/m) could reduce a pulmonary disorder using a bleomycin (BLM)-induced lung injury rat model or exhibit antitumor activity similar to KRN5500. In conclusion, this study demonstrated that KRN/m is superior to KRN5500 because the pulmonary toxicity was reduced and the potent antitumor activity of KRN5500 was retained after the incorporation of KRN5500 into micelles. We think that these results justify a clinical phase I trial of KRN/m.

Animals↗

PubMed2006

[A case of liposarcoma of the sigmoid colon mesenterium successfully treated with chemotherapy].

We report a case of postoperative recurrence of liposarcoma of the mesenterium successfully treated by chemotherapy using ifosfamide (IFM) and cisplatin (CDDP). A 58-year-old man presented with a strange feeling in the lower abdomen. Enhanced computed tomography showed enhanced non-epithelial tumor in the pelvic space. The tumor moved on palpation, so we diagnosed liposarcoma from the mesenterium, and resected the tumor on 22 August, 2002. The pleomorphic liposarcoma was 11 x 14 x 7 cm, growing from the mesenterium of the sigmoid colon, and weighed 640 g. We performed re-operation due to pelvic recurrence on 24 March, 2003. On 18 September of the same year, when we performed re-operation again for pelvic recurrence, there were so many recurrences on the mesenterium of small intestine that resection was impossible. We started chemotherapy 3 days later using 3.0 g/body IFM from 1 October 2003, together with 1,800 mg/body mesna for prevention of hemorrhage cystitis. We continued chemotherapy using 3.0 g/body/day IFM together with 1, 800 mg/body/day mesna on an outpatient basis, upon his weekly visit to the hospital. Patient remission was shown by abdominal enhanced computed tomography on 10 December. Some grade 2 alopecia and grade 2 leukopenia occurred, so we changed to chemotherapy once every two weeks. Then, it continued to decrease, without any side effects. The response appeared to be complete on computed tomography in August 2004, and we have been continuing the same chemotherapy without recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Incorporation of the anticancer agent KRN5500 into polymeric micelles diminishes the pulmonary toxicity.

KRN5500 is a highly active new semi-synthetic water-insoluble anticancer agent. The only mechanism of anticancer activity of KRN5500 described so far is an inhibitory effect on protein synthesis. At the time of writing, a phase I clinical trial is under way at the National Cancer Center Hospital, Tokyo, and at the National Cancer Institute in the USA. Although preclinical data did not indicate lung toxicity, some cases of severe pulmonary disorder were reported in the phase I clinical trials. This study has been conducted to examine whether incorporation of KRN5500 into polymeric micelles (KRN/m) could reduce the toxic effects caused by the current formulation of KRN5500. The in vitro and in vivo antitumor activities of KRN5500 and KRN/m were compared. Pulmonary toxicity of KRN5500 and KRN/m was studied using a bleomycin (BLM)-induced lung injury rat model. In BLM-rats, extensive pulmonary hemorrhage with diapedesis was observed with KRN5500 i.v. bolus injection at the dose of 3 mg/kg, which is equivalent to 21.0 mg/m2 (level 5) of the Japanese phase I trial. However, toxicity was not observed when rats were administered KRN / m at the equivalent dose to KRN5500 in potency. Electron microscopy of the lung treated with KRN5500 showed disruption of the alveolar type II membrane with release of lamellar debris. Furthermore, in vivo, KRN/m showed similar antitumor activity to KRN5500. These results indicate that KRN/m may be useful for reducing the pulmonary toxicity associated with the current formulation of KRN5500, while fully maintaining its antitumor activity.

Animals↗