Linked Life Data

9140117

Source:http://linkedlifedata.com/resource/pubmed/id/9140117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-5-29
pubmed:abstractText
Dolastatin 10, a pentapeptide isolated from the marine mollusk Dolabella auricularia, has antitumor activity. TZT-1027, a dolastatin 10 derivative, is a newly synthesized antitumor compound. We evaluated its antitumor activity against a variety of transplantable tumors in mice. Intermittent injections of TZT-1027 were more effective than single or repeated injections in mice with P388 leukemia and B16 melanoma. Consequently, TZT-1027 shows schedule dependency. TZT-1027 was effective against P388 leukemia not only when administered i.p., but also when given i.v. However, although TZT-1027 given i.v. was active against murine solid tumors, TZT-1027 administered i.p. was ineffective against all the tumors tested with the exception of colon 26 adenocarcinoma. The i.v. injection of TZT-1027 at a dose of 2.0 mg/kg remarkably inhibited the growth of three murine solid tumors; colon 26 adenocarcinoma, B16 melanoma and M5076 sarcoma, with T/C values of less than 6%. The antitumor activities of TZT-1027 against these tumors were superior or comparable to those of the reference agents; dolastatin 10, cisplatin, vincristine, 5-fluorouracil (5-FU) and E7010. In experiments with drug-resistant P388 leukemia, TZT-1027 showed good activity against cisplatin-resistant P388 and moderate activity against vincristine- and 5-fluorouracil-resistant P388, but no activity against adriamycin-resistant P388. TZT-1027 was also effective against human xenografts, that is, tumor regression was observed in mice bearing MX-1 breast and LX-1 lung carcinomas. TZT-1027 at 10 microM almost completely inhibited the assembly of porcine brain microtubules. Therefore, its mechanism of antitumor action seems to be, at least in part, ascribable to the inhibition of microtubule assembly. Because of its good preclinical activity, TZT-1027 has been entered into phase I clinical trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0910-5050
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
316-27
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9140117-Animals, pubmed-meshheading:9140117-Antineoplastic Agents, pubmed-meshheading:9140117-Breast Neoplasms, pubmed-meshheading:9140117-Cell Division, pubmed-meshheading:9140117-Cisplatin, pubmed-meshheading:9140117-Crosses, Genetic, pubmed-meshheading:9140117-Depsipeptides, pubmed-meshheading:9140117-Dose-Response Relationship, Drug, pubmed-meshheading:9140117-Drug Administration Schedule, pubmed-meshheading:9140117-Drug Screening Assays, Antitumor, pubmed-meshheading:9140117-Female, pubmed-meshheading:9140117-Humans, pubmed-meshheading:9140117-Leukemia P388, pubmed-meshheading:9140117-Lung Neoplasms, pubmed-meshheading:9140117-Mice, pubmed-meshheading:9140117-Mice, Inbred BALB C, pubmed-meshheading:9140117-Mice, Inbred C57BL, pubmed-meshheading:9140117-Mice, Inbred DBA, pubmed-meshheading:9140117-Mice, Nude, pubmed-meshheading:9140117-Mollusca, pubmed-meshheading:9140117-Neoplasms, Experimental, pubmed-meshheading:9140117-Oligopeptides, pubmed-meshheading:9140117-Transplantation, Heterologous
pubmed:year
1997
pubmed:articleTitle
Antitumor activity of TZT-1027, a novel dolastatin 10 derivative.
pubmed:affiliation
Pharmacological Research Department, Teikoku Hormone Mfg. Co., Ltd., Kawasaki.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't