Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Antitumor effect  (1)
  • IST-622  (1)
  • Polymer and Materials Science  (1)
  • 1
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Polymeric conjugates of adriamycin (ADR) (2) or daunomycin (DM) (3) were synthesized by reaction of the drugs with the copolymer of divinyl ether and maleic anyhdride (DIVEMA) (1). The content of ADR moieties in the DIVEMA conjugate (4) could be varied depending on the reaction conditions up to 35,8 wt.-%. Considering the low toxicity and the high possibility of renal excretion, DIVEMA with M̄w of 7000 and M̄w/M̄n = 1,6 was used for the conjugation. The rate of drug release from the conjugate was determined under physiological conditions by reversed phase HPLC. Within 14 days only 15% of the attached ADR was released from conjugate 4. The antitumor activity of the conjugates was tested in vitro and in vivo against mouse P388 leukemia. Conjugate 4 proved to be 28 times less active than ADR in vitro, which could be explained from the slow drug-release. On the contrary 50% of the leukemic mice treated by 4 survived more than 60 days, whereas no mice given ADR alone or the admixture of ADR and DIVEMA survived 30 days. An antitumor activity of the polymeric conjugate better than that of the free drug was also observed in vivo with DM. Such a polymeric effect can be attributed either to the change in body distribution, the difference in pharmacokinetics, or the slow drugrelease.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-0843
    Keywords: IST-622 ; Chartreusin derivative ; Orally active antitumor agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effects of 6-O-(3-ethoxypropionyl)-3′,4′-O-exo-benzylidenechartreusin (IST-622), a new synthetic derivative of chartreusin (CT), were investigated. Following oral administration, IST-622 showed marked antitumor effects against various mouse tumors such as P388 and L 1210 leukemias, B 16 melanoma, Lewis lung carcinoma, Colon 26 and Colon 38 adenocarcinomas, and M5076 reticulum-cell sarcoma. The best antitumor effects were obtained by five intermittent treatments given every 4 days. In addition, IST-622 showed a significant growth-inhibitory effect against two human tumor xenografts, a large-cell lung cancer (Lu-116) and a gastric adenocarcinoma (St-4), among the seven lines tested. IST-622, which was rapidly metabolized into 3′,4′-O-exo-benzylidenechartreusin (A-132) and not into CT in vivo or in culture medium, exhibited remarkable growth-inhibitory activity against P388 leukemia in vitro, its 50% growth-inhibitory concentration (IC50) being over 20-fold lower than that of CT. IST-622 showed an in vivo antitumor effect superior to that of authentic A-132, possibly resulting from a higher absorption ratio of IST-622 through the gastrointestinal tract. IST-622 is now under clinical phase I study in Japan.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-0851
    Keywords: ONO-4007 ; Lipid A ; Antitumor effect ; TNF ; TIM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ONO-4007 is a novel synthetic analog of lipid A subunit and has been shown to exert antitumor activities on various experimental tumors with less toxicity than lipopolysaccharide. It remains unclear, however, what biological activities of this compound are relevant to its antitumor effects. We therefore investigated the activation of macrophages by ONO-4007 in vitro and in vivo and its implication in antitumor effects, using mouse MM46 mammary tumor as an experimental model. Intravenous injection of ONO-4007 produced significant therapeutic effects on this solid tumor. ONO-4007 could stimulate glycogen-elicited peritoneal macrophages in vitro, not only to produce tumor necrosis factor (TNF), but also to exert cytocidal activities against MM46 cells in vitro. Substantial TNF production was induced in tumor tissue by i. v. injection of ONO-4007, and its successive administration to tumor-bearing mice gave tumor-infiltrating macrophages a prominent in vitro tumoricidal activity and primed them for in vitro TNF secretion. These results suggest that activation of tumor-infiltrating macrophages to a direct tumoricidal state as well as to TNF secretion in tumor tissues may be at least some of the antitumor effects of this novel lipid A analog.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...