Smmary To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complications, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP. plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPI. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection.
Mer-f3, 12-Hydroxy-ovalicin, Produced by Metarrhizium sp. f3 Sir: In the course of our screening program for new antitumor antibiotics, Mer-f3 (1), a new ovalicin related compound (Fig. 1), was found in the culture nitrate of Metarrhizium sp. f3 which was isolated from a soil sample. In this paper, we report the production, isolation, physico-chemical properties, biological activities and
To enhance the stability in vivo, new derivatives of cytogenin were synthesized, and their biological activity and stability in mice were estimated. 2-(8-Hydroxy-6-methoxyl -oxo-l//-2-benzopyran-3-yl)propionic acid (NM-3) was found to be the most stable among them. It modified collagen-induced arthritis in mice. It also showed potent anti-angiogenic activity in a mousedorsal air sac assay.Cytogenin 1 (Fig. 1) was first found as an immunomodulative antitumor substance produced by Streptoverticillum eurocidiumx\ Later, it was found that cytogenin had an antiinflammatory activity against collagen-induced arthritic model in mice2'3). However, cytogenin readily transformed to the less active sulfate or glucronide, or was oxidized to the 3-carboxylic acid (MC-1) in the biological assessment in mice. These metabolic conversions seemed to reduce efficacy of cytogenin. So we prepared O-acyl and O-alkyl derivatives of cytogenin to prevent glucuronide or sulfate conjugation, and the 3-side chain modified analogues to avoid oxidation. Amongthese derivatives, NM-3(2a in Fig.
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