Cyclosporins: immunosuppressive agents with antitumor activity

Initial screening of the 2 recently developed immunosuppressive agents, cyclosporin A and cyclosporin C, in 11 murine transplantable neoplasms revealed significant increase of lifespan with long-term survivors after i.p. injection to the ascites tumors, Taper liver, Sarcoma 180J and Ehrlich.     

Acylfulvenes,a new class of potent antitumor agents

Acylfulvene, derived from the sesquiterpene illudin S by treatment with acid (reverse Prins reaction), is far less reactive to thiols than illudin S. However, it is reduced readily to an aromatic product, in the same way as illudin S. This may explain its greatly improved therapeutic index compared to that of the parent compound.Unfortunately, publication was held up due to postal delay.     

Marine antitumor agents: 14-deoxycrassin and pseudoplexaurol,new cembranoid diterpenes from the Caribbean gorgonianPseudoplexaura porosa

Two new cytotoxic antitumor diterpenoids of the cembrane class, named 14-deoxycrassin (3) and pseudoplexaurol (4), have been isolated from the Caribbean gorgonian octocoralPseudoplexaura porosa. The structure of lactone3, possessing the infrequently encountered -methylene--lactone ring, has been established from spectral and chemical data and that of alcohol4 has been established from spectral data.     

Immunosuppressive and specific antimitotic effects of ovalicin

Zusammenfassung Ovalicin, isoliert aus dem Kulturfiltrat vonPseudeurotium ovalis, hemmt die Bildung von Antikörpern schon nach einmaliger Applikation. Es kommt zur Ausbildung einer partiellen immunologischen Toleranz. Die Abstossungszeit von homologen Hauttransplantaten wird bei Mäusen durch eine einmalige Ovalicinbehandlung signifikant verlängert. Die Substanz hemmt den Anstieg des Milzgewichtes bei Mäusen, die mit Schaferythrozyten immunisiert und/oder mit lebenden Leukämie-L-1210-Zellen geimpft wurden; letzteres gilt auch für den isologen Wirt (L-1210-Zellen in DBA/2-Mäusen). Die Hemmung des Milzgewichtanstieges durch Ovalicin geht parallel mit einer Reduktion des Mitoseindex in der Milz von immunologisch stimulierten Tieren; die Mitosenzahl im Darmepithel wird hingegen nicht beeinflusst.     

Aragusterol C: A novel halogenated marine steroid from an Okinawan sponge,Xestospongia sp., possessing potent antitumor activity

A novel chlorinated steroid, aragusterol C, was isolated from an Okinawan marine sponge of the genusXestospongia. The compound strongly inhibited the proliferation of KB cells in vitro, and also showed potent in vivo antitumor activity against L1210 cells in mice. The complete structure of aragusterol C was determined by spectroscopic analysis and X-ray crystallographic analysis.     

The cytogenetic efficiency of the antitumor agents bleomycin and peplomycin is enhanced by the heart drug verapamil (isoptin)

Summary The induction of 2-break chromosome aberrations (dicentrics and ring chromosomes) in human lymphocytes by the antitumor agents bleomycin and peplomycin is strongly enhanced when those agents are applied together with the heart drug verapamil (isoptin).We thank Heinrich Mack Nachf./Illertissen (Germany) for generously supplying both the bleomycin and the peplomycin and Dr P. Engel, Illertissen, for valuable informations.     

The cytogenetic efficiency of the antitumor agents bleomycin and peplomycin is enhanced by the heart drug verapamil (isoptin)

The induction of 2-break chromosome aberrations (dicentrics and ring chromosomes) in human lymphocytes by the antitumor agents bleomycin and peplomycin is strongly enhanced when those agents are applied together with the heart drug verapamil (isoptin).     

Preparation and experimental antitumor activity of a new semi-synthetic antibiotic: 14-diethoxyacetoxy daunorubicin (R.P. 33 921)]

14-diethoxyacetoxy daunorubicin (R.P. 33 921) was chosen among a series of new daunorubicin analogues. Its preparation from daunorubicin and its biological activities are described. It displays an antitumoral activity in mice with a better chemotherapeutic index than daunorubicin and doxorubicin.     

Cytological investigations with a new class of cytotoxic agents: Methylhydrazine derivatives

Zusammenfassung Mittels cytologischer Untersuchungen wurde versucht, einen Einblick in den Wirkungsmechanismus der tumorhemmenden Methylhydrazinverbindungen zu gewinnen. 1-Methyl-2-benzyl-hydrazinphosphat bewirkt beim Ehrlich-Ascites-Carcinom der Maus einen Abfall des Mitoseindexes, eine Verschiebung des Mitosephasenindexes zugunsten der Metaphase sowie das Auftreten von Chromatidbrüchen. Diese Befunde werden diskutiert.     

Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles]

Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.     

Immunosuppressive effect of a human serum ferroprotein of hepatic origin: alpha-2-HF-globulin]

alpha 2HF, a serum ferroprotein increased during some malignant diseases, displays a suppressive effect on in vitro antibody responses, whether T-independent or T-dependent. This effect is not related to the presence of iron, nor to the macroglobulin nature of the molecule. The immunosuppressive properties of alpha 2 HF might depend on its carbohydrate moeity.     

Immunosuppressive effect of chronic Strontium-90 administration to miniature swine

Zusammenfassung Antikörperproduktion in Schweinen, die einer chronischen internen Strontium⁹⁰-Bestrahlung ausgesetzt waren.

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This study was conducted under Contract No. AT(45-1)-1830 with the United States Atomic Energy Commission.     

Polarographic activity of the antitumor drug cis-dichlorodiammineplatinum (II). The effect of hydrolysis and trans-isomerization of the drug

Summary Electrochemical activities of cis-dichlorodiammineplatinum(II) (cis-DDP) and its trans isomer were studied by classical and differential pulse polarography (d.p.p.). It was shown that both isomers yielded a polarographic step or peak at about –1.6V (vs. Ag/AgCl), which corresponded to electroreduction of the complex and to catalytic hydrogen evolution. This signal was easily measurable with the aid of d.p.p. and was suitable for investigation of the extent of hydrolysis and trans-isomerization of cis-DDP leading to the formation of toxic products. The detection limit for determination of cis-DDP and its trans isomer by d.p.p. was 1×10^–6 mol/l.Acknowledgment. This work was supported in part by Lachema n.e., Brno (Czechoslovakia).     

Polarographic activity of the antitumor drug cis-dichlorodiammineplatinum (II). The effect of hydrolysis and trans-isomerization of the drug

Electrochemical activities of cis-dichlorodiammineplatinum (II) (cis-DDP) and its trans isomer were studied by classical and differential pulse polarography (d.p.p.). It was shown that both isomers yielded a polarographic step or peak at about -1.6 V (vs. Ag/AgCl), which corresponded to electroreduction of the complex and to catalytic hydrogen evolution. This signal was easily measurable with the aid of d.p.p. and was suitable for investigation of the extent of hydrolysis and trans-isomerization of cis-DDP leading to the formation of toxic products. The detection limit for determination of cis-DDP and its trans isomer by d.p.p. was 1 X 10(-6) mol/l.     

Inhibition of cyclic 3′, 5′-nucleotide phosphodiesterase activity by diuretics and other agents

Résumé Différent composés organo-mercuriels ainsi que l'acide éthacrinique inhibent les phosphodiestérases de l'AMP cyclique, du cur de cobaye, de buf et de rat, des plaquettes de rat et de l'homme ainsi que du cerveau de rat.