Showing papers by "Hiroshi Maeda published in 1978"

Isolation and characterization of a new antitumor polysaccharide, KS-2, extracted from culture mycelia of Lentinus edodes

Abstract: A new antitumor and antiviral substance, KS-2, was prepared by ethanol precipitation of the hot water extract of culture mycelia of Lentinus edodes KSLE 007. It was further purified by ECTEOLA-cellulose and Sephadex G-100 column chromatography based on the interferon-inducing activity. Its homogeneity was revealed by CsCl density gradient centrifugation, electrophoresis on cellulose acetate and Sephadex G-100 and ECTEOLA-cellulose column chromatography. KS-2 is mainly composed of alpha-linked mannose and contains a small amount of peptide which consists of serine, threonine and alanine with residual amounts of the other amino acids. The estimated molecular weight of KS-2 is between 6.0 X 10(4) and 9.5 X 10(4). KS-2 suppressed the growth of EHRLICH as well as Sarcoma-180 tumors in mice when given either orally or intraperitoneally. It is also capable of inducing an interferon in mice when dosed orally or intraperitoneally. The acute LD50 of KS-2 was found to be extremely low, more than 12,500 mg/kg when administered orally to mice.

Assay of an antitumor protein, neocarzinostatin, and its antibody by fluorescence polarization.

Abstract: I evaluated use of the fluorescence polarization technique to measure neocarzinostatin, a proteinaceous antitumor antibiotic, and its antibody, in serum. The antigen (neocarzinostatin), labeled with fluorescein isothiocyanate, was allowed to interact with its antibody in a cuvet, in the instrument, yielding an increase in the fluorescence polarization value. Antibody content was determined in the presence of a definite amount of the labeled antigen, fluorescence polarization values increasing in parallel with each addition of antibody. Antigen content was determined with a known amount of antibody, which reacted at first with an unknown amount of antigen in samples, followed by addition of a definite amount of the labeled antigen (competition). I used the method to determine a pharmacokinetic parameter, the apparent volume of distribution for neocarzinostatin in rabbits, using drug-injected rabbit sera. I evaluated precision, accuracy, and reproducibility, using various samples or possible interfering substances such as bilirubin and hemoglobin, and also compared results for antigen with those by single radial immunodiffusion assay. The present assay is fast (less than 2 min), sensitive (less than 10 nmol/liter can be detected), and simple (there is no separation step before readout of the results).

Neocarzinostatin derivatives and a process for producing the same

Abstract: Neocarzinostatin derivatives having the formula; ##STR1## wherein N represents a neocarzinostatin residue, and R 1 +R 2 represents a residue of polystyrene-maleic acid copolymer having a molecular weight of 2,500 to 80,000. These neocarzinostatin derivatives are prepared by reacting neocarzinostatin with a polystyrene-maleic acid copolymer containing at least one maleic anhydride residue per molecule. The neocarzinostatin derivatives exhibit anticarcinogenic activity.

Ks-2-a

Abstract: KS-substance was obtained as raw material from the cultured mycelium of Daedalea dickinsii KSDD 6 (FERM-P No. 3993), Lentinus edodes KSLE 7 (FERM-P No. 3994) or Lentinus edodes KSLE 28 (FERM-P No. 4196), and by refining this substance a novel substance KS-2-A was obtained. This substance KS-2-A and also the KS-substance as the raw material both enhance the host defense function of the living body.

Experimental and clinical studies on the formation of antibodies to neocarzinostatin, a new protein antibiotic.

Abstract: The injection of clinical doses of neocarzinostatin (NCS) in guinea pigs did not result in antibody formation as judged by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, fluorescence polarization, and passive cutaneous anaphylaxis reaction. This confirmed previous work on passive hemagglutination and passive cutaneous anaphylaxis reaction in a heterocytotropic system in guinea pigs. Forty-eight serum samples from 28 patients who were previously treated with NCS alone (8--161 mg) for a period of 8-85 days did not show any sign of antibody formation as revealed by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, and fluorescence polarization techniques. In a homocytotropic system, the passive cutaneous anaphylaxis reaction was carried out with sera of sensitized guinea pigs and test guinea pigs which revealed that no IgE and IgA antibody to NCS was present in the sensitized sera. Those patients with bladder cancer who did not respond to NCS therapy or exhibit any side effects even after 21 mg were found to have proteolytic activity in their sera which degraded NCS very rapidly as revealed by the fluorescence polarization technique.

Evaluation of succinyl neocarzinostatin in vivo.

Abstract: The toxicity of the bis-succinyl derivative of the protein antibiotic, neocarzinostatin, was compared with the parent compound, neocarzinostatin (NCS), in rats. The derivative was found to be about two to five fold more active than NCS in vivo. The antitumor activity in rats bearing eleven distinct YOSHIDA hepatoma ascitic cell lines was tested under four possible combinations with regard to sites of drug and tumor cell administration. The results indicate that the antitumor spectrum of the derivative had changed slightly. Antitumor activity in mice was also tested with L1210 and P388 lymphatic leukemia, and with B16 melanocarcinoma. When the effect of the derivative was compared with parental NCS at the molecular level with respect to the inhibition of DNA synthesis in vitro, the specific activities of the two were found to be almost identical. These results were interpreted to indicate that the succinyl derivative of NCS was more stable to inactivation and proteolytic break-down in vivo than NCS as observed previously in in vitro studies.

Substance antitumorale obtenue par culture de mycelium.

Abstract: Substance extraite d'un mycelium obtenu par culture en presence de produits solubles qui se forment dans la distillation de l'eau de vie de cereales. Les champignons particuliers, utilisees a cet effet, sont les Daedalea dickinsii KSDD-6, Lentinus edodes KSLE 7 et Lentinus edodes KSLE 28. Cette substance, appelee KS, et sa forme purifiee KS-2-A, exercent une action antitumeur lorsqu'elles sont administrees a des souris. La figure montre le spectre infrarouge de la substance.