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Biomedical subjects

L J Hanka

Publications and source records attributed to L J Hanka.

At least 19 recordsLinked to original sources
PubMed1979

Proceedings of the Workshop on Amino Acid Imbalance in the Treatment of Cancer. Introduction: possibilities for biochemically rational chemotherapy for some malignancies with depleting enzymes and antimetabolites of specific amino acids.

A number of recent investigations have documented that, in several cancers, the malignant cells are no longer capable of synthesizing a specific amino acid, while the normal cells continue such biosynthesis at a normal rate. Enzymes degrading amino acids have demonstrated therapeutic value against such cancers. Significant progress was made recently in technology related to enzyme preparations. These are highly specific, have long half-lives, and can be chemically modified to eliminate their immunogenicity to man or animals. A practical in vitro system for detection of antimetabolites of different amino acids in natural materials was developed. It appears reasonable to expect that, in a specific malignancy, after the available pools of such deficient amino acids are exhausted by administration of the depleting enzyme, an additional, perhaps synergistic, effect could be obtained by utilizing an analog of such an amino acid. A brief review of the pertinent existing information will be presented in this communication.

Amino Acids↗
PubMed1979

In vitro system for detection of antimetabolites of specific amino acids.

An in vitro system was developed to detect antimetabolites in fermentation liquors of soil microorganisms. This system effectively uncovers antimetabolites of purines and pyrimidines and of selected amino acids with established differences in their biosynthesis by normal cells versus certain malignant cells. Currently these amino acids include: L-asparagine, L-aspartic acid, L-glutamine, L-cysteine (cystine), L-methionine, L-arginine, L-histidine, L-tyrosine, L-phenylalanine, L-tryptophan, L-threonine, and L-serine. It is expected that these antimetabolites could be useful either alone or in combination with specific depleting enzymes in the treatment of malignancies where such an imbalance was established.

Amino Acids↗
PubMed1978

Detection and assay of antitumor antibiotics.

Cell culture techniques and antimicrobial systems can be used as detection systems for new antibiotic structures. Antimicrobial systems by virtue of their speed, economy, ease of use, and adaptation to chromatographic (bioautographic) techniques are definitely superior for assay and for dereplication purposes. A prescreen assay system which combines the advantages and minimizes the disadvantages of the two approaches is described.

Animals↗
PubMed1978

A multi-end point in vitro system for detection of new antitumor drugs.

By utilizing new types of producing microorganisms and isolating these on rather unusual growth media, we hope to produce new classes of antitumor drugs. In the detection system, we included the highly sensitive L1210 in vitro assay. But be requiring additional antimicrobial activity, we were able to eliminate rather early most of the previously known drugs from further work-up. The screening protocol was arranged so as to detect antimetabolites of a few rationally selected compounds.

Animals↗
PubMed1978

CC-1065 (NSC-298223), a new antitumor antibiotic. Production, in vitro biological activity, microbiological assays and taxonomy of the producing microorganism.

A new antitumor antibiotic is produced in fermentation liquors of Streptomyces zelensis sp.n. The antibiotic is biologically active at extremely low concentrations. At 40 pg/ml, it inhibited 90% of the growth of L1210 cells in culture in tube dilution assays. The minimal inhibitory concentrations against Gram-positive bacteria is between 1 approximately 10 ng/ml, while these values for Gram-negative bacteria and fungi are mostly under 1 microgram/ml. A microbiological assay with Bacillus subtilis can detect concentrations of 1 approximately 2 ng/ml.

Animals↗
PubMed1977

Chartreusin: production and microbiological assay.

Chartreusin was produced in the fermentation liquors of Streptomyces chartreusis at peak concentrations of 200 to 300 mug/ml. The titers could be increased by 200 to 300% or more by incorporating d-fucose, a part of the chartreusin molecule, into the fermentation media. A microbiological assay with Sarcina lutea could detect concentrations of the drug of 0.5 to 1.0 mug/ml.

Antibiotics, Antineoplastic↗
PubMed1977

Detection and microbiologic assays of antimetabolites.

The biochemical considerations applicable in the detection of new antimetabolites are very similar to those used in developing microbiologic assays for these drugs. An in vitro system for detection of antimetabolites was developed based on different sensitivities to such drugs of bacteria cultivated in complex versus completely synthetic media. A number of new antimetabolites of amino acids, vitamins, and purines or pyrimidines were isolated and microbiologic assays for these drugs were developed. As an example of the technology utilized and possibilities available, an assay for cytosine arabinoside was described. It can detect 0.5-microgram/ml concentrations of this drug even in the presence of other antitumor or antibacterial antibiotics.

Anti-Bacterial Agents↗
PubMed1976

U-43,120; a new antitumor antibiotic. I. Production, biological activity, microbiological assay and taxonomy of the producing microorganism.

A new antitumor antibiotic, U-43,120 was discovered. It is produced by fermentation of a new species of Streptomyces, designated Streptomyces paulus DIETZ sp. n. Its antimicrobial activity is limited to bacteria. A microbiological assay with Bacillus subtilis was developed that can be detect concentrations of 1 approximately 2 mug/ml of the drug in fermentation liquors. U-43,120 was active in vivo against P-388 leukemia in mice.

Animals↗
PubMed1973

U-42, 126, a new antimetabolite antibiotic: production, biological activity, and taxonomy of the producing microorganism.

A new antimetabolite antibiotic, U-42,126, was discovered by use of a specific in vitro screen. U-42,126 was produced by the fermentation of Streptomyces sviceus. Its antimicrobial activity in vitro was limited to fungi. Certain bacteria were inhibited only when cultivated in completely synthetic media. U-42,126 was active in vivo against L1210 leukemia in mice.

Antibiotics, Antineoplastic↗
PubMed1972

Two new antimetabolites of biotin: alpha-methyldethiobiotin and alpha-methylbiotin.

Two new antimetabolites of biotin were isolated from culture filtrates of Streptomyces lydicus: beta-methyldethiobiotin and beta-methylbiotin. (14)C-biotin or (14)C-pimelic acid was not incorporated into either of these antimetabolites by the growing culture. Neither of the compounds could substitute for the biotin requirement in Saccharomyces cerevisiae. Both compounds had a strong and rather specific antimicrobial effect against mycobacteria. Their antimicrobial activities were reversed by biotin. Both compounds had an affinity for avidin.

Antimetabolites↗