Ribonucleases and their antitumor activity
Autor: | Josef Matoušek |
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Rok vydání: | 2001 |
Předmět: |
Angiogenin
Physiology RNase P Health Toxicology and Mutagenesis Antineoplastic Agents Toxicology Biochemistry law.invention Ribonucleases Antigen Immunotoxin law Tumor Cells Cultured Animals Humans Ribonuclease chemistry.chemical_classification biology Immunogenicity Ribonuclease Pancreatic Cell Biology General Medicine Enzyme chemistry biology.protein Recombinant DNA |
Zdroj: | Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 129:175-191 |
ISSN: | 1532-0456 |
Popis: | The antitumor effect of ribonucleases was studied with animal ribonucleolytic enzymes, bovine pancreatic RNase A, bovine seminal RNase (BS-RNase), onconase and angiogenin. While bovine pancreatic RNase A exerts a minor antitumor effect, BS-RNase and onconase exert significant effects. Angiogenin, as RNase, works in an opposite way, it initiates vascularization of tumors and subsequent tumor growth. Ribonunclease inhibitors are not able to inhibit the antitumor effectiveness of BS-RNase or onconase. However, they do so in the case of pancreatic RNases. Conjugation of BS-RNase with antibodies against tumor antigens (preparation of immunotoxins) like the conjugation of the enzyme with polymers enhances the antitumor activity of the ribonuclease. After conjugation with polymers, the half-life of BS-RNase in blood is extended and its immunogenicity reduced. Recombinant RNases have the same functional activity as the native enzymes. The synthetic genes have also been modified, some of them with gene sequences typical for the BS-RNase parts. Recent experimental efforts are directed to the preparation of 'humanized antitumor ribonuclease' that would be structurally similar to human enzyme with minimal immunogenicity and side effects. The angiogenesis of tumors is attempted to be minimized by specific antibodies or anti-angiogenic substances. |
Databáze: | OpenAIRE |
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