Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amifostine is a radioprotective agent that prevents radiation- and chemotherapy-induced cellular injury through free-radical scavenging, hydrogen donation, and inhibition of DNA damage. Amifostine is metabolised and accumulated to a much greater extent in normal cells than in tumour cells. As a result, it exerts a protective effect from toxicity on normal tissues induced by chemo- or radiotherapy without reducing the antitumour effects of cancer therapy. Extensive preclinical studies have shown that amifostine protects against radiation damage and against the myelotoxic, nephrotoxic and neurotoxic effects of chemotherapeutic agents such as alkylating agents and platinum compounds. In some cases, the antitumour effects of these agents have been potentiated by amifostine. Amifostine has also been shown to protect against radiation- and chemotherapy-induced mutagenesis and, as a result, carcinogenesis. Use of amifostine allows for safer and more effective administration of radio- and anticancer therapy.
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PMID:Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (WR-2721): preclinical aspects. 757 93

Specific radioprotection of normal tissue represents a promising approach to improve radiotherapy. The ultimate feature of a normal tissue selective radioprotector is that tumor tissue is excluded from protection. Radioprotectors of the current generation, such as Ethyol, are not explicit normal tissue specific. In contrast, the Bowman Birk protease inhibitor, which is known to prevent in vitro and in vivo radiation-induced carcinogenesis, was found to be normal tissue specific. Moreover, the molecular restrictions for this specificity were identified. The radioprotective effect is dependent upon the presence of a functional wt. TP53. Since a high amount of tumors have lost TP53 function during tumor development, the clinical application of BBI to protect normal tissue from radiation damage would effectively improve the therapeutic outcome of radiation therapy. We succeeded to identify stimulation of DNA-repair mechanisms, such as nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), as molecular mode of action. These results are in good agreement with the observations that BBI concomitantly exhibits anticarcinogenic effect and radioprotective effects. Taken together, BBI is recommended as a radioprotector for normal tissue expressing wild type TP53 during treatment of tumors characterized by a mutant TP53.
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PMID:Radioprotection of normal tissue to improve radiotherapy: the effect of the Bowman Birk protease inhibitor. 1287 Oct 82