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Pifithrin-alpha as a Potential Cytoprotective Agent in Radiotherapy: Protection of Normal Tissue without Decreasing Therapeutic Efficacy in Glioma Cells.

06:00 EDT 20th August 2010 | BioPortfolio

Summary of "Pifithrin-alpha as a Potential Cytoprotective Agent in Radiotherapy: Protection of Normal Tissue without Decreasing Therapeutic Efficacy in Glioma Cells."

Abstract Activation of p53 has been causally linked to normal tissue damage after irradiation. Pifithrin-alpha (PFT-alpha), a specific inhibitor of p53, has been suggested as a combinatory agent in the treatment of p53-deficient tumors in which inhibition of p53 would not compromise therapeutic efficacy but would decrease p53-mediated side effects in normal tissue. We tested this concept for radiotherapy of p53-deficient and -proficient glioma. We observed significant interaction of PFT-alpha with radiation-induced G(1) checkpoint activation and plating efficiency only in glioma cells expressing at least one wild-type allele of p53. This interaction was correlated with PFT-alpha-mediated inhibition of radiation-induced expression of the p53 target gene p21(Waf1). Despite inhibition of p53 function we did not observe significant changes in radiosensitivity after treatment with PFT-alpha in either p53-deficient or p53-proficient tumor cells. We confirmed these results in p53-proficient lung cancer cells. In contrast, PFT-alpha significantly increased the fraction of normal astrocytes and fibroblasts surviving irradiation; this was accompanied by improved DNA damage repair, speaking against an accumulation of cells with genetic lesions after PFT-alpha treatment. In conclusion, PFT-alpha might prove useful in protecting normal tissue from the side effects of radiotherapy without reducing the efficacy of treatment for both p53-proficient and -deficient tumors.

Affiliation

a Translational Radiobiology & Radiooncology Research Laboratory, Department of Radiotherapy.

Journal Details

This article was published in the following journal.

Name: Radiation research
ISSN: 1938-5404
Pages:

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Medical and Biotech [MESH] Definitions

Radiotherapy given to augment some other form of treatment such as surgery or chemotherapy. Adjuvant radiotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

The total amount of radiation absorbed by tissues as a result of radiotherapy.

Radiotherapy using high-energy (megavolt or higher) ionizing radiation. Types of radiation include gamma rays, produced by a radioisotope within a teletherapy unit; x-rays, electrons, protons, alpha particles (helium ions) and heavy charged ions, produced by particle acceleration; and neutrons and pi-mesons (pions), produced as secondary particles following bombardment of a target with a primary particle.

An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.

Radiotherapy where there is improved dose homogeneity within the tumor and reduced dosage to uninvolved structures. The precise shaping of dose distribution is achieved via the use of computer-controlled multileaf collimators.

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