[Acoustic neurinoma. Neurosurgical treatment by suboccipital approach].
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Biomedical subjects
Publications and source records attributed to J Overgaard.
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The influence of hyperthermia on the fraction of clonogenic hypoxic cells in a CaH mammary carcinoma was investigated using the TCD50 values for radiation treatment under normal or clamped conditions. A one-hour heat treatment at 41.5 and 42.5 degree C given four hours after radiation reduced the hypoxic fraction to 2.3 X 10(-1), 7.4 X 10(-3) and 6.5 X 10(-3) respectively, when compared with the content of hypoxic cells in non-heated tumours. The results indicate that moderate hyperthermia is able to destroy selectively a large proportion of the fraction of radioresistant hypoxic cells in a solid tumour. This effect is probably due to the increased heat sensitivity of cells in a chronically hypoxic and nutritionally deprived acidic environment.
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Both misonidazole (MISO) and hyperthermia are known to enhance the radiation response of hypoxic cells, and to be selectively cytotoxic against cells in a hypoxic and acidic environment. The ability of these conditions to modify the effect of irradiation and their individual relationship was studied in a C3H mammary carcinoma and its surrounding skin. Simultaneous treatment with MISO, hyperthermia and radiation increased the radiation effect, with enhancement ratios (ER) of up to about 15 (1 mg/g MISO and 43.5 degrees C for 60 min.). However, such treatment also caused a smaller hyperthermic radiosensitization of the normal tissue, so that the therapeutic ratio was only increased by a factor of about 3 compared to radiation alone. Simultaneous MISO and radiation followed by hyperthermia 4 h later gave a moderate enhancement, with ER up to 3 in the tumour, but with no enhancement of the normal tissue, so that there is a similar 3-fold increase in therapeutic gain. The mechanism by which MISO and hyperthermia enhanced the radiation response may be explained as an independent action of the hypoxic radiosensitization of MISO and the selective hyperthermic cytotoxicity against acidic and chronic hypoxic cells; simultaneous hyperthermia added a further heat-induced general radiosensitization. Surprisingly, no MISO cytotoxicity could be detected in this tumour system, with or without simultaneous hyperthermia. The results indicate that in the proper treatment schedule, MISO may be a valuable addition to a combined hyperthermia and radiation treatment.
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The potential radiation protective effect of orgotein, a metalloprotein with superoxide dismutase activity, was investigated in L1A2 tumour cells in vitro, jejunal crypt cells and C3H mouse mammary carcinoma in vivo. No effect of orgotein, given either 2 hours before irradiation or 30 min after, was observed compared to the effect of irradiation alone. Thus, it was concluded that orgotein did not influence the primary radiation response in air in mammalian cells.
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