Mathematics – Logic
Scientific paper
Jan 1993
adsabs.harvard.edu/cgi-bin/nph-data_query?bibcode=1993phdt........32w&link_type=abstract
Thesis (PH.D.)--CARLETON UNIVERSITY (CANADA), 1993.Source: Dissertation Abstracts International, Volume: 54-11, Section: B, page
Mathematics
Logic
Scientific paper
The prognosis for adult patients with primary malignant brain tumours is poor. Radiation therapy is a standard adjutant to surgery in the treatment of these patients, but is rarely curative. The extreme radio-resistance of primary malignant brain tumours is due in part to their enhanced capacity for repair of potentially lethal radiation damage. The chemotherapeutic agent cisplatin has been shown to inhibit repair of radiation damage. Therefore combined cisplatin and radiation therapy could be a key to enhanced therapeutic gain in the treatment of primary malignant brain tumours. In this project, the 9L rat brain tumour model was used to investigate combined radiation and cisplatin treatments. In vitro experiments showed the 9L cell line to be highly radioresistant and, like human malignant brain tumour cells, to have a high capacity for repair of potentially lethal radiation damage. These cells were found to be moderately resistant to the cytotoxic effects of cisplatin. In vitro exposure to cisplatin at clinically relevant concentrations caused inhibition of potentially lethal damage repair, with the amount of inhibition depending on cisplatin dose and treatment sequence. Magnetic resonance imaging (MRI) was used to monitor the effects of combined radiation and cisplatin treatments of implanted intracranial 9L tumours in rats. A new technique for implanting experimental tumours was developed which resulted in more uniform tumour growth, and methods for radiation and cisplatin treatment of experimental intracranial tumours were developed and evaluated. Non-invasive measurements of tumour size using MRI were found to correlate well with measurements made from histological sections. Intraperitoneal administration of gadolinium contrast agent immediately before T1-weighted MRI was shown to be the most accurate and reliable method for MRI measurement of intracranial tumour size. The capability of MRI to provide early indications of radiation injury to normal brain tissue was evaluated in the rat, and MRI changes were found to occur on average 130 days following partial brain irradiation. Combined radiation and cisplatin treatments of intracranial 9L tumours did not result in tumour regression observable by MRI, despite histopathological evidence of increased tumour necrosis compared with radiation or cisplatin treatments alone.
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