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Radiosensitivity in lung cancer with focus on p53
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Sweden approximately 2800 new lung cancer patients are diagnosed every year. Radiotherapy is used with curative intention in certain groups of patients. The aim of this thesis is to study the basis of differences in radioresistance and the possibility to predict response to radiotherapy.

In the first study we investigated, using the comet assay, four lung cancer cell lines with different sensitivity towards radiation. A clear dose-response relationship for radiation-induced DNA single strand and double strand breaks were found. All cell lines showed a remarkably efficient repair of both the DNA single strand and double strand breaks one hour after irradiation. However, further studies in one radioresistant and one radiosensitive cell line demonstrated that repair during the first 15 min had the best accordance with radiosensitivity measured as surviving fraction.

In the second and third study, sequencing studies of the p53 gene were performed on cell lines as well as on tumour material. Cell lines that were expressing a mutation in exon 7 were associated with increased radiosensitivity compared with tumor cell lines with mutations in other exons. In the clinical study, 10 patients were found to be mutated in the p53 gene whereas the other 10 patients were not. No correlation to clinical parameters could be drawn.

In the fourth study, serum from 67 patients with a confirmed diagnosis of non-small cell lung cancer was investigated for the presence of p53 antibodies. P53 antibodies in sera, taken prior to radiation treatment, were associated with increased survival.

The summary of this thesis indicates that the p53 gene has an impact on the effect of radiotherapy in lung cancer. The presence of p53 antibodies might be of clinical interest for predicting survival after radiotherapy. Further studies on the importance of the p53 gene on early repair are of interest.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2002. , p. 59
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1182
Keywords [en]
Oncology, Lung cancer, comet assay, p53, cDNA, p53 antibodies, Lungcancer, Komet metoden, p53 antikroppar
Keywords [sv]
Onkologi
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-2673ISBN: 91-554-5405-4 (print)OAI: oai:DiVA.org:uu-2673DiVA, id: diva2:162015
Public defence
2002-10-19, Skoog salen, Uppsala, 13:00
Opponent
Available from: 2002-09-27 Created: 2002-09-27Bibliographically approved

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Citation style
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