Effects of radiotherapy and chemotherapy on angiogenesis and leukocyte infiltration in rectal cancer
- Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Internal Medicine, University Hospital Maastricht, Maastricht (Netherlands) and Angiogenesis Laboratory, Research Institute for Growth and Development - GROW, Department of Pathology, University Hospital Maastricht, Maastricht (Netherlands)
- Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Internal Medicine, University Hospital Maastricht, Maastricht (Netherlands)
- Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Radiotherapy, University Hospital Maastricht, Maastricht (Netherlands)
- Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Pathology, University Hospital Maastricht, Maastricht (Netherlands)
Background: We and others have shown that angiogenesis and leukocyte infiltration are important prognostic factors in rectal cancer. However, little is known about its possible changes in response to radiotherapy (RTX), which is frequently given to rectal tumors as a neoadjuvant treatment to improve the prognosis. We therefore investigated the biologic effects of RTX on these parameters using fresh-frozen biopsy samples of tumor and normal mucosa tissue before and after RTX. Methods: Biopsy samples were taken from a total of 34 patients before and after either a short course or long course of RTX combined with chemotherapy. The following parameters were analyzed by immunohistochemistry, flow cytometry, or quantitative real-time polymerase chain reaction: Microvessel density, leukocyte infiltration, proliferating epithelial and tumor cells, proliferating endothelial cells, adhesion molecule expression on endothelial cells, and the angiogenic mRNA profile. Results: The tumor biopsy samples taken after RTX treatment demonstrated a significant decrease in microvessel density and the number of proliferating tumor cells and proliferating endothelial cells (p < 0.001). In contrast, the leukocyte infiltration, the levels of basic fibroblast growth factor in carcinoma tissue, and the adhesion molecule expression on endothelial cells in normal as well as carcinoma tissue increased significantly (p < 0.05). Conclusion: Our data show that together with an overall decrease in tumor cell and endothelial cell proliferation, RTX results in an increase in the expression of adhesion molecules that stimulate leukocyte infiltration. This suggests the possibility that, in addition to its direct cytotoxic effect, radiation may also stimulate an immunologic tumor response that could contribute to the documented improvement in local tumor control and distal failure rate of rectal cancers.
- OSTI ID:
- 20850242
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 66, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2006.07.1362; PII: S0360-3016(06)02574-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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