| At present, radiotherapy is the most important non-surgical treatment method for cancer. However , there exists a wide variation of the response of tumors to radiotherapy. If the radiosensitivity of tumor for radiotherapy could be determined before or during the therapy, it is possible to avoid the overdose or less dose. In other words, individualization of radiation dose prescriptions still is an important problem for the radiation medical staff. The radiation response of tumor is determined by the intrinsic cellular radiosensivitivity, hypoxia and cell proliferation. However, the intrinsic cellular radiosensitivity is more critical factor for optimization of radiation treatment schedules and individualization of dose prescription. Though tumor biomarkers were studied as the predictors to the radiotherapy, no special one was obtained.Generally, about 70% patients with malignant tumors need radiotherapy in spite of tumor control probability (TCP) is lower. Radiotherapy is the major method for the uterus cervical carcinoma, especially the above IIA stage. However, recent 20 years does not witness the improvement in the radiotherapeutic effect.The prediction of current radiosensitivity may be defined as evaluation TCP in the laboratory, however, TCP should have not any relationship with clinical other factors influencing the clinical outcome. With the development of molecular biology, the correlation between apoptosis, proliferation, protooncogene and anti-oncogene expression and radiosensitivity were investigated broadly. On account of this, we have studied patients with the cervical squamous cell carcinoma ( CSCC ) before and at the dose of lOGy irradiation. Thirty-six patients with CSCC received radiothrapy alone using Philip SL-14 linear accelerator 8MV X-ray at the XiJing hospital between July 2000 and February 2001. Tissue samples of patients were obtained by punch biopsy before and after the dose of 10 Gy irradiation, one part of each sample was fixed in 10% formalin and embedded in paraffin, another was stored at -70 癈. Five-micrometer serial sections were cut from the paraffin blocks and one section was stained with hematoxylin and eosin (HE), squamous cell carcinoma was diagnosed with clinical features and histology. 26 blood samples were obtained from 36 patients with CSCC and centrifuged at 10,000 rmp for 15min, and then immediately frozen at -70 癈 until assayed. The study was divided into three parts.Part I The correlation between apoptosis and radiosensitivity of uterus cervical cancinomaDNA was isolated from frozen samples and performed the agarose gel electrophoresis. Spontaneous and radiation-induced apoptosis was detected by TUNEL assay in formalin-fixed, paraffin-embedded slides. Part II Expression of p53 and bcl-2 family gene in the tissue of uterus cervical carcinomap53, bcl-2 family gene expression (bcl-2, bcl-xt and bax) were examined by immunohistochemistry . The roles of those were assessed in apoptosis and radiosensitivity in human cervical carcinoma. Part III Expression of fas gene in tissues and sFas level in serum of uterus cervical carcinomasFas level was detected from frozen serum of the patients with CSCC on the one hand, fas gene was stained by immunohistochemistry on the other.It was found that the mean of AI of spontaneous and radiation-induced apoptosis was significantly different (p<0.01) and the mean of p53, bax and bcl-xL gene expression ratio increased significantly after lOGy irradiation. However, bcl-2 gene expression had decreased after therapy. According to the clinical response, we found that better local tumor control was accompanied by increased AI (i.e., in CR group, AI of 64% (16 of 25) cases were higher than AI mean but in PR and NC, only 18% (2 of 11 ) was higher than mean). Whereas after lOGy irradiation, better local tumor control had the correlation with the AIio, bcl-2/bax(ioGy) ratio.These data demonstrate that apoptosis and expression of p53 gene, fas, bax and bcl-xL gene were induced in cervical cancer during... |
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