Purpose The purpose of this study was to compare the results of postoperative adjuvant radiotherapy (RT) and concurrent chemoradiotherapy (CRT) in stage I-II endometrial carcinoma. Materials and Methods We analyzed a total of 64 patients with surgically staged I-II endometrial carcinoma who were treated with postoperative adjuvant RT or concurrent CRT between March 1999 and July 2013. Thirty-two patients who received postoperative RT alone were matched with those who received postoperative CRT (n=32) in accordance to age, stage, and tumor histology. Overall survival and relapse-free survival, as well as toxicity of the RT and CRT arms were evaluated and compared. Results The 5-year overall survival rate was 90.0% for the RT arm and 91.6% for the CRT arm. There was no significant difference in overall survival between the two treatment arms (p=0.798). The 5-year relapse-free survival rate was 87.2% in the RT arm and 88.0% in the CRT arm. Again, no significant difference in relapse-free survival was seen between the two arms (p=0.913). In a multivariate analysis, tumor histology was an independent prognostic factor for relapse-free survival (hazard ratio, 3.67; 95% of CI, 2.34 to 7.65; p=0.045). Acute grade 3 or 4 hematologic toxicities in the CRT arm were significantly higher than in the RT alone arm (6.2% vs. 31.2%, p=0.010). Conclusion Adjuvant pelvic concurrent chemoradioherapy did not show superior results in overall survival and relapse-free survival compared to RT alone in stage I-II endometrial carcinoma.
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Cancer Res Treat. 2003;35(5):451-459. Published online October 31, 2003
PURPOSE The molecular pathology of cervical cancers associated with human papillomavirus infection is presently unclear. In an effort to clarify this issue, the gene expression profiles and pathogenic cellular processes of cervical cancer lesions were investigated. MATERIALS AND METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The tissue samples of 11 patients (invasive cancer stage Ib- IIIa) were investigated by a cDNA microarray of 4, 700 genes, hierarchical clustering and the Gene Ontology (GO). Total RNA from cervical cancer and non-lesional tissues were labeled with Cy5 and Cy3. The HaCaT human epithelial keratinocyte cell line was used as a negative control cell. The stages of invasive cancer were Ib to IIIb. All specimens were obtained by punch-biopsies and frozen in liquid nitrogen until required. RESULTS: 74 genes, showing more than a 2 fold difference in their expressions, were identified in at least 8 of the 11 patients. Of these genes, 33 were up-regulated and 41 were down-regulated. The gene expression profiles were classified into 345 mutually dependent function sets, resulting in 611 cellular processes according to their GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis and nucleic acid metabolism. The genes related to nucleic acid binding and structural molecule activity were also significantly down-regulated. In contrast, significant up-regulation was shown in the skeletal development, immune response and extracellular activity. CONCLUSION: These data are suggestive of potentially significant pathogenetic cellular processes, and showed that the down-regulated functional profiling has an important impact on the discovery of pathogenic pathways in cervical carcinogenesis. GO analysis can also overcome the complexity of the expression profiles of the cDNA microarray via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at the cellular process levels.
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PURPOSE Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa.
The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns. CONCLUSION The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.
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