Expression Of Telomerase And Effect Of Vitamin A In Development Of Nephroblastoma

Nephroblastoma is the most common renal malignancy of childhood, which is histologically composed of undifferentiated blastema, epithelial and stromal component. Its histogenesis and pathogenesis are always arousing the enthusiasm of many researchers. For these years, residua of metanephric blastema and delay of differentiation in the development of kidney have been considered the cause of nephroblastoma. The activity of telomerase has been detected in lots of tumor tissues, and been believed to be closely related to the initiation and development of malignancy. Vitamin A plays an import part in biological embryogenesis, generative differentiation and normal homeostasis. People now have paid more attention to the role of Vitamin A in treatment and prophylaxis of tumor, because of the increasing rate of blindness, infection and carcinogenesis due to Vitamin A deficiency (VAD). In order to find the correlated factors in the pathogenesis of nephroblastoma, we first designed the expression of telomerase as a clue to discover its role in development of fetal kidney and nephroblastoma. Then we set the changes after chemotherapy as a maker to find the action of telomerase on the progress of nephroblastoma. At last we devised VAD as the intervention condition to observe its effect on tumorigenesis of nephroblastoma induced by injection of DMH subcutaneously. Section 1 Expression of Telomerase in Fetal Kidney and NephroblastomaMATERIALS AND METHODSThe objects were divided into three groups. Tumor group included 18 cases of fresh human nephroblastoma samples, which hadn't experienced chemotherapy. Fetal kidney group included 24 cases of normal fetal kidneys. They are divided into 3 subgroups according to pregnant weeks, which were 12-20 weeks, 21-28 weeks and 29-36 weeks respectively. Every subgroup consisted of 8 cases of fetal kidney. The control group included 8 cases of normal kidney. The whole samples were detected for the expression of telomerase by in situ hybridization and were quantified for expressive intensity by image analysis system. RESULTSThe positive rate of tumor group was 72.2%(13/18), and was significantly higher than that of the control group which was 0%(0/8). In such 13 cases with positive expression, theintensities of blastemal components and epithelial components were similar, which were 8.1077±0.1935 and 8.0308±0.2810, respectively. But both of them expressed higher than that of stromal components (4.6000±0.2582), and the difference was significant. In 18 cases of nephroblastomas, 8 cases were NRs(Nephrogenic rests) positive, among which 7 cases express telomerase-RNA, and the rate was 38.9%. Comparing the morphosis and express intensity between NRs and three components of nephroblastoma, we have found that the forms of NRs were just like that of blastemal and epithelial components of nephroblastoma, and the expressive intensities of NRs were 7.8857±0.2545, which were similar to that of blastemal components (8.1143±0.1952) and epithelial components (8.0000±0.2309). All of them expressed more highly than stromal components, whose intensities were 4.6000±0.3266, and the difference was significant. In fetal kidneys, the site of telomerase-RNA expression transfered from cortex to medulla and the expressive intensity decreased gradually as the fetus grew.Section 2 The Effect of Preoperative Chemotherapy, Clinical Stage and Histological Type on Temolerase Expression in NephroblastomaMATERIALS AND METHODS24 cases of fresh human nephroblastoma samples were collected, male 14 and femal 10. 13 cases were less than 2 years old, and 11 cases were above 2 years old. They were staged according to NWTS system: 4 cases in stageⅠ,8 cases in stageⅡ, 9 cases in stage Ⅲ, 3 cases in stage Ⅳ, and 0 case in stage Ⅴ. 15 cases were favorable histology and 9 cases were unfavorable histology. 18 cases had not experienced chemotherapy and others accepted preoperative chemotherapy. The whole samples were detected for the expression of telomerase by in situ hybridizati...