| Glioma is a group of tumors derived from gliacytes and characterized by glial differentiation. It is the most common tumor in the central nervous system and accounts for 40%~50% of all brain tumors. Although comprihensive treatments, most of which comprise especially surgery removal, have been applied in clinical management, the outcome is not promising, especially in malignant cases. Recent research in oncology shows that the occurrence of tumor is caused by uncontrolled division or proliferation of normal cells and the ultimate pathway is the progression of cell cycle. Alteration of cell cycle regulators' function will arrest the cell cycle and the unlimited proliferation of tumors. Further research into the function of cell cycle regulators may reveal new effective targets for gene therapy of malignant tumors.Cyclin D is an important positive regulator in cell cycle. Its three subtypes, Cyclin D1, Cyclin D2 and Cyclin D3, are coded by CCND1, CCND2 and CCND3 respectively, which locate in 11q13, 12p13 and 6p21 of human chromosomes. Cyclin D may enforce cell cycle through the check point and cause independent cell division. It is recently reported that aberrant expressionof Cyclin D is found in various solid tumors and malignant lymphoma, such as breast cancer, oesophageal cancers, lung cancers, liver cancer and lymphoma. Our experiment is aimed at the expression of three Cyclin D subtypes and their relationship with proliferation activity of tumor cells in human brain gliomas. The mechanism of aberrant expression is also discussed.Part One: Cyclin Dl, Cyclin D2, Cyclin D3 and PCNA expression in gliomaImmunohistochemistry was used to detect the expression of Cyclin Dl, Cyclin D2 and Cyclin D3 in gliomas and normal brain tissues. Their relationship with proliferation activity of normal cells and neoplasia were analyzed by using proliferating cell nuclear antigen (PCNA) as indices for cell proliferation activity.Cyclin D1 was expressed in normal brain tissues limitedly, and its positive rate and labeling index were 25.0% and 0.51+0.98. Overexpression was seen in glioma cells and positive rate and labeling index were 55.8 % and 12.75+14.54, which is significantly higher than those of normal brain tissues (P<0.01). With the increase of clinicopathological grades, Cyclin Dl expression increased accordingly. Positive rate and mean labeling index were significantly higher in malignant gliomas than in benign gliomas (P<0.05). Bivariant correlation analysis revealed that there is a significant positive correlation between Cyclin Dl and PCNA (r=0.705, P<0.01). These findings showed that Cyclin Dl was closely related with glioma malignancy and its proliferation activity, indicating its role as an important part in the transformation of gliacyte.Expression of Cyclin D2 was found only in a small fraction of glioma cases (21.2%). Although positive rates and mean labeling indices showed a tendency of increasing with pathological grades, no remarkable difference was seen between different grades (P>0.05). Meanwhile, we observed the plasmic staining in 22 cases, whose intensity increased with tumor malignancy. Cyclin plasmic expression has been reported in a few tumors, but its plasmic stainingin glioma has never been seen. Both nuclear staining and plasmic staining had no significant correlation with PCNA expression (P>0.05) . No statistical difference was seen between high and low pathological grades (P>0.05). This indicated that Cyclin D2 may have a very limited influence on glial tumorigenesis.Cyclin D3 was not expressed in normal brain tissues, but expressed aberrantly in glioma, whose positive rate and mean labeling index were 34.6% and 8.14+14.03 respectively and were remarkably higher in malignant glioma than in benign tumors. However, mean labeling indices of Cyclin D3 was not significantly correlated with those of PCNA. These evidences showed that Cyclin D3 may be an important regulator in the transformation to malignancy and have been involved in the formation of biological features of malignant glioma.
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