Study of biomarker panel and system biology analysis in human superficial bladder transitional cell carcinoma / 中华泌尿外科杂志

Objective To study the biomarker panel of superficial bladder transitional cell carcinoma(SBTCC)and analyze the biological pathway in tumorigenesis by Shotgun proteomics strategy.Methods Normal urothelium cells and cancer cells were harvested by laser capture microdissection from clinical specimen and the proteomic expression profile was identified by two-dimensional liquid chromatography tandem mass spectrometry.The isoelectric point,molecular weight,grand average of hydropathicity,transmembrane helices were analyzed by using proteomics tools.Gene ontology was used to comment the identified proteins.The pathway analysis was performed by ArrayTrack software,and visualized by GenMAPP.Results There were 440 and 218 proteins expressed in cancer cells and normal cells respectively,among them 388 proteins were differerntially expressed.All the database about identified proteins was deposited in an accessible form to researchers at http://www.Proteome-SBTCC.org.cn and http://www.Proteome-NHTE.org.cn.There were 267(68.8%)differentially expressed proteins which had GO biological process comments.The biological pathwavs of these proteins included MAPK signaling pathway,focal adhesion,oxidative phosphorylation,ECMreceptor interaction,etc.Conclusion Shotgun strategy proteomies database of normal transitional epithelium and SBTCC is successfully constructed.And the basis for the understanding of cell biology and discovery of biomarker panel for SBTCC iS provided.

Study on Correlation between the Expression of P-Glycoprotein and the Effect of Chemotherapy in Transitional Cell Carcinoma / 대한비뇨기과학회지

The resistance of neoplastic cells to chemotherapeutic agents may develops by a variety mechanisms. One of these mechanisms seems to be the amplification or overexpression of the multidrug resistance(MDR) gene. The MDR phenotype is conferred by a 170kD membrane protein, P-glycoprotein. This protein acts as a drug efflux pump for a variety of structurally unrelated antineoplastic agents, especially hydrophobic natural products such as adriamycin and vincristine. In the present study, immunohistochemical stain for P-glycoprotein was performed in paraffin section of 41 specimens of transitional cell carcinoma of the bladder obtained prior to chemotherapy to investigate the usefulness of P-glycoprotein as a predictor of response to M-VAC ( methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy. The overall clinical response rate to chemotherapy was 65.9%. The overall 3- year survival rate was 63%, with 80% in responder group( clinical complete and partial remission) and 36.3% non-responder group(minor response, stabilization and progression ) (P<0.05). In the responder group, 7.4% expressed strongly positive P-glycoprotein, 63% weakly positive and 29.6% negative. In the non-responder group, 28.6% expressed strongly positive P-glycoprotein, 64.3% weakly positive and 7.1% negative. The negative expression rate was high in responder group than non-responder, but this difference was not statistically significant. There was no correlation of expression of P-glycoprotein with either tumor stages or grades. In conclusion, these results suggest that tumors with negative expression of P-glycoprotein seem to have a better clinical response to chemotherapy, and further investigation of other mechanisms of cellular drug resistance should be required.

Clinical significance of silver binding nucleolar organizer regions(AgNORs) in transitional cell carcinoma of the bladder : The correlative study with flow cytometric SPF, PI and PCNA / 대한비뇨기과학회지

Nucleolar organizer regions(NORs) contain coding genes for ribosomal RNA and contribute the regulation of cellular protein synthesis. AgNORs numbers correlate with growth fraction and have been reported the AgNORs counts may have a diagnostic and prognostic utility in other human tumors. We investigated the diagnostic usefulness of AgNORs staining technique as a discriminant for malignancy and assessed the value as a potential method for the estimation of cell kinetics. In addition. we compared the AgNOR counts with flow cytometric analysis of ploidy, S-phase fraction, proliferation index, and PCNA expression rate. There was a statistically significant difference of AgNORs counts between superficial bladder tumor and invasive bladder tumor. But there was no relationship between the mean number of AgNORs per nucleus and histological grade. DNA aneuploid group was associated with higher AgNORs counts than diploid group, but the difference was statistically insignificant. The mean number of AgNORs per nucleus had significant relationship to SPF(r=0.43, p<0.05) and PI(r=0.41, p<0.05.) We concluded that this method alone does not offer a reliable histological discriminant for malignancy. Further studies are needed to confirm that AgNORs counting is a useful method for evaluating the proliferative activity and this technique may serve as a prognostic factor additional to the current histopathological grading criteria of the bladder cancer.