angiogenin and Carcinoma--Transitional-Cell

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n = 50), benign (n = 20) and healthy (n = 20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Case-Control Studies; Clusterin; Cytodiagnosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Ribonuclease, Pancreatic; ROC Curve; Urinary Bladder; Urinary Bladder Neoplasms; Urine

We evaluated the diagnostic efficacy of urinary angiogenin (ANG) and cytokeratin 20 (CK-20) mRNA in comparison with voided urine cytology in the detection of bladder cancer patients.. A total of 97 Egyptian patients provided a single voided urine sample for ANG, CK-20 and cytology before cystoscopy. Of the 97 cases, 63 were histologically diagnosed as bladder cancer; 33 with transitional cell carcinoma (TCC) and 30 with squamous cell carcinoma (SCC), whereas the remaining 34 had benign urological disorders. A group of 46 healthy volunteers were also included in this study. Voided urine was centrifuged and the supernatant was used for estimation of ANG by EIA and confirmed by Western blotting (WB). The urine sediment was used for cytology and RNA extraction. CK-20 RNA was detected by RT-PCR.. The best cutoff value for ANG was calculated by a ROC curve as 322.7 ng/mg protein. The median urinary ANG level in bladder carcinoma, benign urological disorders and healthy volunteer groups was: 802.7, 425 and 33 pg/mg protein, respectively. The positivity rate for urinary CK-20 mRNA of the control, benign and malignant groups was 0%, 2.9% and 82.3%, respectively (P = 0.000); while the rates for ANG were 11.6%, 54.8% and 75.4%, respectively (P = 0.000). There was no significant difference in positivity rates of CK-20 and ANG with respect to sex, smoking, schistosomiasis, urine cytology, tumor grade, tumor stage, hematuria or pus cells. The overall sensitivity and specificity were 71.4% and 90% for voided urine cytology, 75.4% and 70.3% for ANG, and 82.3% and 98.8% for CK-20. Combined sensitivity of voided urine cytology with ANG and CK-20 together (98.2%) was higher than either the combined sensitivity of voided urine cytology with ANG (96.5%) or with CK-20 (91.6%) or than that of the biomarker alone. We demonstrated significant positive correlation between CK-20 positivity with age (P = 0.043) and nodal involvement (P = 0.037); however, there was no significant correlation between CK-20 and ANG with the other clinicopathological parameters.. Our data indicate that CK-20 and ANG in voided urine had higher sensitivities compared to voided urine cytology. However, when specificity was considered, CK-20 alone had superior sensitivity and specificity compared to ANG and voided urine cytology.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Chi-Square Distribution; Female; Humans; Intermediate Filament Proteins; Keratin-20; Male; Middle Aged; Prospective Studies; Ribonuclease, Pancreatic; RNA; Statistics, Nonparametric; Urinary Bladder Neoplasms

The concentration of angiogenin in the tumor tissues and corresponding normal tissues of 20 superficial bladder cancer patients was measured using a sandwich enzyme immunoassay (ELISA). In addition, immunohistochemical assays were performed in order to clarify the localization of angiogenin expression in bladder tissue. The mean concentration of angiogenin in the carcinoma tissues was significantly lower than that in the corresponding normal tissues (P < 0.001). Angiogenin expression was weak in the bladder cancer cells. The present results show that the expression of angiogenin is lower in superficial bladder cancer tissues than in corresponding normal tissues. The biological role of angiogenin in carcinogenesis of bladder cancer may be different from those of other angiogenic factors.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Proteins; Ribonuclease, Pancreatic; Urinary Bladder Neoplasms

An angiogenic factor from human transitional cell cancer of bladder was purified by protein extraction, cation exchange chromatography, gel filtration high-performance liquid chromatography (GE-HPLC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The purified substance was named as bladder cancer angiogenic factor (BCAF). Biological activity of the BCAF was assessed by using the method of chick embryo chorioallantoic membrane (CAM) assay and 3H-TdR incorporation into DNA in Balb/c 3T3 cells. The BCAF displayed the potent activities of neovascularization in CAM and DNA synthesis in Balb/c 3T3 cells. The ultrastructural features of blood vessels induced by the BCAF were similar to the blood vessels in tumors. The BCAF contained a protein with an approximate molecular weight of 15,000 D, which was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and silver staining. Amino acid compositions of the BCAF were also analysed by acid hydrolysis.

Topics: 3T3 Cells; Animals; Carcinoma, Transitional Cell; Chick Embryo; DNA; Guinea Pigs; Mice; Neoplasm Proteins; Proteins; Ribonuclease, Pancreatic; Urinary Bladder Neoplasms