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Inducible nitric oxide synthase with transitional cell carcinoma of the bladder
H S Swana1, S D Smith, P L Perrotta
1Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.
Purpose:
Nitric oxide (NO) plays a critical role as both a cell signaling molecule and as a cytotoxic/cytostatic mediator. Nitric oxide synthase (NOS) present in macrophages and neutrophils produces NO in response to immune stimulation. We evaluated NO production in both bladder tissue and urine from patients with transitional cell carcinoma (TCC) of the bladder.
Materials And Methods:
Inducible NOS (iNOS) RNA and protein were evaluated in bladder tissue from patients with and without TCC. Human iNOS-RNA products were identified with the reverse transcriptase-polymerase chain reaction (RT-PCR). Western blot analysis using a polyclonal antibody directed against iNOS recognized immunoreactive iNOS protein. Using the same iNOS antibody, the distribution of iNOS was examined in formalin-fixed, paraffin embedded samples of various grades of TCC. NOS activity was measured in the urine particulate fraction from patients with TCC and from controls by the conversion of [14C]-L-arginine to [14C]-L-citrulline.
Results:
Inducible NOS-RNA products and iNOS specific proteins were found in bladder tissue that contained TCC but not in control bladder tissue. Inducible NOS was uniformly localized in inflammatory cells within the carcinomas. Scattered tumor cells expressed iNOS in 8 of 12 specimens. There was no clear relationship between tumor immunoreactivity and tumor grade. NOS activity in urine from patients with TCC was not significantly elevated or decreased in comparison with control urine.
Conclusions:
Inducible NOS is expressed by cells comprising and surrounding human bladder tumors. It is primarily localized to inflammatory cells, but also is demonstrated within individual tumor cells.
Insights
Inducible nitric oxide synthase (iNOS) is present in bladder cancer tissue, mainly in inflammatory cells and some tumor cells. Urine nitric oxide levels did not significantly change in patients with transitional cell carcinoma (TCC).
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Nitric oxide (NO) is a key signaling molecule and mediator of cytotoxicity.
- Nitric oxide synthase (NOS) enzymes produce NO, particularly in immune cells like macrophages and neutrophils.
- Transitional cell carcinoma (TCC) is a common type of bladder cancer.
Purpose of the Study:
- To evaluate nitric oxide (NO) production in bladder tissue and urine of patients with transitional cell carcinoma (TCC).
- To investigate the expression and localization of inducible nitric oxide synthase (iNOS) in TCC.
- To assess the correlation between iNOS expression and tumor characteristics.
Main Methods:
- Inducible NOS (iNOS) RNA and protein were assessed in bladder tissue using RT-PCR and Western blot analysis.
- Immunohistochemistry was employed to determine iNOS distribution in TCC samples.
- NOS activity was measured in urine from TCC patients and controls.
Main Results:
- iNOS RNA and protein were detected in TCC bladder tissue, but not in healthy bladder tissue.
- iNOS was primarily localized in inflammatory cells within the tumors, with scattered expression in tumor cells.
- No significant difference in urinary NOS activity was observed between TCC patients and controls.
Conclusions:
- Inducible NOS is expressed in cells within and surrounding human bladder tumors.
- The primary localization of iNOS is in inflammatory cells, with additional expression in individual tumor cells.
- Urinary NO levels may not be a reliable indicator of iNOS activity in TCC.