Nitric oxide in patients with transitional bladder cancer.

BACKGROUND AND OBJECTIVES: One of the current challenges in clinical oncology is the identification of patients with superficial transitional bladder carcinoma (TBC) at high risk of recurrence or myoinvasive disease. Recently, inducible nitric oxide synthase (iNOS) expression was detected in urinary bladder cancers. Because iNOS produces a high concentration of nitric oxide (NO), we thought it possible that urine from TBC patients produces high levels of NO. The aim of this study was to determine urine NO levels in TBC compared with healthy controls and with patients bearing other nonrelated tumors, as well as to examine iNOS expression in bladder cancer tissue. METHODS: This study evaluated patients with TBC (n = 33), with gynecological tumors (GT) (n = 19), TBC patients with no evidence of tumor (no evidence of disease [NED]) (n = 19), and healthy subjects (n = 39). Urine NO levels were determined by Griess reagent, expressed as microM NO(2) (-)/100 mg creatinine. RESULTS: TBC patients produced significantly higher urine NO median values (4.2 microM; range, 2.1-91.6) than were produced by healthy individuals (2.1 microM; range, 0.4-4.9), by the NED group (1.7 microM; range 1.2-5.4), and by GT patients (2.0 microM; range, 0.8-58.1) (P = 0.000, Kruskal-Wallis test). iNOS was detected by Western blot in 52% (13/25) of bladder tumors examined. CONCLUSIONS: Although a wider study is necessary, our results suggest that the enhanced NO levels could perhaps be considered as a putative marker in TBC patients.

Reactivity of tumor-draining lymph nodes and the nitric oxide pathway.

Regional lymph nodes are important in the generation of tumor-directed immune responses. The relationship between nitric oxide synthase (NOS) expression and the biological behavior of tumor-draining lymph node (TDLNs) cells in vivo was determined using a spontaneously arising BALB/c mammary adenocarcinoma S13. We first demonstrated a reduction of tumor size and tumor-induced angiogenesis by blocking NOS activity in vivo. TDLNs harvested from tumor-bearing mice (TBM) on day 16 after tumor implant, showed enhanced NOS activity and NOS expression compared to control nodes. Identification of the NOS isoforms present in TDLNs resulted in expression of neuronal NOS (nNOS), endothelial NOS (eNOS) and absence of inducible NOS (iNOS). TDLN cells admixed with tumor cells and inoculated into normal mice (Winn assay) induced a reduction of tumor growth although, when inoculated alone, were able to induce the formation of new blood vessels (angiogenesis). Our data indicate that the in vivo antitumor activity of TDLN cells is modulated by a balance between angiogenesis and antitumor effectors. In our model, when trafficking of leukocytes is obviated, the control of tumor growth by TDLN cells can be explained in part by an antitumor activity great enough to exceed the angiogenic component elicited by the same cells, leading to a reduction of tumor size.