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The object of this study is to evaluate the usefulness of the ATP sensitivity assay for appropriate selection of anticancer drugs for prophylactic bladder instillation therapy in patients with superficial bladder cancer.The ATP assay was performed using the method reported previously. The anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non-recurrence in group A (32 cases) which had been treated using the results of ATP assay, was compared with that of group B (37 cases), for which the ATP assay was not performed.The most sensitive anticancer drug was THP-ADM. The 5-year rate of non-recurrence in group A (80.9%) was significantly higher than that in group B (39.4%) (p0.001). Tumor recurrences in group A was observed within 2 years post-operatively in all cases. When the ATP assay was re-performed in 3 cases with recurrent disease, altered antitumor sensitivity was observed.These findings suggested that ATP assay was useful for choosing effective anti-cancer drugs for prophylactic instillation, especially for patients with primary or solitary tumor, grade 2 disease or tumor of a certain size (or = 1 cm). It also appeared that the ATP assay should be performed for patients with primary superficial bladder cancer as a screening test for the selection of drugs for prophylactic instillation therapy.

Seven steroids in normal adrenal gland and those of patients with aldosteronoma or Cushing's adenoma were measured by liquid chromatography/mass spectrometry with an atmospheric pressure ionization interface system. Using this system, quasi-molecular ions [M + H]+ of standard cortisol, corticosterone, 17α-hydroxyprogesterone, 11β-hydroxyandrostenedione and Δ4-androstenedione and [(M + H) − H2O]+ ions of aldosterone and dehydroe-piandrosterone were observed as their base peaks, and quasi-molecular ions [M + H]+ and [(M + H) − H2O]+ ions of seven steroids were clearly observed in chromatograms of biological samples. The ratio of glucocorticoid (cortisol) to mineralocorticoid (corticosterone) content was measured, and found to be significantly lower for aldosteronomas and higher for Cushing's adenomas than for normal adrenals. These findings indicate that the method had suffficient sensitivity for the identification and simultaneous measurement of a variety of adrenal gland steroids.

The distribution of S-100 protein positive dendritic cells (S100-DCs) inside the cancer nest and the expression of HLA-DR alpha antigen (HLA-DR) and blood group antigen (BGA) on cancer cells in 90 cases of transitional cell carcinoma (TCC) of the urinary bladder were immunohistochemically investigated in relation to the degree of malignancy and its prognosis. A dense infiltration of S100-DCs inside the cancer nest ("many", i.e. more than 10DCs/HPF) was detected in 47 (52%) out of 90 cases. The HLA-DR positive cancer cells (DR-CCs) were detected in 24 cases (27%), including in the 16 most dense cases ("many", i.e. more than 100DR-CCs/HPF). BGA positive cancer cells (BGA-CCs) were detected in 49 cases (54%) ("positive", i.e. more than 100BGA-CCs/HPF). In connection with the degree of malignancy and with the number of cases affected by S100-DCs infiltration. HLA-DR expression and BGA expression. A statistical analysis showed significant correlation between the number of cases affected by S100-DC and each clinicopathological factor including G, pT, ly, v, and showed also between that affected by BGA expression and each clinicopathological factor including G, pT, INF, but showed no significant correlation between that affected by HLA-DR and each clinicopathological factor. As regards the prognosis, the 10-year survival rates for all 90 cases were 60.4%. In the 10-year survival rate, S100-DCs "many'' (77.7%) and "few'' (39.0%), DR-CCs "many'' (85.7%) and "no'' (56.9%), DR-CCs "many'' and "few'' (43.8%), BGA-CCs "positive'' (74.3%) and BGA-CCs "negative'' (46.5%) were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of S-100 protein positive dendritic cells (S100-DCs) in cancer nests and the expression of HLA-DR antigen on cancer cells in 90 patients with transitional cell carcinoma of the urinary bladder were studied immunohistochemically. A dense infiltrate of S100-DCs (more than 10 S100-DCs/high power field) was detected in 47 out of 90 cases, while in the remaining tumours the infiltrate was sparse. HLA-DR positive cancer cells (DR-CCs) were detected in 24 cases, including 16 with dense DR-CCs (more than 100 DR-CCs/high power field); no expression was observed in the remaining tumours. In terms of the numbers of S100-DCs infiltrating the following statistically significant differences were observed: tumour grading G1G3, depth of penetration pT0pT3; (p0.05), G2G3, lymphatic invasion -+ and venous invasion -+; (p0.01). A multivariate analysis demonstrated that the most important factor affecting prognosis was distant organ and/or lymph node metastasis (p0.01) the number of S100-DCs, with a hazard ratio (HR) of 0.26 (p0.01), and the number of DR-CCs with HR of 0.18 (p0.05); these were statistically significant. S100-DCs and DR-CCs may be regarded as independent prognostic factors of tumour growth and progression.

Polymorphonuclear leukocytes (PMNs) play an important role in host defense system. Upon interaction with soluble or particulate matter, PMNs generate active oxygen species (AO), which act on killing of bacteria. In urinary tract infection, urinary PMNs are assumed to have bactericidal activity in urine. Basal experiments were studied on the AO generation of urinary PMNs, monitored by mainly the luminol-dependent chemiluminescence. It was indicated that urinary PMNs, isolated from patients with urinary tract infection, generated AO in physiological medium. This activity of urinary PMNs was found to be significantly inhibited rather than that of PMNs in blood, and this suppression was suggested to be time-dependent. PMNs were affected significantly by osmolarity of reaction medium. These changes were associated with intracellular free calcium. PMNs exposed in hyposmotic medium generated AO, just as they were stimulated. However PMNs exposed in hyperosmotic medium did not generate AO. The stimulation-dependent AO generation of PMNs was increased in hyposmotic solution, while in PMNs incubated at 37 degrees C for 60 min in hyposmotic solution, this generation was decreased than controls. On the other hand, the stimulation-dependent generation was decreased in hyperosmotic solution, while incubated in hyperosmotic solution, this generation was increased. These results suggest that ability of urinary PMNs is regulated by urine osmolarity and retaining time or many other factors, however urinary PMNs are primed and maintain bactericidal activity.

Intravesical instillation of anti-cancer drugs for superficial urinary bladder cancer is generally carried out with the aim of prophylaxis against recurrence and chemotherapy against tumor. But since sensitivity of tumor cells to each anti-cancer drug differs individually, the anti-cancer drug to be used should also be decided individually. We selected a new sensitivity test, ATP-sensitivity-assay, which measures intracellular adenosine triphosphate (ATP) volume by Luciferin-Luciferase reaction, for the decision of the anti-cancer drug. In this paper, we evaluated the direct anti-tumor activity of the drugs that were decided by ATP-sensitivity-assay of intravesical chemotherapy. Six drugs, that are Doxorubicin (ADM), Mitomycin C (MMC), Pirarubicin (THP-ADM), Cytarabine (Ara-C), Bleomycin (BLM) and Cisplatin (CDDP) were tested in this research and size of tumors of six patients reduced to 34-93% after 6 times' installation. A woman got cystitis induced by ADM after 3 times' instillation but instillation was completed. ATP-sensitivity-assay is useful for deciding the anti-cancer drugs for intravesical chemotherapy and prophylaxis for superficial bladder cancer.

In order to examine its clinical efficacy, recombinant human interferon-β (rIFN-β) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3−36) × 106 U rIFN-β on days 1–3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3−36) × 106 U every day for 10–20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 × 106 U twice a day every day for 10–20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN-β varies with treatment protocol. Frequent and longer exposure to rIFN-β may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN-β is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects.

We investigated natural killer (NK) activity and T-lymphocyte subsets in peripheral blood and regional lymph nodes in order to examine the host's defence mechanisms against cancer. The materials were obtained from 26 patients with genitourinary cancer and 9 patients with benign diseases, who were used as controls. NK activity was measured by ATP-chemiluminescence (ATP) assay, a new method which is well correlated to the 51Cr-release assay, and T-lymphocyte subsets were stained with anti-Leu-2, -3, -4, -7, and -11 monoclonal antibody. The NK activity of regional lymph nodes was lower than that of the peripheral blood in all 35 cases, and the percentage of Leu 7+ and Leu 11+ cells was in agreement with that of the NK activity detected by ATP assay. In the peripheral blood, the percentage of Leu 3+ cells was lower in high stage patients than it was in low stage patients and controls, but in the regional lymph nodes it was paradoxically higher. The NK activity of regional lymph nodes against autologous tumor cells was low in 8 patients with bladder cancer. It appears from this study that the regional lymph nodes have no function as immunological barriers for metastasis and we therefore conclude that they should be dissected during surgery.