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Although intravesical instillation of bacillus Calmette-Guerin (BCG) is a clinically well-recognized therapy for bladder carcinoma in situ and recurrence prophylaxis, these mechanisms have not been fully understood. We studied the effects of BCG infection (Connaught strain) on target cancer cells and host immune systems in murine bladder cancer. The bladder cancer cell line, MB49, was used in C57/BL6 mice in vivo and in vitro. In vitro cytotoxicities against the cancer cell line were measured by 24-h 51Cr release assay. For effector cells, spleen mononuclear cells were obtained from mice injected intraperitoneally with BCG or BCG-infected irradiated MB49 cells. Although BCG infection of cancer cells did not affect the proliferation speed in vitro, the mice injected subcutaneously with BCG-infected MB49 cells survived significantly longer than those given untreated cancer cells. The mice surviving without tumor growth after injection of BCG-infected cancer cells could not reject a second injection of intact MB49 cells. In vitro cytotoxicity was enhanced by BCG infection of target cancer cells, but not by immunizing the mice with BCG from which effector cells were obtained. Moreover, cytotoxicity disappeared by depleting natural killer (NK) cells from effector cells. Although in vitro cytotoxicity was increased by immunizing the mice with BCG-infected irradiated MB49 cells, survival did not improve in these mice. These results suggest that a major part of BCG's anti-tumor effects can be attributed to the elimination of BCG-infected cancer cells by NK cells.

Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases reported to date. In this study, we report on a case of a 73-year-old male who presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right nephrectomy and left ureterocutaneoustomy were performed, and histological study disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the tumor was highly aggressive with a short clinical course, and the patient died of carcinomatous pleuritis at one month after surgery. Subsequently, we successfully established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion of the patient.

Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases reported to date. In this study, we report on a case of a 73-year-old male who presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right nephrectomy and left ureterocutaneoustomy were performed, and histological study disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the tumor was highly aggressive with a short clinical course, and the patient died of carcinomatous pleuritis at one month after surgery. Subsequently, we successfully established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion of the patient.

Arachidonic acid (AA) metabolites derived from both the lipoxygenase (LOX) and cyclooxygenase (COX) pathways transduce a variety of signals related to cell growth. Selective blockade of the different metabolic pathways of AA (using a general LOX inhibitor NDGA, a 5-LOX inhibitor AA861, a 12-LOX inhibitor baicalein and a general COX inhibitor ibuprofen) revealed that murine bladder cancer cell line (MBT-2) cell proliferation was inhibited by the LOX inhibitors concentration-dependently, but not by the COX inhibitor. Among the LOX inhibitors, baicalein showed the strongest inhibition and induced apoptosis of MBT-2. Proliferation of MBT-2 was also significantly inhibited by 12-LOX antisense oligonucleotides. In an in vivo experiment, the antitumor effects of baicalein administration on C3H/HeN mice implanted with MBT-2 were recognized. These results suggested that LOX inhibition may be significant in the treatment of bladder cancer.

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors. Especially so MMP-7, as it is mainly produced by the actual cancer cells. However, the expression of MMP-7 in transitional cell carcinoma (TCC) of the urinary bladder has not been previously investigated. We examined expressions of MMP-7 and MMP-2 in TCC, and compared them with clinicopathological characteristics in TCCs. Tumor samples from 20 patients with TCC of the urinary bladder who had surgery performed at the Osaka City University Medical School Hospital were immunohistochemically stained. Expression of MMP-2 was significantly stronger in advanced stage and high grade tumors than in low stage and low grade tumors. MMP-7 was also expressed in TCC, having a tendency to be more strongly expressed in high than in low grade tumors. However, there was no significant difference of MMP-7 expression between advanced and low stages. This increased expression of MMP-7 in high grade TCC of the urinary bladder may be associated with tumor invasion and metastasis.

The accurate diagnostic localization of extra-adrenal pheochromocytoma is important in the treatment of primary and metastatic tumors. In this study, we report on a case of extra-adrenal pheochromocytoma in which the tumor could not be diagnosed by 131I-metaiodobenzylguanidine (MIBG) scintigraphy but only by 123I-MIBG scintigraphy. Our patient was a 16-year old girl whose chief complaint was headaches. High levels of catecholamines were detected in the blood and urine samples. 131I-MIBG scintigraphy could not detect any abnormal accumulation, but an accumulation of 123I-MIBG was found in the pelvis. Magnetic resonance imaging (MRI) revealed a broad-based bladder tumor at the site of the accumulation. Partial cystectomy was performed, and immunohistochemical staining examination confirmed the diagnosis of extra-adrenal pheochromocytoma in the urinary bladder. In this report, we compare 131I-MIBG scintigraphy with 123I-MIBG scintigraphy and discuss their characteristics.

In the two cases we report here, tumors were diagnosed as nephrogenic adenoma by pathohistological examination. Case 1 was a 72-year-old female presenting with a bladder tumor 8 months after receiving ureteral tumor surgery. Transurethral resection of bladder tumor (TUR-Bt) was performed. Case 2 was a 57-year-old female who had received intravesical bacillus Calmette-Guérin (BCG) treatment 6 times after her fifth TUR-Bt. Two tumors were found by cystoscopy, and TUR-Bt was performed. There have been 39 cases of nephrogenic adenoma of the bladder reported in Japan; 21 were male and 18 female with a mean age of 56.5 years. The main complaint was hematuria, which was seen in 16 cases followed by pollakisuria in 6 cases. Nephrogenic adenoma occurred after surgery of the urinary tract in 16 cases, followed by urinary tract infection in 9 cases and intravesical BCG treatment in 6 cases. The ratio of cases occurring after intravesical BCG treatment has increased since BCG approval for bladder carcinoma treatment in December 1996 in Japan, and an increase in the number of cases is expected in the future.