Eijiro Okajima

Inhibitory Effect of Tomato Juice on Rat Urinary Bladder Carcinogenesis after N-Butyl-N-(4-hydroxybutyl)nitrosamine Initiation

The effects of tomato juice on urinary bladder carcinogenesis were studied in male Fischer 344 rats initiated with N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN) in rats. The animals (6 weeks old) were given 0.05% BBN in their drinking water for 8 weeks, followed by diluted tomato juice for 12 weeks, and killed at 20 weeks after the beginning of the experiment. Lycopene concentrations in the livers of rats given tomato juice were elevated. Histopathological analysis of urinary bladder lesions revealed the numbers, but not incidences, of urinary bladder transitional cell carcinomas (TCCs) to be decreased in the group given tomato juice. No influence on the incidence of simple and nodullopapillary hyperplasias, invasion or differentiation of TCC was noted. These results indicate that tomato juice, presumably the contained lycopene and other anti‐oxidants in combination, exerts an inhibitory effect on the development of TCCs in the rat urinary bladder.

Effect of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine

SummaryMale and female Wistar strain rats were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 6 weeks and then water without BBN for 18 weeks. Diethylstilboestrol and testosterone were implanted subcutaneously into both intact and gonadectomised animals before or after treatment with BBN to evaluate their effects on the development of bladder tumours. Diethylstilboestrol reduced the incidence of bladder tumours significantly in male rats. The incidence was higher in female rats after spaying and administration of testosterone after BBN treatment, than in the intact female.-These results suggest that diethylstilboestrol inhibits carcinogenesis of the urinary bladder induced by BBN and growth of bladder tumours induced by BBN, in male rats. On the other hand, testosterone seems to stimulate the growth of bladder tumours induced by BBN in female rats.

Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and β-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment

The effects of the non‐steroidal anti‐inflammatory drug (NSAID) piroxicam and the carotenoids lycopene and β‐carotcnc, alone or in combination, on the development of rat superficial urinary bladder carcinomas induced by N‐butyl‐N‐(4‐hydroxybutyI)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old, were given 0.05% BBN in the drinking water for 8 weeks followed by administration of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water) and/or β‐carotene (0.0025% in the drinking water) for 12 weeks, then killed for histological analysis of urinary bladder lesions. Cell proliferation potential was analyzed by immunohistochemical staining of the proliferative cell nuclear antigen (PCNA). Piroxicam alone, piroxicam+lycopene, and piroxicam +lycopene+β‐carotene all significantly decreased the incidences and numbers of transitional cell carcinomas (TCCs), but the combination of piroxicam with carotenoids did not result in a clear improvement in the preventive potential of piroxicam. Piroxicam +β‐carotene also caused a significant reduction and lycopene alone a slight but not significant reduction in the number of TCCs. In contrast, β‐carotene alone and lycopene +β‐carotene were without inhibitory influence on any of the lesion categories examined, and the latter significantly increased the proportion of high‐grade TCCs. Nevertheless, all of the chemopreventive agents, either alone or in combination, significantly decreased the TCC PCNA index, the effect extending to the surrounding epithelium in the piroxicam 4‐lycopene and piroxicam+lycopene+β‐carotene groups. These results indicate that the NSAID piroxicam may he a more effective chemopreventive agent than lycopene and β‐carotene for superficial urinary bladder carcinogenesis.

Prognostic factors of renal cell carcinoma with extension into inferior vena cava

Objective:  To evaluate the prognosis of our series of patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy.

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid‐production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0–215.7 times the low levels found in control pancreas and spleen tissues. Late‐passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase. Mol. Carcinog. 18:153–159, 1997.

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan : 1999-2001 report from the Japanese Urological Association

Objective:  To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non‐muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette‐Guérin (BCG) therapy.

Infrequent somatic alteration of p16/MTS1 in human primary superficial bladder cancers

Although superficial bladder cancer, usually presenting as low grade transitional cell carcinomas, are easily resected by transurethral intervention, their frequent recurrence and progression of satage or grade of the recurrent tumors in some cases is a major problem in urology. Deletion of chromosome 9, bands 9p21-22 in bladder cancers including the lowest grade and stage, suggest potential location of candidate tumor suppressor genes. Recently, p16/MTS1 was isolated from 9p21-22 as a multiple tumor suppressor gene, which regulates the cyclin dependent kinase 4 in the G1/S phase of the cell cycle. In the present study, somatic alterations of p16/MTS1 were examined concentrating on histologically defined superficial bladder carcinomas by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) technique using paraffin embedded materials. Infrequent alterations of p16/MTS1 in superficial bladder cancers, one deletion and one silent mutation in 15 cases, were detected. The results suggest that p16/MTS1 mutation is not involved in the development of superficial urinary bladder carcinomas.

Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association

Objectives:  It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.

Disturbance of the Cell Cycle with Colchicine Enhances the Growth Advantage of Diethylnitrosamine‐initiated Hepatocytes in Rats

The effect of cell cycle disturbance due to colchicine on the induction of enzyme‐altered foci during liver regeneration in rats was studied. For initiation, diethylnitrosamine (DEN) at a dose of 10 mg/ kg was injected intraperitoneally and partial hepatectomy (PH) was performed 4 h thereafter. Colchicine at doses of 0, 0.1, 0.25 and 0.5 mg/kg was injected intraperitoneally 1 and 3 days after the initiation, followed by application of selection pressure consisting of 2‐acetylaminofluorene (AAF) and carbon tetrachloride (CCl4) administration. As end point lesions, γ–glutamyltransferase (GGT)‐positive enzyme‐altered foci were assayed at week 5. There was no significant effect of colchicine on numbers of foci. However, a significant, dose‐dependent increase in the area of GGT‐positive lesions in the groups treated with colchicine was observed. Bromodeoxyuridine labeling indices were higher in foci induced in colchicine‐treated rats than in the untreated rats. In a separate experiment, serum glutamic pyruvic transaminase was not increased significantly after DEN and colchicine treatment, and the mitotic index at 6 days after PH was increased in the liver of colchicine‐treated rats. These results suggest that the cell cycle disturbance induced by colchicine causes more pronounced selective growth of cells initiated by DEN and colchicine, and this experimental model may be useful for analyzing the mechanisms underlying that growth advantage and the effects of cell cycle abnormalities in liver carcinogenesis.

Effects of single chemotherapeutic agents on development of urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats

SummaryChemotherapeutic agents were evaluated for effect on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in male Wistar strain rats. Seven hundred and two rats were given 0.05% BBN in drinking water for 8 weeks. After BBN treatment, the animals were divided into 26 groups to follow regimens of single chemotherapy. All drugs were administered intraperitoneally except in one group that was treated orally. In our experimental series, 5-fluorouracil (5-FU), N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207), carbazilquinone (CQ), vincristine (VCR) and cis-diamminedichloroplatinum (CDDP) were effective in inhibiting the incidence of bladder tumor, however, adriamycin (ADM), mitomycin C (MMC), neocarsinostatin (NCS), cyclophosphamide (CPM) and bleomycin (BLM) were not effective.