Hisashi Matsuki

Promoting effect of 2,4-diaminoanisole sulfate on rat thyroid carcinogenesis

Two experiments were conducted to examine the effects of 2,4-diaminoanisole sulfate (2,4-DAAS) on thyroid function and carcinogenesis in male Wistar rats. In experiment 1, feeding with 2,4-DAAS resulted in significantly elevated levels of thyroid stimulating hormone (TSH), reduced thyroxine (T4) and triiodothyronine (T3) in the serum, although the latter had almost recovered to normal levels by week 6. However, skin application did not affect serum levels. In experiment 2, administration of 0.5% 2,4-DAAS in the diet for 19 weeks, a week after a single 210 mg/100 g body weight i.p. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN), significantly increased the incidence and numbers of preneoplastic lesions (focal hyperplasia), adenomas and carcinomas developing in the thyroid gland. Histologically, brown pigment was usually observed within follicular epithelial cells in non-tumorous regions, but not in the tumors themselves.

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.

Neoadjuvant Therapy for Locally Invasive Bladder Cancer: Results of Randomized Trials in 40 Patients

The present investigation was conducted to examine the effect of a neoadjuvant cyclophosphamide, doxorubicin and cisplatin (CAP) regimen with radiotherapy for locally invasive bladder cancer as a well-controlled randomized trial. Since 1986, a total of 40 patients with primary transitional cell carcinoma of the urinary bladder have been randomized into two groups: neoadjuvant CAP plus radiation-treated group and control group. Of 18 patients who received neoadjuvant chemotherapy, complete and partial responses were observed in 52.9% of 17 measurable and evaluable patients and downstaging was observed in 92.9% of 14 evaluable patients. The 3-year survival rates of the neoadjuvant-treated and control group were 93.8 and 83.6%, respectively. No statistical significance was achieved in the survival rates. These results indicated that neoadjuvant CAP would be useful in the management of invasive bladder cancer.

Effects of trisodium nitrilotriacetate monohydrate, nitrilotriacetic acid and ammonium chloride on urinary bladder carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine

The effects of trisodium nitrilotriacetate monohydrate (Na3 NTA.H2O) nitrilotriacetic acid (H3NTA) and ammonium chloride (NH4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na3NTA.H2O, Na3NTA.H2O plus NH4Cl, H3NTA, H3NTA plus NH4Cl, or without these chemicals for 28 weeks. Na3NTA.H2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na3NTA.H2O, without the initiation, itself induced papillary or nodular (PN)-hyperplasia. H3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na3NTA.H2O was more effective than H3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.