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Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 163 records · Page 9Linked to original sources
PubMed1990

Mutagenicity of oxidized microsomal metabolites of 1-nitropyrene in Chinese hamster ovary cells.

1-Nitropyrene, a tumorigenic environmental pollutant, is mutagenic in Chinese hamster ovary (CHO) cells in the presence of a liver homogenate 9000 g supernatant fraction (S9). The metabolic pathways involved in this response were studied by comparing the mutagenicities at the hypoxanthine-guanine phosphoribosyl transferase locus of 1-nitropyrene, some oxidized microsomal metabolites of 1-nitropyrene, and related compounds. In the absence of S9, pyrene 4,5-oxide and 6-hydroxy-1-nitropyrene displayed the highest mutagenicities, followed by 1-nitropyrene 9,10-oxide and 1-nitropyrene 4,5-oxide; 3- and 8-hydroxy-1-nitropyrene were weaker mutagens, while pyrene and 1-nitropyrene were essentially without activity. With S9, the order of mutagenic potency was 1-nitropyrene 4,5-oxide greater than 6-hydroxy-1-nitropyrene approximately 1-nitropyrene 9,10-oxide greater than 1-nitropyrene approximately 3-hydroxy-1-nitropyrene approximately 8-hydroxy-1-nitropyrene greater than pyrene approximately pyrene 4,5-oxide, with the latter two compounds being essentially inactive. Inclusion of the epoxide hydrolase inhibitor 1,2-epoxy-3,3,3-trichloropropane during the S9-mediated treatment of CHO cells with 1-nitropyrene increased mutation induction 5-fold. Also, liver microsomes prepared from guinea-pigs treated with Aroclor 1254 mediated a stronger mutagenic response with 1-nitropyrene than microsomes from Aroclor-treated rats. 1-Nitropyrene was essentially non-mutagenic in the presence of microsomes from untreated and phenobarbital-treated rats. Examination of the 1-nitropyrene metabolites produced during the microsomal incubations indicated that Aroclor-induced guinea-pig microsomes yielded substantial amounts of 1-nitropyrene 4,5-dihydrodiol, while Aroclor-induced rat microsomes produced 6-fold more 6- and 8-hydroxy-1-nitropyrene than phenobarbital microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Detection of the c-myc gene product in urinary bladder cancer.

Expression of the c-myc gene product in urinary bladder cancer was investigated by immunohistochemical staining with anti-c-myc monoclonal antibody (mAb) MYC-1. Positive staining was observed in the cytoplasm, but not in the nucleus in tissues fixed with 10% formalin. On the other hand, positive staining was localized in the nucleus in cryopreserved tissues. Of 34 cryopreserved specimens examined, positive staining with MYC-1 mAb was observed in 1 of 12 (8.3%) of grade 1 (G1), 12 of 15 (80%) of G2 and 6 of 7 (86%) of G3. Positive staining with Ki-67 mAb was observed in 2 of 12 (17%) of G1, 12 of 15 (80%) of G2, and 6 of 7 (86%) of G3. These results suggest that tumors with higher nuclear pleomorphism contain more proliferating cells.

Carcinoma, Transitional Cell↗
PubMed1990

[Upper urinary tract tumors following bladder cancer].

We treated in total 795 patients with primary transitional cell carcinoma of the urinary bladder between April, 1964 and December, 1988. Eighteen patients of them had upper urothelial cancer during the follow-up period. Thirteen of the 18 patients had received transurethral resection for the initial bladder cancer, while 3 total cystectomy and 2 segmental resection. The over-all incidence of bladder cancer patients who subsequently developed upper urinary tract tumors was 2.3 per cent. The interval between initial treatment of the bladder cancer and treatment for the upper urinary tract tumor ranged from 2 to 74 months (median 20 months). The five-year survival rate after treatment for the upper urinary tract tumor was 31.7 per cent. We conclude that the following are high risk patients for development of upper urinary tract recurrences: 1) patients with bladder cancer near orifices, 2) patients with recurrent bladder cancer under bladder preserving treatment for a long time, 3) patients with G2 multifocal bladder cancer.

Aged↗
PubMed1990

[Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer].

Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer.

Animals↗
PubMed1989

Correlation of c-myc expression with nuclear pleomorphism in human renal cell carcinoma.

The expression of the c-myc gene product in renal cell carcinomas was examined by immunostaining with monoclonal antibody (mAb) MYC-1. The effects of preservation and fixation of tissues on staining were first examined. In cryostat sections fixed with 4% buffered formalin for 15 min, staining was observed in the nucleus. On the other hand, in paraffin sections after fixation with 10% formalin, staining was observed in the cytoplasm, but not in the nucleus. Because c-myc protein has been shown to be a nuclear protein, the finding that c-myc protein was not detectable in the nucleus appeared to be due to the preservation or fixation procedures used. Therefore, cryostat sections fixed with 4% formalin were used to investigate the correlation between the reaction of MYC-1 mAb and nuclear pleomorphism in primary and metastatic renal cell carcinomas. Among 41 primary tumors, positive staining was observed in 2 of 17 tumors (12%) of grade 1, 17 of 21 (81%) of grade 2, and all 3 (100%) of grade 3. Among 17 metastatic tumors, positive staining was not observed in any of the 5 (0%) of grade 1 but was observed in 2 of 4 (50%) of grade 2 and all 8 (100%) of grade 3. Thus, the frequency of the positive reaction with MYC-1 mAb was correlated with nuclear pleomorphism in primary and metastatic renal cell carcinomas. The reaction of Ki-67 mAb, which recognized a nuclear antigen present in proliferating cells, was also correlated with nuclear pleomorphism. These findings suggest that the c-myc gene product plays a role in cell proliferation in renal cell carcinomas.

Antibodies, Monoclonal↗
PubMed1989

[VM-26 and VP-16 salvage therapy for refractory germinal testicular cancers].

Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients received salvage chemotherapy with VM-26 (50 mg/m2, twice a week X 6 weeks) and cisplatin (CDDP, 20 mg/m2 for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100 mg/m2) and CDDP (20 mg/m2) (P-VP), all given daily for 5 consecutive days every 3-4 weeks for 4-5 courses. Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxicity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatin offers potentially curative treatment to patients with refractory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective.

Adult↗
PubMed1989

[A case of primary ureteral squamous cell carcinoma associated with calculus].

A case of primary squamous cell carcinoma of the ureter associated with ureteral calculus is presented. A 66-year-old woman was admitted to our hospital, with the chief complaint of macroscopic hematuria in October, 1985. A kidney-ureter-bladder X-ray and drip intravenous pyelography failed to reveal the calculus shadow clearly. However, computerized tomographic scan revealed the calculus shadow clearly adjacent to the ureteral tumor, and retrograde pyelography revealed the filling defect on a third lower portion of the left ureter. She was diagnosed with tumor of the ureter associated with the calculus. She underwent complete nephroureterectomy with excision of a periureteral cuff of the bladder. The tumor was diagnosed histologically as squamous cell carcinoma. Metastases and recurrence of tumor have never occurred on July, 1987. Forty-four cases of the primary ureteral squamous cell carcinoma could be collected in the Japanese literature. Moreover, we deal with this disease associated with the ureteral calculus.

Aged↗
PubMed1988

Mutagenicity and nitropyrene concentration of indoor air particulates exhausted from a kerosene heater.

The particulates in a room warmed with a radiant kerosene heater were collected, extracted and fractionated into diethyl ether-soluble neutral, acidic and basic fractions. The mutagenicity of these fractions was measured with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8-DNP6 and TA100 in the presence and absence of S9 mix. Room air without the heater showed very low mutagenicity. However, a sample from a room at the beginning of the burning period showed very high mutagenicity (237 His+ revertants/plate/m3 of air in strain TA98 in the absence of S9 mix). In contrast, emissions from the heater after it was burning stably showed low mutagenicity (9 His+ revertants/plate/m3). The crude extract of particulates from the heater at the beginning of the burning period was analyzed by high-pressure liquid chromatography (HPLC) and showed a considerable amount of nitropyrenes (NPs); the concentrations of 1-NP and 1,6-diNP were 1.62 ng and 0.149 ng/m3 of air, respectively, and accounted for 1.2% and 17.6%, respectively, of the mutagenicity in strain TA98 in the absence of S9 mix. In addition, an HPLC-Ames histogram showed that peaks of mutagenicity corresponding to 1-NP and diNPs accounted for 75.7% (1-NP, 4.9%; 1,6-diNP, 17.1%; 1,8-diNP, 46.3%; 1,3-diNP, 7.4%) of the HPLC-recovered mutagenicity for strain TA98 without S9 mix. These results that kerosene heaters, especially immediately after ignition, create mutagenic substances such as NPs.

Air Pollutants↗
PubMed1988

DNA adduct formation during continuous feeding of 2-acetylaminofluorene at multiple concentrations.

A linear relationship was observed between the administered dose and DNA adduct levels in the livers and bladders of BALB/c mice fed the carcinogen, 2-acetylaminofluorene (2-AAF), continuously for one month. A similar linear correlation was found between the probit of the liver tumour incidence and the log of the liver DNA adduct levels; however, because there is a no-observable-effect level for bladder tumour induction, the relationship between the probit of the bladder tumour incidence and bladder DNA adduct levels was not linear. These data suggest that the relationship between DNA adduct formation and tumour incidence may be tissue specific.

2-Acetylaminofluorene↗
PubMed1987

Postoperative systemic adjuvant chemotherapy for bladder cancer.

Forty-six patients with bladder cancer without distant metastasis (M0) were treated by chemotherapy as an adjuvant after total cystectomy using three protocols (protocol I: adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and cis-platinum 50 mg/m2 i.v., starting at least 2 weeks after surgery every 3 weeks for three cycles; protocol II: adriamycin 30 mg/m2 on the 1st postoperative day, cyclophosphamide 300 mg/m2 on the 1st and the 7th days; protocol III: FT-207 60 mg/m2, p.o. every day for 1 year). Average follow-up periods after surgery by protocol were 18 months for protocol I, 31 for protocol II, and 43 for protocol III. Analysis of the survival curves showed no statistically significant differences among the three groups or between a historical control group of 106 patients and the entire patient population examined in the present study. The histopathological grades recorded in the 46 patients were G1, G2, and G3 in 1, 22, and 23, respectively. However, from a study of 48 pT3 and pT4 cases, the survival rate of 10 patients receiving protocol I therapy was statistically significantly higher than those of 12 patients treated according to protocol II and of 26 historical controls, at 1 year and 2 years, respectively. Toxic effects, with gastrointestinal symptoms including nausea and vomiting and myelosuppression (including leukopenia and anemia) were more frequent with protocol I. Alopecia occurred in about 80%-90% of patients treated according to either protocol I or II. Almost all patients could tolerate adjuvant chemotherapy, and none of them died as a result of these regimens. The results recorded in this study justify the evaluation of combination adjuvant chemotherapy with adriamycin, cyclophosphamide and cis-platinum in a prospectively randomized trial.

Adult↗
PubMed1987

Genotoxicity of a variety of nitroarenes and other nitro compounds in DNA-repair tests with rat and mouse hepatocytes.

Genotoxicity of a variety of nitroarenes and other compounds was examined in DNA-repair tests with rat or mouse hepatocytes. Out of 15 nitroarenes tested, 9 compounds, i.e., 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene, 1-nitro-3-acetoxypyrene, 3-nitrofluoranthene, 2-nitrofluorene, 2,7-di-nitrofluorene and 5-nitroacenaphthene elicited positive response of DNA repair in the tests with rat and mouse hepatocytes. Among the positive chemicals, the DNA-repair level of the 3 dinitropyrene isomers was much higher than other nitroarenes. The results indicate that a number of nitroarenes are metabolically activated in the primary culture of rodent hepatocytes, and suggest potential carcinogenicity of 1-nitropyrene and 1-nitro-3-acetoxypyrene the carcinogenicity of which is either not clear or unknown. Of the other nitro compounds, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide as well as 4-nitroquinoline 1-oxide were clearly genotoxic in the assays with hepatocytes of both species. However, 5-nitro-2-furaldehyde semicarbazone was negative in both assays with hepatocytes of 2 species.

Animals↗