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Biomedical subjects

T Andoh

Publications and source records attributed to T Andoh.

266 records · Page 15Linked to original sources
PubMed1975

Breakage of a DNA-protein complex induced by 4-nitroquinoline 1-oxide, 4-nitropyridine 1-oxide, and their derivatives in cultured mouse fibroblasts.

The effects of a number of 4-nitroquinoline 1-oxide and 4-nitropyridine 1-oxide derivatives, with varying carcinogenic potencies, on the scission of proteins linking DNA were studied in cultured mouse fibroblasts, strain L-P-3. With twenty-two 4-nitroquinoline 1-oxide derivatives and twelve-4-nitroquinoline 1-oxide derivatives tested, an excellent correlation was found between the scission effect of each compound and its carcinogenicity. All carcinogens, whether strong or weak, showed positive results in the scission test. Strong carcinogens such as 4-nitroquinoline 1-oxide, 2-methyl-4-nitroquinoline 1-oxide, 6-methyl-4-nitroquinoline 1-oxide, 6-chloro-4-nitroquinoline 1-oxide,and 4-hydroxyaminoquinoline 1-oxide induced the scission at a low concentration of 1 x 10-5 M, while weak carcinogens such as 3-methyl-4-nitroquinoline 2-oxide, 6-n-butyl-4-nitroquinoline 1-oxide, 6-tert-butyl-4-nitroquinoline 1-oxide, 6-n-hexyl-4-nitroquinoline 1-oxide, and 6-carboxy-4-nitroquinoline 1-oxide only produced the same effect a dose levels higher than 5 x10-5 M. On the other hand, some noncarcinogenic derivatives such as 8-nitroquinoline 1-oxide, 4-hydoxy-quinoline 1-oxide, 4-aminoquinoline 1-oxide, and 6-nitroquinoline could not induce the scission, while other noncarcinogens such as 3-nitroquinoline 1-oxide, 5-nitroquinoline 1-oxide, and 5-nitroquinoline did induce scission at concentrations higher than 1 x 10-4 M. Throughout these tests the effective concentrations of active compounds were generally much lower than the concentration at which the compounds were cytotoxic. The implication of the results and the feasibility of the present method of analysis as a screening procedure for potential carcinogens and muagens are discussed.

Animals↗
PubMedDate not supplied

Regulation of estrogen receptor and epidermal growth factor receptor by tamoxifen under high and low estrogen environments in MCF-7 cells grown in athymic mice.

The purpose of this study was to investigate whether tamoxifen (TAM) treatment causes a downregulation of estrogen receptor (ER) and whether TAM induces epidermal growth factor receptor-1 (EGFR). We investigated the expression of ER and EGFR after the treatment of TAM in MCF-7 tumors grown in athymic mice under high and low estrogen environments. MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release 17beta-estradiol (E2) pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into the following 4 groups: i) an E2 (0. 72 mg/pellet) pellet [E2(+)]; ii) an E2 and a TAM (5 mg/pellet) pellets [E2(+)TAM]; iii) no treatment [E2(-)]; iv) a TAM pellet [E2(-)TAM]. A significant reduction in tumor size was observed in the estrogen-depleted group [E2(-) and E2(-)TAM] compared with the estrogen-completed group [E2(+) and E2(+)TAM]. TAM inhibited estrogen-stimulated growth in the estrogen-completed mice. No additional reduction of the tumor by TAM was observed in the estrogen-depleted mice. Both ER and EGFR protein levels in the tumors of the estrogen-depleted mice were higher than in the estrogen-completed mice. Expression of ER and EGFR protein was increased by TAM in the estrogen-completed mice, however it was decreased by TAM in the estrogen-depleted mice. Changes of ER and EGFR protein levels were similar in all treatments. Transforming growth factor-alpha (TGF-alpha) in tumors, which is known as a ligand of EGFR and as an estrogen-inducible protein in ER positive MCF-7 cells, was decreased by TAM in the estrogen-completed mice, by contrast, it was increased by TAM in the estrogen-depleted mice. Downregulation of ER was observed in TAM-treated mice in an estrogen-depleted environment, this action of TAM was similar to E2. These results suggest that increase of EGFR expression does not lead to a loss of ER after short-term TAM treatment in MCF-7 tumors.

Animals↗
PubMedDate not supplied

Effect of a combined administration of 5-fluorouracil and medroxyprogesterone acetate on pyrimidine nucleoside phosphorylases and thymidylate synthetase in 7,12-dimethylbenz.

The effect of a combined therapy of medroxyprogesterone acetate (MPA) and 5-fluorouracil (5-FU) on tumor size, pyrimidine nucleoside phosphorylase (PyNPase) activity, and thymidylate synthetase (TS) activity was examined in Sprague-Dawley (SD) rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. MPA augmented the antitumor activity of 5-FU and protected against body weight-loss due to 5-FU administration. PyNPase activity of both the MPA group and the MPA+5-FU group tended to increase compared with that of the 5-FU alone group. TS inhibition levels in the MPA+5-FU group tended to increase compared with those in the 5-FU alone group. These results indicate that MPA tended to augment antitumor activity of 5-FU and to reduce the side effects caused by 5-FU.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Antitumor effect of 22-oxacalcitriol on estrogen receptor-negative MDA-MB-231 tumors in athymic mice.

The purpose of this study was to evaluate the usefulness of 22-oxacalcitriol (OCT) in the treatment of estrogen receptor (ER)-negative breast cancer. The antitumor effect of this agent and its effect combined with doxifluridine (5'-DFUR) on MDA-MB-231 tumors in female athymic mice were investigated. We also examined the effect of OCT on the expression of vascular endothelial growth factor (VEGF) which had been reported to generate angiogenesis in tumors. OCT significantly suppressed the growth of tumors without inducing hypercalcemia in a dose dependent manner. The effect of OCT combined with 5'-DFUR did not exceed the effect of a single agent therapy. The expressions of VEGF analyzed by enzyme-linked immunosorbent assay were significantly decreased in the OCT-treated group. These results suggest that OCT may partially suppress tumor growth by inhibiting neovascularization and it would likely have positive application as a treatment of ER-negative breast cancer.

Animals↗
PubMedDate not supplied

Subcutaneous mastectomy with axillary dissection plus breast reconstruction using latissimus dorsi myocutaneous flap (or latissimus dorsi muscle) for breast cancer.

Subcutaneous mastectomy with axillary dissection plus breast reconstruction using latissimus dorsi myocutaneous flap (or latissimus dorsi muscle) was carried out for 8 patients with breast cancer. These consisted of 1 patient with non-invasive ductal carcinoma, 5 with stage I (4 invasive ductal carcinomas and 1 invasive lobular carcinoma) and 2 with stage II (1 invasive ductal carcinoma and 1 invasive lobular carcinoma). Cancer cells were recognized histopathologically in the resection margins of the small mammary gland resting under the nipple in only 1 case, and the remaining 7 cases underwent a curative resection. In the prognosis, 7 patients were disease-free and 1 showed a local recurrence. The patient with local recurrence showed no metastasis after the resection of the local lesion. The cosmetic results of this operation were excellent in all patients. This operation was effective both for these patients with breast cancer who did not want to undergo breast conserving surgery or modified radical mastectomy and for those who were excluded from the criteria of breast conserving surgery from the prognostic and cosmetic points of view.

Adult↗
PubMedDate not supplied

The combination of different types of antitumor topoisomerase II inhibitors, ICRF-193 and VP-16, has synergistic and antagonistic effects on cell survival, depending on treatment schedule.

VP-16 and ICRF-193 are different types of antitumor topoisomerase II inhibitors, being cleavable and non-cleavable complex-stabilizing types, respectively. To examine the possibility of enhancing the efficacy of combination chemotherapy, we carried out simultaneous and sequencial treatment of cells with the two drugs. When KB cells were exposed continually to low concentrations (0.05 - 0.2 microM) of the drugs, the effects were synergistic. In contrast, when the cells were treated with high concentrations of ICRF-193 and VP-16 for 1 hour, the VP-16-induced cytotoxicity was prevented by ICRF-193 and the degree of prevention was increased by the pretreatment of cells with ICRF-193, while post-treatment with ICRF-193 had little effect on the cytotoxicity of VP-16. ICRF-193 at 1 microM was found to interact with about half molecules of topisomerase IIa and II beta in cells, as judged by increased amounts of a salt-stable complex. ICRF-193 inhibited in vitro VP-16-induced cleavable complex formation, but a much higher concentration was needed to reverse the cleavage already generated by VP-16. Thus, the antagonistic or synergistic effects of ICRF-193 and VP-16 depend on the concentration of the drug, as it may be critical as to how many molecules of cellular topoisomerase II interact with the drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Breast conserving surgery with nipple resection.

Breast conserving surgery with nipple resection was carried out on 4 patients with early breast cancer because location of each tumor was very close to nipple. These consisted of 3 patients with state I invasive ductal carcinoma and 1 patient with stage II invasive ductal carcinoma. Cancer cells were not recognized histopathologically in the resection margins of each case and all cases underwent a curative resection with axillary dissection (up to level III). The rested areola in each case was made to be round-shaped by skin suture and the edge of the wound located in the center of areola looked like a small nipple. The cosmetic result of this operation were excellent in all patients. This operation may be effective both for these patients with early breast cancer locating under the nipple or areola and for those whose tumor was very close to nipple.

Adult↗
PubMedDate not supplied

Antitumor effects of SEF19, a new nonsteroidal aromatase inhibitor, on 7,12-dimethylbenz[a]anthracene-induced mammary tumors in rats.

The antitumor and endocrine effects of a new nonsteroidal aromatase inhibitor, 2-(imidazol-1-yl)-4,6-dimorphorino-l, 3, 5-triazine (SEF19) were examined in female Sprague-Dawley rats bearing estrogen dependent 7,12-dimethylbenz[a]anthracene(DMBA)-induced mammary tumors, and the effects were compared with those of CGS20267. The rats bearing DMBA-induced mammary tumors within 6-15 weeks after the DMBA administration were divided into the treatment groups once a week every week, and they were treated with SEF19, CGS20267 and vehicle for 4 weeks. One hundred rats were sacrificed 4 hours after the last administration, and the remaining 60 rats were sacrificed after a 4-week recovery period. During the treatment and recovery period, the tumor size was generally smaller in the SEF19 and CGS20267-treated subgroups than in the control subgroup. Tumor sizes in the subgroups treated with high doses of SEF19 (25 mg/kg/day and 50 mg/kg/2 days) were reduced to the size of the CGS20267-treated subgroup. The CGS20267-treated rats showed decrease in the serum estradiol level and an increase in the serum testosterone level. Their uterine weights were reduced. SEF19 treatment failed to show any effect on the serum levels of estrone, estradiol, testosterone and androstenedione, but it suppressed uterine weight in a dose-dependent manner. After the recovery period, no effect was detected in the serum concentrations of steroid hormones and the weight of the organs. At every dose used in the present study the aromatase inhibitory activity of SEF19 was weaker than that of CGS20267, but the inhibitory effect on mammary tumor growth of SEF19 at high doses was comparable to that of CGS20267. We conclude that the antitumor effect of SEF19 is not due to aromatase inhibition but mainly to its direct cytotoxicity.

9,10-Dimethyl-1,2-benzanthracene↗