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Biomedical subjects

N Sugamata

Publications and source records attributed to N Sugamata.

At least 19 recordsLinked to original sources

[A case of lung and pleural metastases from breast cancer responding to toremifene].

A patient with lung and pleural metastases from breast cancer treated effectively with toremifene is reported. A 62-year-old woman underwent mastectomy for breast cancer, and had high levels of estrogen and progesterone receptor. After 2-years of adjuvant UFT therapy, lung and pleural metastases were seen on a chest x-ray. The patient received a high-dose of toremifene (120 mg/day). After five months with toremifene, a chest x-ray and CT scan showed the disappearance of lung and pleural metastases. No recurrence or metastases have been detected for twenty months to date. No serious side effects were noticed. High-dose toremifene might be an effective therapy for cases of postmenopausal metastatic breast cancer, with high levels of estrogen and progesterone receptor.

Antineoplastic Agents, Hormonal↗

The mechanisms of antitumor effects of luteinizing hormone-releasing hormone agonist (buserelin) in 7, 12-dimethylbenz(a)anthracene-induced rat mammary cancer.

We evaluated the mechanism of antitumor effects of buserelin, which is one of LH-RH agonists, on a hormone dependent breast cancer model, using 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancer. Rats developing solid mammary tumors within 5-7 weeks following the DMBA administration were divided into groups weekly, and treated without delay. The tumor bearing rats were randomized into five groups with regard to tumor size or average weight (15 rats per group). Each group received one of the following treatments during 4 weeks: a) no treatment (NT); b) ovariectomy (Ovx); c) buserelin; d) Ovx and 17beta-estradiol (E2) (Ovx+E2); e) Ovx+E2+buserelin. Tumor regression immediately began at one week after both buserelin treatment and ovariectomy. A significant reduction of tumor size was observed in both buserelin-treated rats and Ovx rats compared with NT rats (p<0.01). No significant difference of tumor size was observed between buserelin-treated rats and ovariectomized rats. No reduction of tumor size was observed in Ovx+E2 rats and Ovx+E2+buserelin rats. Although the mean uterine wet weight of the buserelin group was significantly higher than that of the Ovx group, it was significantly lower than that of the NT group. The mean uterine wet weight of the NT group, the Ovx+E2 group and the Ovx+E2+buserelin group was similar and was significantly higher than that of the Ovx group. Buserelin did not inhibit exogenous estrogen-dependent tumor growth in DMBA-induced rat mammary cancers. These results suggest that buserelin has no direct effects on DMBA-induced rat mammary cancers, and the main mechanism of action of buserelin for tumor-reduction is due to ovarian estrogen deficiency.

9,10-Dimethyl-1,2-benzanthracene↗

A novel aromatase inhibitor, vorozole, shows antitumor activity and a decrease of tissue insulin-like growth factor-I level in 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumors.

Effects of vorozole, a potent and specific non-steroidal aromatase inhibitor, were evaluated on female Sprague-Dawley (SD) rats with 7, 12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Vorozole at a dose of 0.25, 1.0 and 4.0 mg/kg was orally administered once a day for 28 consecutive days. A significant regression in tumor size was observed in each treated group at 1, 2, 3 and 4 weeks after the start of treatment compared with control group. Tissue insulin-like growth factor I (IGF-I) in the DMBA-induced tumors in each treated group significantly decreased in a dose-dependent fashion compared with control group. These results show the mechanism of vorozole in DMBA-induced rat mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗

A new triphenylethylene derivative, TAT-59; hormone receptors; insulin-like growth factor 1; and growth suppression of hormone-dependent MCF-7 tumors in athymic mice.

TAT-59 ((E)-4-[1-[4-[2-(dimethylamino)ethoxy]-phenyl]-2-(4- isopropyl)phenyl-1-butenyl]-phenyl-monophosphate) treatment was performed on hormone-dependent MCF-7 tumors in athymic mice. TAT-59 given at 1, 5, and 20 mg/kg inhibited the estrogen-stimulated growth of MCF-7 tumors in athymic mice in a dose-dependent fashion. The most clear decrease in tumor growth was shown in the TAT-59 alone group, although it was not dramatic. Average serum concentrations of DP-TAT-59((Z)-[1-[4-[2-(dimethylamino)- ethoxy]phenyl]-2-(4-isopropyl)phenyl-1-butenyl]-4-hydroxybenzene) and DM-DP-TAT-59(desmethyl-DP-TAT-59), metabolites of TAT-59, increased in a dose-dependent manner. Much higher levels of DP-TAT-59 and DM-DP-TAT-59 were shown in tumors (target tissues of estrogen) as compared with muscles (nontarget tissues of estrogen) or serum. A serum concentration of DP-TAT-59 or DM-DP-TAT-59 corresponding to the physiologic levels of serum estradiol in premenopausal women was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors in mice. TAT-59 induced a dose-dependent increase in estrogen receptor levels in the MCF-7 tumors. In contrast, it prevented the estradiol (E2)-induced increase in progesterone receptor levels in a dose-dependent manner. Insulin-like growth factor 1 levels measured in the MCF-7 tumors significantly decreased in the TAT-59 alone group and in the no treatment group as compared with the E2 alone group. These results show the pronounced antiestrogenic action of TAT-59 on hormone-dependent MCF-7 tumors in athymic mice.

Animals↗

Effect of toremifene on the growth, hormone receptors and insulin-like growth factor-1 of hormone-dependent MCF-7 tumors in athymic mice.

Toremifene given in different sizes of silastic capsules was used to treat MCF-7 tumors in athymic mice. Toremifene inhibited the estradiol-stimulated growth of MCF-7 tumors in athymic mice. Average serum concentrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased gradually in a capsule-size-dependent fashion. Much higher levels of toremifene or N-demethyl-toremifene were detected in tumors (target tissues of estrogen) as compared with muscles (non-target tissues of estrogen). The concentration of toremifene in serum (i.e., 10-30 ng ml-1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors at physiological (i.e., 200-400 pg ml-1) serum estradiol concentrations in premenopausal women. No significant difference in estrogen receptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-alone group and the no-treatment group (no toremifene or estradiol) tended to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor levels in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) levels in the MCF-7 tumors significantly decreased in the toremifene-alone group as compared with the estradiol-alone group. These results show the antiestrogenic action of toremifene on hormone-dependent MCF-7 tumors in athymic mice.

Animals↗

1 alpha-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] was administered to female Sprague-Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. 1 alpha(OH)D3 suppressed the growth of the rat mammary tumors dose-dependently, and in the high dose groups treated with 0.5-1.0 micrograms/kg of 1 alpha(OH)D3, significant inhibition of tumor growth was observed. But daily oral administration of 1 alpha(OH)D3 for four consecutive weeks caused side effects such as hypercalcemia and weight loss. We compared 0.5 microgram/kg of 1 alpha(OH)D3 three times weekly with the same dose six times weekly to discover whether or not the side effects can be reduced by treatment schedule. Both groups showed a significant oncostatic effect, compared with the control group, while the side effects were relieved in the three times weekly group. Regarding estrogen receptors (ER) in the tumors, there was no significant difference among the groups. These results suggested that the antitumor effect of 1 alpha(OH)D3 on DMBA-induced mammary tumors was not related to ER status. Combined use of 1 alpha(OH)D3 with 5-fluorouracil (5-FU) or medroxyprogesterone acetate (MPA) was also examined. No significant augmentation of the antitumor effect was seen in the two combinations, although the combined therapy with MPA showed a significant inhibition of weight loss in the rats.

9,10-Dimethyl-1,2-benzanthracene↗

Intersite variation of estrogen receptors in human breast cancers and response to endocrine therapy. Which section of a large tumor is the best for estrogen receptor assay?

Estrogen receptor (ER) assays were performed by sucrose gradient centrifugation method at multiple sites in large breast cancers. Intersite variation of ER in a tumor was observed in 24 out of 35 cases. 16 tumors with relatively low ER levels showed different ER status with multiple assays. The results suggest that an assay performed on a small random part of a large tumor may not yield the true ER status. ER value at the largest cross-section was almost the same as the average ER values in each tumor. In addition, 21 cases were examined in relation to ER values at multiple sites in the large tumors and response to endocrine therapy. As the ER value at the largest cross-section was highly correlated with the therapeutic response to endocrine therapy of breast cancer, it would represent true ER status and level. The results suggest that the ER assay at the largest cross-section of a large tumor is an appropriate method to predict response to endocrine therapy.

Breast Neoplasms↗

Antitumor effects of a nonsteroidal aromatase inhibitor (CGS 16949A) on 7, 12-dimethylbenz[alpha]anthracene-induced mammary tumors in rats.

The effects of a nonsteroidal aromatase inhibitor, CGS 16949A, on female Sprague-Dawley (SD) rats with 7, 12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary cancers were examined in relation to estrogen receptors (ER). Rat tumor sizes in each treated group were significantly smaller (P less than 0.05) and rat body weights in most treated groups were significantly increased (P less than 0.05) compared to those in the control group (no treatment) at all measurement points during treatment. Rat uterine weights in each treated group decreased significantly compared with those in the control group (P less than 0.05). There was no significant difference between ER-positive and ER-negative groups in tumor size, body weight or uterine weight. At increased doses of CGS 16949A in the experiment, further increases in testosterone levels and further decreases in estradiol levels were shown to occur. The results suggest the mechanisms of CGS 16949A action not to be influenced by the presence or absence of ER, but to be due to its potent aromatase inhibition of the conversion of androgens to estrogens.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of sequential and combined immuno-endocrine therapies using OK-432 (Picibanil) and tamoxifen on the growth of 7,12-dimethylbenz [alpha] anthracene-induced rat mammary carcinoma.

Effects of sequential and combined immuno-endocrine therapies using OK-432 (Picibanil) and tamoxifen (TAM) on the growth of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced carcinoma were examined in 128 female Sprague-Dawley (SD) rats. The rats were divided into six groups: control (no treatment), tamoxifen, OK-432, simultaneous immuno-endocrine OK-432 and TAM (OK-432 + TAM) therapy, two types of sequential immuno-endocrine therapy of the OK-432 and TAM groups [OK-432 (1 wk)----TAM (4 wk) and OK-432 (2 wk)----TAM (3 wk)]. Each group was treated consecutively for five weeks. The response rates in the TAM alone group, the [OK-432 (1 wk)----TAM (4 wk)] group and the [OK-432 + TAM (5 wk)] group were significantly higher than in the control group. When the results among the treated groups were compared, the response rate in the [OK-432 (1 wk)----TAM (4 wk)] group was significantly higher than in the OK-432 alone or TAM alone groups. The response rate in the [OK-432 (2 wk)----TAM (3 wk)] group, however, was lower than in the TAM alone group. The response rate in the OK-432 + TAM group was, moreover, not significantly superior to that in the TAM alone group. These results suggest OK-432 not to potentiate the antitumor effect of TAM since the response rate of the combined OK-432/TAM therapy was not always significantly superior to that of the TAM treatment.

9,10-Dimethyl-1,2-benzanthracene↗

Enhancement of immunohistochemical reactivity for thymidine phosphorylase in breast carcinoma cells after administration of docetaxel as a neoadjuvant chemotherapy in advanced breast cancer patients.

For the purpose of demonstrating possible effects of docetaxel on thymidine phosphorylase (TP) activity in human breast carcinoma, we examined breast carcinoma tissues pre- and post-administration of docetaxel, by an immunohistochemical method using an anti-TP monoclonal antibody. Eight patients with advanced breast carcinoma were initially treated with 3 cycles of 60 mg/m2 of docetaxel once every 3 weeks after incisional biopsy of tumors, and following 3 cycles of docetaxel, they underwent mastectomy with axillary dissection. Grades of immunohistochemical reactivity for TP of carcinoma cells in pre- and post-treatment specimens were compared. Five biopsy specimens (62.5%) were positive for TP. After administration of docetaxel, 6 of 8 cases (75.0%) revealed significant enhancement of reactivity for TP. Increased reactivity was recognized diffusely as well as focally in carcinoma tissues. From these results, we believe that administration of docetaxel to breast cancer patients evokes enhancement of immunohistochemical reactivity for TP in breast carcinoma cells in situ. Furthermore, we consider that docetaxel treatment might improve efficacy of additional doxifluridine and capecitabine therapy.

Adult↗

Relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis in invasive ductal carcinoma of the breast.

Specimens obtained from 92 patients with invasive ductal carcinoma of the breast by quadrantectomy and axillary lymph node dissection were examined to evaluate the relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis. The number of lymphatic invasions was classified into 4 groups (ly0-3) by counting the number of peritumoral lymphatic invasions. In addition, immunohistochemistry for cytokeratin was performed to locate micrometastasis in the dissected lymph nodes. Thirty-seven (40.2%) of 92 cases had foci of lymphatic invasion and 29 (31.5%) cases revealed lymph node metastasis on initial routine examination. The rate of diagnosis of lymph node metastasis assessed by the existence of lymphatic invasion had an accuracy of 84.8%, a sensitivity of 89.7% and a specificity of 82.5%. On the other hand, all 3 cases (4.8%) with micrometastasis detected by immunohistochemistry for cytokeratin, showed lymphatic invasion. The rate of diagnosis after detection of micrometastasis increased and exhibited 88.0% accuracy. In addition, the rate of prediction of lymph node metastasis in cases with tumor larger than 15 mm was also high, and its accuracy was 88.2%. These results suggest that the assessment of peritumoral lymphatic invasion is very useful for predicting the presence of axillary lymph node metastasis including micrometastasis. They also suggest that excision specimens should be examined for lymphatic invasion, and that the results of the examination might be necessary to pick up false-negative cases and those at high risk for lymph node metastasis among patients who have not undergone lymph node dissection based on the result of sentinel lymph node biopsy.

Adult↗

PSK (krestin) potentiates chemotherapeutic effects of tamoxifen on rat mammary carcinomas.

A total of 20 mg of 7,12-dimethylbenz[a]anthracene (DMBA) was administered orally to 41 female Sprague-Dawley (SD) rats (control group), and 60 mg/kg of Krestin (PSK) were orally administered daily to 38 rats (PSK group) after DMBA administration. The average development period (9.6 weeks) of DMBA-induced tumors in the PSK group was significantly longer (P < 0.02) than that (7.9 weeks) in the control group. Average estrogen receptor (ER) levels of established tumors were almost the same between these two groups. However, the chemotherapeutic effect of tamoxifen (TAM) was significantly enhanced by PSK pretreatment.

9,10-Dimethyl-1,2-benzanthracene↗

Oral high-dose medroxyprogesterone acetate treatment for recurrent breast cancer.

Oral high-dose medroxyprogesterone acetate (MPA) treatment (600, 800, 1200 mg/day or changed dosage) was given to 49 patients with recurrent breast cancer from January 1979 to December 1992. The overall response rate to MPA was 38.8% (19/49). The response rate in the soft tissue was significantly higher compared with that in bone metastases or in visceral metastases. MPA was effective on patients both with or without previous treatment. Several side effects were recognized, but they were mild and tolerable. These results demonstrate that MPA is effective when used as first line or second line treatment.

Administration, Oral↗

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↗

Nonpalpable breast cancer.

Thirty-seven patients with nonpalpable breast cancer treated between 1981 and 1992 were analysed. Twenty-five (68%) of the patients were detected by microcalcification of mammogram, 8 by nipple discharge and 4 by other means. Biopsy was carried out in all patients to get a final diagnosis and histopathological examinations were performed using continuous sections (especially the section with microcalcification). The incidence of noninvasive carcinoma was 59% (22 cases) and the remaining invasive carcinomas were 3 minimal lesions less than 0.5 cm, 3 lesions from 0.5 to 1.0 cm, 3 diseases more than 1.0 cm, and 6 invasive carcinomas with noninvasive ductal carcinoma predominant. Modified radical mastectomy was performed in 16 cases, partial glandectomy in 10 and other surgery including subcutaneous mastectomy in 11. All of the patients with nonpalpabl breast cancer showed a good prognosis because of early detection and early treatment. Mammography was useful to detect nonpalpable breast cancers with microcalcification.

Adult↗