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Biomedical subjects

Y Horii

Publications and source records attributed to Y Horii.

262 records · Page 15Linked to original sources

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

Antineoplastic Agents↗

Local resection after breast-conserving therapy.

We analyzed the results of local re-excision after radiation therapy on seven patients with positive surgical margins at the initial breast-conserving surgery. The age of the patients ranged from 30 to 55 years, and the tumor sizes from 1.1 to 4.7 cm. Both estrogen receptor and progesterone receptor status were positive in two patients, negative in four, and unknown in one. Pathological examination revealed residual carcinoma in one (14.3%) of seven patients. The immunohistochemical results of the initial specimen were estrogen receptor-positive, c-erbB-2-positive, and Bax-negative. We performed local re-excision after radiation therapy and found only one incidence of residual carcinoma in the conserved breast.

Adult↗

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↗

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↗

Effects of interferon-alpha on cellular proliferation and adhesion of breast carcinoma cells.

We examined the potent inhibitory effects of interferon-alpha (IFN-alpha) on both cellular adhesion and cell proliferation of MCF-7 breast carcinoma cells. When MCF-7 cells were exposed to IFN-alpha at a concentration of 5x10(3) IU/ml for 5 days, cell proliferation was markedly inhibited. Cell attachment assay demonstrated that incubation with IFN-alpha for up to 48 h reduced alpha2beta1 integrin-mediated cellular adhesion. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with IFN-alpha for 24 h had no effect upon the cell surface expressions of either alpha2 and beta1 integrin on MCF-7 cells. These antiproliferative and antiadhesive actions of IFN-alpha may be applied to treatment for patients with metastatic breast carcinoma.

Breast Neoplasms↗

Quantitative analysis of seminiferous epithelium in subfertile carriers of chromosomal translocations.

In order to study the effect of structural chromosomal aberrations on spermatogenesis, quantitative analysis of the germinal epithelium was performed on testicular specimens from 12 carriers of balanced chromosomal translocations diagnosed at male infertility clinics: a Y-autosome translocation, eight reciprocal translocations, and three D/D Robertsonian translocations. Spermatogenic arrest at the spermatocyte stage was revealed in the Y-autosome translocation and four of the reciprocal translocations. The number of spermatids was selectively reduced in three carriers, while normal spermatogenesis was found in three. Thus, the majority of carriers with impaired semen quality showed a complete or partial reduction in the number of spermatids, suggesting that the effect of chromosomal aberrations is to arrest the spermatogenic process at the spermatocyte stage.

Adult↗

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↗

Multidisciplinary treatment with anthracyclines in inflammatory breast cancer.

Twenty-two patients with inflammatory breast cancer treated between 1962 and 1994 were analyzed. Before the introduction of multidisciplinary treatment with anthracycline agents between 1962 and 1981, 11 patients out of 14 were resected, however, a curative operation was performed for only 3 of these patients (29.3%). Ablative endocrine therapy, intraarterial infusion of anticancer drugs (mitomycin C or 5-fluorouracil), and radiation were carried out as the preoperative induction therapy for inflammatory breast cancer. All 14 patients died within 36 months. After the introduction of multi-disciplinary treatment with anthracycline agents between 1981 and 1994, preoperative induction chemotherapy or chemoendocrine therapy using anthracyclines was carried out on 7 out of 8 patients and the remaining patient received radiation. Of the former 7 patients, 6 (85.7%) underwent a curative operation. There was approximately a 35 percent cumulative survival rate observed 60 months after operation, and 3 patients out of the 7 lived for more than 5 years. To conclude, multidisciplinary treatment including systemic induction chemotherapy with anthracyclines was an effective treatment for inflammatory breast cancer.

Adenocarcinoma↗

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↗

Age-dependent characteristics of screen-detected patients with breast cancer.

A consecutive series of 128 breast cancer patients detected by breast screening were enrolled in this study to analyze their age-dependent characteristics. They were classified into three groups; 40 years or less (young): 26 patients, 41-55 years (middle-aged): 67 patients and 56 years or over (old): 35 patients. The percentage of patients who had noticed breast abnormality by self-examination at the time of the breast screening increased from the young patients to the old without statistical significance. Nonpalpable breast cancer was more frequently (p < 0.05) observed in the young patients or the middle-aged rather than the old patients. The incidence of noninvasive carcinoma decreased from the young patients to the old without statistical significance. Decreased survival was seen in older patients rather than younger patients, without statistical significance. As a result, prognostic features were more favorable in patients aged 40 years or less than the other. Women aged 35-40 years should be recommended to attend breast screening.

Adult↗