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Biomedical subjects

Y Koibuchi

Publications and source records attributed to Y Koibuchi.

67 records · Page 4Linked to original sources

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↗

A comparative study of subcutaneous mastectomy with radical mastectomy.

The purpose of this study was to compare the results of 133 cases (131 patients) of subcutaneous mastectomy with axillary dissection between 1983 and 1999 and 910 cases of radical mastectomy during the same period. The median follow-up period of the subcutaneous mastectomy group and the radical mastectomy group were 66 months and 81 months, respectively. The age at operation was significantly (p<0.01) younger in the subcutaneous mastectomy group than in the radical mastectomy group and the clinical stage was significantly (p<0.01) earlier. Lymph node metastasis was significantly (p<0.01) higher in the radical mastectomy than in the subcutaneous mastectomy group. There was no difference in ER status between the two groups. There was local recurrence in 5 (3.8%) members of the subcutaneous mastectomy group and in 12 (1.3%) members of the radical mastectomy group. There was no difference in disease-free survival and overall survival between the two groups. Divided into two subgroups by lymph node status, there was no difference in disease-free survival and overall survival between the two groups. Local recurrence occurred more frequently (p<0.05) in the subcutaneous mastectomy group, however, than in the radical mastectomy group when no lymph node metastasis was found. Multivariate analysis using the Cox hazard model showed that operation method and lymph node status were independent prognostic factors for local recurrence, whereas, lymph node status and ER status were independent prognostic factors of disease-free survival. In conclusion, subcutaneous mastectomy presents a risk factor for local recurrence, but the survival rate of the subcutaneous mastectomy group is as favourable as the radical mastectomy group.

Adult↗

Predictive value of estrogen receptor status as assessed by ligand-binding assay in patients with early-stage breast cancer treated with breast conserving surgery and radiation therapy.

It is important to determine which factors are predictive for the prognosis of patients treated with breast conserving surgery (BCS) and radiation therapy (RT) in order to make a decision as to the adjuvant treatment. Although estrogen receptor (ER) is known to be a predictive marker for antiestrogens in breast cancer, the prognostic effect of hormone receptors has not been fully analyzed in Japanese breast cancer patients treated with BCS and RT. A total of 153 breast cancer patients having up to three positive nodes in the axilla as identified histologically and treated with both BCS and RT with or without systemic therapy were enrolled in this study. All tumors were measured for ER and progesterone receptor (PR) using ligand-binding assay (LBA). ER was inversely related to patients' age, however, PR was not related to any clinical features. When ER was classified into negative, weakly positive and strongly positive categories, with cut-off levels of zero and 50 fmol/mg protein, the relapse-free survival (RFS) was significantly better in patients with tumors having strongly positive ER than in patients with tumors having negative ER. Multivariate analysis revealed that ER as well as nodal status, was an independent predictive factor for RFS, however, PR was not. As a result, we believe that ER measured by LBA is valuable for predicting prognosis of early-stage breast cancer patients treated with BCS and RT.

Adenocarcinoma↗

Effects of nilvadipine, a new calcium entry blocker, on systemic blood pressure, cardiac hypertrophy and venous distensibility in spontaneously hypertensive rats.

We investigated the effects of three different drugs, nilvadipine (NV), nicardipine (NC) and hydralazine (HD), having calcium entry blocking and/or vasodilating properties, on blood pressure, heart weight and venous distensibility in spontaneously hypertensive rats (SHRs). All of these drugs (1.0 and/or 3.2 mg/kg/day, s.c., 12-14 weeks) countered to almost the same extent the development of hypertension in young SHRs and lowered high blood pressure in the older SHRs. In both age-groups, on the other hand, ventricular weight/body weight ratios for the NV-treated group, but not for the NC- or HD-treated group, were significantly smaller than those for the corresponding vehicle-treated group. In addition, lower body venous pressure-volume curves, which were measured on the day after the last drug administration, shifted dose-dependently in the direction of the volume for the NV-treated group, indicating that venous distensibility was expanded by NV. NC and HD did not have such an effect at the same hypotensive doses. We conclude that NV prevented the development of hypertension and lowered high blood pressure in SHRs. NV also improved cardiac hypertrophy and decreased venous capacity. The depressant effect of NV on cardiac hypertrophy may be due not only to its hypotensive effect, but also, at least partially, to its venodilating effect.

Aging↗

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↗

Relationship between thyroid-pituitary function and response to therapy in patients with recurrent breast cancer.

In this study, thyroid (T3, T4, free T3, free T4) and pituitary function (thyrotropin (TSH), growth hormone (GH), prolactin (PRL)) in 38 patients with recurrent breast cancer were examined. The patients were divided into three groups according to their response to the therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. The maximum and the minimum value for each hormone throughout the course of treatment were compared between three groups. The PD group showed significantly lower minimum T3 levels than the other two groups (p < 0.05). The maximum TSH level in the PD group was significantly higher than that of the other groups. The minimum TSH level in the PD group was significantly lower than that in the PR group (p < 0.05). The minimum TSH level in the NC group was also lower than that in the PR group. The maximum PRL level in the NC and the PD group was higher than that in the PR group (p < 0.05, p < 0.01, respectively). The tumors of the patients with temporal increase of TSH level were resistant to all subsequent therapies. These five patients died within four months followed by decreasing of the TSH level. It is concluded that thyroid and pituitary function, especially free T4, TSH and PRL, are predictive indicators of therapeutic response and the prognosis of the patients with recurrent breast cancer.

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↗

Changes of cytokines and thyroid function in patients with recurrent breast cancer.

The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer. High levels of cytokines are frequently observed in critically ill patients. Recent studies have shown that interleukin (IL)-6 may be a cause of nonthyroidal illness. We reported the relationship between thyroid function and the prognosis of the patients with recurrent breast cancer. In this study, we measured the serum level of cytokines (IL-2, IL-6, IL-8) and thyroid function (free T3, free T4, and thyrotropin (TSH)) in 38 patients with recurrent breast cancer. All patients had received three or more different courses of therapy before they were entered the study. The patients were divided into three groups according to their response to therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. They did not receive any medication that influenced the thyroid hormone level other than medication for cancer. The IL-2 level was under the detectable limit in all groups. No abnormal levels of cytokines were observed in the PR group. IL-6 and IL-8 levels in the PD group were significantly higher than that in the NC group (p < 0.05). Significant negative correlation was observed between IL-6 and thyroid hormones (free T3, free T4). Patients whose IL-6 level was 20 pg/ml or more died within four months after the beginning of the treatment. We concluded that IL-6 may lead to a hypothyroid state in patients with recurrent breast cancer. A high level of IL-6 and IL-8 means the confusion of the defense system in hosts. Therefore, these cytokines will be predictive indicators of the therapeutic response and the prognosis of the patients with recurrent breast cancer.

Adult↗

HLA antigen as predictive index for the outcome of breast cancer patients with adjuvant immunochemotherapy with PSK.

We demonstrated that the prognosis of breast cancer patients who received adjuvant immunochemotherapy with Krestin (PSK) showed a tendency to be better than that of breast cancer patients receiving chemotherapy only. We retrospectively investigated the usefulness of HLA typing for selecting patients to receive adjuvant immuno-chemotherapy with PSK. One hundred and thirty-four patients with operable breast cancer were typed as HLA-A, -B, -C by a lymphocytotoxicity test. Patients without vascular invasion had no adjuvant therapy (NA group). Patients with vascular invasion in the tumor and/or in the metastatic lymph node were randomized into two groups. In group 1 (FEMP only), a combination chemotherapy of 100 mg of 5-fluorouracil (F), 50 mg of cyclophosphamide (E), 2 mg of mitomycin C (M), and 5 mg of predonisolone (P) was orally administered daily for 28 days (one course). In group 2 (FEMP+PSK), FEMP and 3.0 g of PSK were orally administered for 28 days (one course). Two courses a year of these agents were given for five years in both groups. Each group (NA, FEMP, FEMP+PSK) was stratified by the presence of HLA B40 type (B40(+)) or not (B40(-)). Five- and 10-year disease-free survival (DFS) rates (93%, 80%, respectively) of patients with B40(+) seemed to be better than those (83% and 51%) of patients with B40(-). In the NA group, 5- and 10-year DFS were 100% and 71% in patients with B40(+), 92% and 76% in those with B40(-), respectively. In the FEMP group (chemotherapy only), 5- and 10-year DFS of patients with B40(+) were both 84%. These were not statistically significant compared with those (82% and 33%) of patients with B40(-). On the other hand, in the FEMP+PSK group, 5- and 10-year DFS of patients with B40(+) were both 100%, and those of patients with B40(-) were 76% and 55%, respectively. DFS of patients with B40(+) was significantly better than that of patients with B40(-). It is concluded that HLA typing may be a predictive index in determining the use of immunochemotherapy combined with PSK for patients with operable breast cancer.

Adjuvants, Immunologic↗

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↗

Efficacy of mammography for detecting early breast cancer in women under 50.

Screening mammography (MMG) for women aged 50 years and older has been widely accepted all over the world. However, the efficacy of screening mammography for women aged under 50 years has not been established. We compared mammographic findings of the patients under age 50 (the younger group) and those of patients 50 and older (the older group). From 1992 to 1997, 107 patients with early breast cancer (non-invasive and Stage I) were treated in our hospital. There was no difference between the groups in background. Of 53 patients in the younger group, 40 (75.5%) were diagnosed as having cancer using mammography, while 44 of 54 (81.5%) of the older group were diagnosed as having cancer. A total of 46 (86.8%) patients in the younger group were diagnosed using MMG and physical examination (PE), and 50 (92.6%) in the older group were diagnosed as cancer using MMG and PE. There was no difference in the successful diagnosis rate using mammography in the two groups. Breast cancer screening using MMG may also be useful for women aged under 50.

Adult↗