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Biomedical subjects

T Fukutomi

Publications and source records attributed to T Fukutomi.

At least 145 records · Page 8Linked to original sources

The prognostic value of tumor-associated carbohydrate structures correlated with gene amplifications in human breast carcinomas.

The effects of cell surface sugar chains combined with certain gene amplifications of breast cancers on the prognosis of patients were studied and the relationships between the sugar chains of cancer cells and amplifications of the proto-oncogenes c-myc, int-2 and c-erb B-2, evaluated. One hundred and fifty three human breast carcinoma tissues were investigated by an immunohistochemical technique using the avidinbiotin-peroxidase method with 1 lectin (HPA; Helix Pomatia) and 4 monoclonal antibodies (B-72-3, St-439, anti-Tn and anti-T). The positive rates of HPA, St-439, B-72-3, anti-Tn and anti-T were 43 per cent (63/153), 52 per cent (80/153), 53 per cent (81/153), 64 per cent (98/153) and 89 per cent (136/153), respectively. Patients whose cancers had positive HPA staining were found to have a lower survival rate than those with negative HPA staining (p less than 0.05), whereas those whose cancers had positive St-439 staining showed a better prognosis than those with negative St-439 staining (p less than 0.01). The positive rate of HPA was related to the gene amplification of c-myc proto-oncogene (p less than 0.01), whereas the negative rate of St-439 was correlated with the gene amplification of c-erb B-2 (p less than 0.01). These data indicate the prognostic value of HPA and St-439 and also the relationships between the gene amplifications and carbohydrate structures in breast cancer cells.

Antibodies, Monoclonal↗

Nuclear p53 immunoreaction associated with poor prognosis of breast cancer.

p53 protein has been frequently detected at high levels in the nuclei of human breast cancer cells. We analyzed immunohistochemically the association between nuclear localization of p53 protein and clinical and histological parameters of breast cancer patients. Surgically resected tissues of 73 primary breast cancers were processed by acetone fixation and paraffin embedding and examined using an anti-p53 monoclonal antibody, PAb1801. p53 immunoreactivity was detected in the nuclei of cancer cells in 17 cases (23%). The nuclear p53 immunoreaction was closely associated with overexpression of c-erbB-2 protein (P less than 0.05), high histologic grade (P less than 0.01), advanced clinical stage (P less than 0.05), and negative estrogen receptor status (P less than 0.01). When 31 cases which had been followed up for more than 50 months were examined, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival of patients (P less than 0.01). These results suggest that immunohistochemical examination of nuclear p53 protein is clinically useful as an indicator of breast cancer aggressiveness.

Antibodies, Monoclonal↗

Inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia.

A patient with inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia (M4) is reported. He had spiking fever, epigastralgia, and elevated levels of serum C-reactive protein (CRP) and alkaline phosphatase (ALP). Ultrasonography showed a hypoechoic mass in the liver, and ultrasonically guided fine needle aspiration biopsy of the mass revealed that it was composed of fibrous connective tissue infiltrated with plasma cells, eosinophils, and neutrophils. Accordingly, a diagnosis of inflammatory pseudotumor of the liver was made. Marked reduction in the size of the lesion and a decrease of the levels of the CRP and ALP occurred without specific treatment. We emphasize the importance of ultrasonically guided aspiration biopsy in diagnosis of inflammatory pseudotumor of the liver without the need for surgery.

Biopsy, Needle↗

The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients.

The effects of medroxyprogesterone acetate (MPA) on the mechanism of coagulation in postmenopausal patients were studied and compared with those of tamoxifen by a retrospective analysis. The coagulation test parameters tested included platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time, and the levels of fibrinogen, fibrin degradation products, factor II, factor V, plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI) and alpha 2-plasmin inhibitor-plasmin complex (alpha 2-PI-P). A shortened APTT was noted and the levels of factors II, V, alpha 2-PI and alpha 2-PI-P were also out of the normal range during treatment in the MPA-treated group. However, these abnormal parameters recovered to within the normal range from 6 months or more after the commencement of treatment without any termination of drug administration. The patients were all asymptomatic. In contrast, a slight prolongation of bleeding time which persisted for more than 6 months was observed in the patients treated with tamoxifen. These data suggest that MPA causes a hypercoagulable state and that any change must be carefully monitored during treatment with either MPA or tamoxifen.

Antineoplastic Agents↗

[A case of hypopituitarism associated with empty sella and agenesis of corpus callosum, a variant form of septo-optic-pituitary dysplasia].

A 41-year-old man was referred to Kyushu University Hospital for evaluation of hypothyroidism and hypocortisolemia. Pituitary function test revealed the deficiency of GH(growth hormone), ACTH(adrenocorticotropic hormone), prolactin and TSH(thyroid stimulating hormone). MRI showed empty sella and agenesis of corpus callosum. Clinical diagnosis was hypopituitarism with midline brain anomaly. Septo-optic-pituitary dysplasia (SOPD) is a syndrome characterized by agenesis of septum pellucidum or corpus callosum, optic nerve hypoplasia and congenital hypothalamic-pituitary insufficiency. Our case had no ocular anomalies, but today it is regarded as a variant form of SOPD. Evaluation of the integrity of midline brain structures in patients with congenital hypopituitarism is thus thought to be important for their etiology.

Adult↗

The effects of estrogen on human breast carcinomas serially transplanted into nude mice.

The effect and mechanisms of 17 beta-estradiol (E2) on breast cancer cells were studied in vivo and in vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E2 at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E2 in 3 out of the 4 ER positive tumors, the Td of the E2 treated groups being 17.6 days for MCF-7 (control: -17.8 days), 12.8 days for R-27 (control: -12.5 days approximately 14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E2 in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E2. Discrepancies between the effects of E2 on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conducting in vitro growth studies. In vitro clonogenic cell assay reproduced the antitumor activity of E2, indicating that E2 directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.

Animals↗

[Experimental multihormone therapy on human breast carcinomas grown in nude mice].

Experimental multihormone therapy with tamoxifen (TAM), aminoglutethimide (AMG) and medroxyprogesterone acetate (MPA) was investigated using three hormone-dependent human breast carcinomas serially transplanted into nude mice. TAM was the most effective of these agents, showing an efficacy rate of 100%, whereas MPA was the least effective, showing an efficacy rate of only 17%. The combination treatment of TAM and AMG was more effective than that of either TAM or AMG used alone. The antitumor effect of TAM was considered to be related to the changes of the hormone receptor levels. Since AMG significantly reduced the estrogen level and the uterine weight in normal female mice, the antitumor effect of combined TAM and AMG was assumed to be a result of the low estrogen level caused by AMG, enhancing the ability of TAM to compete with estrogen receptors. There was no additional antitumor effect of the combination of TAM and MPA, although serum MPA levels in mice were almost equivalent to those in humans who were treated with 1200mg of MPA po daily. These results indicated that combination hormone therapy, particularly with TAM and AMG, might be a promising method for the clinical treatment of human breast cancer.

Aminoglutethimide↗

[Influences from the treatment of thyroid disease and diabetes mellitus on breast cancer prognosis].

We have studied influences from the treatment of a thyroid disease and diabetes mellitus on breast cancer prognosis. Forty-one breast cancer patients with a thyroid disease and 16 cases with diabetes mellitus under medical treatment have been investigated. There was no special clinicopathological characteristics found in patients with a thyroid disease. The 5-year relapse-free survival rate (5 Y-RFS) of these patients was 95% and the 5-year overall survival rate (5 Y-OS) was 100%. Therefore, the presence of a thyroid disease showed no significant effect on the survival of breast cancer patients. In contrast, the prognosis of a group of diabetes mellitus was relatively poor, the 5 Y-RFS showing 75% and 5 Y-OS 81%. A significantly worse survival rate was found in cases of insulin treated subgroups compared to orally treated patients.

Adult↗

A rare case of asynchronous bilateral B-cell lymphoma of the breast.

We report an asynchronous bilateral malignant lymphoma of the breast, in a 56-year-old woman, presenting unusual clinical signs and histological features. The patient, who had a family history of breast cancer, had undergone a standard right radical mastectomy four years previously for a non-epithelial malignant tumor. At that time, the tumor was thought to be a stromal sarcoma, because some of the neoplastic cells were elongated or vacuolated. The patient recently became aware of a rapidly growing tumor of the left nipple without erosion or pain. This tumor underwent biopsy, and the histological examination showed a non-Hodgkin's lymphoma of diffuse mixed type. Staging procedures demonstrated no sign of generalized disease. Following a modified left radical mastectomy for optimal local control and accurate staging, adjuvant chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and doxorubicin was initiated. Immunohistochemical staining for PAN-B and leucocyte common antigen revealed both tumors to be malignant lymphomas of B-cell type, and the first lymphoma of the right breast was thought to be showing 'signet ring' cell change. Since the two tumors were morphologically quite different from each other, it was suggested that they were asynchronous bilateral primary malignant lymphomas; however, the possibility remains that the recent left breast tumor is a recurrence of the malignant lymphoma of the right breast. The patient is currently disease-free, 10 months after surgery.

B-Lymphocytes↗

Prognostic contributions of Helix pomatia and carcinoembryonic antigen staining using histochemical techniques in breast carcinomas.

Helix Pomatia (HPA) and carcinoembryonic antigen (CEA) staining were studied in 113 primary breast carcinomas, 63 metastatic lymph nodes and 10 resected local recurrences, using the avidin-biotin-peroxidase complex (ABC) method. Positive percentage rates were 41 (46/113) for HPA and 24 (27/113) for CEA in primary tumors, and 80 (8/10) for HPA but only 10 (1/10) for CEA in metastatic lesions. HPA staining showed a statistically significant correlation with negative estrogen receptor (ER) status (r -0.25, P = 0.05) and high nuclear grade (r 0.20, P = 0.04). Cancers with positive HPA staining were associated with a lower survival rate than those without (P = 0.0001), irrespective of menopausal status. CEA staining showed a marginal correlation with survival (P = 0.06: log rank test). The five-year survival rate of 21 cases positive for these two markers was only 5%. Multivariate analysis revealed HPA staining to be the best prognostic factor. The data indicated that HPA staining might be a valuable prognostic factor for breast cancer patients, especially when combined with CEA staining.

Breast Neoplasms↗

[Changing trends in the surgical management of breast carcinoma in Japan].

Modified mastectomy, which involved removal of the breast, overlying skin and axillary contents but spares the pectoralis muscle, has recently been established as an entirely satisfactory approach for Stage I and Stage II breast carcinoma. In a sequential series of patients, we noted that the traditional mastectomy followed by radiation to axilla and adjacent area failed to confirm the efficacy to support the prevention for local relapse in the past decade. The concepts of adjuvant chemotherapy evolved primarily from clinical trials: CMF and CAMF have been shown to influence favorably the therapy of premenopausal women with positive. nodes. Additional endocrine adjuvant treatment in postmenopausal women with positive nodes was significantly superior to that with CAMF. Immediate breast reconstruction following modified mastectomy or subcutaneous mastectomy was safe, simple, and possible to produce the patient's satisfaction. There was a positive effect on life style and on sexual, social or work relationships. Finally, in recent years, several studies have reported that more conservative treatment, such as partial mastectomy and nodes dissection with postsurgical radiotherapy are as effective as modified mastectomy. Present research will likely continue to modified current treatment as more data are gathered and analyzed clinically and histologically.

Adult↗

Cell kinetic analysis of human tumor xenografts using anti-bromodeoxyuridine monoclonal antibody.

The cell kinetics of human tumor xenografts serially transplanted into nude mice was examined using bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody. After various doses of BrdU were given intraperitoneally into tumor bearing nude mice, the tumors were resected and stained immunohistochemically, using the anti-BrdU monoclonal antibody. The number of stained cells was demonstrated as the labeling index (LI). The optimal condition for BrdU staining was assumed to be 300 mg of BrdU per kg followed by an incubation period of one hour. Since the LI by BrdU closely correlated with that in autoradiography by 3H-TdR, this method is more useful and safer than the conventional autoradiographic study for investigating clinical cell kinetic analysis, as there is no need to use potentially hazardous radioactive compounds and the period of assay is shorter.

Animals↗

Pharmacodynamic aspects of in vitro and in vivo chemosensitivity tests.

To determine the optimal conditions for clonogenic assay, the antitumor activities of 5-fluorouracil (5-FU) in vitro and in vivo were compared from a pharmacodynamic viewpoint in a human carcinoma xenograft-nude mouse system. In the clonogenic assay, tumor cells were exposed to 5-FU continuously for 2 weeks, and the results of the assay were evaluated in terms of colony survival rates (T/C). Tumor-bearing BALB/c male nude mice were treated with 5-FU, and the results were evaluated in terms of the lowest values of relative mean tumor weights (T/C). To compute the area under the curve (AUC) after administration of 5-FU in vitro and in vivo, agar and serum levels of 5-FU were measured by bioassay. Antitumor activities in terms of T/Cs against a gastric carcinoma strain (H-111) depended highly on the AUCs in vitro and in vivo. The T/C in vitro (z) was correlated with the AUC in vitro (w), z = 58.4 x 0.99331w, and the T/C in vivo (y) was also correlated with the AUC in vivo (x), y = 52.1 x 0.88552x. On the assumption that the T/Cs of these two regression equations were equivalent (y = z), a correlation between w and x was derived. To predict the T/C at the maximum tolerated dose of 5-FU in mice, the optimal drug concentration in vitro was calculated to be 2.7 micrograms/ml, which also proved to be suitable for seven other carcinoma strains. Our experimental system was thought to be adequate for selecting the optimal drug concentration in the clonogenic assay.

Animals↗

Experimental combined hormone therapy on human breast carcinomas serially transplanted into nude mice.

Experimental combined hormone therapy with tamoxifen, aminoglutethimide and medroxyprogesterone acetate was investigated using three hormone-dependent human breast carcinomas serially transplanted into nude mice. The antitumor effect of combined tamoxifen and aminoglutethimide was better than that of either tamoxifen or aminoglutethimide alone. Since aminoglutethimide significantly reduced the level of estrogen and the uterine weight in normal female mice, the antitumor effect of combined tamoxifen and aminoglutethimide was assumed to be a result of the low estrogen level produced by aminoglutethimide, favoring the competition of tamoxifen with estrogen receptors. There was no additive antitumor effect of the combination of tamoxifen and medroxyprogesterone acetate, although serum medroxyprogesterone acetate levels in nude mice were almost equivalent to those of humans. These results indicate that combination hormone therapy, especially with and aminoglutethimide, might be a promising method for clinical application.

Adult↗