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Biomedical subjects

T Yokoe

Publications and source records attributed to T Yokoe.

At least 37 records · Page 2Linked to original sources

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↗

Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer.

The serum concentration of hepatocyte growth factor (HGF) was examined in 34 patients with metastatic breast cancer. Although no significant difference was observed between HGF concentration and the site of metastasis, serum HGF levels were slightly higher in patients with liver metastasis and in patients with multiple metastatic sites than in patients with other lesions. Significantly higher levels of serum HGF were observed in patients with progressive metastasis of breast cancer compared with those with stable metastasis. The patients with high HGF levels exhibited a significantly shorter survival rate than those with low HGF levels. Circulating HGF levels may be a useful indicator for the progression of metastatic lesions and the prognosis of patients with metastatic breast cancer.

Adult↗

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↗

Effect of rush immunotherapy on airway inflammation and airway hyperresponsiveness after bronchoprovocation with allergen in asthma.

BACKGROUND: Rush immunotherapy (RIT) has been shown to be effective in allergic asthma. OBJECTIVE: We investigated the mechanisms of RIT on the basis of cytokine production by T-cell lines and airway inflammation and responsiveness. METHODS: Subjects were 8 patients with house dust mite-allergic asthma treated with dust mite extract RIT for 6 months and 6 RIT-untreated control patients. IL-5 production by Dermatophagoides farinae -specific T-cell lines, eosinophil percentages, and eosinophil cationic protein (ECP) in induced sputum and airway responsiveness to allergen and histamine were evaluated before and after treatment. Changes in eosinophil percentages and ECP in induced sputum and responsiveness to histamine 24 hours after allergen inhalation were also studied. RESULTS: After 6 months of RIT, percentages of total eosinophils (43. 0% +/- 6.90% to 16.8% +/- 2.48%; P <.01), percentages of EG2(+ ) eosinophils (32.6% +/- 6.39% to 19.7% +/- 4.68%; P <.01) and ECP (362.7 +/- 125.3 ng/mL to 26.2 +/- 5.15 ng/mL; P <.05) decreased in induced sputum, and IL-5 production by T-cell lines decreased (617 +/- 93.2 pg/mL to 200.0 +/- 34.1 pg/mL; P <.01). RIT decreased both early- and late-phase bronchoconstriction (early phase: 33.2% +/- 3. 46% to 25.4% +/- 1.42%; P <.03; late phase: 16.2% +/- 3.52% to 6.2% +/- 1.96%; P <.03) and suppressed increases in the percentages of total (61.8% +/- 4.89% to 42.0% +/- 4.67%; P <.01) and EG2-positive eosinophils (55.54% +/- 7.21% to 36.5% +/- 6.43%; P <.01) and ECP (685.6 +/- 217.0 ng/mL to 85.4 +/- 23.4 ng/mL; P <.05) in induced sputum after allergen inhalation. RIT also decreased airway responsiveness to dust mite (1:303.7 +/- 123.7 wt/vol to 1:65.0 +/- 13.2 wt/vol; P <.03) and to histamine before (397.1 +/- 206.9 microgra/mL to 1391.3 +/- 283.3 microgram/mL; P <.03) and after allergen inhalation (139.2 +/- 36.5 microgram/mL to 629.1 +/- 196.3 microgram/mL; P <.03). CONCLUSION: RIT decreases airway inflammation and airway hyperresponsiveness before and after bronchial provocation with allergen, possibly by inhibiting both allergen-specific T-cell- and mast cell-dependent pathways. RIT is an effective antiinflammatory treatment in allergic asthma.

Adult↗

Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell death of synovial cells in patients with rheumatoid arthritis (RA).

Synovial cell hyperplasia is a characteristic of patients with RA. Excessive proliferation of RA synovial cells is, in part, responsible for the synovial cell hyperplasia. In addition, synovial cell death that would reduce synovial cell number may be defective, leading to the hyperplasia. Thus, the defective control of cell death as well as cell proliferation may be of central importance in the pathogenesis of RA. In this study we analysed effects of proinflammatory cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated apoptosis-associated protein expression in the synovial cells in patients with RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA synovium expressed FasL. Apoptotic synovial cells were detected within the sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells. Thus, we found that although RA synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of synovial cells was inhibited by proinflammatory cytokines present within the synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute outgrowth of synovial cells that leads to pannus formation and the destruction of joints in patients with RA.

Antibodies, Monoclonal↗

Phyllodes tumor showing intracystic growth: a case report.

A phyllodes tumor often grows rapidly and occasionally contains microcysts; however, the tumor rarely shows a morphologically intracystic pattern. We experienced a rare case of a phyllodes tumor with a solid mass growing into the cyst. A 62-year-old female noticed a tumor in her right breast in January 1995. The tumor grew rapidly and she visited our out-patient clinic in February 1995. On physical examination, a 10 x 8 cm, well defined and movable mass with a smooth surface was palpated in the upper outer quadrant of the right breast. Mammography showed a large tumor shadow in the upper outer quadrant of the right breast without any microcalcification. Ultrasonography revealed a large cystic shadow with a low echoic lesion and solid component with heterogeneous internal echo in the cyst. Under general anesthesia, the tumor was widely excised. The resected specimen was 11.5 x 11 x 11 cm in size and the tumor was not invasive to surrounding tissues. Old bloody fluid was contained within the cyst. The gross appearance showed papillary process protrusions into a central cystic cavity. Histological examination revealed a borderline case of phyllodes tumor. Two years after the operation, she is doing well without any recurrence.

Breast Neoplasms↗

c-erbB-2 status is an independent predictor of survival after first recurrence.

We studied retrospectively the interaction between c-erbB-2 overexpression and the prognosis in 239 invasive breast cancer patients who underwent radical operations between January 1984 and April 1991. The c-erbB-2 protein was overexpressed in 42 (17.6%) of 239 patients. There was no correlation between c-erbB-2 overexpression and age at operation, tumor size, lymph node involvement, or clinical stage. Only an inverse correlation was found between c-erbB-2 overexpression and hormone receptor levels. Patients with c-erbB-2 overexpression had a significantly worse overall survival than those without c-erbB-2 overexpression. In relation to lymph node involvement or estrogen receptor status, a significant difference in overall survival between the c-erbB-2-positive and -negative groups was found in patients with lymph node metastasis or in those with estrogen receptor-negative tumors. Out of 237 patients (two were lost to follow-up), 42 recurred and 25 died of breast cancer. The c-erbB-2-negative patients survived significantly longer after the time of first recurrence than the c-erbB-2-positive patients. In a multivariate analysis using Cox proportional-hazard regression model, c-erbB-2 status and disease-free interval were independent predictors of survival after first recurrence. In conclusion, c-erbB-2 status is an independent prognostic indicator of survival after first recurrence.

Biomarkers, Tumor↗

Angiogenesis and stromal fibronectin expression in invasive breast carcinoma.

Angiogenesis and stromal fibronectin (SFN) expression were immunohistochemically analyzed in 83 breast cancer specimens. Microvessel count (MVC), which correlated with lymph node metastasis, TNM stage, recurrence, and mortality, was relatively low in SFN-positive tumors. SFN expression did not correlate with lymph node metastases or tumor size. However, SFN positivity was less likely in patients with recurrent disease than in those without recurrence, and relapse-free survival was significantly better in patients with SFN-positive tumors than in those with SFN-negative tumors. MVC and SFN positivity were significant independent predictors of relapse-free survival as well as tumor size and axillary nodal status (Cox's proportional hazards regression analysis). Angiogenesis and SFN expression, both of which are inversely related, can be used prognostically in patients with breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Inhibitory effects of an antiestrogen, toremifene, on the phorbol ester-induced adhesive capacity of breast carcinoma cells.

Previous studies have revealed that protein kinase C (PKC) is responsible for malignant progression. In the present study, we investigated the potent inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly enhanced alpha2beta1 integrin-dependent adhesion of MCF-7 breast carcinoma cells. This PMA-induced adhesion was partially inhibited by incubating cells with toremifene prior to PMA exposure in a time- and dose-dependent manner. FACS analysis demonstrated that the PMA-induced alpha2beta1-dependent cellular adhesion was accompanied with elevated expression of alpha2beta1+integrin subunit on the cell surface. However, toremifene did not affect the elevated expression levels of these integrins but rather the avidity of alpha2beta1 integrin. We concluded that toremifene inhibited cellular adhesion activated by PMA, probably through mechanism which inhibits PKC.

Breast Neoplasms↗

[Genetic testing for ret mutation for early diagnosis and treatment in familial medullary thyroid carcinoma: a case report].

A 13-year-old girl and her older sister were referred to our hospital because her father and another older sister and been suffering from medullary thyroid carcinoma (MTC). Physical examinations revealed no thyroid mass. Ultrasonography (US) detected a small hypoechoic lesion in the right thyroid lobe, 3 mm in size. The serum calcitonin level was slightly elevated for their age. One and half year later, US finding showed a slightly larger mass, 7 mm in size, which was not palpable. Genetic testing for ret protooncogene mutation revealed a point mutation at codon 634 (Cys-->Arg) in exon 11. Surgical treatment was recommended, however, the patient wanted to receive it only after the admission to senior high school. Her sister had no mutation in ret protooncogene. The patient underwent total thyroidectomy with modified neck dissection at 16 years of age. At that time, a new mass emerged in the left thyroid lobe and the serum calcitonin level increased to 171 pg/ml. MTC was found in each lobe with positive staining of CEA and carcitonin. No lymph node metasis was found. Her postoperative course was uneventful. Genetic testing for ret mutation is effective for early diagnosis and treatment of patient with FMTC, and is recommended as standard management for hereditary MTC in affected families.

Adolescent↗

Effect of theophylline withdrawal on airway inflammation in asthma.

Theophylline has been used as a bronchodilator in acute and chronic asthma management, although there is accumulating evidence that it may have anti-inflammatory effects. We have investigated the effect of theophylline withdrawal for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were more than 80% of the predicted value and its variability was less than 20% (Green Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP), 400-800 microg/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum, and airway reactivity to histamine were investigated. One half of the patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when receiving treatment with theophylline were 8.08 microg/mL in the theophylline withdrawal group and 7.64 microg/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emerged in the theophylline group, there were no significant changes in the theophylline administration group. In the theophylline withdrawal group, there were small but significant falls in PEF in the morning, FEV1 and V50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2+) eosinophils only in those patients who withdrew from theophylline. These results indicate that chronic treatment with low dose theophylline exerts an anti-inflammatory effect and that the additional use of theophylline with inhaled corticosteroids provides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long-term beneficial effects on the chronic asthma management.

Administration, Oral↗

A New Endocrine Therapy Strategy for Bone Metastasis of Breast Cancer: The Effect of Biological Response Modifiers and 22-Oxacarcitriol on Animal Models.

To consider the treatment order of hormonal agents is very important in order to achieve a higher quality of life (QOL) and better survival rates in breast cancer patients with bone metastasis. Tamoxifen (TAM) or a luteinizing hormone-releasing hormone (LH-RH )analogue is the first-line, an LH-RH analogue (or TAM) the second-line, and medroxyprogesterone acetate(MPA) the third-line treatment in premenopausal patients with breast cancer. In postmenopausal patients, TAM (or toremifene) is the first-line, an aromatase inhibitor the second-line, and MPA the third-line treatment. In experimental studies using female Sprague-Dawley rats with 7, 12-dimethylbenz ma]anthracene (DMBA)-induced mammary carcinoma, biological response modifiers (BRM)(Krestin, Picibanil) and a vitamin D3 analogue, 22-oxacarcitriol (OCT)augmented the antitumor effect of hormonal agents. A combination of hormonal agents and BRM or OCT may be the endocrine therapy of choice for bone metastasis of breast cancer.

Journal Article↗

Spindle cell carcinoma of the breast.

Spindle cell carcinoma is a rare breast tumor. We present herein three cases of spindle cell carcinoma of the breast and review its characteristics from the literature. Spindle cell carcinoma frequently forms a large and well-circumscribed tumor with gross cyst formation. Histologically, its dominant component is of sheets of spindle shaped cells, and it includes such contiguous carcinoma components as squamous differentiation or invasive ductal carcinoma. Estrogen receptor expression and lymph node metastasis tend to be low. Despite the sarcomatous features, spindle cells are likely to be derived from epithelial cells of mammary glands. Immunohistochemical and ultrastructural examination demonstrated the expression of keratin and the desmosome-like junctional structure in the spindle cell components. Relatively favorable prognosis is expected in spindle cell carcinoma of the breast compared to common breast carcinoma.

Aged↗