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Biomedical subjects

H Sonoo

Publications and source records attributed to H Sonoo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression levels of estrogen receptor-alpha, estrogen receptor-beta, coactivators, and corepressors in breast cancer.

Recent studies have indicated that a complex machinery of transactivation of target genes by estrogen or antiestrogen through estrogen receptor (ER) exists. However, the substantial roles of ER-beta, coactivators, and corepressors in the development and progression of breast cancer remain to be elucidated. To obtain some clue to these roles, we screened the expression levels of ER-alpha, ER-beta, coactivators (SRC-1, TIF2, AIB1, CBP, and P/CAF) and corepressors (N-CoR and SMRT) in 6 normal mammary glands, 6 intraductal carcinomas, 22 invasive ductal carcinomas, and 7 breast cancer cell lines using a multiplex reverse transcription-PCR. ER-alpha mRNA expression levels significantly correlated with ER-alpha protein levels measured by enzyme immunoassay in the breast cancer tissues and cell lines. A significant correlation of expression levels was observed between ER-alpha and TIF2, AIB1, P/CAF, and N-CoR, and between ER-beta and AIB1 and CBP in the tissue samples. A significant correlation was also observed between ER-alpha and ER-beta and between ER-beta and CBP in the cell lines. The expression levels of ER-alpha, TIF2, and CBP were significantly higher in the intraductal carcinomas than those in the normal mammary glands. In addition, the expression levels of ER-alpha and N-CoR were significantly higher in the intraductal carcinomas than those in the invasive ductal carcinomas. These findings suggest a positive correlation of expression levels among ER-alpha and cofactors and among ER-beta and cofactors, an up-regulation of expression levels of ER-alpha and cofactors during the development of intraductal carcinomas from normal mammary glands, and a decrease in their expression levels during the progression of breast cancer.

Breast↗
PubMed2000

[Comparison of whole-body MR imaging and bone scintigraphy in the detection of bone metastases from breast cancer].

The aim of this study was to investigate the usefulness of whole body MR imaging (WB-MRI) in the detection of bone metastases from breast cancer and to compare the results with those from bone scintigraphy. In 21 patients with suspected bone metastasis from breast cancer, both bone scintigraphy and WB-MRI were performed. With WB-MRI, coronal images were obtained using a body coil in an FOV of 48 cm, and sequences of fast short TI inversion recovery (STIR) and gadolinium-enhanced fast spoiled GRASS (SPGR) were used in three parts: from the head to the thorax, the abdomen to the pelvis, and the lower extremities. Of the total 105 metastatic bone lesions, 65 (61.9%) were detected by bone scintigraphy, 98 (93.3%) by fast STIR, and 74 (70.5%) by fast SPGR. Thus, the detection of bone metastases by WB-MRI was excellent. However, detectability in the ribs was lower for WB-MRI than for bone scintigraphy. Contrast-enhanced MRI was useful in the differentiation of osteosclerotic lesions, in which high signal intensity is rare, pleural effusion, which has high signal intensity on STIR, and bone metastatic lesions. In conclusion, WB-MRI showed high reliability in the detection of bone metastatic lesions from breast cancer.

Adult↗
PubMed2000

[A case of advanced breast cancer associated with humoral hypercalcemia that responded to medroxyprogesterone acetate and docetaxel].

A 67-year-old woman with a left advanced breast cancer was admitted to our hospital. Chest CT revealed a parasternal lymph nodal metastasis invading into the sternum, an axillary lymph nodal metastasis, and a lung metastasis. The clinical stage of the patient was i.v. (T4bN2M1). Laboratory examination showed humoral hypercalcemia. After controlling the hypercalcemia with alendronate, sodium hydrate she received chemoendocrine therapy with medroxyprogesterone acetate (MPA) (800 mg/day) and docetaxel (60 mg/body once every three weeks). A complete response was obtained in the primary and metastatic lesions after 3 cycles of docetaxel. This case suggests the efficacy of the combined therapy with MPA and docetaxel on advanced breast cancers.

Administration, Oral↗
PubMed1999

Current Status and Controversial Issues concerning Endocrine Therapy for Patients with Recurrent Breast Cancer in Japan.

BACKGROUND: Four different endocrine therapeutic agents have been used in Japan since 1996. However, a consensus regarding proper use of these agents has notyet been established. Therefore, a questionaire survey of Japanese breast cancer authorities on endocrine therapy and a multi-institute survey to investigate the efficacy of a single first-line endocrine therapy for recurrent breast cancerwere conducted. MATERIALS AND PATIENTS: A total of 279 questionaires were sent to the Councilors of the Japanese Breast Cancer Society. The clinico-pathological data of 77 breast cancer patients who underwent a single first-line endocrine therapy were collected from five institutes. RESULTS: The response rate to this questionaire survey was 67.4%. The resultsshow that many authorities consider that: 1) both ER and PgR in primary tumors should be measured, 2) patient age, the disease-free interval and postoperative adjuvant therapy do not provide enough information for the selection of endocrine therapies, 3) antiestrogen and LH-RH agonists should be used as first-line endocrine therapies, 4) combined endocrine therapies, such as an antiestrogen plus an LH-RH agonist, should be used, 5) the optimal sequence of use of endocrine therapeutic agents is most controversial. The objective response rate to first-line endocrine therapies was 40.3% and the duration of response was over 15 months.The objective response rate to second-line endocrine therapies was 42.1%. A multiple regression analysis of predictive factors for the efficacy of first-line endocrine therapies indicated two factors, the disease-free interval and dominantsite of metastasis, to be significant. Conclusions: This questionaire survey suggests that clinical trials to investigate the optimal sequence of use of endocrine therapies and to clarify the usefulness of combined endocrine therapies should be conducted. Single first- or second-line endocrine therapies for recurrent breast cancer are effective and should be carried out by general clinicians.

Journal Article↗
PubMed1999

Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect.

Interleukin 6 (IL-6) is a multifunctional cytokine. Recent reports suggest that circulating IL-6 secreted from tumour cells plays an important role in cancer-induced cachexia. Medroxyprogesterone acetate (MPA) has been used as an endocrine therapeutic agent for patients with breast cancer. It has been suggested that MPA decreases serum IL-6 levels and preserves the bodyweight of patients with advanced breast cancer. However, the mechanisms of action responsible for the anticachectic effect of MPA have not been elucidated. Therefore, the effects of MPA on IL-6 secretion were studied both in vitro and in vivo using a human breast cancer cell line, KPL-4, which secretes IL-6 into medium and induces cachexia when injected into female nude mice. MPA (10-1000 nM) dose-dependently decreased basal IL-6 secretion into medium, and also suppressed tumour necrosis factor (TNF-alpha)-induced IL-6 secretion. Both basal and TNF-alpha-induced IL-6 mRNA levels were dose-dependently lowered by MPA. Moreover, intramuscular injections of MPA (100 mg kg(-1) twice a week) into nude mice bearing KPL-4 transplanted tumours significantly decreased serum IL-6 levels without affecting tumour growth and preserved the bodyweight of recipient mice. These findings suggest that suppression of IL-6 secretion from tumour cells, at least in part, causes the anticachectic effect of MPA.

Animals↗
PubMed1999

Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6.

A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. Reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.

Animals↗
PubMed1999

Analyses of the outcome of locally invasive papillary thyroid carcinomas.

We retrospectively analyzed the outcome for patients with locally invasive papillary carcinoma. The study group comprised 40 patients with locally invasive papillary thyroid carcinoma first diagnosed between 1981 and 1995. The enrolled patients were divided into two groups according to whether they underwent complete resection (n = 19) or not (n = 21). All patients were followed-up for a maximum of 206 months and a minimum of 33 months until 1998. There were no significant differences among these two groups with regard to age, sex, or tumor size. Recurrence of the disease was recognized in four patients in the complete resection group and ten in the incomplete group. There were no significant differences in the recurrence rate between both groups. Five patients from the incomplete resection group died of disease, and all patients from the complete resection group were alive. The percentage of surviving patients in the complete resection group was significantly higher than that in the incomplete group. The 15-year survival rates of the complete resection group and incomplete resection group were 100% and 74.2%, respectively. The 15-year survival rate of patients younger than 45 years in the incomplete resection group was 100%. The 15-year survival rate of the complete resection group was significantly higher than that of the incomplete group. In conclusion, complete resection without tumor residue should be performed for patients older than 45 years.

Adolescent↗
PubMed1999

Biochemical markers of bone turnover in breast cancer patients with bone metastases: a preliminary report.

BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the disease activity of metastatic bone tumor. In the present study six biochemical markers were evaluated to determine appropriate markers for the detection of metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover markers was assessed in 11 normocalcemic patients with bone metastases from BC and in 19 BC patients without clinical evidence of bone metastases. Bone formation was investigated by measuring serum bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I procollagen (PICP): Bone resorption was investigated by measuring serum carboxy-terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and menopausal status. Significant correlations were observed between each of bone turnover markers except between BALP and OC. The mean levels of the six bone turnover markers were higher in patients with bone metastases than in those without them and significance was observed except for OC. The best diagnostic efficiency by receiver-operating characteristic (ROC) analysis was provided by ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed between ICTP and OC. Multiple logistic regression analysis adjusted by age revealed that the only significant marker related to bone metastases was ICTP. CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from BC. However, to reveal the clinical usefulness of these markers, further examination will be needed to account for the ease and cost-effectiveness of the measurements.

Adult↗
PubMed1999

Expression of vascular endothelial growth factor (VEGF) family members in breast cancer.

Vascular endothelial growth factor (VEGF)-A is known to play an important role in tumor angiogenesis. Three additional members of the VEGF family, VEGF-B, -C and -D, have recently been discovered. VEGF-C and VEGF-D are ligands for VEGF receptor-3, which is expressed in the endothelium of lymphatic vessels. The expression of VEGF-C is known to be associated with the development of lymphatic vessels. Therefore, it is conceivable that VEGF-C and VEGF-D might play a role in the development of lymphatic vessels in solid tumors. To obtain some clue as to this role, we developed a semi-quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression levels of each VEGF family member in breast cancer. All the VEGF family members were expressed at different levels in seven human breast cancer cell lines explored. Although VEGF-A and VEGF-B expressions were detected in both node-positive and node-negative breast tumors, VEGF-C expression was detected only in node-positive tumors. VEGF-D expression was detected only in an inflammatory breast cancer and a tumor which developed an inflammatory skin metastasis. These findings suggest a possible relationship between the expression level of VEGF-C and/or VEGF-D and the development of lymphatic tumor spread.

Adult↗
PubMed1999

Basaloid type adenoid cystic carcinoma of the breast.

We report a case of adenoid cystic carcinoma (ACC) of the breast with a prominent basaloid feature. The patient was a 62-year-old Japanese woman with a right breast mass, measuring 1.5 cm in diameter. Histologically, the tumor was composed of basal cell-like tumor cells, and it was originally diagnosed as invasive ductal carcinoma. The presence of PAS-positive basement membrane material around the tumor cell nests may be a diagnostic clue to ACC. The prognosis of ACC of the breast is considered to be favorable. However, basaloid type ACC may represent a poor prognosis, since our case revealed an aggressive behavior in spite of its small size.

Breast Neoplasms↗
PubMed1999

[Usefulness of low dose 5'-DFUR (5'-deoxy-5-fluorouridine) for advanced or recurrent breast cancer].

The usefulness of low dose (600 mg/day) 5'-DFUR for advanced or recurrent breast cancer was evaluated. Eight patients out of 38 showed a partial response (response rate 21.1%), 22 patients had no change, and 8 patients had progressive disease. The response rate was 31.0% in soft tissue and 9.1% in bone, both of which were slight. In both one-shot (200 mg) and continuous (1-4 months) administration of 5'-DFUR (600 mg/day), the concentration of 5'-DFUR of 5-FU in sera reached a plateau from 30 minutes to 2 hours after administration of 5'-DFUR, and disappeared after 3 hours. There were no significant differences in the concentration of 5'-DFUR of 5-FU in sera between one-shot and continuous administration. It is concluded that there was no accumulation of the drug after continuous administration of 5'-DFUR, and that low dose 5'-DFUR is a useful therapy for advanced or recurrent breast cancer.

Administration, Oral↗
PubMed1999

[Doxifluridine decreases serum levels of interleukin-6 in a cancer cachexia model].

Cancer cachexia is a common paraneoplastic syndrome in patients with advanced malignancies. However, the mechanisms of the development of cancer cachexia remain to be elucidated. Interleukin (IL)-6 is known to be involved in the development of cancer cachexia. The KPL-4 human breast cancer cell line, which was recently established in our laboratory, secretes IL-6 into the culture medium. Oral administration of doxifluridine (5'-DFUR, 60 mg/kg or 120 mg/kg) significantly inhibited the growth of KPL-4 tumors, reduced the tissue levels of IL-6, and alleviated body weight loss. Serum IL-6 levels were also lowered by 5'-DFUR in nude mice bearing KPL-4 tumors. Additionally, it is suggested that tumor necrosis factor (TNF)-alpha is involved in the cachexia induced by KPL-4 tumors. We suggest that 5'-DFUR suppresses cancer cachexia by lowering IL-6 levels in the tumor tissues and serum.

Animals↗
PubMed1999

[Significance and problems of quality-of-life assessment in clinical trials].

The importance of quality of life (QOL), as an outcome variable of cancer treatments, has rapidly become recognized not only in western countries but also in Japan. However, many problems remain to be resolved for QOL assessment methods. In this paper, we give outlines for the position of QOL as an outcome variable, the standpoint and purpose for QOL assessment, the appropriate range of QOL domains to be assessed, and the appropriate QOL measures. Furthermore, we introduce key points for the success of QOL assessment in clinical trials, the appropriate way to deal with missing data and appropriate methods for analysis in longitudinal studies.

Clinical Trials as Topic↗
PubMed1998

S-100 protein-positive dendritic cells in follicular lesions of the thyroid.

Little is known about the role of S-100 protein-positive dendritic cells in follicular lesions of the thyroid. In 36 cases of adenomatous goitre, 18 cases of follicular adenoma, and 7 cases of follicular carcinoma, we investigated the incidence and distribution of S-100 protein-positive dendritic cells using immunohistochemical staining. Four cases (10.5%) of adenomatous goitre, five cases (31.3%) of follicular adenoma, and 6 cases (85.7%) of follicular carcinoma contained S-100 protein-positive dendritic cells in the subcapsular area and/or the hyalinized stroma. Dendritic cells in the subcapsular area were observed only in lesions with thick capsules and not those with thin capsules. In most cases of follicular carcinoma, + + to + + + of the dendritic cells was seen together with a few lymphocytes and fibroblasts in the subcapsular areas. In contrast, cases of adenomatous goitre and follicular adenoma showed only a few dendritic cells without any inflammatory cells. Dendritic cells in follicular thyroid lesions may play some role in capsular formation or may be a secondary phenomenon due to capsular formation.

Adenocarcinoma, Follicular↗
PubMed1998

A pure antiestrogen, ICI 182,780, stimulates the growth of tamoxifen-resistant KPL-1 human breast cancer cells in vivo but not in vitro.

The critical mechanisms responsible for antiestrogen resistance have not yet been elucidated. We previously established a breast cancer cell line, KPL-1, derived from a patient with recurrent disease which appeared under tamoxifenadministration. In a previous study, we suggested that this cell line is estrogen receptor (ER)-positive but tamoxifen-resistant. In the present study, the effects of a pure antiestrogen, ICI 182,780, on this cell line were investigated. Although tamoxifen inhibited neither cell growth nor estradiol-stimulated transcriptional activity in vitro, ICI 182,780, significantly inhibited both of them. Tamoxifen and ICI 182,780 were then administered to female nude mice bearing KPL-1 tumors. Tamoxifen had no effect on tumor growth, but ICI 182,780 unexpectedly stimulated it (p = 0.022). Estradiol tended to inhibit tumor growth (p = 0.198). Immunohistochemical analysis revealed that ICI 182,780 significantly increased the Ki6-labeling index (p<0.001) but estradiol decreased it (p = 0.035). To explore the possible mechanisms of these phenotypes, the mRNA levels of ER-alpha,ER-beta, transforming growth factor-beta1, fibroblast growth factor (FGF)-1 and FGF-4 in KPL-1 cells were compared with those in other ER-positive human breast cancer cell lines by reverse-transcription polymerase chain reaction. FGF-1 was overexpressed only in KPL-1 cells. This cell line is the first breast cancer cell line to be growth-stimulated by ICI 182,780 in vivo. Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells.

Animals↗
PubMed1997

Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells.

We recently established a human breast cancer cell line, KPL-3C, from a breast cancer patient with humoral hypercalcaemia. This cell line possesses oestrogen receptor (ER) and secretes parathyroid hormone-related protein (PTHrP) into medium. To investigate the effects of oestrogen and antioestrogens on PTHrP secretion, KPL-3C cells were cultured for 48 h in an oestrogen-eliminated medium with 17beta-oestradiol (E2), tamoxifen (TAM) and/or a pure antioestrogen, ICI182,780 (ICI), and PTHrP secretion was measured using an immunoradiometric assay. The effects of these agents on cell cycle progression were also studied using flow cytometry. E2 (1-100 nM) significantly inhibited PTHrP secretion, whereas both TAM (0.1-10 microM) and ICI (1-100 nM) significantly stimulated it. These effects were completely blocked by the simultaneous addition of 1 nM E2 to the medium. At the same time, E2 significantly increased the percentage of cells during the S and G2/M phases, whereas both antioestrogens significantly increased the percentage of cells during the G0/G1 phase. Again, these cytostatic effects were completely reversed by the addition of E2. These findings indicate that antioestrogens inhibit the growth of ER-positive breast cancer cells but may stimulate PTHrP secretion and that these effects may be mediated by ER.

Analysis of Variance↗