Biomedical subjects

H Sonoo

Publications and source records attributed to H Sonoo.

At least 55 records · Page 3Linked to original sources

PubMed1997

Lithium associated autoimmune thyroiditis.

A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration. Some areas showed a moderate degree of stromal fibrosis and atrophic thyroid follicles. Lymphoid follicles with germinal centres, disrupted thyroid follicles with lymphocytic infiltration, and Hürthle cells were also observed. The differential diagnosis in patients presenting with these histological features includes painless (silent) thyroiditis, autoimmune thyroiditis and lithium associated autoimmune thyroiditis. A detailed clinical history is essential if the correct diagnosis is to be reached.

Adult↗

PubMed1997

Postsurgical oral administration of uracil and tegafur inhibits progression of micrometastasis of human breast cancer cells in nude mice.

We recently established a metastasis model in nude mice using the MKL-4 cell line, a contransfectant of the MCF-7 human breast cancer cell line with fgf-4 and lacZ in which micrometastases in several organs can be quantitatively observed. First, to develop a new postsurgical metastasis model, we investigated the timing of occurrence of micrometastasis and the influence of tumor removal on the progression of micrometastasis in this model. Micrometastases into lymph nodes and lungs were detected 3 weeks after the cell injections. Tumor removal 3 weeks after the injections significantly enhanced the progression of micrometastasis into lymph nodes and bone. Second, to study the effect of a mixed compound, UFT (a molar ratio of uracil:tegafur of 4:1), which has been widely used in the postsurgical adjuvant setting in Japan, 15 or 20 mg/kg UFT were administered p.o. for 4 weeks to tumor-bearing mice or to mice in which transplanted tumors were resected 3 weeks after the injections. Either dose of UFT significantly inhibited the tumor growth as well as the progression of micrometastasis into lymph nodes, lungs, liver, and brain. In addition, enhanced progression of micrometastasis in all explored organs by the tumor removal was significantly inhibited by the administration of either dose of UFT. In conclusion, this new postsurgical metastasis model may be useful for evaluating the efficacy of agents used in the postoperative adjuvant setting. UFT may be an effective drug for inhibiting the progression of micrometastasis after surgery.

Animals↗

PubMed1996

Invasion-inhibiting factor 2-albumin conjugate inhibits invasion and spontaneous metastasis of MKL-4 human breast cancer cells transplanted into female nude mice.

Invasion-inhibiting factor 2 (IIF-2) and its albumin conjugate have been reported to inhibit spontaneous metastasis of highly metastatic cancer cells with no effect on primary tumor growth. To confirm the inhibitory effects of the IIF-2 conjugate on tumor invasion and spontaneous metastasis, we administered the conjugate intra-peritoneally (i.p.) to female nude mice bearing transplanted tumors with MKL-4 cells, which are MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and lacZ. Neither 10 nor 20 mg/kg doses of the conjugate caused any inhibition of primary tumor growth, but 20 mg/kg significantly inhibited tumor invasion and spontaneous metastasis. Tumor invasion was measured by a novel computer-assisted image analysis. Spontaneous microscopic metastases into lymph nodes and distant organs were measured by whole organ staining for beta-galactosidase activity and observed with a dissecting microscope. The dose of 10 mg/kg significantly inhibited tumor invasion but not metastasis. Interestingly, the number of factor VIII-positive microvessels in the tumors was not reduced by treatment at either dose level. These findings suggest that the anti-invasive effect of the IIF-2 conjugate may reduce both lymphatic and hematogenous metastases in this MKL-4 metastasis model without affecting angiogenesis.

Angiogenesis Inhibitors↗

PubMed1996

Serum tumor marker kinetics and the clinical course of patients with advanced breast cancer.

Serum carcinoembryonic antigens (CEA), CA 15-3, and tissue polypeptide antigens (TPA) have been used in monitoring the clinical course of patients with breast cancer. However, recent reports have suggested that the serial levels of these markers during therapy do not always correlate with the response to therapy. To clarify the usefulness of the serial combination assay of these markers in monitoring the clinical course of patients during therapy, we investigated the relationship between the initial changes and the kinetic patterns of the markers after therapy and the objective responses. When an increase or decrease of over 20% in these markers is taken to be significant, then the initial changes in all three markers significantly correlated with the therapeutic responses (P < 0.01). Five distinct kinetic patterns in the marker levels were observed. A paradoxical kinetic pattern of CEA and CA 15-3 levels--that is, an "initial surge and subsequent drop"--was seen in one-third of the responders. The TPA levels tended to exhibit a "steady decline" pattern in those responders. The sensitivity and specificity of the kinetic patterns to predict the clinical courses were significantly higher than those obtained from the analysis of initial changes. These findings thus suggest that adequate knowledge of the unique kinetics of each marker may help to make a more accurate prediction of the therapeutic responses.

Adult↗

PubMed1996

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice.

Parathyroid hormone-related protein (PTHrP) is the main cause of humoral hypercalcaemia of malignancy (HHM). We recently established a new human breast cancer cell line, designated KPL-3C, from the malignant effusion of a breast cancer patient with HHM. Morphological, cytogenetic and immunohistochemical analyses indicated that the cell line is derived from human breast cancer. The KPL-3C cells stably secrete immunoreactive PTHrP measured by a two-site immunoradiometric assay, possess both oestrogen and progesterone receptors and are tumorigenic in female nude mice. The addition of phorbol-12-myristate-13-acetate to the medium significantly increased PTHrP secretion from the cells. In contrast, hydrocortisone, medroxyprogesterone acetate and 22-oxacalcitriol decreased PTHrP secretion in a dose-dependent manner. Unexpectedly, a number of microcalcifications were observed in the transplanted tumours. Radiographical examination indicated that the microcalcifications in the tumours are very similar to those commonly observed in human breast cancer. These findings suggest that this KPL-3C cell line may be useful for studying the regulatory mechanisms of PTHrP secretion and the mechanisms that lead to the deposition of microcalcifications in breast cancer.

Adult↗

PubMed1996

[Effectiveness of combination hormonal therapies in advanced or recurrent breast cancer--a randomized trial of tamoxifen (TAM), medroxyprogesterone acetate (MPA), their simultaneous combination, and an alternating sequential combination of TAM plus MPA].

The effects of tamoxifen (TAM), medroxyprogesterone acetate (MPA), their simultaneous combination or an alternating sequential combination of TAM plus MPA (TAM-MPA), was evaluated in 52 patients with advanced or recurrent breast cancer in a randomized controlled trial. The response rates of TAM, MPA, TAM & MPA, and TAM-MPA were 13.3%, 36.4%, 7.1% and 25.0%, respectively. All four therapies showed a higher response rate in the patients with soft tissues or with no previous therapy. However, there were no significant differences between the patient's characteristics and response rate among these four therapies. The differences in the frequency of adverse effects among these therapies were not significant, and there were no severe adverse effects with any therapy. In the cross-over trial of TAM and MPA, although 15.4% of patients who failed to show a response to TAM showed an objective response to MPA, no response to TAM was seen in the patients who had failed to show a response to MPA. In conclusion, TAM & MPA was not more effective than TAM or MPA, and TAM-MPA was not more effective than MPA. Adverse effects were not increased with TAM & MPA or TAM-MPA. MPA was useful as a second-line therapy after TAM.

Aged↗

PubMed1995

Comparison of Modified Radical Mastectomy with Quadrantectomy, Axillary Dissection, and Radiation Therapy in Early Breast Cancer in Japaness Women.

From January 1987 to December 1993, Stage I (T1N0M0) breast cancers were treated by quadrantectomy with axillary lymph node dissection plus radiation therapy (QUART) in 57 cases and by modified radical mastectomy (MRM) in 57 cases. The results for these two treatment groups were compared retrospectively. Booster irradiation of 10 Gy to the tumor bed was given to 1 of 5 cases with a positive resection margin. The remaining 56 cases received 50 Gy lineac X-ray to the ipsilateral breast. Systemic adjuvant therapy, tamoxifen and /or 5-FU derivatives p.o., were given to the majority of cases in both groups. There were no significant differences between the two groups with regard to the patient background; ie, age, tumor size, pathological node status, histology and estrogen receptor status. During the follow-up period of 12 to 89 months (median 55 months) in the QUART group, no local recurrence was observed and only 1 case of bone metastasis occurred. In the MRM group, recurrence occurred in 4 cases during the follow-up period of 12 to 95 months (median 52 months). These consisted of 2 cases of regional lymph node recurrence and 2 cases of lung metastases. The differences in the disease-free survival rate and the overall survival rate between the two groups were not significant. In the QUART group, mild radiation pneumonitis and mild telangiectasia in the breast skin were observed in 2 cases(3.5%) and 1 case, respectively. Mild arm edema was observed in 4 cases (7%) in each group. These results demonstrated that QUART was as effective as MRM in treating T1M0M0 breast carcinoma in Japanese women.

Journal Article↗

PubMed1995

Medical Economics and Quality of Life: Analysis of Factors That Influence the Perception of Medical Cost by Post-surgical Breast Cancer Patients.

Recently, the importance of achieving a balance in terms of length of life (LL), quality of life (QOL) and medical costs has been emphasized in the evaluation of cancer treatment, and it is also said that the cost should be seen from the viewpoints of both the society and the patient. Few studies, however, have been performed to investigate how the patients bear the cost and the influence of this factor. Therefore, in the present study we examined the perception of medical care cost (PMC) in 83 non-recurrent post-surgical breast cancer patients. The factors that influence the PMC were analyzed by univariate and multivariate analyses using the variables representing QOL, sociodemographic and clinical characteristics, types of therapy, and various types of medical cost. First, the results of the relationship between the variables and the PMC revealed that the patients with better QOL, especially those with better social category QOL, tended to have a lower PMC. However, no other variable had any significant associations with the PMC. Second, the results of multiple regression analyses revealed that patients with better QOL, especially those with better social category QOL, in the elderly, and/or those with higher level of education tended to show a lower PMC. In conclusion, the results of the present study suggest that, when we consider evaluating the cost of cancer treatment for postsurgical breast cancer patients, we should take into account the patients' QOL, age, and their level of education.

Journal Article↗

PubMed1995

The Impacts of Breast Conserving Treatment and Mastectomy on the Quality of Life in Early-stage Breast Cancer Patients.

The quality of life (QOL) in 55 early-stage breast cancer patients after surgery was prospectively assessed using a newly developed Japanese QOL questionnaire: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The impacts of breast conserving treatment (BCT) (22 cases) and modified radical mastectomy (MRM) (33 cases) on the QOL in those subjects were compared. The overallQOL scores were evaluated during four periods (before surgery, 0-2, 3-12, and 13-24 months after surgery). The mean scores of the four categories of the QOL-ACD (activity, physical condition, psychological condition, and social relationships) were also compared. The results demonstrated that a significant improvement was observed in the overall QOL scores among the three periods after surgery (0-2, 3-12, and 13-24 months) only in the BCT group (p<0.05). There were no significant differences between the two groups in the overall QOL scores during any of the three periods after surgery, and the mean score of the 'psychological condition' during 0-2 months period in the BCT group was significantly lower than that in the MRM group (p<0.05). These results suggest that BCT does not always improve the patients' QOL more than MRM does, and that the patients receiving BCT require more psychological support than those receiving MRM during the early postoperative period.

Journal Article↗

PubMed1995

Timing of surgery in relation to the menstrual cycle and its influence on the survival of Japanese women with operable breast cancer.

It has been suggested that the timing of surgery during periods of unopposed estrogen circulation, when high blood levels of estrogen and low blood levels of progesterone exist, has a deleterious effect on the survival of premenopausal patients with breast cancer. We studied this controversial issue by examining the serum estradiol and progesterone levels of 38 premenopausal patients with primary breast cancer, and by analyzing data on 100 premenopausal patients treated for primary breast cancer. The survival of 31 patients who had undergone initial surgery between days 3 and 12 after their last menstrual period (group E) was compared with that of 69 patients who had undergone surgery between days 0 and 2 or from 13 days after their last menstrual period (group P). The overall survival of group E was significantly worse than that of group P (P = 0.049). This difference was especially notable in patients with node-positive tumors or tumors larger than 2 cm in size; however there was no significant difference in disease-free survival between the two groups. On a multivariate analysis, nodal status was the only significant prognostic factor for both overall and disease-free survival. Thus, these findings suggest that unopposed estrogen circulation may be detrimental to the overall survival of premenopausal women with breast cancer.

Adult↗

PubMed1995

Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer.

To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.

Activities of Daily Living↗

PubMed1995

A new human breast cancer cell line, KPL-1 secretes tumour-associated antigens and grows rapidly in female athymic nude mice.

We recently established a new human breast cell line, designated KPL-1, which was derived from the malignant effusion of a patient with breast cancer. This cell line is highly tumorigenic and grows rapidly in female nude mice. Cytogenetic analysis indicated its human origin and revealed a hypertriploid modal number of chromosomes. Electron microscopic examination suggested that the KPL-1 cells are of epithelial origin. Immunohistochemical studies revealed that the cells express cytokeratin, carcinoembryonic antigen and CA 15-3. They also possess a large number of oestrogen receptors but not progesterone receptors. Interestingly, KPL-1 cells seem to grow oestrogen independently in vitro. No amplification of c-erbB-2, c-myc, H-ras and N-ras genes was detected. KPL-1 cells secrete a large amount of tissue polypeptide antigen (TPA). Although the secretion of CA 15-3 seemed to be constant throughout all cell growth phases, TPA secretion increased during the exponential growth phase and decreased during the plateau phase. Serum TPA levels significantly correlated with the volume of KPL-1 tumours transplanted into nude mice. These data suggest that this KPL-1 cell line may be useful for studying oestrogen-independent growth and the kinetics of tumour-associated antigens in vivo as well as in vitro.

Animals↗

PubMed1995

[Analysis of factors that improve quality of life of patients with advanced or recurrent breast cancer].

The quality of life (QOL) of 21 patients with advanced or recurrent breast cancer was assessed using a QOL measure developed by the Ministry of Welfare in Japan: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The factors that improve the QOL were analyzed by multiple regression analysis. The difference of the QOL score between pre- and post-treatment was set as a dependent variable, and sociodemographic and therapeutic characteristics were set as independent variables. The results revealed that the improvement of the QOL score had close associations with therapeutic efficacy (TE) and shorter disease-free interval (DFI). In the analysis using the mean scores of the four categories of the QOL (activity, physical, psychological and social aspects) as dependent variables, activity had a close association with shorter DFI; physical aspect had close associations with TE and shorter DFI; and the psychological aspect had close associations with chemoendocrine therapy and less lines of previous therapies. The results suggest that, to improve the QOL of patients with advanced or recurrent breast cancer, we should attempt to obtain higher efficacy of treatments such as endocrine therapy for patients with shorter DFI in the earlier period of their clinical course.

Adult↗

PubMed1995

[Antiproliferative and antimetastatic effects of UFT on MKL-4 human breast cancer cells transplanted into nude mice].

Prospective studies have suggested that postoperative adjuvant chemotherapy for breast cancer resulted in a lower recurrence rate and a better survival rate. However, there have been little experimental data on the chemotherapeutic agents for the suppression of progression of micrometastasis from breast cancer focus. We recently established a spontaneous metastasis model of MKL-4 human breast cancer cells transplanted into nude mice. In the present paper, both antiproliferative and antimetastatic effects of UFT were studied with this metastasis model. Oral administration of UFT (20 mg/kg daily) given 4 weeks inhibited significantly the growth of MKL-4 tumors in mice. Histological examination revealed a massive necrosis in the treated tumors. UFT also seemed to decrease the frequency of lymph node and distant metastases. In particular, no metastasis was observed in tumor-bearing mice in which the volume of tumors after the UFT-treatment was smaller than that before the treatment. It is premature to conclude that UFT has an antimetastatic effect because the volumes of the tumors of the control group and the treatment groups differed, but at least UFT may have an antimetastatic effect.

Animals↗

PubMed1995

[Systemic therapy, pain relief and quality of life of breast cancer patients with bone metastasis].

Systemic therapy, pain relief and the quality of life (QOL) of breast cancer patients with bone metastasis were described. QOL was measured using a "QOL questionnaire" developed by the Ministry of Welfare in Japan. It was proved objectively that QOL scores in the cases with bone metastasis were significantly low in terms of activity, physical psychological conditions. Chemoendocrine therapy, endocrine therapy and outpatient therapy showed a high QOL score. The cases with bone pain showed a low QOL scores. In the 45 cases whose first metastatic site was bone only, there were no differences between endocrine therapy and chemoendocrine therapy in the rate and period of response or the total QOL score. MPA showed a higher response rate and a higher pain relief rate than TAM. In the cases with bone metastasis but without severe visceral metastasis, MPA monotherapy showed an excellent response when the tumor was ER or PgR positive, or when there was a long disease-free interval of more than three years, or if there was no previous therapy. MPA monotherapy is a suitable firstline therapy in such cases. Radiation therapy was more effective for bone pain (response rate 96.3%), and it was also effective in cases in which systemic therapy was not.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

[Clinical effects of carmofur (Mifurol) on advanced and recurrent breast cancer in a cooperative study. Research association for re-evaluation of direct effects of Mifurol on breast cancer].

The direct effect and safety of carmofur (Mifurol) in cases of advanced and recurrent breast cancer were evaluated as a cooperative study at twenty-two facilities nationwide. Carmofur 12 mg/kg/day within the maximum daily dose of 600 mg was administered orally for eight weeks or longer. Of 42 patients registered for the study, 38 met the eligibility criterial (qualified patients), of whom 31 completed all tests for evaluation (completely qualified patients). The response rates were 18.4% with the qualified patients (PR, 7; Long NC, 3; NC, 11; PD, 12; NE, 5; ie, 7/38), and 22.6% with the completely qualified patients (PR, 7; Long NC, 2; NC, 10; PD, 12; ie, 7/31). The interval before the onset of PR after administration of carmofur was started was a minimum 29 days, a maximum 190 days and a median 82 days. Side effects were observed in eighteen patients (42.9%). Frequent micturition, loss of appetite, dizziness or feverish feeling were major symptoms, but none were serious.

Administration, Oral↗

PubMed1995

[A dose-comparative study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

A comparative phase II study was performed with different doses of TAP-144-SR in ER-positive or ER-unknown premenopausal patients with advanced or recurrent breast cancer. One hundred and six patients were randomly allocated to either 3.75 mg or 7.5 mg treatment by a centralized telephone registration system. TAP-144-SR was administered sc at 4-week intervals for 12 weeks (a total of 3 injections). Ninety-five cases were evaluated with the response rate of 30.4% (14/46) in the 3.75 mg group and 24.5% (12/49) in the 7.5 mg group, respectively. Serum estradiol was decreased to postmenopausal level (< 30 pg/ml) within 3-4 weeks after the first dose in the both dose groups, and this suppression was maintained throughout the treatment period. The adverse reactions most frequently observed were climacteric disturbances like hot flashes which was likely to be due to the hypoestrogen status. In conclusion, there was no significant difference between both dose groups in terms of response rates, adverse effects, and hormonal suppression. Therefore, the lower dose is recommended for the further study.

Adult↗

PubMed1995

[Long-term clinical study on TAP-144-SR, an LH-RH agonist depot formulation, in premenopausal patients with advanced or recurrent breast cancer. TAP-144-SR Breast Cancer Study Group].

Efficacy and safety of long-term treatment with an LH-RH agonist, TAP-144-SR were studied in premenopausal patients with advanced or recurrent breast cancer. The drug was given sc every 4 week at the dose of 3.75 or 7.5mg. The best objective response rates were 37.0% (17/46) in 3.75mg group, 30.6% (15/49) in 7.5mg group, respectively. The median duration of 12 PR patients in 3.75mg group was 280 (range: 84-830+) days. Serum estradiol level was maintained at < 30pg/ml in most patients given 3.75mg or 7.5mg as scheduled. There was no adverse reactions specific to the longterm administration subsequent to the foregoing 12-week administration study in both dose groups. In conclusion, TAP-144-SR is expected to be one of the first line therapies for patients with premenopausal breast cancer.

Adult↗