Biomedical subjects

K Shimozuma

Publications and source records attributed to K Shimozuma.

At least 19 recordsLinked to original sources

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

Gastric metastasis from breast cancer: a pitfall in gastric biopsy specimens.

A 49-year-old woman presented with abdominal discomfort and weight loss. Gastroduodenoscopy showed small polypoid lesions and biopsy specimens suggested primary adenocarcinoma with neuroendocrine differentiation. As the patient had a prior history of metachronous breast cancer, it was concluded that the case was metastatic carcinoma from the breast. The usefulness of a panel of selected immunohistochemical markers to determine the primary site of the breast in an appropriate clinical setting is greatly emphasized.

Adenocarcinoma↗

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↗

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

[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

[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↗

PubMed1994

The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer.

Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P < 0.05). The mean maximum tumor diameters for the three groups were 1.7 cm, 2.5 cm, and 3.0 cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group at P < 0.01 and P < 0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P < 0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P < 0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.

Adult↗

PubMed1994

[Early phase II study of MST-16 (sobuzoxane) for breast cancer].

An early phase II study of MST-16 for breast cancer was conducted with the participation of 9 hospitals. MST-16 was administered at three doses; 1) 1,600 mg/body for 5 consecutive days repeating every 4 weeks, 2) 1,200 mg/body for 10-14 consecutive days every 5 weeks, and 3) 1,200 mg/body daily for at least 4 weeks. A total of 28 patients were entered, and 27 cases were eligible. Twenty-five cases were evaluated for efficacy and 27 cases for safety. One patient achieved complete response, 2 patients attained partial response, and the response rate thus obtained was 12.0%. Major side effects observed were myelosuppression represented by leukopenia (69.2%) followed by gastrointestinal disorders. These symptoms, however, were reversible by the cessation of administration.

Adult↗

PubMed1991

[Predictability of preclinical evaluation of anticancer drugs by human gastrointestinal cancer--nude mouse panel].

We evaluated the predictability to clinical response of experimental effects of various anticancer agents on human cancer--nude mouse panel established in our department. The human cancer lines used were 12 gastric, 4 colorectal, 3 breast, 2 pancreatic cancers and 1 melanoma xenografted into BALB/c athymic nude mice under SPF conditions. Seven mice each with equivalent mean volume of sc inoculated tumor (about 100 mm3) were subjected to the treatment and control groups. Experimental treatment was conducted daily 25 times for antimetabolites, and intermittently 5 times once or twice a week for other drugs. Dosage of each drug adopted was maximal tolerated dose predetermined for the treatment schedule. Four weeks after the initiation of treatment, the therapeutic effect of each experiment was evaluated by the tumor growth inhibition rate (IR) based on the comparison of mean tumor weight between the 2 groups. When the IR was greater than 58%, the drug was evaluated as effective. The clinical response rate of each drug was referred from the result of the phase II study. Direct comparison of effects on 16 experimental chemotherapies in xenografts with responses to the corresponding clinical therapy of each donor patient revealed a fairly high accordance rate (94%). To elucidate the value of human cancer--nude mouse panel as the preclinical secondary screening, the response rates of 8 anticancer drugs treated to 15 cancer xenografts were compared with the cumulative clinical data available in each drug. Generally, the response rates of the human cancer xenografts to the drugs showed fairly good correlations with the cumulative clinical response rates of the corresponding drugs to the same organs. Using this panel, preclinical examinations of 6 new agents under development, including 254 S and other 2 CDDP derivatives, were performed in expectation the positive correlation with further clinical data.

Animals↗

PubMed1991

[Notification of cancer in breast cancer patients].

The notification of the name of disease is a premise for making the system of informed consent more complete in case of cancer treatment. In Japan, however, the notification of cancer can hardly be said to have an attained social consensus. Considering that the notification can ultimately improve patients quality of life (QOL), the breast cancer group of our department informs all breast cancer patients of their diseases in principle. This paper reports and discusses the results of a survey by questionnaire on the notification of cancer in 100 patients with breast cancer. The notification of cancer was received favorably in 83% of the patients. For those who answered, the explanation on the notification was convincing and it accounted for 81%. An examination of background factors of patients who had not been convinced revealed that many of them were suffered from advanced cancer. After the notification, a human relationship with the family and friends aggravated few of them and improved in 30% (family) and 18% (friends), respectively. The notification of cancer was thus suggested to contribute to the improvement of QOL. Although 83% well received the notification of their own diseases, only 21% were affirmative for the notification of cancer in case of a member of the family. We medical professionals should make a further effort not to make the notification of cancer the pronouncement death but to make it an aid for patients to live better.

Breast Neoplasms↗

PubMed1990

Effect of CGS 16949A plus tamoxifen on induced mammary tumours in rats.

The antitumour effect of CGS 16949A, an aromatase inhibitor, was investigated in rats with mammary tumours induced by 7,12-dimethylbenz[a]anthracene. A dose-dependent antitumour effect was observed after daily oral administration of CGS 16949A for 3 weeks. The tumour did not recur in the groups treated with 4.0 and 8.0 mg/kg per day. The complete remission rate increased and the time required to achieve complete remission became shorter with increasing daily doses. After daily administration for 3 weeks, a significant antitumour effect was observed in the group treated with CGS 16949A plus tamoxifen compared with that seen either with CGS 16949A or with tamoxifen alone. At the end of treatment, the group treated with CGS 16949A had significantly decreased oestradiol-17 beta and prolactin levels and increased levels of follicle stimulating hormone, but oestrone was not affected.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1989

Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice.

The results of single-agent chemotherapy, with 11 anticancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3-4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.

Animals↗

PubMed1989

[Evaluation of predictability of in vitro SDI assay in comparison with in vivo nude mouse assay].

Twenty lines of human gastro intestinal and breast cancer xenografts, in which chemosensitivity spectra by the in vivo nude mouse assay had been clarified. were subjected to the in vitro SDI (succinate dehydrogenase inhibition) assay using MTT dye to assess the accuracy of this drug sensitivity test against 4 drugs i.e., mitomycin C (MMC), adriamycin (ADM) 5 fluorouracil (5-FU), and cisplatin (CDDP). After 3 days incubation, the suspension of every tumor cells including small fragments showed a marked decrease of SD activity even when no anticancer drug was added to the assay medium. Among these 4 drugs evaluated MMC exhibited a statistically significant correlation between chemosensitivity values of the in vitro SDI assay and those of the nude mouse assay. However, the other 3 drugs demonstrated no correlation between the values of these two methods. Since the primary cultured fibroblasts revealed, in general, lower sensitivity to these drugs, contamination of fibroblast may decrease the SDI values when materials from solid tumors with rich stroma such as a type of stomach cancer were subjected. It is considered that the prediction of chemosensitivity to every drug will be impossible by a in vitro SDI assay.

Animals↗

PubMed1987

[Combination chemotherapy with 3 or 4 drugs on human breast and gastrointestinal cancer xenografts in nude mice (II)].

Because of the limited effects of single-agent chemotherapy for solid tumors, combination therapy was employed in an attempt to enhance the clinical effects. Following our former report in which the combination effects of mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) were clarified, combined applications of 4 drugs, vindesine (VDS), methotrexate (MTX), cisplatin (CDDP) and 5'-DFUR against 3 lines of human breast cancer (H-62, H-31, H-71), and one line each of gastric cancer (H-55) and colon cancer (H-110) xenografted into nude mice were evaluated in comparison with CAF (cyclophosphamide, adriamycin and 5-FU) therapy which is commonly used for breast cancer. Treatment was initiated in groups of 7 mice each when the mean tumor volume of subcutaneous tumors had reached about 100mm3, and the therapeutic effect was evaluated in terms of the inhibition rate (I.R.). A synergistic effect is said to exist when the combination therapy is superior to each single drug therapy at the maximal tolerated dose. Combination therapy with 3 drugs (VDS, CDDP and 5'-DFUR) or 4 drugs (VDS, CDDP, MTX and 5'-DFUR) achieved an I.R. of over 98%, i.e., a marked effect with tumor shrinkage, in 3 lines of tumors (H-55, H-31 and H-62). Moreover, remarkable effects were shown even in the other 2 lines which were insensitive to every single-agent therapy, the I.R. values being 85.7% (H-71) and 78.5% (H-110). A synergistic effect was obtained in 3 of the 5 lines examined. These combination therapies were histologically superior to therapies employing each single-drug therapy or CAF therapy. The side effects for combination of these 3 or 4 drugs evaluated by body weight loss were transient and equivalent to maximal dose of VDS or CDDP. Clinically, it is thought that these combined therapies of 3 or 4 drugs will bring about a considerable response in practice.

Animals↗

PubMed1987

[Effects of alternating chemotherapy with 2 non-cross-resistant drug combinations on human alimentary and breast cancer xenografts in nude mice].

Despite the recent advances made in the development of anticancer drugs, any single chemotherapy treatment has only limited effects on cancers of the stomach, colon and breast, so that the combined use of multiple drugs is necessary for the treatment of solid tumors. In our previous studies with human gastrointestinal and breast cancers xenografted into nude mice, combination therapy with mitomycin C (MMC) and 5'-deoxy-5-fluorouridine (5'-DFUR) [I] or cisplatin (CDDP), vindesine (VDS) and 5'-DFUR [II] produced higher response rates than single-agent therapy with any one of these drugs. In the present study, the effectiveness of alternating chemotherapy with the combination regimens I and II was evaluated using 3 lines of cancer xenografts with special emphasis on relapse-free survival. Even in untreated controls, different influences of these cancers on the host as well as differences in their growth rates resulted in delayed tumor death in breast cancer (H-31) compared with pancreas (H-48) and colon (H-110) cancers. Four cycles of the regimen I drug combination failed to prolong life due to toxic side effects in every cancer line. In H-48 cancer, although regimen I alternated with regimen II achieved an inhibition rate (IR) of 96% with tumor shrinkage, 2 of 7 mice died of toxicity. In H-110 cancer, which is only sensitive to VDS, 4 cycles of regimen II alone produced an IR of 83.5%, which was slightly superior to alternating chemotherapy. In H-31 cancer, which retains considerable sensitivity to CDDP, MMC and 5'-DFUR, mice treated with alternating chemotherapy starting from regimen I for a total of 5 cycles attained a maximal IR of over 99% including disappearance of the tumor in 6 of 7 mice during the treatment course, and at the end of the experiment (20th week), all had survived with one in a relapse-free state, compared with the control group which had only 2 survivors. Thus, cyclic delivery of two non-cross-resistant drug combinations with optimal treatment doses and timing prevented toxic effects and induced long-term survival without relapse. Also, this appears to be the first study that has evaluated the effects of cancer chemotherapy in a human solid tumor-nude mouse system according to survival rate.

Animals↗

PubMed1987

[Subrenal capsule assay for chemosensitivity testing].

The subrenal capsule (SRC) assay for cancer chemotherapy was tested according to Bogden's methodology. Of 37 patients providing tumor tissue for assay, 29 cases were considered suitable for evaluable assays. Fourteen patients had clinically evaluable diseases and 10 cases were evaluable for SRC assays. Correspondence between sensitive assay and clinical sensitivity was seen in 2 cases, and that between resistant assay and clinical resistance was seen in 4 cases. Discordance between sensitive assay and clinical resistance was seen in 4 cases. In histological studies, cancer tissues implanted in the subrenal space in immunocompetent mice did not show marked proliferation and were replaced by prominent leukocyte infiltration and fibrosis on day 6 after inoculation. The degree of leukocyte infiltration in the xenografts in the mice administered some anti-cancer drugs was slight in comparison with that in untreated control mice, which showed a remarkable trend in xenografts treated with 5-fluorouracil and cyclophosphamide, respectively. Our study suggests that there are many problems involved in the SRC assay methodology of Bogden, and that careful examination of this aspect will be required.

Animals↗

PubMed1987

[Subrenal capsule assay as a chemosensitivity test (III)--Comparison of host reaction, experimental chemotherapy and use of nude mice].

We studied fundamentally subrenal capsule assay, using human tumor specimens (gastric, breast and pancreas cancers) serially transplanted in nude mice. Any prominent difference of host reaction was not found between the host of BALB/c-nu/+, BALB/c-+/+ and CDF1 mice. Using immunocompetent BALB/c-nu/+ mice, experimental chemotherapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) was carried out. On day 6, macroscopic and histological findings corresponded relatively well with 5-FU effect but not with MMC. Using BALB/c-nu/nu mice, we tried 15-day SRC assay. When the sensitivity of anti-cancer drugs was compared between early and intermediate phase after inoculation, no obvious difference was found macroscopically and histologically. BALB/c-nu/nu mouse will be useful as a host of SRC assay, and could be applicable to clinical fresh cases.

Animals↗