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Biomedical subjects

I Kimijima

Publications and source records attributed to I Kimijima.

At least 37 records · Page 2Linked to original sources

[Correlation between apoptotic index, bcl-2 protein expression and progression and prognosis in breast carcinoma].

Apoptosis is considered to play a critical role in tumorigenesis. It has been shown that apoptosis is controlled by both pro-oncogenes bcl-2, c-myc and tumor-suppressor genes p53. We determined the apoptotic index (AI) on light microscopy and detected immunohistochemically the expression of bcl-2 and p53 in patients with breast cancer. The correlations between AI and clinicopathological factors, bcl-2 and p53 were also analyzed. Our results showed that bcl-2 expression was down-regulated in the process from normal breast epithelial cells to intraductal carcinoma and from intraductal carcinoma to invasive carcinoma. We failed to detect p53 protein in normal breast epithelial cells, and p53 positivity was 24% and 30% in intraductal and invasive cancer tissues, respectively. Moreover, AI was significantly associated with histological grade, mitotic index, and bcl-2 and p53 expression. In univariate analyses, lower AI and bcl-2 expression was significantly predictive of a better prognosis for both disease-free survival and overall survival. These results suggest that apoptosis and apoptosis-related gene (bcl-2, p53) are related to progression and prognosis in breast cancer.

Adult↗

Clinical characteristics of breast cancer patients with family history.

This study was conducted to acquire information as to the clinicopathological characteristics of breast cancer patients with family history. Of 583 patients with breast cancer, 60 (10.3%) had family history in at least one relative within the second-degree. The affected family member was most frequently a sister (43%), followed by the mother (23%) and an aunt (20%). Comparison of the data for the patients between with and without family history revealed no significant differences for any of mean age, menopausal status, histological type, histological staging, and estrogen receptor status. Although the sample size was small, neither the survival rate nor the bilaterality of disease was influenced by the family history of breast cancer.

Adult↗

Role of age as a prognostic factor in breast cancer.

The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or II breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.

Adult↗

Correlation between the expression of apoptosis-related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas.

The proto-oncogene bcl-2, which is implicated in the regulation of cell death by inhibiting apoptosis, is reported to be expressed in breast tissues. The wild-type p53 has been shown to induce apoptosis, which can be inhibited by bcl-2 expression. However, the role of bcl-2 and p53 expression in breast carcinogenesis has not been clarified. The purpose of this study was to evaluate bcl-2 and p53 expression in normal breast epithelia cells, as well as in intraductal and invasive cancerous lesions of breast cancer tissue using an immunohistochemical method and to clarify their role in the development of breast cancer. The nuclear accumulation of p53 was also evaluated by quantitative image analysis. Expression of bcl-2 was found in 79 of 82 (96%) normal ductal epithelial cells, in 50 of 63 (79%) intraductal carcinomas, and in 62 of 137 (45%) invasive carcinomas, respectively. Higher bcl-2 expression was observed in normal epithelial cells than in intraductal and invasive cancerous cells (P < 0.0001). Furthermore, bcl-2 positivity in intraductal lesions was significantly higher than in invasive cancerous lesions (P < 0.05). No p53 nuclear accumulation was observed in normal breast epithelial cells. Fifteen of 63 (23.8%) intraductal cancerous lesions and 41 of 137 (30%) invasive cancerous lesions were positive for p53 expression. An inverse relationship was shown between bcl-2 and p53 expression in invasive carcinomas. We demonstrated that bcl-2 expression exists in most of normal ductal epithelial cells and gradually decreases during the development of breast cancer, i.e. , from a normal epithelium to intraductal carcinoma, and from intraductal to invasive carcinoma, and that p53 expression may occur early in breast cancer development and increases during progression.

Apoptosis↗

Immunohistochemical evaluation of lymph node micrometastases from breast cancer.

The lymph node micrometastasis was retrospectively immunohistochemically investigated in 185 patients with node-negative breast cancer and compared with the routine conventional findings. The monoclonal antibodies to epithelial membrane antigen (EMA) and mucinous-like carcinoma antigen (MCA) were used. Of 19 EMA-positive cases, 16 were false positive. Therefore only 3 cases were found to show staining with both EMA and MCA. The patients are all living and well and free of recurrence. No micrometastasis was immunhistochemically demonstrated in 11 node-negative breast cancer patients with subsequent metastases. The results of the present study indicate that the detection rate containing occult cells afforded by conventional routine evaluation is sufficient, at least in Japanese.

Adult↗

[Flow cytometric DNA analysis of malignant potential in colorectal cancer].

Significance of flow cytometric DNA analysis for assessing malignant potential and survival of colorectal cancer was investigated using paraffin-embedded materials from 163 patients who underwent resection of curability A from 1971 to 1985, excluding intramucosal carcinoma. DNA diploid was confirmed in 46% (75 cases) of the patients and DNA aneuploid in 54% (88 cases). No significant correlation was seen between DNA ploidy and clinicopathological factors, such as tumor location, macroscopic type, histological type, depth of invasion, lymph node metastasis and stage. Cumulative survival rates after curable resection of colorectal cancer were significantly lower in patients with DNA aneuploid tumor than those with DNA diploid tumor. Furthermore, in patients in stage of II and III, survival rates were lower in DNA aneuploid patients than DNA diploid patients, respectively. A multivariate analysis of survival data using Cox's proportional hazard model showed that DNA ploidy was the significant discriminating factor on survival in stage II and III cancer. In conclusion, nuclear DNA ploidy in patients with stage II and III colorectal cancer undergoing curable resection may represent malignant potential and may be an independent prognostic factor.

Colorectal Neoplasms↗

Lack of the relationship between menstrual status and timing of surgery in survival of premenopausal patients with breast cancer.

To clarify the relation between menstrual cycle at surgery for breast cancer and prognosis, we have retrospectively investigated 159 women with premenopausal breast cancer. The end of follicular phase was determined putatively as 15 days before the coming menstrual period, and the luteal phase was assumed to commence with the fourteenth day. The mean observation period was 49.7 months. At surgery, 86 patients were in the follicular phase and 73 in the luteal. There was no difference in distribution of age, family history, parity, tumor size or nodal status between the two groups. There were no differences in disease-free or overall survival rate. The follow-up period was not sufficient, but the current result found no relation between the timing of surgery and prognosis.

Adult↗

The evaluation of mammographic microcalcification as biological malignancy in breast cancer.

The biological significance of mammographic microcalcification (MM) was investigated in breast cancer. 119 (39.8%) had evidence of microcalcification, while 170 were negative. Fifty-three (44.5%) of those with MM had nodal metastases. There is no significant correlation between MM and nodal metastases. Five-year survival of patients with MM was significantly shorter than that without. This suggests that MM may be of biological significance in breast cancer, and thereby attention should to be paid to assessing breast cancer patients with mammographic microcalcification.

Adult↗

Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems.

BACKGROUND: Intraductal tumor extension is a characteristic feature of primary breast carcinoma, and is an important consideration in patients undergoing breast conservative surgery. However, there have been no reports of studies of intraductal extension within the mammary ductal tree. METHODS: Quadrantectomy specimens from 20 patients with primary invasive breast carcinoma were examined by subgross and stereomicroscopic technique to visualize intraductal tumor extension. Serial 2 mm-thick sections were subjected to two-dimensional (2-D) tumor mapping, measuring the distances and angles of extension, and to three-dimensional (3-D) reconstruction of the mammary duct-lobular systems by means of computer graphics. RESULTS: Intraductal tumor extension was found in 16 of 20 specimens (80.0%), extending continuously from the primary invasive carcinoma through the mammary ductal tree. The distances and angles of extension were larger in tumors with microcalcifications, papillotubular invasive ductal carcinoma, 30% or more of intraductal component, and comedo-type intraductal tumor extension. The 3-D reconstructions demonstrated three types of extension; central (11 cases), peripheral (3 cases), and mixed (2 cases). Further, there were some ductal branches anastomosing with different mammary duct-lobular systems at various sites. In one specimen, intraductal tumor extended widely from the primary invasive carcinoma through a branch connecting adjacent mammary duct-lobular systems. CONCLUSIONS: Three-dimensional reconstruction images of intraductal extension of invasive breast carcinomas are presented for the first time to the authors' knowledge. Examples of ductal anastomoses were observed, and should be considered as a risk factor for possible widespread intraductal extension through multiple mammary duct-lobular systems.

Adult↗

Evaluation of aspiration biopsy cytology and combined preoperative tests in the diagnosis of breast cancer.

This study was conducted to investigate the usefulness of aspiration biopsy cytology (ABC) and other combined tests for the preoperative diagnosis of breast cancer. In an analysis of 599 aspirates of breast tumors, "suspicious" cases were included among the positive, while "borderline" cases were considered to be negative. The sensitivity of ABC was 87.3%, the specificity was 92.3%, and the predictive value of a positive diagnosis was 92.8%. A total of 207 cases of breast cancer were evaluated to determine the diagnostic significance of breast cancer, particularly for tumors less than 2.0cm by means of quadruple test including physical examination, mammography (MMG), ultrasonography (US), and ABC. The combined tests of MMG or US, and ABC resulted in a sensitivity of 96.2% and 94.9%, respectively, and were considered to complement each other in the diagnosis of small breast cancer. Surgical biopsy is thus not always necessary in malignant cases that are conclusively diagnosed by the combined quadruple test.

Biopsy, Needle↗

p53 mutations and overexpressions in Japanese breast cancer.

Mutations in the p53 gene were analysed in 50 cases with breast cancer by PCR-SSCP and direct DNA sequencing. Mutations were found in 10 of 50 cases (20%) including a case with Tis, and loss of the normal allele was found in five of these cases. Eight of the 10 mutations occurred within highly conserved domains, but no mutational hot spots were found. GC to AT transitions were the most frequent mutations (six of 10 cases), while mutations at CpG dinucleotides were found in three cases (30%). AT to TA transversions were the second most frequent mutation (20%). The level of expression of p53 protein was assessed by Western blot analysis in 62 cases. Overexpression of p53 protein was detected in 21 of 62 cases (34%) including a case with Tis. There was a strong correlation between missense mutations in the p53 gene and overexpression of p53 protein. Overexpression of p53 protein was closely associated with increasing tumour size and ER-negative status among the various factors investigated, suggesting that p53 overexpression may reflect the lack of differentiation in breast cancer.

Base Sequence↗

Six cases of heterochronous gastrointestinal cancer preceded by breast cancer.

Among 432 women with primary breast cancer, six (1.4%) were diagnosed as having gastrointestinal cancer more than six months after operation for the breast cancer. This paper presents these six cases. The patients ranged from 56 to 78 years of age at the time of breast cancer surgery, and the interval after surgery until diagnosis of the second cancer ranged from 7 months to 5 years 1 month. The second cancer was gastric cancer in 3, esophageal cancer in 2, and hepatic cancer in 1. All of the 6 patients had received postoperative adjuvant chemotherapy for breast cancer. The most frequent histological type of breast cancer was solid-tubular carcinoma (3 patients). Three patients died, due to the second cancer, 4 days, 2 months, and 6 months, respectively, after diagnosis of the second cancer, and the other patients are alive 2, 3, and 4 years after diagnosis. The Japanese literature regarding multiple cancer among breast cancer patients is reviewed. It is concluded that care should be taken to examine breast cancer patients with gastrointestinal symptoms, which are likely to be dismissed as a side effect of postoperative chemotherapy.

Aged↗

[Efficacy of combination therapy consisting of cyclophosphamide, adriamycin, UFT and oophorectomy/tamoxifen for advanced or recurrent breast cancer].

Combination therapy consisting of cyclophosphamide (CPA), adriamycin (ADR), UFT and endocrine therapy of oophorectomy or tamoxifen (TAM) was given female patients with advanced or recurrent breast cancer. Premenopausal patients initially underwent oophorectomy, then were administered 300 mg/day of CPA and 30 mg/day of ADR intravenous injection every 2 weeks, and 300 mg/day of UFT orally every day. Postmenopausal patients, on the other hand, were administered the same three chemotherapeutic drugs and 30 mg/day of TAM orally every day instead of receiving castration. A total of 10 patients were registered, and nine of them were eligible. Premenopausal cases were six, and postmenopausal cases were three. The objective response rates were 50% (3/6) for premenopausal women and 33% (1/3) for postmenopausal women. Complete response was observed in one patient and partial response in three patients. The therapy was effective for lymph nodes (2/2), lung (3/4), breast (2/3), skin or subcutis (1/2), but it showed no effect on bone, pleural effusion or ascites. The overall 5-year survival rate was 53.3%. The main side effects of more than Grade 1 were leucopenia 33% (3/9), anorexia 22% (2/9) and malaise 22% (2/9). They were relatively mild for therapy involving ADR. This therapy was considered useful for advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Diagnosis in early breast cancer].

To improve the survival in breast cancer, it is important to detect and treat breast cancer early. Physical examination (PE), mammography (MMG), ultrasonography (US), and aspiration biopsy cytology (ABC) are routinely assessed in the diagnosis of breast cancer. When three procedures including ABC are positive in a diagnosis of breast cancer, it is an absolute indication for surgery. Of all 238 breast cancers between 1987 and 1992, 86 cases were T1. The sensitivity of each procedure was PE 58.9%, MMG 70.0%, US 74.4% and ABC 86.2%, indicating that PE was less sensitive for small cancer. The recent accuracy of ABC in our series was satisfactory, and the combination diagnosis had a good result for T1 tumor because the findings from these procedures were complimentary. The high accuracy of ABC therefore suggests that lumpectomy has two aspects, definite diagnosis, and therapy as conservative surgery for breast cancer. The nineteen cases of T0 cancer encountered were almost entirely detected by nipple discharge or MMG. In conclusion, the combination diagnosis including ABC was very effective, and it is very important to detect and diagnose clinically small or non-palpable breast cancer.

Biopsy, Needle↗

Immunohistochemical overexpression of C-erbB-2 in the prognosis of breast cancer.

Immunohistochemical c-erbB-2 protein overexpression was detected in 34 of 124 (27.4%) paraffin-embedded breast cancer specimens. Although no difference was seen between the c-erbB-2 positive and negative groups in 5-year disease-free survival, 5-year overall survival was significantly less favorable in the c-erbB-2 positive group. Furthermore, patients graded as having positive c-erbB-2 staining and aneuploid DNA showed significantly poorer survival than those in other categories. The significant prognostic factors, determined by a multivariate analysis, were nodal status and c-erbB-2 overexpression. Our findings therefore suggest that c-erbB-2 expression is a prognostic factor in breast cancer and that it could be useful in the determination of postoperative adjuvant therapy.

Adult↗

[Different growth rate and contracting activity of collagen gel between fibroblasts from breast cancer tissue and normal breast tissue].

We have already reported that stromal fibroblasts of breast cancer tissue (CaF) promoted the growth of breast cancer cells in vitro. It was found that CaF and fibroblasts in normal breast tissue (NF) showed the different growth and contracting activity. Materials were obtained from cancer tissue and normal breast tissue. Cells were prepared by collagenase digestion. The CaF's growth was more rapid than NF's. After a reconstitution of type I collagen, monolayer cultures of CaF and NF were done on collagen gel for 24 hours, then collagen gel was detached from the dish and was being float. After 2 days incubation, an area of collagen gel was measured. A contraction of CaF's gel was greater than that of NF. This showed that CaF had more contracting activity than NF. These results might be indicated that the function of CaF was to contribute the invasive growth of breast cancer cell as well as to secrete the growth factors. Therefore, it is considered, a control of the fibroblasts derived from cancer stroma may play an important role in the treatment of breast cancer.

Breast↗

[S-phase fraction and malignant potential in DNA diploid colorectal cancer].

Patients with DNA diploid tumor have a significantly longer survival than those with DNA aneuploid in colorectal cancer, but some patients with diploid tumor show poor survival. For assessing malignant potential in diploid colorectal cancer, flow cytometric analysis of S-phase fraction (SPF) was investigated using paraffin-embedded materials from 79 carcinoma patients who had been treated from 1971 to 1989. There was no significant correlation between SPF and clinicopathological factors (such as sex, tumor size, tumor location, macroscopical type, depth of invasion, node metastasis, peritoneal dissemination, liver metastasis and clinical stage). Mean SPF was significantly higher in poorly differentiated type carcinomas than in well differentiated type carcinomas. Patients with higher SPF had a tendency to poorer survival than those with lower SPF. From these results, it was concluded that SPF represents histological differentiation and that SPF may be a prognostic indicator, in diploid colorectal cancer.

Carcinoma↗

The relationship of estrogen receptor status to DNA ploidy in breast cancer.

The relationship of estrogen receptor (ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg.protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three percent of the specimens were ER+, while 37 percent were negative. Sixty-one patients (50.4 percent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation.

Biomarkers, Tumor↗