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Biomedical subjects

A Tsuchiya

Publications and source records attributed to A Tsuchiya.

At least 73 records · Page 4Linked to original sources

K-ras and p53 gene mutations in colorectal cancer in 57 Japanese patients.

Fifty-eight tissue specimens from 57 Japanese patients with colorectal cancer were analyzed for the K-ras and p53 gene mutations by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing. K-ras mutations were detected in 21 cases (36.2%) and p53 mutations in 20 cases (34.5%). Eight specimens had both gene mutations. The K-ras mutation was associated with higher degrees of differentiation (p = 0.0019). The P53 mutation was associated with Duke B to D staging (p = 0.028), lymph vessel invasion (p = 0.021), and venous invasion (p = 0.03). Interestingly, a mutation in only exon 7 of the P53 gene was associated with lymph node metastasis. These results suggest the important effect of the mutations of the K-ras and p53 genes, especially p53 gene on colorectal carcinogenesis in Japanese patients. The grades of malignancy of the specimens with the mutations in both genes were not different significantly from those with a single (K-ras or p53) or no mutation, suggesting no cooperation between K-ras and p53 gene mutations on carcinogenesis or tumorigenesis.

Adenocarcinoma↗

Nuclear DNA content, S-phase fraction analysis and expression of proliferating cell nuclear antigen (PCNA) of normal and hyperplastic/neoplastic parathyroid glands.

To clarify the biological behavior, the flowcytometric nuclear DNA content, S-phase fraction(SPF) and proliferating cells by immunostaining of proliferating cell nuclear antigen(PCNA) were investigated in 13 patients with hyperparathyroidism (10 adenomas, 2 hyperplasias and 1 cancer) and 10 normal controls. No. of parathyroid glands or tissues examined was as follows: 10 adenomas, three hyperplasias from one case, one primary and one recurrent carcinoma of the same case, two secondary hyperplasias from one case and 10 normal glands. All controls and hyperplasias showed diploid DNA, but the 10 adenomas aneuploid in four and diploid in six. The carcinoma showed diploid in the primary lesion, aneuploid in the recurrence. DNA index in recurrent carcinoma was higher than that in aneuploid adenoma. SPF in primary and recurrent cancers and adenomas as higher than that in the others. The expression of PCNA in all hyperparathyroidism except for hyperplasias was higher than that in normal controls. In conclusion, there might be some premalignant potential in the adenomas from the view of DNA flowcytometry and PCNA immunostaining. Therefore, aneuploid adenoma should be strictly followed up.

Adenoma↗

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↗

Cloning and nucleotide sequence of the mono- and diacylglycerol lipase gene (mdlB) of Aspergillus oryzae.

Aspergillus oryzae IFO4202 produces at least two extracellular lipolytic enzymes L1 and L2 (cutinase, and mono- and diacylglycerol lipase, respectively). Southern hybridization of restriction enzyme-digested genomic DNA fragments with 23-mer oligonucleotides synthesized according to the amino acid sequence of the L2 as probe suggested the presence of the L2 gene (tentatively designated as mdlB) and an additional weakly hybridizing region. A fragment containing the genomic mdlB gene was cloned in Escherichia coli. Nucleotide sequencing of the fragment revealed an open reading frame, comprising 1021 nucleotides, which contains two introns (51 and 52 nucleotides). Putative polyadenylation signals were found 182 and 287 bp downstream of the stop codon. The deduced amino acid sequence of the mdlB gene corresponds to 306 amino acid residues including a leader sequence of 28 amino acids and is highly similar to that of the mdlA gene of Penicillium camembertii. Three residues presumed to form the catalytic triad (serine, aspartic acid and histidine) of lipases were also conserved.

Amino Acid Sequence↗

A Case of Breast Cancer Metastatic to the Pituitary Gland.

A case of breast cancer that developed pituitary metastasis 22 years after mastectomy is reported. The pituitary metastasis was associated with hypopituitarism, impairment of the visual field and later diabetes insipidus. The serum levels of CA15-3 and NCC-ST-439, tumor markers of breast cancer, were increased, and CA15-3 (DF3) and NCC-ST-439 were demonstrated in the resected pituitary metastatic lesion immunohistochemically.

Journal Article↗

Differences in mechanisms for cell-free NADPH oxidase activation between arachidonate and sodium dodecyl sulfate.

Mechanisms for the cell-free activation of NADPH oxidase by sodium dodecyl sulfate (SDS) and arachidonate were compared in relation to their responsiveness to short chain diacylglycerols. The plasma membrane and cytosol prepared from guinea pig neutrophils were used for the cell-free system. The activation of NADPH oxidase by SDS was enhanced about 5- to 10-fold by 1,2-dioctanoylglycerol (diC8), but not by either 1,2-dihexanoylglycerol (diC6) or 1,2-didecanoylglycerol (diC10). However, none of these diacylglycerols potentiated the NADPH oxidase activation by arachidonate. The maximal extent of activation by the combination of SDS and diC8 was similar to that by arachidonate alone. In the presence of sufficient amounts of diC8 and SDS, GTP gamma S potentiated the activation of NADPH oxidase. The potentiating activity of diC8 was preserved in the membrane fraction, not in the cytosol fraction. These results suggest that arachidonate may possess the functions of both SDS and diC8 in the activation. In addition, diC8 and GTP gamma S seem to independently enhance the NADPH oxidase activation.

Animals↗

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↗

[A case report of ileovesical fistula in radiation enteritis].

A 49-year-old female was admitted with chief complaint of fecaluria on March 4th 1993. A radiation therapy had been performed for uterocervical cancer 18 years ago. The small intestine and bladder was detected by DIP- and cystogram simultaneously. It was diagnosed as an ileovesical fistula. A segmental resection of the ileum with partial cystectomy was performed on March 23rd. Histopathologically, the ileum showed a radiation enteritis. Eventually, we diagnosed that this ileovesical fistula was caused by radiation. After operation, an incompletion of suture occurred. So we made an ileostomy secondarily and performed hyperbaric oxygen therapy. The patient was getting well temporarily but died of gastric hemorrhage on May 1st.

Female↗

[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↗

[K-ras gene mutations in adenomas from familial adenomatous polyposis].

A 18-year-old woman underwent total colectomy for familial adenomatous polyposis. In order to clarify the significance of K-ras mutations in early colorectal carcinogenesis, K-ras mutations were analyzed in multiple adenomas by PCR-SSCP method. A total of 256 adenomas were found throughout the entire colon and rectum, and the distribution was a sparse type. The correlation between K-ras gene and clinicopathological factors was examined in 90 adenomas. There was no correlation among K-ras mutations and anatomical distribution, or morphological classification, but K-ras mutation was more frequent in severe compared with slight atypia. We investigated the correlation between the size of adenoma in the horizontal and vertical directions and K-ras mutation. K-ras mutation was more frequent in the horizontal size greater than 6 mm in diameter, and also more frequent in vertical size greater than 20 mm in height. It was concluded that the adenomas detecting K-ras mutations might have proliferating potential, and would be applied to determine polypectomy.

Adenoma↗

Flow cytometric DNA analysis of gastric cancer that is invading the muscularis propria.

OBJECTIVE: To find out if there is any correlation between the DNA aneuploidy in gastric cancer that is invading the muscularis propria and survival. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 52 patients who underwent gastric resection for gastric cancer that was invading the muscularis propria, and for whom clinical follow-up data were available. INTERVENTIONS: Flow cytometric measurement of DNA in paraffin-embedded tissue. MAIN OUTCOME MEASURES: Correlation between survival and clinicopathological variables including ploidy. RESULTS: 22 (42%) of the cases were aneuploid and 30 (58%) were diploid. The lymph node status and DNA ploidy were the significant prognostic variables, but a multivariate analysis showed that only DNA ploidy was significant. CONCLUSIONS: Nuclear DNA ploidy is an independent prognostic factor in gastric cancer that is invading the muscularis propria.

Aneuploidy↗

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↗

Correlation between expression of sialosyl-T antigen and survival in patients with gastric cancer.

Intestinal metaplasia of the gastric mucosa is an important lesion in the pathogenesis of gastric cancer. The expression of a mucin-associated antigen, sialosyl-T antigen, in the tissue of gastric cancer was investigated immunohistochemically to assess its biological role. Sialosyl-T antigen, detected by the monoclonal antibody TKH2, was present in 30 (23.6 per cent) of 127 lesions, and expressed sporadically in intestinal metaplasia. Patients negative for sialosyl-T had a significantly better 5-year survival than those who were positive (70.4 per cent versus 47.2 per cent). Grading by sialosyl-T antigen expression and the DNA ploidy pattern had a predictive value for prognosis in patients with gastric cancer. The biological role of sialosyl-T antigen is not clear but the mucin alteration reflects upon the biological behaviour of gastric cancer.

Follow-Up Studies↗

Prognostic factors associated with differentiated thyroid cancer.

A multivariate analysis was conducted on the survival data of 180 patients who underwent curative resection for differentiated thyroid cancer between 1966 and 1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%, respectively. A survival analysis was also performed, testing the following factors: the patient's age at the time of diagnosis, tumor size, extraglandular extension, nodal status, distant metastases, operative procedure, sex, and histology. A univariate analysis found the initial six factors to be significant prognostic variables, but the latter two to be of no significance. On the other hand, the multivariate analysis showed that distant metastases, age, and tumor size were the most significant prognosticators. Thus, the age of the patient should be taken into consideration during the follow-up of treatment for differentiated thyroid cancer.

Adenocarcinoma, Follicular↗