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K Shiga

Publications and source records attributed to K Shiga.

153 records · Page 9Linked to original sources

Analysis of c-myc oncogene in human esophageal carcinoma: immunohistochemistry, in situ hybridization and northern and Southern blot studies.

We have examined the c-myc gene expression and the gene organization in resected human esophageal squamous cell carcinomas, and in the adjacent normal esophageal mucosa from 20 patients undergoing radical surgery. Immunohistochemistry of p62c-myc was compared with that of proliferating cell nuclear antigen (PCNA) in order to examine the biologic significance of p62c-myc. Relative c-myc expression detected by Northern blot analysis ranged from 0.41 to 2.8, but the degree of c-myc expression did not correlate with other clinicopathological prognostic parameters. In sity hybridization localized the elevated c-myc mRNA expression to tumor cells and basal and parabasal cells of the adjacent normal mucosa. Immunohistochemistry showed altered localization of p62c-myc, i.e., both cytoplasmic and nuclear immunostaining in advanced carcinomas. c-myc immunoreactivity exhibited wider distribution compared with that of PCNA, a cell cycle related antigen, which may indicate induction of cell proliferation by p62c-myc. DNA hybridization showed mild amplification in one out of 17 tumors and no evidence of gene rearrangement. There was no distinct correlation between the results of Northern or Southern blot analysis and the results of in situ hybridization or immunohistochemistry. Gene alteration of the c-myc locus, as well as overexpression of the c-myc oncogene, appeared to be limited, and analysis of the c-myc gene yielded limited prognostic value in human esophageal carcinomas.

Aged↗

Expression of c-erbB-2 in human esophageal carcinoma cells: overexpression correlated with gene amplification or with GATA-3 transcription factor expression.

Amplification and expression of the c-erbB-2 protooncogene was studied in 60 primary human esophageal carcinomas and 12 cell lines established from the carcinomas. Amplification of the c-erbB-2 gene was found in 4 out of 60 (6.7%) and 1 out of 12 (8.3%) DNA samples from the primary carcinomas and cell lines, respectively. Overexpression of c-erbB-2 gene product, as determined by both Northern blot hybridization and immunohistochemical analysis, was found in the cells with c-erbB-2 amplification, but not in normal esophageal mucosae or in primary esophageal carcinomas without gene amplification. In contrast, c-erbB-2 overexpression was clearly observed in 7 cell lines in which gene amplification was not found. We analyzed expression of the GATA-3 transcription factor in the carcinoma cell lines and found that the level of GATA-3 mRNA expression showed very good correlation with that of c-erbB-2 gene expression. This observation suggested that the GATA-3 transcription factor and c-erbB-2 protein play important roles in the process of immortalization and/or maintenance of the transformed phenotype of human esophageal carcinoma cells in vitro.

Adenocarcinoma↗

Prognostic significance of hst-1 gene amplification in primary esophageal carcinomas and its relationship to other prognostic factors.

We studied hst-1 gene amplification in 50 primary human esophageal carcinomas using Southern blot analysis. We found 3- to 9-fold amplification of the hst-1 gene in 15 out of 50 (30.0%) DNA samples from primary tumors. There was no evidence of a correlation between hst-1 gene amplification and several prognostic factors other than the histological type; hst-1 gene amplification was more common in well differentiated squamous cell carcinoma. Survival rates for patients bearing tumors with and without hst-1 gene amplification were calculated by the Kaplan-Meier method and evaluated by the log-rank test. The survival curves for the two groups were almost identical. These results suggest that amplification of the hst-1 gene is a poor indicator of the prognosis of patients who have undergone surgery for primary esophageal carcinoma.

Adult↗

[Myocardial ischemia and abnormality of cardiac sympathetic nervous function in apical hypertrophic cardiomyopathy].

Exercise 201Tl myocardial scintigraphy of patients with apical hypertrophic cardiomyopathy (AH) often shows transient perfusion defect in the apex. Catecholamine may be related to the pathogenesis of AH, but this is not certain. The relationship between hypertrophy, myocardial ischemia, and cardiac sympathetic nervous function were investigated by comparing 123I-MIBG myocardial SPECT with exercise 201Tl myocardial SPECT especially at the apex which is the hypertrophic region. Seventeen patients with AH, mean age of 53 +/- 11 years old, underwent 123I-MIBG myocardial SPECT and exercise 201Tl myocardial SPECT on separate days. Decreased tracer uptake regions and the severity and extent of the defect were evaluated visually and compared. Myocardial clearance of 123I-MIBG in apical, midventricular, and basal regions was calculated from the bull's eye display. 123I-MIBG SPECT showed a decreased uptake or defect in the apex of all patients. 201Tl SPECT showed a reversible perfusion defect in the apex of 10 patients, an irreversible perfusion defect in the apex in 3, and normal perfusion in 4. Comparing decreased uptake on the exercise 201Tl myocardial image and 123I-MIBG 4-hour delayed image, the severity of the defect was: MIBG > Tl in 12 patients (71%), MIBG = Tl in 5 (29%), and the extent of the defect was: MIBG > Tl in 11 (65%), MIBG = Tl in 6 (35%). Mean clearance of 123I-MIBG in the apical and midventricular regions was significantly higher than that in the basal region (apical 46.2 +/- 7.1%, midventricular 44.4 +/- 7.8%, basal 38.7 +/- 7.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

[Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy: evaluation by exercise thallium-201 SPECT].

The effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise myocardial 201Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.1 +/- 6.1 weeks of oral administration of verapamil (240 mg/day) on 20 patients with HCM who showed transient 201Tl perfusion defects under control conditions. SPECT images were divided into nine segments. The 201Tl perfusion defect was visually scored and evaluated for four grades in each segment and the sum total grade was calculated as the defect score. Transient dilation index was calculated as a reflection of subendocardial ischemia. Improvements in defect score were demonstrated in 18 of 20 patients after administration of verapamil. The mean defect score decreased significantly from 5.1 +/- 2.3 to 2.5 +/- 2.4 (p < 0.001). Although 18 of 20 patients showed abnormal transient dilation index under control conditions, 16 showed improvement and 12 were normalized after verapamil therapy. Mean transient dilation index decreased from 1.24 +/- 0.19 to 1.08 +/- 0.10 (p < 0.01). Verapamil improves myocardial ischemia in patients with HCM.

Cardiomyopathy, Hypertrophic↗

Glutathione S-transferase in human esophageal carcinoma.

The expression of human glutathione S-transferase-pi (GST-pi) in esophageal squamous cell carcinoma and in corresponding morphologically normal mucosa from 17 patients was examined by Northern blots, in situ hybridization and immunohistochemistry. Relative GST-pi expression (tumor/mucosa) ranged from 0.31 to 1.52 (0.821 +/- 0.40: mean +/- SD), and only 6 out of 17 cases demonstrated increased GST-pi transcripts in tumor tissue over normal tissue. In situ hybridization and immunohistochemistry showed that morphologically normal esophageal mucosa, especially in its basilar two thirds, expressed the enzyme as strongly as did carcinoma cells. No significant correlation was observed between the amount or pattern of GST-pi expression by carcinomas and the clinicopathological findings in the cases. The marked expression of GST-pi by non-pathologic mucosa obtained from the patients with esophageal carcinoma suggests that GST-pi may be a marker of increased carcinogen exposure, but not necessarily a marker of developed human esophageal cancer.

Aged↗

Abnormalities and the implication of retinoblastoma locus and its protein product in head and neck cancers.

Abnormalities in the Retinoblastoma tumor suppressor gene (Rb) have been observed in a large number of human cancers. Loss of heterozygosity (LOH) is a common mode of allelic inactivation of Rb and other tumor suppressor genes. We investigated DNA from 45 primary human head and neck cancers to determine LOH at the Rb locus using a polymerase chain reaction-based restriction fragment length polymorphism assay. Of informative cases, we found LOH in 4 of 28 (14%) head and neck cancers. Of immunohistochemical staining of Rb protein, we found that in one of ten LOH negative cases the nuclei of fibroblasts were stained with anti-Rb antibody but there was no nuclear staining tumor cells. These results suggest that inactivation of Rb protein is involved in the carcinogenesis of head and neck cancer at all levels of the process of protein expression: DNA, mRNA and protein.

Base Sequence↗

Loss of heterozygosity of chromosome 9p21 and 7q31 is correlated with high incidence of recurrent tumor in head and neck squamous cell carcinoma.

To examine whether genetic factors influence the prognosis of cancer patients, several polymorphic markers were used to determine the allelic loss of certain areas of the genome. Two polymorphic markers, IFNA and D9S171 were used to study the loss of heterozygosity (LOH) of chromosome 9p21 in 75 head and neck squamous cell carcinomas. LOH was detected in 14 out of 64(22%) DNA samples obtained from cancer specimens when at least one marker was used. The frequency of LOH was not correlated with the localization of the tumor, clinical stage of the patient, tumor size and lymph node involvement. However, the frequency of LOH was significantly higher in the recurrent tumors than in the non-recurrent tumors, suggesting that the allelic loss at 9p21 can be correlated with the short term prognosis of the patients. LOH was identified in only three out of 19(16%) samples when D7S522 was used as a marker. However, all of these three cases were recurrent, and two of the three showed the allelic loss at 9p21 at the same time. These results indicate that LOH of 9p21 and/or 7q31 is a novel prognostic factor independent of other clinical factors for head and neck squamous cell carcinoma. Replication error (RER) was observed in 4 cancers, implicating genetic instability in the carcinogenesis of a subset of head and neck squamous cell carcinoma.

Adult↗