Biomedical subjects

I Okayasu

Publications and source records attributed to I Okayasu.

At least 109 records · Page 6Linked to original sources

PubMed1997

Low epithelial cell proliferation and absence of oncoprotein expression in juvenile polyposis of the stomach, with or without tumors.

OBJECTIVES: To assess cell proliferation and analyze oncogenetic abnormalities in cases of juvenile polyposis of the stomach (JPs), with or without coexisting tumors. METHODS: The Ki-67 labeling indices (KLI) were compared for juvenile polyps and coexisting tumors in three cases of JPs along with values for gastritis, foveolar epithelial hyperplastic polyps, adenomas, and carcinomas. Expression of p53, Bcl-2, and c-ErbB-2 in tumors was examined immunohistochemically, and a search for c-Ki-ras mutations was made by DNA direct sequencing. RESULTS: The KLI for JPs did not significantly differ between cases, being consistently lower than the values for both hyperplastic polyps and gastritis. The KLI for the papillary tumors and a signet ring cell carcinoma found in association with JPs tended to be lower than those for their conventional counterparts. P53, but not Bcl-2 and c-ErbB-2, was focally expressed in the papillary tumors, whereas all three were absent in the signet ring cell carcinoma, in the JPs. No c-Ki-ras mutations were detected in the papillary tumors. CONCLUSIONS: The cell proliferation of JPs is relatively low and the polyps can be considered hamartomatous. However, neoplastic change clearly can occur in association with a relative increase in proliferative activity being observed in coexisting tumors. Low cellular proliferative activity and absence of oncogenetic abnormalities in tumors of JPs, compared with their conventional counterpart tumors, suggest that pathways of tumorigenesis and genetic alteration in JPs may be different from those in their conventional counterparts.

Adenocarcinoma↗

PubMed1997

[Immunohistochemical expression of p53 oncoprotein in large bowel adenomas and carcinomas].

BACKGROUND: Colorectal carcinoma is the sixth cause of death in Chile. Half of malignant tumors in humans have genetic alterations in protoncogenes, tumor suppressing genes or both. One of the most frequent alterations is that involving p53 tumor suppressor gene. AIM: To study, using immunohistochemical methods, alterations in p53 gene expression in colorectal carcinomas and adenomas. MATERIAL AND METHODS: A random sample of 28 large bowel adenomas and 44 carcinomas was studied. Determination of p53 protein was made with an immunohistochemical method using monoclonal antibodies. Patients were followed for a mean of 36 months (range 1 to 100 months). RESULTS: p53 immunostaining was obtained in one adenoma (3.5%) and in 18 carcinomas (41%, p = 0.01). There were no differences in survival during follow up, between cancer patients that expressed or did not express p53 protein. CONCLUSIONS: About half of colorectal tumors have immunohistochemical expression of p53 protein, as published abroad. We did not find a prognostic value for this protein in our sample.

Adenocarcinoma↗

PubMed1996

Bcl-2 expression is correlated with a low apoptotic index and associated with progesterone receptor immunoreactivity in endometrial carcinomas.

A total of 103 endometrial carcinomas (endometrioid type), as well as 15 samples of normal (atrophic or proliferative phase) and 26 of hyperplastic endometrium, were immunohistochemically investigated for expression of Bcl-2, and oestrogen and progesterone receptors (ER and PR), and the results compared with findings for apoptosis and cell proliferation. Carcinoma cases were subdivided into tubular and solid components on the basis of tumour growth patterns. Immunopositivity for Bcl-2, ER, and PR in tubular components was significantly higher than in the solid category, being negatively associated with histological grading. Immunoreactivity scores revealed that Bcl-2 in the tubular group was positively correlated with PR but not ER, while its expression in normal and hyperplastic endometrium was closely linked with both. Apoptotic and mitotic indices (AI and MI) were both significantly lower in tubular than in solid areas. In the tubular areas, AI, values were significantly lower in the subgroup with a high level of Bcl-2 expression than in either low-level or negative groups. These results indicate that Bcl-2 expression may play a central role in the inhibition of apoptosis in endometrial carcinoma, in particular those cases with tubular components, possibly being associated with PR rather than ER. Changes in the propensity for apoptosis may be related to alterations of tumour growth pattern and of features of differentiation.

Apoptosis↗

PubMed1996

Apoptosis of colon cancer: comparison with Ki-67 proliferative activity and expression of p53.

The role of apoptosis in colon cancer was investigated in terms of control of growth and expression on p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.

Apoptosis↗

PubMed1996

Population changes in immunoglobulin-containing mononuclear cells in dextran sulfate sodium-induced coltitis.

To investigate the relation of immunoglobulin-containing cells in the colonic mucosa to mucosal inflammation, we immunohistochemically examined the localization of immunoglobulin-containing mononuclear cells in the lamina propria in dextran sulfate sodium induced colitis in mice. Mice were treated repeatedly with 3% dextran sulfate sodium (MW 54,000) solution or distilled water for a total of 170 days (chronic model), or for 85 days (subacute model) or for 10 days (acute model). IgG, IgA, and IgM-containing mononuclear cells were studied by enzyme immunostaining. The number of IgA- and IgG-containing cells gradually and significantly increased in the acute, subacute, and chronic models, in that order (P < 0.01 or 0.05). However, the numbers of IgM-containing cells in the three models were similar to that in the controls. These findings resembled those of human ulcerative colitis. In this dextran sulfate sodium-induced colitis, IgA-containing mononuclear cells may play an essential role in the mucosal immune system is the acute, subacute, and chronic phases. The finding that IgG-containing mononuclear cells increased substantially in the chronic phase suggests that IgG plays an important role in the mucosal inflammatory reaction during the chronic phase.

Acute Disease↗

PubMed1996

Apoptosis of colon cancers assessed by in situ DNA nick end-labeling method.

Apoptosis in colon cancers was investigated using in situ DNA nick end-labeling. Seventy-six colon cancer cases were divided according to histologically defined malignant grading, degree of invasion and other pathologic indicators. The apoptotic labeling index (ALI) was highest in cases with invasion limited to the submucosa, the difference as compared to other stages being statistically significant, while no correlation was noted between ALI and histological type. ALI significantly decreased with lymph node involvement of cancers. In contrast, there appeared to be no link with vessel invasion. ALI was significantly higher in lesions smaller than 2 cm in diameter. These results indicate that apoptosis in colon cancers is more frequent at a relatively early stage when the lesions are small, and suggest that the apoptotic phenomenon may play some role in regulating the size and progression of such tumors.

Adenocarcinoma↗

PubMed1996

Simplified rapid non-radioactive PCR-SSCP method applied to K-ras mutation analysis.

A newly modified non-RI, PCR-SSCP method is presented and applied to K-ras analysis of colorectal tumors. It comprises five steps: (1) sampling of tiny pieces of fresh solid tissue by scraping with disposable bamboo combs (thin bars made of bamboo, 3 x 3 x 120 mm in size); (2) one-step DNA extraction with lysis buffer containing proteinase K, Nonidet P-40 and Tween 20; (3) PCR with 108 bp, c-ki-ras 2 gene primers; (4) SSCP analysis with 10% formamide-added polyacrylamide gels; and (5) detection with silver staining. In comparison with conventional RI- or non-RI-PCR-SSCP, It can give reliable and clear results in a much shorter time (within a total of 6 h). This novel approach should allow more frequent use of molecular diagnosis in biopsies and surgical pathology.

DNA Mutational Analysis↗

PubMed1996

Different expression of Bcl-2 protein in gastric adenomas and carcinomas.

In order to cast light on the possible role of bcl-2 protein (Bcl-2) expression in gastric tumorigenesis, 33 cases of gastric adenomas and carcinomas originating from the same stomachs were immunohistochemically investigated for Bcl-2 protein (Bcl-2) expression, accumulation of p53 protein and cell proliferation as determined by the Ki-67 labeling index (LI). Bcl-2 expression was detected in 24/33 (72.7%) adenomas and in 6/33 (18.2%) carcinomas, the difference being statistically significant (P = 0.0001). Only 4 of 33 (12.1%) cases exhibited expression in both adenoma and carcinoma lesions in the same stomachs. Immunoreactivity was decreased in areas of cellular and structural atypia in adenoma lesions (P < 0.008), and appeared to be positively linked to the tumor progression and the degree of differentation in carcinomas, although it did not reach statistical significance. Accumulation of p53 protein was rare in the adenomas but was found in 15/33 (45.5%) of carcinoma lesions, with a significant dissociation from Bcl-2 immunoreactivity. No apparent relation between Ki-67 LI and either adenoma grading or carcinoma typing was noted, although average Ki-67 LI of the highest labeling areas in carcinomas was statistically higher than in adenomas (P = 0.0001). These results indicate that the regulation of Bcl-2 expression may differ between gastric adenomas and carcinomas, may be correlated with tumor differentiative features. In addition, p53 accumulation may play an important role in the onset of malignancy.

Adenoma↗

PubMed1996

Promotion of colorectal neoplasia in experimental murine ulcerative colitis.

BACKGROUND: The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. AIMS: To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. RESULTS: In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.

Animals↗

PubMed1996

Correlation of apoptosis with tumour cell differentiation, progression, and HPV infection in cervical carcinoma.

AIMS: To clarify the significance of apoptosis in the progression of uterine cervical neoplasias, including cervical intraepithelial neoplasia (CIN), microinvasive carcinoma (MIC), and invasive squamous cell carcinoma (ISCC) categories, in relation to cell proliferation and human papilloma virus (HPV) infection. METHODS: Forty six cases of CIN I/II, 75 of CIN III, 16 of MIC, and 44 of ISCC were examined using formalin fixed and paraffin wax embedded samples. The TdT mediated dUTP-biotin nick end labelling (TUNEL) method for detection of apoptotic cells was performed along with Ki-67 immunohistochemistry. Presence of HPV-DNA was confirmed by PCR-RFLP assay. RESULTS: Apoptotic labelling indices, calculated after counting positive nuclei among at least 2000 nuclei, showed significant positive correlation with histological malignant grading in CIN and tumour cell invasion into stroma. In contrast, similar Ki-67 labelling index values were found in CIN, MIC, and ISCC. Although HPV-DNA was detected in 35/46 CIN I/II (76.1%), 53/74CIN III (71.6%), 9/16 MIC (56.3%), and 36/44 ISCC (81.8%), there was no apparent relation with the apoptotic labelling indices. CONCLUSIONS: Apoptosis in cervical neoplasias may be closely related to tumour cell differentiation and progression. It also seems unlikely that HPV itself is directly related to pathways regulating apoptosis.

Apoptosis↗

PubMed1995

The possible role of bcl-2 expression in the progression of tumors of the uterine cervix.

BACKGROUND: A close link between human papillomavirus (HPV) and the development of uterine cervical neoplasias has been proposed. However, other cofactors also are required for malignant transformation. METHODS: Forty-six cervical intraepithelial neoplasias (CIN) I/II, 75 CIN III, and 60 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 protein (bcl-2), bax protein (Bax), estrogen receptor (ER), and progesterone receptor (PR). The presence of HPV-DNA was examined using the polymerase chain reaction assay. RESULTS: bcl-2 immunoreactivity was found in 17 of 46 (37%) CIN I/II, 48 of 75 (64%) CIN III, and 12 of 60 (20%) ISCC, the positivity in CIN III being significantly higher than in CIN I/II or ISCC (P < 0.004, P = 0.0001). The bcl-2 immunostaining pattern could be subdivided into two groups, basal type and diffuse type, with the incidence of the latter being clearly increased, in line with tumor progression. In the Bax or HPV-DNA positive groups, bcl-2 positive cases in CIN I/II were in the minority, whereas in CIN III they constituted the majority. In ISCC, bcl-2 positive was significantly lower than negative cases, not being associated with Bax and HPV-DNA. Estrogen receptor and PR immunoreactivity were rare. CONCLUSIONS: These results indicate that bcl-2 may play an important role in a relatively early stage of cervical tumorigenesis, in association with Bax expression and HPV infection.

Carcinoma, Squamous Cell↗

PubMed1995

Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese, and white and African Americans.

BACKGROUND: An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To determine a definite statistical relation, a histopathologic study was performed on tissues from in three races, because there is a racial and age-related difference in the susceptibility to thyroiditis. METHODS: The prevalence and severity of thyroiditis combined with adenomatous goiter, follicular adenoma, or papillary carcinoma was defined by examination of surgically resected materials from Japanese (626 patients), and white and African Americans (330 and 90 patients, respectively). RESULTS: The prevalence of lymphocytic infiltrates, which are indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma than in patients with adenomatous goiter or follicular adenoma among Japanese females (63.0%) and males (50.0%), white females (76.0%), and African American females (46.2%). Lymphocyte infiltration into the follicular adenoma or papillary carcinoma correlated with the severity of combined thyroiditis. CONCLUSION: An association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed in the Japanese, and white and African American populations. The possibility of autoimmune thyroiditis as a predisposing factor for papillary thyroid carcinoma, is suggested.

Adenoma↗

PubMed1995

Detection of Helicobacter pylori infection in early stage gastric cancer. A comparison between intestinal- and diffuse-type gastric adenocarcinomas.

BACKGROUND: Helicobacter pylori (H pylori) infection has been suggested to be a risk factor for gastric carcinogenesis. However, those previous studies have been concerned with advanced cancer cases. To the authors' knowledge, no detailed investigation on the prevalence of H pylori in early stage gastric cancer tissue has been performed. The relationship between early stage gastric cancer and the prevalence of H pylori was studied by a immunohistochemical staining analysis. METHODS: Sixty-eight patients who were endoscopically and surgically diagnosed as having early stage gastric cancer were enrolled in this study. All tissue specimens were obtained from patients by endoscopic biopsy, and were classified histopathologically as the intestinal-type of early stage gastric cancer in 34 patients (male-to-female ratio, 28:6; age, 64 +/- 11 years) and the diffuse-type of early stage gastric cancer (male-to-female ratio, 23:11; age, 57 +/- 14 years) in the other 34 patients. The amount of H pylori in tissue samples was graded from 0 (no characteristic bacteria) to 3 (numerous bacteria) using the fluorescent microscopic and an immunohistochemical technique. RESULTS: Twenty-nine of the 34 cases of the intestinal-type of gastric cancer had H pylori infection, as compared with 11 of the 34 cases of diffuse-type early stage gastric cancer. A significantly higher incidence (85%; P < 0.001) of H pylori infection and, thus, higher grading scores of the number of H pylori were found in the intestinal-type early stage gastric cancer. CONCLUSIONS: These findings suggest that the infection of H pylori may have a crucial relationship to the early stages of carcinogenesis of intestinal-type gastric cancer.

Adenocarcinoma↗

PubMed1995

Prediction of relapses after interferon-alpha therapy by hepatitis C virus RNA in peripheral blood mononuclear cells.

To investigate the predictive value of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in the response to interferon therapy in patients with chronic hepatitis C, 15 patients with histologically proven chronic active hepatitis and who were positive for serum HCV-RNA were treated with interferon-alpha (6 million units; i.m.) every day for two weeks and then three times a week for 22 weeks. Ten of the 15 patients were responders whose alanine aminotransferase levels decreased to the normal range at the end of interferon therapy. In four of the 10 responders, HCV-RNA was not detected by reverse transcription-polymerase chain reaction in peripheral blood mononuclear cells nor in serum at the end of treatment. These four patients were complete responders, with alanine aminotransferase levels remaining normal for the next 24 weeks. In five of the 10 responders, HCV-RNA was detected in peripheral blood mononuclear cells but not in serum at the end of treatment. All of these relapsed within the next 24 weeks. In the remaining responder, HCV-RNA was detected both in peripheral blood mononuclear cells and in serum at the end of treatment. This responder also had a relapse within the next 24 weeks. Five of the 15 patients were non-responders, in whom HCV-RNA was detected both in peripheral blood mononuclear cells and in serum. Thus, detection of HCV-RNA in peripheral blood mononuclear cells may be a good clinical marker to predict relapse after interferon treatment.

Adult↗

PubMed1995

Apoptosis and cellular proliferation in oesophageal squamous cell carcinomas: differences between keratinizing and nonkeratinizing types.

To assess cell death and cellular proliferation activity, the apoptosis index, the Ki67 proliferative index and overexpression of p53 protein were evaluated in 69 oesophageal squamous cell carcinomas (ESCC), all surgically resected from Japanese patients. Apoptosis was examined by Gavrieli's method in histological sections, and proved to be significantly related to keratinization and ESCC progression. Overall labelling indices were 15.68 +/- 4.04 (positive/1,000 nuclei) and 6.79 +/- 0.64 respectively, in keratinizing and nonkeratinizing types. The apoptosis labelling index increased, especially in keratinizing lesions, from 4.50 +/- 0.59 with cancer invasion to mucosa through 11.46 +/- 2.70 with involvement of the submucosa up to 21.18 +/- 3.72 in cases of penetration to the muscularis propria or adventitia. The relationship between apoptosis, Ki67 scores and p53 expression was determined in identical cancer nests on serial sections. An inverse correlation was shown between the apoptosis score and the Ki67 score in both keratinizing and nonkeratinizing types. There was no significant correlation between apoptosis score and p53 expression, either overall or separately in keratinizing or nonkeratinizing types of ESCC. Our results suggest that a mechanism of induction of apoptosis similar to that operating in normal epidermis acts in keratinizing ESCC, and that as tumour volume increases, single cell death becomes more frequent.

Apoptosis↗

PubMed1995

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma.

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.

Carcinoma, Papillary↗

PubMed1995

Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia.

The bcl-2 protooncogene was initially discovered at the t(14;18) chromosomal breakpoint in follicular lymphomas. It has been demonstrated that bcl-2 protein (Bcl-2) expression blocks apoptosis and plays an important role in cell development and maturation. In the present study, Bcl-2 expression was immunohistochemically examined in 103 cases of gastric carcinoma, as well as 64 cases of non-carcinous gastric mucosa, and its correlation with apoptosis, cell proliferation and p53 immunoreactivity was investigated. Bcl-2 was detected in 18.0% of differentiated-type gastric carcinomas (9 of 50) and 7.5% of the undifferentiated type (4 of 53). In adjacent intestinal metaplastic gastric epithelium, the incidence of Bcl-2 positivity in the incomplete type (21/23, 91.3%) was significantly higher than in the complete type (23/41, 56.1%) (P < 0.04). Double immunostaining for Bcl-2 and Ki-67 clearly revealed the majority of Bcl-2-positive cancer cells to be in a nonproliferating state, although some cancer cells expressed both proteins together. Statistical assessment demonstrated that the average Ki-67 labeling index and apoptotic labeling index in Bcl-2-positive foci were significantly lower than in Bcl-2-negative foci (P < 0.0001, P < 0.0003). In addition, a significant dissociation between Bcl-2 and p53 immunoreactivity was found in cancer tissues. These results indicate that aberrant Bcl-2 expression in gastric carcinomas possibly originates from intestinal metaplastic epithelium, and suggest a possible role in tumor development and growth.

Adenocarcinoma↗

PubMed1995

Apoptosis in gastric carcinomas and its association with cell proliferation and differentiation.

The significance of apoptosis in human gastric carcinomas was investigated in comparison with proliferative activity and p53 accumulation, using an in situ DNA nick end labeling method and immunohistochemistry for both Ki-67 antigen and p53 protein. Apoptotic labeling indices (LI) of 51 differentiated carcinomas (21 of early and 22 of advanced stage) were significantly lower than for 33 undifferentiated tumors (9 of early and 24 of advanced stage) (P < 0.05). In both types, apoptotic LI of advanced stage lesions were significantly higher than for the early stage cases (P < 0.005, P < 0.03). The distribution of apoptotic cells was different from that of Ki-67-positive cells, generally exhibiting an inverse correlation for areas of predominance. In contrast, there was no significant correlation between p53 immunoreactivity and either apoptotic LI or Ki-67 LI. It is concluded that in human gastric carcinomas the susceptibility to apoptosis is related to tumor cell differentiation and depth of invasion, and may play a role in selection of clonal subpopulations with high growth potential.

Antigens, Neoplasm↗