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Biomedical subjects

M Saegusa

Publications and source records attributed to M Saegusa.

At least 55 records · Page 3Linked to original sources
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

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

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

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↗
PubMed1995

HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma.

AIMS: To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. METHODS: Sixteen cases of papilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. RESULTS: HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases of dysplasia and squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p < 0.01). CONCLUSIONS: Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events.

Adult↗
PubMed1993

Comparative analysis of p53 and c-myc expression and cell proliferation in human hepatocellular carcinomas--an enhanced immunohistochemical approach.

Expression of p53 and c-myc was investigated and compared with cell proliferative activity in a series of 40 hepatocellular carcinomas (HCC), by means of enhanced immunohistochemistry. p53 expression was demonstrated in 5 out of 40 HCC (12.5%) with the incidence increasing in 5 out of 40 HCC (12.5%) with the incidence increasing in proportion to the histological grading of malignancy: thus, 0% of well-differentiated, 6.9% of moderately differentiated and 33.3% of poorly differentiated lesions were positive. The proliferating-cell nuclear antigen (PCNA) labeling index also showed a statistically significant increase with this grading. Distribution patterns of PCNA-positive cell were divided into four types: scatter, marginal, mosaic and diffuse. Four HCC cases, predominantly of the poorly differentiated type, exhibited the diffuse pattern. Generally, p53 overexpression corresponded well with PCNA positivity. In contrast, there was no correlation between c-myc overexpression, found in 19 out of 40 HCC (47.5%), and histological grading of HCC or PCNA labeling index. The distribution pattern of c-myc-positive HCC cells was also different from that of PCNA and p53. Our results suggest that p53 overexpression closely relates to proliferation of HCC cells. Furthermore, there may be a consistent difference in regulatory mechanisms between p53 and c-myc expression in multistep hepatocarcinogenesis.

Adult↗
PubMed1993

Pathologic analyses of non-overt necrotizing type Kikuchi and Fujimoto's disease.

Twenty-eight cases of non-overt necrotizing type Kikuchi-Fujimoto disease (KF disease, histiocytic necrotizing lymphadenitis) were investigated clinicopathologically, immunohistochemically and electron microscopically in order to analyze the nature of this disease. In addition, investigations to detect the presence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization (ISH) were also performed as a high incidence of positive serum immunoreactivity to EBV had been revealed in the cases examined. The clinical features were an equal male to female ratio, mean age of 26 years, mild leukopenia and about 40% association with fever over 38 degrees C. The major particular pathologic features were: (i) varying amounts of nuclear debris in the pathologic areas, identified as apoptosis by electron microscopy; (ii) presence of medium to large sized transformed lymphocytes (immunoblasts), a very small number of them positive for both UCHL1 and L26, and plasmacytoid cells, some of them positive for UCHL1; and (iii) characteristically shaped histiocytes predominant in the pathologic areas, with irregular nuclei and strongly positive for anti-lysozyme and anti-alpha 1-antitrypsin antibodies. Investigations with PCR and ISH revealed a complete absence of EBV in these cases despite excellent results for positive controls. It was therefore considered that EBV was not a causative virus for KF disease.

Adolescent↗
PubMed1993

Human hepatic infarction: histopathological and postmortem angiological studies.

Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were investigated to clarify the pathogenetic aspects of this disease. Additional postmortem angiological studies of 24 normal human livers obtained at autopsy were also further performed to analyse the effects of blocking vascular structures on lesion development. Seventeen of the 20 cases (85%) were clinically associated with systemic circulatory insufficiency, especially hepato- and/or renal failure. Histopathologically, there was a significantly closer relationship between the location of infarcted regions and portal vein thrombosis than with either hepatic vein thrombosis or hepatic arterial damage. The borders between infarcted regions and surviving hepatic parenchyma were located around central veins, corresponding with the microcirculatory periphery of the portal venous system. Postmortem angiographic studies revealed that hepatic lobuli mainly consist of portal vein branches. Moreover, postmortem embolization studies of six normal livers using glass beads and barium-gelatin injection showed that physical occlusion of portal vein branches produced defects in broad areas of the hepatic parenchyma. Therefore, it is suggested that the development of hepatic infarction principally depends on disturbances of the portal venous system. In addition, systemic circulatory insufficiency, which reduces the intrahepatic blood flow, probably contributes greatly to the development of hepatic infarction.

Adult↗
PubMed1993

[Lymphangiomyomatosis involving the kidney: a case report].

A 58-year-old female was admitted with a chief complaint of gross hematuria. A diagnosis of carcinoma of the left kidney with lymphnode metastasis was made on the basis of computerized tomography and angiography. Left nephrectomy and lymphnode dissection were performed. Histological examination revealed lymphangiomyoma, and the final clinical diagnosis was changed to lymphangiomyomatosis with pulmonary, retroperitoneal, and left renal lesions. Lymphangiomyomatosis with renal lesions is extremely rare, and differentiation from renal carcinoma is important, though difficult.

Diagnosis, Differential↗
PubMed1990

[Isoantigens ABH in bladder tumors as an indicator of malignant potential. The staining pattern by PAP method and its correlation with prognosis].

Blood group antigens (BGA) were stained by PAP methods and the relation between staining pattern (classified into five types: I, II, IIIa, IIIb and IV) and tumor prognosis was examined in 54 patients with primary superficial bladder tumor. The recurrence rate was significantly higher in BGA negative (Type IIIb or IV) or Type IIIa cases than in antigen positive (Type I or II) cases. Stage-up was observed only in BGA negative cases. Although staining pattern of recurrent tumor differed from that of primary tumor in some cases, it is believed that prediction of malignant potential should be performed at the primary development, when tumor has not been influenced by treatments. With regard to the relation between staining pattern and tumor prognosis, no significant difference was found between the cases of A, B and AB blood groups and those of O group.

ABO Blood-Group System↗
PubMed1989

Cushing's syndrome due to huge nodular adrenocortical hyperplasia with fluctuation of urinary 17-OHCS excretion.

A 51-yr-old male patient with Cushing's syndrome due to huge nodular adrenocortical hyperplasia is described. Urinary 17-OHCS was not suppressed by a high dose of (8 mg) dexamethasone and showed rather a tendency to paradoxical response. There was no response to metyrapone. Plasma cortisol showed a hyperresponse to insulin-induced hypoglycemia and a rapid response to corticotropin releasing hormone-lysine vasopressin (CRH-LVP) administration without an obvious ACTH response. Plasma cortisol responded to synthetic ACTH. Urinary 17-OHCS did not show parallel changes with plasma cortisol. These results and computerized tomography data suggested huge multiple nodular adrenocortical hyperplasia, which was confirmed later by surgery. The left and right adrenal glands weighed 105 and 45 g, respectively. Hyper-reaction of the adrenal gland to a small change in plasma ACTH or "unknown factors" may cause not only the discrepancy between cortisol and ACTH response but also the development of autonomous nodules in the adrenal gland.

17-Hydroxycorticosteroids↗
PubMed1989

[Isoantigens ABH in bladder tumors as an indicator of malignant potential: a combined study with CEA, BMG, Leu-M1 and H-Ag].

The author performed immunohistochemical staining of blood group antigen (BGA), CEA, BMG, Leu-M1 and H-Ag on 43 patients with primary superficial bladder tumor to evaluate the malignant potential of bladder tumor. There were no obvious relationships among reactivities to BGA, CEA, BMG, Leu-M1 and H-Ag in identical tissue. Although BGA, CEA and Leu-M1 could be used individually as indicators of malignant potential, of the three, BGA was found to be most useful. Concomitant use of Leu-M1 with BGA might compensate for the disadvantages of BGA alone and make prediction of prognosis more objective. Then, a new evaluation criteria for detecting malignant potential of bladder tumor was proposed.

ABO Blood-Group System↗
PubMed1987

[Alternating combination chemotherapy (VIP-DMF) in patients with advanced adenocarcinoma of the prostate].

Eleven patients with advanced adenocarcinoma of the prostate were treated with a cyclic alternating chemotherapy (VIP-DMF therapy), consisting of a three-drug combination of vincristine, ifosfamide, and peplomycin; and a three-drug combination of adriamycin, mitomycin C and 5-fluorouracil. Each cycle was repeated every 3 or 4 weeks. Of these patients, 9 were refractory to prior hormonal therapy and 8 (89%) achieved an objective response (3 partial, 6 stable) using the criteria of the U.S. National Prostatic Cancer Project. In the patients showing objective response, the duration was from 3 to 18 months with a median duration of 6 months. The survival periods from the initiation of chemotherapy in effective cases ranged from 6 to 20+ months with a median duration of 11 months. The major toxicity was myelosuppression, although no patients suffered life-threatening toxicity. We consider that VIP-DMF therapy is a useful regimen for the treatment of advanced prostatic cancer.

Adenocarcinoma↗