Search PubMed⌕ Search

Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 91 records · Page 5Linked to original sources
PubMed1990

Heterogeneity of proliferative activity in nodule-in-nodule lesions of small hepatocellular carcinoma.

Surgically resected small hepatocellular carcinomas showing "nodule-in-nodule" formation were analyzed in terms of cell proliferative activity. The analysis was achieved by successful immunohistochemical demonstration of proliferating cell nuclear antigen in formalin-fixed paraffin-embedded tissue sections. Eight nodules (up to 3 cm in diameter) examined were either atypical adenomatous hyperplasia or hepatocellular carcinoma of low histologic grade, containing a discrete inner nodular area composed of obvious hepatocellular carcinoma of higher histologic grade. In all cases, the proliferating cell nuclear antigen labeling index of the latter area was much higher than that of the former, which in turn was slightly higher than that of the non-cancerous liver of the patient in 6 cases. The data presented here provide supporting evidence that the successive emergence and expansion of a more rapidly proliferating subclone within a nodule result in the stepwise progression of malignancy of human hepatocellular carcinoma.

Antigens, Neoplasm↗
PubMed1990

Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma.

By restriction fragment length polymorphism analysis, we examined loss of heterozygosity at 34 loci on 23 chromosomes in 35 surgically resected human hepatocellular carcinomas. Allele losses at the HP locus on chromosome 16q22 and at the MT2P1 locus on chromosome 4p11-q21 were detected in 57% (8/14) and 50% (8/16) of cases, respectively. Loss of heterozygosity on chromosomes 16q and 4 occurred simultaneously in 4 of 7 informative cases for both loci, and seemed to be important in the development of human hepatocellular carcinoma irrespective of the presence of hepatitis B virus infection. In contrast, the incidence of allele loss was low at the other loci, e.g., chromosome 1p, 3p, 11p, 13q or 17p, where one allele is frequently lost in other cancers.

Carcinoma, Hepatocellular↗
PubMed1990

Detection of Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin's disease using the polymerase chain reaction and in situ hybridization.

Thirty-one cases of Hodgkin's disease were examined for the occurrence of Epstein-Barr virus (EBV) genome by using the polymerase chain reaction (PCR) of DNA in formalin-fixed paraffin-embedded tissues and in situ hybridization technique. The cases were subdivided into 17 cases of nodular sclerosis (NS), nine cases of mixed cellularity (MC), four cases of lymphocyte predominance (LP), and one case of lymphocyte depletion (LD). EBV DNA was detected in eight cases including four cases of NS, three cases of MC and one case of LP. The sensitivity of PCR was higher than that of Southern blot hybridization of DNA from fresh frozen tissue, because Southern blot hybridization using the BamHI-W fragment of EBV detected virus DNA only in two of three cases which were positive by PCR. The results of in situ hybridization studies confirmed that EBV genome was localized within the nuclei of Reed-Sternberg (RS) cells and their mononuclear variants. Furthermore, double-labeling studies combining in situ hybridization and immunocytochemistry using CD30 (BerH2) and CD15 (LeuM1) as markers of RS cells, as well as pan B-marker (L26) and pan T-marker, CD45RO (UCHL1), were performed to demonstrate the phenotype of EBV DNA-positive cells, confirming that EBV DNA was present in RS cells but not in lymphocytes. The results of this study indicate a significant association between EBV and some cases of Hodgkin's disease.

Adult↗
PubMed1990

Immunohistochemical study on overexpression of c-erbB-2 protein in human breast cancer: its correlation with gene amplification and long-term survival of patients.

Using a polyclonal antibody monospecific to the c-erbB-2 oncogene product, an immunohistochemical study on the expression of c-erbB-2 protein was performed in formalin-fixed, paraffin-embedded tissue sections from 176 primary breast carcinomas in which amplification of the c-erbB-2 gene had been detected in 28 cases. Expression of the c-erbB-2 protein was detected in 44 cases (25%), being strongly positive in 27 (15%) and weakly positive in 17 (10%). All cases with amplification of c-erbB-2 showed positive staining of its protein. There were only four cases in which c-erbB-2 was strongly expressed without amplification of the gene. In the group showing strongly positive staining, both overall and disease-free survival were significantly poorer than in the remainder of the cases. Using Cox's regression model analysis, overexpression of c-erbB-2 protein was demonstrated to be an effective prognostic factor independent of nodal status or tumor size.

Amino Acid Sequence↗
PubMed1990

Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line.

Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line.

Animals↗
PubMed1990

Preservation of cluster 1 small cell lung cancer antigen in zinc-formalin fixative and its application to immunohistological diagnosis.

Monoclonal antibodies reactive with cluster 1 small cell lung cancer antigen have been shown to be useful for the distinction of small cell from non-small cell tumours. In previous studies the antibodies have been applied to frozen sections and cold acetone-fixed tissues. However, one of three monoclonal antibodies that we produced, NCC-LU-243, reacted with some small cell lung carcinomas fixed in formalin solution and embedded in paraffin. The addition of zinc sulphate to the formalin solution at a concentration of 2% (v/w) greatly improved antigen immunoreactivity, and reactivity was retained even after prolonged fixation. Occasionally, immunoreactivity was present in a poorly differentiated adenocarcinoma with rosette-like structures. The monoclonal antibody NCC-LU-243 is thus of considerable potential value in the immunohistochemical diagnosis of small cell lung cancers.

Antibodies, Monoclonal↗
PubMed1990

Alveolar soft part sarcoma. A clinicopathologic and immunohistochemical study of 12 cases.

Twelve cases of alveolar soft part sarcoma (ASPS) were reviewed. Seven of them arose primarily in the lower extremities, three in the head and neck region, and two in other parts. ASPSs in the head and neck region occurred in children before 10 years of age, whereas ASPSs in the other regions occurred in rather older patients. Moreover, ASPSs of the head and neck were relatively small in size, and were diagnosed earlier than those in other regions. Histologically, six cases (including all the head and neck cases) contained considerable area of small and indistinct alveolar structures. Four cases showed remarkable cellular pleomorphism. Immunohistochemical demonstration of vimentin, desmin, the beta-subunit of enolase and the MM isozyme of creatine kinase, together with the absence of immunoreactive cytokeratin, supported the myogenic nature of this rare tumor. A small number of S-100 protein-positive tumor cells were also observed. Follow-up data for these cases disclosed that the tumors containing considerable area of small alveoli and uniform small tumor cells formed distant metastases at an early stage.

Adolescent↗
PubMed1990

Immunohistochemical analysis of human adenocarcinomas of the lung using the monoclonal antibody 44-3A6.

In this study, 39 primary, surgically resected, pulmonary adenocarcinomas of the following cell types were investigated: 19 Clara cell, 4 bronchial-gland, 15 goblet cell, and 1 type II alveolar epithelial adenocarcinoma. They were analyzed for the expression of the glandular differentiation-associated antigen recognized by the monoclonal antibody 44-3A6. Formalin-fixed, paraffin-embedded tissue sections were immunostained using the avidinbiotin complex/peroxidase method. All of the Clara cell tumors (19/19) expressed this antigen as well as 3/4 bronchial-gland tumors, as compared to only 2/15 goblet cell tumors. The single type II pneumocyte neoplasm studied was found to express this antigen. These findings parallel our earlier observations based on cytological features, and provide supportive evidence that there may be biological differences between human pulmonary adenocarcinomas and bronchioloalveolar carcinomas.

Adenocarcinoma↗
PubMed1990

Detection of human papillomavirus DNA in laryngeal squamous cell carcinomas by polymerase chain reaction.

The presence of human papillomavirus genomes-16 and -6b in metastatic cervical lymph nodes was examined in 34 cases of laryngeal carcinomas by means of polymerase chain reaction, which had been fixed in formalin and embedded in paraffin. Human papillomavirus DNAs extracted from paraffin-embedded tumor tissues were used for polymerase chain reaction with amplification of the E6 region of human papillomavirus genome-16 and the E1 region of human papillomavirus genome-6b. Human papillomavirus genome-16 sequences were positively amplified in six (17.6%) metastatic tumors; -6b sequence was positively amplified in one (2.9%) metastatic tumor. Laryngeal carcinomas of glottic origin showed high human papillomavirus genome-16 DNA-positive rates (4 of 9 cases, 44.4%) compared to those of other sites. These results suggest that human papillomavirus genome-16 infection might be closely associated with the development of some laryngeal squamous cell carcinomas of glottic origin similar to uterine cervical carcino-genesis.

Carcinoma, Squamous Cell↗
PubMed1990

Transferrin receptor expression in adenocarcinoma of the lung as a histopathologic indicator of prognosis.

Immunohistochemical reactivity with OKT9 (antitransferrin receptor) monoclonal antibody was studied in 58 surgically resected adenocarcinomas of the lung. The cell surface and cytoplasm of the tumor cells were stained in 44 cases (76 percent). The expression of the transferrin receptor (TrfR) in tumor cells was compared with histopathologic prognostic factors, such as TNM factors, degree of histologic differentiation, degree of nuclear atypia, and frequency of mitotic figures. The expression of TrfR showed significant correlation with the degree of histopathologic differentiation (p less than 0.025), degree of nuclear atypia (p less than 0.025), and frequency of mitotic figures (p less than 0.001). However, there was no definite correlation with TNM factors. These results indicate that the expression of the TrfR in pulmonary adenocarcinoma corresponds to the elevated proliferative activity of the tumor cells, and that immunohistochemical reactivity with OKT9 can be used as one of the histopathologic indicators of prognosis of pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1990

Regulation of the epidermal growth factor receptor gene expression in a morphological variant isolated from an epidermal growth factor receptor-deficient small cell lung carcinoma cell line.

Most cell lines derived from small cell lung carcinoma grow in an anchorage-independent manner; they neither possess epidermal growth factor binding activity nor express epidermal growth factor receptor (EGFR) mRNA. A variant AD320, which grew in an anchorage-dependent manner with altered morphology, was isolated from the small cell lung carcinoma cell line Lu134 by treatment with the demethylating agent 5-azacytidine. The analysis, using methylation-sensitive restriction enzymes, revealed that the methylation pattern was altered only in the structural region of the EGFR gene; EGFR mRNA and epidermal growth factor binding activity could be detected in the variant. In addition, drastic changes in gene expression including a decrease of creatine kinase B mRNA and an increase of c-myc mRNA were observed. The EGFR in the variant appeared to be an active part of the transmembrane signaling machinery since c-fos and c-jun mRNA accumulated after epidermal growth factor treatment, followed by EGFR and c-myc mRNA accumulation. A potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, also induced EGFR mRNA. Thus, the inducible regulatory mechanism for the EGFR gene was activated in the variant even though the EGFR gene was constitutively expressed.

Blotting, Northern↗
PubMed1990

An immunohistochemical study of thymic epithelial tumors. III. The distribution of interdigitating reticulum cells and S-100 beta-positive small lymphocytes.

We report an immunohistochemical study of the distribution and number of interdigitating reticulum cells (IDC) and S-100 beta-positive small lymphocytes (S-100 beta + lymphocytes) in 53 thymomas and 11 thymic carcinomas. All 53 thymomas showed the presence of IDC in the tumor parenchyma. In most cases of predominantly lymphocytic and mixed-type thymoma, IDC clustered in areas, that corresponded to locations that had medullary differentiation and contained accumulated mature lymphocytes. By contrast, in most of the predominantly epithelial-type thymomas, IDC were scattered rather than forming clusters. The distribution and number of IDC were correlation with the histological type of thymoma but not with invasiveness. In thymic carcinomas, IDC were scattered in tumor nests. In 47 of the 53 thymomas (89%), infiltrating S-100 beta + lymphocytes were readily recognized. The remaining six cases without S-100 beta + lymphocytes were noninvasive thymoma. We conclude that the degree of S-100 beta + lymphocyte infiltration is correlated with the stage of thymoma and may be a marker of thymoma malignancy.

Adult↗
PubMed1990

Clonal growth of atypical adenomatous hyperplasia of the lung: cytofluorometric analysis of nuclear DNA content.

The nuclear DNA content of 13 cases of atypical adenomatous hyperplasia (AAH) associated with adenocarcinoma, eight cases of small-sized well differentiated adenocarcinoma in which the tumors were less than 2.5 cm in size with no tumor recurrence within 5 yr after surgery, and eight cases of reactive type 2 pneumocyte hyperplasia of the lung was determined by cytofluorometry. Of the AAHs, four were solitary and composed entirely of cells of AAH (Group 1), and the remaining nine were in continuity with the focus of adenocarcinoma (Group 2). The average mean nuclear DNA content of the AAHs was significantly greater than that of reactive type 2 pneumocyte hyperplasia (p less than 0.005) and significantly smaller than that of adenocarcinoma associated with AAH (p less than 0.05). However, no significant difference was found in nuclear DNA content between AAH and small-sized well differentiated adenocarcinoma. Aneuploid stem lines were found in seven of the 13 (53.8%) AAHs, ten of the 13 (76.9%) adenocarcinomas associated with AAH, and five of the eight (62.5%) small-sized well differentiated adenocarcinomas but in none of the reactive type 2 pneumocyte hyperplasias. DNA histogram patterns I and II, in which aneuploid cells were less frequently present than in patterns III and IV, were more common in AAH than in adenocarcinoma associated with AAH and small-sized well differentiated adenocarcinoma. All of the reactive type 2 pneumocyte hyperplasia showed pattern I. As to the average mean nuclear DNA content, incidence of aneuploid stem lines, and DNA histogram pattern, there was no significant difference between groups 1 and 2 of the AAHs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

The AMeX method: a multipurpose tissue-processing and paraffin-embedding method. II. Extraction of spooled DNA and its application to Southern blot hybridization analysis.

In our previous report, we described a new fixation and paraffin-embedding method (the AMeX method) that preserves many of the antigens that are normally destroyed by routine formalin fixation. The current study was conducted to examine the preservation of high-molecular-weight DNA in tissues processed by this method. DNA was extracted from AMeX-processed tissue sections after deparaffinization by the same method as that used to extract DNA from fresh tissues. The total amounts of DNA extracted from 10 mg each in wet weight of AMeX-processed and fresh mouse liver tissues were identical. In tissues of malignant lymphoma, the total amount of spooled DNA extracted from 50 sections, each 20 microns thick, was about 8 micrograms/mm2. The electrophoretic pattern of DNA digested with restriction endonucleases on agarose gel from AMeX-processed tissue sections did not differ from that of fresh materials. Southern blot hybridization analysis also revealed that the mobility of specific DNA fragments was identical for AMeX-processed and fresh tissues. The AMeX method was thus proved to be a versatile multipurpose tissue-processing procedure, which is expected to provide important information regarding the correlation between morphology, phenotypic expression, and gene alteration.

Blotting, Southern↗
PubMed1989

A cell kinetic study of pulmonary adenocarcinoma by an immunoperoxidase procedure after bromodeoxyuridine labeling.

By in vitro labeling with bromodeoxyuridine (BrdU) and immunohistochemical staining with anti-BrdU monoclonal antibody, the tumor cell kinetics were investigated in 52 resected pulmonary adenocarcinomas. The values of the BrdU labeling index (LI) varied widely among cases of adenocarcinoma in comparison with four cases of small cell carcinoma and ten cases of squamous cell carcinoma examined as controls. The LI was below 3.0 in 60% of the adenocarcinomas. When the LI was analyzed according to the cytologic subtypes of adenocarcinoma, the values were low for goblet cell type and type II alveolar cell type, whereas the values for the bronchial surface epithelial cell type varied widely (average, 5.2) and those for the Clara cell type were intermediate (average, 1.8). A comparison of the LI with TNM classification, histologic differentiation, degree of nuclear atypia, and mitotic cell count showed a correlation between the LI and each of these prognostic factors. Thus, the possibility of the BrdU LI being a useful new prognostic factor of pulmonary adenocarcinomas was suggested.

Adenocarcinoma↗