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Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 127 records · Page 7Linked to original sources
PubMed1989

A unique verrucous anogenital tumor associated with type 6b-related human papillomavirus.

Multiple dark brown papillomatous tumors, showing some histological features of verrucous carcinoma or giant condyloma, developed mainly in the anogenital region of a Japanese woman. The tumors first appeared when she was 51 years old and annoyed her for over 20 years with several recurrences without any frank malignant transformation, after surgery. Immunohistochemically, papillomavirus genus-specific antigen was demonstrated only in small foci of the lesions resected at first operation. Southern blot analysis revealed human papillomavirus type 6b-related DNA in a surgically resected specimen. The possible role of the human papillomavirus in the genesis of this unique tumor is discussed.

Aged↗
PubMed1989

Immunohistochemical and immunoblot analyses of ras-p21 expression in lung carcinomas.

Immunohistochemical and immunoblot analyses were performed on 49 cases of surgically resected primary lung carcinoma to examine the expression of ras oncogene product using monoclonal antibodies to ras-p21. Two different monoclonal antibodies, NCC-RAS-001 and RAP-5 were used for immunohistochemical study. Cancer cells of 16 cases (33%) and 15 cases (31%) were strongly positive for NCC-RAS-001 and RAP-5, respectively. The staining pattern of antibodies was heterogenous among cancer cells, even in the same case. Among various histologic type of lung cancers, squamous cell carcinomas and well-differentiated adenocarcinomas had a tendency to react more intensively than other histologic types of carcinoma. Immunoblot analysis using monoclonal antibody NCC-RAS-004 revealed the presence of ras-p21 not only in cancer tissues but also in non-cancerous tissues in all cases analysed. In 13 cases (27%), cancer tissue expressed more than twice as much ras-p21 as non-cancerous tissues. Our study showed that the over-expression of ras-p21 in lung carcinomas compared with non-cancerous tissues was a relatively common phenomenon, especially in squamous cell carcinomas and adenocarcinomas.

Adenocarcinoma↗
PubMed1989

Histochemical and immunohistochemical evidence of glandular differentiation in thymic carcinoma.

Eighteen cases of primary thymic carcinoma were reviewed from the viewpoint of glandular differentiation. Squamous differentiation was evident in 14 cases (83%). Immunohistochemical study revealed secretory component (SC)-positive carcinoma cells in 12 cases (67%), most of which were also associated with squamous differentiation. Three of these 12 cases contained areas with a definite glandular or microcystic structure with occasional epithelial mucin, and were diagnosed as adenosquamous carcinoma. Review of patients' medical records revealed that thymic carcinomas with a glandular element were more often resectable at surgery, and had a much better prognosis than those without a glandular element. However, further study on larger number of cases is necessary to confirm this relationship. Because SC-positive epithelial cells do exist in the non-neoplastic thymus, the presence of a glandular component suggests another direction of morphological and/or functional differentiation of thymic carcinoma cells in addition to the well-known squamous differentiation.

Biomarkers, Tumor↗
PubMed1989

In situ hybridization and immunohistochemical study of human papillomavirus infection in adult laryngeal papillomas.

Routinely processed paraffin sections from 20 patients with adult laryngeal papillomas were examined for the presence of human papillomavirus type 11 (HPV-11) DNA and its specific mRNA by in situ hybridization methods using 35S-labeled RNA probes. Immunohistochemical techniques were also used to identify papillomavirus genus-specific common antigen (pgs-antigen). HPV-11 DNA signals and/or papillomavirus genus-specific common antigen were detected in all eight samples of multiple laryngeal papilloma. On the other hand, in 12 samples of single laryngeal papilloma, neither papillomavirus genus-specific common antigen nor HPV-11 DNA were detected. Four patients were positive for both HPV-11 DNA and pgs-antigen. In three of these four patients, HPV-11 mRNA signals were also detected. These results provided direct evidence of the association of HPV and adult multiple laryngeal papilloma.

Adult↗
PubMed1989

Nuclear DNA content by cytofluorometry of stage I adenocarcinoma of the lung in relation to postoperative recurrence.

Forty-six cases of adenocarcinoma of the lung, categorized as stage I (T1N0M0, T2N0M0) pathologically, were studied in terms of nuclear DNA content (NDC) determined by cytofluorometry. They comprised 23 cases each with and without tumor recurrence within five years postoperatively, and the NDC was compared in 23 pairs in which the tumor size and the degree of histologic differentiation were completely matched. The NDC was larger in the recurrent group than in the nonrecurrent group in terms of mean nuclear DNA content (MNDC), DNA histogram pattern, and occurrence of the aneuploid stem cell line, of which the difference in MNDC was statistically significant (p less than 0.05). When the comparison of NDC was made between the nonrecurrent and recurrent groups in the well differentiated (W/D), moderately to poorly differentiated (M.P/D), T1, and T2 subgroups, the NDC of the recurrent group was significantly larger than that of the nonrecurrent group in the W/D (MNDC, p less than 0.01 and DNA histogram pattern, p less than 0.005) and T1 subgroups (MNDC, p less than 0.05), but not in the M.P/D and T2 subgroups. The results indicate that the NDC is a good predictor of prognosis in stage I adenocarcinoma of the lung and its prognostic importance increases in more differentiated and smaller tumors, compared to less differentiated and larger tumors.

Adenocarcinoma↗
PubMed1989

Thiosemicarbazide used after periodic acid makes methenamine silver staining of renal glomerular basement membranes faster and cleaner.

The periodic acid-methenamine silver staining technique, which is frequently used for demonstrating the renal glomerular basement membrane, requires a high degree of skill, and in some cases it may be difficult to obtain a good result. To overcome such difficulty and inconsistency, we have improved the method by performing methenamine silver staining after oxidation with periodic acid and subsequent application of thiosemicarbazide. In this procedure, this semicarbazide enhanced the reaction of methenamine silver with the glomerular basement membrane and the reaction was completed within a shorter time in comparison with the conventional method. This modification also eliminated any nonspecific reaction with the surface of the glass slide and the solution container and yielded excellent and reproducible results irrespective of the fixation method and material employed. It was also found to stain the renal glomerular basement membrane of rabbits, which is demonstrable only with difficulty by the conventional method.

Animals↗
PubMed1989

Lymphocyte subsets in pulmonary venous and arterial blood of lung cancer patients.

Lymphocyte subsets in pulmonary venous blood (PVB) smears from 42 patients with lung cancer were immunocytochemically determined. In four patients, pulmonary arterial blood (PAB) smears were also studied for comparison with PVB. Seven healthy donor peripheral blood (PB) smears were used as controls. The percentage of T cells, helper/inducer T (Th) cells and B cells were significantly lower (P less than 0.01) than in normal controls but those of suppressor/cytotoxic T (Ts) cells, natural killer (NK) cells (P less than 0.01) and S100+ small lymphoid cells (P less than 0.05) were higher. This resulted in a decrease in the Th:Ts value in cancer patients (1.46 vs. 2.28 for normal controls; P less than 0.01). The Th and Ts value of PVB from patients in pathological Stages III and IV was lower than from those in Stages I and II because of the increase in Ts cells in the former (P less than 0.05). S100+ small lymphoid cells were increased in cancer patients, especially in those with adenocarcinoma. The present study demonstrates immunoregulation abnormalities in cancer bearing hosts, the results correlating well with the stage of the cancer. Determining lymphocyte subset alterations in PVB did not, however, enable us to detect the changes associated with local immune responses against cancer.

Adult↗
PubMed1989

[Recent advances in pathology and biology of small cell lung cancer].

Small cell lung cancer (SCLC) is histologically simple and looks undifferentiated, but possesses cytoplasmic dense-cored granules resembling neuroendocrine granules, and frequently produces amine and peptide hormones, occasionally presenting related symptoms. Among these bioactive substances, gastrin releasing peptide (GRP) is most important, which is known as autocrine growth factor and one of the useful monitoring markers for SCLC together with neuron-specific enolase. Aromatic L-amino acid decarboxylase is another important enzyme in SCLC. Abnormality of myc family oncogenes is occasionally noted in SCLC, which appears related to proliferative activity of the tumor rather than development. Deletion of chromosomes 3p, 13q and 17p is noted in almost every SCLC, where antioncogene is suspected to be present, and inactivation of antioncogene may play an important role in development of SCLC. Nucleolar size is the important parameter for proliferative potential of SCLC. The larger the nucleoli, the faster is the growth of SCLC. Phenotypes of SCLC in vitro may be altered by change of microenvironment, although it may be due to the selective growth of a certain clone. SCLC and nervous tissue specific membrane antigen is named cluster 1 SCLC antigen, the monoclonal antibody to which will be utilized for immunohistological diagnosis, imaging and treatment of SCLC. Accumulation of basic knowledge is now leading to reconsideration of histological subtyping of SCLC.

Antibodies, Monoclonal↗
PubMed1989

Multiple genetic alterations in small-cell lung carcinoma.

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Small Cell↗
PubMed1988

Increasing incidence of hepatocellular carcinoma possibly associated with non-A, non-B hepatitis in Japan, disclosed by hepatitis B virus DNA analysis of surgically resected cases.

At the National Cancer Center Hospital in Japan, the total number of surgically treated hepatocellular carcinomas (HCCs) has been increasing steadily and rapidly over the last 10 years, whereas the number of cases positive for hepatitis B surface antigen in sera (HBsAg) has remained almost stable. Thus, the relative percentage of HCC cases with serum HBsAg has shown a marked decrease. In order to examine whether this increased proportion of HBsAg-seronegative patients carries hepatitis B virus (HBV) DNA in the liver, we extracted DNA from the formalin-fixed and paraffin-embedded cancerous and noncancerous liver tissues of 79 patients with HCC. The HCCs examined included 49 specimens resected during a period from 1970 to 1980 and 30 resected in 1986 and 1987. We were able to detect reliably the presence of HBV DNA by dot-blot hybridization. The presence of HBV DNA in liver tissues showed a good correlation with positivity for serum HBsAg in both examined groups. In total, HBV DNA was detected in 81% (21 of 26) of HBsAg-seropositive cases and in only 8% (4 of 53) of HBsAg-seronegative cases, indicating that the increased number of HBsAg-seronegative cases had no HBV involvement. Among these HBsAg-seronegative HCC patients, 89.7% showed a histology of cirrhosis or chronic active hepatitis in the noncancerous liver and 29.1% had a history of blood transfusion. These results suggest an increasing incidence of non-A, non-B hepatitis-associated HCCs in Japan and the possible transmission of factors by means other than blood transfusion.

Carcinoma, Hepatocellular↗
PubMed1988

myc family gene abnormality in lung cancers and its relation to xenotransplantability.

In order to study the relationship between tumor transplantability to the nude mouse and abnormality of the myc family genes (c-myc, N-myc, L-myc) in human primary lung cancers, 32 various lung cancers were analyzed for abnormality of the myc family genes by Southern blot hybridization, and were transplanted s.c. into nude mice. Southern blot analysis showed that four non-small cell carcinomas and three small cell carcinomas had amplified c-myc and L-myc genes, respectively. Allelic deletion of the L-myc gene was observed in seven cancers, of which two also had an additional band of the c-myc gene or amplification of the L-myc gene. No abnormality of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable to nude mice. Of 19 tumors without any abnormalities of the myc family genes, however, only five were transplantable to nude mice (P less than 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.

Animals↗
PubMed1988

Histopathologic classification of small cell lung cancer. Changing concepts and terminology.

Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

Carcinoma, Small Cell↗
PubMed1988

Proliferative potential of brain metastases.

Thirteen patients with metastatic brain tumors received an intravenous infusion of bromodeoxyuridine (BUdR) 200 mg/m2 at craniotomy) to label S-phase tumor cells. Excised tumors were stained immunohistochemically for BUdR. The percentage of BUdR-positive cells was calculated to determine the BUdR labeling index (LI) (or fraction of S-phase cells), which provides an estimate of the proliferative potential. Histologically, 11 patients had adenocarcinoma (four well-differentiated, three moderately differentiated, and four poorly differentiated), one had a large cell carcinoma, and one had a small cell carcinoma. All tumors had a BUdR LI greater than 5% (mean, 13.3 +/- 7% standard deviation). Moderately and poorly differentiated adenocarcinomas had a higher LI than well-differentiated adenocarcinomas (median, 15.3% versus 8.2%). These LI values are considerably higher than those reported for primary tumors with comparable histologic features. Thus, metastatic tumors in the brain may grow faster than the primary tumors from which they originate.

Adenocarcinoma↗
PubMed1988

Selection of a monoclonal antibody reactive with a high-molecular-weight glycoprotein circulating in the body fluid of gastrointestinal cancer patients.

The monoclonal antibody NCC-CO-450 (IgM kappa) was selected by screening of reactivity with high-molecular-weight antigens (Mr greater than 10(6] isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Lea, Lex, LeY, Tn, sialyl-Lea, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.

Animals↗