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Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 145 records · Page 8Linked to original sources

Histopathologic prognostic factors in adenocarcinomas of the peripheral lung less than 2 cm in diameter.

The histologic prognostic factors of pulmonary adenocarcinomas of the lung less than 2 cm in diameter were analyzed in 75 patients who had undergone surgical resection. The pathologic stage, lymph node involvement, and pleural involvement were found to be the major determinants of prognosis (P less than 0.01). In addition, other single factors, such as tumor differentiation (P less than 0.01), vascular invasion (P less than 0.01), the degree of collagenization in the fibrotic focus (P less than 0.01), the standard deviation (SD) of nuclear areas (P less than 0.05), and mitotic index (P less than 0.05) correlated significantly with prognosis by the log-rank test on the Kaplan-Meier survival curves of these factors. Patients with dense infiltration of "T-zone histiocytes" survived significantly longer than those with less infiltration (P less than 0.05). Cox's proportional hazard general linear model analysis showed the importance of factors, such as lymph node or pleural involvement and the SD of nuclear area, when the pathologic stage was excluded, and of the mitotic index when all four factors were excluded to emphasize the cellular characteristics. It is possible to predict the postoperative prognosis of patients with small pulmonary adenocarcinoma more precisely by combination of the above histopathologic factors.

Adenocarcinoma↗

Solitary mast cell tumor of the lung.

An extremely rare solitary mast cell tumor of the lung was studied histologically, immunohistochemically, and ultrastructurally. The histologic features of the tumor included nodular growth of well-differentiated mast cells and clear cells with no granules. The current case is the third case of a solitary mast cell tumor (granuloma) of the lung in the literature. Clinicopathologic features of this tumor are compared with the other two cases reported previously in the international literature, and the nature of the clear cells is discussed.

Antigens, Neoplasm↗

Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas.

Eighty-nine primary lung carcinomas and 23 metastatic lung tumors were immunohistochemically studied for the expression of pulmonary surfactant apoproteins, by using monoclonal (PE-10) and polyclonal antibodies. Surfactant apoprotein was demonstrated in the cytoplasm and/or nuclear inclusion bodies of only primary lung adenocarcinomas (36 of 75 cases), not in any other histologic type of primary lung carcinoma or in metastatic lung tumors. In primary lung adenocarcinoma, although typical type II pneumocyte type adenocarcinoma was not included in the current series, the majority of surfactant apoprotein-positive single cell type tumors were of the Clara cell type, with a single bronchial surface epithelial cell type, according to the light microscopic subclassification of adenocarcinoma cells. The Clara cell type adenocarcinomas could at times be distinguished only with difficulty from adenocarcinoma of type II pneumocyte type. Normal and hyperplastic type II pneumocytes were of course positive for surfactant apoprotein in the cytoplasm. However, none of the positive cells could definitely be identified as Clara cells in non-neoplastic lungs. The findings obtained in this study indicate that surfactant apoprotein is a good marker to distinguish adenocarcinoma of the lung from other histologic types of lung cancer and from neoplasms metastatic to the lung, and that type II pneumocytes and Clara cells, non-neoplastic and neoplastic, are morphologically and functionally closely related and might belong to the same cell lineage.

Adenocarcinoma↗

Clonal origin of atypical adenomatous hyperplasia of the liver and clonal identity with hepatocellular carcinoma.

We present details of two separate nodular lesions of atypical adenomatous hyperplasia, within one of which a small area of overt hepatocellular carcinoma was detected. The patient was positive for serum hepatitis B surface antigen, and Southern blot analysis revealed that deoxyribonucleic acid from the lesions of hepatocellular carcinoma and surrounding atypical adenomatous hyperplasia showed the same restriction pattern of integrated hepatitis B virus deoxyribonucleic acid, indicating that the two lesions were derived from an identical clone. It was also indicated that the two separate lesions of atypical adenomatous hyperplasia were independently derived through clonal expansion of different cells.

Blotting, Southern↗

Sandwich radioimmunometric assay with murine monoclonal antibody, NCC-ST-439, for serological diagnosis of human cancers.

Sandwich radioimmunometric assay (RIA) for a new tumor-associated carbohydrate antigen defined by a monoclonal antibody (MoAb), NCC-ST-439, was developed and the antigen levels were determined in sera of normal donors, and patients with various malignant and non-malignant disorders. In normal donors, 97.0% (226/233) of sera were antigen-negative (less than 12 units/ml) except for 7 serum samples from young females. In patients with malignant disorders, 34.2% (82/240) were antigen-positive, in particular 64.0% (16/25) of patients with pancreatic carcinoma, 66.7% (16/24) of patients with recurrent colorectal carcinoma and 54.5% (6/11) of patients with recurrent breast carcinoma. In patients with non-malignant disorders, 6.0% (7/116) were antigen-positive. The positive rate in benign hepatobiliary disorders, including gallstones, hepatitis and liver cirrhosis, was especially low at 4.3% (1/23). We concluded that determination of serum NCC-ST-439 antigen would be useful in serodiagnosis of carcinoma patients.

Adult↗

Methylation status of epidermal growth factor receptor gene in lung carcinoma cells.

The methylation status of the epidermal growth factor receptor (EGFR) gene was compared in cell lines from four major types of lung carcinoma, small cell lung carcinoma (SCLC), large cell lung carcinoma, squamous cell carcinoma and adenocarcinoma, in order to examine whether DNA methylation is responsible for the suppression of EGFR gene in SCLC cells. Southern blot analysis revealed that the structural region of the EGFR gene is methylated to various degrees regardless of the expression of EGF receptor on the surface. An 8-kilobase EcoRI fragment which contains the EGFR gene promoter region is readily digested with various methylation-sensitive restriction enzymes in all types of cells, indicating that the EGFR gene 5' region is barely methylated. Thus, a mechanism other than DNA methylation appears to control EGFR gene expression and the lack of EGFR gene expression in SCLC cells may be caused by a paucity of some transcription regulatory factor(s).

Adenocarcinoma↗

Expression of various antigens by different components of uterine mixed müllerian tumors. An immunohistochemical study.

An immunohistochemical study of keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, myoglobin and S-100 protein in 15 cases of uterine mixed Müllerian tumor was performed in order to analyze the expression of various antigens in different elements of this tumor. In general, the epithelial and mesenchymal components were separated easily by the presence of keratin/EMA or vimentin, respectively. However, in eight cases vimentin was expressed by epithelial cells and in four cases keratin by solid "sarcomatous" element. EMA was also identified in the "sarcomatous" areas of two cases. Specific differentiation was much easier to identify by immunohistochemical staining than by routine histologic examination. Areas with muscle differentiation were positive for desmin; myoglobin was identified in rhabdomyoblasts. S-100 protein was present in chondrosarcomatous and liposarcomatous areas. S-100 protein was also widely distributed in other elements. Quite diverse expression of various antigens revealed by immunohistochemistry reflects the histologic multiplicity of this tumor.

Antigens, Neoplasm↗

Bronchial carcinoid tumor mimicking acinic cell tumor.

A rare case of carcinoid tumor mimicking an acinic cell tumor is presented. A bicameral tumor measuring 8 x 6 mm in size was recognized in the right lung (B5bi) upon gross examination. Microscopically, the tumor consisted of basophilic polygonal cells forming an acinar pattern. Ultrastructurally, the majority of tumor cells had large membrane-bound cytoplasmic granules, measuring about 600 nm in diameter, which were similar to secretary granules of serous acinar cells (zymogen granules). These findings suggested that the tumor might be an acinic cell tumor originating from the bronchial gland. However, tumor cells were shown to be negative for periodic and Schiff (PAS) stain or lactoferrin, lysozyme and amylase immunohistochemically. On the other hand, they were shown to be argyrophilic by Grimelius stain and showed immunohistochemically positive reaction for serotonin, suggesting that the granules were neurosecretory granules and not zymogen granules. Based on these findings, we concluded that this tumor was an unusual variant of carcinoid tumor mimicking acinic cell tumor. Although carcinoid tumor has a wide histological spectrum, there has been no reported case, to our knowledge, of acinic cell tumor-like carcinoid tumor.

Bronchial Neoplasms↗

Non-Hodgkin lymphoma of the skin excluding mycosis fungoides and cutaneous involvement of adult T-cell leukemia/lymphoma.

Forty-nine cases of cutaneous malignant lymphoma were reviewed in order to analyze the clinicopathological features of these neoplasms. Excluding 13 cases of mycosis fungoides and 4 cases of cutaneous involvement of proven adult T-cell lymphoma/leukemia, the remaining 32 cases were further classified according to their pathological and clinical features. There were 12 primary cutaneous lymphomas, 15 cases of secondary cutaneous involvement of systemic lymphoma, and 5 cases of concurrent skin and lymph node involvement. Histologically, large cell lymphoma predominated in both primary and secondary cutaneous lymphomas. Immunohistochemical study using monoclonal antibodies reactive with B- and T-cells in paraffin sections revealed the cellular lineage in 30 cases. Nineteen cases were of T-cell origin and 11 cases were of B-cell derivation. The prognosis of these patients was rather poor; 25 patients died within 5 years. The predominance of T-cell lymphoma contrasts with a higher frequency of cutaneous B-cell lymphoma in Western countries. As the clinicopathological features of cutaneous lymphomas are diverse, it is suggested that cutaneous lymphomas should be classified and studied in a similar way to their nodal counterparts.

Adolescent↗

Electron microscopical observation of RNA on the surface of Ehrlich ascites tumor cells.

The structure of RNA on the surface of Ehrlich ascites tumor cells was studied under an electron microscope using both plasma polymerization replica films and ultrathin sections of the cells. Necklace-like structures were found on the cell surface where anti-RNA antibody was bound in replica film, and particles which resemble cytoplasmic ribosomes in size and density were found distributed sparsely on the cell surface in ultrathin sections. These particles were found to gather at one pole of the cell surface after the cell was incubated at 4 degrees C with anti-RNA antibody and then incubated at 37 degrees C for 10 min in antibody-free medium. On the other hand, L1210 cells which do not bind with anti-RNA antibody showed hardly any such structures on the cell surface. These results suggest that RNA on the surface of Ehrlich ascites tumor cells is present in the form of particles.

Animals↗

A simple and highly reproducible staining method for fungi and other polysaccharide-rich microorganisms in animal tissues.

A newly devised, simple and highly reproducible method for fungal staining is reported. Grocott's method, in which methenamine-silver nitrate solution is employed, has been widely used for the staining of fungi in tissue sections, but it frequently produces heavy background staining because of sudden and progressive reaction in the methenamine-silver nitrate solution. We therefore replace the latter solution with an ammoniacal silver nitrate solution. This new method yields more consistent results in fungal staining without background staining, since the reaction time in the ammoniacal silver nitrate solution is prolonged. The present method is considered superior to Grocott's method with regard to its simplicity and reproducibility.

Actinomyces↗

Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes.

Seventy lung tumors from 53 patients were analysed for alterations of myc family oncogenes, c-myc, N-myc and L-myc, to evaluate when activation of these genes occurs during tumor development. The 53 cases were 17 small cell carcinomas (SCCs), 18 adenocarcinomas, 12 squamous cell carcinomas (SqCs), 4 large cell carcinomas and 2 adenosquamous carcinomas. Either N-myc or L-myc was amplified in 4 of the 17 (one N-myc and 3 L-myc) SCCs (24%), while c-myc was amplified in 3 of the 12 SqCs (25%). In one SCC, amplification of N-myc was found in the primary tumor, a pulmonary hilar lymph node metastasis and a pleural metastasis, but not in a liver metastasis or a para-aortic lymph node metastasis. In one SqC, c-myc was amplified in a pleural metastasis and a lymph node metastasis, but not in the primary tumor. In 2 cases of SCCs, amplification or rearrangement of c-myc was detected only in the cell lines, but not in the original tumors taken from the same individuals. These results indicate that tumor cells were heterogeneous for amplification and rearrangement of myc family oncogenes, and suggest that activation of these oncogenes in SCCs and SqCs occurs not at the time of malignant transformation but during tumor progression.

Chromosome Mapping↗

[Pathology and biology of small cell lung cancer].

Small cell lung carcinoma (SCLC) is histologically simple, and shows a characteristic ultrastructure and very complex functions. Recently, a large amount of information has been accumulated by fundamental research, largely involving studies on many cultured cell lines. Now their potential application to the therapy of SCLC is being sought. A characteristic ultrastructural feature is the presence of dense-cored neurosecretory-type granules 100-200 nm in diameter. In addition, epithelial cell characteristics are noted. Predominance of either a neurosecretory or epithelial nature may affect the responsiveness of tumors to therapy. Many kinds of brain-gut hormones are produced by SCLC. Gastrin-releasing peptide (GRP) has attracted much attention as an autocrine growth factor for SCLC. Aromatic L-amino acid decarboxylase (AADC), neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) are rather specific to SCLC. NSE and CK-BB together with GRP are good monitoring markers during treatment. Amplification of c-myc, N-myc and L-myc is seen in SCLCs. Areas both with and without N-myc amplification are found in both the primary site and metastatic sites in a single case. Del 3p(14-23) is characteristic for SCLC but SCLCs without such deletion are also present. A cytologically "variant" type is composed of cells simulating "large cells", in which the doubling time is short, AADC and GRP are undetectable, granules are rare, and the cells are resistant to radiation. However, one cell line of the classic type has revealed reversible squamous cell change in the absence of retinoic acid, becoming radioresistant without showing any remarkable changes in AADC, NSE or CK-BB. Since SCLC mixed with "large cells" or "small cell carcinoma of undifferentiated type" is resistant to therapy and possesses a more epithelial nature, small cell carcinoma with a large cell component has been proposed as a subtype. The question of whether this subclassification is practical should be confirmed by prospective study.

Biomarkers, Tumor↗

Four new human germ cell tumor cell lines.

Four new human tumor cell lines, NCC-EC-1, NCC-EC-2, NCC-EC-3, and NCC-IT, were derived from different germ cell tumors established in vitro. On the basis of morphologic studies of cell cultures and nude mice xenografts, it was concluded that NCC-EC-1, and NCC-EC-2 cell lines are equivalent to developmentally nullipotent embryonal carcinoma; cell line NCC-EC-3 showed trophoblastic differentiation, whereas the NCC-IT cell line was composed of developmentally pluripotent cells capable of somatic and extraembryonic differentiation. Nude mouse-xenografts of NCC-IT contained foci of embryonal carcinoma, yolk sac tumor, immature somatic tissues, and trophoblastic giant cells indicating that this cell line is indeed developmentally pluripotent. We conclude that human embryonal carcinoma cell lines may be developmentally nullipotent, show restricted capacity for differentiation, or be developmentally pluripotent.

Animals↗

[Pathology of early lung cancer].

Lung cancer is divided into hilar and peripheral types by its site of origin, because of the difference in the structures between bronchi and bronchiolo-alveoli. Accordingly, the definition of early lung cancer differs depending upon the site of tumor origin. At present, however, there is no agreement as to the definition of early lung cancer of both types. Most early cancer of the hilar region are squamous cell type. Squamous cell carcinoma in situ should be differentiated from dysplasia with marked atypia. On the other hand, many early cancer of the peripheral type are adenocarcinoma. Atypical adenomatous hyperplasia or adenoma may necessitate differentiation from very well differentiated adenocarcinoma. Problems on the definition and differential diagnosis are discussed.

Carcinoma, Small Cell↗

Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung.

Nine lung small-cell carcinoma (SCC) cell lines and 9 lung non-SCC cell lines were examined for structural changes of the retinoblastoma (RB) gene as well as its expression using a complementary DNA probe. The RB protein product was investigated using an anti-RB antibody which we produced. Although homozygosity or hemizygosity of the RB gene was suggested in 8 of 9 SCCs and one of 2 large cell carcinomas (LCCs) by Southern blot analysis using an RB cDNA probe and polymorphic DNA markers for chromosome 13, no obvious structural changes of the RB gene were detected in these 18 cell lines. However, RB transcripts were either markedly reduced in quantity or abnormal in length in 3 of 9 SCCs. The specific 115 kD protein was not immunoprecipitated by the anti-RB antibody in all 9 SCCs with either normal or abnormal size RB mRNA. Three of 4 adenocarcinomas (AdCs), all 3 squamous cell carcinomas, and one of 2 LCCs expressed normal size RB mRNA, and the 115 kD protein was immunoprecipitated by the anti-RB antibody. The 115 kD protein was also absent in one of 2 LCCs with shortened RB mRNA and in one of 4 AdCs with low level of RB mRNA expression. These results strongly suggest that inactivation of the RB gene might be involved in the development of lung cancers, especially of SCCs.

Adenocarcinoma↗

Degree of malignancy of thymic epithelial tumors in terms of nuclear DNA content and nuclear area. An analysis of 39 cases.

For determination of the degree of malignancy among thymic epithelial tumors, the DNA content and area of nuclei in 13 cases each of noninvasive thymoma, invasive thymoma, and thymic carcinoma were investigated by cytofluorometry and morphometry. The nuclear DNA content was determined in terms of the mean nuclear DNA content, DNA histogram pattern, and the occurrence of the aneuploid stem cell line. The mean nuclear DNA content of the thymic carcinoma was significantly higher than that of both subgroups of thymoma (P less than 0.01), but there was no significant difference between noninvasive and invasive thymomas. The aneuploid stem cell line appeared in 92.3% of thymic carcinomas, one case (7.7%) of invasive thymomas, and none of noninvasive thymomas. Abnormal DNA histogram patterns were seen in 53.8% of thymic carcinomas and none of the thymomas. The mean nuclear area increased significantly in the increasing order of noninvasive thymoma, invasive thymoma, and thymic carcinoma (P less than 0.01). The cytofluorometric and morphometric results demonstrated a significant difference in degree of malignancy between thymic carcinoma and thymoma; however, there was a trend toward an increasing degree of malignancy from noninvasive to invasive thymomas, yet there was a sizeable overlap in results between the two groups. Therefore, these two methods are not satisfactory for predicting the behavior of an individual case of noninvasive or invasive thymoma.

Adult↗