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Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 19 recordsLinked to original sources
PubMed1992

Proliferative activity of cutaneous melanocytic neoplasms defined by a proliferating cell nuclear antigen labelling index.

To evaluate the proliferative activity of benign, borderline and malignant cutaneous melanocytic neoplasms, 30 cases of malignant melanoma (MM) and 41 cases of naevi were studied by immunostaining using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). PCNA is a nuclear antigen expressed in the late G1 and S phase and serves as a marker of proliferating cells. Invasive MM and MM in situ showed much higher PCNA positivity rates than melanocytic naevi (invasive MM, 18.0%; MM in situ, 11.3%; ordinary melanocytic naevi, 2.6%). The PCNA positivity rate did not increase significantly with the thickness of MM. Among ordinary melanocytic naevi, junctional naevi had a higher PCNA positivity rate than compound or intradermal naevi. Mean PCNA positivity rates for Spitz's naevi and sporadic dysplastic naevi were within the range for ordinary melanocytic naevi, indicating the benign nature of both types of naevus. Contrary to some previous studies, MM in situ showed high proliferative activity, indicating that cells of MM in situ are actively proliferating. This study clearly demonstrates that MM and various types of naevi can be separated according to differences in proliferative activity defined by the PCNA labeling index.

Antibodies, Monoclonal↗
PubMed1992

Malignant pleural mesothelioma producing human chorionic gonadotropin. Report of two cases.

Two cases of malignant pleural tumor producing human chorionic gonadotropin, one confirmed at surgery and autopsy and the other by biopsy, are reported. Both of the patients had bilateral gynecomastia with high levels of serum human chorionic gonadotropin. The first patient underwent panpleuropneumonectomy because of diffuse malignant pleural tumor, but died five months later due to recurrent disease. The histological diagnosis was diffuse, malignant, monophasic mesothelioma of the epithelial type. Immunostaining for alpha-, beta-human chorionic gonadotropin and human placental lactogen was positive in syncytiotrophoblast-like cells. The second patient had diffuse pleural tumor with massive effusion. A pleural biopsy specimen showed diffuse proliferation of epithelioid large cells. Immunostaining for alpha, beta-human chorionic gonadotropin and human placental lactogen was positive in mono- and multinucleated bizarre giant cells mimicking trophoblasts. A diagnosis of malignant mesothelioma with trophoblastic differentiation seemed most likely in both cases in view of the clinical and pathological findings. In both cases, results of mucin histochemistry and various immunohistochemical stains for antigens or with antibodies were consistent with diagnosis of mesothelioma except in a few cells in the choriocarcinomatous portion. This may be the first report describing human chorionic gonadotropin-producing malignant mesotheliomas of the pleura.

Adult↗
PubMed1992

Detection of Epstein-Barr virus DNA in a Japanese case of lymphoepithelioma-like thymic carcinoma.

Epstein-Barr virus DNA was detected in a case of lymphoepithelioma-like thymic carcinoma. A homogeneous terminal structure of the viral DNA was demonstrated in this case, indicating the presence of the viral genome in clonally expanded tumor cells. Since all of 26 other thymic epithelial tumors (eight non-invasive, 13 invasive thymomas and four non-lymphoepithelioma-like thymic carcinomas) in Japanese were negative by polymerase chain reaction, it is suggested that lymphoepithelioma-like thymic carcinoma may represent a unique pathological entity distinct from Epstein-Barr virus-negative thymic epithelial tumors, which are in the majority in Japan.

Carcinoma, Squamous Cell↗
PubMed1992

Adenocarcinoma of the lung with selective metastasis to the lung: clinical, histologic and DNA-cytofluorometric analyses.

In order to examine selective lung metastasis in lung adenocarcinoma, 7 patients who had died due to metastasis exclusively to the lung were analyzed. Because all of the tumors had been well differentiated adenocarcinoma, 21 cases of well differentiated adenocarcinoma which had metastasized to both the lung and other distant organs were selected as controls. Histologically, 6 of the 7 study cases were bronchiolo-alveolar carcinoma (BAC) of variable cytological type or papillary adenocarcinoma with a thin fibrovascular stroma without apparent destruction of the alveolar wall. There was no difference in clinical findings or nuclear DNA content (NDC) between the BAC and papillary adenocarcinoma with thin fibrovascular stroma. The fibrovascular stroma in the study cases was significantly thinner than that in the control cases (P less than 0.01). Cytofluorometrically, the study cases had a significantly lower and less abnormal NDC than the control cases in terms of the mean NDC and DNA histogram patterns (P less than 0.01 and P less than 0.05, respectively). On the basis of these findings, we conclude that 1) BAC can be classified within the same spectrum as well differentiated papillary adenocarcinoma, and 2) selective lung metastasis occurs in well differentiated adenocarcinomas showing mild NDC abnormalities and having a thin fibrovascular stroma without apparent destruction of the alveolar wall.

Adenocarcinoma↗
PubMed1992

Clinicopathological significance of nuclear accumulation of tumor suppressor gene p53 product in primary lung cancer.

Since the nuclear accumulation of p53 protein is known to correspond well with mutation of the p53 tumor suppressor gene, the authors examined 88 primary lung cancer specimens immunohistochemically using anti-p53 mouse monoclonal antibody, pAb1801, and analyzed the relationship between the immunohistochemical results and clinicopathological features. Nuclear localization of p53 protein was found in 43/88 (49%) tumor specimens, but not in the corresponding normal lung tissues. The percentage of cases showing nuclear p53 localization varied according to the histological type. In squamous cell carcinoma, nuclear p53 localization was found in 15/26 (57%), appearing more frequently than in other histologic types. However, no obvious correlation was observed between nuclear p53 localization and patients' age, sex, history of smoking, TNM factor, degree of differentiation, or any other clinicopathological features analyzed. In adenocarcinoma, nuclear p53 localization was found in 20/46 (43%). Incidence of positive cases was significantly correlated with regional lymph node metastasis, distant metastasis, and pathological stage (P less than 0.05). These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1992

Sebaceous gland and sweat gland carcinomas of the skin. Clinicopathological study and significance of c-erbB-2 oncoprotein expression.

Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined to elucidate any important histological parameters influencing their prognosis, and the relationship between immunohistochemical expressions of c-erbB-2 oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis, and without lymphoid cell infiltration in tumor nests and stroma had a higher incidence of tumor recurrence and tumor-related death than tumors with vacuolated cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland carcinomas of all cases with fatal outcomes demonstrated tubular differentiation in 20% or less of whole tumor area, lymphatic permeation and desmoplastic reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were positive for c-erbB-2 oncoprotein. Two of three sebaceous gland carcinomas, and all three sweat gland carcinomas developed tumor recurrence and ended in tumor-related deaths. Sweat gland carcinomas with c-erbB-2 expression had significantly shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic permeation, and growth patterns of sweat gland carcinoma are considered to closely correlate to the prognosis. Immunohistochemically detected c-erbB-2 oncoprotein may be an indicator of bad prognosis.

Adolescent↗
PubMed1992

Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness.

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.

Adenocarcinoma↗
PubMed1992

Experience and present status of telepathology in the National Cancer Center Hospital, Tokyo.

The optical fiber high definition television (HDTV) live image system with a remote control microscope is an ideal telepathology system. Diagnostic accuracy with this system is high enough for pathology consultation. However, it is very expensive to set up. The integrated services digital network (ISDN)-HDTV still image system using public telephone lines presently available in Japan INS 64 (64 kb/s), is not suitable for frozen section diagnosis and diagnosing difficult lesions. However, it functions very well for cytology consultation. When INS 1500 (1.5 Mb/s) becomes available in practice, it can substitute the optical fiber-HDTV live image system in terms of cost and efficacy. Pathologists must become accustomed to making diagnosis from images on the monitor. They must be very careful in making diagnosis, when images are transmitted from institutions without pathologists, since selection error may occur at the time of frozen section and at the time of transmission of images.

Cancer Care Facilities↗
PubMed1992

Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma.

To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Allelic losses and mutations of the p53 gene were detected in 24 out of 25 informative cases (96%) and 23 out of 27 cases (85%) respectively. Simultaneous losses and mutations were detected in all 16 stage III-IV tumors, while these alterations were detected only in 3 of 6 stage I-II tumors. When allelic losses and/or mutations were detected in the primary tumors, the same alterations were always maintained in the process of metastasis. In three cases, identical p53 alterations were detected among different organ metastases. The mutations detected in five cell lines were also detected in the corresponding original tumors. These results suggest that the alterations of the p53 gene are common and early events, but probably not the first events, in the development of SCLC, and that these alterations are essential for the maintenance of malignant phenotypes in the progression of SCLC.

Base Sequence↗
PubMed1992

Immunohistochemical detection of cluster 1 small cell lung cancer antigen and chromogranin A in lung carcinomas.

Eighteen small cell lung cancers (SCLCs), 108 non-SCLCs (67 adenocarcinomas, 29 squamous cell carcinomas and 12 large cell carcinomas) were immunohistochemically examined for expressions of cluster 1 SCLC antigen/N-CAM and chromogranin A with monoclonal antibodies NCC-Lu-243 and anti-chromogranin A. The cell membranes of all the SCLCs and three of the 67 adenocarcinomas (4.5%) were stained for cluster 1 SCLC antigen/N-CAM. Eight of the 18 SCLCs (44.4%), and three of the 67 adenocarcinomas (4.5%) were stained for chromogranin A, but no squamous cell carcinoma or large cell carcinoma was stained for both antigens. Two of the three adenocarcinomas which expressed cluster 1 SCLC antigen/N-CAM had been suspected of being either SCLC or poorly-differentiated adenocarcinoma cytologically, and were resected after chemotherapy and radiotherapy. Histologically, they were poorly-differentiated adenocarcinoma with rosette-like tubules. The remaining one was moderately-differentiated papillary adenocarcinoma resembling bronchial surface epithelial cells without mucin (BSE type adenocarcinoma). The three adenocarcinomas which expressed chromogranin A were well- to moderately-differentiated BSE type adenocarcinomas, and stained tumor cells were distributed sparsely as neuroendocrine cells in the normal bronchial mucosa. One of them also expressed cluster 1 SCLC antigen/N-CAM. In the present study, we demonstrated the usefulness of NCC-Lu-243 in the immunohistochemical detection of adenocarcinomas with neuroendocrine features.

Antigens, Neoplasm↗
PubMed1991

Qualitative and quantitative changes of human tenascin expression in transformed lung fibroblast and lung tumor tissues: comparison with fibronectin.

Qualitative and quantitative alterations of human tenascin (TN) expression in virally transformed lung fibroblasts and in lung tumor tissues were investigated using S1 nuclease protection analysis in comparison with those of fibronectin (FN). Transformed fibroblasts and fetal lung tissues expressed more TN mRNA with an extra sequence encoding the sixth FN type III repeat than did normal cells and adult tissues. The splicing pattern of TN mRNA was also altered in many lung cancer tissues, showing increased or sometimes decreased expression of the TN mRNA with the extra sequence when compared with their surrounding normal tissues. These results provide additional evidence for the oncodevelopmental regulation of alternative RNA splicing in human lung tissues, first observed with FN mRNA (F. Oyama, et al., Cancer Res., 50: 1075-1078, 1990). Quantitative analysis of the levels of TN and FN mRNAs showed that the ratio of TN mRNA to FN mRNA was significantly increased in transformed fibroblasts and in some lung tumor tissues, when compared with their normal counterparts. Among different types of lung tumors, a significant increase of the TN/FN ratio was observed with most squamous cell carcinoma but with only a small fraction of adenocarcinoma. Since TN has been shown to inhibit cell adhesion to FN, the altered ratio of TN mRNA to FN mRNA may well affect the adhesive and migratory properties of tumor cells in lung cancer tissues.

Base Sequence↗
PubMed1991

Cytofluorometric analysis of metastases from lung adenocarcinoma with special reference to the difference between hematogenous and lymphatic metastases.

Metastatic tumors in the brain, liver, and regional lymph nodes (20 cases each) from patients with adenocarcinoma of the lung were examined by cytofluorometric analysis, and compared with the respective primary lung tumors. The nuclear DNA content of tumor cells was significantly increased in metastatic tumors in the brain and liver compared with the primary (P less than 0.01). However, the DNA content of metastatic tumors in regional lymph nodes was almost identical to that of the primary tumor in many instances. From the viewpoint of the nuclear DNA content of lung adenocarcinoma, blood-borne tumor cells in the brain and liver were considered likely to constitute a discrete tumor cell subpopulation, i.e., probably a more malignant one, different from the major subpopulation in the primary tumor, whereas lymphatic metastases in regional lymph nodes were similar to the primary. The subpopulation with an increased DNA content in hematogenous metastases were thought to have originated from a minor subpopulation in the primary tumor or to have developed at the metastatic site.

Adenocarcinoma↗
PubMed1991

In vitro and in vivo antitumor effects of murine monoclonal antibody NCC-ST-421 reacting with dimeric Le(a) (Le(a)/Le(a)) epitope.

A murine monoclonal antibody (MAb), NCC-ST-421 (IgG3), was raised by using a human gastric cancer xenograft St-4 as immunogen. Immunization was achieved by transferring immunocompetent normal BALB/c mouse spleen cells into BALB/c-nu/nu mice bearing St-4 tumors. Hybridomas were produced from spleen cells of the mice after rejection of the tumors and were screened for preferential reactivity with cancers on formalin-fixed paraffin sections, as described previously for establishment of MAb NCC-ST-439 (M. Watanabe et al., Jpn. J. Cancer Res., 76: 43-52, 1985). The immunobiological and immunochemical properties of the new MAb NCC-ST-421 are described here. The MAb is essentially directed to a structure with dimeric Le(a) (V4III4Fuc2Lc6Cer) epitope (Gal beta 1----3[Fuc alpha 1----4]GlcNAc beta 1----3Gal beta 1----3[Fuc alpha 1----4]GlcNAc beta 1----3Gal beta 1----4Glc beta 1----1 Cer). It cross-reacts with Le(a) but does not show any effect on Le(a)-positive RBC in vitro or on Le(a)-positive tissue loci in vivo. ST-421 strongly induced antibody-dependent cellular cytotoxicity using human peripheral blood leukocytes as effector cells with a variety of human tumor cells, using the short-term 51Cr release assay. It also showed striking complement-dependent cytotoxicity with a human complement source and was able to produce lysis of a variety of human cancer cell lines, supporting its observed ability to cause cytotoxic suppression of tumor growth in nude mice. In another series of experiments, i.p. injection of ST-421 completely inhibited growth of human tumor xenografts in nu/nu mice, and this inhibitory activity was closely dependent on expression of the dimeric Le(a) antigen on the cell surface. While Le(a) antigen was expressed in the kidneys of nu/nu mice, infusion of ST-421 in these mice did not cause histological change in kidney tissue. This finding suggests that the MAb does not damage normal cells or tissues which contain cross-reacting Le(a) antigen. These results demonstrate that ST-421 exerts a significant antitumor effect in vitro as well as in vivo, does not affect Le(a) antigen expressed on normal tissues, and therefore has potential application in therapy of certain types of human cancer which express the dimeric Le(a) antigen.

Animals↗
PubMed1991

Clinicopathologic characteristics of adenosquamous carcinoma of the lung.

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.

Adenocarcinoma↗
PubMed1991

The AMeX method: a multipurpose tissue-processing and paraffin-embedding method. III. Extraction and purification of RNA and application to slot-blot hybridization analysis.

RNA was extracted from tissues processed by a new fixation and paraffin-embedding method (the AMeX method) and examined by Northern blot analysis and slot-blot analysis. The RNA extraction method for AMeX-processed tissue sections after the deparaffinization step was the same as that for fresh materials. The total amount of cellular RNA extracted from AMeX-processed mouse liver tissue was slightly less than that extracted from fresh tissue. In tissues of malignant lymphoma, the total amount of cellular RNA extracted from 25 sections each 20 microns thick was about 1.6-1.8 micrograms/mm2, regardless of the histological subtype and period of storage. The extracted RNA was moderately degraded, and usually could not be used for Northern blot hybridization analysis. The intensity of ethidium bromide staining and the hybridization signals of RNA extracted from AMeX-processed tissues were usually reduced in comparison with RNA from fresh material, but specific signals could be detected by slot-blot hybridization analysis. We have demonstrated previously that the AMeX method preserves high-molecular-weight DNA and various antigens. Since the present study showed that information on mRNA can be obtained from AMeX-processed tissue, the versatility and usefulness of this method were further proven.

Animals↗
PubMed1991

The prognostic value of tumor-associated carbohydrate structures correlated with gene amplifications in human breast carcinomas.

The effects of cell surface sugar chains combined with certain gene amplifications of breast cancers on the prognosis of patients were studied and the relationships between the sugar chains of cancer cells and amplifications of the proto-oncogenes c-myc, int-2 and c-erb B-2, evaluated. One hundred and fifty three human breast carcinoma tissues were investigated by an immunohistochemical technique using the avidinbiotin-peroxidase method with 1 lectin (HPA; Helix Pomatia) and 4 monoclonal antibodies (B-72-3, St-439, anti-Tn and anti-T). The positive rates of HPA, St-439, B-72-3, anti-Tn and anti-T were 43 per cent (63/153), 52 per cent (80/153), 53 per cent (81/153), 64 per cent (98/153) and 89 per cent (136/153), respectively. Patients whose cancers had positive HPA staining were found to have a lower survival rate than those with negative HPA staining (p less than 0.05), whereas those whose cancers had positive St-439 staining showed a better prognosis than those with negative St-439 staining (p less than 0.01). The positive rate of HPA was related to the gene amplification of c-myc proto-oncogene (p less than 0.01), whereas the negative rate of St-439 was correlated with the gene amplification of c-erb B-2 (p less than 0.01). These data indicate the prognostic value of HPA and St-439 and also the relationships between the gene amplifications and carbohydrate structures in breast cancer cells.

Antibodies, Monoclonal↗
PubMed1991

Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma.

From a series of 320 heptocellular carcinoma (HCC) cases treated surgically, we selected small nodular lesions that had not destroyed the preexisting liver structure grossly. After excluding metastases and large regenerative nodules, 58 lesions from 41 cases were chosen. All the lesions were hypercellular. Among them, 33 lesions showing histologic features of very well-differentiated HCC (Edmondson grade I), that is, small hepatocytes with little cellular atypia but with structural atypia, such as a thin trabecular structure of acinar formation in some areas, were classified as early HCC (eHCC). In seven eHCCs, areas of overt carcinoma, classified as Edmondson grade II, were found in the background of Edmondson grade I carcinoma. The remaining 25 lesions lacked structural atypia and were classified as adenomatous hyperplasia (AH). Among the AHs, 10 nodules with a very focal abnormal structure were subclassified as atypical adenomatous hyperplasia (AAH). There was a tendency for the size and cellularity of the atypical lesions to increase in order from AH to AAH to eHCC. All nodules larger than 1.5 cm were eHCC. A degree of cellularity more than twice that of a regenerative nodular was suggested to be an indicator of HCC. All small nodular lesions were associated with chronic liver disease. These histologic observations appear to explain the stepwise development of overt HCC from very well-differentiated eHCC, and of eHCC from AH probably through AAH, at least in cases of HCC associated with chronic liver disease.

Adenoma↗