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Biomedical subjects

T Nagasaka

Publications and source records attributed to T Nagasaka.

At least 55 records · Page 3Linked to original sources

Imbalance between neutral endopeptidase 24.11 and endothelin-1 expression in human endometrial carcinoma.

OBJECTIVES: Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that degrades various bioactive peptides including endothelin-1 (ET-1). This enzyme is known to play a role in maintaining ET-1-regulated vascular homeostasis in the normal human endometrium. The purpose of the present study was to investigate the expression and localization of NEP and ET-1 in neoplastic endometria, and also to clarify the correlation of their expression with the tumor grade of endometrial carcinoma. METHODS: Immunohistochemical analysis for NEP and ET-1 expression was performed on paraffin-embedded tissue sections of 7 normal endometria (after menopause), 5 atypical endometrial hyperplasias (AEH), and 32 endometrial endometrioid adenocarcinomas. RESULTS: In normal endometrium and AEH, NEP immunoreactivity was detected in stromal cells, but not in glandular cells. In contrast, ET-1 immunoreactivity was detected in both glandular and stromal cells. In the stromal cells of grade 1 endometrial adenocarcinoma, NEP was detected at high or moderate quantities. However, significantly decreased NEP immunoreactivity was observed in the stromal cells of grade 2 and 3 adenocarcinomas. However, NEP was not immunostained in adenocarcinoma cells except for the lesions of squamous differentiation. ET-1 immunoreactivity was weakly detected in the stromal cells of grade 1 adenocarcinoma, but the intensity of ET-1 staining increased with advancing tumor grade. The ratio of the staining scores of stromal ET-1 to stromal NEP was positively correlated with the tumor grade. CONCLUSIONS: These findings demonstrate that NEP expression in the stromal cells of endometrial adenocarcinoma is downregulated, while stromal ET-1 is upregulated, with increasing tumor grade. The present findings also suggest that NEP may play a role in the regulation of neoplastic transformation, tumor progression, and differentiation in endometrial neoplasms, possibly by degrading certain peptide growth factors such as ET-1.

Adult↗

Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors.

An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-beta, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures.

Adult↗

Recurrence of a neurenteric cyst with malignant transformation in the foramen magnum after total resection. Case report.

A 53-year-old man presented with recurrence of a neurenteric cyst with malignant transformation in the foramen magnum 3.5 years after total resection of the original tumor had been reported. For 2 years following the initial surgery, the patient had been in good condition, but then underwent ventriculoperitoneal shunt placement for intracranial hypertension. At the time there was no evidence of recurrence of the tumor on magnetic resonance (MR) images. One and one-half years later, he presented with headache and anorexia. A massive recurrent tumor was identified on MR images. The tumor was severely adhesive to the brainstem, cranial nerves, and vessels, allowing only partial resection. Histological examination of tumor specimens obtained during the first and second craniotomies indicated a malignant change from a typical neurenteric cyst with a one-layer epithelium in the first specimen to an adenocarcinoma with papillary proliferation in the second. The results of various immunohistochemical studies of the first specimen were typical of those of a neurenteric cyst. The second specimen displayed stronger staining of carbohydrate 19-9 and carcinoembryonic antigens than the initial specimen. The percentage of Ki-67 antigen (MIB-1)-positive cells increased from 0% in the first specimen to 6.7% in the second. To the authors' knowledge this is the first case in which malignant transformation has been demonstrated after total resection of a neurenteric cyst in the foramen magnum.

Adenocarcinoma, Papillary↗

Squamous cell carcinoma of the vulva and adjacent lesions treated at Nagoya University Hospital from 1965 to 1997.

Japan has a lower incidence of vulvar squamous cell carcinoma (VSCC) than Western nations. To pin-point the reasons for this, we reviewed biopsy samples from all cases treated at Nagoya University Hospital over the past 33 years in order to investigate the background lesions for VSCC. Two of 36 VSCC patients had adjacent or coexisting lichen sclerosus (LS), 5 had squamous cell hyperplasia (SCH), and 16 had vulvar intraepithelial neoplasia (VIN). There were 8 cases in which these lesions were thought to be the origin of the VSCC, 1 in which keratinizing squamous cell carcinoma (KSC) was seen in LS, 1 in which verrucous SCH was the origin, and 6 in which 4 basaloid carcinoma and 2 warty carcinoma developed from basaloid VIN and warty VIN, respectively. Although 8 other cases of keratinizing or non-keratinizing squamous cell carcinomas (NSC) coexisted with VIN NOS (not otherwise specified), differentiated VIN or basaloid VIN, we could not be histologically certain of the origin. Among 22 VSCC patients tested for HPV DNA, only an 84-year-old woman presenting a histological feature of KSC tested positive by in situ hybridization (ISH). It was considered that LS and SCH had little and VIN considerable capacity to cause the malignancy of VSCC. We surmise that in Japan the majority of squamous cell carcinoma is unrelated to HPV. One reason for the low incidence of VSCC is largely due to race; the homogeneous, monoethnic Japanese population, as well as the few cases of HPV-related VSCC.

Adult↗

Neuroendocrine-like differentiation in patients with pancreatic carcinoma.

BACKGROUND: The accurate estimation of the rate and the clinicopathologic significance of neuroendocrine-like differentiation (NED) in patients with pancreatic carcinoma have not been studied in detail. METHODS: Forty-four patients with pancreatic carcinoma who underwent surgical resection at the Department of Surgery II, Nagoya University Hospital, were included in this study. For immunostaining, antibodies against neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA) were used at given dilutions. At least two positive results with antibodies were considered as NED. Statistical analysis was performed by chi-square and Spearman rank correlation tests for group differences. Survival rates were calculated by the Kaplan-Meier method, and statistical significance was examined using the log rank test. Prognostic factors were tested by univariate and multivariate analyses (proportional hazards regression model). P < 0.05 was considered statistically significant. RESULTS: Of 44 patients examined, 20 showed NED. The distribution of patients with positive or negative NED in terms of age, tumor differentiation, tumor size, and the extent of tumor or lymph node metastasis showed no significant difference. The cumulative survival rates of patient groups according to NED status were then calculated, and NED positive patients showed a significantly better survival rate (P < 0.05). Univariate and multivariate analyses of those factors showed that only NED status and TNM stage were significantly related to overall survival. CONCLUSIONS: The current study suggests the significance of NED status in determining the outcome of patients with pancreatic adenocarcinoma, giving solid evidence to encourage further studies on the differentiation and origin of tumor cells in the pancreas.

Adult↗

Syndecan-4 deficiency impairs the fetal vessels in the placental labyrinth.

Syndecan-4 is a transmembrane protein bearing heparan sulfate chains, involved in anticoagulation and focal adhesion formation. Here, we revealed that syndecan-4 was expressed in the fetal vessels in the placental labyrinth by in situ hybridization and immunohistochemical staining. At 17.5 gestational days, the area of degenerated fetal vessels in the placental labyrinth was more diffuse and larger in Synd4(-/-) embryos than wild-type controls. Calcium and fibrin(ogen) depositions in the degenerated vessels were also more extensive and more severe in the placentas of Synd4(-/-) embryos. These findings suggest that syndecan-4 deficiency impairs the fetal vessels in the placenta, probably due to a deficit in the anticoagulation mechanism. This article is the first report demonstrating that among a large number of core proteins of heparan sulfate proteoglycans, a defect of a single core protein caused impaired anticoagulation in a specific site.

Animals↗

Clinicopathological study of oligodendroglial tumors: the effectiveness of interferon beta, ACNU/MCNU, and radiation (IAR/IMR) for anaplastic tumors.

The retrospective clinicopathological characteristics of oligodendroglial tumors were investigated in patients who underwent surgery, radiotherapy, and/or chemotherapy. Regarding oligodendroglioma and oligoastrocytoma without malignancy, patients who had undergone radiation therapy at a total dose of 40-50Gy had relatively long postoperative survival. Of these 15 patients, 6 showed signs of recurrence, and after additional treatment, 5 patients are still alive. On the other hand, regarding anaplastic oligodendroglial tumors, patients with anaplastic oligoastrocytoma responded well to combination chemotherapy with interferon beta, nitrosourea derivatives (ACNU/ MCNU), and radiation therapy (referred to as IAR/IMR) and survived longer than patients with anaplastic oligodendroglioma. In conclusion, patients with oligodendroglial tumors could survive longer by treatment involving surgery and radiotherapy. As for malignancy, cases of anaplastic oligoastrocytoma could be effectively treated by adjuvant therapy using IAR/IMR after surgery, but in cases of anaplastic oligodendroglioma, the response to IAR/IMR was not good, and another strategy of treatment should be recommended.

Adolescent↗

Role of ultrasonography in the detection of intraductal spread of breast cancer: correlation with pathologic findings, mammography and MR imaging.

The purpose of this study was to assess the role of US in the detection of intraductal spread of breast cancer in comparison with mammography (MMG) and MRI. In 46 patients with breast cancer, US features of the intraductal component were classified as ductal type or distorted type. Histopathologically, 29 of 46 (63%) cases had intraductal components, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 89, 76, and 85%, respectively. Each US pattern demonstrated good correspondence to the histologic components, and the distorted type correlated well with comedo-type carcinoma. Mammography was performed in all cases, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 55, 100, and 72%, respectively. In comedo type, MMG could diagnose the extent of intraductal spread more accurately compared with US examination. Magnetic resonance imaging comparison was available in 25 cases. Magnetic resonance imaging depicted intraductal extension as an enhanced area during the early phase of a contrast enhancement study with a sensitivity of 93%. Ultrasound and MRI were closely related in terms of morphologic characteristics: the ductal type of US image correlated well with linear enhancement on MRI, whereas the distorted type correlated with regional or segmental enhancement. Current US examination is useful in depicting the intraductal spread of breast cancer; however, US has a tendency to underestimate intraductal component of comedo type compared with MMG and MRI.

Breast↗

Initial and maintenance combination treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy for patients with previously untreated malignant glioma.

Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.

Adolescent↗

Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies by double filtration plasmapheresis.

Successful clinical ABO-incompatible renal transplantation has been achieved by the removal of anti-A or anti-B antibodies using double filtration plasmapheresis (DFPP). We have compared changes in the levels of anti-donor antibodies and the histopathology of the renal grafts following human ABO-incompatible allotransplantation and pig-to-baboon xenotransplantation using pretransplant DFPP. DFPP was performed on days 6, -4, -2 and -1 before the ABO-incompatible transplants (n=25) and on days -2 and 0 (immediately before reperfusion) in the xenotransplants (n=4). In two baboons (XenoTx Group I) the extent of antibody removal was comparable to that in the ABO-incompatible patients, and an even greater level of removal was achieved in another two baboons (XenoTx Group II). Anti-A and anti-B and anti-pig IgM and IgG antibodies were measured by flow cytometry. All clinical ABO-incompatible renal grafts are functioning, except two which were lost from recurrence of the original disease or from chronic rejection. Three other grafts underwent humoral rejection episodes, which were successfully treated. DFPP reduced the mean anti-A/B IgM and IgG antibody levels to 8% and 13% of pretreatment levels, respectively. After kidney transplantation, they were maintained at 37% and 46% of pre-DFPP level. No antibody binding to the transplanted kidney was detected at any time (1 h to 2 yr) after ABO-incompatible allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody removal (90%) prevented hyperacute rejection, but the two grafts were rejected on days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II, the additional DFPP that was required to deplete the remaining 10% of anti-pig antibody was poorly tolerated and the two baboons died 4 h and 2 days, respectively, after renal transplantation. Although anti-pig IgM antibodies were reduced to 2% of pre-treatment level, IgM and C3 binding were detected in the graft as early as 1 h posttransplantation. These data suggest that the concentration of xeno-antigen epitopes expressed on pig organs may need to be reduced by genetic engineering to the much lower level of blood group A/B antigens on human kidneys if discordant xenotransplantation is to be successful.

ABO Blood-Group System↗