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Seiichi Tamai

Publications and source records attributed to Seiichi Tamai.

15 recordsLinked to original sources

Significance of lymphatic invasion on regional lymph node metastasis in early gastric cancer using LYVE-1 immunohistochemical analysis.

It has been reported that lymphatic invasion is a predictor for lymph node metastasis in early gastric cancer (EGC); however, it has been impossible to differentiate between lymphatic invasion and blood vessel invasion using current staining techniques. We studied the significance of lymphatic invasion on regional lymph node metastasis in EGC by using human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) antibody, specific to lymphatic vessels, and von Willebrand factor (vWF) antibody, specific to the blood vessels, to clearly distinguish these vascular tissues.EGC tissues were obtained from 66 node-positive and 66 node-negative subjects and were matched by age and sex. These tissues were immunostained with antibodies against LYVE-1 and vWF. Multivariate logistic regression analysis demonstrated that lymphatic invasion was a significant independent predictor for regional lymph node metastasis (odds ratio, 4.667; P = .0094), whereas blood vessel invasion was not. Thus, lymphatic invasion identified by LYVE-1 antibody could predict the existence of regional lymph node metastasis in EGC.

Biomarkers, Tumor↗

Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging.

OBJECTIVES: We sought to elucidate the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques. BACKGROUND: Regression of thoracic aortic plaques by simvastatin was demonstrated using magnetic resonance imaging (MRI). However, the effects of different doses of statin have not been assessed. METHODS: Using MRI, we investigated the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques in 40 hypercholesterolemic patients who were randomized to receive either dose. Treatment effects were evaluated as changes in vessel wall thickness (VWT) and vessel wall area (VWA) of atherosclerotic lesions from baseline to 12 months of treatment. RESULTS: The 20-mg dose induced a greater low-density lipoprotein (LDL) cholesterol reduction than did the 5-mg dose (-47% vs. -34%, p < 0.001). Although 20 mg and 5 mg reduced C-reactive protein (CRP) levels (-47% and -28%), the degree of CRP reduction did not differ between the two doses. The 20-mg dose reduced VWT and VWA of thoracic aortic plaques (-12% and -18%, p < 0.001), whereas 5 mg did not (+1% and +4%). Regarding abdominal aortic plaques, even 20 mg could not reduce VWT or VWA (-1% and +3%), but instead progression was observed with 5-mg treatment (+5% and +12%, p < 0.01). Notably, the degree of plaque regression in thoracic aorta correlated with LDL cholesterol (r = 0.64) and CRP (r = 0.49) reductions. Although changes in abdominal aortic plaques only weakly correlated with LDL cholesterol reduction (r = 0.34), they correlated with age (r = 0.41). CONCLUSIONS: One-year 20-mg atorvastatin treatment induced regression of thoracic aortic plaques with marked LDL cholesterol reduction, whereas it resulted in only retardation of plaque progression in abdominal aorta. Thoracic and abdominal aortic plaques may have different susceptibilities to lipid lowering.

Aged↗

Associations of plasma C-reactive protein levels with the presence and extent of coronary stenosis in patients with stable coronary artery disease.

Prospective studies showed plasma high sensitivity C-reactive protein (hsCRP) levels to be a powerful predictor of cardiac events. However, the association between hsCRP levels and the extent of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. We investigated the association between hsCRP levels and the extent of coronary stenosis in 273 patients undergoing elective coronary angiography. Plasma hsCRP levels were higher in patients with CAD than in those without CAD (0.70 mg/l versus 0.56 mg/l, P < 0.02), but hsCRP levels did not correlate with the number of >50% stenotic vessels and were not a significant factor for CAD. However, after the exclusion of 76 patients taking statins, a step-wise increase in hsCRP levels was found depending on the number of >50% stenotic vessels: 0.50 in CAD(-), 0.68 in 1-vessel, 0.77 in 2-vessel, and 0.88 mg/l in 3-vessel disease (P < 0.01). The hsCRP levels also correlated with the numbers of >50% and >25% stenotic segments (r = 0.30 and 0.32, P < 0.001). Multivariate analysis revealed the hsCRP levels to be a significant factor for CAD. Thus, after the exclusion of patients with statins, plasma hsCRP levels were found to be associated with the presence and extent of coronary stenosis in patients with stable CAD.

Aged↗

Prognostic implication of laminin-5 gamma 2 chain expression in the invasive front of colorectal cancers, disclosed by area-specific four-point tissue microarrays.

The laminin-5 gamma 2 chain (LN-5gamma2) is known to be a marker of invasion in several cancer types. Our purpose was to examine the prognostic significance of LN-5gamma2 expression in different areas of individual colorectal cancers (CRCs) by using tissue microarrays (TMAs), and to clarify the optimal areas for prognostic assessment. Using formalin-fixed paraffin-embedded tissue blocks of pT3 primary CRCs resected from 120 patients, we constructed TMA blocks of tissue core specimens taken from the submucosal invasive front, subserosal invasive front, central area, and rolled edge of each tumor. Using these four-point TMA sets, cytoplasmic LN-5gamma2 expression was immunohistochemically surveyed, and the area-specific prognostic significance of LN-5gamma2 expression was evaluated. The data revealed that 35, 30, 15 and 10% of the 120 CRCs showed high-grade LN-5gamma2 expression in the submucosal invasive front, subserosal invasive front, central area and rolled edge, respectively. Disease-specific survival curves for the groups with high- and low-grade LN-5gamma2 in the submucosal invasive front and subserosal invasive front were different significantly or of marginal difference (respective 5-year survival rates: 54 and 78% for submucosal invasive front (P=0.030) and 58 and 75% for subserosal invasive front (P=0.055)). Multivariate analysis revealed that the grades of LN-5gamma2 expression in submucosal invasive front (hazard ratio=2.0, P=0.047) and subserosal invasive front (hazard ratio=2.9, P=0.0033) were independent prognostic factors. In contrast, the grades of LN-5gamma2 expression in the central area and rolled edge did not have a significant impact on patient prognosis. Analysis using area-specific four-point TMAs clearly demonstrated that LN-5gamma2 expression in the invasive front largely influences the degree of clinical aggressiveness of CRC and its tendency to metastasize.

Aged↗

Green tea consumption and serum malondialdehyde-modified LDL concentrations in healthy subjects.

OBJECTIVE: Green tea was shown to inhibit LDL oxidation, platelet aggregation, and matrix metalloproteinases (MMPs) activities in vitro. We tried to elucidate whether or not green tea consumption may have these effects in vivo, which may be protective against atherosclerotic disease. METHODS: We measured serum malondialdehyde-modified LDL (MDA-LDL) concentrations and urine 8-epi-prostaglandin (PG) F(2alpha) in 22 healthy male nonsmokers. They drank 7 cups/day of water for 2 weeks and drank 7 cups/day of green tea for the next 2 weeks. Regarding platelet aggregation, plasma thromboxane B(2) (TXB(2)) and 6-keto-PGF(1alpha) concentrations and ex vivo platelet aggregation were evaluated. Plasma MMP-2 and -9 concentrations were also measured. RESULTS: Of the 22 subjects, 20 had been in the habit of drinking green tea before the study. Plasma catechins concentrations significantly decreased at the end of the water period and then increased at the end of the green tea period. Although no change in plasma LDL-cholesterol concentrations (110 +/- 33 vs. 113 +/- 28 mg/dL, p = NS) was found, MDA-LDL concentrations (84 +/- 45 vs. 76 +/- 40 IU/L, p < 0.05) and the ratio of MDA-LDL/LDL-cholesterol (0.74 +/- 0.21 vs. 0.65 +/- 0.20, p < 0.02) significantly decreased at the end of the green tea period. However, no significant changes were observed in urine 8-epi-PGF(2alpha) concentrations, in platelet aggregation, nor in plasma TXB(2), 6-keto-PGF(1alpha) or MMP concentrations. CONCLUSION: Daily consumption of green tea decreased serum MDA-LDL concentrations, but it had no significant effects on platelet aggregation, platelet TX production or plasma MMPs concentrations. Our results suggest that green tea consumption may inhibit LDL oxidation in vivo.

Adult↗

Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation.

Although KIT and EGFR overexpressions are reported to occur in breast cancer, their pathological significance is still unclear. We examined KIT, EGFR, and c-erbB-2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and/or myoepithelial immunophenotype of primary tumors. To facilitate the analysis, we constructed a tissue microarray comprising 2-mm diameter tissues cored from the representative tissue block of each tumor. KIT, EGFR, and c-erbB-2 overexpressions were detected in 15 (10%), 12 (8%), and 23 (15%), respectively. The KIT was more frequent in the group comprising comedo-type ductal carcinoma in situ and invasive ductal carcinomas (IDCs) of the solid-tubular subtype than in the group of other histological types (P=0.027), and the EGFR was more frequent in IDCs of solid-tubular type than in other histological types (P <0.05). KIT and EGFR overexpressions were correlated with nuclear grade 3 (P=0.0095 and 0.0005) and tended to be concurrent (P=0.005). KIT overexpression was correlated with vimentin and S-100 expression (P=0.003 and P=0.005), and EGFR overexpression was correlated with S100 expression (P=0.0001). These correlations with grade and mesenchymal/myoepithelial markers were not observed for c-erbB-2 overexpression. KIT and EGFR appeared to be indicators of high-grade breast carcinoma groups that often contain the carcinomas with mesenchymal and/or myoepithelial differentiation, which are distinct from the group with c-erbB-2 overexpression.

Biomarkers, Tumor↗

Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated-type breast carcinomas with 'stem-cell-like' features.

It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.

Biomarkers, Tumor↗

Bronchiolar expression of aquaporin-3 (AQP3) in rat lung and its dynamics in pulmonary oedema.

Aquaporins (AQPs) are water channel proteins that permit osmotically driven water movement. To determine their dynamics in pulmonary oedema, we examined the expression of mRNA and protein for AQP1, AQP3, AQP4, and AQP5 in the lungs of normal and thiourea-treated rats. In the thiourea group, lung water content increased significantly (vs. controls) with the peak at around 4 h. Semi-quantitative RT-PCR showed that AQP3 mRNA in the thiourea group rose significantly, peaking at around 4-8 h. The expression of AQP1, AQP4, AQP5, ENaC and CFTR mRNA each decreased significantly some time after the peak in lung water content. Immunoblot analysis showed that glycosylated AQP3 protein was increased 4-10 h after treatment. Expression of the other AQP proteins was not significantly altered, except for that of AQP4. Immunohistochemical examination revealed that AQP1 was expressed in endothelia, AQP3 in the basal cells of the large airways and in cuboidal cells in the bronchioles, AQP4 in the basolateral membrane of airway cells and AQP5 in type-I pneumocytes. Our results suggest that AQP3 is expressed not only in large airways, but also in bronchioles, and is related to water movement in pulmonary oedema.

Animals↗

Adenolipoma of the thyroid gland: report of a case.

We report a case of adenolipoma of the thyroid gland, which is very unusual because thyroid adenoma rarely contains mature adipose tissue. A 55-year-old Japanese woman presented with a 1-month history of a neck mass. A blinded fine-needle aspiration biopsy showed benign follicular cells with no adipose cells, and we performed a left hemithyroidectomy. The specimen measured 7.0 x 4.4 cm and weighed 59.9 g. The cut surface of the tumor revealed a solid yellowish mass, and hematoxylin-eosin staining showed that the solid tumor was well separated from the adjacent thyroid tissue by a thin fibrous capsule. The tumor was found to be follicular adenoma composed of epithelial cells arranged in monotonous microfollicular patterns, intermingled with mature adipose tissue. No adipose tissue was found outside the tumor, and there were no signs of amyloid deposits in the tumor or adjacent thyroid tissue. The pathological diagnosis was adenolipoma of the thyroid gland. We discuss the pathogenesis of this entity and review the previously documented cases.

Adipose Tissue↗

Biotin-rich, optically clear nuclei express estrogen receptor-beta: tumors with morules may develop under the influence of estrogen and aberrant beta-catenin expression.

Recent studies have indicated that aberrant beta-catenin expression may be a common denominator for the morular formation of tumors from various anatomic sites. The evidence for the influence of female sex hormones in the formation of morules has been circumstantial, most previous studies having failed to demonstrate female sex hormone receptors in the morular cells. We investigated a possible role of estrogen receptor (ER)-beta in the occurrence of tumors that form morules with biotin-rich optically clear nuclei (BROCN)(BROCN-family tumors) and its possible relationship with aberrant nuclear/cytoplasmic (N/C) beta-catenin expression. We immunostained 14 BROCN-family tumors, including 6 low-grade adenocarcinomas of the fetal lung type, 3 papillary thyroid carcinomas of cribriform-morular variant (CMV), 2 ovarian endometrioid tumors, 2 colonic adenocarcinomas, and 1 gallbladder adenoma, as well as 4 cases of endometrial tissue with BROCN during gestation, for ERbeta, ERalpha, progesterone receptor (PgR), beta-catenin, and, on a subset of cases, c-Fos and MIB-1 as well. BROCN in all 18 cases expressed ERbeta but not ERalpha or PgR. In the BROCN-family tumors, the morular cells and budding glandular cells expressed ERbeta in the cytoplasm and BROCN, which overlapped with the N/C expression pattern of beta-catenin. Beta-catenin showed only membranous expression in the endometrial glands during gestation. In CMV and ovarian endometrioid tumors, nuclear expression of ERalpha and PgR were observed in association with N/C beta-catenin expression only in the glandular component. C-Fos was also constantly and strongly expressed in BROCN in all cases examined. The MIB-1 labeling index was low in the morular area, ranging from 1% to 3%. The present study indicates that N/C co-localization of ERbeta and beta-catenin is a feature common to the morules with BROCN that appear in the BROCN-family tumors from various anatomic sites. Whether the estrogen-signaling pathway and the Wnt-signaling pathway have crosstalk, cooperating in the development of the BROCN-family tumors, awaits further study.

Adult↗

The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma.

OBJECTIVES: Recent studies have shown that some growth factor receptors with tyrosine kinase activity, eg, the epidermal growth factor receptor (EGFr) and the c-erbB-2 (HER-2) oncoprotein, are associated with aggressive biologic behavior of various cancer cell types. We examined the clinicopathological significance of the expression and localization of EGFr and HER-2 in both invasive and intraductal components of ductal adenocarcinomas of the pancreas. METHODS: Tissue samples from 76 archival cases of pancreatic ductal adenocarcinoma were immunohistochemically analyzed for both membrane and cytoplasmic overexpression of EGFr and HER-2 oncoprotein. The rate of incidence between the invasive and intraductal components was analyzed and then their correlation with tumor differentiation and patient prognosis was analyzed. RESULTS: Cytoplasmic EGFr overexpression was more frequent in invasive components (47 of 76, 62%) than in intraductal components (19 of 76, 25%), while membrane EGFr overexpression was more frequent in intraductal components (41 of 76, 54%) than in invasive components (11 of 76, 14%). The membrane HER-2 overexpression was also more frequent in intraductal components (15 of 76, 20%) than in invasive components (2 of 76, 3%), but the incidence of cytoplasmic HER-2 overexpression did not differ between intraductal components (12 of 76, 16%) and invasive components (8 of 76, 11%). The cytoplasmic EGFr overexpression in invasive components was more frequent in grade 3 group (32 of 33, 97%) than in grade 2 (15 of 32, 47%) and grade 1 groups (0 of 10, 0%) (P < 0.001). Patients with adenocarcinoma with cytoplasmic EGFr overexpression showed shorter overall survival than those with adenocarcinoma without cytoplasmic EGFr overexpression (P = 0.02). CONCLUSION: It is suggested that the cytoplasmic overexpression of EGFr plays a significant role in the progression of pancreatic ductal adenocarcinoma, especially in the invasion and acquisition of aggressive clinical behavior. Both membrane and cytoplasmic expression of HER-2 showed no significant correlation between tumor differentiation and poor survival.

Aged↗

Feasibility and cost-effectiveness of sentinel lymph node radiolocalization in stage N0 head and neck cancer.

OBJECTIVES: To determine the feasibility of sentinal lymph node (SN) radiolocalization and to assess the cost-effectiveness of the SN navigation surgery strategy in patients with stage N0 squamous cell carcinoma (SCC) of the head and neck. Patients Eleven consecutive patients with stage N0 SCC of the head and neck. METHODS: Head and neck lymphoscintigraphy was performed 2 hours after the injection of technetium Tc 99m tin colloid or phytate. A handheld gamma probe was used to detect the SN before and directly after making a skin incision. Nodes were evaluated histopathologically for micrometastasis. To determine the expected cost savings, a decision tree sensitivity analysis was designed based on the 2 competing strategies: ipsilateral neck dissection vs SN navigation surgery. The costs referred to billed costs based on the Japanese national insurance reimbursement system. RESULTS: The sensitivity of SN navigation surgery in our series was 100% (11/11) on a patient-by-patient basis and 94% (17/18) on a node-by-node basis. Micrometastasis was found in 36% (4/11). Assuming the micrometastasis prevalence, sensitivity, and specificity of navigation surgery for detecting SN to be 30%, 90%, and 100%, respectively, the decision tree sensitivity analysis showed that introduction of SN navigation surgery in place of ipsilateral neck dissection would yield cost savings of $1218 (US) per stage N0 patient in Japan and avoid 7 surgical deaths per 1000 patients who are supposed to undergo neck dissection in the neck dissection strategy. Break-even point analysis for the SN navigation surgery strategy showed that the threshold value required more than 41 patients for the savings to begin to accrue. CONCLUSION: Our results indicate that SN navigation surgery using radiolocalization is feasible and cost-effective, based on decision tree sensitivity analysis, in patients with stage N0 SCC of the head and neck.

Adult↗