Search PubMed⌕ Search

Biomedical subjects

A Ochiai

Publications and source records attributed to A Ochiai.

At least 55 records · Page 3Linked to original sources
PubMed2000

Proliferative activity of intratumoral fibroblasts is closely correlated with lymph node and distant organ metastases of invasive ductal carcinoma of the breast.

Mitotic figures of fibroblasts are seen within invasive ductal carcinoma (IDC) of the breast. This suggests that the proliferative activity of fibroblasts may play an important role in IDC tumor progression. The purpose of this study was to examine whether the proliferative activity of fibroblasts can predict lymph node metastasis (LNM) or distant-organ metastasis (DOM) of IDCs. Two hundred four consecutive patients with IDC of the breast surgically treated at the National Cancer Center Hospital East constituted the basis of this study. Proliferative activity of fibroblasts was immunohistochemically evaluated by the mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index was the percentage of fibroblasts with positively stained nuclei, and fields for cell counting were selected in inner and outer areas within IDCs. In both areas, 300 fibroblasts were counted in each high-power field. The significance of proliferative activity of fibroblasts on LNM or DOM was compared with well-known prognostic parameters. Multivariate analyses demonstrated that a MIB-1 labeling index of more than 10% of fibroblasts in the inner area of IDCs significantly increased the relative risk of LNM and hazard rate of DOM (P < 0.001 and P = 0.007, respectively). The present study indicated that the metastatic ability of IDCs is closely dependent on proliferative activity of fibroblasts in the inner area.

Adult↗
PubMed2000

Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer.

BACKGROUND & AIMS: Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression. METHODS: The dissemination potential of 10 human gastric cancer cell lines in mice with severe combined immunodeficiency (SCID) was compared with the expression of various integrins. The relationship between integrin expression and peritoneal dissemination was also investigated in surgically resected gastric cancer cases. RESULTS: The level of integrin beta4 subunit expression was inversely correlated with dissemination potential. Introduction of a full-length complementary DNA (cDNA) for beta4 subunit into cancer cells showing negligible beta4 subunit expression markedly suppressed peritoneal dissemination and inhibition of endogenous integrin alpha6beta4 by introduction of a cytoplasmic domain-deleted beta4 subunit cDNA into cells showing high expression of beta4 subunit promoted peritoneal dissemination. Apoptosis, which was histologically evident in peritoneal nodules of SCID mice, was induced in the cells with high beta4 subunit expression by attachment to laminin and stimulation with growth factors in vitro. An immunohistochemical study of specimens from 120 cases of primary gastric cancer showed that patients with beta4 subunit-positive tumors exhibited peritoneal dissemination only infrequently (P < 0.0001) and had a better outcome (P < 0.01). CONCLUSIONS: These results indicate that integrin alpha6beta4 is both a suppressor and a predictive marker for peritoneal dissemination in gastric cancer.

Animals↗
PubMed2000

High prevalence of atypical adenomatous hyperplasia of the lung in autopsy specimens from elderly patients with malignant neoplasms.

Atypical adenomatous hyperplasia (AAH) is a possible precursor lesion of adenocarcinoma of the lung, but there have been no reports of AAH focusing on autopsy studies of the lungs of elderly patients, who have higher lung cancer mortality rates. We intended to clarify the characteristics of AAH in the general elderly population on the basis of the findings in autopsy cases. A total of 19 AAH lesions were found microscopically in 16 out of 241 autopsy cases (6.6%). AAH was found in only two cases of adenocarcinoma among 28 lung cancer cases. p53 immunoreactivity was observed in one of 11 low-grade AAH lesions (9.1%), but in three of four high-grade AAH lesions (75%, P=0.03) and the cases of high-grade AAH were more frequently positive for Ki-67 and CEA than the low-grade cases and less positive for pro-surfactant apoprotein C. Four of 123 patients without malignant neoplasms (3.4%) and 12 of 118 patients with malignant neoplasms (11.1%) had AAH (P=0.03). The finding that AAH was more common in the cases with malignancy than in those without malignancy indicated that genesis of AAH may be closely associated with that of malignant neoplasms.

Adenocarcinoma↗
PubMed2000

Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma of the lung 3 cm or less in diameter.

Many small adenocarcinomas can be detected as a result of recent advances in diagnostic radiology. Since the histological and biological heterogeneity of adenocarcinoma often makes it difficult to predict the outcome of operated patients, clarifying the morphological prognostic factors of the tumor is indispensable to the selection of appropriate treatment. We examined 200 cases of adenocarcinoma of the lung 3 cm or less in diameter (T1). Tumor size, tumor cell characteristics, growth pattern, characteristics of fibrosis, vessel and stromal invasion, and metastasis were evaluated to define favorable and unfavorable morphological prognostic factors by univariate and multivariate statistical analysis. There were no deaths in the 66 cases with more than a 75% of lepidic growth component defined as a region of tumor cells growing along alveolar walls and without stromal invasion, central focus of fibrosis 5 mm or less in maximum diameter, or no elastic fiber framework destruction by tumor cells. Multivariate analysis to investigate unfavorable factors revealed that vascular invasion (P<0.001) and a greater than 25% papillary growth component (P=0.043) were the most significant determinants of an unfavorable outcome. The favorable and unfavorable factors demonstrated in this study will be of great value in selecting the treatment of patients with small peripheral adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed2000

Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung.

A low incidence of lung carcinoma has been reported in cases of prolonged use of aspirin. Cyclooxygenase (COX) 2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in atypical adenomatous hyperplasia (AAH), a possible precursor lesion of adenocarcinoma of the lung, is not known. COX-2 expression was immunohistochemically evaluated in a cohort of 20 cuboidal cell hyperplasias (CCH), 81 atypical adenomatous hyperplasias (AAH), 18 bronchioloalveolar carcinomas (BAC), and 88 invasive adenocarcinomas (I-Ad). The relationship between COX-2 expression and clinicopathologic factors and survival was examined. COX-2 overexpression was detected in over 80% of CCH, AAH, BAC, and I-Ad. However, overexpression was diffuse in AAH (71.6%) and BAC (66.7%). No relationship was found between COX-2 expression and clinicopathological factors or survival. COX-2 expression was most frequently detected in AAH. These findings, taken with previous reports that treatment with COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed2000

Assessment of arterial tumor vascularity in small hepatocellular carcinoma. Comparison between color doppler ultrasonography and radiographic imagings with contrast medium: dynamic CT, angiography, and CT hepatic arteriography.

Hepatocellular carcinoma (HCC) is characterized by tumor vascularization from the hepatic artery. The objective of our work was to compare color Doppler ultrasonography (CDU), including power Doppler ultrasonography (PDU) with radiographic imagings with contrast medium in regard to the detection of the arterial tumor vascularity of small hepatocellular carcinomas (HCC). We examined 42 small HCC lesions 2 cm or less in diameter in 37 patients for arterial tumor vascularity by conventional CDU, PDU, dynamic computed tomography (dCT), digital subtraction angiography (DSA), and CT hepatic arteriography (CTA). Color images were detected in 25 (59.5%) and 28 (66.7%) of the 42 lesions with conventional CDU and PDU, respectively, and tumor vascularity was detected in 26 (61.9%) by dCT, 23 (54.8%) by DSA, and 29 (69.0%) by CTA. Tumor vascularity could be detected in 51.9% by PDU and CTA, more than by conventional CDU, dCT, and DSA (44.4, 44.4, and 33.3%, respectively) in well-differentiated HCC, whereas the detection rates by these techniques were almost equal (86.7% by CDU, 93.3% by PDU, dCT, and DSA, 100% by CTA, respectively) in moderately and poorly differentiated HCC. PDU is superior to CDU, dCT and DSA and equal to CTA for the detection of tumor vascularity in small HCC, particularly in well-differentiated HCC.

Aged↗
PubMed2000

New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus.

Immunohistochemistry, DNA ploidy analysis and molecular genetics have made it possible to predict the outcome of breast cancer more precisely than routine histological examination alone. However, in routine practice, it is difficult to incorporate these methodologies in all cases. If certain histological parameters can accurately predict the outcome of patients with breast cancer, they would be more practical for routine use. We showed that the presence of fibrotic focus (FF) in invasive ductal carcinoma (IDC) is closely associated with c-erbB-2 or p53 protein expression, high proliferative activity, and high angiogenesis of the tumors. Furthermore, multivariate analyses with well-known prognostic parameters for IDC demonstrated that the presence of FF is the most useful independent parameter to predict IDC patient outcome. In addition, our data suggested that the interaction between tumor cells and stromal fibroblasts may play an important role in the formation of FF in IDC based on growth factor and growth factor receptor protein expression in the tumor cells and fibroblasts forming FF. Based on the results of our clinicopathological studies, we propose a new prognostic classification scheme for the prediction of IDC patient outcome, which consists of FF, nuclear atypia, and fat invasion. This classification has superior predicting power to existing prognostic classifications.

Breast Neoplasms↗
PubMed2000

Detection of thioredoxin in gastric cancer: association with histological type.

Thioredoxin (TRX) is a redox-active protein with multiple intra- and extracellular functions. This protein exists ubiquitously in all life forms, from primitive living cells, such as Escherichia coli and yeast, to higher mammals. Recently, augmentation of the expression and transcription level of TRX has been reported in tumors of various organs. In this study, we examined the expression of TRX in gastric cancer with respect to its histological type and depth of invasion. The association with cell proliferation was also studied. Results of histochemical analysis of surgical specimens as well as cytochemical analysis and Northern blot analysis of gastric cancer cell lines indicated that TRX is predominantly expressed in undifferentiated type gastric cancer rather than in the differentiated type. Neither the depth of tumor invasion nor cell proliferation significantly determined the staining intensity for TRX.

Adenocarcinoma↗
PubMed2000

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with pulmonary amyloid nodules.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type lymphoma) is a rare thymic tumor, with only seven previous cases described worldwide to date. We describe the only case to have presented with pulmonary amyloid nodules. A 63-year-old Japanese female was found to have an anterior mediastinal tumor and multiple bilateral pulmonary nodules during a medical check-up in 1990 followed by chest radiography and computerized tomography. Because the mediastinal tumor grew larger, she was referred to the National Cancer Center Hospital East and hyperglobulinemia was pointed out. The thymus was resected through median sternotomy and pulmonary nodules were also resected through left thoracotomy. The solid and nodular tumor with several small satellite extensions and cyst formation was completely confined to within the thymus and the resected pulmonary nodules consisted of solid masses with a rough surface. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions) and the resected pulmonary nodules consisted of eosinophilic amorphous deposits which showed birefringence on Congo Red staining. Immunohistochemically, the tumor cells were positive for CD20 and CD79a. IgG and kappa light chain restrictions were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. We diagnosed this case as low-grade B-cell MALT-type lymphoma in the thymus and nodular pulmonary amyloidosis. Since the patient had only localized amyloid deposits in the lung far from the thymic malignant lymphoma and had high serum immunoglobulins, the pulmonary amyloid deposits might be derived from a circulating precursor associated with hyperglobulinemia.

Amyloidosis↗
PubMed2000

Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human colorectal cancer.

The membranous, cytoplasmic and nuclear levels of beta-catenin were evaluated immunohistochemically in archival tissue specimens from 96 Japanese patients with primary colorectal carcinoma who had undergone surgery. The relationships between beta-catenin and clinicopathological variables were analyzed statistically. Reduced beta-catenin immunoreactivity in the cell membranes of cancer cells was found in 70% of the tumors, and cytoplasmic and nuclear accumulation of beta-catenin were found in 68 and 66% of tumors, respectively. Significant correlations between cytoplasmic beta-catenin accumulation and the depth of invasion, venous invasion and focal dedifferentiation were observed. Cytoplasmic beta-catenin accumulation was also found to be a useful predictor of hematogenous metastasis (hazard ratio = 8.94, p = 0.054), though neither a reduced cell membrane level nor nuclear accumulation of beta-catenin correlated with metastasis.

Adenocarcinoma↗
PubMed2000

Doppler resistive index in benign prostatic hyperplasia: correlation with ultrasonic appearance of the prostate and infravesical obstruction.

OBJECTIVE: This study was designed to characterize the resistive index (RI) of prostatic blood flows obtained by transrectal power Doppler sonography (TRPDS) in benign prostatic hyperplasia (BPH). METHOD: In 140 patients with lower urinary tract symptoms, the RI was measured using TRPDS and compared with age and planimetric parameters of the prostate obtained by conventional transrectal sonography. In addition, the RI was related with pressure flow studies. RESULTS: The RI was significantly higher in patients with BPH (0.72+/-0.06, p<0.0001) than those with a normal prostate (0. 64+/-0.04). Although the RI correlated significantly with age and all prostatic planimetric parameters, multiple regression analysis revealed that age and presumed circle area ratio were independent predictors for RI. The RI was also higher in patients with infravesical obstruction than those without (0.74+/-0.06 vs. 0. 70+/-0.05, p<0.005). There was a significant correlation between RI and urodynamic parameters obtained in pressure flow studies. Out of 33 patients with obstruction, 28 (85%) had an RI of 0.7 or more, while 11 out of 24 patients (46%) without obstruction had an RI less than 0.7. CONCLUSION: The RI is promising as a new parameter to estimate the intraprostatic pressure to investigate BPH. Its value to represent urodynamic information during voiding remains to be studied.

Aged↗
PubMed2000

Clinical implications of immunoreactivity of thymidylate synthase and dihydropyrimidine dehydrogenase in gastric cancer treated with oral fluoropyrimidine (S-1). Study Group of S-1 for Gastric Cancer.

Many reports have demonstrated that thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. A newly developed orally administered drug, fluoropyrimidine (S-1), has been developed with clinical efficacy when combined with an inhibitor of DPD. In this study, the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer. Response rates were 54% (13/24) in TS(+) and 53% (9/17) in TS(-) patients (p=0.938), and those of DPD(+) and (-) patients were 61% (11/18) and 48% (11/23) (p=0.397), respectively. The median survival time of all the subjects was 253 days. There was no significant difference in median survival time between TS(+) patients (284 days) and (-) patients (189 days: p=0.670). The 18 DPD(+) patients had median survival times slightly longer (338 days) than the 23 patients with DPD(-) (207 days: p=0.206). This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. Further studies are needed to confirm these results with larger numbers of patients.

Adult↗
PubMed2000

A case of small polypoid esophageal carcinoma with multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components.

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Actins↗
PubMed2000

Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and clinicopathological factors (gender, tumor location, histological factors, and clinical tumor-node-metastasis stage), expression of apoptosis-related proteins (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase-mediated nick end labeling method, expression of cell proliferation-related proteins (Ki-67-labeling index and epidermal growth factor receptor overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with a high MVD (> or =35 vessels/field) showed better radiosensitivity than those with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling index (> or =40%) was weakly associated with radiosensitivity (P = 0.056). Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy (P = 0.012, 0.0003, respectively). No significant association between clinicopathological factors, or of overexpression of p53, bax, bcl-2, epidermal growth factor receptor, or apoptotic index, with radiosensitivity was found. These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment.

Aged↗
PubMed1999

Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody.

In-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.

Animals↗
PubMed1999

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the lung: a report of a case with pleural dissemination.

A 79-year-old man with an abnormal shadow on a chest radiograph was referred to our hospital for further examination. Open lung biopsy revealed numerous nodules on visceral pleura and the tumor, obtained by wedge resection of the left upper lobe of the lung, consisted of centrocyte-like cells and lymphoplasmacytoid cells, expressing CD20 and CD79a. These cells invaded bronchiolar epithelium to form lymphoepithelial lesions. The pleural-based nodules were similarly composed of the same cells as those in the left upper lobe tumor. To our knowledge, pleural dissemination of low grade B-cell lymphoma of mucosa-associated lymphoid tissue has not been reported previously.

Aged↗
PubMed1999

Effect of lecithinized superoxide dismutase (PC-SOD) on experimental pulmonary metastasis in mice.

The inhibitory effect of lecithinized superoxide dismutase (PC-SOD) on pulmonary metastasis in mice was investigated. In an experimental pulmonary metastasis model employing Meth A-T cells, significant and dose-dependent inhibition was observed after i.v. pre-administration of PC-SOD. Unmodified SOD (U-SOD) was also effective, but a 10-times higher dose was necessary to be significant. The pulmonary accumulation of Meth A-T cells labeled with 5-[125I]iodo-2'-deoxyuridine was not reduced by either PC-SOD or U-SOD, and neither of the compounds decreased pulmonary MPO activity. However, PC-SOD increased pulmonary SOD activity for longer, compared with U-SOD. In vitro addition of PC-SOD dose-dependently suppressed the growth of Meth A-T cells, while U-SOD had little effect. The combination of PC-SOD and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitric oxide (NO)-generating agent, had an additive effect. It was also found that PC-SOD prevented a decrease of pulmonary NOx level following tumor cell inoculation. It was concluded that PC-SOD possessed antimetastatic activity, and its potency was superior to that of U-SOD. These results suggest that PC-SOD may prevent the excessive formation of oxygen radicals and peroxynitrite (ONOO-) which cause cell damage and facilitate tumor metastasis.

Animals↗