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H Tsuda

Publications and source records attributed to H Tsuda.

At least 163 records · Page 9Linked to original sources
PubMed1998

Apocrine Carcinoma of the Breast: Clinicopathological Analysis and Histological Subclassification of 12 Cases.

BACKGROUND: Apocrine carcinoma is rare and most of its clinicopathological features are still unknown. The purpose of this study was to identify the clinicopathological characteristics of apocrine carcinoma. METHODS: We clinicopathologically analyzed apocrine breast carcinomas resected from 12 Japanese women and subclassified them histopathologically. RESULTS: The average age of the patients at diagnosis was 60.1 years (range: 38-78). Tumor diameters ranged from 0.5 to 4.5 cm (median 2.4). Mammography revealed tumor shadows without microcalcifications in all patients. Two (17%) of the12 patients were lymph node metastasis-positive, and lymphatic permeation by tumor cells was observed in 3 (25%). Apocrine carcinoma in this study could be classified into three subtypes according to predominant histopathological growth pattern: type I, intraductal spreading type (4 patients); type II, adenosis-associated type (3 patients); and type III, infiltrating type (5 patients). Types I and II showed no lymph node metastasis and had an excellent prognosis, whereas theinfiltrating type was associated with lymph node metastasis and death from cancer. Estrogen receptors and progesterone receptors were positive in 17% (1/6) and 60% (3/5), respectively, of the tumors tested. CONCLUSION: In the present study, apocrine carcinoma of the breast was characterized by higher patient age and tumor shadows without microcalcifications on mammography. However, the tumors were heterogenous with regard to pattern of local spread.

Journal Article↗
PubMed1998

Japanese Late-Onset Breast Cancer Families: Their Clincopathological Characteristics and Absence of BRCA1 and BRCA2 Germline Mutations.

BACKGROUND: The causes and pathologic and prognostic phenotypes of late-onsetfamilial breast cancers are still unknown. The purpose of this study was to document the clinicopathological features of late-onset familial breast cancers using genetic testing of BRCA1 and BRCA2. METHODS: We analyzed 11 breast cancers from 10 patients from 8 Japanese late-onset Breast cancer families. RESULTS: The average age of the patients was 55 years (range 43 to 89). Bilateral occurrence was noted in 2 patients (8%). All the tumors were invasive ductal carcinomas, except for 1 case of invasive lobular carcinoma. Tumor size rangedfrom 0.8 cm to 7.8 cm (median 2.3 cm) and lymph node metastasis occurred in 6 of the 11 patients (55%). Six (55%) of the 11 tumors were histologically grade 2 and 5 (45%) were histologically grade 3. Estrogen receptor (ER) positivity was 80% (8/10). Overexpression of c-erbB-2 and p53 protein was detected in 18% (2/11)and 9% (1/11) of the tumors, respectively. Five patients from 4 families received genetic testing but all were negative for BRCA1 and BRCA2 germline mutations.All the patients were alive after a median follow-up period of 32 months, except for 1 patient. CONCLUSION: In this study, no germline mutations of BRCA1 or BRCA2 were detected. However, there was a tendency towards ER-positive tumors, but the positivity of p53 protein was considered to be lower then that of sporadic tumors.

Journal Article↗
PubMed1998

p16 gene overexpression in mouse bladder carcinomas.

Deletion of 9p21 has frequently been observed in human bladder carcinomas. A candidate target suppressor gene, p16, was recently identified within this deleted region. In this study, we therefore investigated the loss of heterozygosity (LOH) of the p16 gene which is located on mouse chromosome 4, as well as its expression in mouse bladder carcinomas. We also studied the effects of normal cell contamination on LOH analysis using xenografts in CD-1(ICR) nude mice from B6C3F1 bladder carcinomas. We could not detect any LOH at the p16 locus in the mouse primary bladder carcinomas and xenografts. Surprisingly, overexpression of p16 was found in all primary mouse bladder carcinomas. Using microsatellite polymorphisms, a distinction could be made between PCR products derived from B6C3F1 and CD-1(ICR) nude mice. It was thereby confirmed that effects of normal cell contamination on LOH analysis are negligible when only tumor tissue is carefully sampled. The results suggest that abnormalities of p16 expression may be involved in mouse bladder carcinogenesis, but that gene deletion is not involved.

Animals↗
PubMed1998

Orthotopic growth and metastasis of human non-small cell lung carcinoma cell injected into the pleural cavity of nude mice.

We have constructed a metastatic model of human non-small cell lung cancer (NSCLC) by injection of NSCLC cell lines directly into the left pleural cavity of BALB/c nude mice. All of seven NSCLC cell lines, which are tumorigenic after subcutaneous injection, were successfully transplanted in the pleural cavity, while only three of the seven cell lines produced lung metastatic colonies after intravenous injection. Tumors grew extensively in the pleural cavity and infiltrated into the lung parenchyma directly. Furthermore, tumors metastasized to the mediastinum and contralateral pleural cavity through lymphatic routes. Since this model is easy to perform and the result is reproducible, it would be useful for studies on the biological behavior and treatment of human NSCLC in vivo.

Animals↗
PubMed1998

Local Recurrence after Conservative Surgery without Postoperative Radiation for Pure Tubular Carcinoma of the Breast:A Case Report with Reference to Multifocality of Tubular Carcinoma.

A 49-year-old premenopausal woman with stage I breast carcinoma underwent left quadrantectomy with axillary dissection in 1992. The tumor was 0.7x0.5 cm Histopathologically, this was a pure tubular carcinoma without lymph node metastasis or lymphatic or vascular invasion. Although the surgical margin was pathologically negative, atypical ductal hyperplasia was present close to the cut margin's edge. Neither adjuvant chemotherapy nor radiotherapy had been given after the operation. Approximately 5 years after the first surgery, she had a local recurrence in the vicinity of the operative wound. There was no clinical evidence of distant metastasis. A salvage mastectomy was performed. Histopathological examination revealed that the second tumor was an invasive ductal carcinoma, histological grade 2, with extensive intraductal component. It was difficult to determine whether this was a true in-breast recurrence or a second primary cancer. Overexpression of p53 and c-erbB-2 was observed in the second tumor. Estrogen receptor and progesterone receptor were both negative. No postoperative chemotherapy was given. Multifocality and atypical ductal hyperplasia were observed in 7(87.5%)and 6(75%) of 8 patients, respectively, with tubular carcinoma between 1991and 1997 at the National Cancer Center Hospital. Coexisting disease associated with tubular carcinoma suggests that radiotherapy may be an important component of breast conservation treatment to prevent local recurrence in this type of tumor.

Journal Article↗
PubMed1998

Structure, chromosomal locus, and promoter of mouse Hes2 gene, a homologue of Drosophila hairy and Enhancer of split.

Hes2 encodes a mammalian basic helix-loop-helix transcriptional repressor homologous to the products of Drosophila hairy and Enhancer of split. Here, we isolated and characterized the mouse Hes2 gene. This gene consists of four exons, and all the introns are located within the protein-coding region at positions homologous to those of other Hes genes. On the inter-specific backcross analyses, mouse Hes2 is mapped to the distal region of Chromosome 4 near the Hes3 and Hes5 loci, which are different from the Hes1 locus on Chromosome 16. Upstream of the transcription initiation site, there are GC-rich regions, but a typical TATA box is not present. Transient transfection analyses demonstrated that, while Hes1 and Hes5 promoter activities are significantly upregulated by the active form of Notch, a key regulator of cellular differentiation, Hes2 and Hes3 promoter activities are not. These results suggest that Hes genes are functionally classified into two groups: those that are regulated by Notch and those that are not.

Amino Acid Sequence↗
PubMed1998

Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Actinin↗
PubMed1998

Structure and promoter analysis of Math3 gene, a mouse homolog of Drosophila proneural gene atonal. Neural-specific expression by dual promoter elements.

ath3, a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal, can directly convert non-neural cells into neurons with the anterior features. In the mouse, ath3 expression initially occurs widely in the developing nervous system and then gradually becomes restricted to the neural retina. Here, we characterized the genomic organization and promoter activity of mouse ath3 (Math3). Math3 gene consists of two exons separated by an 8-kilobase intron, and the whole protein-coding region is located in the second exon. Transcription starts at two sites, which are 75 nucleotides apart from each other, and there is no typical TATA box in the upstream region of either start site. Transient transfection analysis showed that the 5'-region of Math3 can direct efficient expression in neuroblastoma cells but not in glioma or fibroblast cells. Deletion studies revealed that the proximal 193-base pair region, which contains the downstream transcription initiation site but not the upstream site, is essential for the Math3 promoter activity and can direct efficient expression in neuroblastoma cells. In contrast, retrovirus-mediated promoter analysis demonstrated that a region further upstream is additionally necessary for retinal expression. These results indicate that Math3 promoter contains two essential regulatory regions, the proximal 193-base pair region, which confers efficient neural-specific expression, and a region further upstream, required for retinal expression.

Animals↗
PubMed1998

A major common trisulfated hexasaccharide core sequence, hexuronic acid(2-sulfate)-glucosamine(N-sulfate)-iduronic acid-N-acetylglucosamine-glucuronic acid-glucosamine(N-sulfate), isolated from the low sulfated irregular region of porcine intestinal heparin.

The major structure of the low sulfated irregular region of porcine intestinal heparin was investigated by characterizing the hexasaccharide fraction prepared by extensive digestion of the highly sulfated region with Flavobacterium heparinase and subsequent size fractionation by gel chromatography. Structures of a tetrasaccharide, a pentasaccharide, and eight hexasaccharide components in this fraction, which accounted for approximately 19% (w/w) of the starting heparin representing the major oligosaccharide fraction derived from the irregular region, were determined by chemical and enzymatic analyses as well as 1H NMR spectroscopy. Five compounds including one penta- and four hexasaccharides had hitherto unreported structures. The structure of the pentasaccharide with a glucuronic acid at the reducing terminus was assumed to be derived from the reducing terminus of a heparin glycosaminoglycan chain and may represent the reducing terminus exposed by a tissue endo-beta-glucuronidase involved in the intracellular post-synthetic fragmentation of macromolecular heparin. Eight out of the 10 isolated oligosaccharides shared the trisaccharide sequence, -4IdceA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-, and its reverse sequence, -4GlcA beta 1-4GlcNAc alpha 1-4IdceA alpha 1-, was not found. The latter has not been reported to date for heparin/heparan sulfate, indicating the substrate specificity of the D-glucuronyl C-5 epimerase. Furthermore, seven hexasaccharides shared the common trisulfated hexasaccharide core sequence delta HexA(2-sulfate)alpha 1-4GlcN(N-sulfate)alpha 1-4IdceA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-4GlcN(N-sulfate) which contained the above trisaccharide sequence (delta HexA, IdceA, GlcN, and GlcA represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, L-iduronic acid, D-glucosamine, and D-glucuronic acid, respectively) and additional sulfate groups. The specificity of the heparinase used for preparation of the oligosaccharides indicates the occurrence of the common pentasulfated octasaccharide core sequence, -4GlcN(N-sulfate)alpha 1-4HexA(2-sulfate)1-4GlcN(N-sulfate) alpha 1-4IdceA alpha 1-4GlcNAc alpha 1-4GlcA beta 1-4 GlcN(N-sulfate)alpha 1-4HexA(2-sulfate)1-, where the central hexasaccharide is flanked by GlcN(N-sulfate) and HexA(2-sulfate) on the nonreducing and reducing sides, respectively. The revealed common sequence constituted a low sulfated trisaccharide representing the irregular region sandwiched by highly sulfated regions and should reflect the control mechanism of heparin biosynthesis.

Animals↗
PubMed1998

Multiple myeloma associated with serum amino acid disturbance and high output cardiac failure.

We experienced a plasma cell leukemia (PCL) patient complicated with high output cardiac failure (HOCF), proved as his elevated cardiac index and pulmonary artery wedge pressure and decreased systemic vascular resistance index in a hemodynamic study. We found no possible causes of HOCF. Interestingly, HOCF was improved as PCL responded to intensive chemotherapy. On the other hand, he showed consciousness disturbance, and had frequent attacks of generalized seizure. His electroencephalogram showed slow waves, and a spike and wave complex. Hyperammonemia and abnormal amino acid distribution were also found. This abnormal serum amino acid distribution, especially elevated glycine level, was different from that seen in chronic liver failure, and he had no hepatic disease. After intensive chemotherapy, the serum ammonia level and glycine level decreased. In this patient, PCL seemed to be responsible for HOCF, hyperammonemia, and abnormal amino acid distribution. We experienced two more cases of multiple myeloma (MM) with HOCF, hyperammonemia, abnormal serum amino acid distribution, and consciousness disturbance of unknown origin. Those two cases showed slow waves in the electroencephalogram. Improvement was seen in their HOCF, hyperammonemia, and abnormal amino acid levels after chemotherapy. The possibility of MM as a cause of HOCF is discussed.

Adult↗
PubMed1998

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Animals↗
PubMed1998

A prospective study of the significance of gene and chromosome alterations as prognostic indicators of breast cancer patients with lymph node metastases.

In 150 surgically resected primary breast carcinomas that had axillary lymph-node metastases, we examined the incidence of loss of heterozygosity on chromosomes 16p, 16q, 17p, 17q, and 18q, point mutation of the p53 tumor-suppressor gene, nuclear immunoreaction of p53 protein, and amplifications of the c-erbB-2 and int-2 oncogenes by Southern blotting, single-strand conformation polymorphism analysis, and immunohistochemistry. We analyzed the association of these factors and conventional prognostic parameters with outcome of the patients, using Cox's univariate and multivariate analyses. The univariate analysis revealed that nuclear p53 immunoreaction, p53 mutation, and c-erbB-2 amplification as well as the number of metastatic lymph nodes, histological grade, and hormone-receptor statuses were significant prognostic indicators for both recurrence and cancer death. p53 immunoreaction was correlated more strongly with a poor prognosis than p53 mutations. The combination of p53 and c-erbB-2 effectively identified the high-risk patient group, and even among Grade 3 cases the subgroup with these alterations tended to have poorer clinical outcomes. The multivariate analysis including p53, c-erbB-2, and conventional factors. Lymph node status, grade, and p53 had independent impacts on the survival of patients. Under identical adjuvant systemic therapies, prognoses differed between the patient groups with and without alterations of p53 or c-erbB-2. Appropriate combinations of conventional factors with nuclear p53 immunoreaction and c-erbB-2 amplification would help to identify highly aggressive node-positive breast carcinomas and would aid stratification of patient groups in randomized clinical trials of adjuvant systemic therapies.

Adult↗
PubMed1998

Diagnostic value of contrast-enhanced computed tomography for diagnosing the intraductal component of breast cancer.

BACKGROUND: It is important to reduce local residual cancer to avoid local recurrence after breast conserving treatment. We therefore tried to detect the intraductal components and small invasive foci of breast cancers by contrast-enhanced helical computed tomography (CE-CT). METHODS: In 122 women whose breasts were examined by CE-CT preoperatively, intraductal spread detected on ultrasound (US), mammography (MMG), and CE-CT, and extensive intraductal components (EICs) detected by histological examination were analyzed for correlations among the extent and subtypes of intraductal components, and deviations in tumor size. RESULTS: EICs were present in 44 patients. The sensitivities of EIC detection by US, MMG, and CE-CT were 35%, 61%, and 88%, respectively, and the corresponding specificities were 83%, 86%, and 79%, respectively. The sensitivities of detecting EIC and small invasive foci were 34%, 57%, and 91%, respectively. In 5 patients, EIC could only be visualized by CE-CT. The median deviation of the size of intraductal spread revealed by CE-CT from pathological EIC was 0.0 cm (range + 3.0 to - 1.7 cm). CONCLUSIONS: CE-CT is useful for visualizing intraductal spread and small invasive foci of breast cancer.

Adult↗
PubMed1998

Fibrotic focus in infiltrating ductal carcinoma of the breast: a significant histopathological prognostic parameter for predicting the long-term survival of the patients.

The presence of fibratic fows (FF) in infiltrating ductal carcinoma (IDC) has been shown to be an important histological factor associated with high tumor aggressiveness, or early tumor recurrence or death. However, the clinicopathological significance of FF for predicting the long-term survival of the patients with IDC has not been fully investigated. In order to elucidate this aspect, we divided 140 IDCs with at least 10 years of follow up into tumors with FF and those without. IDC with FF showed significantly higher histologic grade (P=0.02), higher frequency of tumor necrosis (P=0.02), higher frequency of cases with more than three positive lymph node metastases (P=0.04), higher T classification (P=0.009), and higher pathological stage (P=0.0002) than those without FF. Relative risk (RR) of tumor recurrence and death was significantly higher in tumors with FF than in those without (RR=4.5, P < 0.00001 and RR=5.6, P < 0.00001, respectively). In cases of early stage cancer (stages I, IIA, and IIB), or in those with less than four lymph node metastases, IDCs with FF demonstrated a significantly higher risk than those without. Multivariate adjustments for other pathological factors did not change the RRs significantly. These results indicate that in long-term follow up the presence of FF is a significant prognostic parameter for IDC, and therefore strongly suggest that IDCs must be divided into those with and without FF.

Adult↗
PubMed1998

Peripheral ulcerative keratitis associated with erythema elevatum diutinum and a positive rheumatoid factor: a report of three cases.

Peripheral ulcerative keratitis (PUK) is a complication of collagen-vascular diseases such as rheumatoid arthritis (RA) and other systemic vasculitides. We report three cases of erythema elevatum diutinum with PUK. These patients presented with nodules and plaques consistent with erythema elevatum diutinum on the extremities and crusted or ulcerated purpuric lesions on the soles. Histopathological examination of these lesions revealed a dense neutrophilic infiltrate with nuclear dust and fibrin around blood vessels. All the patients developed PUK concomitant with the development of the skin lesions. The rheumatoid factor was positive at high titre in all three patients; this was associated with probable RA in one. Cutaneous lesions were dramatically improved by administration of dapsone in all cases. Dapsone was also effective in treating the ocular lesions in two patients.

Aged↗
PubMed1998

Th1/Th2 balance alteration in the clinical course of a patient with pure red cell aplasia and thymoma.

Peripheral T helper subsets in a patient with acquired pure red cell aplasia (PRCA) and thymoma were analysed by flow cytometry. Thymectomy resulted in a transient but definite improvement in anaemia. A continuous remission was attained by cyclosporin A (CsA) therapy. The changes in Th1/Th2 ratios corresponded with the haematological changes. Specifically, Th2 type lymphocytes were dominant during a haemopoietic suppression and elevation of the Th1/Th2 ratio was concomitant with haematological improvement. These observations suggest that polarization of Th subsets to Th2, induced by clonally expanded (gammadelta-type) T cells in thymoma, are involved in the pathogenesis of PRCA.

Aged↗
PubMed1998

Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.

The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.

1,2-Dimethylhydrazine↗