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Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 181 records · Page 10Linked to original sources

Breast cancer in Cowden's disease: a case report with review of the literature.

We report a case of invasive breast cancer in a 62-year-old female patient with Cowden's disease. A left modified radical mastectomy was performed and histopathology of the tumor showed invasive ductal carcinoma, histological grade 3, without lymph node metastasis. The patient had a past history of endometrial cancer at 55 but did not have a family history of malignant disease. Goiter was palpable but aspiration cytology revealed no malignancy. There were several papillomas on the oral mucosa and multiple papillomatous lesions on the right femur. Barium X-ray and endoscopic examination revealed multiple, small, hyperplastic polypoid lesions on the esophagus, stomach and rectum. Histopathology of the biopsy specimens from the esophagus and stomach showed acanthotic squamous epithelium and foveolar hyperplastic polyps. The patient was followed up closely to monitor the thyroid lesions and polyposis of the digestive tract. A total of 12 breast cancer patients who also had Cowden's disease have been reported in Japan and these cases are reviewed in this report.

Breast Neoplasms↗

Microinvasive breast carcinoma with extensive involvement of level III axillary lymph nodes: a case report.

A 44-year-old woman presented with a right huge axillary mass. Both mammography and ultrasonography revealed a primary cancer of 2.8 cm maximum diameter in the right breast and metastases in the axillary lymph nodes, both being confirmed by aspiration cytology as ductal carcinoma. Right standard radical mastectomy with level III axillary lymph node dissection was carried out. Pathologically, the tumor was diagnosed as ductal carcinoma in situ with microinvasion (DCISM), histologic grade 3. The area of stromal invasion measured 1 mm at its widest point. Sixteen of the 17 resected axillary lymph nodes contained metastases, including six level III lymph nodes. Immunohistochemical studies of the tumor revealed overexpression of p53 protein, but not that of c-erbB-2 protein. The frequency of lymph node metastases from DCISM is reported to be very low. Therefore, the present case with extensive involvement of level III lymph nodes was unusual.

Adult↗

Prognostic significance of accumulation of gene and chromosome alterations and histological grade in node-negative breast carcinoma.

The histological grade of atypia is a known prognostic indicator for breast cancer patients and correlates with many gene and chromosome alterations. To investigate the independent prognostic significance of gene and chromosome alterations in axillary node-negative (n0) breast cancers of the invasive ductal and invasive lobular types, the prevalence of eight gene and chromosome alterations and their association with histological grade and recurrence was studied in 129 consecutive patients who had undergone resection over an average follow-up period of 43.4 months. Loss of heterozygosity on 16q, 17p, 16p, 17q and 18q, p53 gene mutation and c-erbB-2 and int-2 gene amplifications were detected in 55%, 37%, 25%, 24%, 22%, 23%, 15% and 11% respectively. Individual alterations in 17p, 17q, 18q, c-erbB-2 and p53 were detected most frequently and gene and chromosome alterations tended to be accumulated in Grade 3 n0 invasive ductal/lobular carcinomas. Histological grade, 18q, int-2 and the number of these gene and chromosome alterations were significant prognostic indicators on Cox's univariate proportional hazard model, and 18q and int-2 were still significant after adjustment for histological grade. Results suggested that examination of the presence of certain gene and chromosome alterations, as well as histological grade, were effective in identifying n0 breast cancer patients at high risk of early recurrence.

Breast Neoplasms↗

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup.

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.

Adult↗

Establishment of histological criteria for high-risk node-negative breast carcinoma for a multi-institutional randomized clinical trial of adjuvant therapy. Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section.

BACKGROUND: A multi-institutional randomized clinical trial of adjuvant therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in order to establish histological criteria to identify patient groups with higher rates of recurrence. METHODS: Initially, three pathologists independently judged the nuclear grade, composed of nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing on interobserver variation of the nuclear grade and its correlation with patient prognosis. These pathologists then gave consensus histological types and nuclear grades for 130 other n0 breast carcinomas and examined the prognostic significance of the grade. RESULTS: In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreement for the grade was fair. In the second study, the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not generate any significant difference in mitotic counts. CONCLUSIONS: The histological type and the nuclear grade clearly identified a higher-risk patient group with n0 breast carcinoma, and may be applied to the multi-institutional protocol study when the criteria have been well standardized by the pathologists.

Antineoplastic Combined Chemotherapy Protocols↗

Characterization of heparinase from an oral bacterium Prevotella heparinolytica.

Heparinase was purified to homogeneity from the cell extract of an oral bacterium, Prevotella heparinolytica, by a combination of anion exchange chromatography, gel filtration chromatography, and hydroxyapatite chromatography. Properties of the purified P. heparinolytica heparinase (P. heparinase) were investigated. The enzyme exhibited a maximum activity in 50 mM Tris-HCl buffer, pH 7.5-8.0, containing 75 mM sodium acetate, 0.1 M NaCl, and 1 mM CaCl2. Optimum conditions for the maximum activity of P. heparinase were similar to those of the heparinase from Flavobacterium heparinum (F. heparinase). The two enzymes also yielded similar digestion profiles of various glycosaminoglycans and heparin tetrasaccharides, suggesting that they have a similar substrate specificity. Kinetic study of the P. heparinase reaction using porcine intestinal heparin as substrate gave a Km value of 3.8 x 10(-5) M and a Vmax value of 11.4 micromol/min x mg protein. The Michaelis constant of P. heparinase was slightly larger than but not significantly different from that of F. heparinase. The amino acid composition of P. heparinase was also similar to that of F. heparinase, but its N-terminal sequence of 20 amino acid residues was different and hitherto unreported. These results together indicate that these heparinases are different proteins with closely similar enzymatic properties. Since F. heparinum produces not only heparinase but also heparitinase II, which has a broad substrate specificity, F. heparinase may be contaminated with this enzyme. In contrast, P. heparinolytica does not produce heparitinase II, and P. heparinase should prove a useful tool for degrading heparin without the risk of contamination with heparitinase II.

Amino Acid Sequence↗

Physical exercise: a pillar for cancer prevention?

Both epidemiological and experimental studies have shown that physical exercise deserves particular attention in any consideration of approaches to the prevention of neoplasia, especially since it also exerts consistent beneficial effects on the other major chronic diseases prevalent in the Western world, atherosclerosis and non-insulin dependent diabetes mellitus (NIDDM). The organ sites for which strong evidence has been gained for a protective influence of exercise or an elevated risk with a sedentary existence include the colon, prostate, breast and endometrium. The underlying mechanisms appear to centre on the hormones insulin and oestrogen, serum elevation of both of these endocrine factors being associated with increased risk of neoplastic development. The immense potential benefit of an increased level of exercise in the general population suggests that commensurate measures should be taken in the field of cancer education.

Chronic Disease↗

Chronically elevated proliferation as a risk factor for neoplasia.

Chronic disease conditions that are associated with elevated proliferation are well established as risk factors for cancer development. These may be due to viruses (for example, in the case of hepatitis and liver cancer), bacterial infections, parasite infestation or physical trauma. In addition to these exogenous agents there are also metabolic abnormalities that can contribute, caused by genetic or epigenetic influence. In the latter case, an increase in serum levels of the hormones oestrogen, testosterone and insulin may be of special importance. The present review concentrates attention on factors that induce elevated cell turnover and for which there is epidemiological and/or experimental evidence of a link with neoplasia, with particular stress on the individual organ or tissue level.

Animals↗

Co-ordination and ecology in practical cancer prevention.

A great deal of information is already available regarding modifiable factors affecting cancer development in a negative or positive fashion. Thus, avoidance of harmful agents like tobacco, vaccination against virus infections, prompt treatment of inflammatory conditions and increased exposure to beneficial influences hold great promise for the achievement of effective prevention. However, this requires a co-ordinated strategy and an integration of efforts in epidemiological and biological research, medical practice and education, and is essential for optimal use of the resources available. In addition, more stress needs to be placed on community approaches. Concentration of particular attention on the 'ecological' interactions among a triad of the major areas of action: (1) information generation; (2) intervention efforts; (3) government policy, appears warranted.

Health Planning↗

European country comparisons provide evidence of a link between colon cancer and adenocarcinoma development in the lung but not the oesophagus.

Relative incidence rates of lung cancers demonstrate marked international variation in values for the different histological sub-types. In order to determine whether adenocarcinomas (ACs) in this site might share risk factors with other ACs, for example, in the breast, prostate, oesophagus and colon, a comparison of data in the IARC/WHO Cancer Incidence in Five Continents (Volume VII) was made for selected registries in Europe. Significant correlations were found between lung AC incidences/100,000 population and prostate and colon cancers in males (P < 0.005 and P < 0.05, respectively) and for breast and colon in females (P < 0.05 for both). Partial correlation coefficients were significant for lung and colon (P < 0.001) and prostate and colon (P < 0.005) in men, and for breast and colon in women (P < 0.005). A significant negative correlation with prostate cancer was noted for lung ACs in men. The results provide support for shared risk factors between lung Acs and colon cancers but do not indicate any link with AC development in the oesophagus. Data from registries in the UK and Italy were remarkable for high incidences of oesophageal and lung ACs, respectively, pointing to major differences in environmental risk factor or beneficial influence acting on these sites between the two countries.

Adenocarcinoma↗

Modulation of dihydroxy-di-n-propylnitrosamine-induced liver lesion development in Opisthorchis-infected Syrian hamsters by praziquantel treatment in association with butylated hydroxyanisole or dehydroepiandrosterone administration.

The effects of praziquantel coupled with dehydroepiandrosterone (DHEA) or butylated hydroxyanisole (BHA) administration 16 weeks subsequent to dihydroxy-di-n-propylnitrosamine (DHPN) treatment and infection with Opisthorchis viverrini (OV) on lesion development in the liver of Syrian hamsters were investigated. Animals were given 80 OV metacercariae and then two i.p. injections of DHPN (500 mg/kg body weight) 4 and 5 weeks thereafter. At week 16, groups received praziquantel (250 mg/kg, i.g.) and were placed on normal diet or diet supplemented with BHA (1%) or DHEA (0.6%) until they were killed at week 24. Histopathological assessment revealed that, whereas antihelminthic treatment alone resulted in a clear reduction in hepatocellular lesion development, effects on cholangiocellular lesions were equivocal. BHA and DHEA, in contrast, were both associated with a significant reduction in frequency of cholangiofibrosis and cholangiocellular carcinoma. The former chemical, however, increased the numbers of liver nodules while the hormone brought about a decrease as well as a shift in the phenotype of the lesions. The results thus indicate that although cholangiocellular lesion development may, unlike generation of hepatocellular nodules, be to a certain extent independent of the continued presence of parasite, it can be influenced by exogenous treatments.

Animals↗

Enhanced tumorigenicity of rat bladder squamous cell carcinoma cells after abrogation of gap junctional intercellular communication.

We previously demonstrated a clear tendency for actively communicating rat bladder carcinoma cell lines with elevated expression of connexin 43 mRNA to possess strong tumorigenicity. In the present study, immunohistochemical analysis established that normal bladder epithelium did not express connexin 43 protein, but bladder carcinomas often expressed the protein, particularly on the membranes of cells within areas of squamous cell differentiation. To investigate the role of connexin 43 overexpression in rat bladder carcinoma cells, an anti-sense connexin 43 expression vector was transfected into BC31 cells having a high communication capacity. In the resultant transfectants, there was little or no communication capacity and connexin 43 expression. The growth rate in vitro was not changed compared to that of cells treated with the vector alone (without the anti-sense sequence), but tumorigenicity in nude mice was dramatically enhanced. The results indicate that connexin 43 overexpression in rat bladder carcinogenesis is related to squamous cell differentiation, and the protein can have tumor suppressor characteristics, as in other organs.

Animals↗

Binding of the capsule-like serotype-specific polysaccharide antigen and the lipopolysaccharide from Actinobacillus actinomycetemcomitans to human complement-derived opsonins.

We investigated the molecular mechanism of resistance of Actinobacillus actinomycetemcomitans to complement-dependent chemiluminescence response by human polymorphonuclear leukocytes. Whole cells of serotype b-specific polysaccharide antigen-defective mutants ST2 and ST5 were constructed by inserting transposon Tn916 into A. actinomycetemcomitans strain Y4. These strains induced strong chemiluminescence response by human polymorphonuclear leukocytes and markedly bound to human complement-derived opsonins. In contrast, strain Y4 induced weak chemiluminescence response and weakly bound to complement-derived opsonins. The biosensor analysis revealed that lipopolysaccharide from strain Y4 strongly bound to human C3b, but serotype b-specific polysaccharide antigen did not. The serotype b-specific polysaccharide antigen molecule might sterically hinder the interaction between complement-derived opsonins and lipopolysaccharide to reduce complement-dependent chemiluminescence response by human polymorphonuclear leukocytes.

Adult↗

Multiple developmental pathways of highly aggressive breast cancers disclosed by comparison of histological grades and c-erbB-2 expression patterns in both the non-invasive and invasive portions.

To determine the developmental stages at which the highly malignant phenotype of breast carcinoma is acquired, the histological grade and c-erbB-2 oncoprotein expression status were examined for both the ductal carcinoma in situ (DCIS) and invasive components of 437 separate invasive breast carcinomas. In 218 invasive carcinomas with high-grade atypia (grade 3), the DCIS components were grade 2-3 in 158 cases (73%). Twenty-seven (12%) showed an obvious stepwise increase from grade 1 DCIS to grade 3 invasive carcinoma, and 25 of these tumors had DCIS components covering < 25% of their area. Ductal carcinoma in situ components were undetectable in 33 (15%) of invasive carcinomas. The incidence of c-erbB-2 overexpression was higher in grade 3 carcinomas with grade 2-3 DCIS components (55%, 80 of 146) than in those with grade 1 DCIS components (5%, one of 25). The incidence was also higher in grade 3 carcinomas with DCIS components covering > or =25% of the tumor area (71%, 39 of 55) than in those with DCIS over < 25% of the total area (36%, 42 of 116) or without DCIS components (6%, two of 33). There appeared to be three prototypic pathways to high-grade breast carcinoma: (i) invasion by a high-grade DCIS regardless of the extent of DCIS spread; (ii) invasion by a low-grade DCIS during the microscopic stages, accompanied by an obvious enhancement of the grade; and (iii) development of an invasive carcinoma ab initio. c-erbB-2 overexpression appeared to be frequently involved in the early development of the first group but showed little relation to the invasive process in any of these three pathways. The histological grade and c-erbB-2 overexpression appeared to be largely established during the early microscopic stages of a DCIS or invasive carcinoma.

Adult↗

Outcome of collagen vascular diseases by treatment with plasmapheresis.

The outcome of collagen vascular diseases after treatment with plasmapheresis was studied in 9 patients with polyarteritis nodosa (PN), in 2 patients with Wegener's granulomatosis (WG), in 1 patient with allergic granulomatous angitis (AGA), and in 20 patients with systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). Improvement after treatment with plasmapheresis was observed in 41.7% of the patients with PN, WG, and AGA. On the other hand, with the exception of 1 patient with thrombocytopenia and 1 patient with renal failure, all of the clinical manifestations, including thrombocytopenia, central nervous system (CNS) lupus, thrombophlebitis, lung infarction, and recurrent abortions in the SLE patients with APS, improved after plasmapheresis. Plasmapheresis is thought to be an influential strategy of treatment for patients with collagen vascular diseases.

Adult↗

Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.

Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer.

Biopsy, Needle↗