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Biomedical subjects

M Yashiro

Publications and source records attributed to M Yashiro.

At least 37 records · Page 2Linked to original sources
PubMed2000

ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node metastasis by human gastric cancer cells.

Lymph node metastasis is one of the prognostic factors in gastric cancer. We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression on cancer cells is associated with lymph node metastasis using a gastric cancer cell. In this study, we transfected ICAM-1 gene into a gastric cancer cell line, 2MLN, and analyzed the effect on lymph node metastasis in vitro and in vivo. A significantly greater amount of peripheral blood mononuclear cells (PBMC) adhered to ICAM-1 transfected 2MLN cells, 2MLN / ICAM cells, than to 2MLN / Vector cells. The lysis of 2MLN / ICAM cells by PBMC was significantly increased compared with that of 2MLN / Vector cells. The tumor growth rate of 2MLN / ICAM cells was significantly decreased in vivo. Lymph node metastases caused by 2MLN / ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases were caused by 2MLN cells. Histologic findings showed that leukocytes were heavily infiltrated in both the 2MLN / ICAM tumors and metastatic lesions, while only a few leukocytes were observed in the lesions associated with 2MLN cells. The above findings indicate that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer.

Animals↗
PubMed2000

Significant suppressive effect of low-dose temocapril, an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats.

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril - TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Increased expression of alpha2beta1-integrin in the peritoneal dissemination of human gastric carcinoma.

The prognosis of advanced gastric cancer remains poor, given the frequent incidence of peritoneal metastasis. beta1-integrin is known to be associated with metastasis, though few reports have addressed the expression of beta1-integrin subunits in gastric cancer at primary and peritoneal lesions from the perspective of individual cases. We studied specimens from primary tumors from 50 patients and from metastatic peritoneal lesions from 27 patients with gastric carcinoma, including specimens from 22 metastatic lesions taken from the same patients whose primary tumors were sampled. Expression of beta1-integrin subunits, alpha2-alpha6beta1 integrins, was studied using an immunohistochemical method. alpha2beta1-integrin was significantly expressed on a larger proportion of tumor cells in peritoneal metastasis (70.4%) than in primary tumors (48%) (p<0.05), though alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1-integrins did not demonstrate significant discrepancy. The expression of alpha2beta1-integrin in peritoneal lesions was significantly increased compared with its expression in the primary lesion in the same individual. In contrast, no relationship was found between the expression level of beta1 integrins and clinicopathological parameters. Peritoneal implantation of gastric carcinoma might be closely associated with alpha2beta1-integrin.

Adult↗
PubMed2000

Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Solid tumors require neovascularization for growth and metastasis. Vascular endothelial growth factor (VEGF) is a well-characterized inducer of angiogenesis, while, thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the expressions of these antigens and their relationship with microvessel density, and determined their prognostic significance. One hundred specimens resected from patients with colorectal adenocarcinoma were examined using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were VEGF-positive and TSP-1-negative than in other tumors. Patients with VEGF-positive tumors had a significantly worse prognosis than did those with VEGF-negative tumors, and TSP-1 expression was inversely correlated with prognosis. The frequency of hepatic recurrence was significantly higher in patients with tumors that were VEGF-positive and TSP-1-negative than in all other patients. In conclusion, VEGF and TSP-1 are important regulators of tumor angiogenesis, and combined analysis of VEGF and TSP-1 may be useful for predicting recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Caspase-1 activity as a possible predictor of apoptosis induced by cisplatin in gastric cancer cells.

Recent studies have shown that caspases, which are cystein proteases, elevate endonuclease activity and induce apoptosis. Caspase-1, an interleukin-1beta converting enzyme, has been reported to be related with anti-cancer drug induced apoptosis as well as with caspase-3. To elucidate the caspase-1 activity, which might be a predictor for the effect of chemotherapy, we examined the changes of caspase-1 activity induced after exposure to cisplatin (CDDP) in six gastric cancer cell lines. A high correlation between the 50% inhibitory concentration (IC50) and caspase-1 activity ratio was shown (r=0.83, p=0.041) (caspase-1 activity ratio: the caspase-1 activity of cells at 4 h after CDDP treatment/the caspase-1 activity of untreated cells). Further, we examined the correlation between caspase-1 activity and apoptosis induced by CDDP in two cell lines that have very different CDDP sensitivities; OCUM-2M and OCUM-2M/DDP (IC50; 0. 85+/-0.4 microg/ml and 9.0+/-1.2 microg/ml, respectively). The apoptotic index of OCUM-2M was significantly higher than that of OCUM-2M/DDP (19.8+/-3.8% vs. 4.5+/-1.2%, respectively; p=0.0005). In both cell lines, caspase-1 activity began to increase immediately after exposure to CDDP and peaked at approximately 4 h after cessation of exposure to CDDP, and gradually decreased thereafter. The caspase-1 activity of OCUM-2M was approximately 1.8-times higher than that of OCUM-2M/DDP at 4 h after exposure to CDDP. Taken together, our results indicate that evaluating the changes of caspase-1 activity after exposure to CDDP may be useful to predict apoptosis following CDDP treatment in gastric cancer cells.

Antineoplastic Agents↗
PubMed2000

TGF-beta1 secreted by gastric fibroblasts up-regulates CD44H expression and stimulates the peritoneal metastatic ability of scirrhous gastric cancer cells.

Gastric fibroblast-derived conditioned medium and TGF-beta1 stimulated the adhesion ability of scirrhous gastric cancer cells to mesothelial cells, but not that of well-differentiated gastric cancer cells. The CD44H expression of scirrhous gastric cancer cells was significantly up-regulated by gastric fibroblast-derived CM and TGF-beta1. The stimulated adhesion ability and CD44H expression was significantly inhibited by anti TGF-beta1 neutralizing antibody. These findings suggested that TGF-beta1 secreted by gastric fibroblasts up-regulated the CD44H expression of scirrhous gastric cancer cells, which resulted in the stimulation of the adhesion ability of scirrhous gastric cancer cells to the mesothelium, and increased the peritoneal dissemination potential. These results might explain one of the reasons why scirrhous gastric carcinomas develop frequent peritoneal dissemination.

Adenocarcinoma, Scirrhous↗
PubMed2000

Clinical significance of serum soluble intercellular adhesion molecule 1 in gastric cancer.

We studied the correlation between serum soluble intercellular molecule 1 (sICAM-1) and clinicopathological features in patients with gastric cancer. The impact of sICAM-1 on prognosis was also evaluated. The sera from 224 patients with gastric cancer, 44 healthy individuals, and 35 patients with benign gastrointestinal diseases (4 patients with submucosal stomach tumors, 6 patients with gastric ulcers, 1 patient with Crohn disease, 2 patients with ulcerative colitis, 7 patients with gall stones, 5 patients with chronic pancreatitis, and 10 patients with liver cirrhosis) were measured for sICAM-1 titer using a sandwich enzyme immunoassay method. There was no correlation between the serum titer of sICAM-1 and the age or gender of healthy controls. Among patients with benign gastrointestinal diseases, the patients with liver cirrhosis had a significantly higher mean serum sICAM-1 titer than that of healthy controls (P < 0.0001). The mean serum sICAM-1 titer of all patients with gastric cancer was not significantly different from that of healthy controls. However, among the patients with stage IV and recurrent disease, the serum sICAM-1 titer of those with hematogenous metastasis was significantly higher than that of patients without hematogenous metastasis (P = 0.001). The patients with a high serum sICAM-1 titer of more than 304 ng/ml (mean of healthy controls plus SD) showed a significantly worse prognosis than patients with a low serum sICAM-1 titer (P = 0.010). Nevertheless, serum sICAM-1 titer was not an independent predictor of prognosis by multivariate analysis. In conclusion, serum sICAM-1 cannot be used as a tumor marker for early diagnosis. However, sICAM-1 in sera may still be worthwhile to measure for monitoring hematogenous metastasis.

Adult↗
PubMed2000

[Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease].

Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.

Adult↗
PubMed2000

[Three cases of metastatic breast cancer, resistant to pre-chemo and/or endocrine therapy, markedly improved with UFT and cyclophosphamide oral combination therapy].

The cases of 3 female patients with metastatic breast cancer treated with oral UFT and cyclophosphamide (CPA) are reported. Patient 1 had lymph node and bone metastases. Patient 2 had bone metastasis. Patient 3 had skin, lymph node, and peritoneal metastases. All had a history of mastectomy and chemo- and/or endocrine therapy for metastatic lesions. Patients 2 and 3 had also undergone CAF combination chemotherapy. However, the lesions did not change. UFT 400 mg and CPA 100 mg, everyday, were administered to patient 1. UFT 400 mg and CPA 100 mg, 2 weeks, and UFT 400 mg, 2 weeks, were given every 4 weeks to patient 2. UFT 300 mg and CPA 150 mg, 6 weeks per 8 weeks were given to patient 3. Improvements in the metastatic lesions were seen 4 weeks after the beginning of UFT and CPA therapy. Therapy is now continuing, and no patients had a progression of the disease. All had leukopenia 2 or 4 weeks after the beginning of this therapy, and two temporarily stopped the therapy. No other side-effect was observed. Oral UFT and CPA combination therapy was considered useful for metastatic breast cancer. To prevent leukopenia and prolong the term of treatment efficacy, a treatment regimen will need to be established.

Administration, Oral↗
PubMed2000

[Validity of the infectious disease surveillance system on comparison of nationwide surveys of Kawasaki disease during a 10 year period].

PURPOSE: To verify the validity of the infectious disease surveillance system in Japan using data for Kawasaki disease. MATERIALS AND METHODS: Data from nationwide surveys of Kawasaki disease conducted by the Kawasaki Disease Research Committee every two years over the 10 years (120 months) from 1989 through 1998 were used to calculate a gold standard. Then, the monthly numbers of patients with Kawasaki disease reported by monitoring hospitals (about 550 hospitals) to the surveillance system were compared with this gold standard. Each of the monthly numbers was standardized by division by the average monthly number of patients over the 120 months. Observations for 3 districts (eastern part, central part, and western part of Japan) were conducted as well as for the whole country. RESULTS: The number of patients reported to the surveillance system varied more widely than in the nationwide survey, but directions of the fluctuations were similar to the chronologic changes in nationwide numbers. Accordingly, a high correlation coefficient value of 0.794 was obtained (p < 0.01). Similar results were observed in all 3 districts. The correlation coefficients were 0.709 for the eastern part, 0.561 for the central part, and 0.712 for the western part, respectively, and all of them were of statistically significant. CONCLUSION: Changes in number of patients with Kawasaki disease reported to the surveillance system resemble the pattern of the gold standard.

Communicable Diseases↗
PubMed1999

Factors related to cardiac sequelae of Kawasaki disease.

Among the 35.210 patients with Kawasaki disease who were reported in nationwide surveys from 1991 to 1996, 83% were treated with gamma-globulin (GG). Those treated with a total dose of 1000 mg/kg (9098 patients) and 2000 mg/kg (7012 patients) were selected as the subjects of the study on the relationship between the development of cardiac sequelae, in particular of giant aneurysms, and related factors using logistic regression models. Among the two groups that received 1000 mg/kg and 2000 mg/kg, respectively, the odds ratios for cardiac sequelae were significantly high for males, those < 6 months and > or = 7 years of age, and typical or recurrent cases. Except for those < 6 months of age, the odds ratios of all the factors mentioned above were higher for the incidence of giant coronary aneurysms than those for cardiac sequelae. The preventive effects of GG therapy for cardiac sequelae and in particular giant aneurysms, were significantly low when GG administration was initiated on day 8 or later after onset. In the group treated with 1000 mg/kg, the preventive effect was low when GG administration was spread over 3 days or longer. To prevent the development of cardiac sequelae, in particular giant coronary aneurysms, gamma-globulin therapy should be started as soon as possible and be completed within 2 days.

Child↗
PubMed1999

Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice.

BACKGROUND: RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. METHODS: Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C3), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-beta, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. RESULTS: High levels of serum IgA and IgG from as early as 20 weeks of age were noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL-lpr/lpr mice, and serum C3 concentration significantly decreased with age, reaching lower levels than that of BALB/c mice. IgA-IC levels were significantly high compared to BALB/C mice both in the early and late stages of life, whereas IgG-IC levels were high only in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-beta1 (TGF-beta1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly up-regulated in the early stage of life, the differences between the mice disappeared in the late stage of life. CONCLUSIONS: These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrix accumulation in glomeruli was induced by up-regulated expression of TGF-beta with inappropriate regulation of protein turnover-related enzyme production.

Age Factors↗
PubMed1999

Direct inhibitory effects of simvastatin on matrix accumulation in cultured murine mesangial cells.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been demonstrated to suppress glomerular injuries in various renal diseases. These agents inhibit in vitro proliferation of several cell types, including mesangial cells. This effect indicates the ability to ameliorate mesangioproliferative lesions, independent of the improvement of hypercholesterolemia. On the other hand, it is not clear whether HMG-CoA reductase inhibitors directly regulate extracellular matrix (ECM) accumulation from mesangial cells. METHODS: In this study, to examine the in vitro effects of simvastatin, an HMG-CoA reductase inhibitor, on mRNA expressions of matrix proteins, growth factors, and matrix turnover proteins, we incubated cultured murine mesangial cells stimulated by fetal calf serum (FCS) with or without simvastatin for 24 hours, and Northern analysis was performed. RESULTS: Simvastatin showed a slightly suppressive effect on mRNA expression of type IV collagen and fibronectin and a slightly up-regulative effect on that of type I collagen, whereas mRNA expression of type III collagen was markedly up-regulated. mRNA expression of platelet-derived growth factor (PDGF)-B chain and PDGF receptor beta-subunit was suppressed, whereas that of transforming growth factor-beta (TGF-beta) was not affected by simvastatin. Concerning matrix turnover proteins, simvastatin markedly reduced mRNA expression of plsminogen activator inhibitor-1 (PAI-1) without affecting the expression of tissue-type plasminogen activator (tPA). CONCLUSION: These results suggest type-specific modulation of matrix protein production independent of TGF-beta and the suppressive effects of autocrine PDGF by administration of HMG-CoA reductase inhibitors in mesangial cells. Moreover, the beneficial effects of these agents on matrix protein accumulation may be through promoting ECM degradation derived from PAI-1 suppression.

Animals↗
PubMed1999

Changes in epidemic patterns of Kawasaki disease in Japan.

OBJECTIVE: Clustering of cases of Kawasaki disease throughout Japan was noted three times during the period before 1986. During the ensuing 10 years, however, no nationwide epidemic has been recognized. The purpose of this study is to test the hypothesis that local outbreaks have persisted after 1987. METHOD: The data on 56 980 patients reported from 1987 through 1996 were classified according to the area of residence. The time trend of the incidence rate was compared by year and by quarter of the year (January to March, April to June, July to September and October to December) in 10 geographical areas in Japan. RESULTS: No nationwide outbreaks have been noted since 1987 in Japan, but the existence of local outbreaks of various magnitudes was recognized as occurring in different periods in certain areas. The incidence rates were continuously high in Area 1 between 1987 and 1988 and in Area 4 between 1995 and 1996. In Area 9 local outbreaks were noted on three separate occasions (from 1987 to the first half of 1988, between 1990 and 1991 and from the second half of 1992 to 1993). No clusterings were witnessed in other areas during the 10-year period. CONCLUSION: The current annual number of patients ranges from 5000 to 6000, and local epidemics occur in various areas. The current epidemiologic patterns support the infection theory for the etiology of this disease.

Cluster Analysis↗
PubMed1999

Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer.

Proteolytic activity of cancer cells is an important factor in metastasis. This study examined the relationship between MMP-1 expression of gastric cancer cells and peritoneal metastasis. MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a prognostic factor in case of advanced gastric cancer and might be useful in determining whether or not adjuvant therapy was indicated for patients at high risk of peritoneal recurrence.

Adult↗
PubMed1998

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis.

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metastasis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mechanism and therapeutic approach of lymph node metastasis.

Adenocarcinoma, Scirrhous↗
PubMed1998

Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer.

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both alpha2beta1 and alpha3beta1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.

Adenocarcinoma, Scirrhous↗