PubMed Health⌕ Search

Biomedical subjects

Shinji Tanaka

Publications and source records attributed to Shinji Tanaka.

At least 145 records · Page 8Linked to original sources
PubMed2002

Thrombospondin-1 mediates smooth muscle cell proliferation induced by interaction with human platelets.

OBJECTIVES: Platelet adherence and activation are associated with smooth muscle cell (SMC) proliferation and arterial restenosis. This study examined platelet-SMC interaction on fibrillar type I collagen and analyzed the role of thrombospondin (TSP)-1 in platelet-induced SMC proliferation. METHODS AND RESULTS: When SMCs cultured on fibrillar collagen were treated with human platelets (5 preparations), 7.45+/-2.94% of the cells passed through S phase within 24 hours, as determined by bromodeoxyuridine nuclear labeling. The addition of platelets markedly induced SMC TSP-1 mRNA expression and cell surface protein accumulation, which colocalized with adhered platelets, as determined by alpha(IIb) integrin immunostaining. Direct interaction of platelets with SMCs was necessary for its effect on proliferation and TSP-1 accumulation, as determined in the transwell culture system. The anti-TSP-1 blocking antibody strongly inhibited platelet-induced SMC proliferation by approximately 60%. Analysis of the receptors for TSP-1 accumulation on the SMC surface revealed that beta1 integrins are mainly involved. The anti-beta1 integrin blocking antibody, which potently suppressed TSP-1 accumulation on SMCs, also markedly inhibited platelet-stimulated SMC proliferation. CONCLUSIONS: TSP-1 and beta1 integrin interaction is involved in platelet-stimulated SMC proliferation. This in vitro coculture system could prove useful for examining the molecular mechanism underlying platelet-induced vascular remodeling and for studying the mechanism of a tested drug for restenosis.

Arteriosclerosis↗
PubMed2002

p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis.

p53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis (H. pylori-CG). We, therefore, examined the polymorphism in 117 gastric cancer patients (72 intestinal type and 45 diffuse type) with H. pylori-CG and 116 H. pylori-CG patients without gastric cancer as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the p53 codon 72 polymorphism. The crude genotypic frequencies in the gastric cancer patients were similar to those of the controls. However, when gastric cancers were classified by histologic subtype, the Pro/Pro was more frequent in the patients with diffuse type gastric cancer than in the controls (22.2% of cases vs. 12.1% of controls). The Pro/Pro genotype was associated with a 2.98-fold higher risk of diffuse-type cancer compared to the Arg/Arg genotype (95% confidence interval [CI] 1.07-8.32, p = 0.038). These results suggest that the Pro/Pro genotype at p53 codon 72 contributes to susceptibility for diffuse-type gastric cancer in patients with H. pylori-CG. The p53 codon 72 polymorphism may serve as the genetic marker for the risk assessment of the diffuse-type gastric cancer development in patients with H. pylori-CG.

Adult↗
PubMed2002

(P(C(6)H(5))(3))CpRu(+)-catalyzed deprotection of allyl carboxylic esters.

A new and efficient catalytic method for deprotection of allyl carboxylic esters using a transition metal complex is reported. The reaction proceeds with a high substrate/catalyst ratio and without use of additional nucleophiles, giving the deprotected carboxylic acid in a quantitative yield. A variety of substrates, including the multifunctional amino acids and peptides, are also usable. The new method is more efficient, safe, and operationally simple in comparison to the conventional palladium-catalyzed method.

Journal Article↗
PubMed2002

K-ras mutation in helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer.

Mutations of an oncogene, K-ras, are associated with the development and progression of many types of human cancer. To elucidate the significance of K-ras mutations in gastric carcinogenesis, we examined K-ras mutations in gastric cancers and in Helicobacter pylori-associated chronic gastritis (H. pylori-CG), which is associated with an increased risk for the gastric cancer development. Specimens of gastric cancer and H. pylori-CG were obtained from 64 gastric cancer patients with H. pylori-CG, 99 cancer-free H. pylori-CG patients and 30 H. pylori-negative healthy subjects. K-ras mutations were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by DNA sequencing analysis. K-ras mutations were detected in 4 of 48 (8.3%) gastric cancers, in 10 of 163 (6.1%) H. pylori-CG and none of the 30 H. pylori-negative healthy subjects. In the gastric cancer patients, mutated K-ras was detected in differentiated type cancers but not in any of the undifferentiated type cancers. K-ras mutations in H. pylori-CG were significantly more frequent in gastric cancer patients than in cancer-free patients (10.9% vs. 3.0%, p = 0.044). In addition, K-ras mutations in H. pylori-CG were significantly more frequent in patients with K-ras mutated gastric cancer than in patients with K-ras unmutated gastric cancer (50.0% vs. 3.7%, p = 0.037). These data suggest that the genetic mechanism(s) of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric cancer and that K-ras mutations may be involved in the early stages of gastric carcinogenesis of the differentiated type.

Biopsy↗
PubMed2002

Electroporation-mediated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L gene therapy for hepatocellular carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L) has been identified as important in promoting programmed cell death in breast and colon cancer xenografts. More importantly, normal liver tissue appears not to be susceptible to the cytotoxic effects of TRAIL/Apo2L, although activation of the related Fas ligand receptor system is known to promote massive liver apoptosis terminating in fulminant hepatitis. In the present study, we investigated the therapeutic potential of TRAIL/Apo2L gene therapy in hepatocellular carcinoma (HCC) and evaluated its side effects in an immune-competent mouse model. Intratumoral administration of the TRAIL/Apo2L vector by electroporation elevated serum TRAIL/Apo2L through at least day 28 after gene therapy and significantly inhibited the growth not only of the HCC directly administered TRAIL/Apo2L vector, but also of distant subcutaneous HCC. In addition, intratumoral administration of the TRAIL/Apo2L vector inhibited spontaneous lung metastasis. Serum alanine aminotransferase was mildly elevated by TRAIL/Apo2L gene therapy, but without showing such histological signs as TUNEL staining. These results demonstrate that TRAIL/Apo2L gene therapy for HCC by electroporation in vivo is efficient without significant side effects, and is thus promising for use in future clinical trials.

Animals↗
PubMed2002

Usefulness of hydrophilic coating on arterial sheath introducer in transradial coronary intervention.

Radial artery spasm is one of the major problems during transradial coronary intervention (TRI). The sheath introducer with hydrophilic coating may reduce the incidence of spasm and reduce the difficulty in removing it from the radial artery under the situation of spasm artery spasm. After we compared the friction resistance between the sheath introducer with hydrophilic coating and that without coating (nine samples each) in vitro, the sheath introducers with and without hydrophilic coating were randomly used in 37 and 36 patients, respectively, who underwent elective TRI with a 6 Fr introducer sheath. Hydrophilic coating of sheath introducer reduced friction resistance by 70% (P < 0.00001) in in vitro model and facilitated sheath removal after finishing TRI (P = 0.0003). Hydrophilic coating of sheath introducer is useful in TRI.

Catheterization, Peripheral↗
PubMed2002

Implication of anti-parietal cell antibody levels in gastrointestinal diseases, including gastric carcinogenesis.

We investigated serum levels of anti-parietal cell antibody (APCA) in relation to various gastric diseases. Subjects were 224 Japanese patients including 58 with gastric cancer. All patients underwent gastroscopy, and APCA was investigated by enzyme-linked immunosorbent assay. Unexpectedly, there was no difference in APCA levels between patients with gastric cancer and those with gastritis. Among H. pylori-positive patients, APCA levels were closely correlated with grades of atrophy when no gastric cancer was present, but no correlation was found when gastric cancer was present. APCA-negative gastric cancer was found mainly in males and was characterized by massive infiltration of neutrophils in the background mucosa. The 24 patients with gastric cancer were APCA-negative and showed low pepsinogen levels. The odds ratio for the incidence of gastric cancer in these patients was 7.90 (95% CI 3.4-18.4). This suggests APCA-negative gastric cancer is the predominant form of gastric cancer in Japan.

Adult↗
PubMed2002

Interrelation between expression of matrix metalloproteinase 7 and beta-catenin in esophageal cancer.

Matrix metalloproteinase 7 (MMP-7) may play a key role in the progression of various human malignant tumors. Nuclear beta-catenin enhances the activating expression of MMP-7 genes by binding with the T-cell factor/lymphoid enhancer factor family of transcription factors. We immunohistochemically examined the expression of MMP-7 and beta-catenin to better understand the significance of these factors in the progression of esophageal squamous cell carcinoma. The entire coding region of beta-catenin exon 3 was also analyzed by direct sequencing in all cases. We found that MMP-7 was expressed in 7 (20.6%) of 34 esophageal squamous cell carcinomas. There was a significant relationship between MMP-7 expression and tumor invasion into adjacent structures (P < 0.05). Aberrant nuclear expression of beta-catenin was found in 12 of 34 (35.3%) esophageal cancers and correlated with MMP-7 expression, the statistical difference being (P < 0.05). None of the 34 esophageal cancers examined carried mutations in beta-catenin exon 3. MMP-7 expression correlates with penetrating tumor progression in esophageal cancer. Nuclear translocation of beta-catenin, without mutations in beta-catenin exon 3, is associated with MMP-7 expression.

Adult↗
PubMed2002

Clinical characteristics and natural history of patients with low-grade reflux esophagitis.

BACKGROUND AND AIM: Although the incidence of reflux esophagitis (RE) has recently increased in Japan, the majority of these cases are mild (Los Angeles classification grades A and B). In order to consider therapy for these patients, it is important to understand the natural history of mild RE. There is little information concerning the natural course of RE, particularly low-grade disease. The goal of this study is to elucidate the natural course of patients with mild RE and to identify specific prognostic indicators associated with a poor outcome. METHODS: One hundred and five patients with mild RE were followed, without medical treatment, by endoscopy in addition to a questionnaire regarding symptomatology, for a mean of 5.5 years (range, 2.0-8.8 years) after initial diagnosis. Factors associated with the development of severe esophagitis were analyzed. RESULTS: Endoscopically, 11 patients (10.5%) progressed to more severe forms of RE (recurrent progressive (RP) group), 60.0% of patients relapsed without disease progression (recurrent non-progression group), and the remaining 29.5% of patients had no further episodes of RE (isolated episode group). Risk factors for progressive disease were increased age, female sex, the presence of symptoms at initial diagnosis by endoscopy, presence of a hiatal hernia, absence of atrophic gastritis, and absence of Helicobacter pylori infection. Despite having all risk factors, there were six patients who did not progress to more severe forms of RE. The primary esophageal peristaltic amplitude in these patients was significantly higher than in the RP group. CONCLUSIONS: Among patients with mild RE, only 10.5% progressed to more severe forms of RE. The patients with risk factors are candidates for aggressive therapy in order to prevent the progression of the RE disease process.

Aged↗
PubMed2002

Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is generally characterized as a hypervascular tumor of rapid growth. We have previously reported that angiopoietin (Ang), a ligand for Tie2 vascular endothelial-specific receptor tyrosine kinase, may play a role in the progression of human HCC (J Clin Invest 1999;103:341-345) and matrix proteinase expression (Cancer Res 2001;61:2145-2153). However, the role of Tie2 receptor in hepatic oncogenesis is unknown. The Tie2 receptor protein was overexpressed in the neovascular endothelium of 31 of 39 (80%) human HCC tumors by immunohistochemical analysis with significant correlation to cell dedifferentiation and tumor size (P <.05). In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Ang protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells and matrix metalloproteinase 9 (MMP-9) suppression. In conclusion, tumorigenicity with neovascularization was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for Tie2 expression in the induction of HCC neovascularization and disease progression. Inhibition of the Ang/Tie2 signal transduction cascade is a promising approach for tumor treatment.

Angiopoietin-1↗
PubMed2002

The mechanisms of angiogenesis in hepatocellular carcinoma: angiogenic switch during tumor progression.

Solid tumors constantly require a vascular supply for their progression and metastasis. Hepatocellular carcinoma (HCC) is known to gain its hypervascularity during the process of dedifferentiation and progression. Various angiogenic growth factors and inhibitors regulate this angiogenic switch of HCC. The known endothelial cell-specific growth factors and their receptors can be classified into the vascular endothelial growth factor and angiopoietin families. Both vascular endothelial growth factors and angiopoietins have been found to work cooperatively, and both are essential for HCC angiogenesis. Because small and ill-vascularized HCCs slowly progress and only rarely metastasize, antiangiogenic therapy could therefore be a promising anticancer strategy for HCC.

Carcinoma, Hepatocellular↗
PubMed2002

Oncogenic signal transduction and therapeutic strategy for hepatocellular carcinoma.

Discoveries of oncogenic signaling molecules lead to the comprehension of molecular mechanisms of tumor progression, as well as to the development of novel therapeutic tools for hepatocellular carcinoma. We have identified critical functions of intracellular signals transmitted from insulin-like growth factor and Wnt oncoprotein in carcinogenesis. The insulin-like growth factor system activates a number of signaling cascades resulting not only in hepatic mitogenesis, but also in cell survival. The secreted oncoprotein Wnt transforms beta-catenin potentials as a component of cell adhesion complexes with cadherins, into a transcription factor in the nucleus. Here, the important role of such signal transduction is reviewed, and we emphasize its control as a promising approach for the treatment of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed2002

Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma.

BACKGROUND: The long-term prognosis after resection for patients with hepatocellular carcinoma is still unsatisfactory because of the high recurrence rate. The survival of patients with multiple intrahepatic or extrahepatic recurrence is especially poor. METHODS: Among the patients who underwent hepatic resection for hepatocellular carcinoma between 1981 and 2000, 216 patients with 3 or less than 3 intrahepatic recurrences (group B); 156 patients with more than 3 intrahepatic recurrences, extrahepatic recurrences, or both (group C); and 51 patients who survived more than 5 years without recurrence (group A) were clinicopathologically studied. RESULTS: The period to recurrence of group C was significantly earlier than that of group B and also showed a significantly poor prognosis after recurrence. Tumor factors, including size, portal venous invasion, intrahepatic metastasis, histologic grade, or the number of tumors at resection in group C was significantly worse than in groups A and B. Although no differences are recognized in the tumor factors between groups A and B, except for the alpha-fetoprotein level, liver function in group B was significantly worse than that in group A. In addition, the frequency of hepatitis B surface antigen in group B and that of hepatitis C virus in group B was significantly less and higher than that in group A, respectively. CONCLUSION: Similar to extrahepatic metastasis, multinodular recurrences are also mainly caused by metastatic recurrence from the main tumor by means of the portal system, and recurrences with up to 3 intrahepatic nodules are mainly caused by metachronous multicentric hepatocarcinogenesis. Because the mechanisms of recurrence differed, determining the patterns of recurrence on the basis of the clinicopathologic findings is important for selecting the optimal postoperative therapy for each individual patient.

Alanine Transaminase↗
PubMed2002

Clinical significance of PEA3 in human breast cancer.

BACKGROUND: Recently, PEA3 has been reported to suppress HER-2/neu overexpression by promoter activity and thereby inhibit tumorigenesis of breast cancer both in vitro and in vivo. METHODS: The expression of PEA3 and the clinicopathologic features of 89 patients with breast cancer were investigated. The expression of PEA3 was immunohistochemically detected in 42 (47.2%) of 89 patients. RESULTS: The correlation between the expression of PEA3 and the clinicopathologic features were nil with regard to lymph node metastasis, hormone receptor, blood vessel invasion, and lymphatic vessel invasion. The disease-free survival rate was shorter for the PEA3-negative groups than for the PEA3-positive ones, but with no statistically significant difference. The overall survival rate after surgical resection in patients who were PEA3-positive vs PEA3-negative was 100% vs 87.2%, respectively, at 3 years and 89.8% vs 72.7%, respectively, at 6 years (P =.0472). CONCLUSIONS: The expression of PEA3 in breast cancer might therefore be a novel prognostic factor.

Adult↗
PubMed2002

Evaluation of genetic heterogeneity in neuroblastoma.

BACKGROUND AND METHODS: The prognosis in neuroblastoma, which is the most common solid tumor in children, tends to vary greatly, and many studies have demonstrated both clinical and biological factors to be closely correlated with the outcome. In order to select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic heterogeneity associated with the prognosis. We assessed the status of some genetic abnormalities (MYCN amplification, deletion of the short arm of chromosome 1, DNA ploidy, and a gain of the chromosome 17q region) associated with the prognosis using several molecular biological methods. RESULTS AND CONCLUSIONS: The combination of several molecular biological techniques is thus considered to be useful for elucidating the degree of malignancy of neuroblastoma. In particular, diagnostic analyses based on a combination of the fluorescence in situ hybridization (FISH) method and the quantitative polymerase chain reaction (PCR) method may be considered to be the most effective methods for quickly and accurately evaluating any aberrations in the gene dosages associated with the patients' outcomes.

Chromosomes, Human, Pair 1↗