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Yutaka Shimada

Publications and source records attributed to Yutaka Shimada.

At least 55 records · Page 3Linked to original sources
PubMed2005

CDC2/CDK1 expression in esophageal adenocarcinoma and precursor lesions serves as a diagnostic and cancer progression marker and potential novel drug target.

Esophageal adenocarcinoma arises through well-defined precursor lesions (Barrett esophagus), although only a subset of these lesions advances to invasive adenocarcinoma. The lack of markers predicting progression in Barrett esophagus, typical presentation at advanced stage, and limitations of conventional chemotherapy result in >90% mortality for Barrett-associated adenocarcinomas. To identify potential prognostic markers and therapeutic targets, we compared gene expression profiles from Barrett-associated esophageal adenocarcinoma cell lines (BIC1, SEG1, KYAE, OE33) and normal esophageal epithelial scrapings utilizing the Affymetrix U133_A gene expression platform. We identified 560 transcripts with >3-fold up-regulation in the adenocarcinoma cell lines compared with normal epithelium. Utilizing tissue microarrays composed of normal esophageal squamous mucosa (n = 20), Barrett esophagus (n = 10), low-grade dysplasia (n = 14), high-grade dysplasia (n = 27), adenocarcinoma (n = 59), and node metastases (n = 27), we confirmed differential up-regulation of three proteins (Cdc2/Cdk1, Cdc5, and Igfbp3) in adenocarcinomas and Barrett lesions. Protein expression mirrored histologic progression; thus, 87% of low-grade dysplasias had at least focal surface Cdc2/Cdk1 and 20% had >5% surface staining; 96% of high-grade dysplasias expressed abundant surface Cdc2/Cdk1, while invasive adenocarcinoma and metastases demonstrated ubiquitous expression. Esophageal adenocarcinoma cell lines treated with the novel CDC2/CDK1 transcriptional inhibitor, tetra-O-methyl nordihydroguaiaretic acid (EM-1421, formerly named M4N) demonstrated a dose-dependent reduction in cell proliferation, paralleling down-regulation of CDC2/CDK1 transcript and protein levels. These findings suggest a role for CDC2/CDK1 in esophageal adenocarcinogenesis, both as a potential histopathologic marker of dysplasia and a putative treatment target.

Adenocarcinoma↗
PubMed2005

Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines.

The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2005

Effect of curcuma herbs on vasomotion and hemorheology in spontaneously hypertensive rat.

Curcuma herbs have a vasodilator effect. The effects of C. longa, which induces only endothelium-independent vasodilatation, and C. zedoaria, which induces both endothelium-dependent and -independent vasodilatation, were studied on vasomotion and hemorheology in spontaneously hypertensive rats. Spontaneously hypertensive eight-week-old male rats were assigned to five groups. For 12 weeks, the control group received standard chow. The 3%CL (C. longa) group received standard chow containing 3% (wt/wt) C. longa. The 1%CZ and 3%CZ (C. zedoaria) groups received standard chow containing 1% and 3% (wt/wt) C. zedoaria, respectively. The captoril group received standard chow and 100 mg/kg/day of captoril in drinking water. Blood pressure, vasomotion, hemorheology, etc. were examined. Systolic blood pressure of the 3%CZ and captoril groups decreased significantly as compared to the control group. Acetylcholine-induced endothelium-dependent relaxations of the 3%CZ and captoril groups were increased to a greater degree, significantly, than the control group. When testing xanthine oxidase-induced contraction, the 3%CZ group was significantly decreased as compared to the control group. Low shear stress of whole blood viscosity showed the 3%CL and 3%CZ groups to be decreased significantly compared to the control group. Thus, Curcuma herbs have hypotensive and protective effect on the endothelium in spontaneously hypertensive rats. Especially, C. zedoaria is more effective than C. longa, and its mechanism is thought to be related to a radical scavenging effect and improvement of hemorheology.

Animals↗
PubMed2005

Long-term treatment with Hachimi-jio-gan attenuates kidney damage in spontaneously diabetic WBN/Kob rats.

Diabetes mellitus is now the most common cause of end-stage renal failure. In this study, the effects of Hachimi-jio-gan on diabetic kidney damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of Hachimi-jio-gan to WBN/Kob rats for 25 weeks significantly suppressed urinary protein excretion. It did not affect body weight loss or blood glucose levels, whereas it reversed the increase in kidney weight of WBN/Kob rats. Hachimi-jio-gan also reduced fibronectin and transforming growth factor beta1 (TGF-beta1) protein expression in the renal cortex. Furthermore, renal lipid peroxidation levels of WBN/Kob rats given Hachimi-jio-gan were significantly lower than those of untreated controls. Renal superoxide dismutase activity was elevated by Hachimi-jio-gan treatment in a dose-dependent manner. These results suggested that Hachimi-jio-gan could prevent diabetic kidney damage by reducing renal oxidative injury and expression of fibronectin and TGF-beta1 proteins, which are all involved in the pathophysiology of diabetic nephropathy.

Administration, Oral↗
PubMed2005

Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits.

In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.

Animals↗
PubMed2005

Inhibitory effects of Stephania tetrandra S. Moore on free radical-induced lysis of rat red blood cells.

Crude preparations of Stephania tetrandra S. MOORE (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. In this study, we demonstrated that ST in vitro protects red blood cells from 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 10 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of ST that exerts a scavenging effect on free-radicals. Three representative alkaloids, tetrandrine, fangchinoline, and cyclanoline, isolated from ST, were found to have inhibitory activities against AAPH-induced lysis of red blood cells (RBC). Furthermore, the ingestion of 200 mg of ST extract was associated with a significant increase in free-radical scavenging effect of plasma in rats. These results suggest that ST as antioxidant inhibits AAPH-induced hemolysis of RBC both in vitro and in vivo.

Alkaloids↗
PubMed2005

Inhibitory effects of triterpenes isolated from Chuling (Polyporus umbellatus Fries) on free radical-induced lysis of red blood cells.

Chuling, sclerotia of Polyporus umbellatus FRIES, has long been used for urological disorders in traditional medicine. In this study, we demonstrated that Chuling in vitro protects red blood cells from 2,2-azo-bis(2-amidinopropane)dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 50 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of Chuling with scavenging effect on free radicals. Triterpene carboxylic acids isolated from the methanol extract of Chuling, namely, polyporusterone A and polyporusterone B, were found to have inhibitory activities against AAPH-induced lysis of red blood cells. The anti-hemolytic effect was significantly stronger in polyporusterone B compared with polyporusterone A. Furthermore, the ingestion of 150 mg of Chuling was associated with a significant increase in free-radical scavenging effect of plasma in rats.

Dose-Response Relationship, Drug↗
PubMed2005

Potential in a single cancer cell to produce heterogeneous morphology, radiosensitivity and gene expression.

Morphologically heterogeneous colonies were formed from a cultured cell line (KYSE70) established from one human esophageal carcinoma tissue. Two subclones were separated from a single clone (clone13) of KYSE70 cells. One subclone (clone13-3G) formed mainly mounding colonies and the other (clone 13-6G) formed flat, diffusive colonies. X-irradiation stimulated the cells to dedifferentiate from the mounding state to the flat, diffusive state. Clone 13-6G cells were more radiosensitive than the other 3 cell lines. Clustering analysis for gene expression level by oligonucleotide microarray demonstrated that in the radiosensitive clone13-6G cells, expression of genes involved in cell adhesion was upregulated, but genes involved in the response to DNA damage stimulus were downregulated. The data demonstrated that a single cancer cell had the potential to produce progeny heterogeneous in terms of morphology, radiation sensitivity and gene expression, and irradiation enhanced the dedifferentiation of cancer cells.

Cell Differentiation↗
PubMed2005

Evaluation of esophageal peristalsis in patients with esophageal tumors: initial experience with cine MR imaging.

We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR using steady-state free precession (SSFP) sequence and correlated the alteration of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen patients with pathologically proven esophageal tumors, including 12 esophageal cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging with steady precession (trueFISP) sequence, which is one SSFP sequence, after contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images were obtained within 60 s through the plane along the long axis of the esophagus while patients chewed gum. The serial trueFISP images were evaluated for the presence, frequency, speed of progression, and passage of peristalsis through the tumor. The data from cine MRI were compared with clinical symptoms and tumor stages. Peristalsis was clearly identified in all patients. Seven patients with complete interruption of peristalsis had dysphagia; one with partially impaired peristalsis could intake solid foods with discomfort; and two with partially impaired peristalsis and three with preserved peristalsis remained asymptomatic. Patients with complete or partial interruption of peristalsis had Stage T3 or T4 esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct visualization of esophageal peristalsis in relation to esophageal tumors. Complete interruption of peristalsis causes dysphagia, whereas partial interruption of and preserved peristalsis usually do not cause digestive problems. Interruption of peristalsis may indicate impaired muscle function caused by invasion of advanced esophageal cancers.

Esophageal Neoplasms↗
PubMed2005

Multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas in Japan.

The molecular mechanisms responsible for the development and/or progression of gastrinomas are largely unknown. Studies involving sporadic enteropancreatic neuro-endocrine tumors suggest that mutations in the MEN1 gene occur in some tumors and probably play an important role in their pathogenesis. In this study, we examined whether somatic mutations in the MEN1 gene are also responsible for sporadic gastrinomas and correlate with clinical manifestations of gastrinomas in Japanese patients. Genomic DNA was extracted from paraffin-embedded gastrinoma tissues from 12 patients. Nucleotide sequences in the MEN1 genes were determined by direct sequencing. We identified 6 mutations in 7 out of 12 examined gastrinomas (58%). The identified mutations were 1 non-sense, 2 missense, 1 deletion leading to frame shifts, 1 insertion and 1 splicing mutation. Identical mutations were found in three gastrinoma tissues. The age at surgery, the rate of hepatic metastasis, and tumor status were not significantly different in the 2 groups. This study demonstrates that alterations in the MEN1 gene are involved in about half of all sporadic gastrinomas, although no correlation between the presence of mutations and location and clinical phenotype or severity of disease has been found.

Adult↗
PubMed2004

Myocyte differentiation generates nuclear invaginations traversed by myofibrils associating with sarcomeric protein mRNAs.

Certain types of cell both in vivo and in vitro contain invaginated or convoluted nuclei. However, the mechanisms and functional significance of the deformation of the nuclear shape remain enigmatic. Recent studies have suggested that three types of cytoskeleton, microfilaments, microtubules and intermediate filaments, are involved in the formation of nuclear invaginations, depending upon cell type or conditions. Here, we show that undifferentiated mouse C2C12 skeletal muscle myoblasts had smoothsurfaced spherical or ellipsoidal nuclei, whereas prominent nuclear grooves and invaginations were formed in multinucleated myotubes during terminal differentiation. Conversion of mouse fibroblasts to myocytes by the transfection of MyoD also resulted in the formation of nuclear invaginations after differentiation. C2C12 cells prevented from differentiation did not have nuclear invaginations, but biochemically differentiated cells without cell fusion exhibited nuclear invaginations. Thus, biochemical differentiation is sufficient for the nuclear deformation. Although vimentin markedly decreased both in the biochemically and in the terminally differentiated cells, exogenous expression of vimentin in myotubes did not rescue nuclei from the deformation. On the other hand, non-striated premyofibrils consisting of sarcomeric actinmyosin filament bundles and cross-striated myofibrils traversed the grooves and invaginations. Time-lapse microscopy showed that the preformed myofibrillar structures cut horizontally into the nuclei. Prevention of myofibril formation retarded the generation of nuclear invaginations. These results indicate that the myofibrillar structures are, at least in part, responsible for the formation of nuclear grooves and invaginations in these myocytes. mRNA of sarcomeric proteins including myosin heavy chain and alpha-actin were frequently associated with the myofibrillar structures running along the nuclear grooves and invaginations. Consequently, the grooves and invaginations might function in efficient sarcomeric protein mRNA transport from the nucleus along the traversing myofibrillar structures for active myofibril formation.

Actins↗
PubMed2004

Prediction of lymph node metastasis with use of artificial neural networks based on gene expression profiles in esophageal squamous cell carcinoma.

BACKGROUND: The aim of the study was (1) to detect candidate genes involved in lymph node metastasis in esophageal cancers and (2) to investigate whether we can estimate and predict occurrence of lymph node metastasis by analyzing artificial neural networks (ANNs) using these gene subsets. METHODS: Twenty-eight primary esophageal squamous cell carcinomas were used. Gene expression profiles of all primary tumors were obtained by cDNA microarray. Lymph node metastasis-related genes were extracted with use of Significance Analysis of Microarrays (SAM). Predictive accuracy for lymph node metastasis was calculated by evaluation of 28 cases by ANNs with leave-one-out cross-n. The results were compared with those of other analyses such as clustering or predictive scoring (LMS). RESULTS: Our ANN model could predict lymph node metastasis most accurately with 60 clones. The highest predictive accuracy for lymph node metastasis by ANN was 10 of 13 (77%) in newly added cases that were not used for gene selection by SAM and 24 of 28 (86%) in all cases (sensitivity: 15/17, 88%; specificity: 9/11, 82%). Predictive accuracy of LMS was 9 of 13 (69%) in newly added cases and 24 of 28 (86%) in all cases (sensitivity: 17/17, 100%; specificity: 7/11, 67%). It was difficult to extract useful information for the prediction of lymph node metastasis by clustering analysis. CONCLUSIONS: ANN had superior potential in comparison with other methods of analysis for the prediction of lymph node metastasis. This systematic analysis combining SAM with ANN was very useful for the prediction of lymph node metastasis in esophageal cancers and could be applied clinically in the near future.

Adult↗
PubMed2004

Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma.

Low-density lipoprotein receptor-related protein 1B (LRP1B) is frequently deleted in tumors of various types, but its status and expression in esophageal squamous cell carcinomas (ESCs) have never been reported. In the course of a program to screen ESC cell lines for copy-number aberrations using array-based comparative genomic hybridization, we identified a homozygous deletion of LRP1B. Genomic PCR experiments revealed homozygous deletions of LRP1B in additional ESC cell lines (total, 6 of 43; 14.0%) and in primary esophageal tumors (30 of 70; 42.9%). Moreover, expression of LRP1B mRNA was frequently silenced in ESC lines without homozygous deletions (14 of 37; 37.8%). Using bisulfite-PCR analysis and sequencing, we found that LRP1B-nonexpressing cells without homozygous deletions were highly methylated at a CpG island of LRP1B, a sequence possessing promoter activity. Treatment with 5-aza-2'-deoxycytidine restored expression of LRP1B in those ESC lines. Histone acetylation status correlated directly with expression of LRP1B and inversely with the methylation status of the CpG island. Methylation of LRP1B was also detected in primary esophageal tumors. Restoration of LRP1B expression in ESC cells reduced colony formation. These results suggest that loss of LRP1B function in esophageal carcinogenesis most often occurs either by homozygous deletion or by transcriptional silencing through hypermethylation of its CpG island.

Acetylation↗
PubMed2004

Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells.

Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barrett's esophagus and esophageal carcinoma. And it is well known that the incidence of adenocarcinoma arising from Barrett's esophagus has been increasing during the past decade. On the other hand, cyclooxygenase-2 and prostaglandins, produced by the catalytic reaction of cyclooxygenase-2, are considered to relate to carcinogenesis of the digestive tract and other malignant tumors. Recent reports suggest that cyclooxygenase-2 is induced in Barrett's esophagus and esophageal carcinoma. The purpose of this study is to investigate the reaction of cyclooxygenase-2 expression and prostaglandinE2 production on normal human esophageal epithelial cells cultured with gastroduodenal components. Normal human esophageal epithelial cells were cultured with chenodeoxycholic acid, trypsin and in acidic condition, individually and with different combinations of these three factors. After culturing, cyclooxygenase-2 expression in the cells and amount of prostglandinE2 in culture media was evaluated by immunoblotting and enzyme-immunoassay, respectively after culturing the cells. Cyclooxygenase-2 expression was up-regulated by bile acid and prostaglandinE2 production was enhanced by bile acid with trypsin, acidic condition or both of these components, without a synergistic effect on cyclooxygenase-2 expression. Production of prostaglandinE2 via these factors was suppressed by the cyclooxygenase-2 selective inhibitor JTE-522. The results suggest that duodenogastroesophageal reflux may induce cyclooxygenase-2 expression and prostaglandinE2 production in esophageal epithelial cells, cyclooxygenase-2 specific inhibitors may have a chemopreventive effect on esophageal carcinoma.

Benzenesulfonates↗
PubMed2004

Clinical significance of dysadherin expression in gastric cancer patients.

PURPOSE: Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients. EXPERIMENTAL DESIGN: Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects. RESULTS: Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not. CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.

Aged↗
PubMed2004

Over-expression of gastrin-releasing peptide in human esophageal squamous cell carcinomas.

Gastrin-releasing peptide (GRP) is known as an autocrine growth factor for a number of gastrointestinal cancers. There is, however, little information on the expression of GRP in the squamous epithelia and squamous cell carcinoma, particularly in the esophagus. With a differential display approach, up-regulated GRP was observed in human esophageal squamous cell carcinoma (ESCC) samples obtained from a high-risk area for esophageal cancer, Linzhou in northern China. Up-regulation of phosphoglycerate mutase and P311 HUM (3.1) and down-regulation of keratin 13, cystatin B, endoglin and annexin I were observed. Using a reverse transcription-polymerase chain reaction (RT-PCR) method, significant over-expression of GRP was observed in 10 out of 12 ESCC samples (83.3%) and all four ESCC cell lines. With in situ hybridization, GRP mRNA expression was detected in nine out of 21 (42.8%) samples with basal cell hyperplasia (BCH), five out of seven (71.4%) samples with dysplasia (DYS) and 17 out of 24 (70.9%) ESCC samples. In contrast, GRP was expressed only in three out of 16 (18.7%) normal epithelium. Digital image analysis revealed that the mean value of GRP expression index, determined by intensity and area ratio of staining, was 0.19 in normal epithelium, 1.23 in BCH, 2.94 in DYS and 2.38 in ESCC, showing a progressive increase. Studies on ESCC cell lines showed GRP increased cell growth in a dose-dependent pattern in GRP receptor-positive ESCC cells, but not in GRP receptor-negative ESCC cells. GRP (1 mM) also increased cyclooxygenase-2 protein expression by 3.4-fold. This is the first demonstration that GRP is over-expressed in ESCC, and its over-expression may play a role in ESCC development and growth.

Base Sequence↗
PubMed2004

The effect of a herbal medicine (Mao-to) for the prevention of interferon-induced psychiatric complications in chronic hepatitis C: a pilot study.

OBJECTIVE: To evaluate the efficacy of a herbal medicine (Mao-to) on psychiatric complications caused by IFN, and to examine the relationship between depression and microcirculation. METHODS: Twelve patients with chronic hepatitis C and a past history of IFN-induced depression were enrolled in this study. Their mental state was evaluated by the self-rating depression scale (SDS)> or =40, or M-R of the Cornell medical index (CMI)> or =10. Each patient received a daily dose of 6 million units of IFN-beta for 8 weeks, and Mao-to was given orally four times a day during the IFN-beta course. RESULTS: All patients in this study completed a full course of IFN. Mean CMI scores (M-R) had significantly decreased at the end of the treatment. Mean erythrocyte aggregability and erythrocyte deformability had also significantly decreased at the end of treatment. CONCLUSION: Mao-to might be useful for preventing the incidence of depression in patients with chronic hepatitis C being treated with IFN. The mechanism by which Mao-to prevents depression is suggested to be through the improvement of microcirculation.

Adult↗