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Biomedical subjects

Akira Terano

Publications and source records attributed to Akira Terano.

At least 19 recordsLinked to original sources
PubMed2007

Mutational analysis of the BRAF gene in colorectal mucinous carcinoma in association with histological configuration.

Genetic alterations and their association with clinicopathological features in colorectal mucinous carcinoma (MC) remain unknown. In particular, little is known about the mutational status of the BRAF gene, which is activated by oncogenic Ras. This study aimed to evaluate the status of BRAF together with K-ras, p53 and mismatch-repair deficiency to clarify their association with tumorigenesis of colorectal MC. BRAF and K-ras mutations were determined in 43 colorectal MCs by direct sequencing. p53 alteration was investigated immunohistochemically. The status of mismatch-repair deficiency was assessed by microsatellite analyses and immunohistochemistry for hMLH1. We also examined the association between these molecular alterations and clinicopathological features including histological configuration. BRAF mutation was detected in 4 (9.3%) tumors and was located at codon 599 of exon 15 in all cases. K-ras mutation was detected in 13 tumors (30.2%). No BRAF and K-ras mutations were identified simultaneously in the same tumor. The incidence of mismatch-repair deficiency tended to be higher in MC with BRAF mutation than without. In terms of histological configuration, we classified the cases according to growth type by tumor edge morphology. All MCs with BRAF mutation and 9 of 13 MCs (69.2%) with K-ras mutation were classified as polypoid type. BRAF and K-ras mutation did not affect patient prognosis, but non polypoid type was significantly more aggressive than polypoid type. Our findings indicate that BRAF mutation plays an important role in the tumorigenesis of colorectal MC and in tumor edge morphology, similar to K-ras mutation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates trefoil factor family 2 (TFF2) expression in gastric epithelial cells.

Although trefoil factor family 2 (TFF2) plays a critical role in the defense and repair of gastric mucosa, the regulatory mechanism of TFF2 expression is not fully understood. In this study, we investigated the regulation of TFF2 expression by peroxisome proliferator-activated receptor gamma (PPARgamma) in gastric epithelial cells. MKN45 gastric cells were used. TFF2 mRNA expression was analyzed by real-time quantitative RT-PCR. The promoter sequence of the human TFF2 gene was cloned into pGL3-basic vector for reporter gene assays. Ciglitazone was mainly used as a specific PPARgamma ligand. MKN45 cells expressed functional PPARgamma proteins. Endogenous TFF2 mRNA expression and TFF2 reporter gene transcription was significantly up-regulated by ciglitazone in a dose-dependent manner. Reporter gene assays showed that two distinct cis-elements are involved in the response to PAPRgamma activation. Within one of these element (nucleotides -558 to -507), we identified a functional peroxisome proliferator responsive element (PPRE) at -522 (5'-GGGACAAAGGGCA-3'). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay confirmed the binding of PPARgamma to this sequence. Another element (nucleotides -407 to -358) appeared to be a composite enhancer element indirectly regulated by PPARgamma and a combination of these two cis-elements was required for the full response of the human TFF2 gene expression to PPARgamma. These data demonstrate that human TFF2 gene is a direct target of PPARgamma in gastric epithelial cells. Since TFF2 is a critical gastroprotective agent, PPARgamma may be involved in the gastric mucosal defense through regulating TFF2 expression in humans.

Base Sequence↗
PubMed2006

Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan.

OBJECTIVE: Studies in Western populations have shown the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and upper gastrointestinal bleeding (UGIB). The role of Helicobacter pylori infection in NSAIDs-related UGIB remains to be studied. We conducted a case-control study in Japan to investigate these related topics. METHODS: Cases of UGIB due to duodenal or gastric ulcer, or gastritis were identified in 14 study hospitals in various areas of Japan. For each case, two controls were identified from population registries in the same district. Information on drugs and other risk factors was obtained from 175 cases and 347 controls by telephone interviews. Anti-H. pylori antibody in the urine was measured in a single laboratory for all the cases and 225 controls. RESULTS: The odds ratio (OR) of UGIB was 5.5 for aspirin and 6.1 for other NSAIDs (NANSAIDs) (p<0.01). The OR for regular use was higher than for occasional use both for aspirin (7.7 vs 2.0) and NANSAIDs (7.3 vs 4.1). Loxoprofen (5.9), frequently used in Japan as a safe 'prodrug', was significantly associated with UGIB. The odds ratio for H. pylori infection was 4.9 and the relative excess risk due to the interaction between H. pylori and the use of NSAID was 1.2 (95% CI: -5.8-8.1). CONCLUSION: NSAIDs including loxoprofen increase the risk of UGIB in Japan as in Western countries, with a similar magnitude of association. There was no evidence of biological interaction between NSAIDs and H. pylori infection.

Adult↗
PubMed2006

Magnifying pharmacoendoscopy: response of microvessels to epinephrine stimulation in differentiated early gastric cancers.

BACKGROUND: Magnifying endoscopy is a promising modality for fine observation of minute surface structures and microvessel architecture in gastric lesions. OBJECTIVE: To observe the response of microvessels to epinephrine stimulation in early gastric cancer tissues and to assess the usefulness of magnifying pharmacoendoscopy for histologic diagnosis. DESIGN: This was a prospective pilot study. SETTING: This study was conducted at an academic hospital. PATIENTS: Twenty-nine patients with differentiated early gastric cancer were enrolled. INTERVENTIONS: Microvessels in both the cancerous lesion and its adjacent non-neoplastic gastric mucosa were observed by magnifying endoscopy before and after focal spray with epinephrine solution (0.05 mg/mL). MAIN OUTCOME MEASUREMENTS AND RESULTS: After epinephrine stimulation, noncancerous gastric mucosa surrounding the cancerous lesion showed a change in color from red to white; no microvessels were evident. On the other hand, all the cancerous lesions examined clearly showed enhancement of tumor microvessels. The rate of detection of tumor microvessels by magnifying pharmacoendoscopy (100%) was significantly higher than that by magnifying endoscopy alone (41.3%). LIMITATIONS: This was small pilot study. CONCLUSIONS: Magnifying pharmacoendoscopy with epinephrine is a powerful tool for assessing tumor vascularity and may contribute to the histologic diagnosis of differentiated early gastric cancers before endoscopic treatment.

Aged↗
PubMed2006

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide.

BACKGROUND AND AIM: Controversies remain over the need for antiulcer treatment following 1-week eradication triple therapy for Helicobacter pylori-positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. METHODS: The study was conducted in 52 H. pylori-positive patients with an endoscopically-proven open gastric ulcer. All patients received 1-week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7-week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and (13)C-urea breath test. RESULTS: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non-eradicated patients. The overall gastrointestinal symptom-free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. CONCLUSIONS: The results suggested that the combination therapy for open gastric ulcer was safe, well-tolerated and effective. However, data from a double-blind placebo-controlled study is necessary to confirm these findings.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Prediction of colorectal neoplasia by quantitative methylation analysis of estrogen receptor gene in nonneoplastic epithelium from patients with ulcerative colitis.

PURPOSE: The incidence of colorectal neoplasia has increased among patients with longstanding and extensive ulcerative colitis (UC). Therefore, surveillance colonoscopy has been widely recommended. However, there is controversy about the impact of cancer surveillance, and ways to improve its effectiveness are being sought. The estrogen receptor (ER) gene shows age-related methylation in the colorectal epithelium and is frequently methylated in colorectal neoplasia, suggesting that ER methylation occurs early in the process of colorectal tumorigenesis. EXPERIMENTAL DESIGN: To clarify whether methylation analysis of the ER gene in nonneoplastic epithelium can help predict an increased risk for UC-associated neoplasia, a total of 105 nonneoplastic colorectal epithelia from 18 patients with longstanding and extensive UC, including 8 patients with neoplasia and 10 patients without neoplasia, were analyzed. In all patients, multiple samples were taken from six regions of the colorectum. The combined bisulfite restriction analysis method was used to determine the methylation status of the ER gene. RESULTS: The mean methylation level of the ER gene was 25.4% in the nonneoplastic epithelia from UC patients with neoplasia, whereas it was only 4.0% in those without neoplasia (P<0.001). The methylation level of the ER gene in UC patients with neoplasia was significantly higher than in UC patients without neoplasia throughout the colorectum except for the cecum. In UC patients with neoplasia, the mean ER methylation level in the distal colon (36.1%) was significantly higher than in the proximal colon (14.6%; P<0.001). CONCLUSIONS: These results suggest that the analysis of ER gene methylation in nonneoplastic colorectal epithelium could have the potential to be a useful adjunct for identifying individuals with longstanding and extensive UC who are at increased risk of neoplasia and contribute to more effective cancer surveillance.

Adult↗
PubMed2005

Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.

Central neuropeptides play a role in many physiological functions through the autonomic nervous system. We have recently demonstrated that central injection of a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow through vagal and nitric oxide-dependent pathways. In this study, the central effect of a TRH analog on experimental acute pancreatitis was investigated in rats. Acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5-100 ng), or saline was injected intracisternally 15 min before the first cerulein injection under ether anesthesia. Serum amylase level was measured before and 5 h after the first cerulein injection. Pancreatic wet/dry weight ratio and histological changes were also evaluated. Intracisternal TRH analog inhibited cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry weight ratio and pancreatic histological changes, such as interstitial edema, inflammation and vacuolization. The pancreatic cytoprotection induced by central TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine-methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous administration of the TRH analog did not influence cerulein-induced acute pancreatitis. These results indicate that the TRH analog acts in the central nervous system to protect against acute pancreatitis through vagal and nitric oxide-dependent pathways.

Adrenergic Agents↗
PubMed2005

Interaction of the taxilin family with the nascent polypeptide-associated complex that is involved in the transcriptional and translational processes.

alpha-Taxilin is a novel binding partner of the syntaxin family, which is implicated in intracellular vesicle traffic. We have here found that alpha-taxilin interacts with the nascent polypeptide-associated complex (NAC), which is involved in transferring growing nascent polypeptide chains to appropriate co-translationally acting factors. NAC is composed of two subunits, alpha- and betaNACs. Both these subunits bound to alpha-taxilin through its C-terminal coiled-coil region in dose-dependent and saturable manners. The interactions of alpha-taxilin with alphaNAC and NAC but not with betaNAC were inhibited by syntaxin-4, indicating that alpha-taxilin binds to NAC mainly through its interaction with alphaNAC. When alphaNAC was over-expressed in COS-7 cells, alphaNAC was distributed in the cytosol and nucleus. However, co-expression of the alpha-taxilin fragment containing the alphaNAC-binding region eliminated the nuclear distribution of over-expressed alphaNAC. Moreover, other taxilin family members, beta- and gamma-taxilins, also bound to alphaNAC and thereby affected the nuclear distribution of over-expressed alphaNAC. Taken together with the evidence that alphaNAC functions in the nucleus as a transcriptional coactivator, our results raise the possibility that the taxilin family is involved not only in the translational process through its interaction with NAC but also in the transcriptional process through its interaction with alphaNAC alone.

Animals↗
PubMed2005

Tumor cell dissociation score highly correlates with lymph node metastasis in superficial esophageal carcinoma.

BACKGROUND: It is still not clear which parameters are important for predicting the metastatic potential of superficial esophageal squamous cell carcinoma (SESCC). The purpose of the present paper was thus to investigate tumor cell dissociation (TCD) in SESCC as a predictive factor of lymph node metastasis. METHODS: Thirty-three SESCC were classified into four groups based on the depth of tumor invasion. Carcinomas not invading as far as the muscularis mucosa were classified as group A; carcinomas invading to the muscularis mucosa or less than one-third of the upper submucosa were classified as group B; those invading to the middle layer of the submucosa were classified as group C; and those invading one-third of the lower submucosa were classified as group D. The TCD score was calculated by dividing the length of the TCD region by the maximal longitudinal length of the area of invasion into or beyond the lamina propria, and multiplying by 100. E-cadherin expression of the carcinomas was investigated in the TCD area and the successive area of mucosal invasive carcinoma (SAM). RESULTS: The incidence of lymph node metastasis was 0% in group A, 10% in group B, 36.4% in group C and 57.1% in group D. The mean TCD scores (+/-SEM) of SESCC with lymph node metastasis were higher than that without (85.3 +/- 5.7, 16.3 +/- 3.9, respectively; P < 0.001). In group C, the TCD score of cases with lymph node metastases was higher than in those without lymph node metastasis (P < 0.001). E-cadherin expression was significantly reduced in the area of TCD compared with the SAM located over the TCD area (P < 0.001). CONCLUSIONS: The TCD score is an important predictive marker for lymph node metastasis in SESCC. Clinical evaluation of TCD scores in endoscopic mucosal resection (EMR) specimens would enable accurate prediction of lymph node metastasis and extend the indication of EMR treatment for SESCC.

Aged↗
PubMed2005

Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors.

BACKGROUND AND AIM: Recent advances in colonoscopic techniques have led to the increased detection of, and interest in, superficial type colorectal tumors, and a new category, the 'laterally spreading tumor (LST)', has been proposed. However, the characteristics of the genetic alterations in these LSTs have not yet been fully determined. We therefore classified LSTs as LST-granular (LST-G) or LST-non-granular (LST-NG), according to their macroscopic appearance, and examined the genetic alterations in these two tumor groups compared with those in protruded type tumors. METHODS: We obtained a total of 62 colorectal tumors, including 26 protruded type, 17 LST-G and 19 LST-NG, from specimens resected surgically or endoscopically. We examined K-ras codon 12 mutations by using the polymerase chain reaction-restriction fragment length polymorphism method and by fluorescence direct sequencing. We also performed immunohistochemistry to analyze cyclooxygenase (COX)-2 and gastrin abnormalities. RESULTS: The incidence of K-ras mutation was 50.0% in protruded type tumors, 76.5% in LST-G, and 26.3% in LST-NG. The frequencies of COX-2 overexpression were 73.1, 88.2, and 31.6%, respectively, and those of gastrin overexpression were 61.5, 82.4, and 26.3%, respectively. Therefore, LST-G is similar to protruded type tumors in that the incidence of K-ras mutation and the frequencies of COX-2 and gastrin overexpression are high. LST-NG differs from both of these tumor types in that the values of these three indicators are all low. CONCLUSIONS: These results show that LST-G and LST-NG have different genetic alterations.

Colorectal Neoplasms↗
PubMed2005

[Capsule endoscopy].

Wireless capsule endoscopy is a new diagnostic tool in which a disposable video capsule is swallowed by the patient. This examination enables visualization of the small intestine that is not within the reach of conventional upper and lower endoscopy. The best indications include an obscure source of gastrointestinal bleeding, Crohn's disease, and small intestinal tumors. The disadvantage that biopsy cannot be performed is compensated for by employing double-balloon endoscopy. In particular, this examination can identify the origin of bleeding and diagnose the underlying disease, leading to prompt surgical treatment with better results. In future, capsule endoscopy will become a necessary examination for diagnosing digestive tract disease.

Endoscopes, Gastrointestinal↗