Rena Takakura

Deficiency of KIT-positive cells in the colon of patients with diabetes mellitus.

Diabetes mellitus is a well‐known cause of gastrointestinal dysmotility. The pathogenesis of diabetic gastroenteropathy is mainly considered to be a neuropathy, but the cause of dysmotility remains unknown. Interstitial cells of Cajal (ICC), which express c‐kit receptor tyrosine kinase (KIT), are considered to be pacemaker cells for the gastrointestinal movement. Therefore, we investigated a possible involvement of ICC in the pathogenesis of diabetic gastroenteropathy in humans.

Diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration for suspected pancreatic malignancy in relation to the size of lesions

Background and Aim:  Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is an accurate method for cytological confirmation of pancreatic malignancy, but it has been unknown whether its diagnostic accuracy for pancreatic lesions was affected by their size, location, or size of needles. Our aim was to investigate the accuracy of EUS‐FNA for suspected pancreatic malignancy in relation to these factors, especially to the size of lesions.

PPARγ agonists inhibit cell growth and suppress the expression of cyclin D1 and EGF‐like growth factors in ras‐transformed rat intestinal epithelial cells

Peroxisome proliferator‐activated receptor γ (PPARγ) inhibits the growth of several types of cancer cells. However, the mechanisms by which this occurs are poorly understood. The goal of the present study was to investigate the effects of PPARγ on mutated ras‐induced cell growth, activation of transcription factors and expression of genes associated with cellular transformation in rat intestinal epithelial cells. A human PPARγ cDNA was introduced to the activated H‐ras‐transfected IEC‐6 cells (IECras) and 1 clone (IECrasPR82) that stably expresses both activated ras and PPARγ was obtained. Thiazolidinedione derivatives such as troglitazone and rosiglitazone, selective ligands for PPARγ, inhibited the cellular growth of IECrasPR82 cells in a time‐dependent manner and induced G1 cell cycle arrest. Treatment with troglitazone (20 μM) decreased the expression of cyclin D1, heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and amphiregulin and suppressed the promoter activities of cyclin D1 and HB‐EGF. Furthermore, a luciferase assay and an electrophoretic mobility shift assay showed that thiazolidinedione derivatives suppressed the transcriptional activities of AP‐1 and Ets, both of which play crucial roles in the expression of cyclin D1 and HB‐EGF. These findings suggest that reduction of EGF‐like growth factors and cyclin D1 through the suppression of AP‐1 and Ets may be 1 mechanism whereby PPARγ inhibits their growth.

Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in a murine model of inflammatory bowel disease: Il-10-deficient mice

Abstract:Objective: To elucidate the role of macrophages in the pathogenesis of inflammatory bowel disease, proinflammatory characteristics of macrophages were estimated in a murine model of spontaneous intestinal inflammation. Materials and methods: Peritoneal macrophages from IL-10-deficient mice were stimulated with lipopolysaccharide (LPS) or an anti-CD40 monoclonal antibody (mAb). Cytokine release was assessed by enzyme-linked immunosorbent assay. CD40 expression was examined by two-color flow cytometric analysis. Induction of suppressor of cytokine signaling 3 (SOCS3) mRNA was evaluated by real-time quantitative RT-PCR. Results: In the presence of LPS or anti-CD40 mAb, TNF-α and IL-12p70 release from macrophages of mutant mice was significantly higher than that from macrophages of wild-type mice. This may be due to the difference in IL-10 production by macrophages, since activated macrophages of wild-type mice produced IL-10 in amounts sufficient to suppress an increased release of cytokines from activated macrophages of mutant mice. LPS and CD40 stimulation induced significantly high level of SOCS3 expression in macrophages of mutant mice in comparison to those of wild-type mice. Conclusions: Macrophages from a murine model of inflammatory bowel disease demonstrated enhanced responsiveness to immunological and bacterial stimuli. This suggests significant roles of macrophages in the pathogenesis of inflammatory bowel disease.

Combined brush cytology and stent placement in a single session for presumed malignant biliary stricture

Background and Aim:  Biliary stricture may be benign or malignant and causes obstructive jaundice. Brush cytology is a simple technique for diagnosing the cause of biliary stricture; however, its sensitivity has been reported to be low. A technique that comprises diagnosing the cause of stricture with a satisfactory sensitivity and relieving jaundice is required. This study was designed to evaluate the diagnostic performance of brush cytology and the feasibility of the subsequent stent placement in a single endoscopic retrograde cholangiopancreatography (ERCP) session performed for presumed malignant biliary strictures.

Safety and Effectiveness of Gemcitabine in 855 Patients with Pancreatic Cancer under Japanese Clinical Practice Based on Post-marketing Surveillance in Japan

OBJECTIVE When gemcitabine was approved as an anti-cancer drug, there were limited data for Japanese patients treated with gemcitabine. Generally, advanced or metastatic pancreatic cancer patients experience poor prognosis and suffer from debilitating disease-related symptoms. Reports and information on gemcitabine use within a large patient pool will be beneficial to aid physicians. Therefore, this post-marketing surveillance was conducted as a non-interventional, observational study on the use of gemcitabine in a clinical practice setting in Japan. METHODS Patients had no previous treatment with gemcitabine and were diagnosed with pancreatic cancer by an attending physician. Patients were registered between May 2001 and December 2003 in Japan. The patients were treated with gemcitabine. Data such as patient background, treatment details, adverse events, tumor response, serum CA19-9 levels and drug-related symptom improvement were assessed. RESULTS Of the 890 patients registered for the study, 855 were included in the analysis of gemcitabine for safety. Four hundred and forty-three (51.9%) patients reported drug-related adverse events, with 97 patients (11.4%) experiencing serious adverse events. The incidence of interstitial lung disease was 0.7% (six patients). Six hundred patients were evaluated for tumor response. The overall response rate was 6.0% and the disease control rate was 54.0%. CA19-9 decreased in 63.6% of the 335 evaluable patients, with a ≥75% decrease seen in 19.4% of the total group. Drug-related symptom improvement was observed in 27.0% of the 686 evaluable patients. CONCLUSIONS This large-scale surveillance could confirm the safety of gemcitabine for Japanese pancreatic cancer patients as well as elucidate the efficacy profile, measured by drug-related symptom improvement, for Japanese pancreatic cancer patients.

Basic research on countermeasures against barium sulfate aggregation using a gastric phantom

The principal aim of this study was to conduct basic experiments to examine countermeasures against barium sulfate aggregation caused by denture adhesive in gastric cancer screening test. Experiment 1; barium sulfate aggregation was reconstructed in petri dishes and the degree of reducing aggregation by seven types of commercial drink and tap water was assessed visually. The most effective one was tap water. Experiment 2; two types of aggregation (severe and mild aggregation) were reconstructed using gastric phantom BMU-1, tap water of 30-150ml was added and the degree of reducing aggregation was assessed with the images. In the case of severe aggregation, the most effective quantity of tap water was 120 ml and the next was 150 ml with the following of 90, 60 and 30 ml (P < 0.05). In the case of mild aggregation, the order of effective quantity was 90, 60, 120, 30 and 150 ml (P < 0.05). The results of this study suggested that tap water drinking of the subject was effective for the reduction of barium sulfate aggregation in gastric cancer screening and the most effective quantity of tap water was 120 ml in the case of severe aggregation and 90 ml in the case of mild aggregation.