Showing papers by "Yutaka Shimada published in 2012"

Prognostic significance of aquaporins in human biliary tract carcinoma.

Abstract: Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

Study of the Effects of Monacolin K and Other Constituents of Red Yeast Rice on Obesity, Insulin-Resistance, Hyperlipidemia, and Nonalcoholic Steatohepatitis Using a Mouse Model of Metabolic Syndrome

Abstract: Purpose. Nonalcoholic fatty liver disease (NAFLD) is a progressive and intractable disease associated with metabolic syndrome. Red yeast rice (RYR) contains monacolin K, a potent inhibitor of HMG-CoA reductase, and its consumption decreases cholesterol and triglyceride levels. We examined the efficacy of RYR constituents using a novel metabolic syndrome-NAFLD mouse model (MSG mice). Methods. Two types of RYR grown under different culture conditions were used. 1P-DU contained only 0.002 g/100 g of monacolin K, whereas 3P-D1 contained 0.131 g/100 g. MSG mice were divided into three groups: control (C) group fed standard food, RYR-C group fed standard food with 1% 1P-DU, and RYR-M group fed standard food with 1% 3P-D1. Mice were examined from 12 to 24 weeks of age. Results. Serum insulin, leptin, and liver damage as well as macrophage aggregation in visceral fat in RYR-C and RYR-M groups were lower than those in C group. The serum adiponectin levels in RYR-C group were significantly higher than those in RYR-M and C groups. Conclusions. RYR was effective against obesity-related inflammation, insulin resistance, and NAFLD in MSG mice irrespective of monacolin K levels. GABA and various peptides produced during fermentation were determined as the active constituents of RYR.

Expression Analysis of iPS Cell – Inductive Genes in Esophageal Squamous Cell Carcinoma by Tissue Microarray

Abstract: AIM To understand the role of iPS inductive genes in esophageal cancer, we examined the expression of Sex determining region Y-box 2 (SOX2), Octamer-binding transcription factor 3/4 (OCT3/4), Krueppel-like factor 4 (KLF4), c-Myelocytomatosis viral oncogene (c-MYC) and Tir Na Nog (NANOG) using an esophageal squamous cell carcinoma tissue micrroarray. MATERIALS AND METHODS The immunohistochemical expression levels of the five genes were compared to the clinicopathological data of the 81 patients with esophageal cancer. RESULTS There was no relationship between the expression of the five genes and TNM factors of the patients. High expression of NANOG was an independent favorable prognostic factor (p=0.041). Among the patients who received postoperative cisplatin-based chemotherapy, patients with NANOG-positive tumor had significantly better prognosis than those whose tumors were NANOG negative (p=0.024). On the other hand, those with c-MYC-positive expression tended to have a worse prognosis and were resistant to cisplatin-based chemotherapy. CONCLUSION NANOG expression was found to be an independent prognostic factor for patient with esophageal cancer. Patients with NANOG-positive expression tumor may be good candidates for cisplatin-based treatment.

Establishment and Characterization of a New Human Gallbladder Carcinoma Cell Line

Abstract: Background: Prognosis for patients with gallbladder carcinoma (GBC) is poor and the standard treatment for GBC has not yet been established. Materials and Methods: We established the human GBC cell line TYGBK-1, from a patient with papillary, tubular adenocarcinoma. Results: The doubling time was 48 hours. This cell line has a missense mutation of p53 and no mutation of the K-RAS gene. This cell line was transplantable to nude mice. We characterized the sensitivity of TYGBK-1 to gemcitabine. We also examined the association of two gemcitabine-related genes (deoxycytidine kinase, dCK, and Hu antigen R, HuR). Among four GBC cell lines (TYGBK-1, NOZ, G-415, TGBC2TKB), TYGBK-1 and NOZ exhibited sensitivity to gemcitabine. Furthermore, these cells expressed both dCK and HuR mRNA, rather than gemcitabine-resistant cells. Conclusion: The newly established GBC cell line TYGBK-1, may represent an effective tool for development of chemotherapeutic treatment for GBC. Gallbladder carcinoma (GBC) is a common biliary malignancy with high mortality, generated from the gallbladder or cystic duct. Most patients with GBC are treated at an advanced stage, and the prognosis remains poor despite the development of modern diagnostic modalities. Jaundice and abdominal pain of ten indicate an advanced cancer that is already unresectable (1, 2). GBC resection rate was 69.7% and the rate of curative resection was 37.7%, from 1998 to 2004 (1). Prognosis for patients with GBC is poor compared to that for other types of gastrointestinal cancers. Surgical resection is the only available option for a cure. However, this is possible only for selected patients. The treatment for GBC has not yet been established (3, 4). Although many therapeutic strategies have been developed, the majority have not improved the prognosis of patients with GBC appreciably. Therefore, it is important to establish a human GBC cell line as an in vitro model for studying tumor biology, including susceptibility to drugs. In this study, we report the establishment and characterization of a new human GBC cell line, TYGBK-1. We described the cell phenotypes and checked for genetic alterations of K-RAS and p53 genes. For the treatment of biliary tract carcinoma, gemcitabine (2', 2'-difluorodeoxycytidine) is a key drug. The response rate of biliary tract cancer to gemcitabine monotherapy is 22- 36%. The median survival time (MST) has been reported to range from 7 to 14 months (5-10). Regarding transport into the cell, gemcitabine is phosphorylated to its mononucleotide moiety by deoxycytidine kinase (dCK), a rate-limiting enzyme in the salvage of deoxyribonucleosides that provides deoxynucleotid triphosphates for replicative and repair DNA synthesis. In pancreatic carcinoma cells, HuR associates with dCK mRNA. Exposure to gemcitabine of pancreatic carcinoma cells enhances the association between HuR and dCK mRNA and increases cytoplasmic HuR levels (11). HuR is a useful prognostic biomarker for patients with pancreatic carcinoma (12). On the other hand, even though gemcitabine has been used in patients with GBC, no such studies have been performed. Using this new resource, we assessed GBC's sensitivity to gemcitabine. We also examined the association between the expression levels of dCK, HuR and sensitivity to gemcitabine. Materials and Methods Patients' history. The primary gallbladder adenocarcinoma cells were obtained from a lymph node of a 67-year-old female patient who underwent cholecystectomy in 2008. Macroscopic examination revealed that the gallbladder was occupied by a tumor which was histologically characterized as a papillary, tubular type. The tumor had invaded to the serosa. Defined direct invasion around the

Effectiveness of Keishibukuryogan on Chronic-Stage Lichenification Associated with Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Keishibukuryogan (KBG) is a traditional herbal medicine, composed of five kinds of medical plants and has been administered to patients with blood stagnation in Japan. This study investigated the effect of KBG on the disease activity in AD (n = 45) patients. AD patients were administered KBG for 4 to 6 weeks in addition to their prescribed medications. The results showed that the SCORAD index and VAS score were significantly decreased after the administration of KBG (P < 0.01). KBG also decreased the serum LDH level significantly (P < 0.01). The global assessment of the clinical response in SCORAD index showed that 88.5% of the patients with moderate improvement to excellent response (n = 26) had a high lichenification score (lichenification score ≥2 in SCORAD). On the other hand, only 42.1% of the patients with no improvement to mild improvement (n = 19) had a high lichenification score. Furthermore, long-term administration of KBG for 9–67 weeks showed a marked improvement in patients with a high lichenification score. Therefore, KBG was found to be effective against AD, particularly in cases presenting with lichenified lesions.

Successful enucleation of a fluorine-18-fluorodeoxyglucose positron emission tomography positive esophageal leiomyoma in the prone position using sponge spacer and intra-esophageal balloon compression

Abstract: Recently, prone position esophagectomy for esophageal cancer is thought to be an easier and safer procedure Here, we introduced prone position for enucleation of the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) positive esophageal leiomyoma The patient was a 47-year-old man with a 4 cm mid-thoracic esophageal submucosal tumor The tumor was enucleated safely without injury of the esophageal mucosa under the gravity effect of the prone position with use of a sponge spacer and Sengstaken-Blakemore balloon Postoperative examination revealed that the tumor was a leiomyoma that was positive for smooth muscle actin and negative for CD117 Postoperative course was uneventful and the patient was discharged on day 7 after the operation The prone position with use of a sponge spacer and Sengstaken-Blakemore balloon was a safer and easier procedure for the enucleation of the esophageal submucosal tumor

Therapeutic agent for cancer, and method for determining prognosis of cancer

Abstract: Disclosed are a novel therapeutic agent for cancer such as esophageal squamous cell carcinoma, a method for predicting the prognosis of cancer, and a method for detecting, or predicting the prognosis of, cancer such as esophageal squamous cell carcinoma using a sample that can be collected less invasively. The therapeutic agent for cancer comprises as an effective component an antibody that undergoes antigen-antibody reaction with FGFRL1 to suppress the growth of cancer cells, or an antigen-binding fragment thereof. The method for predicting the prognosis of cancer comprises investigating the expression level of FGFRL1 in a cancer tissue separated from a living body, and, in this method, a high expression level of FGFRL1 indicates poor prognosis. The method for detecting cancer comprises measuring FGFRL1 or a fragment thereof extracted from a body tissue, or FGFRL1 or a fragment thereof in blood separated from a living body, and, in this method, a higher concentration of FGFRL1 or the fragment thereof contained therein than the concentration of FGFRL1 or the fragment thereof in the tissue or blood of a healthy individual indicates the presence of cancer.