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Fusion images of diffusion-weighted whole-body imaging with background body signal suppression and T2-weighted image (DWIBS/T2) demonstrate a strong signal for malignancies, with a high contrast against the surrounding tissues, and enable anatomical analysis. In the present study, DWIBS/T2 was compared with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for diagnosing cancer in the abdomen. Patient records, including imaging results of examination conducted between November 2012 and May 2014, were analyzed retrospectively. In total, 10 men (age, 73.6±9.6 years) and 8 women (age, 68.9±7.1 years) were enrolled into the current study. Of the enrolled patients, 2 were diagnosed with hepatocellular carcinoma, 1 with cholangiocellular carcinoma, 1 with liver metastasis, 2 with pancreatic ductal adenocarcinoma, 1 with renal cell carcinoma and 1 with malignant lymphoma. Benign lesions were also analyzed, including adenomyomatosis of the gallbladder (5 patients), intraductal papillary mucinous neoplasm (4 patients) and right adrenal adenoma (1 case). All the patients with cancer showed positive results on DWIBS/T2 images. However, only 7 out of 8 patients were positive with PET/CT. One patient with right renal cellular carcinoma was positive with DWIBS/T2, but negative with PET/CT. All the patients with benign lesions were negative with DWIBS/T2 and PET/CT. In conclusion, DWIBS/T2 was more sensitive in diagnosing cancer of organs in the abdominal cavity compared with PET/CT. Furthermore, negative results with DWIBS/T2 and PET/CT were useful for the diagnosis of benign lesions, such as adenomyomatosis of the gallbladder and intraductal papillary mucinous neoplasm. [ABSTRACT FROM AUTHOR]

Prompt and accurate diagnosis is critical in the treatment of acute cholecystitis. Diffusion-weighted whole-body magnetic resonance imaging with background body signal suppression/T2 image fusion (DWIBS/T2) identifies areas with high signal intensity, corresponding to inflammation. In the present study, the records and images of patients with acute cholecystitis who underwent DWIBS/T2 between January 2013 and March 2014 were retrospectively analyzed. A total of 11 patients with acute cholecystitis were enrolled. In one patient, DWIBS/T2 identified a thickened wall and high signal intensity, with high signal intensity in the pericholecystic space that suggested localized peritonitis. Positive DWIBS/T2 results indicating acute cholecystitis were obtained in 10/11 patients, with a sensitivity of 90.9%. In addition, wall thickening and high signal intensity were absent in DWIBS/T2 images when wall thickening was not detected by computed tomography. Wall thickening and high signal intensity was attenuated when patients with acute cholecystitis were clinically treated. These data suggest that a thickened gallbladder wall and high signal intensity are indicative of acute cholecystitis and that DWIBS/T2 may be a useful technique in evaluating the severity of acute cholecystitis. [ABSTRACT FROM AUTHOR]

Tissues surrounding hepatocellular carcinomas (HCCs) lack glucose. Hepatocyte selection medium (HSM) is deficient in glucose and is supplemented with galactose. HCC cells were cultured in HSM to investigate the stem cell markers α‑fetoprotein (AFP) and cluster of differentiation 44 (CD44). HCC cells (HLF and PLC/PRF/5 cells) were cultured in HSM. Viable cell numbers were determined on days 0 and 7 following culture in HSM. RNA was isolated and subjected to reverse transcription‑quantitative PCR (RT‑qPCR) to analyze the mRNA expression levels of AFP and CD44. Immunostaining was performed to analyze the protein levels of AFP and CD44. The number of viable cells was significantly decreased on day 7 following culture in HSM. The expression levels of AFP and CD44 increased on day 7 as assessed using RT‑qPCR. Immunostaining confirmed the results of RT‑qPCR analysis. The number of viable HCC cells was decreased in HSM, whereas the expression levels of AFP and CD44 increased. Therefore, HSM is potentially useful for the enrichment of HCC cells with cancer stem cell characteristics. [ABSTRACT FROM AUTHOR]

Hepatocyte selection medium (HSM) is deprived of glucose and supplemented with galactose, and is based on Leibovitz's‑15 (L15) medium. HSM may promote the differentiation of human induced pluripotent stem (iPS) cells towards hepatocyte lineage. These culture conditions result in increased expression of galactokinase (GALK)‑1 and GALK2. However, iPS cells do not survive in HSM. Two potential alternatives to glucose deprivation are treatment with 3‑bromopyruvate (3BP), an analogue of pyruvate, and 2‑deoxy‑d‑glucose (2DG), an analogue of glucose. The promoters of GALK1 and GALK2 were subcloned using the pMetLuc2 reporter plasmid to make pMetLuc2/GALK1 and pMetLuc2/GALK2, respectively. 201B7 human iPS cells were transfected with the reporter plasmids, cultured in HSM and analyzed by luciferase assay. Furthermore, 201B7 cells were cultured in L15, William's E (WE) or Dulbecco's modified Eagle's medium/nutrient mixture F‑12 Ham (DF12) supplemented with 3BP, 2DG or a combination of the two, for 15 days, and subjected to reverse transcription‑quantitative polymerase chain reaction to measure the levels of α‑fetoprotein (AFP) mRNA expression. Metridia luciferase activity was significantly higher in cells cultured in HSM compared with those in ReproFF medium (P<0.05). 3BP and 2DG treatment, alone or in combination, decreased AFP expression levels in cells cultured in L15 and DF12. The combination of 3BP+2DG increased the expression levels of AFP in WE. Without 3BP or 2DG, AFP expression was higher in L15 compared with WE or DF12. The promoters of GALK1 and GALK2 were activated in 201B7 cells cultured in HSM, enabling survival using galactose as an energy source. 3BP and 2DG supplementation in WE medium may promote the differentiation of iPS cells to the hepatocyte lineage. [ABSTRACT FROM AUTHOR]

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI. [ABSTRACT FROM AUTHOR]

To improve the management of patients with acute cholangitis, the present study compared laboratory test variables between acute cholangitis patients with or without common bile duct (CBD) dilatation [CBDdil(+) and CBDdil(.), respectively]. The medical records of patients diagnosed with acute cholangitis and subjected to endoscopic retrograde cholangiopancreatography between February 2008 and May 2015 were retrospectively analyzed. The present study consisted of 40 men (aged 69.4±8.8 years) and 37 women (aged 68.8±11.6 years). It was observed that CBDdil(.) patients were slightly younger than CBDdil(+) patients (P=0.0976), and levels of C.reactive protein (CRP) were significantly higher in CBDdil(.) patients than in CBDdil(+) patients (P=0.0392). In addition, logistic regression analysis indicated that CRP levels were associated with the presence of CBD dilatation (P=0.0392). These data indicate that patients with acute cholangitis without CBD dilatation tend to be younger and have higher levels of CRP. Thus, in acute cholangitis patients without CBD dilatation, diagnosis should be determined using clinical symptoms and laboratory data. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer-binding protein (C/EBP) a, C/EBPß and C/EBPd are involved in inflammation and cell differentiation. In the present study, their roles in human gastric cancer cells were investigated. The human gastric cancer cell lines MKN45 and MKN74 were subjected to the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to analyze the expression levels of C/EBPa, C/EBPß and C/EBPd. The cells were transfected with expression plasmids for either C/EBPa or C/EBPd, and subjected to a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and RT-qPCR for analysis of cyclin D1 expression. Expression levels of C/EBPa and C/EBPd were decreased in MKN45 and MKN74 cells compared with in normal gastric tissue. Expression levels of C/EBPß were decreased in MKN45 cells and increased in MKN74 cells. Viability of MKN45 cells was decreased by C/EBPa and C/EBPd. Viability of MKN74 cells was decreased by C/EBPa, but increased by C/EBPd. Expression levels of cyclin D1 were decreased in association with C/EBPa and C/EBPd overexpression in MKN45 cells. Expression levels of cyclin D1 were decreased in association with C/EBPa overexpression, but increased in association with C/EBPd overexpression, in MKN74 cells. The results of the present study indicate that C/EBPa is potentially useful for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

William's E (WE) is a suitable medium for the differentiation of human induced pluripotent stem (iPS) cells to the hepatocyte lineage. The aim of the present study was to investigate various growth factors in their ability to promote hepatocyte differentiation of iPS cells in WE medium. Human iPS 201B7 cells were cultured in WE medium supplemented with growth factors, and mRNA expression levels and promoter activities of a-fetoprotein (AFP) and albumin were examined by reverse transcription-quantitative polymerase chain reaction and luciferase assay, respectively. In addition, time course analysis of AFP mRNA expression was performed in 201B7 cells cultured in WE medium supplemented with oncostatin M. The results demonstrated that mRNA expression levels of AFP were significantly elevated by most growth factors tested as supplements in WE medium, except all-trans retinoic acid, compared with cells cultured in ReproFF (a medium that maintains pluripotency). The highest increase in AFP mRNA expression levels was observed by oncostatin M stimulation. Albumin mRNA expression levels were increased by all-trans retinoic acid and insulin-transferrin-selenium supplementation in WE medium compared with cells cultured in ReproFF. Oncostatin M supplementation significantly stimulated the promoter activity of the AFP gene, but no growth factor tested significantly stimulated the promoter activity of the albumin gene. By time course analysis, significant increase of AFP mRNA expression was observed on the sixth day post-stimulation, compared with cells cultured in WE medium alone. In conclusion, the present study demonstrated that oncostatin M supplementation in WE medium was sufficient to initiate hepatocyte differentiation in iPS cells. [ABSTRACT FROM AUTHOR]

To initiate hepatocyte differentiation in human induced pluripotent stem (iPS) cells, cells are cultured in a medium lacking glucose but supplemented with galactose (hepatocyte selection medium, HSM) or in medium supplemented with oncostatin M and small molecules (hepatocyte differentiation inducer, HDI). In the present study, 2-Deoxy-D-glucose (2DG), an analogue of glucose, was utilized instead of glucose deprivation and the effect of 2DG supplementation on iPS differentiation was examined. First, 201B7 cells, an iPS cell line, were cultured in HSM or HDI media for 2 days and then subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in order to analyze expression levels of established hepatocyte markers, including cytosolic aspartate aminotransferase (AST), mitochondrial AST, alanine aminotransferase (ALT), and glycerol kinase. mRNA expression levels of mitochondrial AST, ALT, and glycogen synthase significantly increased following culture in HSM and HDI compared with ReproFF media. Cytosolic AST mRNA expression levels significantly increased following culture in HDI compared with ReproFF media, but not in HSM. To test the effect of 2DG on iPS differentiation, 201B7 cells were cultured in ReproFF, a feeder-free medium that retains pluripotency, supplemented with 2DG. Following 7 days of culture, the cells were subjected to RT-qPCR to analyze expression levels of a-fetoprotein (AFP), a marker of immature hepatocytes. AFP mRNA expression levels significantly increased with the addition of 0.1 µM 2DG in the media, and galactose addition acted synergistically with 2DG to further upregulate AFP expression. In conclusion, the present study demonstrated that hepatocyte differentiation was initiated in iPS cells cultured in HSM and HDI media and that 2DG could be used as a supplement instead of glucose deprivation to initiate hepatocyte differentiation in iPS cells. [ABSTRACT FROM AUTHOR]

The utility and limitations of abdominal ultrasonography (US) were retrospectively evaluated as a first-line diagnostic imaging modality in patients with abdominal pain. Hospital records from patients subjected to abdominal US as a first-line diagnostic imaging examination at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from April 2010 to April 2015 were analyzed. Only those patients who underwent abdominal US to diagnose abdominal symptoms were included in the present study. All patients with prior diagnostic imaging examination findings were excluded from the study in order to reduce bias of results. The analyzed patients included 39 males with an average (mean ± standard deviation) age of 65.8±18.8 years and 37 females with an average age of 53.7±19.3 years. Diagnosis with abdominal US was in agreement with the final diagnosis in 66 of the 76 patients. Final diagnosis of symptoms by abdominal US was not successful in the remaining 10 patients who required further investigation. Acute cholangitis, acute cholecystitis, acute pancreatitis, acute appendicitis, colonic diverticulitis and spleen rupture were correctly diagnosed. Different types of cancer, including colorectal cancer, were also successfully diagnosed. Bile duct cancer and sigmoid colon volvulus could not be diagnosed by abdominal US due to the presence of intestinal gas. Abnormal findings were detected using abdominal US, but the diagnosis required additional consultation with gynecologists. Abdominal US was suitable for patients with abdominal symptoms. It is recommended that patients undergo further diagnostic imaging or consultation with gynecologists when large gas bubbles are present or gynecological conditions are suspected. [ABSTRACT FROM AUTHOR]

Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ2, and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at lowering the risk of peptic ulcer bleeding. [ABSTRACT FROM AUTHOR]

Short hairpin RNA of frizzled-2 (shRNA-Fz2) suppresses the cell proliferation of gastric cancer cells. Endoscopic ultrasound (EUS) is considered a suitable method for the introduction of therapeutic plasmids into cells, since the device enables the access and real-time monitoring of gastric cancer tissues. In the present study, plasmids were introduced into cells by sonoporation, as evidenced by the production of H2O2. The production of H2O2 was measured by absorbance of a potassium-starch solution irradiated with EUS. Luciferase activity was analyzed in the cells irradiated with EUS after the addition of a pMetLuc2-control in the media, and cell proliferation was analyzed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay after irradiation with EUS following the addition of shRNA-Fz2. Absorbance levels corresponding to free radical levels were found to be higher in the cells irradiated with EUS. Luciferase activities were found to be significantly higher in the transfected cells (plasmid with Lipofectamine LTX) than in untreated cells and were furthermore found to be higher in MKN45 cells irradiated for 0.5 min than in cells not subjected to irradiation. Luciferase activity was also found to be higher in MKN74 cells irradiated for 2 min than in cells that were not irradiated. Although the cell proliferation of the MKN45 cells tended to be suppressed by irradiation with EUS, this was non-significant suppression, while the cell proliferation of MKN74 cells was found to be suppressed by irradiation with 12 MHz for 2 min (P<0.05). In conclusion, plasmids were introduced into cultured gastric cancer cells by irradiation with EUS due to sonoporation, as evidenced by the production of H2O2; however, the efficiency of the plasmid introduction was low compared with a traditional transfection approach. [ABSTRACT FROM AUTHOR]

Resistance to sorafenib in hepatocellular carcinoma (HCC) cells exhibiting stemness was evaluated using a sphere formation assay. A hepatocyte selection medium (HSM) deficient in glucose and arginine was used to suppress the proliferation of cell spheres composed of HLF and PLC/PRF/5 HCC cells, which were subjected to a sphere formation assay. Cell spheres were cultured with sorafenib and subjected to a cell proliferation assay and the expression levels of cytochrome P450 (CYP3A4) were analyzed in RNA extracted from sphere-forming cells using reverse transcription-quantitative polymerase chain reaction. Sphere-forming PLC/PRF/5 cells were more resistant to sorafenib, as compared with control cells, exhibiting higher expression levels of CYP3A4. When cultured in HSM, suppressed proliferation was observed in the sphere-forming PLC/PRF/5 cells and in the control cells, with no significant variation between them. The results suggest that deprivation of glucose and arginine is a potential novel treatment for HCC. [ABSTRACT FROM AUTHOR]

Human primary hepatocytes are able to survive in a medium without glucose and arginine, but supplemented with galactose and ornithine (hepatocyte selection medium; HSM). To address the possibility of the application of HSM in cancer therapy, hepatocellular carcinoma cells, pancreatic cancer cells and gastric cancer cells were cultured in HSM. Cell proliferation was analyzed using an MTS assay. Morphological changes were analyzed using hematoxylin and eosin staining. Apoptosis was analyzed using a TUNEL assay and cell motility was assessed with a scratch assay. Cell proliferation was significantly suppressed in cell lines grown in HSM (P<0.01 in all the cell lines). Hematoxylin and eosin staining revealed pyknotic nuclei, suggesting that these cells had undergone apoptosis. The number of TUNEL-positive cells was significantly increased in HSM. In the scratch assay, the distance between the growing edge and the scratched edge was significantly lower (P<0.01 in all the cell lines) in cells cultured in HSM, compared with those grown in Dulbecco's modified Eagle's medium or RPMI-1640. Therefore, the proliferation and motility of hepatocellular carcinoma cells, pancreatic cancer cells and gastric cancer cells was suppressed, and these cells subsequently underwent apoptosis in a medium without glucose and arginine, but containing galactose and ornithine. [ABSTRACT FROM AUTHOR]

Diffusion-weighted whole-body imaging with background body signal suppression/T2 image fusion (DWIBS/T2) is useful for the diagnosis of cancer as it presents a clear contrast between cancerous and non-cancerous tissue. The present study investigated the limitations and advantages of DWIBS/T2 with regards to the diagnosis of colorectal polyp (CP) or cancer (CRC). The current study included patients diagnosed with CP or CRC following colonoscopy, who were subjected to DWIBS/T2 between July 2012 and March 2015. Patient records were analyzed retrospectively. Patients were subjected to DWIBS/T2 when they presented with abdominal cancers or inflammation. Colonoscopy was performed as part of screening, or if patients had suspected colon cancer or inflammatory bowel disease. A total of 8 male and 7 female patients were enrolled in the present study. All patients, with the exception of one who had been diagnosed with CRC following colonoscopy, had positive results and all patients diagnosed with CP following a colonoscopy, with the exception of one, had negative results on DWIBS/T2. Thus, CRC was detected by DWIBS/T2, while CP was not (P=0.0028). The diameter of CRC lesions was significantly larger than that of CP (P<0.0001) and that of lesions positive on DWIBS/T2 was significantly larger than that of negative lesions (P=0.0004). The depth of invasion tended to be greater for lesions positive on DWIBS/T2 compared with that of negative ones. This indicated that DWIBS/T2 may be suitable for the detection of CRC but not for detection of CP. The results of DWIBS/T2 may also be affected by lesion diameter and depth of invasion. [ABSTRACT FROM AUTHOR]

Cancer cells consume more glucose than normal cells, mainly due to their increased rate of glycolysis. 2-Deoxy-d-glucose (2DG) is an analogue of glucose, and sorafenib is a kinase inhibitor and molecular agent used to treat hepatocellular carcinoma (HCC). The present study aimed to demonstrate whether combining 2DG and sorafenib suppresses tumor cell proliferation and motility more effectively than either drug alone. HLF and PLC/PRF/5 HCC cells were incubated with sorafenib with or without 1 μM 2DG, and subjected to a proliferation assay. A scratch assay was then performed to analyze cell motility following the addition of 2DG and sorafenib in combination, and each agent alone. RNA was isolated and subjected to reverse transcription-quantitative polymerase chain reaction to analyze the expression of cyclin D1 and matrix metalloproteinase-9 (MMP9) following the addition of 2DG and sorafenib in combination and each agent alone. Proliferation was markedly suppressed in cells cultured with 1 μM 2DG and 30 μM sorafenib compared with cells cultured with either agent alone (P<0.05). In addition, levels of Cyclin D1 expression decreased in cells exposed to 3 μM sorafenib and 1 μM 2DG compared with cells exposed to 2DG or sorafenib alone (P<0.05). Scratch assay demonstrated that the distance between the growing edge of the cell sheet and the scratched line was shorter in cells cultured with sorafenib and 2DG than in cells cultured with 2DG or sorafenib alone (P<0.05). Levels of MMP9 expression decreased more in cells treated with both sorafenib and 2DG than in cells treated with 2DG or sorafenib alone (P<0.05). Therefore, 2DG and sorafenib in combination suppressed the proliferation and motility of HCC cells more effectively than 2DG or sorafenib alone, and a cancer treatment combining both drugs may be more effective than sorafenib alone. [ABSTRACT FROM AUTHOR]

Human primary hepatocytes are able to survive in a medium without glucose and arginine that is instead supplemented with galactose and ornithine (hepatocyte selection medium; HSM). This is because the cells produce glucose and arginine by the action of galactokinase (GALK) and ornithine carbamoyltransferase (OTC), respectively. It was expected that hepatocellular carcinoma (HCC) cells do not survive in HSM. In the current study, HCC cell lines (namely HLE, HLF, PLC/PRL/5, Hep3B and HepG2) and human umbilical vascular endothelial cells (HUVECs) were cultured in HSM, and the expression levels of GALK1, GALK2 and OTC were analyzed by reverse transcription-quantitative polymerase chain reaction. HLE, HLF and PLC/PRL/5 cells died on day 11, while Hep3B, HepG2 and HUVECs died on day 7. HLF cells were further analyzed as these cells had lower expression levels of GALK1, GALK2 and OTC compared with adult liver cells, and survived until day 11. In these cells, the expression levels of GALK1, GALK2 and OTC did not change on days 3 and 7 as compared to day 0. In addition, a co-culture of HLF cells with HUVECs was established and the medium was changed to HSM. It was observed that HLF cells and HUVECs in co-culture were damaged in HSM. In summary, HCC cells and HUVECs died in a medium without glucose and arginine that was supplemented with galactose and ornithine. HCC cells and HUVECs were damaged in HSM, suggesting a potential application for treatment with the medium. [ABSTRACT FROM AUTHOR]

The present study investigated the potential utility of contrast-enhanced abdominal ultrasonography (CEUS), using Sonazoid™, in colorectal cancer (CRC). Three patients were subjected to CEUS with Sonazoid™. Surgical specimens were immunostained for CD31. Numbers of blood vessels positive for CD31 were analyzed in each of five fields at ×400 magnification and averaged to determine blood vessel density. Blood vessel density was compared between non-tumorous and tumorous areas. Prior to the administration of Sonazoid™, CRC was illustrated as irregular-shaped wall thickening. One minute after the administration of Sonazoid™, the majority of the thickened wall was enhanced, while some parts of the thickened wall remained unenhanced. Blood vessel densities of non-tumorous and tumorous areas in patient two were 25.2±2.5 and 5.2±1.1 (P<0.0001). Blood vessel densities of non-tumorous and tumorous areas in patient three were 19.0±3.1 and 2.2±0.8 (P<0.0001). Tumorous areas of CRC were not enhanced 1 min after the administration of Sonazoid™. Blood vessel density was lower in tumorous areas compared with non-tumorous areas, as evidenced by immunohistochemistry for CD31. These findings suggest that CEUS may be useful for the determination of the extent of CRC. [ABSTRACT FROM AUTHOR]

The present study aimed to identify novel predictors of upper gastrointestinal (GI) bleeding by assessing change ratios of blood test variables. Records of 1,023 patients (431 men and 592 women) who underwent endoscopy between October 2014 and September 2015 at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) were retrospectively analyzed. Patients whose blood test variables for the time-point of endoscopy and three months previously were available were enrolled and subsequently categorized into a group with and another one without upper GI bleeding (n=32 and 84, respectively), and the respective change ratios were calculated for each group. One-way analysis of variance revealed that in patients with upper GI bleeding, change ratios of white blood cell count and alkaline phosphatase were significantly higher than those in patients without, while change ratios of hemoglobin (Hb), total protein and albumin were significantly reduced. Logistic regression analysis demonstrated that the change ratio of Hb was significantly correlated with upper GI bleeding. Receiver-operator characteristic analysis revealed that an 18.7% reduction of Hb was the threshold value for the prediction of upper GI bleeding. In conclusion, the present study revealed that a ≥18.7% reduction in Hb over three months has predictive value for upper GI bleeding. [ABSTRACT FROM AUTHOR]

Upper gastrointestinal (GI) bleeding can be fatal. Blood test variables were reviewed in search of threshold values to detect the presence of occult upper GI bleeding. The records of 1,023 patients who underwent endoscopy at the National Hospital Organization Shimoshizu Hospital from October 2014, to September 2015, were retrospectively reviewed. Of those, 95 had upper GI bleeding. One-way analysis of variance was applied to blood test variables comparing patients with and without upper GI bleeding. Logistic regression analysis was applied to detect the association of blood test parameters with upper GI bleeding, and receiver-operator characteristics were applied to establish threshold values. White blood cell count (WBC), platelet (Plt) count, and blood urea nitrogen (BUN) levels were higher, and hemoglobin (Hb) and albumin (Alb) levels were lower in patients with upper GI bleeding. Logistic regression analysis showed that low Hb was significantly associated with upper GI bleeding and a Hb value of 10.8 g/dl was established as the threshold for the diagnosis. In patients with upper GI bleeding, WBC, Plt count, and BUN levels were higher and Hb and Alb levels were reduced. Hb at 10.8 g/dl was established as a threshold value to detect upper GI bleeding. [ABSTRACT FROM AUTHOR]

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) yields positive results for cancer against the surrounding tissues. The combination of DWIBS and T2-weighted images (DWIBS/T2) in the diagnosis of gastrointestinal tract cancers was retrospectively analyzed in the present study. Patients were subjected to magnetic resonance imaging after cancer was diagnosed through specimens obtained via biopsy or endoscopic mucosal resection. Sixteen patients were assessed between July, 2012 and June, 2013 and the correlation between detection with DWIBS/T2 and T staging was analyzed. Regarding patients who underwent surgery, the correlation between detection with DWIBS/T2 and the diameter or depth of invasion was analyzed. All cancers that had advanced to >T2 stage were detectable by DWIBS/T2, whereas all cancers staged as T2) or invading beyond the muscularis propria. [ABSTRACT FROM AUTHOR]

Patient records were retrospectively analyzed to elucidate the characteristics of patients with colorectal cancer (CRC) diagnosed with screening abdominal ultrasound (US). Patients diagnosed with CRC using abdominal US [localized irregular wall thickening (W) or a hypoechoic mass with a hyperechoic mass (M)] were enrolled. The patients were subjected to colonoscopy and treated surgically between March, 2010 and January, 2015. A total of 5 men (aged 74.0±0.8 years) and 10 women (aged 73.0±12.0 years) were analyzed. Stratification was analyzed with abdominal US. The threshold value of wall thickness to diagnose CRC was investigated with receiver operating characteristic (ROC) curve analysis. The average wall thickness was 2.8±0.4 mm in the surrounding normal tissue and 12.7±5.2 mm in CRC (one-way analysis of variance, P<0.0001). The wall was significantly thicker in CRC compared with the normal colonic wall. The calculated threshold value was 4.3 mm for the diagnosis of CRC. Stratification was preserved in W, while it was lost in M (Chi-squared test, P=0.0196). The hemoglobin concentration was lower, while the C-reactive protein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were elevated above normal values. The threshold value was 4.3 mm for the diagnosis of CRC with abdominal US. [ABSTRACT FROM AUTHOR]

Lower gastrointestinal (GI) bleeding can be caused by colorectal polyps or cancer. The aim of the present study was to identify blood test variables and medications that can predict lower GI bleeding, which would allow for appropriate colonoscopy. The medical records of patients who underwent colonoscopy from September 2014 to September 2015 were retrospectively analyzed. The selected patients included 278 men (mean age, 67.0±11.5 years) and 249 women (mean age, 69.6±12.0 years). The diagnosis, medications, and blood test variables were compared between patients with and without bleeding. Logistic regression analysis was performed to determine the factors associated with lower GI bleeding. The presence of colorectal polyp and cancer was associated with lower GI bleeding (P=0.0044) with an odds ratio of 6.71 (P=0.0148). No lower GI bleeding was observed in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or anticoagulants. The C-reactive protein (CRP) levels were significantly higher in patients with lower GI bleeding (P=0.0227). The Hb levels were lower in patients with lower GI bleeding, however this finding was not statistically significant (P>0.05). No blood test variable was associated with lower GI bleeding. Elevated CRP was associated with lower GI bleeding, while there was no association between the medications and lower GI bleeding. [ABSTRACT FROM AUTHOR]

Differentiation between adenomyomatosis (ADM) and cancer of the gallbladder is necessary during diagnosis. Diffusion-weighted whole body imaging with background body signal suppression (DWIBS) images are able to indicate cancer and inflammation. The fusion of a DWIBS with a T2 weighted image (DWIBS/T2) facilitates both functional and anatomical investigations. In the present study, patient records and images from patients with surgically confirmed ADM from April 2012 to October 2014 were analyzed retrospectively. The enrolled patients, including 6 men (64.2±13.1 years) and 4 women (57.3±12.4 years) were subjected to DWIBS/T2 during routine clinical practice. The diagnosis of ADM was based on magnetic resonance cholangiopancreatography, transabdominal ultrasonography, and endoscopic ultrasonography; ADM was diagnosed definitively when cystic lesions were observed, indicating the Rokitansky-Aschoff sinus. A single patient was indicated to be positive by DWIBS/T2 imaging. The Rokitansky-Aschoff sinus revealed a relatively high signal intensity; however, it was not as strong as that of the spleen. The signal intensity was also high on an apparent diffusion coefficient map, suggesting T2 shine-through. The thickened wall displayed low signal intensity. The aforementioned results indicate that ADM may be negative upon DWIBS/T2 imaging; one false positive case was determined to be ADM, accompanied by chronic cholecystitis. The majority of patients with ADM displayed negative findings upon DWIBS/T2 imaging, and chronic cholecystitis may cause false positives. [ABSTRACT FROM AUTHOR]

Colon diverticula cause bleeding and acute diverticulitis. The present study analyzed laboratory test variables, aiming to predict the presence of diverticula. Patient records from between April 2011 and March 2014 were analyzed retrospectively (1,520 patients) and a one-way analysis of variance was performed to analyze the association between the presence of diverticula and each variable. A X2 test was then used to assess the correlation between the prevalence of diverticula and the percentage of patients with uric acid (UA) levels ≥5.1 mg/dl. A receiver operating characteristic (ROC) analysis was performed to determine the threshold values required to predict the presence of diverticula. Hemoglobin (Hb) levels were lower in patients with diverticula than in those without diverticula (P=0.0027), and compared with patients without diverticula, UA and triglyceride (TG) levels were higher in patients with diverticula (P=0.0066 and P=0.0136, respectively). The patients were divided into two groups, as follows: Patients with UA levels ≥5.1 mg/dl (the median value) and those with UA levels <5.1 mg/dl. The prevalence of diverticula was significantly higher in patients with UA levels ≥5.1 mg/dl than in those with UA levels <5.1 mg/dl (P=0.0004). ROC analysis demonstrated that the threshold values of Hb, TG and UA were 12,400, 146 and 5.1 mg/dl, respectively. The sensitivity of the Hb and UA levels at the threshold values was 76.5 and 71.0%, respectively. The prevalence of diverticula was associated with low Hb levels, and high TG and UA levels. [ABSTRACT FROM AUTHOR]

Metastasis negatively affects the prognosis of hepatocellular carcinoma (HCC). In the present study, niclosamide, which is known to suppress the proliferation of HCC cells, was investigated for possible suppressant effects on the migration of HCC cells. HLF and PLC/PRF/5 HCC cells were cultured in the presence of niclosamide. Cell proliferation was analyzed using the MTS assay. Cell migration was measured by performing a scratch assay. Expression levels of cyclin D1 and matrix metalloproteinase 9 (MMP9) were analyzed by performing revers transcription-quantitative polymerase chain reaction. Compared with the control treatment, treatment with 10 µm niclosamide suppressed the proliferation of the HLF and PRL/PRF/5 cells to 49.9±3.7 and 17.9±11.5% (P<0.05), respectively. Furthermore, compared with the control treatment, treatment with 1.0 µM niclosamide downregulated the expression of cyclin D1 to 52.4±4.4 and 23.9±5.4% (P<0.05) in the HLF and PRL/PRF/5 cells, respectively. In the scratch assay, treatment of the HLF cells with niclosamide (1.0 µm) decreased the distance of the scratched line from the growing edge to 4.6±1.0 mm compared with the 9.2±1.4 mm observed with the control treatment (P<0.05). Similarly, treatment of the PRL/PRF/5 cells with niclosamide (1.0 µm) also decreased the distance of the scratched line from the growing edge to 3.0±0.8 mm compared with the 5.5±0.9 mm observed with the control treatment (P<0.05). Further, MMP9 expression levels in the HLF cells treated with 1.0 µm niclosamide decreased to 22.4±1.76% (P<0.05) compared with those in the untreated control HLF cells. Similarly, expression level of MMP9 in the PRL/PRF/5 cells treated with 1.0 µm niclosamide deceased to 18.7±10.7% (P<0.05) compared with those in the untreated control PRL/PRF/5 cells. Overall, niclosamide downregulated the expression of MMP9 in and suppressed the migration of HCC cells. [ABSTRACT FROM AUTHOR]

Activin A maintains the pluripotency of human induced pluripotent stem (hiPS) cells. A combination of activin A and CHIR99021 (CHIR), a specific inhibitor of glycogen synthase-3β, is suitable for feeder-free culture of hiPS cells. In the present study, the specific role of the Wnt signaling pathway in cells cultured under different conditions was investigated. Following transfection with the reporter plasmids, TOPflash and FOPflash, hiPS cells were cultured in medium, containing activin A, CHIR, leukemia inhibitory factor (LIF) or SB431542, a specific inhibitor of activin A. A luciferase reporter assay was performed 48 h later. Western blot analysis was performed to determine the expression levels of β-catenin and tubulin-α. The activity of Wnt in hiPS cells was suppressed by culture in the presence of activin A. The activation of the Wnt pathway was most marked when the cells were cultured with a combination of activin A and CHIR. Addition of SB431542 into the culture revealed no significant change in the Wnt pathway. Western blot analysis revealed that β-catenin accumulated most often in cells cultured with activin A and CHIR. β-catenin also accumulated in cells cultured with activin A alone. Culture with activin A and CHIR most effectively stimulated the Wnt signaling pathway, as measured by luciferase assays using TOPflash and FOP flash as reporter plasmids. β-catenin accumulated in the hiPS cells cultured with activin A, via a mechanism, which remains to be elucidated. The Wnt signaling pathway may be important for hiPS cell growth in feeder-free culture. [ABSTRACT FROM AUTHOR]

Gastric cancer is occasionally diagnosed using transabdominal ultrasonography (US) during screening or investigation of patients with abdominal symptoms. Therefore, the present study analyzed the association of the tumor diameter, pathological T (pT) staging and depth of invasion with the detection of gastric cancer using US. Patient records were analyzed retrospectively and 13 patients were enrolled, who underwent US screening prior to endoscopic mucosal resection, endoscopic submucosal dissection or surgery. In total, 5 patients were diagnosed with gastric cancer using US (positive detection group), while US was unable to detect the gastric cancer in 8 patients (negative detection group). The tumor diameter and depth of invasion were determined by pathologists. One-way analysis of variance or the χ² test was performed. Wall thickness in gastric cancer cases ranged between 7 and 20 mm (mean, 12.2±5.9 mm), as measured using abdominal US. The hemoglobin level was significantly lower in the positive detection patients compared with the negative detection patients (P=0.0455). In addition, the diameters of the gastric wall in the negative and positive detection patients were 24.5±16.4 and 54.4±26.2 mm, respectively (P=0.0266). These results indicate that gastric cancer in the positive detection patients were at a more advanced-stage compared with that in the negative detection patients. Furthermore, gastric cancer with a stage over pT2 was diagnosed using abdominal US (P=0.0242), whereas stage pT1a gastric cancer was not detected by abdominal US. Gastric tumors invading deeper than the submucosa were diagnosed using US (P=0.0242). However, the gastric cancer cases limited to the mucosa remained undetected. In conclusion, the detection of gastric cancer correlated well with the tumor diameter, pT staging and depth of invasion. [ABSTRACT FROM AUTHOR]

Anti-mitochondrial M2 antibody (AMA-M2) is specific to primary biliary cirrhosis (PBC), but can also be found in certain patients with autoimmune hepatitis (AIH). Effective methods of differentiating between PBC and AIH are required, as their clinical course and management are different. Titers of AMA-M2 were analyzed before and after follow-up in patients with PBC or AIH. Patients who underwent liver biopsy and were diagnosed with either AIH (10 patients) or PBC (3 patients) were enrolled in the study. The AMA-M2 antibody titers of these patients were analyzed upon hospital admission. AMA-M2 reacted with the pyruvate dehydrogenase complex-E2, branched-chain 2-oxo acid dehydrogenase complex and 2-oxoglutaric acid dehydrogenase complex in the assay utilized for this study. The cut-off value for A MA-M2 w as 5. Six A IH p atients were A MA-M2(-) and 4 were AMA-M2(+). The titer for the AIH patients who were AMA-M2(+) was 24.8±14.8, compared with 324±174 in the patients with PBC (P=0.0138). Three AMA-M2(+) AIH patients were followed-up after liver biopsy. The AMA-M2 levels had decreased in all 3 patients, becoming undetectable in 2 of them. In conclusion, certain patients with AIH in this study were found to be AMA-M2(+), but the titers were significantly lower than those in the patients with PBC. At follow-up, the AIH patients exhibited decreased AMA-M2 titers. [ABSTRACT FROM AUTHOR]

The present study retrospectively analyzed the laboratory data of patients who had undergone a colonoscopy between April 2011 and March 2014, with the aim of assessing whether these variables could be used to predict the presence of colorectal polyps (CP). A total of 1,471 patients were enrolled (731 men, 68.5±10.8 years; 740 women, 66.7±10.8 years). One-way analysis of variance was performed to analyze the association between the presence of CP and a range of laboratory variables. Logistic regression analysis was performed to establish a regression equation to predict the presence of CP. Receiver-operator characteristics analysis was applied to investigate the performance of the regression equation. Patients with CP were older than those without CP (P<0.0001). Serum uric acid (UA) levels were higher in patients with CP, compared to those without CP (P=0.0007). To investigate the possibility that older age and higher UA levels could predict the presence of CP, logistic regression analysis was performed (P=0.0008). The regression equation was as follows: ln(p/1 - p) = 2.79015 - 0.01836 x age - 0.28542 x UA (mg/dl), where p indicates the presence of CP. Receiver-operator characteristic analysis showed the area under the curve to be 0.62092 and the threshold value of P was 0.4370. Sensitivity and specificity of the threshold value were 77.6 and 44.2%, respectively. Advanced age and higher serum UA levels were associated with the presence of CP. In conclusion, logistic regression analysis obtained a regression equation that predicted the presence of CP with a higher sensitivity, but poorer specificity, compared to fecal occult blood testing. [ABSTRACT FROM AUTHOR]

Mesenchymal-epithelial transition factor (c-Met) is associated with the proliferation and motility of cancer cells. c-Met expression has been detected in surgical pancreatic cancer specimens, and its overexpression is associated with a poor prognosis. SU11274 is a specific inhibitor of c-Met. In the present study, the cell proliferation and motility of pancreatic cancer cells treated with SU11274 was investigated. The PANC-1, MIA-Paca2, NOR-P1, PK-45H, PK-1 and PK-59 pancreatic cancer cell lines were used. The expression of c-Met and cyclin D1 was analyzed by quantitative polymerase chain reaction. In addition, a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxyphen yl)-2-(4-sulfophenyl)-2 H-tetrazolium inner salt assay was performed to assess cell proliferation, and a scratch assay was performed to assess cell motility. c-Met expression was higher in PANC-1, PK-45H, PK-1 and PK-59 cell lines compared with that in normal pancreatic tissue. Following treatment with 30 µM SU11274, the proliferation of MIA-Paca2 and PK-45H cells was suppressed to 19.8±10.7% (P<0.05) and 45.8±14.8% (P<0.05) of the control level, respectively. Furthermore, cyclin D1 expression was downregulated to 43.7±17.9% (P<0.05) and 53.2±18.6% (P<0.05) of the control level in the MIA-Paca2 and PK-45H cell lines, respectively, following treatment with 30 µM SU11274. In addition, cell motility was reduced to 1.0±0.3% in MIA-Paca2 (P<0.05) and 14.7±3.5% in PK-45H (P<0.05) following treatment with 30 µM SU11274, compared with the motility of untreated cells. These results indicated that SU11274 suppresses the proliferation of pancreatic cancer cells via the downregulation of cyclin D1. The present study also demonstrated that cell motility was suppressed by treatment with SU11274. [ABSTRACT FROM AUTHOR]

Mesenchymal-epithelial transition factor (c-Met) is a receptor that binds to the hepatocyte growth factor and is upregulated in hepatocellular carcinoma (HCC). The anti-tumor effects of (3Z)-N-(3-chlorophenyl)-3-({3,5-dimethyl-4-[(4methyl-piperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylene)-N-me thyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide (SU11274), a c-Met inhibitor, were investigated in the present study. HCC cells (HLE, HLF, PLC/PRL/5, Hep3B, Huh-6 and HepG2) and human umbilical vein endothelial cells (HUVECs) were used. Quantitative polymerase chain reaction was performed to detect the expression level of c-Met in HCC and HUVECs, and cyclin D1 in HCC. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay was performed to assess the proliferation of the HCC cells and HUVECs cultured with SU11274. Co-culture of HLF or PLC/PRL/5 cells and HUVECs was established as an in vitro model of HCC tissues. The expression levels of c-Met in HLE, HLF, PLC/PRL/5, Hep3B, Huh-6 and HepG2, adult healthy liver and HUVECs were 4.43±0.50, 1.61±0.18, 3.70±0.08, 0.81±0.18, 6.60±1.29, 1.06±0.35, 1.00±0.09 and 88.8±17.3 (mean ± standard deviation), respectively. SU11274 (30 µM) suppressed the proliferation of HLF, PLC/PRL/5 and HUVECs to 11.0±9.4, 46.5±30.7 and 29.4±5.0%, respectively. SU11274 (30 µM) decreased the expression levels of cyclin D1 in HLF and PLC/PRL/5 cells to 45.1±11.6 and 30.1±10.3%, respectively. SU11274, at a concentration of 30 µM damaged the morphology of the co-cultures of HLF or PLC/PRL/5 cells with HUVECs and all the cells died. c-Met is highly expressed in HUVECs and HCC cells, but not in Hep3B. At a 30-µM concentration, SU11274 suppresses the proliferation of HLF, PLC/PRL/5 and HUVECs. SU11274 (30 µM) damages the co-cultures of HLF or PLC/PRL/5 cells with HUVECs. [ABSTRACT FROM AUTHOR]

Resistance is one limitation of sorafenib in the treatment of hepatocellular carcinoma (HCC). Insulin-like growth factor-1 receptor (IGF-1R) is involved in cancer cell proliferation. To assess the potential synergistic antitumor effects of picropodophyllin (PPP), an IGF-1R inhibitor, HLF and PLC/PRL/5, HCC cells were treated with PPP alone or PPP in combination with sorafenib, a multikinase inhibitor. Normal human umbilical vein endothelial cells (HUVECs) were also used to analyze the antiangiogenic effects of the drugs. HCC cells and HUVECs were cultured on 96-well plates, and then treated with PPP, with and without the addition of sorafenib. A 3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo xymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay and hematoxylin and eosin staining were then performed 48 h later. The HCC cells were also analyzed using scratch assays and hematoxylin and eosin staining after 48 h. The proliferation of HLF, PLC/PRF/5 and HUVEC cells was suppressed by the combination of 0.2 µM PPP and 3 µM sorafenib more effectively than by 10 µM sorafenib alone. The motility of HLF and PLC/PRF/5 cells was also suppressed to a greater extent with the combination of PPP at 0.2 µM and sorafenib at 3 µM than with sorafenib at 10 µM alone. The cells that had been treated with 0.2 µM PPP and 3 µM sorafenib also exhibited pyknotic nuclei, which is characteristic of apoptosis. In conclusion, PPP enhanced sorafenib-mediated suppression of proliferation and motility in HCC cells. Therefore, the combination of PPP and sorafenib may exert antitumor and antiangiogenic effects. [ABSTRACT FROM AUTHOR]

In the present study, Frizzled-2 (Fz2), a receptor of the Wnt ligand, was investigated as a potential target of molecular therapy for hepatocellular carcinoma (HCC). Quantitative polymerase chain reaction (PCR) was performed to determine the expression levels of Fz2. A surgical specimen of HCC was immunostained with an Fz2 antibody. A 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium inner salt assay was performed on HCC cell lines, including HLF and Hep3B, 72 h after the transfection of the short hairpin (sh)RNA of Fz2 (shRNA-Fz2). RNA was isolated from the Hep3B and HLF cells 48 h after transfection and subjected to quantitative PCR. All cell lines had elevated levels of Fz2 compared with those in an adult liver. The highest and lowest expression levels of Fz2 were 246.9±15.7 in the HLF cells and 5.8±1.4 in the Hep3B cells, respectively. Fz2 was expressed in the tumorous HCC tissue, but not in the surrounding non-tumorous tissue. Cell proliferation was suppressed to 28.6±6.4% in the HLF cells and to 29.8±4.3% in the Hep3B cells at 100 ng shRNA-Fz2 per well. Levels of cyclin D1 expression decreased to 65.2±5.9% in the HLF cells and to 60.8±14.6% in the Hep3B cells at 2.5 μg per well. In conclusion, Fz2 was upregulated in the HCC cells. shRNA-Fz2 suppressed the proliferation of the Hep3B and HLF cells, decreasing Fz2 expression. As it was not expressed in the surrounding non-tumorous tissue, Fz2 may be an ideal molecular therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

In the present study, the threshold values of laboratory data for the diagnosis of non-alcoholic fatty liver disease (NAFLD) were investigated. The study enrolled patients who had undergone abdominal ultrasound (US) between April 2013 and August 2013, and for whom laboratory data were available on the same day. NAFLD was diagnosed following observations of a bright liver or hepatorenal echo contrast on the abdominal US scans. Patients were excluded from the study if they had liver diseases or had been prescribed prednisolone or methotrexate. Receiver operating characteristic curves, the Wilcoxon signed-rank test and Fisher's exact probability test were used for data analysis. In total, 80 NAFLD and 94 non-NAFLD patients were enrolled in the study. The threshold levels of alanine aminotransferase (ALT) and triglyceride (TG) for the diagnosis of NAFLD were 19.0 IU/l and 101 mg/dl, respectively. Patients were divided into two groups according to the levels of ALT and TG. Those with ALT levels of >19 IU/l and TG levels of >101 mg/dl were defined as the positive group, while the remaining patients were classified as the negative group. The specificity and positive predictive value using the combined threshold levels of ALT >19 IU/l and TG >101 mg/dl were 80.9 and 75.0%, respectively. Therefore, the results indicated that ALT levels of >19 IU/l or TG levels of >101 mg/dl were useful markers for the screening of NAFLD. However, NAFLD was more strongly suspected in patients with ALT levels of >19 IU/l and TG levels of >101 mg/dl. [ABSTRACT FROM AUTHOR]

The aim of the present study was to reveal the metabolic disorders most commonly associated with nonalcoholic fatty liver disease (NAFLD). Triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), blood glucose (BG) and hemoglobin A1c (HbA1c) were analyzed. NAFLD was diagnosed using abdominal ultrasound (US), and TG, HDL, LDL, BG and HbA1c were immediately collected on the same day and subjected to multivariate regression analysis. Stepwise analysis was performed to select the variables that were closely associated with NAFLD. The patients who were positive for the hepatitis B antigen and hepatitis C antibody were excluded from the study. Additionally, the patients who were prescribed prednisolone or methotrexate were excluded from the study as these agents may cause NAFLD or liver toxicity. The study included 168 and 125 patients with and without NAFLD, respectively. TG, BG and HbA1c were strongly correlated with NAFLD. Among these parameters, TG was the strongest predictor of NAFLD (χ²=9.89, P=0.0017). TG was the parameter that was most strongly associated with NAFLD. In conclusion, elevated TG was a marker of NAFLD. [ABSTRACT FROM AUTHOR]

In the present study, pancreatic cancer cell proliferation was analyzed following the suppression of frizzled (Fz)2 expression. Reverse transcription polymerase chain reaction (PCR) was performed using RNA isolated from pancreatic cancer cell lines, PANC-1, NOR-P1, PK-45H, PK-1, PK-59, MIA-Paca2 and KP4. A surgical specimen of pancreatic cancer was immunostained with antibodies specific to Fz2. Cell proliferation assays were performed with MIA-Paca2 cells transfected with small interfering RNA (siRNA) or short hairpin RNA (shRNA) of Fz2. Fz2 was found to be expressed in all pancreatic cancer cell lines, with the exception of NOR-P1. Immunostaining revealed that Fz2 was not expressed in normal pancreatic tissues, while it was expressed in pancreatic cancer cells. The expression levels of cyclin D1 were analyzed by quantitative PCR. The proliferation and expression of cyclin D1 were suppressed with the siRNA and shRNA of Fz2 in the MIA-Paca2 cells. Therefore, Fz2 is a potential target for the molecular therapy of pancreatic cancer. [ABSTRACT FROM AUTHOR]