Influence of concurrent and staggered dosing of semi-solid nutrients on the pharmacokinetics of orally administered carbamazepine in rats.

In the present study, we examined the effects of concurrent and staggered dosing of PG-soft ace-MP TM (PG), novel semi-solid enteral nutrients, on the pharmacokinetics of orally administered carbamazepine (CBZ) in rats due to the high possibility of drug interaction during the absorption process. The pharmacokinetic behavior of CBZ was considerably altered when administered concurrently with PG. The maximum serum CBZ concentration (Cmax) significantly decreased and the mean residence time (MRT) significantly increased. The elimination constant (ke) also significantly increased, but there were no significant changes in the area under the serum CBZ concentration versus time curve (AUC) and the time to reach Cmax (Tmax). However, these changes in the pharmacokinetic parameters were eliminated by waiting 20 min, the time interval equivalent to the Tmax described above, between CBZ administration and PG dosing. This study suggested that PG interferes with CBZ absorption from the digestive tract, although staggered administration of CBZ and PG prevented their interaction.

Progesterone receptor membrane component 2 expression leads to erlotinib resistance in lung adenocarcinoma cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide a favorable treatment outcome in patients with EGFR mutation-positive non-small cell lung cancer. However, most of such patients become resistant to EGFR-TKIs within a year. Thus, clarifying the mechanism of acquired resistance to EGFR-TKIs has been a research focus. Here, we demonstrated that the expression of progesterone receptor membrane component 2 (PGRMC2) was upregulated in an erlotinib-resistant cell line, PC9/ER, compared with the parental PC9 lung cancer cells. Our previous study showed that PGRMC1 is responsible for acquired resistance to erlotinib; however, PGRMC2 has not been discussed yet. Thus, the aim of this study was to determine the role of PGRMC2 in acquired resistance to erlotinib. Transfection with PGRMC2 siRNA significantly enhanced the sensitivity to erlotinib in PC9/ER cells. Furthermore, knockdown of PGRMC2 reduced the expression of p21, which is known as cell-cycle inhibitor and antiproliferative effector. These results suggest that PGRMC2 partially contributes to erlotinib resistance in PC9/ER cells, and that investigation into the effect of PGRMC2 on apoptosis and the cell cycle are warranted.

Reduced cytotoxicity in doxorubicin-exposed HepG2 cells pretreated with menthol due to upregulation of P-glycoprotein.

The aim of the present study was to examine changes in the expression and activity of P-glycoprotein (P-gp) in human hepatocellular carcinoma HepG2 cells after exposure to menthol, and their relationship to the cytotoxicity of and apoptotic responses to doxorubicin (DOX), a substrate of P-gp, in the cells. The expression of P-gp in HepG2 cells was significantly increased by menthol treatment. Intracellular accumulation of DOX in HepG2 cells was significantly lower in the menthol-treated group than in the control group, but this phenomenon was abolished in the presence of verapamil. Decreased cell viability by DOX was significantly attenuated by 24-h menthol treatment prior to DOX exposure, which coincided with the changes in mRNA expression of Bcl-xl and caspase-3. These results demonstrate that menthol causes hepatocellular carcinoma cells to acquire resistance to DOX by increasing its efflux through the upregulation of P-gp.

Downregulation of organic cation transporter 1 and breast cancer resistance protein with the induction of Pregnane X receptor in rat kidney impaired by doxorubicin.

Transporters expressed in the kidney play an important role in the excretion of endogenous substances and chemical drugs. The Pregnane X receptor (PXR) has been reported to be involved in regulating the expression of numerous transporters. In the present study, we examined the alteration in expression level of PXR, organic cation transporter 1 (OCT1) and breast cancer resistance protein (BCRP) in renal cell lines of rat origin and the kidney of rats when damaged by doxorubicin (DOX). The expression level of PXR in renal tubular epithelium NRK-52E cells was significantly increased by DOX at a concentration confirmed to cause cellular damage. The expression levels of OCT1 and BCRP were significantly lower in the DOX-treated cells than in the untreated cells. In model rats with DOX-induced nephrotoxicity, the alterations in renal expression of PXR, OCT1 and BCRP were similar to those in NRK-52E cells, although there was a difference in the degree of the changes.

Long-term clinical impact of serum albumin in coronary artery disease patients with preserved renal function.

BACKGROUND AND AIMS: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function. METHODS AND RESULTS: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001). CONCLUSION: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function.

Perioperative outcomes of single-port mediastinoscope-assisted transhiatal esophagectomy for thoracic esophageal cancer.

We developed an en bloc lymphadenectomy method in the upper mediastinum with a single-port mediastinoscopic cervical approach. This study was designed to evaluate the safety and efficacy of single-port mediastinoscope-assisted transhiatal esophagectomy for thoracic esophageal cancer. The perioperative outcomes of 60 patients with thoracic esophageal cancer who underwent this operation between March 2014 and June 2016 were retrospectively analyzed. The upper mediastinal dissection including lymphadenectomy along the left recurrent laryngeal nerve, using a left cervical approach, was performed with a single-port mediastinoscopic technique, which was used to improve the visibility and handling in the deep mediastinum around the aortic arch. The lymphadenectomy along the right recurrent laryngeal nerve was performed under direct vision using a right cervical approach. Bilateral cervical approaches were followed by hand-assisted laparoscopic transhiatal esophagectomy with en bloc lymphadenectomy in the middle and lower mediastinum. Tumors were mainly located in the middle thoracic esophagus (n = 33), and most tumors were squamous cell carcinoma (n = 58). Pretreatment diagnoses were stage I, 19; II, 13; III, 24; IV, 4. Preoperative chemotherapy was performed for 40 patients. The median operation time and blood loss were 363 minutes and 235 mL, respectively. There were two patients who underwent conversion to thoracotomy. Perioperative complications were evaluated and graded according to the Clavien-Dindo (CD) and the Esophagectomy Complications Consensus Group (ECCG) classifications. Postoperatively, pneumonia was observed in four patients (CD, Grade II, 2; Grade IIIb, 2), although vocal cord palsy was more frequent (ECCG, Type I, 12; Type III, 8). The median number of thoracic lymph nodes resected was 21, and the R0 resection rate was 95%. Single-port mediastinoscope-assisted transhiatal esophagectomy is feasible, in terms of perioperative outcomes, for a radical surgery for thoracic esophageal cancer, although its safety needs to be further demonstrated.

Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection.

Laparoscopic transhiatal esophagectomy is a minimally invasive approach for esophageal cancer. However, a transhiatal procedure has not yet been established for en bloc mediastinal dissection. The purpose of this study was to present our novel procedure, hand-assisted laparoscopic transhiatal esophagectomy, with a systematic procedure for en bloc mediastinal dissection. The perioperative outcomes of patients who underwent this procedure were retrospectively analyzed. Transhiatal subtotal mobilization of the thoracic esophagus with en bloc lymph node dissection distally from the carina was performed according to a standardized procedure using a hand-assisted laparoscopic technique, in which the operator used a long sealing device under appropriate expansion of the operative field by hand assistance and long retractors. The thoracoscopic procedure was performed for upper mediastinal dissection following esophageal resection and retrosternal stomach roll reconstruction, and was avoided based on the nodal status and operative risk. A total of 57 patients underwent surgery between January 2012 and June 2013, and the transthoracic procedure was performed on 34 of these patients. In groups with and without the transthoracic procedure, total operation times were 370 and 216 minutes, blood losses were 238 and 139 mL, and the numbers of retrieved nodes were 39 and 24, respectively. R0 resection rates were similar between the groups. The incidence of recurrent laryngeal nerve palsy was significantly higher in the group with the transthoracic procedure, whereas no significant differences were observed in that of pneumonia between these groups. The hand-assisted laparoscopic transhiatal method, which is characterized by a systematic procedure for en bloc mediastinal dissection supported by hand and long device use, was safe and feasible for minimally invasive esophagectomy.

Higher gene expression of CYP1A2, 2B1 and 2D2 in the brain of female compared with male rats.

Cytochrome P450 (CYP) in the brain plays an essential role in the local metabolism of various compounds, including clinically used drugs, toxins, and endogenous substances. In the present study, we compared the expression profiles of mRNAs for several CYP subtypes in the brain between male and female rats. The expression of CYP1A2, CYP2B1, and CYP2D2 in females was significantly higher than that in males. On the other hand, the expression level of the other CYP subtypes examined in the male brain was similar to that in the female brain. These results strongly suggest that marked gender differences exist in the expression profiles of some CYP subtypes in rat brain.

Taurine as a protective agent for 5-fluorouracil-induced hepatic damage related to oxidative stress.

5-Fluorouracil (5-FU) is a pyrimidine analog widely used for the treatment of various cancers, but often causes hepatic damage in clinical practice. In this study, we examined the influence of taurine on 5-FU-induced hepatotoxicity in mice with respect to changes in oxidative stress. Elevations in the aspartate aminotransferase and alanine aminotransferase serum levels after 5-FU administration were significantly suppressed in a dosedependent manner by concurrent treatment with taurine. The activity of superoxide dismutase and reduced glutathione content in the liver were significantly decreased following treatment with 5-FU alone, but these changes were markedly inhibited by the administration of taurine. Our findings suggest that taurine protects against 5-FU-induced hepatotoxicity by suppressing oxidative stress.

Overexpression of SMYD2 contributes to malignant outcome in gastric cancer.

BACKGROUND: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer. METHODS: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. RESULTS: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69-10.7)). CONCLUSIONS: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer.

Plumbagin suppresses tumor cell growth in oral squamous cell carcinoma cell lines.

OBJECTIVES: Plumbagin (PL), a naturally occurring quinoid, exerts antitumoral effects in diverse types of cancer cells. However, the effect of PL on tumor cell proliferation in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, we assessed the efficacy of PL, in human OSCC cells. METHODS: The effect of PL on the cell growth and apoptosis of OSCC cell lines was evaluated using MTT and Annexin V assays, respectively. The effect of PL on mitochondrial membrane potential loss and reactive oxygen species (ROS) generation was evaluated using flow cytometry analysis. RESULTS: MTT assay showed that PL dose-dependently suppressed OSCC cell growth, with IC50 values ranging from 3.87 to 14.6 µM. Flow cytometry analysis revealed that PL treatment resulted in a significant decrease in mitochondrial membrane potential and an increase in the number of apoptotic cells. Notably, ROS generation was significantly elevated after PL treatment. Furthermore, a ROS scavenger, N-acetylcysteine (NAC), clearly suppressed the decrease in mitochondrial membrane potential, increase of caspase-3/7 activity, and apoptosis after PL treatment. CONCLUSION: This study provides the considerable evidence of the tumor-suppressive effect of PL, thereby highlighting its therapeutic potential for OSCC treatment.

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC. RESULTS: (1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145). CONCLUSIONS: Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.

Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant.

The standard therapy against hepatitis C virus (HCV) recurrence postliver transplantation includes interferon (IFN)α and ribavirin. IFNL4 ss469415590 polymorphism has been reported as a novel predictor of the response to IFN therapy for chronic HCV infection. We examined the impact of IFNL4 polymorphism on the responsiveness to IFN therapy after liver transplantation. Tissue specimens were collected from 80 HCV-infected recipients and 78 liver donors, and their IFNL4 ss469415590 genotype, hepatic IFNL4 and interferon-stimulated genes' mRNA expression levels were examined. The association of the polymorphism and expression levels in terms of the IFN therapy response to HCV recurrence was analysed. Most individuals who had rs8099917 risk alleles also had ss469415590 risk alleles (R(2) = 0.9). Sustained virological response (SVR) rates were higher in both liver graft recipients and transplants with ss469415590 TT/TT alleles than in those with the risk ΔG allele (P = 0.003 and P = 0.005, respectively). In recipients with ss469415590 TT/TT, IFNL4 TT mRNA levels showed no significant differences between livers of patients who responded to therapy and those who did not (P = 0.4). In recipients with the risk ΔG allele, IFNL4 ΔG mRNA expression levels were significantly lower in SVR patients than in non-SVR patients (P = 0.02). Hepatic interferon stimulable genes and IFNL4 mRNA expression were correlated. Our findings suggest that analysing the ss469415590 genotype and IFNL4 ΔG expression provides a novel prediction strategy for the possible response to IFN therapy after liver transplantation.

Gender differences in the gene expression profiles of glucose transporter GLUT class I and SGLT in mouse tissues.

Glucose transporters play key roles in controlling blood sugar levels and are recognized as the pharmacological targets of antidiabetic agents. In the present study, we compared the gene expression profiles of glucose transporter GLUT class I and SGLT isoforms in the skeletal muscle, heart, liver, kidney, and brain of male and female mice. The expression profiles of GLUT1 -4 and SGLT1 -2 in male mouse tissues were similar to those previously reported. Significant gender differences were observed in mRNA expression in terms of individual these glucose transport systems and the tissues examined. Especially, all of the corresponding mRNAs of renal GLUT class I and SGLT isoforms were expressed at higher levels in female mice than in male mice. However, no significant differences were observed in serum glucose concentrations between male and female mice. These results strongly suggest that prominent gender differences exist in the gene expression profiles of these glucose transporters in mouse tissues, and that the quantitative and functional multiplicities of glucose transporters may contribute to the successful regulation of blood glucose concentrations irrespective of gender differences.

Pharmacokinetic evaluation of intraperitoneal doxorubicin in rats.

The intraperitoneal (ip) administration of doxorubicin (DOX) is considered to be an important approach for the treatment of peritoneal tumors, because the prognosis of peritoneal cancer is generally poor due to its refractoriness to conventional chemotherapy. In the present study, we examined the disposition behavior of DOX after ip administration in rats to evaluate the adequacy of the ip administration of DOX on the basis of pharmacokinetic aspects. By comparing the area under the serum concentration-time curve (AUC) after ip and intravenous (iv) dosing of 5 mg/kg DOX, the bioavailability of intraperitoneally administered DOX was estimated as 43.8%. This finding suggests that the majority of DOX remained in the abdominal cavity without being incorporated into the systemic circulation. The mean residence time (MRT) of DOX after its ip administration was about 80% longer than that after its iv administration, which indicated the slow absorption process associated with ip application. No significant difference was observed in the elimination rates of systemically absorbed DOX. These results indicate that the ip administration of DOX likely provided an adequate opportunity for it to interact with peritoneal tumors by maintaining sufficient DOX levels while reducing its systemic exposure

Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma.

BACKGROUND: Several recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC. METHODS: This study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC. RESULTS: (1) Expression of miR-18a was significantly higher in ESCC tissues (P=0.0020) and ESCC cell lines (P=0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P<0.0001; ESCC patients vs healthy volunteers (mean±s.d.): 11.77±13.45 vs 0.73±0.54 amol µl(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-I showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P=0.0076). CONCLUSION: Plasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.

Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer.

BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa. METHODS: This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients. RESULTS: (1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021). CONCLUSION: Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.

Overexpression of YWHAZ relates to tumor cell proliferation and malignant outcome of gastric carcinoma.

BACKGROUND: Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). METHODS: We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003. RESULTS: Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003-5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047). CONCLUSION: These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma.

BACKGROUND: Recently, it was reported that plasma microRNAs (miRNAs) are low-invasive useful biomarkers for cancer. We attempted to isolate gastric cancer (GC)-associated miRNAs comparing pre- and post-operative paired plasma, thereby excluding the possible effects of individual variability. METHODS: This study was divided into four steps: (1) microarray analysis comparing pre- and post-operative plasma; (2) validation of candidate miRNAs by quantitative RT-PCR; (3) validation study of selected miRNAs using paired plasma; and (4) comparison of the levels of selected miRNAs in plasma between healthy controls and patients. RESULTS: From the results of microarray analysis, nine candidate miRNAs the levels of which were markedly decreased in post-operative plasma were selected for further studies. After confirmation of their post-operative marked reduction, two candidate miRNAs, miR-451 and miR-486, were selected as plasma biomarkers, considering the abundance in plasma, and marked decrease in post-operative samples. In validation, the two miRNAs were found to decrease in post-operative plasma in 90 and 93% of patients (both P<0.01). In comparison with healthy controls, the levels of both miRNAs were found to be significantly higher in patients, and the area under the curve values were high at 0.96 and 0.92. CONCLUSION: Plasma miR-451 and miR-486 could be useful blood-based biomarkers for screening GC.

Recognition of endoscopic diagnosis in differentiated-type early gastric cancer by flexible spectral imaging color enhancement with indigo carmine.

BACKGROUND/AIMS: To evaluate the usefulness of flexible spectral imaging color enhancement with indigo carmine (I-FICE) in early gastric cancer (EGC) demarcation. METHODS: The study participants were 29 patients with differentiated-type EGC. The endoscope was fixed and images of the same area of EGC demarcations in each lesion were obtained using four different methods (WLE, flexible spectral imaging color enhancement (FICE), CE, and I-FICE). FICE mode at R 550 nm (Gain: 2), G 500 nm (Gain: 4), and B 470 nm (Gain: 4) was used. Four endoscopists ranked the images obtained by each method on the basis of the ease of recognition of demarcation using a 4-point system. We calculated the standard deviation of pixel values based on L*, a*, and b* color spaces in the demarcation region (Lab-SD score). RESULTS: The median ranking score for I-FICE images was significantly higher than that obtained from the other methods. Further, the average Lab-SD score was significantly higher for I-FICE images than for images obtained by the other methods. There was a good correlation between the ranking score and Lab-SD score. CONCLUSION: EGC demarcations were most easily recognized both subjectively and objectively using I-FICE image, followed by CE, FICE and WLE images.