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Specific primers for PCR and small interfering RNA

Supplemental Methods

Gene set enrichment analysis of ASGR2 expression in GSE62254

Hematogenous recurrence is a challenging clinical finding that often leads to fatalities of patients with gastric cancer. Therefore, the identification of specific biomarkers and potential therapeutic target molecules for hematogenous recurrence is required to improve the outcomes of these patients. Here, transcriptome and bioinformatics analyses were conducted to uncover candidate molecules differentially expressed in patients with hematogenous recurrence of gastric cancer. One potential candidate identified was asialoglycoprotein receptor 2 (ASGR2), and siRNA experiments were conducted to determine the effect of manipulating ASGR2 expression has on cell phenotypes. ASGR2 mRNA expression analysis using quantitative real-time reverse-transcription PCR was conducted with stage II/III gastric cancer clinical specimens (n = 95). Transcript levels were increased in gastric cancer cells as compared with a control nontumorigenic epithelial cell line. Knockdown of ASGR2 decreased the adhesion and migration potential. Thus, although gastric cancer cell–invasive activity was significantly decreased by knockdown, forced expression of ASGR2 promoted invasive activity. Using a mouse hepatic metastasis model, knockdown of ASGR2 resulted in the absence of hepatic metastasis formation. High ASGR2 expression in primary gastric cancer tissues was an independent predictor of shorter disease-free and overall survival. Finally, patients with high ASGR2 expression were more likely to have a high cumulative rate of hematogenous recurrence but not peritoneal or nodal recurrence.Implications: ASGR2 expression is associated with the malignant phenotypes in gastric cancer and represents a specific biomarker of hematogenous recurrences after curative resection for gastric cancer. Mol Cancer Res; 16(9); 1420–9. ©2018 AACR.

The prognosis of colorectal cancer is closely linked to the occurrence of distant metastases. Systemic dissemination is most likely caused by circulating tumor cells (CTC). Despite the fundamental role of CTC within the metastatic cascade, technical obstacles have so far prevented detailed genomic and, in particular, phenotypic analyses of CTC, which may provide molecular targets to delay or prevent distant metastases. We show here a detailed genomic analysis of single colorectal cancer–derived CTC by array comparative genomic hybridization (aCGH), mutational profiling, and microsatellite instability (MSI) analysis. Furthermore, we report the first gene expression analysis of manually selected colorectal cancer–derived CTC by quantitative real-time PCR (qRT-PCR) to investigate transcriptional changes, enabling CTC to survive in circulation and form distant metastases. aCGH confirmed the tumor cell identity of CellSearch-isolated colorectal cancer–derived CTC. Mutational and MSI analyses revealed mutational profiles of CTC to be similar, but not identical to the corresponding tumor tissue. Several CTC exhibited mutations in key genes such as KRAS or TP53 that could not be detected in the tumor. Gene expression analyses revealed both a pronounced upregulation of CD47 as a potential immune-escape mechanism and a significant downregulation of several other pathways, suggesting a dormant state of viable CTC. Our results suggest mutational heterogeneity between tumor tissue and CTC that should be considered in future trials on targeted therapy and monitoring of response. The finding of upregulated immune-escape pathways, which may be responsible for survival of CTC in circulation, could provide a promising target to disrupt the metastatic cascade in colorectal cancer. Cancer Res; 74(6); 1694–704. ©2014 AACR.

PDF file - 360KB, aCGH analysis of chromosomal aberrations in single CRC-derived CTC and corresponding tumor tissue (S1); An alternative aCGH algorithm confirms the tumor cell identity of the examined single CTC (S2); Validation of the reproducibility of low cell number real-time PCR (S3); Establishment and performance of single cell realtime PCR analysis (S4); Picture of a cluster of 3 CTC from patient HD-2095 (S5).

Objective:This study aimed to develop a gene-expression signature for identification of lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC) patients.Summary of Background Data:LN metastasis is recognized as the most important independent risk factor for therapeutic decision-makin

Due to the considerably reduced boiling point, organic fluids such as ethanol provide an attractive alternative to water as the working fluid in two-phase thermal management systems for high-heat-flux applications. The state-of-the-art enhancement methods for ethanol boiling normally involve surface structure engineering. Here we report, for the first time, enhancement of nucleate boiling of ethanol using wettability-patterned surfaces. By depositing onto a polished copper surface an array of circular spots of superamphiphobic coating of modified halloysite nanotubes (HNT) with fluoropolymer, which was shown to repel low-surface-tension fluids, we managed to create a meaningful biphilic pattern of alternating hydrophobicity (with ethanol contact angle exceeding 100°) and hydrophilicity (with contact angle close to 0°) on the surface. Boiling heat transfer was found to be improved dramatically on the coated surface. Specifically, the onset of nucleate boiling was found to drop by more than 35%. Moreover, at 20 K surface superheat (above the boiling point), a maximum heat transfer enhancement over 300% compared with a plain copper surface occurred on the surface with a pitch-to-spot ratio close to 2.5. The significantly increased heat transfer rate of the biphilic surfaces could be attributed to facilitated bubble nucleation and stronger agitation effect.

Background Neoadjuvant chemotherapy (NAC) has become the standard of care for resectable esophageal squamous cell carcinoma (ESCC) which is one of the most lethal cancers, to improve resectability and prognosis. On this basis, to provide individually optimized therapy for ESCC, a minimally-invasive biomarker for response to NAC is strongly desired. This study aimed to identify the miRNA signature in serum specimens taken from ESCC patients undergoing NAC through genome-wide microarray technology. Methods Comprehensive miRNA-expression profiles of serum specimens from ESCC patients before initial treatment were analyzed using microarray. A qPCR assay was performed to test the robustness of identified serum-based miRNA signature for discriminating response to NAC with serum specimens taken from 100 ESCC cases undergoing NAC. Results We prioritized 62 miRNAs differentially expressed between responders and non-responders (absolute log2 fold change > 1.0, corresponding P

Many landslides occurred around epicentral region and a large debris avalanche occurred on southern slope of Mt. Ontake and travelled about 12 km down due to the 1984 Western Nagano Prefecture Earthquake (Mw = 6.2). Furthermore, many displaced boulders were observed at the mountaintop and ridge near hypocenter. The horizontal and vertical accelerations near hypocenter were estimated to be more than 2G from these dislocated boulders. However there is no near-field strong motion records and the mechanism of the dislocation has not been clarified in detail so far. Therefore, the authors performed the fault rupture simulations considering the dynamic rupture process of the fault plane to estimate the strong motion around hypocentral region. It is shown that large acceleration occurred in the ridge as a result of amplification of the topography if the critical slip displacement Dc and topography were taken into account in 3D FEM mesh. However, the strong motions near the landslide at Mt. Ontake was not high, which was probably due to large FEM mesh size and no consideration of the decrease of shear wave velocity (Vs) in surface layer.

Time-prediction methods based on monitoring the displacement of a slope are effective for the prevention of sediment-related disasters. Several models have been proposed to predict the failure time of a slope based on the creep theory of soil, which describes the accelerating surface displacements that precede slope failure. Fukuzono’s method has been widely adopted in practice. This method can only be applied to the period when the surface displacement accelerates. However, the observed surface displacement appears to increase monotonically, slightly repeating the increase and decrease. These results decrease the accuracy of the predicted failure time. Thinning out the observed data is effective for minimising the influence of fluctuations. In this study, we predicted the failure time of a sandy model slope under artificial rainfall using four methods based on Fukuzono’s model, compared the prediction accuracy of each method and examined the influence of measurement intervals on the predicted failure time using extracted data at different measurement intervals. The results showed that the variation of the extracted data group decreases and the prediction accuracy of the failure time improves if the measurement interval increases. Moreover, when the failure time of a slope is predicted using statistical methods, the accuracy of the prediction is further improved.

In recent years, the exposure dose of the operator's eye lens during interventional radiology operations has become a problem. We therefore evaluated the feasibility of real-time lens dose measurement using scintillator with optical fiber (SOF) dosimeter. Given that the SOF dosimeter is calibrated for direct X-rays, we performed a calibration for scattered X-rays to investigate energy dependence and the accuracy of lens dose measurements. The detection limit was calculated using the Kaiser method. The SOF dosimeter and the radiophotoluminescence glass (RPLG) dosimeter were attached to the protective glasses worn by the operator, and the lens exposure dose of the operator during cardiac catheterization was measured. In the phantom experiment, the SOF dosimeter had an error rate of 5.45% based on the measured value of the ionization chamber dosimeter. The sensitivity characteristics of the SOF dosimeter were slightly reduced on the higher side of the effective energy. The difference in sensitivity was related to variations in the additional filter and energy dependency. The sensitivity difference was 18.5% at maximum. Furthermore, when the additional dose was displayed, the influence of noise on long-term measurement was considerable. Using the Kaiser method to obtain the detection limit, the accuracy of the integrated dose had SOF dosimeter error rates of 4.3% to 15.5% with respect to the integrated value of the RPLG dosimeter when calibrated by the ionization chamber dosimeter. The use of the SOF dosimeter allowed for the real-time visualization of the exposure status of the eye lens and measurements with a relatively high accuracy.

Trial Information Click here to access other published clinical trials. Lessons Learned Two courses of neoadjuvant therapy using S-1 plus cisplatin for clinical stage III esophageal squamous cell carcinoma did not achieve expected response rate according to endoscopic evaluation of primary tumors. Subsequent esophagectomy was safely performed. Background In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the need for a more effective regimen. Methods A single-arm, open-label phase II trial was conducted to evaluate the safety and efficacy of two courses of neoadjuvant chemotherapy using S-1 plus cisplatin (NAC-SP) for clinical stage III ESCC. The primary endpoint was overall response rate as defined by endoscopic evaluation of primary tumors. Results We enrolled 26 patients. The completion rate for the two courses of NAC-SP was 61.5%. Grade 3 or higher adverse events were experienced by 38.4% of patients. The treatment response rate according to endoscopic findings, acquired before the second course, was 34.6% and below the expected level (55.0%). The morbidity rate of patients who underwent radical subtotal esophagectomy (96.2%) was 32.0%. Repeat surgery was unnecessary, and surgery-associated deaths did not occur. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 84.6% and 92.2%, respectively. Conclusion We demonstrate safety of NAC-SP, but not its efficacy, for patients with clinical stage III ESCC. Subsequent esophagectomy was safely performed.

OBJECTIVE The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). BACKGROUND It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. METHODS A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. RESULTS In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. CONCLUSIONS In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.

OBJECTIVES This study aimed to clarify the correlation between image classification and the pathological degree of portal system invasion (PSI) and to evaluate the prognostic impact of PSI in pancreatic cancer (PC). METHODS Pancreatic cancer patients with surgical resections (head, n = 244; body and tail, n = 80) were enrolled in this study. RESULTS Based on imaging findings, portal vein (PV) invasion was classified as type A (absent), B (unilateral narrowing), C (bilateral narrowing), or D (stenosis or obstruction with collaterals). Splenic vein (SPV) invasion was classified as type α (absent), β (stenosis), or γ (obstruction). The pathological grade of venous invasion was classified as grade 0 (no invasion), 1 (tunica adventitia), 2 (tunica media), or 3 (tunica intima). In PV and SPV invasions, image classification and pathological grade showed significant correlation (PV: ρ = 0.696; SPV: ρ = 0.681). Patients with PV invasion deeper than type B exhibited significantly poorer survival than type A (P < 0.0001). In contrast, there was no difference in survival among types α, β, and γ. CONCLUSIONS Image classification was correlated with the pathological grade of PSI in PC. Although not applicable for SPV invasion, image classification of PV invasion is a robust indicator for PC prognosis.

Hematogenous recurrence is a challenging clinical finding that often leads to fatalities of patients with gastric cancer. Therefore, the identification of specific biomarkers and potential therapeutic target molecules for hematogenous recurrence is required to improve the outcomes of these patients. Here, transcriptome and bioinformatics analyses were conducted to uncover candidate molecules differentially expressed in patients with hematogenous recurrence of gastric cancer. One potential candidate identified was asialoglycoprotein receptor 2 (ASGR2), and siRNA experiments were conducted to determine the effect of manipulating ASGR2 expression has on cell phenotypes. ASGR2 mRNA expression analysis using quantitative real-time reverse-transcription PCR was conducted with stage II/III gastric cancer clinical specimens (n = 95). Transcript levels were increased in gastric cancer cells as compared with a control nontumorigenic epithelial cell line. Knockdown of ASGR2 decreased the adhesion and migration potential. Thus, although gastric cancer cell–invasive activity was significantly decreased by knockdown, forced expression of ASGR2 promoted invasive activity. Using a mouse hepatic metastasis model, knockdown of ASGR2 resulted in the absence of hepatic metastasis formation. High ASGR2 expression in primary gastric cancer tissues was an independent predictor of shorter disease-free and overall survival. Finally, patients with high ASGR2 expression were more likely to have a high cumulative rate of hematogenous recurrence but not peritoneal or nodal recurrence. Implications: ASGR2 expression is associated with the malignant phenotypes in gastric cancer and represents a specific biomarker of hematogenous recurrences after curative resection for gastric cancer. Mol Cancer Res; 16(9); 1420–9. ©2018 AACR.

Lysyl oxidase (LOX) family genes, particularly lysyl oxidase-like protein 2 (LOXL2), have been implicated in carcinogenesis, metastasis, and the epithelial-to-mesenchymal transition (EMT) in various cancers. This study aimed to explore the clinical implications of LOXL2 expression in pancreatic cancer (PC) in the context of EMT status. LOX family mRNA expression was measured in PC cell lines, and LOXL2 protein levels were examined in surgical specimens resected from 170 patients with PC. Higher LOXL2 expression was observed in cell lines from mesenchymal type PC than in those from epithelial type PC. A significant correlation between LOXL2 expression and the EMT status defined based on the expression of E-cadherin and vimentin was observed in surgical specimens (P P P = 0.03) was a significant independent prognostic factor for patients with PC. Additionally, LOX inhibition significantly decreased PC cell proliferation, migration, and invasion in vitro. In conclusion, LOXL2 expression is potentially associated with PC progression, and LOXL2 expression represents a biomarker for predicting the prognosis of patients with PC who have undergone complete resection.

Liver metastasis remains a serious problem in the management of gastric cancer (GC). Our aims were to identify through transcriptome analysis a molecule that mediates hepatic metastasis in GC, and to evaluate its potential as a diagnostic marker and a therapeutic target. The effects of knocking out a relevant molecule using genome editing were evaluated in vitro experiments and in mouse xenograft models. Expression levels of candidate molecule in 300 pairs of gastric tissues were determined to assess whether differentially expressed genes predicted hepatic recurrence, metastasis, or both. Transcriptome data identified the overexpression of synaptotagmin VII (SYT7) in GC tissues with hepatic metastasis. Its expression in the GC cell lines was high, particularly in those that exhibited a differentiated phenotype, and positively correlated with the expression of SNAI1 and TGFB3, and inversely with RGS2. SYT7 knockout inhibited the proliferation of GC cells, indicated by increased apoptosis with activated caspase and loss of mitochondria membrane potential, G2/M cell-cycle arrest and attenuated cell migration, invasion, and adhesion. The tumorigenicity of SYT7-knockout cells was moderately reduced in a mouse model of subcutaneous metastasis in which the levels of BCL2 and HIF1A were decreased and was more strikingly attenuated in a model of hepatic metastasis. The SYT7 levels in the primary GC tissues were significantly associated with hepatic recurrence, metastasis, and adverse prognosis. SYT7 represents a tool for prediction and monitoring of hepatic metastasis from GC as well as being a promising therapeutic target.

INTRODUCTION Optical trocar access is a technique to place the initial trocar in laparoscopic surgery. With optical trocar access, each tissue layer can be visualized before insertion, which can help prevent organ injury, and air leaks at the trocar site can be minimized even in obese patients. The aim of this study was to compare the time needed for trocar insertion using optical trocar access and an open method in patients who underwent laparoscopic gastrointestinal surgery. METHODS We reviewed our prospectively collected database and identified 384 patients who underwent laparoscopic gastrointestinal surgery involving initial trocar insertion near the umbilicus by either the optical trocar access or the open method. Before the two methods were compared, propensity score matching was used to adjust for essential variables between the optical trocar access and open groups. RESULTS Patients categorized in the optical trocar access and open groups were matched one-to-one by propensity score matching, and 137 pairs of patients were generated. The time needed for trocar insertion was significantly shorter in the optical trocar access group than in the open group (36.6 vs 209.8 s, P

Objective: To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). Background: Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. Methods: We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. Results: Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. Conclusions: SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC., ファイル公開：2019-03-01

Background/Aims: Do serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels serve as prognostic indicators in patients with gastric cancer (GC)? This is a question that has long been disputed. The aim of this study was to evaluate the significance of perioperative serum levels of CEA and CA19-9 for predicting the recurrence and long-term survival after patients with pT2-4 GC undergo curative gastrectomy. Methods: This study included 251 patients with radically resected pT2-4 GC without preoperative treatment. Associations between the preoperative and postoperative serum levels of CEA or CA19-9 and postoperative long-term outcomes and recurrence patterns were evaluated. Results: Preoperative CEA >5.0 ng/mL was an independent prognostic factor of overall survival. Elevation of both preoperative CEA and CA19-9 levels showed no synergistic adverse effects on prognosis. Preoperative levels of these markers achieved superior predictive performance compared with the postoperative values. Adverse prognosis is significantly associated with persistent elevation of CEA levels before and after gastrectomy. Elevation of CEA levels, particularly at postoperative measurement, was significantly associated with hematogenous recurrence. Conclusion: Determination of perioperative CEA levels facilitated predictions of recurrence patterns and prognosis among patients with pT2-4 GC who underwent curative gastrectomy., ファイル公開日: 2018/12/01

Boiling heat transfer suffers deteriorations under subatmospheric conditions, which can be attributed to a shortage of viable nucleation sites at declining pressures. In this work, the possibility of enhancing low-pressure saturated boiling of water using a combination of wettability patterning and structural modifications was experimentally explored. The copper test surface, comprised of an array of circular “dimples” (0.3 mm in depth, 0.5 mm in diameter, and 3.0 mm in pitch), was spray-coated by polytetrafluoroethylene (PTFE) coatings so as to form a matching biphilic pattern with the surface cavities. The resulting dimpled biphilic surface showed appreciable heat transfer enhancement—with a maximum 60% increase of the average heat transfer coefficient of nucleate boiling compared with a flat biphilic surface—down to about 9.5 kPa. Further lowering the pressure to 7.8 kPa, however, was found to lead to diminished performance gains. The visualization study of the bubble departure dynamics revealed signs of additional vapor trapping of the hydrophobic-coated cavities, which can induce uninterrupted bubble regeneration with zero waiting time and explain the qualified enhancement of subatmospheric boiling. Thanks to a potential secondary pinning of contact line inside the hydrophobic cavities, incomplete bubble detachment could prevail at somewhat lower pressures than was otherwise possible without the dimple structure, leaving behind significantly more vapor residues. However, the vapor-trapping capacity was found to decrease with pressure, which provided clues with regard to the reduced efficacy of the surface at even lower pressures.

The dynamic mechanical behaviour and characteristics of rocks have been investigated using different techniques to evaluate the engineering structures under dynamic loads. The authors devised a new experimental apparatus to investigate the behaviour of rocks under shock waves. A new double shearing jig shown in figure 1 was developed and it was used to study the shearing of rocks and discontinuities under static and impact loading conditions using the device. Double shearing tests involve various rocks and discontinuities. The authors describe the experimental results under shock load and static loading and the results are compared with each other and their implications are discussed in rock mechanics and rock engineering. Although the system is quite simple, it is shown that it is very practical to study the shear behaviour of both intact rocks and discontinuities.

Background: Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy. Methods: A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome. Results: Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence. Conclusions: Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.

The albumin–bilirubin (ALBI) score was initially developed for assessing liver dysfunction severity and was suggested to have prognostic value in patients with hepatocellular carcinoma. We aimed to evaluate the prognostic impact of ALBI grade in patients with advanced gastric cancer (GC) after radical gastrectomy. This study included 283 patients who underwent radical gastrectomy for pT2-4 GC without preoperative treatment. ALBI was calculated as follows: (log10 bilirubin (μmol/L) × 0.66) + (albumin (g/L) × −0.0852) and categorized into grades 1 (≤−2.60), 2 (−2.60

Background Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker. Methods We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection. Results GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences. Conclusions Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection. Electronic supplementary material The online version of this article (10.1186/s12885-017-3629-2) contains supplementary material, which is available to authorized users.

The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC‑associated molecular events to improve the diagnosis, and treatment of this disease. Non‑specific cytotoxic cell receptor protein 1 (NCCRP1) was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of NCCRP1 in ESCC remains unclear. To elucidate the oncological roles of NCCRP1 in ESCC, NCCRP1 expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different NCCRP1 mRNA expression levels and all exhibited hypermethylation of the NCCRP1 promoter, but no copy number loss. Additionally, NCCRP1 expression was determined in 213 surgically resected esophageal tissue samples. NCCRP1 mRNA expression levels were reduced in ESCC tissues compared with corresponding non‑cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low NCCRP1 expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high NCCRP1 expression group. Additionally, multivariate analysis revealed that low NCCRP1 expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08‑2.87; P=0.022). The findings of the current study indicate that NCCRP1 acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.

AIM To identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors. METHODS Three-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy (distal gastrectomy or total gastrectomy) were included in the analysis. Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications (grade II or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage. RESULTS Sixty-six patients (21.1%) experienced grade II or higher postoperative complications. The platelet-lymphocyte ratio (PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value (0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71 (sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94 (95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications (OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications. CONCLUSION The preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer.

Background: Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). Methods: Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. Results: Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). Conclusions: The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.

Introduction Laparoscopy-assisted distal gastrectomy is one of the major treatments for early stage gastric cancer, particularly in the East Asia. In this method, extracorporeal anastomosis is performed via a small laparotomy wound, but excessive tissue traction may be encountered during the anastomotic procedure. Therefore, we developed an original procedure for extracorporeal Billroth-I reconstruction: end-to-end stapling gastroduodenostomy with complete double stapling technique. This procedure aims to reduce the problems related to maneuvers through a small laparotomy. Methods An end-to-end anastomosis is constructed on the transection line using a circular stapler inserted from the distal end of the greater curvature of the remnant stomach. Short-term outcomes were reviewed in 218 consecutive patients who underwent complete double stapling technique reconstruction after laparoscopy-assisted distal gastrectomy between 2002 and 2012. Findings from GI endoscopy were reviewed in 110 patients. Results The mean operative time was 216 min, and mean blood loss was 163 mL. There was no conversion to the open surgery and no operative death. Eight patients (3.6%) had anastomosis-related postoperative complications. In follow-up endoscopic examinations 1 year after surgery, grade 3 or higher residual food was seen in 17.2% of patients. Gastritis extending to the entire remnant stomach was observed in 8.2% of patients, and grade 3 gastritis was seen in 2.7%. Los Angeles classification grade A or higher reflux esophagitis was found in 10.9%. Conclusions Billroth-I reconstruction by the complete double stapling technique is a safe and feasible procedure. This method provides satisfactory short-term outcomes, including the incidence of reflex remnant gastritis and esophagitis.

The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.

BACKGROUND The aim of this paper was to evaluate the validity of tumor volume measurement using diffusion-weighted (DW) imaging in cervical cancer. METHODS In this retrospective study, 22 patients, who underwent preoperative 3.0 T MR examinations with DW imaging were evaluated. Tumor volume measurement by oblique axial (short axis to the uterine cervix) T2-weighted imaging was performed by manually outlining the tumor on the monitor. The area of tumor in each slice was multiplied by the slice profile (slice thickness plus intersection gap), and the total tumor volume was calculated by summation of these obtained volumes. Meanwhile, one experienced radiological technologist generated three-dimensional DW images of cervical cancer using a volume-rendering algorithm at a computer workstation, and tumor volume was automatically calculated in the workstation. Analysis via the intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the validity and reliability of these methods. RESULTS Between tumor volumes measured by T2-weighted imaging methods and DW imaging methods, the ICC was excellent (0.962). The 95% limits of agreement of volume measurement were -52.7 and 35.7 mL (mean difference, -8.5 mL). In regards to intra-observer variability, the ICC was excellent (0.963). The 95% limits of agreement of volume measurement were -42.2 and 47.4 mL (mean difference, 2.6 mL). CONCLUSION DW imaging can be used to measure cervical cancer volume.

Recently, non-invasive, real-time and multi-point measurement of neural activities has become possible by using a multi-electrode array (MEA). Another method for multi-point measurement is the fluorescent imaging technique using voltage indicator dyes or calcium indicator dyes. Especially, calcium imaging using fluorescent calcium indicator dyes is often more useful, because they exhibit larger changes in the fluorescence intensity than voltage indicator dyes and their fluorescence changes can be detect easily. Additionally, calcium signals play key roles in the brain function, such as the long-term potentiation (LTP) in the hippocampus, and calcium imaging can be a powerful tool to elucidate the brain function. In this study, we constructed a measurement apparatus combining the MEA system and laser confocal calcium imaging and simultaneously measured electric signals and calcium signals in acute mouse hippocampal slices. The obtained results showed the availability of the present method.