Search

Gastric cancer is one of the most common causes of cancer-related death worldwide. Helicobacter pylori infection plays an important role in the development and progression of gastric cancer. The expression of astrocyte-elevated gene-1 (AEG-1) is increased in gastric cancer tissues, thereby contributing to the inflammatory response. We investigated whether and how AEG-1 regulated proinflammatory signaling in gastric cancer cells. We used human gastric cancer cell lines and athymic nude mice to investigate the role of AEG-1 in the regulation of the TLR4/nuclear factor-κB (NF-κB) signaling pathway and cancer invasion and compared the expression of AEG-1 and related proteins in 93 patients with gastric cancer by immunohistochemistry. In human gastric cancer cells, both AEG-1 and TLR4 could be induced by lipopolysaccharide (LPS) stimulation. AEG-1 was upregulated via LPS-TLR4 signaling and in turn promoted nuclear translocation of the NF-κB p65 subunit. At the same time, AEG-1 overexpression decreased the levels of suppressor of cytokine signaling (SOCS) protein SOCS-1, a negative regulator of the TLR4 pathway. Furthermore, nude mice engrafted with AEG-1/TLR4-expressing cells demonstrated larger tumor volumes than control animals. In patients with gastric cancer, the expression of AEG-1 correlated with that of TLR4, SOCS-1, and NF-κB and was higher in tumors compared with noncancerous adjacent tissues. Overall survival in patients with gastric cancer with simultaneous expression of AEG-1 and TLR4 was poor. Our results demonstrate that AEG-1 can promote gastric cancer progression by a positive feedback TLR4/NF-κB signaling-related mechanism, thus providing new mechanistic explanation for the role of inflammation in cancer progression. Cancer Res; 74(19); 5541–52. ©2014 AACR.

Supplemental Table 2. The association between AEG-1 and TLR4 , SOCS1, p65 expression.

MicroRNA-188-5p (miR-188) enhances oncologic progression in various human malignancies. This study aimed to explore its role in colorectal cancer (CRC). Human CRC tissues paired with normal tissues, and several CRC cell lines were utilized. Real-time quantitative PCR was applied to measure the expression of miR-188. Overexpression and knockdown were used to access the function of miR-188 and to investigate whether FOXL1/Wnt signaling mediates such function. The proliferation, migration and invasion of cancer cells were evaluated by CCK8, wound-healing and transwell assays, respectively. Whether FOXL1 acted as a direct target of miR-188 was verified by dual-luciferase reporter assays. Levels of miR-188 were upregulated in CRC tissues than in paired-normal tissues, as well as in various CRC cell lines. High expression of miR-188 was strongly associated with advanced tumor stage, accompanied with significant tumor cell proliferation, invasion and migration. It was confirmed that FOXL1 played positive crosstalk between miR-188 regulation and downstream Wnt/β-catenin signaling activation. All findings indicate that miR-188 promotes CRC cell proliferation and invasion through targeting FOXL1/Wnt signaling and could be served as a potential therapeutic target for human CRC in the future.

Introduction The hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely applied in clinical practice for peritoneal carcinomatosis (PC). The temperature is one of the important elements affecting the efficacy of HIPEC, and it can become fluctuant by several factors. This study is aimed to explore the role of a stable perfusion temperature in promoting bowel recovery of PC patients due to gastrointestinal malignancies. Methods Between January 2012 and July 2013, 59 PC patients undergoing cytoreductive surgery and three-cycle HIPEC were included. Patients having stable perfusion temperature for all cycles were assigned into the study group, with the rest having unstable temperature into the control group. Time of flatus and defecation passage and initiation time of enteral nutrition were compared between both groups to detect the significance in bowel function recovery, with visual analogue scale (VAS) pain intensity and overall survival (OS) compared meanwhile. Results In sum, 33 (55.9%) patients obtained stable temperature during HIPEC, and the rest of 26 (44.1%) developed fluctuant perfusion temperature. Average time of flatus (2.3 ± 1.2 vs 3.9 ± 2.2 days, P =.002), defecation passage (5.2 ± 2.1 vs 7.1 ± 2.9 days, P =.004) and enteral nutrition initiation (4.3 ± 1.5 vs 6.7 ± 2.3 days, P

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

Oxaliplatin chemoresistance is a major challenge in the clinical treatment of colorectal cancer (CRC), which is one of the most common malignancies worldwide. In this study, we identified the tryptophan-aspartate repeat domain 43 (WDR43) as a potentially critical oncogenic factor in CRC pathogenesis through bioinformatics analysis. It was found that WDR43 is highly expressed in CRC tissues, and WDR43 overexpression is associated with poor prognosis of CRC patients. WDR43 knockdown significantly inhibits cell growth by arresting cell cycle and enhancing the effect of oxaliplatin chemotherapy both in vitro and in vivo. Mechanistically, upon oxaliplatin stimulation, c-MYC promotes the transcriptional regulation and expression of WDR43. WDR43 enhances the ubiquitination of p53 by MDM2 through binding to RPL11, thereby reducing the stability of the p53 protein, which induces proliferation and chemoresistance of CRC cells. Thus, the overexpression of WDR43 promotes CRC progression, and could be a potential therapeutic target of chemoresistance in CRC.

Background Serum tumor markers are ubiquitously used in the clinic for cancer screening. However, the mechanisms accounting for the elevated levels of the serum tumor markers remain to be explored. Methods We performed a pan-cancer analysis of serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA). The relation between concentration of serum tumor markers and the expression of their coding genes was assessed. Then the expression of AFP and its genomic background in hepatocellular carcinoma (liver cancer) was studied. Results High expression of AFP mRNA was found mainly in liver cancer. In gastric cancer, breast cancer and lung cancer, high AFP mRNA expression was also discovered occasionally. In liver cancer patients, serum AFP levels correlated significantly with AFP mRNA expression in cancer tissues (r = 0.72, p = 1.6e-45). Whole transcriptome analysis revealed that serum AFP levels clearly separated liver cancer into two classes with distinct expression profiles according to PCA analysis. Gene co-expression analysis revealed that AFP expression was connected to a module enriched with genes accounting for cell cycle and cell proliferation regulation. In addition, high AFP expression was associated with the molecular classification of liver cancer, including iCluster (Chi-square: 16.86, P = 0.0002). Methylation analysis revealed de-methylation of AFP promoter occurred in some liver cancer tissues, which was significantly related to AFP mRNA expression. Survival analysis indicated high serum AFP levels was prognostic of poorer survival of the liver cancer patients (Log-rank test: p = 0.046). This was confirmed by an independent dataset in which liver cancer patients with high serum AFP also had poorer survival (Log-rank test: p = 0.024). Conclusion High expression of AFP defined a subtype of liver cancer with distinct gene expression profiles and clinical features. De-methylation of cytosine from CpG di-nucleotides in AFP promoter may be the cause of AFP re-expression in adult human liver cancer tissue.

Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear. Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation. Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection. Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5'UTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation. Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.

Background. In the face of poor prognosis and immunotherapy failure of gastric cancer (GC), this project tried to find new potential biomarkers for predicting prognosis and precision medication to ameliorate the situation. Methods. To form synthetic matrices, we retrieved stomach adenocarcinoma transcriptome data from Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Necroptosis-related prognostic lncRNA was identified by coexpression analysis and univariate Cox regression. Then we performed the least absolute shrinkage and selection operator (LASSO) to construct the necroptosis-related lncRNA model. Next, the Kaplan–Meier analysis, time-dependent receiver operating characteristics (ROC), univariate Cox (uni-Cox) regression, multivariate Cox (multi-Cox) regression, nomogram, and calibration curves were made to verify and evaluate the model. Gene set enrichment analyses (GSEA), principal component analysis (PCA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in risk groups were also analyzed. For further discussing immunotherapy between the cold and hot tumors, we divided the entire set into two clusters based on necroptosis-related lncRNAs. Results. We constructed a model with 16 necroptosis-related lncRNAs. In the model, we found the calibration plots showed a good concordance with the prognosis prediction. The area’s 1-, 2-, and 3-year OS under the ROC curve (AUC) were 0.726, 0.763, and 0.770, respectively. Risk groups could be a guide of systemic treatment because of significantly different IC50 between risk groups. Above all, clusters could help distinguish between the cold and hot tumors effectively and contribute to precise mediation. Cluster 2 was identified as the hot tumor and more susceptible to immunotherapeutic drugs. Conclusion. The results of this project supported that necroptosis-related lncRNAs could predict prognosis and help make a distinction between the cold and hot tumors for improving individual therapy in GC.

Complement activation is associated with regional inflammation during acute gastrointestinal injury (AGI). This study is designed to explore how intracellular C3 activation in Paneth cells (PCs) affects regeneration of intestinal epithelium during AGI. AGI was induced in wildtype C57BL/6 mice, with sham operation employed as control. Exogenous C3 (1 mg, I.P.) was applied at 6 h post-surgery. Intestinal crypts harvested from ileum were cultured with presence or absence of C3 (20 μg/ml), with small interfering RNA against BST1 and complement activation inhibitor selectively applied in vitro. The intestinal integrity, percentage of PCs and intestinal stem cells (ISCs) were evaluated. Importantly, cADPR, C3 fragments, and S6-related proteins were detected in PCs to inspect the mammalian target of rapamycin complex 1 (mTORC1) signaling. AGI caused breakdown of intestinal mucosa integrity and regional inflammation. Exogenous C3 by itself failed to promote the growth of intestinal epithelium, but distinctly enhanced the activity of PCs via intracellular activation, which subsequently supported the expansion of ISCs inside of intestinal crypts. Inhibition of C3 activation was associated with decreased expressions of S6, S6K1 and cADPR, with blocking BST1 found to depress cADPR only. Collectively, these data confirmed intracellular activation of C3 in PCs enhanced expansion of ISCs in response to acute injury. The mTORC1 signaling pathway in PCs contributed to this crosstalk during exogenous C3 treatment.

Background: Specific guidelines recommend at least 15 or 16 lymph nodes (LNs) be examined to adequately assess nodal category of gastric cancer (GC), but the requirement for minimum number of regional LNs retrieval is not mentioned. This study aims to investigate survival significance from various numbers of perigastric (N1) LNs retrieval and to determine an optimal number harvested in such region. Study design: From April 1994 to March 2012, 1003 resectable GC patients with at least 15 LNs examined were included. Patients with at least 15 N1 nodes retrieval were assigned into study group, with the rest into control group. The 5-year overall survival (OS) rate was compared between two groups, and an optimal number of examined N1 nodes was detected by a survival joinpoint analysis. Results: 635 (63.3%) patients in study group had median 22 (range, 15-75) N1 nodes and 3 (range, 0-74) positive N1 nodes retrieval, with median 10 (range, 0-14) N1 nodes and 1 (range, 0-29) metastatic N1 nodes examined in control group. The number of N1 nodes retrieval was associated with tumor location (P=0.007), tumor stage (P

Background Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients’ responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification. Methods A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared. Results In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P Conclusion The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.

Aim: To explore whether Paneth cells (PCs) and complement system collaborate in the repair of enteric epithelia during acute gastrointestinal injury (AGI). Methods: Wild-type C57BL/6 mice were employed to induce AGI by performing colon ascendens stent surgery, with sham-operated as control. Exogenous C3 treatment was applied at 6-h postsurgery. After 48 h, overall survival, intestinal damage severity, and C3 intracellular activation were assessed in both epithelial cells and PCs. Results: AGI caused a high mortality, while C3 therapy significantly attenuated epithelial damages and improved survival. Besides, exogenous C3 in vitro enhanced the proliferation and activity of PCs. Importantly, intracellular C3 activation was observed inside of PCs under C3 co-stimulation in vitro. Conclusion: C3 immunotherapy might play a valuable role in turnover of gut epithelia through intracellular activation in PCs.

Background/Aims: Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. Methods: RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. Results: LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. Conclusions: LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.

Background: Transrectal ultrasound (TRUS) is a cost-effective test for preoperative assessment of rectal cancer. However, whether the accuracy of TRUS staging is correlated with tumor location remains obscured. This study is designed to explore their relationship and confirm an optimal application of TRUS in rectal cancer restaging. Methods: From 2005 to 2011, rectal cancer patients with TRUS data were retrospectively reviewed. Patients were divided into five groups according to tumor-involved rectal segment (SEG) above the anal verge: SEG I 1-3cm, II 3-6cm, III 6-9cm, IV 9-12cm, and V 12-16cm. The accuracy and long-term outcomes of tumor staging were compared between ultrasonographic and pathological stages. Results: 219 patients were included, with 55 (25.1%) in SEG I, 123 (56.2%) in SEG II, 32 (14.6%) in SEG III, 4 (1.8%) in SEG IV and 5 (2.3%) in SEG V. The overall accuracy of TRUS staging was remarkably superior to clinical staging by CT (64.8% vs. 34.7%, P

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon neoplasm arising from the olfactory mucosa. The optimal treatment regimen for ENB remains unclear. This study aims to evaluate its clinical features, long-term outcomes and explore optimal treatment patterns. METHODS: Clinical data of consecutive 44 ENB patients were reviewed retrospectively. The correlation between clinical features and treatment approaches were analyzed, with several prognostic factors explored meanwhile. RESULTS: The age of onset of ENB showed a bimodal distribution, with peaks at 10~20 and 50~60 years. The median follow-up time was 84 months (range, 27~198 months).The 5-year overall and progression free survival rates were 42.7% and 39.1%, respectively, with 10-year rates of 28.9% and 21.7% respectively. Overall, 19 patients developed recurrent disease. Patients undergoing surgery combined with adjuvant radiotherapy had significantly higher 5-year overall survival (67.5% vs. 33.3%, P=0.043) and progress-free survival (60.0%vs. 18.7%, P=0.008) than those receiving other treatment approaches. No-Skin-involved ENB was associated with markedly better 5-year overall survival (45.5%vs.0 %, P=0.038) and progress-free survival (31.3% vs. 0 %, P=0.001) compared with skin-involved tumor. CONCLUSIONS: ENB is a rarely malignant tumor with high probability of locoregional recurrence and poor survival. Surgical resection followed by radiotherapy has been shown to achieve optimal local control and overall survival.

Additional file 2: Table S2. Surgical outcomes of patients with gastric cancer.

Background: Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients’ responses varied. We aimed to develop and validate a radiomics score (rad_score) to predict the treatment response of neoadjuvant chemotherapy, and to investigate its efficacy in survival stratification. Methods: A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n=74; validation cohort: n=32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomized Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. According to the score thresholds (updated with post-operative clinical variables), patients were stratified into two groups and their survivals were compared.Results: In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response of neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P=0.09). The rad_clinical_score could not further improve the performance of rad_score (0.70 [0.51, 0.88], P=0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P

Purpose: To evaluate and improve the 7th edition International Union against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods: A retrospective review of the data from 905 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma was performed. All the patients were examined by magnetic resonance imaging (MRI) and received radiotherapy. Results: Satisfied distributions among the stages were observed in the 7th edition staging systems. LRFS only differed in classifications betweenT1 and T3, T1 and T4 (P=0.022 and P=0.016, respectively). Significant differences were observed between patients without and with masticator space involvement for OS, DMFS and PFS (p

Objectives Endoscopic resection (ER) is becoming an increasingly used treatment option for early gastric cancer (EGC); however, data comparing the long-term outcomes of ER and surgery are limited. Accordingly, we here aimed to perform a meta-analysis to clarify the long-term outcomes and safety of ER and surgery for EGC. Methods Literature on the direct comparison of ER and surgery for EGC was retrieved from the Medline, PubMed and Scopus databases. We selected the eligible studies, extracted data, and assessed the quality scores according to the guidelines. The overall survival (OS), recurrence-free survival (RFS), and adverse event rates were investigated, and the pooled hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were estimated. Results Nine retrospective studies were identified, including 973 and 1190 participants undergoing ER and surgery, respectively. There were no significant differences regarding the OS (HR: 0.995, 95% CI: 0.836-1.185; P = 0.959) and adverse event rates (OR: 0.50, 95% CI: 0.20-1.28, P = 0.148) between ER and gastrectomy. However, patients undergoing ER had significantly shorter RFS (HR: 7.226, 95% CI: 1.718-30.400, P = 0.007) than those undergoing gastrectomy. Conclusions Despite the limitations of this review, including the retrospective nature of all included studies, our results suggest that ER might be a feasible and safe treatment strategy compared to that of gastrectomy for EGC; however, careful endoscopic surveillance is needed for ensuring favorable outcomes. These findings should be confirmed in further large-scale, prospective, randomized, controlled trials from different countries.

Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear. Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation. Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection. Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5ʹUTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation. Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.

To establish multiparametric radiomics of rectal tumor for the preoperative prediction of lymph node (LN) metastasis.This prospective study consisted of 115 consecutive patients with rectal carcinoma between April 2015 and April 2017. The multiparametric radiomics scores were extracted from the endorectal ultrasound (ERUS), computed tomography (CT) and shear-wave elastography (SWE) features of the rectal tumor, LN, and peripheral tissues. The three radiomics scores were generated. Further validation as an independent predictor was performed using multivariate logistic regression together with clinical data, and a nomogram was subsequently developed. The predictive performance of the multiparametric radiomics nomogram was compared with that of conventional radiomics.All three scores (ERUS, CT, and SWE) were significantly higher in patients with LN metastasis than in patients with negative LN metastasis (all P 0.05) in both training and validation set. Multivariate analysis indicated that CT and SWE scores were independent risk variables (odds ratio, OR = 6.764 and 5.482, respectively). In validation cohort, the multiparametric radiomics nomogram showed the highest predictive accuracy for LN metastasis, with a concordance index (C-index) of 0.857 compared with the conventional radiomics nomogram (C-index, 0.703, P = 0.100), resulting in a significantly improved net reclassification index (NRI) (P 0.05) and integrated discriminatory improvement (IDI) (P = 0.002). Decision curve analysis showed that the multiparametric radiomics nomogram had a higher overall net benefit.Multiparametric radiomics of rectal cancer, which captures blood supply and stiffness phenotypes, is a useful tool for predicting LN metastasis preoperatively and has marked discrimination accuracy compared to conventional radiomics.

Summary Background The prognostic value of Helicobacter pylori (H. pylori) infection in gastric cancer patients has been investigated over many years; however, the results remain inconclusive. Thus, we performed a comprehensive review of currently available evidence via a systemic meta-analysis to evaluate the effects of H. pylori infection on the prognosis of gastric cancer patients. Methods Studies that evaluated the prognostic value of H. pylori infection in gastric cancer were extracted in March 2016 by searching PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We obtained or calculated hazard ratios (HRs) and the associated 95% confidence intervals (CIs) from the identified studies, and conducted random-effects model analyses of overall survival and progression-free survival. Twenty-four studies with a cumulative sample size of 7191 patients were included in our analysis. Results Our meta-analysis revealed that H. pylori infection is an indicator of improved overall survival in gastric cancer patients (HR, 0.79; 95% CI, 0.64–0.99); however, this was only true for European patients. The benefits of H. pylori infection were not detected in Asian gastric cancer patients (HR, 1.01; 95% CI, 0.91–1.12) or those in the United States (HR, 0.88; 95% CI, 0.73–1.05). Subgroup analyses revealed that the prognostic significance of H. pylori infection differed with respect to the year of study publication, number of patients, H. pylori detection method, tumor stage, H. pylori-positive rate, and risk of bias. The prognostic value of H. pylori infection on progression-free survival was unclear (HR, 0.84; 95% CI, 0.70–1.01). Conclusions These data provide limited, moderate-quality evidence that H. pylori infection is an indicator of good prognosis in European gastric cancer patients. However, this is not necessarily true for other populations.

Cytoreductive surgery (CRS) plus Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for peritoneal carcinomatosis. The cisplatin (CP) applied in HIPEC carries a risk of kidney injury. This study aims to investigate CP-induced nephrotoxicity post HIPEC and to explore its risk factors.From January 2012 to July 2013, 99 patients undergoing CRS + HIPEC were retrospectively reviewed. Patients were divided into CP and Non-CP HIPEC groups. The RIFLE classification was used to assess the severity of acute kidney injury (AKI). Renal and hepatic function, concentrations of tumor markers, and postoperative outcomes were compared between groups.47 (47.5%) patients were in the CP HIPEC group, with 52 (52.5%) patients in the Non-CP HIPEC group. 11 (11.1%) patients developed AKI, with 10 of them from the CP HIPEC group. Two patients with CP-contained HIPEC developed acute renal failure. Plasma levels of both urea nitrogen and creatinine were significantly increased in the CP HIPEC group compared with the Non-CP HIPEC group (P 0.01). However, postoperative pain (scaled score, 4.2 vs. 3.8; P = 0.279), length of hospital stay (18.1 vs. 20.2 days; P = 0.285), hospital costs ($1 3182 vs. $12 640; P = 0.465) and incidence of postoperative complication (25.5% vs. 17.3%; P = 0.337) were similar in both groups, with comparable 3-year overall survival observed (38.6% vs. 31.8%, P = 0.319). A multivariate analysis indicated that use of CP was an independent risk factor for AKI (P = 0.017, 95% CI: 1.277-4.155).Application of CP during HIPEC is associated with an increased risk of nephrotoxicity, without promising long-term survival benefit.

The 8th edition of AJCC TNM staging manual for gastric cancer (GC) has been validated by several studies. A modified staging system based on it and total harvested number of lymph nodes (LNs; cutoff: 30) is suggested to improve predictive capacities for advanced GC. This study is designed to validate the modified method using a single-center database in Southern China.Clinical data from 684 GC patients with stage II and III according to the 7th edition between 2001 and 2012 were reviewed. A modified staging system was applied to restage the cohort. The three staging systems were compared in terms of prognostic performance on long-term survival.The median follow-up period of this cohort was 52 (range, 6-180) months, with a median 5-year overall survival rate of 52.4%. Stage migration was observed in 159 (23.2%) patients according to the 8th edition of TNM staging, and another migration was observed in 108 (15.8%) patients according to the modified TNM staging system. Compared with the modified staging system, both 7th and 8th edition of AJCC TNM staging systems did not prove survival concordance on stage IIIA (7th edition) and stage IIIC (8th edition) when30 LNs were examined. The survival performance between two AJCC staging systems had no significant improvement (c-index, 0.607 vs. 0.609), with the best prognostic stratification obtained using the modified staging method (c-index, 0.631).The modified staging system on basis of the 8th AJCC classification and the number of harvested LNs could provide an optimal predictive capacities for advanced gastric cancer.

The current study reports the case of a 60-year-old male that presented with a four-month history of recurrent chest pain. Chest X-ray examination revealed a left-sided pleural effusion. A closed thoracic drainage procedure was performed, but the chest pain relapsed shortly afterwards. The pleural fluid was exudative, with no tumor cells detected. A computed tomography scan subsequently revealed a large mass located in the splenic curve of the colon, with involvement of the greater curvature of the stomach. Endoscopic biopsies confirmed the diagnosis of adenocarcinoma. A gastrointestinal stromal tumor was excluded by endoscopic ultrasonography and biopsy. A subtotal colectomy with partial excision of the stomach, diaphragm and left liver lobe was successfully performed, followed by the administration of six cycles of adjuvant chemotherapy. At present, the patient is asymptomatic and there is no evidence of tumor recurrence following a 12-month follow-up. The present study summarizes the characteristics of refractory left pleural effusion by colorectal malignancies.

Mucinous gastric carcinoma (MGC) is a specific type of gastric carcinoma, but its clinicopathologic characteristics remains obscured. Our study aimed to explore clinical features and prognostic value of MGC. This retrospective study included a total of 996 patients with primary gastric carcinoma from June 1994 to December 2006. Patients with gastric carcinoma were divided into MGC, other poorly differentiated (PD), and well or moderately differentiated groups. In all, 68 (6.8%) of 996 patients had MGC, with 599 (60.2%) cases for PD. Our study found that MGC had older age, more distant and peritoneal metastasis, but less radical gastrectomy than PD. Furthermore, the overall survival rate of MGC declined compared with PD gastric cancer (22.3% vs. 28.8%, P=0.032). Younger age (≤60 ys), smaller size (≤5 cm), Bormann III type, and lymph node metastasis were linked to poorer prognosis of MGC. However, MGC itself was not an independent prognostic factor of gastric carcinoma. In conclusion, MGC was associated with poorer prognosis than other types of gastric carcinoma but was not an independent predictive factor for survival, which called for further lucubration of this distinctive type of gastric carcinoma.

Purpose To compare the value of endorectal ultrasonography (US) with shear-wave elastography (SWE) in staging rectal tumors before surgery. Materials and Methods This prospective study was approved by the institutional review board and written informed consent was obtained. In a pilot cohort from April 2015 to January 2016, 70 patients with rectal adenocarcinomas and/or adenomas confirmed with histopathologic examination underwent both endorectal US and SWE. Tumor stiffness and three regions of reference backgrounds, as well as tumor stiffness ratios (SRs) versus these backgrounds, were analyzed. The optimal staging feature was selected by using receiver operating characteristic analysis, and the concordance rate with pathologic stage was analyzed and compared with endorectal US. The results were validated in an independent cohort of 30 patients from February 2016 to July 2016. Results In the pilot study, from rectal adenoma to stage T3 cancers, the tumor stiffness, stiffness of peritumoral fat, tumor SR versus distant perirectal fat, and tumor SR versus normal rectal wall were significantly increased (all P < .05, correlation coefficients between SWE features and pathologic T stages were 0.589-0.853). Receiver operating characteristic analysis of tumor staging demonstrated that tumor stiffness was the optimal feature with the highest area under the receiver operating characteristic curve (AUC = 0.991-1.000). The cutoff values of stage T1, T2, and T3 cancers were 26.9 kPa, 70.3 kPa, and 112.0 kPa, respectively. For SWE, the diagnostic concordance rate with pathologic stage (95.7%, weighted κ = 0.962) was higher than that of endorectal US (75.7%, weighted κ = 0.756). In the validation cohort, similar findings were revealed for diagnostic concordance rate (93.3% vs 76.7%; weighted κ = 0.927 vs 0.651) and diagnostic performance of tumor staging (AUC = 0.950-1.000 vs 0.700-0.833). Conclusion By using the feature of tumor stiffness at SWE, the accuracy of preoperative staging for rectal tumors was improved compared with endorectal US in the pilot study, but was not significantly different in the validation cohort, potentially due to small sample size. © RSNA, 2017 Online supplemental material is available for this article.

Purpose The value of adjuvant radiotherapy for patients with positive lymph nodes after curative resection of oesophageal squamous cell carcinoma is controversial. This study aims to investigate its long-term benefits in a specific cohort. Patients and Methods The charts between 1990 and 2003 from patients with positive lymph nodes were retrospectively reviewed. Those subjects were divided into adjuvant radiotherapy and surgery alone groups, with two subgroups defined by radiation dose (cutoff value: 50 Gy). Overall survival, disease-free survival and locoregional recurrence-free survival were compared between two groups, with predictive factors of overall survival analysed meanwhile. Results In sum, 175 matched patients with 1:2 ratios for group balance were enrolled for final analysis. During the follow-up (median: 37.0 months), 143 (81.7%) deaths were recorded, with 70.6% of deaths from cancer progression. The median overall survival time (19.5, 4 to 172 months) was not significantly different between the two groups (18.9 vs. 20.0 months, P = 0.179). However, the disease-free survival time was significantly shorter in the adjuvant radiotherapy group than that in the control group (median, 11.5 vs. 14.9 months; P = 0.001), with the locoregional recurrence-free survival time impressively prolonged (median: 18.3 vs. 16.5 months; P = 0.022). Age (P = 0.030), number (P = 0.005) and ratio (P = 0.002) of positive lymph nodes were associated with overall survival, but radiation dose was not (P = 0.204). Conclusion Adjuvant radiotherapy with low- or high-dose did not improve survival compared with surgery alone. However, radiotherapy was effective to control locoregional recurrence, and could be applied as salvage therapy when recurrence event occurred.

Gastric cancer is one of the most common causes of cancer-related death worldwide. Helicobacter pylori infection plays an important role in the development and progression of gastric cancer. The expression of astrocyte-elevated gene-1 (AEG-1) is increased in gastric cancer tissues, thereby contributing to the inflammatory response. We investigated whether and how AEG-1 regulated proinflammatory signaling in gastric cancer cells. We used human gastric cancer cell lines and athymic nude mice to investigate the role of AEG-1 in the regulation of the TLR4/nuclear factor-κB (NF-κB) signaling pathway and cancer invasion and compared the expression of AEG-1 and related proteins in 93 patients with gastric cancer by immunohistochemistry. In human gastric cancer cells, both AEG-1 and TLR4 could be induced by lipopolysaccharide (LPS) stimulation. AEG-1 was upregulated via LPS-TLR4 signaling and in turn promoted nuclear translocation of the NF-κB p65 subunit. At the same time, AEG-1 overexpression decreased the levels of suppressor of cytokine signaling (SOCS) protein SOCS-1, a negative regulator of the TLR4 pathway. Furthermore, nude mice engrafted with AEG-1/TLR4-expressing cells demonstrated larger tumor volumes than control animals. In patients with gastric cancer, the expression of AEG-1 correlated with that of TLR4, SOCS-1, and NF-κB and was higher in tumors compared with noncancerous adjacent tissues. Overall survival in patients with gastric cancer with simultaneous expression of AEG-1 and TLR4 was poor. Our results demonstrate that AEG-1 can promote gastric cancer progression by a positive feedback TLR4/NF-κB signaling-related mechanism, thus providing new mechanistic explanation for the role of inflammation in cancer progression. Cancer Res; 74(19); 5541–52. ©2014 AACR.

We investigated the feasibility of using ultrasound colonography (USC) to visualize the healthy colon and rectum and detect colorectal polyps. Eight healthy volunteers underwent USC after standard bowel preparation. The feasibility and image quality of USC in different segments were evaluated. Then, USC was conducted on eight patients with known colonic neoplasms using colonoscopy as the reference standard. For volunteers, USC examinations were successfully performed on four (50.0%) ascending, three (37.5%) transverse and eight (100%) descending colons, as well as all sigmoid colons and rectums. One of four (25.0%) ascending, two of eight (25.0%) descending and all sigmoid colons and rectums were well visualized and free of artifacts. For patients, colonoscopy revealed that eight patients had 17 neoplasms in the distal sigmoid colon and rectum, which included 3 lesions ≤5 mm, 3 lesions 6–9 mm and 11 lesions ≥10 mm. USC visualized 12 of 17 (70.6%) neoplasms. Lesion detection by USC was 0% (0/3), 33.3% (1/3) and 100% (11/11) for neoplasms ≤5, 6–9 mm and ≥10 mm in size. USC can visualize the sigmoid colon and rectum well and detect distal sigmoid and rectal neoplasms ≥10 mm in diameter.

Objectives. The role of complement system in predicting prognosis of gastric cancer (GC) remains obscured. This study aims to explore the incidence of complement C3 depletion and associated outcomes in GC patients. Methods. between August 2013 and December 2013, 106 patients with gastric adenocarcinoma were prospectively analyzed. Plasma levels of complement C3 and C4 were detected at baseline, one day before surgery, and postoperative day 3, respectively. Patients with low C3 levels ( Results. The CD incidence was 28.3% before surgery but increased to 37.7% after surgery. Preoperative CD was related to prolonged hospital stay (22.7 versus 19.2 day, P=0.032) and increased postoperative complications (33.3% versus 14.5%, P=0.030) and hospital costs (P=0.013). Besides, postoperative C3 depletion was significantly associated with decreased 3-year OS (P=0.022) and DFS (P=0.003). Moreover, postoperative C3 depletion and advanced tumor stage were independent predictive factors of poor prognosis. Conclusions. Complement C3 depletion occurring in gastric cancer was associated with poor short-term and long-term outcomes.