A preclinical trial identified 4 of 20 (20%) gastric cancer (GC) patient-derived xenografts responded to cetuximab. Genome-wide profiling and additional investigations revealed that high EGFR mRNA expression and immunohistochemistry score (3+) are associated with tumor growth inhibition. Furthermore, EGFR amplification were observed in 2/4 (50%) responders with average copy number 5.8 and >15 respectively. Our data suggest that a GC subtype with EGFR amplification and overexpression benefit from cetuximab treatment.

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.

Objective: To compare the long-term results of mastoscopic axillary lymph node dissection (MALND) and conventional axillary lymph node dissection (CALND). Patients and Methods: From January 1, 2003, through December 31, 2005, a group of 1027 consecutive patients with operable breast cancer were randomly assigned to 1 of 2 study groups: MALND and CALND. The median follow-up was 63 months. The primary end points of the study were operative outcomes, complication reduction, function conservation, and cosmetics. The secondary end points were disease-free and overall survival. Results: The mean operative blood loss in the MALND group was less than in the CALND group (PϽ.001). The patients who underwent MALND had less axillary pain, numbness or paresthesias, and arm swelling (PϽ.001). The aesthetic appearance of the axilla in the MALND group was much better than that in the CALND group (Pϭ.001 at 6 months and Pϭ.002 at 24 months). A significant difference was found between the 2 groups in distant metastasis (Pϭ.04). The disease-free survival rate was 64.5% in the MALND group and 60.8% in the CALND group (Pϭ.88). The overall survival rate was 81.7% in the MALND group and 78.6% in the CALND group (Pϭ.95).

Background: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

BackgroundMassive abdominal arterial bleeding is an uncommon yet life-threatening complication of radical gastrectomy. The exact incidence and standardized management of this lethal morbidity are not known.MethodsBetween January 2003 and December 2013, data from 1875 patients undergoing radical gastrectomy with D2 or D2 plus lymphadenectomy were recorded in a prospectively designed database from a single institute. The clinical data and management of both early (within 24 h) and late (beyond 24 h) postoperative abdominal arterial hemorrhages were explored. For late bleeding patients, transcatheter arterial embolization (TAE) and re-laparotomy were compared to determine the better initial treatment option.ResultsThe overall prevalence of postoperative abdominal arterial bleeding was 1.92 % (n = 36), and related mortality was 33.3 % (n = 12). Early and late postoperative bleedings were found in 6 and 30 patients, respectively. The onset of massive arterial bleeding occurred on average postoperative day 19. The common hepatic artery and its branches were the most common bleeding source (13/36; 36.1 %). All the early bleeding patients were treated with immediate re-laparotomy. For late bleeding, patients from the TAE group had a significantly lower mortality rate than that of the patients from the surgery group (7.69 vs. 56.25 %, respectively, P = 0.008) as well as a shorter procedure time for bleeding control (2.3 ± 1.1 vs. 4.8 ± 1.7 h, respectively, P < 0.001). Four rescue reoperations were performed for TAE failures; the salvage rate was 50 % (2/4). Ten patients developed massive re-bleeding after initial successful hemostasis by either TAE (5/13) or open surgery (5/16). Three out of the 10 re-bleeding patients died of disseminated intravascular coagulation (DIC), while the other 7 recovered eventually by repeated TAE and/or surgery.ConclusionAbdominal arterial bleeding following radical gastrectomy tends to occur during the later phase after surgery, with further complications such as abdominal infection and fistula(s). For late bleeding, TAE can be considered as the first-line treatment when possible.Electronic supplementary materialThe online version of this article (doi:10.1007/s11605-015-3049-z) contains supplementary material, which is available to authorized users.

Aim: To explore molecular mechanisms underlying liver ischemia-reperfusion injury (IRI). Materials & methods: Four Gene Expression Omnibus datasets comprising liver transplantation data were collected for a comprehensive analysis. A proteomic analysis was performed and used for correlations analysis with transcriptomic. Results & conclusion: Ten differentially expressed genes were co-upregulated in four Gene Expression Omnibus datasets, including ATF3, CCL4, DNAJB1, DUSP5, JUND, KLF6, NFKBIA, PLAUR, PPP1R15A and TNFAIP3. The combined analysis demonstrated ten coregulated genes/proteins, including HBB, HBG2, CA1, SLC4A1, PLIN2, JUNB, HBA1, MMP9, SLC2A1 and PADI4. The coregulated differentially expressed genes and coregulated genes/proteins formed a tight interaction network and could serve as the core factors underlying IRI. Comprehensive and combined omics analyses revealed key factors underlying liver IRI, and thus having potential clinical significance.

Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesisrelated testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-induced FSIP1 knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial-mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1 into nu/nu mice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1 gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed on Western blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial-mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1 on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy.GO analysis | KEGG pathway analysis | gene expression signature | breast cancer therapeutics

Our findings suggest that miR-23 plays a crucial role in controlling VSMCs proliferation and apoptosis by targeting BCL2L11.