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Colorectal cancer cannot be completely cured at present, and it is still an important clinical medical problem. TRAF6 is highly expressed in many malignant tumors. However, the role of TRAF6 in colorectal cancer is still controversial, mainly because the specific regulatory mechanism of colorectal cancer is still unclear, and the death mode of colorectal cancer cells has not been elucidated. The recent study found that TRAF6 inhibits necroptosis in colorectal cancer cells via the RIPK1/RIPK3/MLKL signaling pathway. The RIPK1 inhibitor Necrostain-1 inhibits colorectal cancer cell necroptosis via the RIPK1/RIPK3/MLKL signaling pathway. TRAF6 directly interacts with RIPK1 through the polyubiquitination of Lys48-linked RIPK1 and reduces the levels of RIPK1 protein in colorectal cancer cells, leading to necroptosis, thus promoting the proliferation of colorectal cancer cells. The recent study demonstrated that TRAF6 promotes colorectal cell progression by inhibiting the RIPK1/RIPK3/MLKL necroptosis signaling pathway, which may provide a new therapeutic target for colorectal cancer.

Salt‐inducible kinase 2 (SIK2) functions as a tumor suppressor in gastric cancer (GC). Activation of mTORC1 by SIK2 inhibits autophagic degradation of the PP2A and PHLPP2 protein phosphatases, thereby increasing dephosphorylation and inactivation of AKT/GSK3β/β‐catenin signaling. Our results highlight SIK2 as a potential therapeutic target in GC., Salt‐inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial–mesenchymal transition via inhibition of AKT/GSK3β/β‐catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β‐catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor.

Background and aim Some studies have confirmed that miRNA-140 exhibits a suppressive role in gastric cancer, Wilms' tumor. However, the function of miRNA-140 in colorectal cancer has not been completely elucidated. The present study aims to verify TRAF6 as the targeted gene by miRNA-140 which was investigated in colorectal cancer tissues and cells, and its effects on the biological characteristics of colorectal cancer cells were determined, in order to provide an experimental and theoretical basis for the application of TRAF6 in the treatment of colorectal cancer. Methods qPCR analyzed miRNA-140 expression levels in colorectal cancer tissues, normal colorectal cancer tissues and colorectal cells including SW480 and HCT116 cancer cells and FHC normal colorectal epithetical cells. A serial biological experiment analyzed miRNA-140 effects on cell proliferation, migration and invasion capacities in SW480 and HCT116 cells. miRNA targeting gene prediction and a dual luciferase assay were used to analyze miRNA-140-targeted TRAF6. qPCR and Western blot analyzed miRNA-140 effects on the mRNA and protein expression of TRAF6. Western blot analyzed miRNA-140 effects on NF-κB/c-jun signaling pathways. Animal studies were performed to investigate the effects of miRNA-140 on colorectal cancer implantation tumor growth. Immunohistochemistry analyzed TRAF6 expression in animal experimentation tumors. Results miRNA-140 expression is lower in colorectal cancer tissues and colorectal cancer cells. Over-expression of miRNA-140 inhibited the proliferation, migration and invasion capacities of colorectal cancer cells. miRNA-140 targeted the TRAF6 mRNA 3'UTR area and decreased TRAF6 protein expression. miRNA-140 suppressed p-NF-κB/p-c-jun proteins expression. miRNA-140 inhibited colorectal cancer implantation tumor growth in the mice model. Conclusion miRNA-140 targeting TRAF6 affects the progression and growth of colorectal cancer, the mechanism could be miRNA-140 decreasing the TRAF6 expression effects on the NF-κB/c-jun signaling pathways.

Di-n-hexyl phthalate (DNHP) is commonly used as a plasticizer. However, whether DNHP influences Leydig cell development during puberty remains unexplored. In this study, DNHP (0, 10, 100, and 1000 mg/kg) was administered via gavage to 35-day-old male Sprague-Dawley rats for 21 days. Serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, Leydig cell number, the expression of Leydig and Sertoli cell genes and proteins were investigated. DNHP significantly increased serum testosterone levels at 10 mg/kg but lowered its level at 1000 mg/kg. DNHP significantly increased luteinizing hormone levels at 1000 mg/kg without affecting follicle-stimulating hormone levels. DNHP increased Leydig cell number at all doses but down-regulated the expression of Lhcgr, Hsd3b1, Hsd17b3, and Hsd11b1 in Leydig cell per se at 1000 mg/kg. DNHP elevated phosphorylation of ERK1/2 and GSK-3β at 10 mg/kg but decreased SIRT1 and PGC-1α levels at 1000 mg/kg. In conclusion, DNHP exposure causes Leydig cell hyperplasia possibly via stimulating phosphorylation of ERK1/2 and GSK-3β signaling pathways.

N6,2'-O-dimethyladenosine (m6 A) RNA methylation, which is correlated with cancer initiation and progression, is dynamically regulated by m6 A RNA methylation regulators, including writers, erasers, and readers. Two subgroups of rectal cancer, including cluster1 and cluster2, were identified based on consensus clustering to m6 A RNA methylation regulators. A protein-protein interaction network was constructed and hub genes were identified. The results demonstrated that the expression of WTAP was significantly associated with YTHDC1 and YTHDF2. The principal component analysis was used to compare the transcriptional profile between cluster1 and cluster2 subgroups. By using two identified m6 A RNA methylation regulators, we constructed a risk signature to predict the survival outcomes of rectal cancer. The results revealed that YTHDC2 and YTHDF2 were protective genes with HR < 1. The coefficients obtained from the least absolute shrinkage and selection operator algorithm were used to calculate the risk score. Patients were then divided into low- and high-risk groups based on the median risk score. The survival analysis demonstrated that there were significant differences in overall survival between these two groups (p < .05). The results of the univariate analysis showed that the risk score, AJCC stage, M stage, and age were associated with overall survival. The results of the multivariate Cox regression analysis showed that the risk score and age were still significantly associated with the overall survival (p < .05). To conclude, m6 A RNA methylation regulators can be regarded as potentially useful biomarkers for predicting the prognosis and designing a treatment strategy in rectal cancer.

Background Many studies have been performed to evaluate the effect of subcutaneous suction drainage to prevent incisional surgical site infections (SSIs) after radical colorectal surgery. However, the result has been controversial. The main reason may be that subcutaneous suction drainage is more prone to develop blockages, and the drainage tubes themselves serve as a conduit for bacteria into the wound. Therefore, we modified this method and evaluated this new method (subcutaneous suction drainage and intermittent irrigation) in patients who underwent radical colorectal surgery. Methods A total of 119 patients who underwent open radical colorectal surgery were included in our study from April 2015 to November 2017. A total of 61 patients were included in the irrigation group (subcutaneous suction drainage or intermittent irrigation), and 58 patients were included in the control group (no subcutaneous suction drainage and intermittent irrigation). The key endpoints were the incidence rate of incisional SSIs, the inpatient stay, and hospitalization expenses. All of the patients in our study had the following characteristics: (I) their subcutaneous fat thickness was more than 1.5 cm by means of CT or MRI measure before operation; (II) the patients had at least one of the following cases before operation: diabetes mellitus, hypoalbuminemia (ALB ≤35 g/L), anemia (Hb ≤90 g/L) or tumorous obstruction. Results The incidence of incisional SSIs rate was 27/119 (22.7%) in the overall patients, 22/61 (36.1%) in the control group, and 5/58 (8.6%) in the group. The rate of SSIs in the irrigation group was significantly lower than the control group (P

Background/Aim: Pazopanib (PAZ) can inhibit tumor progression, but whether PAZ inhibits lymph node metastasis and lymphangiogenesis in colorectal cancer is still unknown. The aim of the present study was to determine the efficacy of PAZ on tumor growth, lymph node metastasis and lymphangiogenesis in an orthotopic nude mouse model in colorectal cancer. Materials and Methods: CT-26-green fluorescence protein (GFP)-expressing mouse colon cancer cells were injected into nude mice to establish a subcutaneous colorectal cancer model and were treated with saline and PAZ. Additionals subcutaneous tumors were harvested and cut into 5 mm(3 )fragments, then tumor fragments were implanted orthotopically in the cecum to establish an orthotopic colorectal-cancer nude mouse model. Orthotopic mice were randomized into two groups for the treatment with saline and PAZ, respectively. Tumor width, length and mouse body weight was measured twice a week. The Fluor Vivo imaging system was used to image the GFP. Hematoxylin & eosin staining and immunohistochemical staining was used for histological analysis. Results: PAZ inhibited the growth of subcutaneous colorectal cancer, as wells as orthotopic transplanted colorectal cancer tumors. PAZ suppressed lymph node metastasis and lymphangiogenesis in the orthotopic colon cancer model. No significant changes were observed in the body weight between the control and the mice treated with PAZ. Conclusion: PAZ can inhibit the growth of colorectal cancer and inhibit lymph node metastasis and lymphangiogenesis in orthotopic colon cancer nude mouse models.

Background/Aims: Gastric signet ring cell carcinoma (GSRC), a subtype of adenocarcinoma, has been considered a histological type with poor survival. We aimed to compare the survival outcomes between patients with GSRC and patients with gastric non-signet ring cell adenocarcinoma (NGSRC) and constructed a nomogram to predict gastric adenocarcinoma-specific survival (GCSS). Patients and Methods: We identified 10,031 patients with gastric adenocarcinoma (GA) from the surveillance, epidemiology, and end results (SEER) database and stratified them into two histological type groups: GSRC and NGSRC. We used propensity score matching and identified 4304 patients (training cohort) to assess the effect of the histological type on GCSS with Kaplan–Meier curves, and constructed a predictive nomogram. The accuracy of the nomogram was tested on the remaining 5727 patients (validation cohort) with concordance index (C-index) values, calibration curves, and receiver operating characteristic (ROC) curve analysis. Results: We found that the histological type SRC was not associated with significantly poor survival (5-year survival rate: 46.1% vs 46.7%, P = 0.822). GSRC patients had similar GCSS rates compared to those with NGSRC in each tumor, node, and metastasis (TNM) stage (allP > 0.05). The nomogram showed that histological type was a relatively weak predictor of survival. The C-index value of the nomogram for predicting survival was 0.720, similar to that in the validation cohort (0.724). Conclusions: Patients with GSRC had a similar prognosis to those with NGSRC. The proposed nomogram allowed a relatively accurate survival prediction for operable GA patients after gastrectomy.

Background: The objective of this study was to assess the clinical efficacy of radiotherapy combined with surgery for locally advanced gastric signet-ring-cell carcinoma (GSRCC). Methods: Clinical data of patients with locally advanced GSRCC diagnosed by postoperative pathology from 2000-2016 were collected from the US Surveillance, Epidemiology and End Results (SEER) database. All the enrolled patients were divided into three groups according to treatment type: surgery alone (S; N=727), surgery with preoperative radiotherapy (RT+S; N=138), surgery with postoperative radiotherapy (S+RT; N=548). Results: The median overall survival (OS) time in S, RT+S and S+RT group was 19, 26 and 33 months, respectively; the overall survival (OS) rate was 19.5%, 26.9% and 34.0%, respectively; the median cancer-specific survival (CSS) time was 29, 31 and 43 months, respectively; and the CSS rate was 32,4%, 35.3% and 43.6%, respectively. After performing propensity score matching (PSM), it was found that the OS rate was significantly lower in S group than in RT+S or S+RT group (all PConclusions: Compared to surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced GSRCC.

Parastomal hernia and fecal incontinence cause severe distress to the rectal cancer patients with stoma after abdominoperineal resection. We attempted a new colostomy technique through the gap between the abdominal oblique internal and external muscles to prevent parastomal hernia and improve quality of life. This cohort study retrospectively examined clinical data from a total of 114 consecutive rectal cancer patients who underwent laparoscopic abdominoperineal resection in our center from March 2016 to March 2018 after propensity score matching. Group A included 57 patients who underwent colostomy through the gap between the abdominal oblique internal and oblique external muscles, while group B included 57 patients who underwent extraperitoneal colostomy. Patients’ quality of life was evaluated using Fecal Incontinence Quality of Life (FIQL) Scale. Group A had a lower incidence of parastomal hernia (0% vs. 15.7%, p = 0.004) and higher quality of life, especially in lifestyle, coping/behavior and embarrassment domains (all p values

Background/aim The aim of the present study was to determine the efficacy of trabectedin combined with FOLFIRI (irinotecan, leucovorin and 5-fluorouracil) on a colorectal cancer (CRC) patient-derived orthotopic xenograft (iPDOX) mouse model. Materials and methods A CRC tumor from a patient previously established in nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Mice were randomized into four groups: Group 1, untreated control; group 2, FOLFIRI; group 3, trabectedin alone; group 4, trabectedin plus FOLFIRI. Tumor width, length, and mouse body weight was measured twice every week. Results All three treatment groups showed inhibited tumor growth compared to the untreated control group. Only the combination of FOLFIRI and trabectedin arrested tumor growth. No significant changes was observed in body weight in any group. Conclusion These findings suggest that the combination of trabectedin plus FOLFIRI has clinical potential for patients with CRC.

Uncontrolled recurrence and metastasis are important reasons for the high mortality rate of malignant tumors. Vimentin is positively correlated with the degree of malignancy of cancer cells. Vimentin is also highly expressed in colorectal cancer (CRC) cells and plays a critical role in the metastasis and prognosis of CRC. However, the molecular mechanism of vimentin in the progression of CRC is incompletely understood. Therefore, the most active regions (nucleotides: 785-1085 nt) of the vimentin promoter in CRC were identified using luciferase experiments. By transcription factor sequence search and mutation analysis, the activator protein 1 (AP-1) binding site in the region of 785-1085 nt was confirmed. The vimentin promoter activity was enhanced by overexpression of AP-1. The electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that the binding site was recognized by AP-1. By cell proliferation assay, colony-forming assay, scratch-wound assay, cell migration assay, and cell invasion assay, we demonstrated that the AP-1 overexpression increased CRC cell proliferation, migration, and invasion. However, when vimentin was knocked down by vimentin small hairpin RNA in the CRC cell of AP-1 overexpression, this trend disappeared. Animal experiments and immunohistochemistry showed that AP-1 promoted tumor growth by regulating the vimentin gene. In summary, AP-1 affected metastasis, invasion of CRC cells in vitro, and tumor growth in vivo by activating the vimentin promoter. This study might provide new insights into the molecular mechanisms of the development of CRC and provide potential therapeutic targets for CRC.

Importance The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains uncertain given the lack of high-level clinical evidence. Objective To compare the safety of LTG for clinical stage I gastric cancer with that of conventional open total gastrectomy (OTG). Design, Setting, and Participants The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group CLASS02 study was a prospective, multicenter, open-label, noninferiority, randomized clinical trial that compared the safety of LTG vs OTG with lymphadenectomy for patients with clinical stage I gastric cancer. From January 2017 to September 2018, a total of 227 patients were enrolled. Final follow-up was in October 2018. Interventions Eligible patients were randomized to LTG (n = 113) or OTG (n = 114) by an interactive web response system. Main Outcomes and Measures The primary outcome was the morbidity and mortality within 30 days following surgeries between LTG and OTG with a noninferiority margin of 10%. The secondary outcomes were recovery courses and postoperative hospital stays. Results A total of 214 patients were analyzed for morbidity and mortality (105 patients in the LTG group and 109 patients in the OTG group). The mean (SD) age was 59.8 (9.4) years in the LTG group and 59.4 (9.2) years in the OTG group, and most were male (LTG group, 75 of 105 [71.4%]; OTG group, 80 of 109 [73.4%]). The overall morbidity and mortality rates were not significantly different between the groups (rate difference, −1.1%; 95% CI, −11.8% to 9.6%). Intraoperative complications occurred in 3 patients (2.9%) in the LTG group and 4 patients (3.7%) in the OTG group (rate difference, −0.8%; 95% CI, −6.5% to 4.9%). In addition, there was no significant difference in the overall postoperative complication rate of 18.1% in the LTG group and 17.4% in the OTG group (rate difference, 0.7%; 95% CI, −9.6% to 11.0%). One patient in the LTG group died from intra-abdominal bleeding secondary to splenic artery hemorrhage. However, there was no significant difference in mortality between the LTG group and the OTG group (rate difference, 1.0%; 95% CI, −2.5% to 5.2%), and the distribution of complication severity was similar between the 2 groups. Conclusions and Relevance The results of the CLASS02 trial showed that the safety of LTG with lymphadenectomy by experienced surgeons for clinical stage I gastric cancer was comparable to that of OTG. Trial Registration ClinicalTrials.gov Identifier:NCT03007550

Background/aim Colorectal cancer (CRC) cells secrete inflammatory cytokines that affect CRC progression. The aim of the present study was to determine if micro-RNA-140(miR-140) regulates inflammatory cytokine secretion induced by lipopolysaccharide (LPS) in colorectal cancer cells by targeting tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Materials and methods Fifty fresh colon-cancer specimens and normal colorectal tissues were collected from patients with CRC and tested for the expression miR-140. Human CRC cell lines SW480 and HCT116 were treated with various concentrations and times with LPS. miR-140 and mRNA expression of potentially related genes were analyzed by qPCR. Protein expression was analyzed using western blot or ELISA. Overexpression plasmids with pcDNA3.1-TRAF6, pGL4.10-wtTRAF6 and pGL4.10-mutTRAF6 were constructed. miRNA target gene prediction and a dual luciferase assay were used to analyze miR-140-targeted TRAF6. Results miR-140 expression was up-regulated in CRC tissues. In CRC cells, LPS could increase miR-140 expression in a time- and concentration-dependent manner. LPS increased inflammatory cytokine mRNA expression levels in SW480 and HCT116 human colon-cancer cells. miRNA-140 suppressed TRAF6 expression via targeting the 3'UTR. TRAF6 affected miR-140-mediated inflammatory cytokine expression of SW480 and HCT116 cells under LPS treatment. Conclusion miR-140 regulates inflammatory cytokine secretion of LPS-induced colorectal cancer cells by targeting TRAF6.

AIM To perform a meta-analysis to investigate the correlation between body mass index (BMI) and the short-term outcomes of laparoscopic gastrectomy (LG) for gastric cancer (GC) in Asian patients. METHODS The PubMed, Cochrane, EMBASE, and Web of Science databases were searched for studies that focused on the impact of obesity on the short-term outcomes of LG for GC in Asian patients who were classified into a high BMI (BMI ≥ 25 kg/m2) or low BMI group (BMI < 25 kg/m2). The results are expressed using the pooled odds ratio (OR) for binary variables and standard mean difference (SMD) for continuous variables with 95% confidence interval (CI), and were calculated according to the fixed-effects model while heterogeneity was not apparent or a random-effects model while heterogeneity was apparent. RESULTS Nine studies, with a total sample size of 6077, were included in this meta-analysis. Compared with the low BMI group, the high BMI group had longer operative time (SMD = 0.26, 95%CI: 0.21 to 0.32, P < 0.001), greater blood loss (SMD = 0.19, 95%CI: 0.12 to 0.25, P < 0.001), and fewer retrieved lymph nodes (SMD = -0.13, 95%CI: 0.18 to 0.07, P < 0.001). There was no significant difference between the high and low BMI groups in postoperative complications (OR = 1.12, 95%CI: 0.95 to 1.33, P = 0.169), the duration of postoperative hospital stay (SMD = 0.681, 95%CI: -0.05 to 0.07, P = 0.681), postoperative mortality (OR = 1.95, 95%CI: 0.78 to 4.89, P = 0.153), or time to resuming food intake (SMD = 0.00, 95%CI: -0.06 to 0.06, P = 0.973). CONCLUSION Our meta-analysis provides strong evidence that despite being associated with longer operative time, greater blood loss, and fewer retrieved lymph nodes, BMI has no significant impact on the short-term outcomes of LG for GC in Asian patients, including postoperative complications, the duration of postoperative hospital stay, postoperative mortality, and time to resuming food intake. BMI may be a poor risk factor for short-term outcomes of LG. Other indices should be taken into account.

Purpose Glutamine (Gln) is essential for the proliferation of most cancer cells, making it an appealing target for cancer therapy. However, the role of Gln in gastric cancer (GC) metabolism is unknown and Gln-targeted therapy against GC remains scarce. The aim of this study was to investigate the relevance of Gln in GC growth and targeting. Methods Expression of Gln transporter ASCT2 and glutamine synthetase (GS) in the parental and molecularly engineered GC cells or in human GC specimens was determined by RT-PCR and western blot analysis or immunohistochemistry. Cell proliferation and survival was assessed by CCK-8 assay and colony formation assay. Intracellular Gln content was measured by a HPLC system. Effects of ASCT2 and/or GS inhibitor on tumor growth were investigated in xenograft models. Results A significant heterogeneity of GC cells was observed with respect to their response to the treatment of ASCT2 inhibitor benzylserine (BenSer). Gln deprivation did not affect the BenSer-resistant cell growth due to endogenous GS expression, whose inhibition remarkably reduced cell proliferation. The differential in vitro sensitivity correlated with overall intracellular Gln content. Combined therapy with both ASCT2 and GS inhibitors produced a greater therapeutic efficacy than the treatment of either inhibitor alone. Furthermore, 77% human GC tissues were found to express moderate and high levels of ASCT2, 12% of which also co-expressed relatively high levels of GS. Conclusion Gln mediates GC growth and the therapeutic efficacy of Gln-targeted treatment relies on distinct ASCT2 and GS expression pattern in specific gastric cancer groups.

Purpose: The goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: A colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&E staining and immunohistochemical staining were used for histological analysis. Results: All three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM + PAZ + FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOX mouse model suggesting inhibition of lymphangiogenesis. Conclusion: Our results suggest that the combination of TEM + PAZ + FOLFOX has clinical potential for colorectal cancer patient.

Background/aim Inflammation may play a role in cancer initiation and progression. The molecular mechanisms by which inflammation causes colorectal cancer, remains unclear. The present study investigated a signaling pathway that affects inflammation in colorectal cancer. Materials and methods SW480 cells, HCT116 cells, and cells with knockdown of myeloid differentiation 88 (MyD88), and forced expression of MyD88 were treated with lipopolysaccharide (LPS; 1 μg/ml). Inflammation-related mRNA expression was analyzed by the quantitative reverse transcription polymerase chain reaction and inflammatory cytokines were detected by western blotting. The enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammation-related cytokines in colorectal cancer cells. Cancer cell properties were evaluated using the wound-healing assay, transwell migration assay, transwell invasion assay, colony-formation assay, and CCK-8 assay. Results LPS up-regulated mRNA and protein levels of inflammatory factors in colorectal cancer cells. Knockdown of MyD88 inhibited LPS-induced mRNA expression and inflammatory protein expression in colorectal cancer cells. Similarly, silencing of MyD88 expression suppressed LPS-induced changes in the biological behavior of colorectal cancer cells. Silencing of MyD88 expression down-regulated expression of proteins of the LPS/nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-ĸB)/mitogen-activated protein kinase (MAPK) signaling pathway. Restoration of the expression of MyD88 reversed the effects in LPS-treated HCT116 cells. Conclusion MyD88-regulated LPS/NF-ĸB/MAPK signaling pathway affects the inflammatory and biological behavior of LPS-induced colorectal cancer cells.

The role of myeloid differentiation factor 88 (MyD88) in malignant tumors is largely unknown. Therefore, in this study, we aimed to examine the function and underlying mechanism of MyD88 in colorectal carcinoma in vitro using SW480 and HCT116 cell lines and in vivo using a nude mouse model. SW480 and HCT116 cells were infected with a lentiviral‑based effective MyD88 siRNA virus. CCK‑8 and colony formation assay were used to assess cell proliferation. Transwell and scratch assays were used to test the migration of colorectal cancer cells, and the Transwell assay was further used to analyze the invasiveness of colorectal cancer cells. Western blotting was performed to analyze the underlying mechanism of MyD88 regulation. In vitro experiments demonstrated that silencing MyD88 in SW480 and HCT116 cells markedly suppressed growth and invasion. Furthermore, MyD88 knockdown affected the MyD88‑NF‑κB/AP‑1 signaling pathways in SW480 and HCT116 cells. In vivo, MyD88 knockdown inhibited tumor growth in a HCT116 cell subcutaneous nude model. We found that knockdown of the MyD88 gene can affect proliferation, invasion, and migration of colorectal cancer cells. We further verified that MyD88 knockdown can reduce the activity of NF‑κB and AP‑1 pathways. These results show that MyD88 gene plays an important role in promoting colorectal cancer, and thus can be exploited as a potential diagnostic and prognostic biomarker for colorectal cancer.

Background/aim In the present study, we aimed to determine the efficacy of trabectedin (TRAB) combined with oxaliplatinum (OXA)+5-fluorouracil (5-FU) on a colorectal cancer (CRC) patient-derived orthotopic xenograft (PDOX) mouse model. Materials and methods A patient CRC tumor previously established in nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice. Harvested tumor fragments were transplanted orthotopically in non-transgenic nude mice. Mice were randomized into three groups: Group 1 (G1), untreated-control; Group 2 (G2), OXA+5-FU; Group 3 (G3), TRAB+OXA+5-FU. Tumor width, length, and mouse body weight were measured twice a week. Results Both treatment groups inhibited tumor growth compared to the untreated control group. The combination of TRAB, OXA and 5-FU was significantly more efficacious than OXA+5-FU and arrested tumor growth. No significant changes were observed in body-weight in any of the three groups. Conclusion TRAB, OXA and 5-FU combination has clinical potential for this and other CRC patients.

As water environment is an important part of mangrove ecosystem, an efficient prediction of water quality is the foundation for judging the health of wetland ecosystem. And it also contributes a lot to the smooth development of environmental protection work. Based on the data of water quality and weather in Beilun Estuary, this paper chooses permanganate index and the content of ammonia nitrogen, which can reflect the water quality, as forecasting targets. We propose a multi-feature prediction method called SARIMA-LSTM on the basis of seasonal autoregressive integrated moving average model and long short-term memory. Through the combination of linear and non-linear model, this method can possess a better prediction effect considering the influence of weather on water quality. And the experimental results of four models show that this method has higher accuracy, stability and reliability.

N6,2'-O-dimethyladenosine (m

The gene encoding transmembrane protein 100 (TMEM100) was first discovered to be transcribed by the murine genome. It has been recently proven that TMEM100 contributes to hepatocellular carcinoma and non-small-cell lung carcinoma (NSCLC). This study investigates the impact of TMEM100 expression on gastric cancer (GC). TMEM100 expression was remarkably downregulated in GC samples compared to the surrounding non-malignant tissues (p in vivo examination of TMEM100 activity revealed that its upregulation prohibits the pulmonary metastasis of GC cells and increases the sensitivity of xenograft tumors to 5-FU treatment. In conclusion, TMEM100 serves as a tumor suppressor in GC and could be used as a promising target for the treatment of GC and as a predictor of GC clinical outcome.

Lipopolysaccharide (LPS) exists in the outer membrane of Gram-negative bacteria. Colorectal normal epithelium and colorectal cancer cells in situ are continuously exposed to LPS from intestinal bacteria, while little is known about the influence of LPS on colorectal cancer progression and metastasis. In this study, we investigated the potential role of LPS on colorectal cancer progression and metastasis as well as the underlying mechanisms. We measured higher LPS concentration in colorectal cancer tissues and even higher LPS concentration in colorectal cancer tissues with lymph node metastasis. LPS significantly enhanced cancer cell motility and promoted human dermal lymphatic endothelial cells' (HDLECs') capacity of tube-like formation in vitro, as well as accelerates lymphangiogenesis and lymph node metastasis in nude mice. Furthermore, we demonstrated LPS notably increased the expression of VEGF-C in a time-dependent and concentration-dependent manner. VEGF-C is a key regulator for lymphangiogenesis and lymph node metastasis. By constructing lentivirus-mediated shVEGF-C cells, VEGF-C down-regulation suppressed LPS' promotive effect on cancer cell motility and HDLEC tube-like formation capacity. In addition, we found TLR4- NF-κB/JNK signal pathways were important for LPS to increase VEGF-C expression. All these result suggested a critical role for LPS in migration, invasion, lymphangiogenesis and lymph node metastasis of colorectal cancer, providing evidence that LPS increased VEGF-C secretion to promote cell motility and lymphangiogenesis via TLR4- NF-κB/JNK signaling.

A discrepancy exists between the 7th edition guidelines of the American Joint Committee on Cancer (AJCC) and the 3rd edition Japanese treatment guidelines in terms of the classification of No. 12a lymph nodes as regional or distant lymph nodes in D2 lymphadenectomy for gastric cancer. The scope definition of No. 12a lymph nodes has yet to be fully elucidated. The present study aimed to assess the appropriateness of reclassifying No. 12a lymph node metastasis as distant metastasis according to the survival rate outcome, and to provide a clear and practical definition of the No. 12a group lymph nodes of gastric cancer. A retrospective analysis was performed on patients with gastric cancer who underwent standard or greater lymphadenectomy between January 2000 and December 2009 to find an association between No. 12a node metastasis and survival outcome. The present study first presented a clear and practical scope definition of the No. 12a group lymph nodes of gastric cancer, according to our clinical experiences and practices (Table I and Fig. 1). The survival outcome of patients with gastric cancer and No. 12a lymph node metastasis was poorer compared with that of patients with no No. 12a lymph node metastasis (P=0.0003). The results were similar in stage III patients with gastric cancer (P

The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of RIP-1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and preliminarily analyzed the underlying mechanisms. The results indicated that the expression of RIP-1 in the gastric cancer tissues was significantly higher than the expression in the normal gastric tissues. Additionally, RIP-1 immunoreactivity was positive at the site of invasion, but little or no immunoreactivity was detected at the gastric cancer parts of interstitial substance. Gastric cancer patients with high expression of RIP-1 had a poor survival rate. RIP-1 expression in the gastric cancer cell lines were general. HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in vitro. RIP-NF-κB/AP-1-VEGF-C signaling pathways have a crucial role in the regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor growth in the HGC cell subcutaneous xenograft model. In conclusion, our data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer.

Gastric cancer shows the highest invasive and metastasis features, especially lymph metastasis, which is closely associated with poor prognosis of gastric cancer. Although there is evidence that interleukin-6 (IL-6) can promote gastric cancer progression, the underlying specific mechanisms and the mechanisms of gastric cancer lymphangiogenesis are largely unknown. In the present study, we explore whether IL-6 could promote the proliferation and invasion activity of gastric cancer cells, and whether IL-6 mediating VEGF-C production affected the lymphangiogenesis in gastric cancer cells. Our results revealed that IL-6 and its receptors (IL-6 and gp130) are broadly expressed in various gastric cancer cell lines including SGC-7901, MGC, MKN-28 and AGS. Exogenous IL-6 increased the ability of gastric cancer cell proliferation and invasion, which could be weakened by AG490. in addition, exogenous IL-6 promoted the VEGF-C production of gastric cancer cells and the lymphangiogenesis of HDLECs. As we expected, AG490 was able to reduce these effects. Western blot analysis showed that IL-6 increased JKA, STAT3, p-STAT3 and VEGF-C protein levels in the gastric cancer cells. However, the JKA, STAT3, p-STAT3 and VEGF-C protein expression levels were inhibited by AG490. Our data suggested that IL-6 mediates the singnal pathway of JAK-STAT3-VEGF-C promoting the growth, invasion and lymphangiogenesis in gastric cancer. Thus, IL-6 and its related signal pathways may be a promising target for treatment of gastric cancer growth and lymphangiogenesis.

Graphene is a two-dimensional nanomaterial with high specific surface area, excellent physical and chemical properties with great potential in sensor applications. Uniform nanocrystalline Pt–Pd nanoparticle-decorated reduced graphene oxide (Pt–Pd/RGO) has been synthesized via a one-step chemical reduction. Dielectrophoresis applied to Pt–Pd/RGO fabricated the sensor. The hydrogen sensing properties of Pt–Pd/RGO were studied by recording the resistance changes following exposure to hydrogen at different concentrations, temperatures, flow rate and with different carrier gases. The Pt–Pd/RGO sensor has a stable and repeatable response due to carrier donation and crystal lattice expansion over hydrogenation and dehydrogenation. The maximum response tends to increase with the increase of hydrogen concentration or decrease of operating temperature, but remained almost unaffected by the flow rate. The nitrogen as carrier gas possesses higher response and longer recovery time than air because oxygen participates in the reaction. These studies have potential for the development of novel H2 sensors.