Exosomes Mediate the Production of Oxaliplatin Resistance and Affect Biological Behaviors of Colon Cancer Cell Lines.

BACKGROUND: Colon cancer has high mortality rate which making it one of the leading causes of cancer deaths. Oxaliplatin is a common chemotherapeutic drug, but it has disadvantages such as drug resistance. OBJECTIVE: The purpose of this study is to explore the mechanism of exosomes in the resistance of oxaliplatin and verify whether elemene and STAT3 inhibitors reverse the resistance to oxaliplatin. METHODS: Related cell line models were constructed and the proliferation, migration, invasion, apoptosis and resistance to oxaliplatin were evaluated for all three cells of HCT116/L, sensitive cell HCT116 and HCT116+HCT116/L-exosomes (HCT116-exo). It was to explore probable signaling pathways and mechanisms by Western blotting. RESULTS: HCT116-exo drug-resistant chimeric cells showed greater capacity for proliferation, migration and invasion than HCT116 sensitive cells. After the above cells were treated with oxaliplatin, the apoptosis rate of chimeric drug-resistant cells HCT116-exo and its IC50 increased compared with the sensitive cells HCT116. The proliferation, invasion and migration of cells treated with STAT3 inhibitor or ß-elemene combined with oxaliplatin reduced compared with those treated with oxaliplatin or ß-elemene alone. The STAT3 inhibitor or ß-elemene in combination with oxaliplatin increased the rate of apoptosis relative to oxaliplatin or ß-elemene alone. Drug-resistant cell exosomes could promote the EMT process, related to the participation of FGFR4, SHMT2 and STAT3 inhibitors. CONCLUSION: Drug-resistant cell exosomes could induce resistance, and improve the capacity of colon cancer towards proliferate, invade, migrate and promote the EMT process. The ß-elemene combined with oxaliplatin could reverse the above results which might be related to the STAT3 pathway and EMT pathway in colon cancer.

The expression and clinical significance of serine hydroxymethyltransferase2 in gastric cancer.

Background: Gastric cancer (GC) is one of the most common malignant tumours in the digestive system. Serine hydroxymethyltransferase 2 (SHMT2) is one of the key enzymes associated with serine metabolism. However, the prognostic role of SHMT2 in GC carcinogenesis has yet to be studied. Methods: The expression of SHMT2 in human tumors and normal tissues was detected by the Assistant for Clinical Bioinformatics and Immunohistochemistry (IHC). The relationship of the expression of SHMT2 with clinical characteristics and survival data was analysed by the chi-square test, survival analysis and online databases. Finally, the correlation between SHMT2 expression and associated signalling channels, and molecules was analysed by online databases. Results: SHMT2 was strongly expressed in numerous human cancers. The expression rate of SHMT2 was 56.44% in GC (P = 0.018). The survival analysis indicated that patients with high expression of SHMT2 had the worse overall survival (OS; log-rank P = 0.007). The expression of SHMT2 was correlated with tumour size (P = 0.034) and, TNM stage (P = 0.042). In particular, SHMT2, vessel invasion and M stage were independent factors for OS in GC (P = 0.044, P < 0.001, P < 0.001). The SHMT2 gene was substantially correlated with cell signalling pathways. Conclusions: SHMT2 is highly expressed in GC and is associated with a poor prognosis. The exploration of its mechanism may be related to tumour proliferation, DNA repair and replication. SHMT2 is an independent prognostic risk factor and a potential biomarker for the diagnosis and treatment of GC.

FGFR4 Gly388Arg Polymorphism Affects the Progression of Gastric Cancer by Activating STAT3 Pathway to Induce Epithelial to Mesenchymal Transition.

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays a critical role in cancer progression involving in tumor proliferation, invasion, and metastasis. This study clarified the role of FGFR4-Arg388 variant in gastric cancer (GC), and more importantly highlighted the possibility of this single nucleotide polymorphism (SNP) as potential therapeutic targets. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in advanced GC patients to perform statistical analysis. FGFR4-dependent signal pathways involving cell proliferation, invasion, migration, and resistance to oxaliplatin (OXA) in accordance with the SNP were also assessed in transfected GC cell lines. RESULTS: Among 102 GC patients, the FGFR4-Arg388 patients showed significantly higher tumor stage (p=0.047) and worse overall survival (p=0.033) than the Gly388 patients. Immunohistochemical results showed that FGFR4-Arg388 patients were more likely to have higher vimentin (p=0.025) and p-STAT3 (p=0.009) expression compared with FGFR4-Gly388 patients. In transfected GC cells, the overexpression of FGFR4-Arg388 variant increased proliferation and invasion of GC cells, increasing resistance of GC cells to OXA compared with cells overexpressing the Gly388 allele. CONCLUSION: The exploration mechanism may be through FGFR4-Arg388/STAT3/epithelial to mesenchymal transition axis regulating pivotal oncogenic properties of GC cells. The FGFR4-Arg388 variant may be a biomarker and a candidate target for adjuvant treatment of GC.

Role of fibroblast growth factor 4 in the growth and metastasis of colorectal cancer.

The role of fibroblast growth factor receptor 4 (FGFR4) in colorectal cancer (CRC) is poorly characterized. Therefore, the objective of the current study was to investigate the expression levels of FGFR4 in colorectal cancer and its prognostic value, and clarify the role of FGFR4 in the proliferation and metastasis of colorectal cancer cells. Immunohistochemistry was used to detect the association between FGFR4 expression and clinicopathological features in colorectal cancer tissues. The effect of FGFR4 silencing on tumor cell proliferation, cell cycle, apoptosis, migration and invasion was evaluated via lentiviral transfection of the colorectal cancer cell line SW620. Western blot analysis was used to detect the changes of epithelial­mesenchymal transition (EMT) markers, following FGFR4 silencing. FGFR4 is upregulated in CRC tissues compared with normal tissues. Patients with high FGFR4 expression exhibited a lower 5­year survival rate compared with patients with low FGFR4 expression (64 vs. 74%). FGFR4 silencing reduced proliferation, inhibited cell invasion, arrested cells in S phase and promoted apoptosis in colorectal cancer cells. FGFR4 silencing partially reversed EMT progression and FGFR4 this effect was enhanced in the presence of XAV939 (a ß­catenin inhibitor). The current data suggest that FGFR4 may be associated with prognosis in patients with colorectal cancer. In vitro functional tests revealed that FGFR4 may represent an effective therapeutic target for colorectal cancer. FGFR4 may also regulate EMT via the Wnt/ß­catenin pathway.

High expression of fibronectin 1 indicates poor prognosis in gastric cancer.

Fibronectin 1 (FN1) is involved in the occurrence and development of various tumors and is upregulated in multiple cancer types. FN1 has been demonstrated to promote cell proliferation and migration in gastric cancer cell lines. However, the relationship between the expression of FN1 and clinicopathological factors and prognosis is not clear in gastric cancer (GC). The aim of the present study was to investigate the association between FN1 expression and clinicopathology and prognosis of gastric cancer. In this study, 17 publicly available GC cohorts (n=2,376) with gene expression data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine databases were tested. In addition, FN1 protein expression was validated by immunohistochemistry in a separate cohort (n=190). The meta-analysis results demonstrated an increase in FN1 expression at the protein and mRNA level in GC tissues, and the FN1 gene was highly expressed at the mRNA level in the advanced T stage (T2 + T3 + T4) group compared with that in the early T stage (T1) group. In addition, the expression of epithelial FN1 at the protein level was positively correlated with tumor size. FN1 expression at the protein and mRNA level was a predictor of poor prognosis following radical resection of GC. In conclusion, the expression of FN1 in GC tissues is upregulated compared with adjacent normal tissues, and it is a potential biomarker of poor prognosis in patients with GC.

Bufothionine exerts anti-cancer activities in gastric cancer through Pim3.

AIM: Gastric cancer (GC) is the fourth most common cancer globally. Bufothionine is a major active constituent of Cinobufacini (Huachansu), which is extracted from the skin and parotid venom gland of the toad Bufo bufo gargarizans Cantor. It exhibits anti-cancer activities in vitro. However, whether bufothionine exerts anti-cancer activities against GC is unknown. This study was designed to evaluate the efficacy of bufothionine in vitro and in vivo. MATERIAL AND METHODS: MKN28 and AGS cells were chosen as cell models to study the anti-cancer effect of bufothionine. Cell viability was determined by CCK-8 assay, while the effect of bufothionine on cell membrane integrity was examined by LDH assay. Cell apoptosis was detected by Hoechst/PI staining and Annexin V-FITC/PI staining followed by flow cytometry analysis. The expression levels of proteins involved were examined using western blotting. I-Traq analysis was conducted to identify the differentially expressed genes in AGS cells following bufothionine treatment. The anti-growth effect of bufothionine was validated in vivo using a GC xenograft model. KEY FINDINGS: The results revealed that bufothionine prevented the growth, destroyed cell membrane and promoted apoptotic cell death of GC cells. iTRAQ analysis revealed thatPIM3 might be a molecular target responsible for the anti-cancer effects of bufothionine. It was also found that PIM3 knockdown significantly augmented the anti-growth and pro-apoptotic effects of bufothionine in GC cells. In contrast, ectopic PIM3 expression markedly dampened the anti-neoplastic activities of bufothionine. The expression of PIM3 was also suppressed by bufothionine treatment in xenograft tumor tissue. SIGNIFICANCE: Bufothionine exhibited anti-cancer activities in vitro and in vivo in GC via downregulating PIM3.

The opposite role of alternatively spliced isoforms of LINC00477 in gastric cancer.

Background: Aberrant transcript alternative splicing is an important regulatory process closely connected with oncogenesis. Purpose: The objective of this study was to determine the phenotype and function of a novel long noncoding RNA (lncRNA) LINC00477 in gastric cancer. Patients and methods: The gastric cancer samples of 140 from Oncomine database and 17 from our own hospital, as well as three gastric cancer cell lines MKN-45, AGS and KATO III were used in this study. The expression of the spliced isoforms of LINC00477 were tested. The tumor effects of LINC00477 on gastric cancer were investigated in vitro and in vivo. The mechanism of LINC00477 interacted with aconitase 1 (ACO1) was further examined by RIP and pull down assay. Results: The overall expression of LINC00477 was reduced in gastric cancers compared to normal gastric tissues. The isoform 1 of LINC00477 was down-regulated while the isoform 2 was up-regulated in gastric cancer cells. The opposite role of isoforms 1 and 2 in the proliferation and migration of cancer cells in vitro and in vivo was observed. Furthermore, isoform 1 of LINC00477 was determined to interact with ACO1 and suppress the conversion ability from citrate to isocitrate by ACO1. Conclusion: we presented the important roles of the spliced isoforms of long noncoding RNA, LINC00477 in gastric carcinogenesis.

Combination of FGFR4 inhibitor Blu9931 and 5-fluorouracil effects on the biological characteristics of colorectal cancer cells.

The aim of this study was to explore the effects of single agent treatments and combination of Blu9931 and 5-fluorouracil (5-FU) on the biological characteristics of colorectal cancer cells and its mechanism. Blu9931 is the first selective small molecule inhibitor of the fibroblast growth factor receptor 4 (FGFR4) and exquisitely selective for FGFR4 versus other FGFR family members and all other kinases. The colorectal cancer cells HCT116 and SW620 with high expression of FGFR4 were selected for a series of functional tests including cell viability, cell proliferation, apoptosis and cell cycle detection. Western blotting was used to detect the expression of related molecules including signal pathway (STAT3), apoptosis (cleaved caspase­3), cell cycle (cyclin D1 and P27kip1) and epithelial-mesenchymal transition (E-cadherin and vimentin) in HCT116 and SW620 cells used as single and combination treatments of 5­FU and Blu9931. The cell viability gradually decreased when the concentration of 5­FU and Blu9931 increased. Blu9931 can inhibit FGFR4 protein expression while 5­FU cannot, as assessed by western blot analysis. The single agent treatment and combinations of 5­FU and Blu9931 arrest cell cycle (P<0.05), increased p27kip1 expression and reduced cyclin D1 expression. The single agent treatment and combinations of 5­FU and Blu9931 inhibited EMT. Furthermore, the combination of 5­FU and Blu9931 has a synergistic effect in reducing colorectal cancer cell proliferation and preventing cell cycle. Taken together, this study provides the first evidence that Blu9931 functions as a FGFR4-selective inhibitor in colorectal cancer (CRC) cells, and Blu9931 may be a new targeted drug.

miR-218 Inhibits Proliferation, Migration, and EMT of Gastric Cancer Cells by Targeting WASF3.

MicroRNAs (miRNAs) play an important role in carcinogenesis. miR-218 is one of the most known miRNAs and has been demonstrated to inhibit progression in gastric cancer. However, the underlying molecular mechanism is not established. In this study, qRT-PCR and Western blot indicated that miR-218 was downregulated in gastric cancer cell lines SGC7901 and BGC823 compared to that in normal gastric epithelial cell line GES-1. MTT and wound scratch assays suggested that overexpression of miR-218 markedly suppressed cell proliferation, migration, and EMT of gastric cancer cells. Furthermore, we proved that WASF3 was a direct target of miR-218 by luciferase reporter assay, and restoration of WASF3 expression impairs miR-218-induced inhibition of proliferation, migration, and EMT in gastric cancer cells SGC7901. In summary, our results demonstrated that miR-218 functions as one of the tumor-suppressive miRNAs and inhibits gastric cancer tumorigenesis by targeting WASF3. miR-218 may serve as a potential therapeutic target for the treatment of gastric cancer.

Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway.

Diallyl disulfide (DADS) exerts anticarcinogenic activity in various types of cancer. However, the mechanism underlying its anticarcinogenic activity remains to be elucidated. The aim of the present study was to explore the mechanism of the anticarcinogenic activity of DADS in gastric cancer (GC). The expression levels of microRNA (miR)-34a in GC and normal tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of miR-34a was also measured using RT-qPCR in SGC-7901 cells following treatment with DADS. In addition, the effect of DADS on the invasion capability of SGC-7901 cells was observed in the presence of miR-34a or anti-miR-34a using a Matrigel invasion assay. Furthermore, in identical conditions, the apoptosis of SGC-7901 cells was observed using flow cytometry. Finally, the present study investigated the effects of DADS and miR-34a on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in vitro. The level of miR-34a in GC tissues was reduced compared with that in adjacent normal tissues (P<0.05). Treatment with DADS upregulated miR-34a expression in SGC-7901 cells (P<0.05). In the Matrigel invasion assay, DADS inhibited the invasive capability of SGC-7901 cells (P<0.05 vs. control), which was improved by overexpression of miR-34a (P<0.01 vs. control) but reduced by downregulation of miR-34a (P<0.05 vs. DADS treatment group). Furthermore, DADS induced apoptosis of SGC-7901 cells (P<0.05 vs. control); and DADS and miR-34a synergistically enhanced apoptosis of SGC-7901 cells (P<0.01 vs. control). In addition, DADS and miR-34a inhibited the expression levels of phosphorylated (p)-PI3K and p-Akt (P<0.05 vs. control). By contrast, downregulation of miR-34a alleviated the decrease in p-PI3K and p-Akt expression induced by DADS (P<0.05 vs. DADS treatment group). Cell viability was reduced with increasing concentrations of DADS, however, DADS did not affect cell viability following inhibition of the PI3K/Akt signaling pathway. In conclusion, DADS suppresses invasion and induces apoptosis of SGC-7901 cells by upregulation of miR-34a, via inhibition of the PI3K-Akt signaling pathway.

To drain or not to drain in colorectal anastomosis: a meta-analysis.

BACKGROUND: Currently, many surgeons place a prophylactic drain in the abdominal or pelvic cavity after colorectal anastomosis as a conventional treatment. However, some trials have demonstrated that this procedure may not be beneficial to the patients. OBJECTIVE: To determine whether prophylactic placement of a drain in colorectal anastomosis can reduce postoperative complications. METHODS: We systematically searched all the electronic databases for randomized controlled trials (RCTs) that compared routine use of drainage to non-drainage regimes after colorectal anastomosis, using the terms "colorectal" or "colon/colonic" or "rectum/rectal" and "anastomo*" and "drain or drainage." Reference lists of relevant articles, conference proceedings, and ongoing trial databases were also screened. Primary outcome measures were clinical and radiological anastomotic leakage. Secondary outcome measures included mortality, wound infection, re-operation, and respiratory complications. We assessed the eligible studies for risk of bias using the Cochrane Risk of Bias Tool. Two authors independently extracted data. RESULTS: Eleven RCTs were included (1803 patients in total, 939 patients in the drain group and 864 patients in the no drain group). Meta-analysis showed that there was no statistically significant differences between the drain group and the no drain group in (1) overall anastomotic leakage (relative risk (RR) = 1.14, 95 % confidence interval (CI) 0.80-1.62, P = 0.47), (2) clinical anastomotic leakage (RR = 1.39, 95 % CI 0.80-2.39, P = 0.24), (3) radiologic anastomotic leakage (RR = 0.92, 95 % CI 0.56-1.51, P = 0.74), (4) mortality (RR = 0.94, 95 % CI 0.57-1.55, P = 0.81), (5) wound infection (RR = 1.19, 95 % CI 0.84-1.69, P = 0.34), (6) re-operation (RR = 1.18, 95 % CI 0.75-1.85, P = 0.47), and (7) respiratory complications (RR = 0.82, 95 % CI 0.55-1.23, P = 0.34). CONCLUSIONS: Routine use of prophylactic drainage in colorectal anastomosis does not benefit in decreasing postoperative complications.

Downregulation of non­muscle myosin IIA expression inhibits migration and invasion of gastric cancer cells via the c­Jun N­terminal kinase signaling pathway.

Non­muscle myosin IIA (NMIIA) has been found to be overexpressed in gastric cancer tissues. However, the roles of NMIIA in the migration and invasion of gastric cancer cells have not yet been elucidated. The aim of the present study was to assess the effects of NMIIA knockdown on the migratory and invasive capacities of gastric cancer cells and to investigate the potential underlying mechanisms in vitro. First, the expression of NMIIA was assessed in gastric cancer tissues and non­cancerous tissues using western blot analysis. The expression levels of NMIIA protein in 51 out of 63 gastric cancer tissue specimens were higher compared to those in their matched non­tumoric gastric tissue specimens, and differences between the two groups were statistically significant (P<0.001). After downregulation of NMIIA using RNA interference, the migratory and invasive abilities of the SGC­7901 and MGC­803 gastric cancer cell lines were observed using a wound­healing assay and a Transwell assay, respectively. Knockdown of NMIIA significantly decreased the amount of wound closure as well as the number of cells which transgressed through the Matrigel (P<0.01). Finally, the levels of c­Jun N­terminal kinase (JNK), phosphorylated (p)­JNK, c­Jun and p­c­Jun were detected using western blot analysis in order to explore the association between NMIIA and the JNK signaling pathway. Knockdown of NMIIA decreased the levels of p­JNK and p­c­Jun in the two gastric cancer cell lines (P<0.05). In conclusion, the present study indicated that knockdown of NMIIA inhibited the migration and invasion of gastric cancer cells, which may be, at least in part, mediated via the JNK signaling pathway.

Silencing of FGFR4 could influence the biological features of gastric cancer cells and its therapeutic value in gastric cancer.

To clarify the role of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the therapeutic value of BGJ398 targeted to FGFR4. We constructed lentivirus vectors to stably knockdown FGFR4 expression in GC cells. Function assays in vitro and in vivo, treated with 5-fluorouracil (5-Fu) and BGJ398, were performed to study the change of biological behaviors of GC cells and related mechanism. The proliferation and invasive ability of HGC27 and MKN45 significantly decreased while the apoptosis rate of GC cells obviously increased in shRNA group (P < 0.05). The expressions of Bcl-xl, FLIP, PCNA, vimentin, p-erk, and p-STAT3 significantly reduced while the expressions of caspase-3 and E-cadherin markly enhanced in shRNA group. The proliferation abilities of GC cells were more significantly inhibited by the combination of BGJ398 and 5-Fu in shRNA group (P < 0.05). Compared to negative control (NC), the single and combination of 5-Fu and BGJ398 all significantly increased the apoptosis rate of GC cells, especially in the combination group (P < 0.01). The single and combination of 5-Fu and BGJ398 decreased the expressions of PCNA, Bcl-xl, and FLIP while increased the expression of caspase-3 in GC cells, especially in shRNA groups. Furthermore, knockdown of FGFR4 expression might prevent the growth of GC in vivo. Silencing of FGFR4 expression could weaken the invasive ability, increase the apoptosis rate, and decrease the proliferation ability of GC cells in vitro and in vivo. Furthermore, the combination of 5-Fu and BGJ398 had synergy in inhibiting the proliferation ability and increasing apoptosis rate of GC cells, directing a new target drug in GC.

The over-expression of FGFR4 could influence the features of gastric cancer cells and inhibit the efficacy of PD173074 and 5-fluorouracil towards gastric cancer.

The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biological features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P < 0.05). The proliferation ability of GC cells is reduced when treated by the single and combination of 5-Fu and PD while that of the FGFR4-LV5 group was less inhibited compared with control group (P < 0.05). The apoptosis rates are remarkably increased in GC cells treated with the single and combination of 5-Fu and PD (P < 0.05). However, the apoptosis rate obviously is reduced in GC cells treated with FGFR4-LV5 compared with control group (P < 0.05). The expression of PCNA and Bcl-XL is remarkably decreased, and the expression of Caspase-3 and cleaved Caspase-3 is obviously increased in GC cells treated with the single and combination of 5-Fu and PD. The tumor volumes of nude mice in FGFR4-LV5 group were much more increased (P < 0.05). The over-expression of FGFR4 enhanced the proliferation ability of GC in vitro and in vivo. The combination of 5-Fu and PD exerted synergetic effect in weakening the proliferation ability and promoting apoptosis in GC cells, while the over-expression of FGFR4 might inhibit the efficacy of two drugs.

Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901.

This study was designed to investigate the proliferation inhibition and apoptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05). For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05). 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01). The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05), which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901.

Intensive Versus Conventional Glycemic Control in Patients with Diabetes During Enteral Nutrition After Gastrectomy.

BACKGROUND: This study compared intensive and conventional glycemic management strategies in diabetic patients receiving enteral nutrition after gastrectomy. METHODS: Diabetic patients (n = 212) who underwent gastrectomy between September 2006 and March 2014 were randomized to intensive glycemic (IG) management with continuous insulin infusion (target glucose 4.4-6.1 mmol/l (80-110 mg/dl)) or conventional glycemic (CG) management with intermittent bolus insulin (target glucose <11.1 mmol/l (<200 mg/dl)). Outcomes included blood glucose concentrations, insulin administration, and postoperative morbidity and mortality. RESULTS: Blood glucose levels were lower (5.4 ± 1.2 vs. 9.5 ± 1.8 mmol/l, P < 0.001) and mean insulin dose was higher (55 ± 15 vs.32 ± 16 units/day, P < 0.001) in the IG than in the CG group. Rates of severe hypoglycemia (7.5 vs. 0.9%, P = 0.035) and achievement of target blood glucose (86.3 vs. 72.6%, P = 0.023) were higher, while severe hyperglycemia rate was lower (1.9 vs. 11.3%, P = 0.010), in the IG group. Surgical site infection rate was lower in the IG group (4.7 vs. 13.2%, P < 0.030). Rates of other infective complications, bleeding, delayed gastric emptying, obstruction, hepatic dysfunction, renal dysfunction, and circulatory insufficiency were similar in the two groups. CONCLUSIONS: Intensive glycemic control in diabetic patients receiving enteral nutrition after gastrectomy was associated with a lower surgical site infection rate but a higher hypoglycemia rate.

A single-arm clinical study of continuous usage of bevacizumab as second-line chemotherapy for Chinese patients with metastatic colorectal cancer.

Recent studies demonstrated that second-line chemotherapy of continuous usage of bevacizumab after initial disease progression improved survivals in Caucasian patients with metastatic colorectal cancer (mCRC). We intended to examine this strategy in Chinese patients specifically. Eligible Chinese mCRC patients had disease progression up to 3 months after receiving first-line bevacizumab-included chemotherapy. They were given IV bevacizumab infusion at 5 mg/kg on day 1 every 2 weeks. The primary endpoint is progression-free survival (PFS). One hundred and fourteen eligible patients received second-line chemotherapy plus bevacizumab. Among them, 56.1 % were male patients and median age was 63.4 years (29-81 years). Median follow-up time is 12 months. Median PFS was 7.3 months (95 % CI 3.9-8.9 months), and median OS was 14.7 months (95 % CI 10.7-18.5 months). No patients had complete responses, but 17 patients had partial response and 75 had stable disease. The safety profiles showed that severe adverse events (grades 3-4), such as nausea, proteinuria and hypertension, were often experienced by Chinese mCRC patients received continuous second-line chemotherapy of bevacizumab. Continuous usage of bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer in China showed equivalent improvement on patients' survival as Caucasian counterparts.

The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4.

MicroRNAs (miRNAs) are a series of 18-25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial-mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy.

Pre-operative TNM staging of primary colorectal cancer by (18)F-FDG PET-CT or PET: a meta-analysis including 2283 patients.

The aim of the present study was to perform a meta-analysis to assess the diagnostic value of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-CT/PET in the pre-operative evaluation of TNM staging in patients with primary colorectal cancer (CRC). The Medline, Embase and Web of Knowledge were searched for studies assessing the diagnostic value of (18)F-FDG PET-CT/PET in the pre-operative evaluation of TNM staging in CRC patients. We pooled the sensitivity, specificity, positive and negative Likelihood ratio (LR+ and LR-) and Diagnostic Odds Ratio (DOR) and constructed summary receiver operating characteristic curves. A total of 28 studies including 2283 CRC patients were analyzed. The pre-operative tumor detecting rate of PET-CT was 95.35%, which was superior to CT (P < 0.05). The pooled sensitivity and specificity of pre-operative T staging by PET-CT/PET was 0.73 (95% CI: 0.65-0.81) and 0.99 (95% CI: 0.98-0.99), which the AUC and Q* were 0.96 and 0.91, respectively. Concerning pre-operative N staging, the pooled sensitivity and specificity of PET-CT/PET were 0.62 and 0.70, which the AUC and Q* were 0.76 and 0.70, respectively. As for M staging, the pooled sensitivity and specificity of PET-CT/PET were 0.91 (95% CI: 0.80-0.96) and 0.95 (95% CI: 0.91-0.98), which the AUC and Q* were 0.96 and 0.91, respectively. (18)F-FDG PET-CT/PET had good performance in the pre-operative tumor detecting rate, T staging and M staging in patients with primary CRC, which might alter the therapeutic strategy. However, the diagnostic value of (18)F-FDG PET-CT/PET in pre-operative N staging in CRC patients was not ideal.

Pre-operative lymph node status of gastric cancer evaluated by multidetector computed tomography.

The purpose of the present study was to perform a meta-analysis to evaluate the diagnostic value of Multidetector computed tomography (MDCT) in the pre-operative lymph node (N) staging in gastric cancer (GC) patients. The Medline, Embase and Web of Knowledge were searched for studies assessing the diagnostic value of MDCT in the pre-operative evaluation of TNM staging in GC patients. We pooled the sensitivity, specificity, positive and negative Likelihood ratio (LR+ and LR-), Diagnostic Odds Ratio (DOR) and constructed summary receiver operating characteristic curves (ROC). A total of 30 studies including 6637 GC patients were analyzed. The pooled estimates of sensitivity, specificity, LR+, LR- and DOR of MDCT in the detection of pre-operative N staging in GC patients were 0.67 (95% CI: 0.66-0.69 ), 0.84 (95% CI: 0.83-0.85), 3.25 (95% CI: 2.69-3.93), 0.36 (95% CI: 0.28-0.46) and 10.31 (95% CI: 7.66-13.88), respectively. The results of a summary ROC showed that the AUC and Q* were 0.8338 and 0.7661, respectively. As a control, the AUC and Q* of endoscopic ultrasonography were 0.8063 and 0.7414, respectively. Currently, it is necessary to recommend the routine clinical application of MDCT in the preoperative evaluation of lymph node status in GC patients.