Ultrasonic surgical and electrosurgical system (USES) with conventional ultrasonic scalpel (CUS) in gastrectomy: a retrospective cohort study.

BACKGROUND: Harmonic ACE +7 Shears with Advanced Hemostasis is an upgraded ultrasonic device, an ultrasonic surgical and electrosurgical system (USES). The study aimed to evaluate the economic and clinical effectiveness of the USES compared with the conventional ultrasonic scalpel (CUS) in gastrectomy. METHODS: We conducted a single-center, retrospective cohort study using the electronic medical records in China. We collected intraoperative and postoperative data from gastric cancer patients who underwent the endoscope-assisted distal gastrectomy from 2018 to June 30, 2019. Procedure-related costs were estimated. We used linear regression by controlling a set of covariates to assess the effect of USES on outcomes. RESULT: Out of 87 eligible patients, the USES group (40 patients) and CUS group (47 patients) were comparable in terms of age, medical history and stages of cancer. Compared with the CUS, the USES saved 4.27 hemoclips per person (95% CI 0.57-7.97, p < 0.05) and 34.18 ml intraoperative blood per person (95% CI 8.74-59.62 ml, p < 0.05), respectively. Postoperative length of stay (LOS) was shorter in the USES group (7.90 ± 1.95 vs. 9.26 ± 2.81 days) but the difference was not statistically significant (p = 0.05). CONCLUSIONS: The USES group was associated with fewer hemoclips use and intraoperative blood loss in patients undergoing laparoscopic gastrectomy at comparable costs.

TNFAIP8 regulates gastric cancer growth via mTOR-Akt-ULK1 pathway and autophagy signals.

In this study, the purpose of this study was to investigate the role of TNFAIP8 in gastric cancer (GC). The expression of TNFAIP8 was detected by RT-PCR or western blot . TNFAIP8 was silenced or overexpressed in two cell lines. CCK-8 assay, transwell assay and flow cytometry were used to analyse cell viability, cell invasion capability and apoptosis, respectively. Nude mice were inoculated with TNFAIP8 silencing or overexpressing cells to form transplanted tumours. HE staining and immunohistochemistry assay were performed to assess histopathological changes in tumours. We found that the mRNA and protein expression of TNFAIP8 were significantly up-regulated in GC tumour tissues and cells compared with the normal counterparts. Overexpression of TNFAIP8 in GC cells increased cell viability, decreased apoptosis and promoted the cell migration ability. Meanwhile, increased expression of TNFAIP8 promoted autophagy, while inhibiting mTOR-Akt-ULK1 signal pathway. In conclusions, this study presents data that TNFAIP8 inhibits GC cells presumably by down-regulating mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been reported to critically regulate gastric cancer (GC). Recently, it was reported that LBX2 antisense RNA 1 (LBX2-AS1) is abnormally expressed in GC. However, the role of LBX2-AS1 in the malignancy of GC is worth further discussion. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the LBX2-AS1, miR-4766-5p and C-X-C motif chemokine (CXCL5) expression in GC tissues and cells. Dual-luciferase reporter assay was applied to examine the target relationship between LBX2-AS1 and miR-4766-5p or miR-4766-5p and CXCL5. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect cell proliferation, migration and invasion rates. The protein expression of CXCL5 was confirmed using western blot. The RNA pull down experiment was used to verify the specificity of LBX2-AS1 and miR-4766-5p on BGC-823 and SGC-7901 cells. RESULTS: LBX2-AS1 was up-regulated in GC tissues and cells, and its knockdown suppressed proliferation, migration and invasion of GC cells. While, overexpression of LBX2-AS1 increased proliferation and increased CXCL5 mRNA level. CXCL5 improved cell proliferation, migration and invasion of GC cells. LBX2-AS1 could bind to miR-4766-5p to regulate CXCL5 expression. Overexpression of CXCL5 overturned those effects of miR-4766-5p in GC cells. RNA Pull down shown that BGC-823 and SGC-7901 cells, miR-4766-5p specifically binds to LBX2-AS1. CONCLUSIONS: In short, this study demonstrated that LBX2-AS1 promoted proliferation, migration and invasion through up-regulation CXCL5 mediated by miR-4766-5p in GC. The LBX2-AS1/miR-4766-5p/CXCL5 regulatory axis provides a theoretical basis for the research on lncRNA-directed therapeutics in GC.

Dexamethasone on postoperative gastrointestinal motility: A placebo-controlled, double-blinded, randomized controlled trial.

BACKGROUND AND AIM: Following abdominal surgery, patients usually experience a transient episode of impaired gastrointestinal motility. This study aimed to determine whether a single preoperative dose of dexamethasone can promote the recovery of gastrointestinal function in patients following elective gastrointestinal surgery. METHODS: In this single-center, two-arm, parallel, randomized controlled trial, we studied 126 patients (aged 18-80 years) who underwent elective open or laparoscopic bowel surgery for malignant or benign pathology. At the induction of anesthesia, a treatment group (n = 64) received a single dose of 8-mg intravenous dexamethasone, and a control group (n = 62) received normal saline. RESULTS: Intravenous administration of 8-mg dexamethasone significantly decreased the time to return of flatus by an average of approximately 8 h (P < 0.05). Abdominal distension was significantly reduced on the third day after surgery in the dexamethasone group (P < 0.05), and the time to tolerance of a liquid diet was shorter in the dexamethasone group (P < 0.01). There were no significant differences in other secondary outcomes, including postoperative pain, complication rates, length of hospital stay, or time to first defecation, between the two groups. CONCLUSIONS: A single intravenous dose of 8-mg dexamethasone at induction of anesthesia significantly decreases the time to return of flatus, improves abdominal distension at 72 h, and promotes tolerance of a liquid diet. Although further studies are required to confirm our results, we recommend that dexamethasone should be used more widely in gastrointestinal surgery.

Expression of Interleukin-6 and Integrin ανß6 in Colon Cancer: Association with Clinical Outcomes and Prognostic Implications.

As important factors in the tumor microenvironment, interleukin-6 (IL-6) and integrin ανß6 play significant roles in accumulating mutations that drive the progression and metastatic capacities of cancer. The aim of this study was to investigate the expression of IL-6 and integrin ανß6, their clinical significance, as well as their correlation in the colon cancer tissues of 145 cases using immunohistochemistry. Our results showed that IL-6 and integrin ανß6 are indicators of cancer progression and poor prognosis in patients with colon cancer. Moreover, their relationship may provide clues for further studies on how the tumor microenvironment mediates the development of colon cancer, as well as strategies for the identification of novel therapeutic targets in the prevention and treatment of colon cancer.

Effect of amino acid supplementation on short-term complications after gastrointestinal tumor surgery: the AMIGITS randomized clinical trial.

BACKGROUND: There is a scarcity of large randomized clinical trials on the efficacy and safety of high-dose amino acid supplementation (AAS) in patients with gastrointestinal tumors undergoing surgical treatment. METHODS: This pragmatic, randomized, controlled, single-center, open-label, parallel-group AMIGITS trial was performed in a tertiary care teaching hospital. Patients with gastrointestinal tumors were randomly assigned to receive either AAS or standard care (SC). Amino acid targets were 2.0 g/kg per day in the AAS group and 1.2 g/kg per day in the SC group. The AAS group received additional amino acids intravenously, while the SC group received an iso-energetic 5% glucose intravenously. RESULTS: Overall, 407 patients (AAS group, 204; SC group, 203) were included in this study. During the intervention, the actual mean daily energy intake did not differ significantly between the AAS and SC groups (25.53 vs. 25.16 kcal/kg per day, P=0.493). However, the actual mean daily amino acid intake was significantly higher in the AAS group than that in the SC group (1.81 vs. 0.94 g/kg per day, P<0.001). The infection incidence during hospitalization and that within 30 days of surgery was significantly lower in the AAS group than that in the SC group (P=0.031 and P=0.024, respectively). The 30-day postoperative incidence of amino acid treatment-related adverse events and other complications did not significantly differ between the two groups. The postoperative hospital stay was significantly different between the two groups (P<0.001). CONCLUSIONS: AAS was associated with a reduced infection incidence within 30 days of major surgery in patients with gastrointestinal tumors and can be a promising strategy.

Intravenous dexamethasone administration during anesthesia induction can improve postoperative nutritional tolerance of patients following elective gastrointestinal surgery: A post-hoc analysis.

Aim: To investigate the effect of intravenous dexamethasone administration on postoperative enteral nutrition tolerance in patients following gastrointestinal surgery. Methods: Based on the previous results of a randomized controlled study to explore whether intravenous administration of dexamethasone recovered gastrointestinal function after gastrointestinal surgery, we used the existing research data from 1 to 5 days post operation in patients with enteral nutrition tolerance and nutrition-related analyses of the changes in serum indices, and further analyzed the factors affecting resistance to enteral nutrition. Result: The average daily enteral caloric intake was significantly higher in patients receiving intravenous administration of dexamethasone during anesthesia induction than in controls (8.80 ± 0.92 kcal/kg/d vs. 8.23 ± 1.13 kcal/kg/d, P = 0.002). Additionally, intravenous administration of 8 mg dexamethasone during anesthesia induction can reduce the changes in postoperative day (POD) 3, POD5, and preoperative values of serological indices, including ΔPA, ΔALB, and ΔRBP (P < 0.05). In the subgroup analysis, dexamethasone significantly increased the average daily enteral nutrition caloric intake in patients undergoing enterotomy (8.98 ± 0.87 vs. 8.37 ± 1.17 kcal/kg/d, P = 0.010) or in female patients (8.94 ± 0.98 vs. 8.10 ± 1.24 kcal/kg/d, P = 0.019). The changes of serological indexes (ΔPA, ΔALB, and ΔRBP) in the dexamethasone group were also significantly different on POD3 and POD5 (P < 0.05). In addition, multivariate analysis showed that dexamethasone use, surgical site, and age might influence enteral nutrition caloric tolerance. Conclusion: Postoperative enteral nutrition tolerance was significantly improved in patients receiving intravenous administration of dexamethasone during anesthesia induction, especially in patients following enterotomy surgery, with significant improvements in average daily enteral caloric intake, PA levels, ALB levels, and RBP levels. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR1900024000.

Somatostatin-analog effect on pancreatic fistula after radical gastrectomy: a pilot randomized controlled trial.

PURPOSE: Radical gastrectomy with D2 lymphadenectomy can trigger a high incidence of postoperative pancreatic fistula (POPF), which produces a poor clinical prognosis. We sought to evaluate the effect of somatostatin analogs (SSA) on POPF and clinical prognosis after radical gastrectomy. METHODS: A total of 123 patients with a high risk of POPF after radical gastrectomy (drainage fluid amylase concentration on a postoperative day [POD] 1 > 3 times the upper limit of normal serum amylase value) were randomly divided into the SSA group (n = 61) and the control group (n = 62). The former received continuous intravenous SSA (0.3 mg/8 h) for 3 days from POD1, and the latter normal saline. The primary outcome was the incidence of POPF. RESULTS: The incidence of POPFs in the SSA group was significantly lower than that in the control group (3.3% vs. 14.5%, P = 0.029). The incidence of short-term postoperative complications was significantly lower in the SSA group than in the control group (9.8% vs. 24.2%, P = 0.034). The median white blood cell counts, neutrophil counts, and the percentage of neutrophils on POD4 were significantly lower in the SSA group than in the control group (all P < 0.05). The SSA group had a shorter mean time to the first liquid diet (87.33 ± 17.92 h vs. 93.97 ± 17.29 h, P = 0.039). And the SSA group had less median daily drainage volume (96.33 mL vs. 119.67 mL, P = 0.025) and shorter drainage duration (7.0 days vs. 10.0 days, P = 0.013). CONCLUSION: Postoperative treatment with a somatostatin analog reduced the incidence of POPF and short-term complications after radical gastrectomy. (TRN: ChiCTR2200056201, Reg. Date: 2022/2/1).

Association between multiple coagulation-related factors and lymph node metastasis in patients with gastric cancer: A retrospective cohort study.

Background: Patients with tumors generally present with accompanying activation of the coagulation system, which may be related to tumor stage. To our knowledge, few studies have examined the activation of the coagulation system in reference to lymph node metastasis within gastric cancer. This study aimed to investigate the correlation between multiple coagulation-related factors and lymph node metastasis in patients with gastric cancer after excluding the influence of tumor T stage. Materials and methods: We retrospectively evaluated the relationship between lymph node metastasis and coagulation-related factors in 516 patients with T4a stage gastric cancer. We further analyzed influencing factors for lymph node metastasis and verified the predictive value of maximum amplitude (MA, a parameter of thromboelastography which is widely used to assess the strength of platelet-fibrinogen interaction in forming clots) in reference to lymph node metastasis. Results: Platelet counts (P=0.011), fibrinogen levels (P=0.002) and MA values (P=0.006) were statistically significantly higher in patients with T4a stage gastric cancer presenting with lymph node metastasis than in those without lymph node metastasis. Moreover, tumor N stage was statistically significantly and positively correlated with platelet count (P<0.001), fibrinogen level (P=0.003), MA value (P<0.001), and D-dimer level (P=0.010). The MA value was an independent factor for lymph node metastasis (ß=0.098, 95% CI: 1.020-1.193, P=0.014) and tumor N stage (ß=0.059, 95% CI: 0.015-0.104, P=0.009), and could be used to predict the presence of lymph node metastasis in patients with gastric cancer (sensitivity 0.477, specificity 0.783, P=0.006). The independent influencing factors for MA value mainly included platelet levels, fibrinogen levels, D-dimer and hemoglobin levels; we found no statistically significant correlations with tumor diameter, tumor area, and other evaluated factors. Conclusion: We conclude that MA value is an independent influencing factor for lymph node metastasis and tumor N stage in patients with T4a stage gastric cancer. The MA value has important value in predicting the presence or absence of lymph node metastasis in patients with gastric cancer. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2200064936.

Role of Gut Microbiome and Microbial Metabolites in Alleviating Insulin Resistance After Bariatric Surgery.

Insulin resistance (IR) is the most common pathophysiological change in patients with type 2 diabetes mellitus (T2DM). Several recent studies have suggested that the gut microbiome and microbial metabolites are involved in the pathogenesis of IR. Bariatric surgery, as an effective treatment for T2DM, can markedly alleviate IR through mechanisms that have not been elucidated. In this review, we summarize the current evidence on the changes in the gut microbiome and microbial metabolites (including lipopolysaccharide, short-chain fatty acids, branched-chain amino acids, aromatic amino acids, bile acids, methylamines, and indole derivatives) after bariatric surgery. Additionally, we discuss the mechanisms that correlate the changes in microbial metabolites with the postoperative alleviation of IR. Furthermore, we discuss the prospect of bariatric surgery as a treatment for T2DM.

One-stitch method vs. traditional method of protective loop ileostomy for rectal cancer: the impact of BMI obesity.

PURPOSE: Protective loop ileostomy is an effective diversion measure often used to reduce the risk of anastomotic leakage. The purpose of the present study was to evaluate the surgical outcomes of the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection for BMI obesity patients with rectal cancer compared with the traditional method (TM). METHODS: The patients diagnosed as rectal adenocarcinoma cases by preoperative pathology were included in this retrospective study. The subjects underwent protective loop ileostomy in laparoscopic low anterior resection from January 2016 to June 2019 in the Shandong Provincial Hospital affiliated to Shandong University. The data of loop ileostomy and stoma closure operation were retrieved from the medical cases system of the hospital. RESULTS: 242 patients were included in the present study. In the BMI obese cohort, the OM group showed a shorter operative time both in the loop ileostomy (232.5 vs. 250.0 min, p = 0.04) and stoma closure operation (102.5 vs. 115.0 min, p = 0.001) and a lower peristomal adhesion extent (p = 0.02) and a shorter median postoperative stay (6 vs. 7 days, p = 0.03) during stoma closure operation than that of the TM group. In the TM group, obese cases showed a higher operative time of stoma closure operation (115.0 vs. 95.0, p < 0.001), a higher parastomal hernia rate (p = 0.04), a higher peristomal adhesion extent (p = 0.005) and a longer postoperative stay of stoma closure operation (p = 0.02) compared with the non-obese cases, while in the OM group, no significant differences were observed between the obese and non-obese cases in terms of the above-mentioned factors. CONCLUSIONS: The OM exhibited more advantages than TM, notably in BMI obesity patients.

One-stitch versus traditional method of protective loop ileostomy in laparoscopic low anterior rectal resection: A retrospective comparative study.

BACKGROUND: Protective loop ileostomy is widely performed during rectal resection surgery. The study aimed to introduce the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection and compare this new method with the traditional method (TM). MATERIALS AND METHODS: A retrospective analysis was conducted on 109 patients with pathologically diagnosed adenocarcinoma of the rectum from January 2017 to December 2018 in the study centre, and the intraoperative details and postoperative outcomes of the two groups were measured. RESULTS: A total of 95 patients were included: 54 underwent protective loop ileostomy with the TM, while 41 underwent surgery utilizing the OM. Univariate analysis demonstrated that the operative times of resection and closure were significantly shorter (resection, 200.0 vs. 227.5 min, P = 0.028; closure, 70.0 vs. 92.5 min, P = 0.018) and the peristomal adhesions during closure were milder (P = 0.007) in the OM group than in the TM group. The postoperative complications were similar in both groups. In multivariate analysis, the OM (OR 0.352, 95% CI = 0.155-0.799, P = 0.013) was a significant factor influencing the operative time of resection. The peristomal adhesion extent was the only independent risk factor for the stoma closure time (mild, OR 0.036, 95% CI = 0.010-0.129, P < 0.001; moderate, OR 0.128, 95% CI = 0.033-0.494, P = 0.003). No significant predictive factor of peristomal adhesion extent was identified in multivariable analysis. CONCLUSION: The OM of protective loop ileostomy in laparoscopic low anterior resection was time-saving, simple and easy to popularize and did not lead to more postoperative complications than the TM.

Genetic Fine Mapping and Genomic Annotation Defines Causal Mechanisms at A Novel Colorectal Cancer Susceptibility Locus in Han Chinese.

Genome-wide association studies of colorectal cancer (CRC) have identified two risk SNPs. The characterization of these risk regions in diverse racial groups with different linkage disequilibrium structure would aid in localizing the causal variants. Herein, fine mapping of the established CRC loci was carried out in 1,508 cases and 1,482 controls obtained from the Han Chinese population. One distinct association signal was identified at these loci, where fine mapping implicated rs1010208 as a functional locus. Next, the candidate target genes of functional SNP rs1010208 were analyzed using data from TCGA databases by expression quantitative trait loci analysis method; the data from Peking University People's Hospital were utilized for verification. The dual-luciferase reporter system analysis confirmed that rs1010208 is a regulatory region that can be mutated to decrease the expression of HINT1, resulting in proliferation and invasiveness of CRC.

Clinicopathologic and prognostic characteristics of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2-negative) is a rare subtype with a poor prognosis. However, the clinicopathologic and prognostic characteristics of triple-negative breast cancer remain undetermined. MATERIALS AND METHODS: Immunohistochemical staining was adopted to examine the expressions of ER, PR, p53, C-erbB-2 (HER2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) protein in 116 samples of paraffin-embedded breast cancer tissues. RESULTS: 22 triple-negative breast cancers were found among 116 informative cases (19%). The triple-negative phenotype significantly correlates with tumor size, histological grade, lymph node status, p53, and EGFR (p < 0.05), and not significantly with age, menopausal status, and VEGF protein. After a median follow-up period of 96 months (range: 32-123 months), 12 triple-negative breast cancer patients and 20 patients with non-triple-negative phenotype had distant relapse (p < 0.05). Survival analysis showed that triple-negative phenotype was inversely associated with overall survival (p < 0.05) but not significantly with disease-free survival (p = 0.2877). Multivariate Cox model analysis showed that tumor size, lymph node status, histological grade, and triple-negative phenotype provided independent significant predictive power. CONCLUSION: Triple-negative breast cancer phenotype has specific clinical and biological characteristics. Patients with triple-negative breast cancer have a poorer prognosis. So far, there is no conclusive effective treatment, which necessitates further studies.

The Diagnostic Efficacy and Biological Effects of microRNA-29b for Colon Cancer.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study. METHODS: There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels. RESULTS: It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration. CONCLUSION: In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.

VEZT as a novel independent prognostic factor in gastric cancer.

BACKGROUND: Vezatin is an transmembrane protein associated with cell-cell adhesion junctions. In our previous studies, we found that the tumor suppressor function of VEZT was related to methylation of CpG island and were down-regulated in tumor tissue and cells compared to normal controls. However, the role of VEZT gene as a novel putative tumor suppressor in biological characteristics and the relationship with clinicopathological factors and prognosis of gastric cancer was not yet clear. Therefore, we sought to explore these questions and prepare for further research in this study. METHODS: We examined the vezatin expression levels in 119 gastric cancer tissues and adjacent normal tissues by immunohistochemistry. Furthermore, we evaluated the expression of VEZT and its relationship with clinicopathological factors, lymphatic metastasis and prognostic value for gastric cancer. RESULTS: The expression of VEZT was significantly down-regulated in gastric cancer tissues and cell lines and its expression levels was related to differentiation, TNM staging and lymphatic metastasis. Furthermore, analysis of 5-year survival of 119 gastric cancer patients showed that those with strong vezatin expression had significantly longer overall survival time than those with negative vezatin expression. CONCLUSIONS: These data provided an innovative insight that up-regulation of vezatin can be taken as a meaningful way for treating human gastric and other types of cancers. And VEZT expression levels can be considered as a biomarker for gastric cancer progression, lymphatic metastasis and as a novel independent prognostic factor.

Expression of tumor necrosis factor α-induced protein 8 is upregulated in human gastric cancer and regulates cell proliferation, invasion and migration.

Tumor necrosis factor α-induced protein 8 (TNFAIP8) has been associated with the tumorigenicity of various types of cancer, however, the expression of TNFAIP8 and its function in gastric cancer remain to be fully elucidated. Therefore, the present study examined the expression and biological function of TNFAIP8 in gastric cancer. The expression levels of TNFAIP8 were determined in 86 gastric cancer tissue samples and adjacent normal tissues using immunohistochemistry, and in four gastric cancer cell lines and GES-1 cells using reverse transcription-quantitative polymerase chain reaction. The expression of TNFAIP8 and its association with the tumor, node, metastasis (TNM) status and lymphatic metastasis of gastric cancer was evaluated. Furthermore, the functions of decreased expression levels of TNFAIP8 were analyzed in human gastric cancer cell lines. The expression of TNFAIP8 was significantly upregulated in the gastric cancer tissues and in the gastric cancer cell lines, and its expression levels were associated with the TNM staging and lymphatic metastasis. Furthermore, decreased expression of TNFAIP8 inhibited the growth, invasion and migration of gastric cancer cells. These data provided an innovative insight suggesting the downregulation of TNFAIP8 as a meaningful approach for treating human gastric cancer and other types of cancer. In addition, the expression levels of TNFAIP8 may be considered as a biomarker of gastric cancer progression.

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma.

AIM: To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance. METHODS: Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed. RESULTS: HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P<0.05), but not with age or tumor size (P>0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r=0.567; P<0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P<0.05). CONCLUSION: These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Hypoxia-inducible factor-1α and semaphorin4D genes involved with tumor-associated macrophage-induced metastatic behavior and clinical significance in colon cancer.

BACKGROUND: Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells. METHODS: Immunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., USA). Differences between two groups were analyzed with Student's t test. RESULTS: HIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P < 0.01, for both). Furthermore, HIF-1α and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages (P < 0.05), but not with age and tumor size (P > 0.05). Sema4D expression was correlated with that of HIF-1α (r = 0.567, P < 0.01). TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion. CONCLUSIONS: HIF-1α and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-1α and Sema4D.