Lei Lian

High expression of CD73 as a poor prognostic biomarker in human colorectal cancer

To investigate the expression dynamics of CD73 and its prognostic significance in human colorectal cancer (CRC).

Postoperative Adjuvant Chemotherapy for Stage II Colorectal Cancer: A Systematic Review of 12 Randomized Controlled Trials

BackgroundThe impact of postoperative adjuvant chemotherapy on the oncological outcomes for stage II colorectal cancer remains controversial.MethodsThe literature was searched for studies published between 1985 and 2010 in which patients with stage II colorectal cancer were randomly assigned to receive either surgery combined with postoperative adjuvant chemotherapy or surgery alone. End points included 5-year overall survival, 5-year disease-free survival, recurrence, and mortality.ResultsA significant improvement in 5-year overall survival was associated with surgery combined with postoperative adjuvant chemotherapy for stage II colon cancer (hazard ratio, 0.81; 95% confidence interval (CI), 0.71–0.91) and for stage II rectal cancer (hazard ratio, 0.72; 95% CI, 0.61–0.86). The 5-year disease-free survival also favored the group of surgery combined with postoperative adjuvant chemotherapy for stage II colon cancer (hazard ratio, 0.86; 95% CI, 0.75–0.98) and for stage II rectal cancer (hazard ratio, 0.34; 95% CI, 0.22–0.51). For stage II colon cancer, a significant reduction in risk of recurrence was found in favor of postoperative adjuvant chemotherapy (risk ratio, 0.82; 95% CI, 0.71–0.95).ConclusionsPostoperative adjuvant chemotherapy for stage II colorectal cancer appears to be associated with improved 5-year overall survival and 5-year disease-free survival, and reduction in risk of recurrence.

Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta-analysis of 1,071 patients

BackgroundParastomal hernia is a common complication after colostomy construction. Whether an extraperitoneal route for colostomy creation can reduce the risk of parastomal hernia remains controversial.ObjectiveA meta-analysis was performed to evaluate the value of extraperitoneal route in the prevention of parastomal hernia and other postoperative complications related to colostomy.Data sourcesA literature search of Medline, Embase, Ovid, and Cochrane databases from the years 1966 to 2010 was performed.Study selectionStudies comparing extraperitoneal colostomy with intraperitoneal colostomy were identified.InterventionExtraperitoneal colostomy was performed to prevent colostomy-related complications.Main outcome measuresData on the following outcomes were sought: incidence of postoperative colostomy complications including parastomal hernia, prolapse, and bowel obstruction.ResultsSeven retrospective studies with a combined total of 1,071 patients (250 extraperitoneal colostomy and 821 intraperitoneal colostomy) were identified. There was a significantly lower rate of parastomal hernia (odds ratio, 0.41; 95% confidence interval, 0.23–0.73, p = 0.002) in the extraperitoneal colostomy group. However, the occurrences of bowel obstruction and prolapse were not significantly different between the two groups.LimitationsA limitation of the study lies on the meta-analysis of observational studies.ConclusionExtraperitoneal colostomy is associated with a lower rate of postoperative parastomal hernia as compared to intraperitoneal colostomy. Prospective randomized controlled trial is warranted to further determine the role of extraperitoneal route in the prevention of parastomal hernia.

Tumor-Infiltrating Mast Cells in Colorectal Cancer as a Poor Prognostic Factor

The purpose of this study is to investigate the clinical/prognostic significance of tumor-infiltrating mast cells (TIMs) in patients with colorectal cancer (CRC). TIM infiltration in 325 stage I to III CRC specimens was detected by immunohistochemistry. The optimal cutpoint of TIM density was assessed by the X-tile program. TIM infiltration in CRC was significantly higher than in normal colorectal tissues. According to the X-tile program, the cutpoint for high TIM infiltration in CRC was determined when TIM density was more than 8.0 per high-power field. Correlation analysis between TIM density and clinicopathological variables demonstrated that TIM infiltration was significantly associated with gender, nodal status, and American Joint Committee on Cancer stage. Multivariate Cox regression analysis showed that high TIM infiltration was a risk factor for both overall survival and disease-free survival. Taken together, high TIM infiltration can be an independent and useful biomarker for predicting the poor survival of patients with CRC.

Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn’s Disease

BackgroundMesenchymal stromal cells (MSCs) have been used in the treatment of Crohn’s disease (CD) because of the immunomodulatory ability.AimThe aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD.MethodsMurine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs.ResultsIntraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs.ConclusionsThe therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.

Preoperative Percutaneous Drainage of Spontaneous Intra-Abdominal Abscess in Patients With Crohn's Disease: A Meta-Analysis.

Goals: We aimed to compare clinical outcomes between percutaneous drainage (PD) with or without further elective surgery and initial surgery for patients with Crohn’s disease (CD)-related spontaneous intra-abdominal abscess. Background: Intra-abdominal abscess is common in patients with CD leading to significant morbidity. The role of PD before abdominal surgery in patients with CD remains controversial. Study: We performed a meta-analysis comparing PD and surgery as the initial approach to CD-related spontaneous intra-abdominal abscess. Overall complication and recurrent abscess were assessed. Subgroup analyses on initial PD were performed including preoperative PD and PD alone. Results: A total of 9 studies including 513 patients with CD-related spontaneous intra-abdominal abscesses were included. The overall complication rate was significantly higher in patients undergoing initial surgery compared with those undergoing initial PD [odds ratio (OR)=0.58; 95% confidence interval (CI), 0.35-0.96; P=0.03]. In a subgroup analysis, preoperative PD was associated with a significant reduction in overall complication (OR=0.44; 95% CI, 0.23-0.83; P=0.01) as compared with initial surgery. The risk for recurrent abscess was higher in patients who underwent PD alone than those who underwent initial surgery (OR=2.16; 95% CI, 1.03-4.54; P=0.04). No significance difference in postoperative recurrent abscess was found between preoperative PD group and initial surgery group. Conclusion: Although abdominal surgery appeared to be inevitable in the majority of the patients with CD who develop intra-abdominal abscess, preoperative PD may decrease overall complication after surgery.

Changes of T Cells and Cytokines TGF-β1 and IL-10 in Mice During Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity

BackgroundThe local and systemic regulation of the immune system may play important roles in the process of liver metastasis of colorectal carcinoma. The aim of this study was to establish a reproducible experimental liver metastasis model, to identify changes in T cells and cytokines TGF-β1 and IL-10, and to explore a possible mechanism of liver metastasis of colon carcinoma.MethodsWe used a colon carcinoma liver metastasis model, in which different numbers of CT-26 murine colon carcinoma cells (1 × 103, 5 × 103, 1 × 104, 5 × 104, and 1 × 105) were injected into the spleen. The liver and spleen tissues were examined for T cell markers using flow cytometry. Liver tissues were analyzed for IL-10 and transforming growth factor beta 1 (TGF-β1) expression using immunohistochemistry.ResultsSpleen injection of colon carcinoma cells is a reproducible animal model for liver metastases, which resulted in quantity-dependent metastatic growth. We provided a snapshot of the hepatic immune microenvironment in the mouse liver metastasis model. Injection of A large number of tumor cells (5 × 104 and 1 × 105) decreased anti-tumor cell counts, such as CD4+ and CD8+ T cells, and increased immune-suppressive cell counts (CD4+CD25+ Treg cells). In addition, the expression levels of immunosuppressive cytokines IL-10 and TGF-β1 were also increased with the number of tumor cells.ConclusionsChanges in the systemic and local immunological environment contribute to immunological escape mechanisms during liver metastasis of colon carcinoma, and therapies aiming at immune microenvironment may prove a useful strategy in the treatment of metastatic disease in the future.

Multi-microarray identifies lower AQP9 expression in adjuvant chemotherapy nonresponders with stage III colorectal cancer

Approximately 25% of stage III colorectal cancer patients do not benefit from standard adjuvant chemotherapies. To identify biomarkers for nonresponders, fresh-frozen tissues of 19 nonresponders and 16 responders were analyzed with gene expression and microRNA arrays. Fifty-nine genes and 17 miRNAs were differentially expressed by at least two folds. AQP9, SATB2, and WIF1 were simultaneously lower expressed in the nonresponders and modulated by the differentially expressed miRNAs. RT-PCR validated the differential expression of AQP9 (p=0.035). In conclusion, lower AQP9 gene expression is related with non-response to adjuvant chemotherapy, showing potential as predictive marker and therapeutic target.

MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73

BackgroundMicroRNAs are non-coding RNAs which regulate a variety of cellular functions in the development of tumors. Among the numerous microRNAs, microRNA-30a (miR-30a) is thought to play an important role in the processes of various human tumors. In this study, we aimed to explore the role of miR-30a in the process of colorectal cancer (CRC).MethodsThe quantitative real-time PCR and western blot analysis were used to detect the expressions of miR-30a and CD73 in CRC cell lines and clinical tissues. The luciferase reporter assay was conducted to validate the association between miR-30a and CD73. The CCK-8, terminal deoxynucleotidyl transferase dUTP -biotin nick end labeling (TUNEL) assays and cell cycle flow cytometry were carried out to verify the biological functions of miR-30a in vitro. The nude mouse tumorigenicity experiment was used to clarify the biological role of miR-30a in vivo.ResultsThe expression of miR-30a was significantly reduced in tumor cells and tissues of CRC. The proliferation ability of CRC cells was suppressed and the apoptosis of cells was promoted when miR-30a is over-regulated, however, the biological effects would be inverse since the miR-30a is down-regulated. CD73 is thought to be a target binding gene of miR-30a because miR-30a can bind directly to the 3′-UTR of CD73 mRNA, subsequently reducing its expression. The proliferation suppression of the CRC cells mediated by miR-30a could be rescued after up-regulating the expression of CD73.ConclusionsMiR-30a plays an important role on regulating the cell proliferation and apoptosis, thus affecting the growth of the tumor in CRC. And it may participate in the disease process of CRC by regulating the expression of CD73.

Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways

Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with chronic inflammatory processes. Carnosol has been demonstrated to possess anti-inflammatory properties. This study examined the suppressive effect of carnosol on the expression of cell adhesion molecules (CAMs) and chemokines in human umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism. The effect of carnosol on CAM and chemokine expression in HUVECs was identified by western blotting and ELISA, respectively. nuclear factor (NF)-κB activation of HUVECs was analyzed using the TransAM NF-κB Family kit. The effect of carnosol on the tumor necrosis factor (TNF)-α-induced activation of the NF-κB and mitogen-activated protein kinase (MAPK) pathways, and was subsequently analyzed using western blotting. Carnosol not only inhibited TNF-α-induced protein expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, carnosol inhibited the TNF-α-induced phosphorylation of p-65 and IκB-α, as well as the activation of NF-κB. The same result was observed in TNF-α-stimulated phosphorylation of ERK1/2 and p-38. It was demonstrated that carnosol inhibited TNF-α-induced CAM and chemokine expression in HUVECs. The underlying mechanism may be associated with the blocking of the NF-κB and MAPK pathways. These results indicate that carnosol may be a novel therapeutic agent for targeting endothelial cells in IBDs.