Xiaosheng He

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.

Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer

PurposeTo determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC).MethodsmTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin).ResultsmTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy.ConclusionsmTOR shared predictive significance in stage II CRC patients’ outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.

Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. METHODS MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. RESULTS MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. CONCLUSION MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.

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.

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.

Laparoscopic Colorectal Resection in Octogenarian Patients: Is it Safe? A Systematic Review and Meta-Analysis

Abstract The population older than 80 years has been increasing. A significant proportion of colorectal diseases that require colorectal resection occur in very elderly patients. However, the benefits of laparoscopy remain controversial in octogenarians. A systematic review and meta-analysis of observational study was performed to compare clinical outcomes between laparoscopic versus open colorectal resection in octogenarians. The PubMed, EMBASE, Ovid, Web of Science, and Cochrane databases from the years 1990 to 2015 were searched for studies that compare surgical outcomes between laparoscopic and open colorectal resection in octogenarians (≥80 years old). Seven eligible studies including 528 laparoscopic and 484 open colorectal resections were identified. Laparoscopic approach was associated with lower rate of mortality (odds ratio [OR] 0.48, P = 0.03), overall complications (OR 0.54, P < 0.001), and prolonged ileus (OR 0.56, P = 0.009), quicker bowel function return (standardized mean difference [SMD] −0.50, P < 0.001), and shorter length of hospital stay (SMD −0.47, P = 0.007). No differences were found in anastomotic leak (OR 1.16, P = 0.72), respiratory complication (OR 0.60, P = 0.07), and reoperation (OR 0.85, P = 0.69). Laparoscopic colorectal resection is as safe as open approach, and the short-term outcomes appear to be more favorable in octogenarians.

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.

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.