Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling.

Background: Galectin-1 (Gal-1) expression was positively associated with vasculogenic mimicry (VM) in primary gastric cancer (GC) tissue, and that both Gal-1 expression and VM in GC tissue are indicators of poor prognosis. However, whether Gal-1 promotes VM, and by what mechanismsremains unknown. Methods: To investigate the underlying mechanisms,wound healing assay, proliferation assay, invasion assay, and three-dimensional culture were used to evaluate the invasion, metastasis and promoted VM formation effects of the Gal-1. We monitored the expression level of sociated proteins in GC tissues, cell lines in vitro and nude mice tumorigenicity in vivo by immunohistochemistry and western blot. Results: Gal-1 overexpression significantly promoted the proliferation, invasion, migration, and VM formation of MGC-803 cells. Gal-1 was associated with E-cadherin and vimentin in vitro and in clinical samples. The epithelial-to-mesenchymal transition (EMT) induced in MGC-803 cells by TGF-ß1 was accompanied by Gal-1 activation and promotion of VM formation, while knockdown of Gal-1 reduced the response to TGF-ß1, suggesting that Gal-1 promotes VM formation by activating EMT signaling. Overexpression of Gal-1 accelerated subcutaneous xenograft growth and facilitated pulmonary metastasis in athymic mice, enhanced the expression of EMT markers, and promoted VM formation in vivo. Conclusion: Our results indicated that Gal-1 promotes VM in GC by upregulating EMT signaling; thus, Gal-1 and this pathway are potential novel targets to treat VM in GC.

miR-7 Increases Cisplatin Sensitivity of Gastric Cancer Cells Through Suppressing mTOR.

MicroRNAs have been reported to play an important role in diverse biological processes and cancer progression. MicroRNA-7 has been observed to be downregulated in human gastric cancer tissues, but the function of microRNA-7 in gastric cancer has not been well investigated. In this study, we demonstrate that the expression of microRNA-7 was significantly downregulated in 30 pairs of human gastric cancer tissues compared to adjacent normal tissues. Enforced expression of microRNA-7 inhibited cell proliferation and migration abilities of gastric cancer cells, BGC823 and SGC7901. Furthermore, microRNA-7 targeted mTOR in gastric cancer cells. In human clinical specimens, mTOR was higher expressed in gastric cancer tissues compared with adjacent normal tissues. More interestingly, microRNA-7 also sensitizes gastric cancer cells to cisplatin (CDDP) by targeting mTOR. Collectively, our results demonstrate that microRNA-7 is a tumor suppressor microRNA and indicate its potential application for the treatment of human gastric cancer in future.

[Application study on regional infusion chemotherapy by celiac trunk during operation in advanced gastric cancer patients].

OBJECTIVE: To explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients. METHODS: One hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups. RESULTS: The baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ2=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ2=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ2=5.382, P=0.020; 58.4% vs. 34.4%, χ2=6.636, P=0.010). CONCLUSION: Regional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

[Application of protective appendicostomy after sphicter-preserving surgery for patients with low rectal carcinoma who are at high-risk of anastomotic leakage].

OBJECTIVE: To explore the application of protective appendicostomy after sphicter-preserving surgery for patients with low rectal carcinoma who are at high-risk of anastomotic leakage. METHODS: Clinical data of 74 low rectal cancer cases with high-risk anastomotic leakage undergoing laparoscope-assisted total mesorectal excision(TME) sphincter-preserving operation in our department from September 2013 to September 2014 were analyzed retrospectively. Patients were randomly divided into two groups: 36 patients received appendicostomy and catheter was removed 4 to 6 weeks after operation when sinus tract formation in abdominal wall was identified; 38 patients received traditional ileostomy and stoma closure was performed 3 to 6 months after operation. RESULTS: The operation time was (149.2±9.4) min vs. (146.7±12.7) min, postoperative complication morbidity was 8.3%(3/36) vs. 13.2%(5/38), anastomotic leakage rate was 2.8%(1/38) vs. 2.6%(1/36), mean drainage volume of 1-week stoma was (203.2±76.9) ml vs. (195.8±76.5) ml, intestinal function recovery time was (25.5±5.6) h vs. (24.0±5.8) h in intubation colostomy group and ileostomy group respectively, and these differences were not significant (all P>0.05). While total hospital stay was shorter and cost was less in intubation colostomy group as compared to ileostomy group [(8.8±1.7) d vs. (18.0±1.7) d, (32 000±3000) yuan vs. (51 000±4000) yuan], and these differences were significant (all P<0.05). CONCLUSION: For low rectal cancer patients who are at high-risk of developing anastomotic leakage undergoing sphincter-preserving anterior resection, protective appendicostomy can decrease anastomotic leakage rate, avoid second stoma closure, shorten hospital stay and reduce hospital cost.

[Antisense RNA targeting survivin enhances the chemosensitivity of LOVO/Adr cells to taxotere].

OBJECTIVE: To investigate the ability of antisense RNA eukaryotic expression plasmid pcDNA3.0/survivin targeting survivin gene to inhibit survivin expression and enhance the sensitivity to taxotere in multidrug resistant colon carcinoma cell line LOVO/Adr. METHODS: The antisense RNA eukaryotic plasmid pcDNA3.0/survivin was transfected into LOVO/Adr cells by lipofectamine. The expression of survivin mRNA was measured using RT-PCR. After treated with taxotere, MTT assay and flow cytometry were used to evaluate the proliferation inhibition and apoptosis of LOVO/Adr cells. RESULTS: The expression of survivin mRNA in LOVO/Adr cells transfected with pcDNA3.0/survivin was down-regulated in a time- dependent manner. The inhibitory rate of taxotere (0.5 micromol/L) was (37.3 +/- 2.9)% in pcDNA3.0/survivin transfected cells, significantly higher than (21.9 +/- 2.3)% and (21.1 +/- 1.9)% in pcDNA3.0 transfected and untransfected control cells respectively (P< 0.01). The apoptosis rate of taxotere was (28.7 +/- 1.7)% in pcDNA3.0/survivin transfected cells,significantly higher than (13.4 +/- 1.6)% and (14.3 +/- 1.8)% in pcDNA3.0 transfected and untransfected cells respectively. CONCLUSION: The antisense RNA eukaryotic expression plasmid pcDNA3.0/survivin could down-regulate the expression of survivin gene and enhance the chemosensitivity of LOVO/Adr cells to taxotere, which may provide a novel therapy for colon carcinoma.