CD97 promotes gastric cancer cell proliferation and invasion through exosome-mediated MAPK signaling pathway

AIM: To investigate the mechanism underlying the promoting role of CD97 in gastric cancer cell proliferation and invasion. METHODS: Two types of exosomes released by gastric cancer cells with high(SGC/wt) or low(SGC/kd) CD97 expression were isolated by ultracentrifugation and identified by electron microscopy and western blot analysis. The influences of the two exosomes on gastric cancer cell proliferation and invasion were investigated by proliferation and Matrigel invasion assays. Exosomal mi RNAs were subsequently isolated from the two samples and their mi RNA profiles were compared via microarray assay analysis. Reverse transcriptionquantitative real-time polymerase chain reaction was used to validate the microarray assay. Target genes of the differently expressed micro RNAs were predicted based on five independent algorithms and were then subjected to gene oncology enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis. After identifying the pathway that was the most likely altered, tumor cells were treated with the two exosomes at different concentrations, and the pathway activation was identified through western blot analysis.RESULTS: Exosomes isolated from SGC/wt cells significantly promoted tumor cell proliferation in a dose-dependent manner in vitro. SGC/wt exosomesalso significantly elevated the invasiveness of both SGC/wt(129.67 ± 8.327 vs 76.00 ± 5.292, P < 0.001) and SGC/kd(114.52 ± 9.814 vs 45.73 ± 4.835, P < 0.001) cells as compared to the exosomes released by SGC/kd cells. Microarray assay of the two exosomes revealed that 62 mi RNAs were differently regulated with a signal intensity of > 500 and a false discovery rate < 0.05. The following KEGG analysis defined the MAPK signaling pathway as the most likely candidate pathway that regulated tumor cell proliferation and invasion. Through western blot analysis, significant up-regulations of phosphorylated MAPKs, including extracellular signal-regulated kinase, Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase, were detected in a dose-dependent manner in the SGC/wt exosomes treated groups, confirming activation of the MAPK signaling pathway stimulated by SGC/wt exosomes.CONCLUSION: CD97 promotes gastric cancer cell proliferation and invasion in vitro through exosomemediated MAPK signaling pathway, and exosomal mi RNAs are probably involved in activation of the CD97-associated pathway.

Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.

Anatomic isolated caudate lobectomy: Is it possible to establish a standard surgical flow?

AIM To establish the surgical flow for anatomic isolated caudate lobe resection. METHODS The study was approved by the ethics committee of the Second Affiliated Hospital Zhejiang University School of Medicine(SAHZU). From April 2004 to July 2014, 20 patients were enrolled who underwent anatomic isolated caudate lobectomy at SAHZU. Clinical and postoperative pathological data were analyzed. RESULTS Of the total 20 cases, 4 received isolated complete caudate lobectomy(20%) and 16 received isolated partial caudate lobectomy(80%). There were 4 caseswith the left approach(4/20, 20%), 6 cases with the right approach(6/20, 30%), 7 cases with the bilateral combined approach(7/20, 35%), 3 cases with the anterior approach(3/20, 15%), and the hanging maneuver was also combined in 2 cases. The median tumor size was 5.5 cm(2-12 cm). The median intraoperative blood loss was 600 m L(200-5700 m L). The median intra-operative blood transfusion volume was 250 m L(0-2400 m L). The median operation time was 255 min(110-510 min). The median post-operative hospital stay was 14 d(7-30 d). The 1-and 3-year survival rates for malignant tumor were 88.9% and 49.4%, respectively. CONCLUSION Caudate lobectomy was a challenging procedure. It was demonstrated that anatomic isolated caudate lobectomy can be done safely and effectively.

Phlegmonous gastritis after esophagectomy:A case report

Phlegmonous gastritis is an unusual infection of the gastric wall,which is extremely rare and associated with a poor prognosis.Here,we report the case of a 65-year-old male patient with a history of splenectomy,who had phlegmonous gastritis after esophagectomy.Computed tomography revealed a remarkably distended thoracic stomach,and the gastric wall was locally thickened.Gastric mucosa was red and white in color and significantly edematous on gastroscopy.He was successfully treated with a combination of antibiotics and povidone-iodide intraluminal lavage.In addition to this case,the clinical presentations,imaging examinations as well as treatments of phlegmonous gastritis are discussed.

Hem-o-lok clip migration to the common bile duct after laparoscopic common bile duct exploration:A case report

BACKGROUND Laparoscopic cholecystectomy(LC)and laparoscopic common bile duct exploration(LCBDE)has been widely used for management of gallbladder and common bile duct(CBD)stones.Post-operative clip migration is a rare complication of laparoscopic biliary surgery,which can serve as a nidus for stone formation and cause recurrent cholangitis.CASE SUMMARY A 59-year-old female was admitted to hospital because of fever and acute right upper abdominal pain.She has a history of LC and had a LCBDE surgery 2 mo ago.Physical examination revealed tenderness in the upper quadrant of right abdomen.Computed tomography scan demonstrated a high-density shadow at the distal CBD,which was considered as migrated clips.The speculation was confirmed by endoscopic retrograde cholangiopancreatography examination,and two displaced Hem-o-lok clips were removed with a stone basket.No fever or abdominal pain presented after the operation.In addition to the case report,literature regarding surgical clip migration after laparoscopic biliary surgery was reviewed and discussed.CONCLUSION Incidence of postoperative clip migration may be reduced by using clips properly and correctly;however,new methods should be explored to occlude cystic duct and vessels.If a patient with a past history of LC or LCBDE presents with features of sepsis and recurrent upper quadrant pain,clip migration must be considered as one of the differential diagnosis.

Systematic review of laparoscopy-assisted versus open gastrectomy for advanced gastric cancer

Objective:The study compared laparoscopy-assisted gastrectomy(LAG) with open gastrectomy(OG) in the management of advanced gastric cancer(AGC).Methods:Literature search was performed in the Medline,Embase,and Cochrane Library databases to identify control studies that compared LAG and OG for AGC.A meta-analysis was conducted to examine the surgical safety and oncologic adequacy,using the random-effect model.Results:Seven eligible studies including 815 patients were analyzed.LAG was associated with less blood loss,less use of analgesics,shorter time of flatus and periods of hospital stay,but longer time of operation.The incidence of most complications was similar between the two groups.However,LAG was associated with a lower rate of pulmonary infection(odds ratio(OR) 0.19;95% confidence interval(CI) 0.05 to 0.68;P<0.05).No significant differences were noted in terms of the number of harvested lymph nodes(weighted mean difference(WMD) 1.165;95% CI-2.000 to 4.311;P>0.05),overall mortality(OR 0.65;95% CI 0.39 to 1.10;P>0.05),cancer-related mortality(OR 0.64;95% CI 0.32 to 1.25;P>0.05),or recurrence(OR 0.62;95% CI 0.33 to 1.16;P>0.05).Conclusions:LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG.No differences were found in long-term outcomes.However,these results should be validated in large randomized controlled studies(RCTs) with sufficient follow-up.

HER-2 overexpression and survival in colorectal cancer: a meta-analysis

Objective： Numerous studies examining the relationship between human epidermal growth factor receptor 2 （HER-2） overexpression and survival in patients with colorectal cancer （CRC） have yielded controversial results. We therefore performed a meta-analysis more precisely to estimate its prognostic value. Methods： Published studies investigating the effect of HER-2 overexpression on CRC survival were identified; the hazard ratios （HRs） and their corresponding 95% confidence intervals （95% Cls） were pooled in terms of disease-specific or overall survival. Results Eleven studies were included in the meta-analysis. The pooled data showed that HER-2 overexpression was negatively related to CRC survival （HR=1.10, 95% CI： 0.77-1.44）. Subgroup analyses regarding test method and study quality also demonstrated little association between HER-2 overexpression and CRC survival （HR=0.89, 95% CI： 0.50-1.29; HR=0.90, 95% Ch 0.43-1.37, respectively）, Conclusions： Regardless of several limitations, our study suggested that HER-2 overexpression probably had little impact on CRC survival.

Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature

Differentiated thyroid carcinoma （DTC） is a common malignancy. The general treatments are thyroidec- tomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis loci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and intemal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was （53.9±9.2） years （rang, 42-72 years） and the male to female ratio was 1：2. Nine cases received total/near-total thyroidectomy or Io- bectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation （9/12）, ITM adjuvant therapy （3/12）, chemotherapy （1/12）, and no intervention （1/12）. During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisci- plinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.