G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

Identification of biomarkers for childhood obesity based on expressional correlation and functional similarity.

The aim of the current study was to identify potential biomarkers of childhood obesity, and investigate molecular mechanisms and candidate agents in order to improve therapeutic strategies for childhood obesity. The GSE9624 gene expression profile was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in omental adipose tissues were analyzed with limma package by comparing samples from obese and normal control children. Two­way hierarchical clustering was applied using the pheatmap package. The co­expression (CE) analysis was performed using online CoExpress software. Subsequent to functional classification via the GOSim package, the gene network enriched by DEGs was visualized using the Cytoscape package. The codon usage bias of the DEGs was then examined using the CAI program from the European Molecular Biology Open Software Suite. In total, 583 DEGs (273 upregulated genes and 310 downregulated genes) were observed in the omental adipose tissues between samples from obese and normal control children. Hierarchical clustering identified a significant difference between samples from obese and normal control children. Subsequent to CE analysis, 130 DEGs, which were classified into 4 clusters, were selected. The following 3 upregulated and 2 downregulated genes were identified to be significant: Upregulated genes, microtubule­associated protein tau (MAPT), destrin (actin depolymerizing factor) (DSTN) and spectrin, ß, non­erythrocytic 1 (SPTBN1); downregulated genes, Rho/Rac guanine nucleotide exchange factor 2 (ARHGEF2) and spindle and kinetochore associated complex subunit 1 (SKA1). The top 3 amino acids were identified to be glycine, leucine and serine with a high bias. The DEGs MAPT, DSTN, SPTBN1, ARHGEF2 and SKA1 are suggested to be candidate biomarkers for childhood obesity.

Biglycan stimulates VEGF expression in endothelial cells by activating the TLR signaling pathway.

Biglycan (BGN) is an important component of the extracellular matrix (ECM) that is implicated in a variety of human cancers. In our previous study, we reported that BGN was overexpressed in gastric cancer (GC) tissues and promoted cancer metastasis. Moreover, the tubular formation capacity in HUVECs was promoted by stimulation with culture media from BGN-overexpressing GC cells, but the exact underlying mechanism is still unknown. The purpose of this study was to determine the role and molecular mechanism of BGN in VEGF expression in endothelial cells. We found that BGN stimulation of endothelial cells increased the interaction between NF-kB and the HIF-1α promoter, leading to enhanced promoter activity and increased HIF-1α mRNA levels, as well as augmented HIF-1 activity that resulted in VEGF expression. All of this was dependent on the interaction of BGN with its receptors, TLR2 and TLR4. Moreover, we found that BGN enhanced endothelial cell migration and proliferation, as well as tube formation, in a TLR signaling pathway-dependent manner. In addition, endothelial cell-derived VEGF in turn was found to act on GC cells and promotes their migration. The combined findings of our current and previous studies suggest that BGN secreted from GC cells into the tumor stroma promotes GC development, as well as its progression, potentially through the chronic activation of tumor angiogenesis.

Biglycan enhances gastric cancer invasion by activating FAK signaling pathway.

Biglycan (BGN) is an important member of small leucine-rich proteoglycans family, and has been implicated in oncogenesis and development of various human cancer types. Here we report that BGN promotes tumor invasion and metastasis of gastric cancer both in vitro and in vivo. BGN expression is significantly higher in gastric cancer tissues and associated with lymph node metastasis, depth of tumor invasion and TNM stage. BGN enhances gastric cancer cell wound healing, migration and invasion ability as well as the tube formation ability of endothelial cells in vitro. Animal experiments results in vivo are consistent with outcomes in vitro. BGN induces increased phosphorylation of FAK (Tyr576/577, Tyr925 and Tyr397) and Paxillin. These results indicate that BGN is upregulated, and plays an oncogenic role, in gastric cancer metastasis by activating the FAK signaling pathway.

Nasogastric decompression for radical gastrectomy for gastric cancer: a prospective randomized controlled study.

BACKGROUND: The purpose of this study was to evaluate the necessity of a nasogastric decompression in radical gastrectomy for gastric cancer patients by a prospective randomized controlled trial. METHODS: From 2007 to 2009, 161 gastric cancer patients who underwent radical gastrectomy were randomly selected and entered into three groups: tube group (TG), intra-operative tube group (ITG), and no-tube group (NTG). The variables studied among the groups were demographic characteristics, surgical characteristics, postoperative recovery and complications. RESULTS: With respect to demographic and surgical characteristics, there were no significant differences among the 3 groups. The time of the first passage of flatus, tolerance of water intake, liquid diet and semiliquid diet were similar among TG, ITG and NTG. Postoperative hospital stay was increased in patients from TG compared to NTG (11.3 vs. 10.2 days, p = 0.031). The incidence of nausea was significantly higher in TG than in ITG or NTG (64 vs. 36.8 and 29.6%). The overall postoperative complication rate was not significantly different among these groups (20, 15.8 and 20.4% in TG, ITG and NTG, respectively, p = 0.612). CONCLUSIONS: Radical gastrectomy can be performed safely without nasogastric decompression for gastric cancer patients. The routine prophylactic nasogastric decompression is unnecessary.

[Evaluation of the gastrointestinal decompression after gastrectomy: a prospective randomized controlled trial].

OBJECTIVE: To evaluate the value of using nasogastric tube for patients after gastrectomy. METHODS: One hundred and eight patients undergone gastrectomy were divided randomizely into nasogastric decompression group(n=53) and non-nasogastric decompression group (n=55). Gastrointestinal function and postoperative complications were compared between the two groups. RESULTS: Between nasogastric decompression group and non-nasogastric decompression group, no significant differences in postoperative complications (20.8% vs 23.6%, P=0.719), postoperative time of flatus [(3.2+/-0.9) d vs (3.0+/-0.7) d, P=0.192], recovery time of drinking [(5.9+/-3.4) d vs (5.1+/-1.6) d, P=0.143], eating time of fluid food [(7.8+/-3.6) d vs (6.8+/-1.8) d, P=0.085] and eating time of semi-fluid food [(9.8+/-3.5) d vs (8.8+/-1.9) d, P=0.081] were found. While the recovery time of bowl sound [(1.8+/-0.7) d vs (2.2+/-0.9) d, (P=0.013)] and hospital stay [(10.2+/-2.1) d vs (11.7+/-4.3) d, (P=0.021)] were shorter in non-nasogastric decompression group. CONCLUSION: It is not necessary to use nasogastric decompression for patients after gastrectomy.

Is PET-CT suitable for predicting lymph node status for gastric cancer?

BACKGROUND/AIMS: To verify the value of PET-CT for predicting lymph node status of gastric cancer preoperatively. METHODOLOGY: 78 gastric cancer patients accepted PET-CT preoperatively, the results of lymph node status were compared with the postoperative pathology. CT was used as control. RESULTS: The accuracy of PET-CT and CT in N category was 55.1% vs. 54.4%, respectively. The sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV) of PET-CT in predicting position of positive lymph node were 31.0%, 97.2%, 61.5%, 92.9%, and 54.7%, respectively. While for CT, were 60.5%, 83.3%, 70.6%, 82.1%, and 62.5%, respectively. For tier 1 lymph node metastasis, the sensitivity, specificity, accuracy, PPV, and NPV of PET-CT were 31.6%, 95.0%, 64.1%, 85.7%, and 59.4%, respectively. While for CT, were 60.0%, 78.8%, 69.1%, 75.0%, and 65.0%, respectively. The sensitivity of CT was significantly better (p = 0.031). For tier 2 or tier 3 lymph node metastasis, the sensitivity, specificity, accuracy, PPV, and NPV of PET-CT were 12.0%, 98.1%, 70.5%, 75.0%, and 70.3%, respectively. While for CT, were 22.7%, 93.5%, 70.6%, 62.5%, and 71.7%, respectively, without significance. CONCLUSIONS: PET-CT is not sensitive enough to predict the regional lymph node status of gastric cancer preoperatively.

[Clinical value of routine haematoxylin-eosin stain in diagnosing submucosal lymphatic vessel infiltration in early gastric cancer].

OBJECTIVE: To evaluate the value of routine haematoxylin-eosin(HE) stain for submucosal lymphatic vessel infiltration in early gastric cancer. METHODS: Four thousand four hundred and twenty early gastric cancer patients underwent D2 operation. Submucosal lymphatic vessel was detected by routine HE stain. The results were compared with pathological lymph node metastasis. RESULTS: In early gastric cancer, the sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV) of routine HE stain for submucosal lymphatic vessel infiltration were 54.5%, 82.0%, 78.9%, 27.4%, and 93.5% respectively. In early gastric cancer limited in mucosa, these indexes were 14.5%, 98.0%, 95.8%, 15.8%, and 97.8% respectively. In early gastric cancer infiltrated to submucosa, they were 60.3%, 57.8%, 58.3%, 28.1%, and 84.2% respectively. There were significant differences of submucosal lymphatic vessel infiltration with lymph node metastasis (P< 0.001), but no significant difference with survival rate. The 5-year survival rates of submucosal lymphatic vessel infiltration positive and negative group were 84.4% and 87.3%, median survival time was 6998 d and 7237 d, and mean survival time was 6163.9 d and 6042.6 d respectively (P=0.2495). CONCLUSION: The accuracy of routine HE stain is too low, thus it is not suitable for diagnosing submucosal lymphatic vessel infiltration in early gastric cancer.

Efficacy and safety of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer patients with serosal invasion. A long-term follow-up study.

AIMS: This study was undertaken to investigate the clinical effects and safety of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC) patients. METHODS: A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001, 52 underwent IPHC after gastrectomy and 66 were treated with gastrectomy only. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for the prophylactic study, 22 with peritoneal metastases were selected for the therapeutic study. Postoperative survival, recurrence pattern and incidences of postoperative complications between patients with and without IPHC were analyzed and compared. RESULTS: For the prophylactic study, the IPHC procedure improves postoperative survival rate and decrease the incidence of peritoneal recurrence, and is an independent prognostic factor for these patients. For the therapeutic study, postoperative survival times were longer if IPHC was undertaken. No surgery-related death occurred. The incidence of renal dysfunction was higher in the IPHC group, but all patients recovered without hemodialysis. CONCLUSION: IPHC is a safe procedure that improves the survival prognosis for AGC patients with serosal invasion. It is especially beneficial for patients without peritoneal metastasis due to the reduction of postoperative peritoneal recurrence.

[Clinical effect of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer].

OBJECTIVE: To investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC). METHODS: A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared. RESULTS: For prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC. CONCLUSION: IPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.

The diagnostic value of PET-CT for peritoneal dissemination of abdominal malignancies.

AIM: To evaluate the diagnostic value of PET-CT for predicting peritoneal metastasis of abdominal malignancies. METHODS: One hundred fifty four (154) cases of malignant tumor, including 141 cases of gastric cancer, 9 cases of colon cancer, 2 cases of ovary cancer, and 2 cases of pseudomyxoma, had accepted PET CT from Nov. 2002 to Jan. 2006. One hundred twenty three (123) had also accepted high speed spiral CT (HSSCT) as control. The results were compared with peritoneal lavage, pathological examination and clinical manifestation. RESULTS: The accuracy of PET-CT for peritoneal metastasis was 87.7%, with sensitivity 72.7%, specificity 93.6%, PPV 82.1% and NPV 89.6%. HSSCT showed an accuracy of 79.7%, sensitivity 47.4%, specificity 94.1%, PPV 78.3%, and NPV 80.0%. PET-CT had significantly better sensitivity than HSSCT (p < 0.05). For gastric cancer patients alone, PET CT had an accuracy of 87.9%, sensitivity 74.4%, specificity 93.1%, PPV 80.6% and NPV 90.5%, significantly better than HSSCT's 78.1, 39.4, 93.8, 72.2, and 79.2% (p < 0.01), respectively. In case of Cy1P0, PET-CT showed a seemingly better sensitivity of 53.3% vs. 13.3% of HSSCT, although not statistically significant because of the number of observations (p = 0.053). And in P1 cases, PET-CT and HSSCT manifested sensitivity of 84.2% vs 63.2%, respectively, without significance (p = 0.141). CONCLUSION: PET-CT is useful in predicting peritoneal metastasis of malignancies.

[The results of surgical treatment for pseudomyxoma peritonei].

The surgical results of 37 patients with pseudomyxoma pertonei are reported. Twenty eight patients received laparotomy and complete cytoreduction (CC-0) could be done in 6 patients. However, 13 patients received incomplete cytoreduction, and 9 patients underwent drainage of ascites and peritoneal washing. The Peritoneal Carcinomatosis Index (PCI) was less than 20 in CC-0 patients. CC-0 patients survived significantly better than patients with residual disease. Accordingly, peritoneal washing to remove free cancer cells should be aimed for complete cytoreduction of the solid mucinous nodules.