Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial.

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).

Ribosomal protein L31 (RPL31) inhibits the proliferation and migration of gastric cancer cells.

Gastric cancer (GC) is a digestive tract malignant tumor and causes the third cancer-related mortality in the world. Aberrant expression of Ribosomal Protein L31 (RPL31) has been reported in several human cancers. The aim of this study was to explore the role and possible biological functions of RPL31 in GC. We firstly employed immunohistochemistry to examine RPL31 expression in tumor and para-cancerous tissues. By lentiviral transfection, we successfully constructed an RPL31-knockdown GC cell model and performed functional validation to reveal the effects of RPL31 on proliferation, apoptosis, cycle, migration, and tumor growth. Our data indicated that RPL31 was abundantly expressed in GC tissues and cell lines (AGS and MGC-803). In addition, RPL31 expression was positively correlated with the extent of tumor infiltrate of GC patients. Functionally, silencing RPL31 in AGS and MGC-803 cells significantly limited the ability of proliferation and migration, promoted cell apoptosis. Consistently, RPL31-knockdown GC cells inhibited the growth of xenografts in mice. Moreover, preliminary analysis on the downstream regulation mechanism revealed that RPL31 functioned as a tumor promoter through targeting JAK-STAT signaling pathway. In conclusion, inhibition of abnormally high expression of RPL31 in GC may be a potential therapeutic strategy for this disease.

RPL35A is a key promotor involved in the development and progression of gastric cancer.

BACKGROUND: RPL35A has been reported to work as a biomarker in tumor angiogenesis. However, little work has been performed on the expression level and functional importance of RPL35A in gastric cancer (GC). METHODS: The protein expression level of RPL35A was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound healing assay and the transwell assay were conducted to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed for in vivo experiments. RESULTS: The results demonstrated that RPL35A expression was abundantly up-regulated in GC and positively related to tumor infiltrate. In addition, RPL35A knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study also verified the inhibitory effects of RPL35A knockdown on GC tumorigenesis. CONCLUSIONS: The above mentioned results indicated that the knockdown of RPL35A might be a considerable therapeutic strategy for the treatment of gastric cancer.

Multicenter investigation of bowel evacuation function after transanal total mesorectal excision for mid-low rectal cancer.

PURPOSE: To determine the effect of transanal total mesorectal excision (taTME) procedure on the postoperative bowel evacuation function of patients with low rectal cancer. METHODS: Bowel evacuation function was investigated in 316 patients with rectal cancer after taTME in 18 hospitals in China. Low anterior resection syndrome (LARS) score, Wexner score, and EORTC QLQ-C30 were used for functional evaluation. The association between perioperative risk factors and LARS score was determined by univariate and multivariate analyses. RESULTS: The prevalence rate of no LARS, minor LARS, and major LARS in patients after taTME was 39.9%, 28.2%, and 31.9%, respectively. The two most frequently reported symptoms of LARS after taTME were bowel clustering (72.8%) and fecal urgency (63.3%). Patients with major LARS had significantly higher Wexner score and worse global health status and financial difficulties according to the EORTC QLQ-C30 questionnaire than those without major LARS. Preoperative chemoradiotherapy was an independent risk factor of major LARS occurrence after taTME (OR: 3.503, P = 0.044); existing preoperative constipation (OR: 0.082, P = 0.040) and manual anastomosis (OR: 4.536, P = 0.021) were favorable factors affecting bowel evacuatory function within 12 months after taTME, but for patients whose follow-up time was longer than 12 months, postoperative chemoradiotherapy (OR: 8.790, P = 0.001) and defunctioning stoma (OR: 3.962, P = 0.010) were independent risk factors. CONCLUSIONS: The bowel evacuation function after taTME is acceptable. Perioperative chemoradiotherapy, anastomotic method, and preoperative constipation are factors associated with bowel dysfunction after taTME.

LncRNA DSCAM-AS1 Promotes Colon Cancer Cells Proliferation and Migration via Regulating the miR-204/SOX4 Axis.

INTRODUCTION: Long non-coding RNA (lncRNA) DSCAM-AS1 was reported to be aberrantly expressed and play pivotal roles in various human cancers. The aim of the present study was to investigate the expression and roles of DSCAM-AS1 in colon cancer (CC). METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of DSCAM-AS1, miR-204 and the mRNA level of SOX4. Cell proliferation and cell cycle were analyzed by MTT assay and flow cytometry, respectively. Transwell assay was used for migration capacity detection. Luciferase activity assay was conducted to verify the direct binding of DSCAM-AS1 and miR-204 or miR-204 and SOX4. The protein expression of SOX4 was determined by Western blot. Kaplan-Meier curves were calculated and the Log rank test was performed for the survival data analysis. RESULTS: DSCAM-AS1 was significantly upregulated in CC and high expression of DSCAM-AS1 was associated with poor prognosis in patients with colon cancer. Knockdown of DSCAM-AS1 significantly suppressed CC cells proliferation and migration. In addition, DSCAM-AS acted as a molecular sponge for miR-204 and SOX4 was identified as a direct target of miR-204 in CC. Moreover, the rescue assay revealed that miR-204 inhibition partly abolished the effects of DSCAM-AS1 knockdown on CC cells proliferation, migration and SOX4 expression. DISCUSSION: The present study demonstrated that DSCAM-AS1 acted as an oncogenic lncRNA in CC progression by regulating miR-204/SOX4 axis and DSCAM-AS1 may serve as a novel therapeutic target in the treatment of colon cancer.

Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer.

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/ß-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

Glucagon-like peptide-1 receptor agonist exendin-4 mitigates lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.

Macrophages play a critical role in the immune response against pathogen invasion and injury. However, under pathological stress, macrophages could have aberrant roles and contribute to the pathogenesis of inflammatory associated diseases. Exenatide is a glucagon-like peptide 1(GLP-1) agonist, which belongs to the family of synthetic exendin-based incretin mimetic. Exendin related compounds reduce glucose levels in type 2 diabetes patients. The purpose of this study was to examine the anti-inflammatory effects of exendin-4 in LPS-induced activation of macrophages. We show that exendin-4 inhibits LPS-induced expression of inflammatory mediators (iNOS, COX-2, PGE2 and NO) and pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in RAW264.7 macrophages. Exendin-4 pretreatment mitigates LPS induced cellular ROS production. Mechanistically, Exendin-4 suppresses the LPS-induced activation of the JNK and AP-1 pathway. Furthermore, exendin-4 suppresses both nuclear p65 accumulation and transfected NF-κB promoter activity, indicating it inhibits the activation of the NF-κB pathway. Our study demonstrates that the GLP-1 agonist exendin-4 has a potent anti-inflammatory effect independent on its glucose reducing ability, and exendin-4 has the potential implication to treat inflammatory associated diseases.

Long noncoding RNA AOC4P regulates tumor cell proliferation and invasion by epithelial-mesenchymal transition in gastric cancer.

BACKGROUND: The clinical relevance and biological role of tissular AOC4P in gastric cancer (GC) remains to be clarified. METHODS: The association between AOC4P expression and clinicopathological characteristics was investigated. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of AOC4P on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. In vivo, animal experiments were conducted to confirm the in vitro findings. Quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence were used to investigate the potential mechanisms. RESULTS: Expression levels of AOC4P were significantly higher in tumor tissues than in noncancerous tissues, and patients with high levels of AOC4P had poor overall and disease-free survival. AOC4P expression was correlated with lymphovascular invasion. In vitro, knockdown of AOC4P inhibited tumor cell proliferation, migration, and invasion, and promoted apoptosis of MGC-803 and BGC-823 cells. In vivo, BGC-823 cells transfected with AOC4P siRNA formed smaller and lighter tumors than BGC-823 cells transfected with negative control siRNA in severe combined immunodeficiency mice. Additionally, the si-AOC4P group had less proliferating cells and more apoptotic cells in tumor xenografts compared with the negative control. Mechanistically, knockdown of AOC4P decreased the expression of vimentin and MMP9, while increasing the expression of E-cadherin. Immunofluorescence confirmed the relationship between AOC4P expression and E-cadherin, vimentin, and MMP9 levels in clinical GC specimens. CONCLUSIONS: AOC4P promotes tumorigenesis and progression partly through epithelial-mesenchymal transition in GC. Additionally, AOC4P may serve as a prognostic biomarker for clinical decision making.

Glutaminase sustains cell survival via the regulation of glycolysis and glutaminolysis in colorectal cancer.

Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells. The abrogation of GLS1 function notably inhibited glutaminolysis and aerobic glycolysis, which resulted in the decrease of internal ATP levels and an increase in cell death. In addition, GLS1 expression was significantly elevated in CRC tissues in comparison with adjacent normal tissues (P<0.001), which is associated with the cell differentiation status and tumor node metastasis stage. In conclusion, the present study defined a key role of GLS1 in coupling glutaminolysis with elevated glucose uptake and consequently the growth of colon cancer cells. Due to the functional importance of GLS1 in regulating cell metabolism, it was proposed that GLS1 may serve as a target for colorectal cancer therapy.

Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells.

The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC­27 and MKN­45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma­associated oncogene (Gli)­1, Gli­2 and Gli­3 were examined using western blot and reverse transcription­quantitative polymerase chain reaction analyses. RNA interference was used to detect whether the effects of metformin treatment on the Shh signaling pathway were dependent on AMP­activated protein kinase (AMPK). The results revealed that the protein and mRNA levels of Shh and Gli­1 were decreased by metformin treatment in the two cell lines in a dose­ and time­dependent manner. Metformin also significantly inhibited the gene and protein expression levels of SMO, Gli­2 and Gli­3. The small interfering RNA­induced depletion of AMPK reversed the suppressive effect of metformin on recombinant human Shh­induced expression of Gli­1 in HGC­27 gastric cancer cells. Therefore, metformin inhibited the Shh signaling pathway in the gastric cancer cell lines and the inhibitory effect of metformin on the Shh pathway was AMPK-dependent.

G protein pathway suppressor 2 (GPS2) acts as a tumor suppressor in liposarcoma.

Liposarcoma(LPS) is the most common type of soft tissue sarcoma accounting for 20 % of all adult sarcomas. However, the molecular pathogenesis of this malignancy is still poorly understood. Here, we showed that GPS2 expression was downregulated in LPS and correlated with the prognosis of this disease. In vitro study showed that knockdown of GPS2 resulted in enhanced proliferation and migration of LPS cell line SW872, without significant influence of cell death. Conclusively, our results suggest that GPS2 may act as a tumor suppressor in LPS and serve as a potential prognosis marker for this disease.

miR-217 regulates tumor growth and apoptosis by targeting the MAPK signaling pathway in colorectal cancer.

MicroRNA (miR)-217 has been reported to participate in carcinogenesis and tumor progression in several cancers; however, its expression and biological functions in colorectal cancer (CRC) are still unclear. The present study demonstrated that miR-217 expression was significantly higher in matched adjacent noncancerous tissues than in CRC tissues (P<0.001). In addition, it was observed that low-grade CRC exhibited greater expression of miR-217 compared with high-grade CRC (P<0.05). Kaplan-Meier survival and Cox regression analyses revealed that overall survival rates were significantly poorer in the low-expression group relative to the high-expression group (P<0.005). Next, a potential miR-217 target, mitogen-activated protein kinase (MAPK) 1, was identified. Upregulation of miR-217 could significantly downregulate MAPK1 expression. CRC cells overexpressing miR-217 exhibited cell growth inhibition by significant enhancement of apoptosis in vitro. The present study further investigated the MAPK signaling pathway to verify the mechanisms, and revealed that KRAS and Raf-1 expression was downregulated in miR-217-overexpressing RKO cells. Taken together, our results revealed that miR-217 inhibits tumor growth and enhances apoptosis in CRC, and that this is associated with the downregulation of MAPK signaling. These results indicate that miR-217 is a promising therapeutic target for the treatment of CRC.

[Clinical analysis of diagnosis and treatment for retroperitoneal malignant fibrous histiocytoma].

OBJECTIVE: To explore the clinical characteristics of retroperitoneal malignant fibrous histiocytoma (MFH) and to retrospectively evaluate the outcome of treatment and identify prognostic factors for survival time. METHODS: The records of 38 patients with retroperitoneal malignant fibrous histiocytoma (MFH) managed with surgery from March 2000 to August 2013 were retrospectively reviewed. RESULTS: All patients received surgical resection, including 23 primary tumors and 15 recurrent tumors. 20 patients received radical resection, 18 cases received palliative resection. The 19 patients (95%) received complete resection got tumor recurrence. The overall 1-, 3-,5-year survival rate were 62. 9%, 35. 2% and 4. 4% and the median survival time was 15. 5 (1 - 157) months. Log-rank test indicated that tumor grade (χ2 = 10. 667, P <0. 01) and radical surgery(χ2 =.18. 476, P <0. 01) were associated with postoperative survival time. The difference between gender(χ2 = 3. 329, P = 0 . 068), age (χ2 = 0. 426, P = 0. 514), removal of the joint organs(χ2 = 3. 725, P = 0. 054), blood transfusion (χ2 = 0. 044, P = 0. 833), tumor size (χ2 = 1. 647, P =0. 199), tumor metastasis(χ2 =0. 345, P =0. 557), adjuvant therapy(χ2 = 1. 992, P =0. 158), recurrent disease (χ2 = 0. 163, P = 0. 640)got no statistical significance. Multivariate analysis indicated that radical surgery and tumor grade were prognostic indicators for retroperitoneal malignant fibrous histiocytoma (RR =4.888, P =0. 001; HR =4. 436, P =0. 006). CONCLUSIONS: Malignant fibrous histiocytoma (MFH) has high malignant degree and is difficult to treat. The prognosis is poor. Complete resection remains the main method for retroperitoneal malignant fibrous histiocytoma. It often requires the resection of other adjacent organs in order to reach the goal of radical resection. Incomplete resection and high grade(grade 3) predict shorter postoperative survival time.

[Clinical diagnosis and treatment of primary retroperitoneal schwannoma: a report of 109 cases].

OBJECTIVE: To evaluate the surgical efficacies of primary retroperitoneal schwannoma (PRS) and analyze its risk factors for survival and recurrence. METHODS: From January 1993 to December 2012, 109 patients diagnosed with primary retroperitoneal schwannoma were treated at our department. And their clinical data were retrospectively analyzed. RESULTS: The overall 1,3,5-year survival rates of benign PRS were all 100%. Univariate analyses revealed that tumor size and modus operandi of tumor resection were associated with recurrence rate. For malignant PRS, the overall 1,3,5-year survival and recurrence rates were 89.6%, 62.1%, 41.4% and 41.4%, 65.5%, 72.4% respectively. Univariate analyses revealed that tumor size, modus operandi of tumor resection and tumor grade were associated with survival rate. Tumor grade was associated with recurrence rate and it was also an independent prognostic factor. CONCLUSION: The major management of PRS is complete excision. Benign PRS has an excellent survival rate. And tumor size and modus operandi of tumor resection are associated with recurrence rate. The survival rate of malignant PRS is associated with tumor size, modus operandi of tumor resection and tumor grade. As an independent prognostic factor, tumor grade is associated with recurrence rate.

Comparison of Therapeutic Efficacy between Gastrectomy with Transarterial Chemoembolization Plus Systemic Chemotherapy and Systemic Chemotherapy Alone in Gastric Cancer with Synchronous Liver Metastasis.

BACKGROUND: Systemic chemotherapy (SC) is the recommended treatment for gastric cancer with liver metastasis. However, the improvement in survival has been disappointing. The aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus SC (GTC) and SC alone for gastric cancer with synchronous liver metastasis. METHODS: From January 2008 to December 2013, 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter, ambispective, controlled cohort study. Patients who underwent GTC (n = 32) were compared with controls who were received SC alone (n = 75). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were response rate to treatment and treatment-related adverse effects. RESULTS: The median OS was 14.0 months (95% confidence interval [CI ]: 13.1-14.9 months) in the GTC treatment group and 8.0 months (95% CI : 6.6-9.4 months) in SC group, this difference being statistically significant (P < 0.001). The median PFS was significantly longer in the GTC than in the SC group (5 months, 95% CI : 2.2-7.8 months vs. 3 months, 95% CI : 2.3-3.4 months, respectively) (P < 0.001). The rate of response to treatment was significantly better in the GTC than the SC group (59.4% vs. 37.4%, respectively) (P = 0.035). According to multivariate analysis, OS in patients receiving combination treatment was significantly correlated with the size (P = 0.037) and extent of liver metastases (P < 0.001). PFS was also correlated with the extent of liver metastases (P = 0.003). CONCLUSIONS: GTC is more effective than SC alone in patients with gastric cancer with synchronous liver metastasis. GTC therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis.

Quality of D2 lymphadenectomy for advanced gastric cancer: is laparoscopic-assisted distal gastrectomy as effective as open distal gastrectomy?

OBJECTIVE: To determine by meta-analysis, whether D2 lymphadenectomy at laparoscopic-assisted distal gastrectomy (LADG) is as effective as that during open distal gastrectomy (ODG) for patients with advanced gastric cancer (AGC). DATA SOURCES AND REVIEW METHODS: All clinical trials that compared laparoscopic with open D2 lymphadenectomy for AGC published in English from January 1995 to June 2013 were identified in PubMed, Embase, Web of Science, and Cochrane library searches. A modified scale was used to assess the quality of the literature. We analyzed the number of harvested lymph nodes (HLNs), body mass index (BMI), tumor size, serosa invasion status, and positive lymph node rate. Meta-analyses were performed using weighted mean differences (WMD) for continuous variables, and risk differences (RD) or odds ratios (OR) for dichotomous variables. RESULTS: No eligible randomized trials were identified, but eight non-randomized trials were analyzed. In the pooled data of 677 patients who underwent LADG and 687 ODG, there were no significant differences the number of HLN (WMD: -0.98, 95 % confidence interval, CI -3.21 to 1.26), BMI (WMD: -1.20, 95 % CI -2.64 to 0.24), tumor size (WMD: -0.30, 95 % CI -0.65 to 0.05), serosa invasion status (RD: 0.04, 95 % CI -0.03 to 0.11), and positive lymph node rate (OR: 0.66, 95 % CI -0.44 to 1.01) between the groups. CONCLUSION: Our findings suggest that for patients with comparable BMI and tumor status, surgical technique did not significantly influence the number of HLNs, suggesting that D2 lymphadenectomy performed laparoscopically is as effective as an open procedure in AGC.

CD133 and Ki-67 expression is associated with gastrointestinal stromal tumor prognosis.

CD133+ tumor cells have a greater potential ability for tumorigenesis, proliferation, invasion and metastasis compared with CD133- tumor cells. Ki-67 is associated with cell proliferation in various tumors and has a markedly positive correlation with the prognosis of patients. However, there are a limited number of studies that have investigated the association between the prognosis of gastrointestinal stromal tumors (GISTs) and the two markers. The present study aimed to investigate CD133 and Ki-67 expression in GISTs and to explore their clinicopathological significance in the prognosis of patients with GISTs. A total of 111 GIST patients from the Chinese People's Liberation Army (PLA) General Hospital were retrospectively followed up and immunohistochemistry was used to detect CD133, Ki-67 and CD117 expression in the tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. The log-rank test, χ2 test and Cox's proportional hazards model were used to determine the association between CD133, Ki-67, CD117 expression and the prognosis of GIST. The 1-, 3- and 5-year survival rates were 93.0, 89.0 and 82.0%, respectively, in all the patients. However, in the patients with CD133+ or Ki-67+, the 1-, 3- and 5-year survival rates were 81.0, 61.5 and 50.0% and 83.0, 66.6 and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were statistically lower (CD133 log-rank, P=0.028; Ki-67 log-rank, P=0.002). The multivariate Cox analysis revealed that CD133 and Ki-67 expression were considerable factors in the prognosis of GIST patients (CD117, P=0.495; CD133, P=0.036; Ki-67, P=0.003). In conclusion, the positive expression of CD133 and Ki-67 was associated with a poor prognosis of GIST.

Not all side population cells contain cancer stem-like cells in human gastric cancer cell lines.

INTRODUCTION: Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissue have demonstrated presence of SP cells including different gastric cancer cell lines. However, is that true all SP cells contain cancer stem-like cells in gastric cancer cell lines? MATERIALS AND METHODS: MKN-45 and BGC-823 cells labeled with Hoechst 33342 were chosen to obtain SP cells, then characterized the cancer stem-like properties of SP cells both in vitro and in vivo. Five stemness-related genes expression profiles, including OCT-4, SOX-2, NANOG, CD44 and ATP-binding cassette transporters gene ABCG-2, were tested in SP and MP cells using quantitative real-time RT-PCR. Western blot was chosen to show the difference of protein expression between SP and MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells from MKN-45 showed higher tumorigenesis tendency than MP cells, but SP cells from BGC-823 showed same tumorgenesis tendency as MP cells. CONCLUSION: SP cells from MKN-45 possess cancer stem cell properties and proved that they were gastric cancer stem-like cells. SP cells from BGC-823 didn't possess cancer stem cell properties and proved that not all SP cells contain cancer stem-like cells in gastric cancer cell lines.

Evaluation of DNA repair gene XRCC1 polymorphism in prediction and prognosis of hepatocellular carcinoma risk.

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.