Multicenter analysis of gastrointestinal stromal tumors in inner Mongolia of China: A study of 804 cases.

INTRODUCTION: To analyze the clinicopathological characteristics, immunohistochemistry, genotyping and prognosis of patients in the multicenter GIST data in Inner Mongolia, China. METHODS: Retrospective analysis was performed on GIST data from January 2013 to January 2018 in Inner Mongolia. Descriptive statistics were used to analyze the clinical characteristics of GIST patients. The Chi-square test was performed on the modified NIH criteria by age distribution, and Kaplan-Merie method was used for survival analysis. RESULTS: A total of 804 patients were included in the GIST database in Inner Mongolia, with a male to female ratio of 1.1102:1. The most common location was the gastric (465). Mitotic count ≤5/50HPFs was found in 67.3 % patients. There were 276 patients with tumor diameter of 2-5 cm and 354 patients with tumor diameter of 5.1-10 cm.The modified NIH criteria was mainly of intermediate risk (210) and high risk (342). The recurrence and metastasis of patients were related to the tumor location, mitotic index, tumor size, and modified NIH criteria. All patients were followed up for 1-10 years, in which 63.1 % of them were followed up for at least three years. The 3-year survival rates of patients with modified NIH criteria of very low risk, low risk, intermediate risk, and high risk were 100 %, 100 %, 100 %, and 96.3 %, respectively. CONCLUSIONS: The incidence of GIST in middle-aged and elder people in Inner Mongolia is high, and the long-term prognosis of patients after surgical treatment is good, which can objectively reflect the incidence, diagnosis and treatment of GIST in Inner Mongolia.

RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Ribosome biogenesis regulatory protein homolog (RRS1) is an essential factor involved in ribosome biogenesis, while its role in CRC remains largely unclear. Here, we found that RRS1 expression was significantly higher in CRC tissues compared with adjacent normal tissues. RRS1 High expression also predicted poor overall survival of CRC patients. Knockdown of RRS1 induced the G2/M cell cycle arrest, apoptosis and suppressed the proliferation of RKO and HCT-116 CRC cells. Furthermore, angiogenesis was also reduced in CRC cells after RRS1 knockdown. In addition, suppression of RRS1 blunted the tumor formation of CRC cells in nude mice. At the molecular level, silencing of RRS1 decreased the expression of M-phase inducer phosphatase 3 (CDC25C), Cyclin-dependent kinase 1 (CDK1), antigen KI-67 (KI67) and increased the protein level of cyclin-dependent kinase inhibitor 1 (CDKN1A) and tumor suppressor p53 (p53). Taken together, our findings provide evidence that RRS1 may promote the development of colon cancer. Therefore, targeting RRS1 may be a promising therapeutic strategy for CRC patients.

Clinical investigation of combined Billroth II with Braun anastomosis for patients with gastric cancer.

BACKGROUND/AIMS: This study gives insight into the effect of combined Billroth II with Braun anastomosis for patients with gastric cancer. METHODOLOGY: The clinical data of 720 patients with gastric cancer who underwent surgical treatment in our hospital from 1997 to 2011 were reviewed retrospectively. The results of different operative approaches were analyzed. RESULTS: Combined Billroth II with Braun anastomosis was performed in 378 cases, and Billroth II in 342 cases. The Gastrointestinal Quality of Life Index (GIQLI) was used to evaluate postoperative quality of life. CONCLUSIONS: If the indications for combined Billroth II with Braun anastomosis are strictly controlled, and more attention is paid to perioperatively support, combined Billroth II with Braun anastomosis can prolong the life span of the patients with gastric cancer rather than increase the surgical complications and the mortality.

Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells.

AIM: To investigate the effects of osteopontin (OPN) gene expression knockdown on colon cancer Lovo cells in vitro. METHODS: Four candidate small interfering RNA (siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC-siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector. After confirmation by restriction enzyme digestion and DNA sequencing, the recombinant plasmids were subsequently transfected into a human colon cancer cell line (Lovo) using a liposome transfection method. Stably transfected cells were maintained with G418 selection and referred to as Lovo-OPN-1, -2, -3, -4, and Lovo-NC cells. Knockdown efficiency of each of the four siRNA constructs was determined by real-time reverse transcription polymerase chain reaction assays and western blotting, and the construct with the most effective silencing was used for subsequent experiments. Cell proliferation, adhesion, and Matrigel invasion assays were performed to analyze the effects of OPN knockdown in stably transfected Lovo cells. The levels of four angiogenic factors, namely vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator were detected by enzyme-linked immunosorbent assays (ELISA). RESULTS: Recombinant vectors containing OPN-specific and scrambled siRNA sequences were successfully constructed and stably transfected into Lovo cells. Compared with the control Lovo and Lovo-NC cells, the levels of OPN mRNA and protein expression in Lovo-OPN-1, -2, -3, and -4 were significantly reduced (all P < 0.05), with the most efficient reduction observed in Lovo-OPN-4 cells (P < 0.05). Relative to untransfected Lovo cells, OPN mRNA expression levels in Lovo-NC and Lovo-OPN-4 cells were 1.008 ± 0.067 and 0.160 ± 0.023, respectively. The relative OPN protein expression levels in Lovo, Lovo-NC, and Lovo-OPN-4 cells were 3.024 ± 0.211, 2.974 ± 0.630, and 0.121 ± 0.008, respectively. Moreover, transfection with the scrambled sequence had no effect on the expression of OPN. After 24, 48, 72, and 96 h of cultivation, absorption values at 450 nm to assess proliferation of Lovo-OPN-4 cells were 0.210 ± 0.017, 0.247 ± 0.024, 0.314 ± 0.037, and 0.359 ± 0.043, respectively, which were significantly lower than those of Lovo (0.244 ± 0.031, 0.313 ± 0.024, 0.513 ± 0.048 and 0.783 ± 0.051) and Lovo-NC cells (0.241 ± 0.029, 0.309 ± 0.022, 0.563 ± 0.023, and 0.735 ± 0.067) (all P < 0.05). The absorption values at 595 nm, which were measured in a cell adhesion assay, showed that adhesion of Lovo-OPN-4 cells (0.215 ± 0.036) was significantly decreased compared to Lovo (0.490 ± 0.037) and Lovo-NC cells (0.462 ± 0.043) (P < 0.05). The number of invasive Lovo-OPN-4 cells (16.1 ± 1.9) was also significantly decreased compared to Lovo (49.9 ± 5.4) and Lovo-NC cells (48.8 ± 4.5) (P < 0.05). ELISA assays showed significant reductions in Lovo-OPN-4 cells compared to Lovo and Lovo-NC cells with regard to the expression of VEGF (1687.85 ± 167.84 ng/L vs 2348.54 ± 143.80 ng/L and 2284.39 ± 138.62 ng/L, respectively), MMP-2 (2966.07 ± 177.36 µg/L vs 4084.74 ± 349.54 µg/L and 4011.41 ± 424.48 µg/L, respectively), MMP-9 (3782.89 ± 300.64 µg/L vs 5062.90 ± 303.02 µg/L and 4986.38 ± 300.75 µg/L, respectively) and uPA (1152.69 ± 120.79 µg/L vs 1380.90 ± 147.25 µg/L and 1449.80 ± 189.92 µg/L, respectively) (all P < 0.05). CONCLUSION: Knockdown of OPN gene expression suppresses colon cancer cell growth, adherence, invasion, and expression of angiogenic factors.

Clinicopathologic characteristics and prognosis of gastric cancer patients underwent gastrectomy combined with splenectomy.

BACKGROUND/AIMS: This study gives insight into the effect of splenectomy in radical surgery for gastric cancer. METHODOLOGY: The study included 631 patients who underwent radical resection for gastric cancer. Of these 631 patients, 105 underwent splenectomy and 526 had splenic preservation. The clinicopathologic features of 105 patients underwent gastrectomy combined with resection of the spleen (splenectomy group) and 526 patients underwent gastrectomy (spleen-preservation group) were compared. RESULTS: Gastric cancer with splenectomy was characterized by tumor located in gastric cardia (33.3%), positive lymph node metastasis (91.4%), and serosal invasion (94.3%). For age, gender, and tumor size, there was no significant difference between the patients with splenectomy and spleen-preservation. The 5-year survival of splenectomy group was 21.3% as compared with 38.6% for spleen-preservation group (P<0.001). With respect to patients with splenectomy, multivariate analysis showed that lymph node metastasis was significant factors affecting survival. CONCLUSIONS: Compared with spleen-preservation group, patients who underwent gastrectomy combined with splenectomy have a greater chance of tumor located in gastric cardia, positive lymph node metastasis, and serosal invasion and a significantly poor prognosis.

[Effect of human colon carcinoma-associated fibroblasts on biological behavior of colon carcinoma Lovo cells].

OBJECTIVE: To investigate the effects of human colon carcinoma-associated fibroblasts (CAFs) on proliferation, adhesion, migration and invasion of colon carcinoma Lovo cells. METHODS: The co-culture models among colon CAFs, NFs and Lovo cell were established by conditioned medium (CM) of human colon CAFs and colon normal fibroblasts (NFs). Lovo cells in the blank control group was treated with serum-free culture medium. The effects of human colon CAFs on proliferation, adhesion, migration and invasion of colon carcinoma Lovo cells were detected by cell proliferation assay, adhesion assay, migration assay and Transwell invasion assay. RESULTS: After co-culture with colon CAFs, the absorbance (A) value of Lovo cells was (0.667±0.059) in 48 h and (0.709±0.030) in 72 h. The A value of Lovo cells adhesion to fibronectin was (0.588±0.067). The cell mobility rates were (35.2±8.7)% in 12 h and (64.6±7.1)% in 24 h. The number of invasive cell was (56.2±4.8). All the above parameters were increased compared with those in the blank control group and NFs group (all P<0.01). CONCLUSION: Human colon CAFs can promote the proliferation, adhesion, migration and invasion of colon carcinoma Lovo cells.

Probing the hepatic progenitor cell in human hepatocellular carcinoma.

Objective. The intrahepatic stem cells, also known as hepatic progenitor cells (HPCs), are able to differentiate into hepatocytes and bile duct epithelia. By exposure of different injuries and different hepatocarcinogenic regimens, the mature hepatocytes can no longer effectively regenerate; stem cells are involved in the pathogenesis of hepatocellular carcinoma. Methods. Immunohistochemistry was performed on 107 paraffin-embedded hepatocellular carcinoma specimens with the marker of hepatocyte and hepatocellular carcinoma (HepPar1), biliary differentiation (CK7,CK19), haemopoietic stem cell (HSC) (c-kit/CD117, CD34, and Thy-1/CD90), HPC specific markers (OV-6), and Ki-67, p53 protein. Results. HPCs can be identified in the tumor nodules, around the edge of tumor nodules, and in the portal tracts of the paracirrhosis nodules being positive in HepPar1, CK7, CK19, and OV-6, but they failed to immunostain with CD117, CD34, and CD90. The HPCs positive in Ki-67 are observed in the tumor and paracirrhosis tissues. In 107 specimens, 40.2% (43/107) HCC tissues expressed p53 protein, lower than that of the HPCs around the tumor nodules (46.7%, 50/107) and much higher than that of the HPCs around the paracirrhosis nodules (8.41%, 9/107). Conclusion. Human hepatocellular carcinogenesis may be based on transformation of HPCs, not HSCs, through the formation of the transitional cells (hepatocyte-like cells and bile ductal cells).

Predictive role of glutathione-S-transferase gene polymorphisms in the survival of gastric cancer cases.

AIM: We conducted a prospective study in an Chinese population to detect the association between GSTM, GSTT and GSTP gene polymorphisms and survival of gastric cancer. METHODS: A prospective follow-up study with 317 gastric cancer patients was conducted between January 2003 and January 2005. GSTM1, GSTT1 and GSTP1 genotyping was performed using ABI TaqMan Gene Expression assays. RESULTS: Of 317 patients, 5 were lost to follow-up due to migration, while the remaining 302 patients completed the study. The median follow-up time was 34.2 months (range: 2 to 60 months), during which a total of 120 (39.1%) died of gastric cancer. The GSTT1-null genotype showed a significant increased risk of death from gastric cancer, with an HR (95% CI) of 1.59 (1.04-3.58). Moreover, we found individuals carrying null-GSTM1 and null-GSTT1 had a moderate higher risk of death from gastric cancer, with an HR of 1.92 (1.05-3.65). CONCLUSION: This study reported the carriage of null GSTT1 and null GSTM1 might be linked to the higher death risk from gastric cancer in Chinese population.

[Expression of metabolic enzymes of fluoropyrimidines in primary colorectal cancer and its clinical significance].

OBJECTIVE: To investigate the expression of metabolic enzymes of fluoropyrimidines in primary colorectal cancer. METHODS: Sixty-one cases of pathological confirmed primary colorectal cancer were collected in Beijing Cancer Hospital from August 2003 to February 2004. The expressions of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) were detected in paired tumor tissues and non-cancerous tissues by RT-PCR. RESULTS: Expression of each enzyme in tumor tissues was positively correlated with that in paired non-cancerous tissues respectively. Compared with the expression of each enzyme in cancer with that in non-cancer, OPRT was higher in cancer while that of DPD and TS was comparable. The expression of OPRT was approximately 4.38-folds higher in colorectal cancer tissues than that in non-cancerous tissues (P=0.000). The lowest expression of OPRT was found in mucinous carcinoma while the highest levels in poorly-differentiated adenocarcinoma. There were correlations between the ratio of tumor tissues/non-cancerous tissues OPRT expression (T/N) and metastasis to the lymph nodes (r=0.36; P=0.005), small vessel invasion (r=0.26; P=0.041) and differentiation (r=-0.33; P=0.009). CONCLUSION: The detection of three enzymes by means of RT-PCR is practical and can be used in clinical application. Our results also suggest that OPRT is a potential biomarker in predicting prognosis of colorectal cancer.