ObjectiveTo summarize the diagnosis and treatment of a primary gastric colon cancer, and to explore its safety and feasibility.MethodThe clinical data of a patient with gastric cancer and sigmoid colon cancer who admitted to The Affiliated Yantai Yuding Hospital of Qingdao University in October 2017 was analyzed.ResultsThe patient underwent laparoscopic radical gastrectomy plus π anastomosis and laparoscopic radical resection of colon cancer. The operation time was 330 min and the intraoperative blood loss was 120 mL. There were no complications such as stomach cramps and sputum after operation and he was successfully discharged on the 9th day after surgery. Postoperative pathological staging: gastric cancer (pT3N3M0, ⅢB) and sigmoid colon cancer (pT2N0M0, Ⅰ B).ConclusionsMultiple primary cancer of the simultaneous gastric colon should be diagnosed before operation. Laparoscopic minimally invasive treatment for gastric cancer with sigmoid colon cancer is safe and feasible, and can benefit patients.
ObjectiveTo investigate effect of Notch pathway regulating by inhibiting expression of forkhead box protein A1 (FOXA1) on proliferation and invasion of colon cancer SW480 cells. MethodsThe colon cancer tissues and their corresponding paracancerous tissues of 45 patients with colon cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from June 2019 to February 2021 were selected. The immunohistochemistry and real-time fluorescent quantitative PCR (qRT-PCR) methods were used to detect the expressions of FOXA1 protein and mRNA in the tissues, respectively. In addition, SW480 cells were divided into control group (untreated), shRNA-NC group (transfected with shRNA-NC), sh-FOXA1 group (transfected with sh-FOXA1), sh-FOXA1+sodium valproate group (Add 8 mmol/L Notch pathway activator sodium valproate after transfection with sh-FOXA1). Then the qRT-PCR, MTT, clone formation test, and Transwell methods were used to detect the expressions of FOXA1 mRNA, proliferation, clonogenic ability, invasion and migration of cells in each group. Western blot method was used to detect the proliferation (c-Myc, cyclinD1), invasion and migration [matrix metalloproteinase (MMP）9, MMP2], epithelial-mesenchymal transition (Vimentin, N-cadherin, E-cadherin) and Notch pathway (Notch-1, Hes-1) related protein expressions of cells in each group. Results① In the clinical cases, the expression levels of FOXA1 protein and mRNA in the colon cancer tissues were higher than those in the corresponding paracancerous tissues (protein: 0.085±0.028 vs. 0.034±0.010, t=11.036, P<0.001; mRNA: 1.62±0.34 vs. 1.00±0.09, t=11.671, P<0.001). ② In the cell experiment, compared with the control group and shRNA-NC group, the cell survival rate, and numbers of cloned cells, invasion and migrating cells were significantly reduced (P<0.05), correspondingly, the related proteins expression levels of c-Myc, cyclinD1, MMP9, MMP2, Vimentin, N-cadherin, Notch-1, Hes-1 were significantly reduced (P<0.05) and the protein expression level of E-cadherin was significantly increased (P<0.05) in the sh-FOXA1 group, which were reversed after adding the Notch pathway activator sodium valproate (P<0.05). ConclusionFOXA1 highly expresses in colon cancer tissues and colon cancer cells and it might promote the proliferation, invasion and migration of SW480 cells by activating the Notch pathway.
Objective
To investigate the effects of recombinant adenovirus-mediated co-transfection of carcinoembryonic antigen (CEA) gene and erythropoietin (EPO) gene on promoting hematopoietic stem cells directly producing erythrocyte vaccine against colon cancer.
Methods
The expression adenovirus vectors carrying CEA and EPO or green fluorescent protein (GFP) gene were constructed respectively, and recombinant adenovirus carrying CEA, EPO or GFP were packaged and produced respectively. The bone marrow-derived mesenchymal stem cells (MSCs) of mice were isolated and cultured in vitro by anti-CD117 magnetic bead separation, and were transfected with CEA (CEA group), EPO (EPO group) or GFP (blank vector group), co-transfected with CEA and EPO (CEA-EPO group). The expressionsof CEA and EPO gene and its protein after transfection in supernatant fluid of culture were detected by realtime-PCR and Western blot method in each group. We had checked and obtained the vaccine with co-transfection of CEA gene and EPO gene by cell red line marker antibody CD71 and GPA, then we carried on experiments with the vaccine in vitro and in vivo. There were 4 groups in our trail: blank vector group, CEA group, EPO group, and CEA-EPO group.
Results
We had successfully gathered the hematopoietic stem cells, flow cytometry analysis result showed that there were significant differences before and after purification for positive selected samples (P<0.05). The expressions of double genes (CEA-EPO gene) and protein showed CEA-EPO gene were successfully transfected into the hematopoietic stem cells. We had confirmed erythrocyte vaccine with co-transfection of CEA and EPO gene by antibody CD71 and GPA with flow cytometry. The monocytes cytotoxicity on colon cancer cell line CT26 showed that lysis of target cells of CEA-EPO group were higher than those of other 3 groups when in proportion of 40∶1 (P<0.05). In the experimentation of neoplasma format, the volume of tumor and mortality were smaller or lower, but survival time was longer of CEA-EPO group in2 weeks after treatment (P<0.05).
Conclusions
The erythrocyte vaccine with co-transfection of CEA gene and EPO gene has efficient anti-tumor effects on colon cancer. Not only can promote hematopoietic stem cell directly producing erythrocyte vaccine, but also can produce tumor antigen vaccine against colon cancer.
Objective To investigate the expression of Bloom syndrome (BLM) helicase and tumor infiltrating dendritic cells (TIDC) in colon cancer tissues and their relationship with the prognosis of patients after surgery. Methods Onehundred and sixty-eight patients with colon cancer who underwent surgical resection in our hospital from June 2014 to August 2016 were selected as the research objects. The specimens of surgically resected colon cancer tissues and adjacent tissues archived by the pathology department were obtained, and the expression of BLM helicase and TIDC density were detected by immunohistochemistry. Pearson was used to analyze the correlation between BLM helicase expression and TIDC density, and the relationship between the expression of BLM helicase and TIDC density and the clinicopathological features of colon cancer was analyzed by using χ2 test or Wilcoxon rank test. The influencing factors of postoperative survival of patients with colon cancer were analyzed by Cox proportional hazards regression model. Results The relative expression of BLM helicase in colon cancer tissues was higher than that in adjacent tissues (1.49±0.33 vs. 1.02±0.17), while the TIDC density was lower than that in adjacent tissues [(9.53±2.36)% vs. (12.36±2.37)%], the differences were statistically significant (P<0.05). Pearson correlation analysis showed that there was a negative correlation between the expression of BLM helicase and TIDC density (r=–0.588, P<0.05). The expression of BLM helicase and TIDC density were correlated with tumor differentiation, clinical stage and lymph node metastasis (P<0.05). That is, those with high expression of BLM helicase and low density of TIDC had low degree of tumor differentiation, late clinical grade, and higher ratio of lymph node metastasis. Sixty-three cases died (37.5%) during the follow-up period (16–60 months, medium follow up 45 months). Log-rank analysis showed that the 5-year cumulative survival rate of the BLM helicase-low expression group was higher than that of the high expression group, and that of the TIDC-low density group was lower than that of the high density group (P<0.05). Cox regression analysis showed that the high expression of BLM helicase, low density of TIDC, low degree of tumor differentiation, late stage and lymph node metastasis were risk factors affecting the postoperative survival of patients with colon cancer (P<0.05). Conclusion The abnormal expression of BLM helicase and TIDC density in colon cancer tissues are related to the degree of differentiation and lymph node metastasis, which are risk factors affecting the long-term survival of patients with colon cancer.
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Objective To investigate the relationship between preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) score, and clinicopathologic features of colon cancer, and to analyze the predictive value of HALP score for postoperative liver metastasis. Methods The clinical data of 163 patients with colon cancer admitted to the 909th Hospital of Joint Logistic Support Force (Dongnan Hospital of Xiamen University) from January 2018 to December 2019 were retrospectively analyzed. According to the occurrence of postoperative liver metastasis, the patients were divided into metastatic group (n=35) and non-metastatic group (n=128). The correlation between preoperative HAPL score and clinicopathologic features of colon cancer was analyzed. The predictive value of HALP score for postoperative liver metastasis of colon cancer was analyzed by using receiver operating characteristic (ROC) curve. The risk factors of liver metastasis after colon cancer surgery were analyzed by using univariate and multivariate logistic analysis. Kaplan-Meier risk curve was drawn, and log-rank test was used to analyze the predictive value of different HALP score for postoperative liver metastasis. Results HALP score were decreased in patients with maximum tumor diameter ≥5 cm, preoperative carcinoembryonic antigen (CEA) ≥5 μg/L, serous membrane and extrasserous infiltration, lymph node metastasis and vascular invasion, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that HALP score [OR=1.467, 95%CI (1.253, 1.718), P<0.001], maximum tumor diameter [OR=3.476, 95%CI (1.475, 5.358), P=0.013], preoperative CEA level [OR= 6.197, 95%CI (2.436, 6.248), P=0.005], and lymph node metastasis [OR=2.593, 95%CI (1.667, 6.759) , P=0.003] were risk factors for postoperative liver metastasis of colon cancer. ROC curve analysis showed that the area under the curve of HALP score for predicting liver metastasis after colon cancer surgery was 0.908 (0.841, 0.974), the maximum value of the Youden index was 0.738, the optimal cut-off value of the HALP score was 35.5, the sensitivity was 0.852, the specificity was 0.886. Kaplan-Meier risk curve showed that the risk of early postoperative liver metastasis in the low HALP score group was higher than that in the high HALP score group (χ2=8.126, P=0.004). Conclusion Low HALP score in patients with colon cancer is associated with adverse prognosisi related pathological features, and is an influential factor for postoperative liver metastasis of colon cancer, and has predictive value for patients with postoperative liver metastasis of colon cancer.
Objective To investigate the role of long non-coding RNA metastasis-associated in colon cancer 1-antisense RNA （MACC1-AS1）in cisplatin resistant gastric cancer and its possible mechanism. Methods Human gastric cancer cell line BGC823 and cisplatin resistant gastric cancer cell line (BGC823/DDP) were selected as the research objects. BGC823/DDP cells were transfected and divided into negative control group (si-NC group, transfected with si-NC empty plasmid) and MACC1-AS1 gene silencing group (si-MACC1-AS1 group, transfected with si-MACC1-AS1 plasmid). The BGC823 cells were transfected and divided into positive control group (pcDNA-NC group, transfected with pcDNA-NC empty plasmid) and MACC1-AS1 gene overexpression group (pcDNA-MACC1-AS1 group, transfected with pcDNA-MACC1-AS1 plasmid). MTT was used to detect the inhibition and 50% inhibition concentration (IC50). Flow cytometry was used to detect apoptosis. Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of MACC1-AS1, B-lymphoma-2 gene (Bcl-2), Bcl-2 related X gene (Bax), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), protein kinase B (AKT), and phosphorylated AKT (p-AKT). Western blot was used to detect the protein expression levels of Bax, Bcl-2, p-mTOR, mTOR, AKT, and p-AKT. Results The relative expression level of MACC1-AS1 mRNA in BGC823/DDP cells was higher than that in BGC823 gastric cancer cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the si-MACC1-AS1 group cells was lower than that in the si-NC group cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the pcDNA-MACC1-AS1 group cells was higher than that in the pcDNA-NC group cells (P<0.01). The cell growth inhibition rate and IC50 of the si-MACC1-AS1 group were higher than those of the si-NC group (P<0.01). The cell growth inhibition rate and IC50 of the pcDNA-MACC1-AS1 group were lower than those of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the pcDNA-MACC1-AS1 group were significantly higher than those in the pcDNA-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the pcDNA-MACC1-AS1 group were significantly lower than those in the pcDNA-NC group (P<0.01). The apoptosis rate of the pcDNA-MACC1-AS1 group was significantly lower than that of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the si-MACC1-AS1 group were significantly lower than those in the si-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the si-MACC1-AS1 group were significantly higher than those in the si-NC group (P<0.01). The apoptosis rate of the si-MACC1-AS1 group was significantly higher than that of the si-NC group (P<0.01). Conclusions MACC1-AS1 highly expresses in cisplatin resistant gastric cancer cells. Overexpression of MACC1-AS1 regulates AKT/mTOR pathway mediated apoptosis and enhances cisplatin resistance of gastric cancer cells.
ObjectiveTo explore the correlation of BMI and 25 hydroxyvitamin D3 level with colon cancer.MethodsA total of 100 cases who underwent colonoscopy and were excluded from bowel diseases at the physical examination center of the First Hospital of Qinhuangdao from March 2017 to October 2017 were retrospectively selected as the control group. A total of 100 patients who underwent colonoscopy at general surgery or physical examination center and were confirmed to have colon cancer by pathological examination were included in the colon cancer group. The height, weight and body mass index (BMI) were measured in the morning, and the level of 25 hydroxyvitamin D3 (25(OH)D3) was determined by fasting blood sampling.Results① There was no statistical significance in age and 25(OH)D3 level between the two groups (P>0.05), and BMI of the colon cancer group was significantly higher than that of the control group (P<0.05). ② The proportion of overweight and obesity in the colon cancer group was significantly higher than that in the control group (P<0.05), and the proportion of vitamin D deficiency was significantly higher as well (P<0.05). ③ Logistic regression analysis showed that the incidence of colon cancer in patients with vitamin D deficiency was 12.263 times higher than that in patients without vitamin D deficiency, and the incidence of colon cancer in patients with overweight and obesity was 2.215 times higher than that in patients with normal BMI, with statistically significant differences (P<0.05).ConclusionThe incidence of colon cancer in patients with vitamin D deficiency and those with BMI of overweight or obesity is significantly increased.
ObjectiveTo investigate the clinical effect and prognosis of laparoscopic complete mesocolic resection (CME) in the treatment of elderly patients with stage Ⅲ right colon cancer.MethodsClinical data of 280 elderly patients (aged 60 years or older) who underwent stage Ⅲ right hemicolectomy in the First Hospital of Lanzhou University from 2010 to 2015 were collected. Among them, 160 patients underwent laparoscopic CME treatment were set as the observation group, and 120 patients underwent conventional laparotomy were set as the control group. The mean operative time, intraoperative blood loss, postoperative first anal exhaust time, number of lymph nodes dissection, number of positive lymph nodes, length of hospital stay and postoperative complications were compared between the two groups. The postoperative local recurrence rate, distant metastasis rate, 3-year cumulative survival rate and postoperative recurrence risk factors were analyzed.ResultsThere were no statistically significant differences between the observation group and the control group in operative time, number of lymph node dissection, number of positive lymph nodes and postoperative distant metastasis rate (P>0.05). The amount of intraoperative blood loss, postoperative anal first exhaust time, days of hospitalization, and postoperative recurrence rate in the observation group were less or shorter or lower than those in the control group, with statistically significant differences (P<0.05). The 3-year survival rate in the observation group was higher than that in the control group (log-rank χ2 =11.865, P=0.001), and the disease free survival in the observation group was also higher than that in the control group (log-rank χ2=7.567, P=0.006). Logistic regression was used to analyze the cases of postoperative recurrence in the two groups, and it was found that the degree of tumor differentiation, vascular invasion and lymph node metastasis were independent risk factors for postoperative tumor recurrence.ConclusionLaparoscopic CME in the treatment of elderly patients with stage Ⅲ right colon cancer is effective, it is safe and feasible, which can effectively prolong the survival time of patients.
ObjectiveTo compare clinical outcomes between laparoscopic (LAP) and open surgery for non-metastatic colon cancer of T4a stage.MethodsWe retrospectively analyzed clinical data of non-metastatic colon cancer patients of T4a stage with confirmed pathological results who underwent curative resection in Peking Union Medical College Hospital between January 2011 and December 2017. These patients were allocated into LAP group (n=107, underwent laparoscopic radical operation) and open group (n=52, underwent open surgery).ResultsThere were no significant difference in operating time, number of lymph nodes harvested, number of positive lymph nodes, incidence of complications within 30 days, and Clavien-Dindo grading between the LAP group and open group (P>0.05), but intraoperative blood loss, postoperative exhaust time, and postoperative hospital stay in the LAP group were less than (shorter than) those of the open group (P<0.05).ConclusionLaparoscopic approach for non-metastatic colon cancer of T4a stage is safe and feasible, and it has advantages including less intraoperative blood loss, faster recovery, and shorter hospital stay.
