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.
ObjectiveTo investigate the most appropriate culture time with the action of EGF in colon cancer stem cells enrichment by suspension culture.MethodsDLD-1 cells were cultured in serum-free medium containing 20 ng/mL EGF to generate spheroid cells. The time gradient was set to 10 d, 20 d, 30 d and 40 d, the cell proportion of CD133+, CD44+ and CD133+CD44+ were confirmed by flow cytometery. The ability of self-renewal was detected by the sphere forming assay and the limited dilution assay, and the in vitro tumorigenicity of the cells was detected by the colony formation assay.ResultsIn the 30 d group, the proportion of CD133+ and CD133+ CD44+ cells were significantly higher than those in the other groups (allP<0.05), the CD44+ cell was higher than that in the 20 d group (P<0.05), but there was no significant difference with the other two groups (P>0.05). The results of the limited dilution assay and the colony formation assay, the number of spheres in the 30 d or 40 d group was the highest among the 4 groups, and there was no statistical difference between the 30 d group and 40 d group (P>0.05), with statistically significant difference between the 30 d, 10 d and 20 d groups (all P<0.05). The results of the sphere forming assay and the self-renewal ability of 30 d group was significantly higher compared with other groups (all P< 0.05).ConclusionThe cancer stem cells could be enriched more efficiently by suspension culture using 20 ng/mL EGF for 30 days.
ObjectiveTo investigate the influence of surgical treatment on early postoperative anal function in left colon cancer patients with acute complete obstruction. MethodsThe clinical data of left colon cancer patients with acute complete obstruction were retrospectively chosen from January 2017 to June 2020 in Yibin Second People’s Hospital. The patients were grouped according to the treatment plan including emergency operation group (54 cases), stent+operation group (46 cases) and stent+neoadjuvant chemotherapy (NAC)+operation group (44 cases). The anal function was evaluated at 4 weeks, 1 month and 6 months after operation, and quality of life was evaluated at 12 months after operation. Unconditional logistic regression model was used to explore the factors influencing early postoperative anal function injury. Results The proportion of open surgery in the emergency operation group was statistically higher than the stent+operation group and stent+NAC+operation group (P<0.05). The low anterior rectum resection syndrome (LARS) score at 4 weeks after operation of the emergency operation group was statistically higher than those of the stent+operation group and stent+NAC+operation group (P<0.05). However there was no statistical difference in LARS score at 1 month and 6 months after operation among the three groups (P>0.05). The score of social function in the emergency operation group at 12 months after operation was statistically lower than those of the stent+operation group and stent+NAC+operation group (P<0.05). Multivariate logistic regression analysis showed that body mass index (BMI) ≥24 kg/m2, emergency operation, and Eastern Collaborative Oncology Group (ECOG) score were the risk factors for early postoperative anal dysfunction in the left colon cancer patients with acute complete obstruction (P<0.05). ConclusionsLeft colon cancer patients complicated with acute complete obstruction who only received emergency surgery, BMI≥24 kg/m2, or one score of ECOG are more likely to have functional impairment, and the quality of life of those patients underwent emergency surgery alone is decreased. In addition, the stent placement at the obstruction site should be helpful to avoid the above problems.
ObjectiveTo investigate the feasibility and safety of the double cavity casing negative pressure drainage by inside and outside of the intestine in the primary resection and anastomosis of left colon cancer combined with acute obstruction. MethodsEighty-one cases of left colon cancer combined with acute obstruction who underwent surgeries in our hospital from January 2009 to December 2012 were collected prospectively, and were divided into one-stage surgery group (n=41) and control group (n=40). Cases of one-stage surgery group received double cavity casing negative pressure drainage by inside and outside of the intestine in the primary resection and anastomosis, and cases of control group underwent two-stage surgeries. Comparison of operation time, blood loss, time of anal exhaust after operation, hospital stay, hospital expense, and incidence of complication between the 2 groups was performed. ResultsThere were no significant difference in the operation time[(166±19) minutes vs. (173±23) minutes], blood loss[(253±42) mL vs. (273±50) mL], and time of anal exhaust after operation[(3.24±0.73) days vs. (3.50±0.95) days]beeween one-stage surgery group and control group, but hospital stay[(15.1±2.3) days vs. (23.1±4.1) days]and hospital expense[(3.70±0.68) ×105 yuan vs. (5.77±0.95) ×105 yuan]of one-stage surgery group were lower than those of control group (P<0.05). In addition, there were no significant difference in the incidences of wound infection[7.3% (3/41) vs. 10.0% (4/40)], intraabdominal infection[4.9% (2/41) vs. 10.0% (4/10)], pulmonary infection[12.2% (5/41) vs. 15.0% (6/40)], and anastomotic leakage[2.4% (1/41) vs. 5.0% (2/40)]beeween one-stage surgery group and control group (P>0.05). All of the cases were followed up for 1-36 months, and the median time were 22 months. There were no significant difference in the mortality[0 (0/41) vs. 2.5% (1/40)], recurrence rate[2.4% (1/41) vs. 5.0% (2/40)], and metastasis rate[7.3% (3/41) vs. 10.0% (4/40)]beeween one-stage surgery group and control group too (P>0.05). ConclusionIn the case of negative pressure drainage of double cavity casing, underwent decompression of the small bowel, and irrigation of colon, the primary resection and anastomosis of left colon cancer combined with acute obstruction was safe and feasible.
Objective To determine feasibility of texture analysis of CT images for the discrimination of hepatic epithelioid hemangioendothelioma (HEHE) and liver metastases of colon cancer. Methods CT images of 9 patients with 19 pathologically proved HEHEs and 18 patients with 38 liver metastases of colon cancer who received treatment in West China Hospital of Sichuan University from July 2012 to August 2016 were retrospectively analyzed. Results Thirty best texture parameters were automatically selected by the combination of Fisher coefficient (Fisher)+classification error probability combined with average correlation coefficients (PA)+mutual information (MI). The 30 texture parameters of arterial phase (AP) CT images were distributed in co-occurrence matrix (22 parameters), run-length matrix (1 parameter), histogram (4 parameters), gradient (1 parameter), and autoregressive model (2 parameters). The distribution of parameters in portal venous phase (PVP) were co-occurrence matrix (18 parameters), run-length matrix (2 parameters), histogram (7 parameters), gradient (2 parameters), and autoregressive model (1 parameter). In AP, the misclassification rates of raw data analysis (RDA)/K nearest neighbor classification (KNN), principal component analysis (PCA)/KNN, linear discriminant analysis (LDA)/KNN, and nonlinear discriminant analysis, and nonlinear discriminant analysis (NDA)/artificial neural network (ANN) was 38.60% (22/57), 42.11% (24/57), 8.77% (5/57), and 7.02% (4/57), respectively. In PVP, the misclassification rates of RDA/KNN, PCA/KNN, LDA/KNN, and NDA/ANN was 26.32% (15/57), 28.07% (16/57), 15.79% (9/57), and 10.53% (6/57), respectively. The misclassification rates of AP and PVP images had no statistical significance on the misclassification rates of RDA/KNN, PCA/KNN, LDA/KNN, and NDA/ANN between AP and PVP (P>0.05). Conclusion The texture analysis of CT images is feasible to identify HEHE and liver metastases of colon cancer.
Objective To investigate whether miRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colon cancer cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway. Methods miR-34a expression levels were detected in colon cancer tissues and colon cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Computational search, functional luciferase assay, and Western blotting method were used to demonstrate the downstream target of miR-34a in colon cancer cells. Cell viability was measured with cell counting kit-8. Apoptosis and macroautophagy of colon cancer cells were analyzed by flow cytometry and transmission electron microscopy, and expressions of Beclin1 and LC3Ⅱ protein were detected by Western blotting method. Results Expression of miR-34a was significantly reduced while expressions of TGF-β and Smad4 mRNA were increased in colon cancer patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a expression levels and increased TGF-β and Smad4 expression levels in both parental cells and the OXA-resistant colon cancer cells. Activation of macroautophagy contributed to OXA resistance in colon cancer cells. Expression levels of Smad4 and miR-34a in colon cancer patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in colon cancer cells. Conclusion miR-34a mediates OXA resistance of colon cancer by inhibiting autophagy via the TGF-β/Smad4 pathway.
摘要:目的：回顾性分析比较左半结肠癌急性梗阻一期手术与同期左半结肠癌根治术患者的手术临床资料,探讨左半结肠癌急性梗阻一期手术的可行性。方法： 回顾性将我中心2004年1月至2007年3月收治的59例左半结肠癌急性梗阻一期手术病例分为A组,将同期226例左半结肠癌根治术病例分为B组,比较两组之间清除淋巴结数、术后进食时间、吻合口漏发生率、肺部感染率、切口感染率、住院时间、复发和转移率。结果： 在上述观察指标中,在A组分别为（133±18）枚,（36±09）d,1/59（169%）,4/59（678%）,2/59（339%）,(124±09)d,6/59（1017%）；B组分别为128±15,32±08,1/226（044%）,8/226（354%）,6/226（265%）,117±15,23/226（1062%）；经统计学处理,两组间没有显著性差异。结论：术中合理应用结肠灌洗,良好的手术技巧,术后积极辅助治疗,左半结肠癌急性梗阻一期手术是安全可行的,可避免二次手术带给患者的痛苦,术后并发症也无明显增加。Abstract: Objective: Retrospective analysis and comparison of acute obstruction of left colon cancer onestage surgery and the same period a radical mastectomy in patients with left colon cancer surgery clinical data,To study the possibility of acute obstruction of left colon cancer onestage surgery. Methods:A retrospective of my center from January 2004 to March 2007 were treated 59 cases of acute obstruction of left colon cancer onestage surgery patients were divided into A group, will be left over the same period 226 cases of radical resection of colon cancer patients were divided into group B, compare the number of lymph nodes removed between the two groups, after the consumption of time, the incidence of anastomotic leakage, pulmonary infection, incision infection, length of stay, recurrence and metastasis rate. Results: Observed in the above indicators, in the A group were 133±18,36±09,1/59 (169%),4/59 (678%), 2/59 (339%),124±09,6/59 (1017%); B group were 128±15,32±08,1/226 (044%), 8/226 (354%), 6/226 (265%), 117±15,23/226 (1062%); Statistical analysis between the two groups there was no significant difference. Conclusion: Rational application of intraoperative colonic irrigation, good surgical technique, postoperative adjuvant treatment of active, acute obstruction of left colon cancer onestage surgery is a safe and feasible, it may avoid the second operation to bring the patient’s pain, postoperative complications and no increased significantly.
ObjectiveTo summarize the experience of diagnosis and treatment of a patient with liver and lung metastasis and retroperitoneal metastasis from right colon cancer.MethodsA retrospective analysis of a patient with liver, lung, and retroperitoneal metastasis from right colon cancer who received treatment at The First Affiliated Hospital of Kunming Medical University in August 2016 was conducted. In order to provide reference for domestic doctors to treat advanced colorectal cancer.ResultsAfter receiving several cycles of chemotherapy and three surgical resections of the primary and metastatic lesions before the MDT, the patient again found a retroperitoneal mass. After discussions of Department of Imaging, Oncology, Radiotherapy, and Gastrointestinal and Hernia Surgery, we thought that, at present, the treatment of the patient was mainly surgery and oral chemotherapy. So the patient underwent retroperitoneal tumor resection+abdominal adhesion release, and had been interviewed for 3 months. No recurrence or metastasis was found during follow-up.ConclusionThe therapy of liver-lung metastasis and retroperitoneal metastasis in right colon cancer are mainly based on surgical resection of lesions, postoperative combined with radiotherapy and chemotherapy, molecular targeted therapy, and postoperative monitoring of CEA changes.
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.
Objective To explore the relationship between Epstein-Barr virus (EBV) infection with serum human kissin-1 (KISS-1) and matrix metalloproteinase 2 (MMP2) levels and prognosis in patients with colon cancer. Methods A total of 86 colon cancer patients who were hospitalized in our hospital from April 2015 to April 2016 were selected as the colon cancer group; in the same period, 84 cases of physical examination person in our hospital were selected as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to test colon cancer patients for EBV DNA, and divided the patients into EBV DNA negative group and EBV DNA positive group according to the test results. Enzyme-linked immunosorbent (ELISA) method was used to detect serum KISS-1 and MMP2 levels. Pearson method was used to analyze the correlation between serum KISS-1 and MMP2 levels in patients with colon cancer infected with EBV. The survival curve was drawn by Kaplan-Meier method, and the relationship between EBV infection and prognosis of colon cancer patients was analyzed by log-rank test. Multivariate Cox regression analysis were used to analyze the factors affecting the prognosis of colon cancer patients. Results Compared with the control group, the positive rate of EBV DNA in the colon cancer group was higher (χ2=21.854, P<0.001). The EBV DNA positive rate of patients with lymph node metastasis, TNM stage Ⅲ–Ⅳ, tumor low differentiation and tumor infiltration T3–T4 was higher than those without lymph node metastasis, TNM stage Ⅰ–Ⅱ, tumor high/medium differentiation and tumor infiltration T1–T2 (P<0.05). Compared with the EBV DNA negative group, the serum KISS-1 level of the EBV DNA positive group decreased, and the MMP2 level increased (P<0.001). There was a negative correlation between serum KISS-1 and MMP2 levels in colon cancer patients with EBV infection (r=–0.510, P<0.001). The 5-year survival rates of colon cancer patients in the EBV DNA-negative group and the EBV DNA-positive group were 52.94% (27/51) and 14.29% (5/35), respectively, the difference between the two groups was statistically significant (χ2=13.274, P<0.001). EBV infection, MMP2 high expression, and lymph node metastasis were independent risk factors affecting the prognosis of colon cancer patients (P<0.05), and KISS-1 low expression was a protective factor affecting the prognosis of colon cancer patients (P<0.05). Conclusions EBV infection is closely related to the progression and prognosis of colon cancer. The down-regulation of KISS-1 and the up-regulation of MMP2 may be related to EBV infection.