Objective To study effect of carcinoembryonic antigen (CEA) positive targeted lymphocytes on gastric cancer cells in vitro and in vivo. Methods The peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of healthy volunteers. The recombinant vector anti-CEA-scFv-CD3ζ-pcDNA3.0 was transfected into the PBMCs by lipofectamine 2000, by this means, the CEA special lymphocytes were obtained. Meanwhile, the PBMCs transfected with empty plasmid pcDNA3.0 were used as control (empty vector lymphocytes). The different lymphocytes and gastric cancer cells (CEA positive KATOⅢ gastric cancer cells and CEA negative BGC-823 gastric cancer cells) were co-cultured, then the ability to identify the gastric cancer cells and it’s effect on apoptosis of gastric cancer cells were observed at 24 h or 36 h later respectively. The CEA special lymphocytes and empty vector lymphocytes were injected by the tail vein of nude mice bearing gastric cancer cells, then it’s effect on the tumor was observed. Results ① The CEA special lymphocytes could strongly identify the KATOⅢ gastric cancer cells (identification rate was 72.3%), which could weakly identify the BGC-823 gastric cancer cells (identification rate was 7.8%). ② The apoptosis rate of the co-culture of CEA special lymphocytes and KATOⅢ gastric cancer cells was significantly higher than that of the co-culture of empty vector lymphocytes and KATOⅢ gastric cancer cells (P=0.032), which had no significant difference between the co-culture of CEA special lymphocytes and BGC-823 gastric cancer cells and the co-culture of empty vector lymphocytes and BGC-823 gastric cancer cells (P=0.118). ③ The tumor volume of the co-culture of CEA special lymphocytes and KATOⅢ gastric cancer cells was significantly smaller than that of the co-culture of empty vector lymphocytes and KATOⅢ gastric cancer cells (F=5.010, P<0.01) or the co-culture of CEA special lymphocytes and BGC-823 gastric cancer cells (F=4.982, P<0.01), which had no significant difference between the co-culture of CEA special lymphocytes and BGC-823 gastric cancer cells and the co-culture of empty vector lymphocytes and BGC-823 gastric cancer cells (F=1.210, P>0.05). Conclusion CEA special lymphocytes can promote cell apoptosis and inhabit tumor reproduction of CEA positive gastric cancer cells in vitro and in vivo.
ObjectiveTo explore the effect of La-related protein 6 (LARP6) gene on the survival of postoperative patients with gastric cancer, and to explore its relationship with immune cell infiltration.MethodsThe clinical survival information and gene expression information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The relationship between LARP6 gene expression and clinical characteristics of patients were analyzed. Cox proportion hazard regression model was used to find out the prognostic risk factors of gastric cancer patients, and then Kaplan-Meier plotter database was used to verify. Then the correlation between LARP6 gene expression and immunity was proved by Tumor IMmune Estimation Resource (TIMER) immune database.ResultsIn gastric cancer patients, the expression of LARP6 gene was related to pathological stage, T stage, and N stage (P<0.05), but not related to M stage and sex (P>0.05). Multivariate Cox proportion hazard regression analysis showed that age [HR=2.022, 95%CI was (1.287, 3.176), P=0.002] and LARP6 gene expression [HR=1.176, 95%CI was (1.070, 1.293), P<0.001] were prognostic factors. Further verified by Kaplan Meier plotter database, the results also showed that the overall survival (OS) and progression-free survival (PFS) of gastric cancer patients with high expression of LAPR6 gene were worse than those with low expression of LARP6 gene (P<0.001). TIMER database was used to explore the correlation between the expression level of LARP6 gene and immune cell infiltration in patients with gastric cancer, and the results showed that the expression level of LARP6 gene in gastric cancer patients was positively correlated with the infiltration number of CD4+ T cells and macrophage cell (P<0.001). Log-rank results showed that infiltration number of macrophage cell and LARP6 gene expression were risk factors for clinical prognosis of gastric cancer patients (P<0.05).ConclusionsMacrophage cell andcell and LARP6 gene expression are risk factors for gastric cancer patients. LARP6 may be a new target for the treatment of gastric cancer.
Objective To investigate the clinical effects and safety differences of open surgery and laparoscopy primary lesion resection combined with D2 lymph node dissection in the treatment of elderly patients with advanced gastric cancer. Methods One hundred and forty elderly patients with advanced gastric cancer were chosen and randomly divided into two group including open operative group (70 patients) with primary lesion resection combined with D2 lymph node dissection by open operation and laparoscopic surgery group (70 patients) with primary lesion resection combined with D2 lymph node dissection by laparoscopy; and the operative time, intraoperative bleeding amount, the levels of PaCO2 in operation, liquid diet eating time, postoperative anal exhaust time, postoperative gastric tube indwelling time, postoperative ambulation time, the level of haemoglobin (Hb) after operation, the hospitalization time, the number of lymph node dissection, the survival rate with followed-up and postoperative complication incidence of both groups were compared. Results There was no significant difference in the operative time between 2 groups (P>0.05). The intraoperative bleeding amount, the level of PaCO2 in operation, liquid diet eating time, postoperative anal exhaust time, postoperative gastric tube indwelling time, postoperative ambulation time, the level of Hb after operation and the hospitalization time of laparoscopic surgery group were significantly better than open operative group (P<0.05). The level of PaCO2 in operation of laparoscopic surgery group was significantly higher than open operative group (P<0.05). There were no significant difference in the gastric lymph node dissection number and the peripheral lymph node dissection number of gastric artery between 2 groups (P>0.05). There were no significant difference in the survival rates between the 2 groups after 3-year followed-up (P>0.05). The complication incidence after operation of laparoscopic surgery group was significantly lower than open operative group (P<0.05). The quality of life scores of patients in laparoscopic surgery group were significantly higher than those in open operative group on 7 days and in 3 months after operation, and the difference were statistically significant (P<0.05). Conclusion Compared with open operation, primary lesion resection combined with D2 lymph node dissection by laparoscopy in the treatment of elderly patients with advanced gastric cancer can efficiently possess the advantages including minimally invasive, shorter recovery time and less postoperative complications.
ObjectiveTo explore the influence of different radiation doses of 125Ⅰseed on human poorly differentiated gastric cancer cells (BGC823). MethodsSixty four male nude mice of BLAB nu/nu inoculated with human poorly differentiated gastric cancer cells (BGC823) were took as animal models. When tumors of nude mice grew to 0.7-1.2 cm, the nude mice were randomly divided into blank control group, low dose group, middle dose group, and high dose group (n=16). The tumors of nude mice in blank control group were implanted with blank seed, but tumors of nude mice in low dose group, middle dose group, and high dose group were implanted with 125Ⅰseed (the radiation doses of 3 groups were 1.48×10-7 Bq, 2.22×10-7 Bq, and 2.96×10-7 Bq respectively). Four nude mice of 4 groups were randomly collected to measure the tumor volume and weight before implantation, and on 7, 14, 21, and 28 days after implantation, but apoptosis rates and expression levels of cyclinE mRNA were measured on 14 days and 28 days after implantation, by using flow cytometer and semi quantitative RT-PCR method respectively. Results①Except for the blank control group, the tumor volume and weight decreased over time in low dose group, middle dose group, and high dose group. The tumor volume and weight in blank control group were higher than those of other 3 groups on 7, 14, 21, and 28 days after implantation (P < 0.05);in addition, on 28 days after implantation, tumor volume and weight in low dose group were lower than those of middle dose group and high dose group (P < 0.05).②On 14 days and 28 days after implantation, the apoptosis rates of blank control group were lower than those of other 3 groups (P < 0.05), but expression levels of cyclinE mRNA were all higher than those of other 3 groups (P < 0.05). In addition, on 28 days after implantation, apoptosis rate of low dose group was higher than both of middle dose group and high dose group (P < 0.05), but expression level of cyclinE mRNA was lower (P < 0.05). Compared with 14 days in the same group, except for the blank control group (P > 0.05), the apoptosis rates in other 3 groups on 28 days were higher (P < 0.05), with the lower expression levels of cyclinE mRNA (P < 0.05). Conclusions125Ⅰseed in organizational implantation can effectively inhibit the expression of cyclinE mRNA and the growth of human poorly differentiated gastric cancer tissue. Compared with doses of 2.22×10-7 Bq and 2.96×10-7 Bq of 125Ⅰ, low dose (1.48×10-7 Bq) contributes to the apoptosis of human poorly differentiated gastric cancer cells (BGC823).
Objective To assess safety and feasibility of laparoscopic gastrectomy in the elderly with gastric cancer. Methods From January 2010 to September 2014, 146 elderly (age ≥65 years old) patients with gastric cancer underwent radical operations in the Department of General Surgery, Guangdong Academy of Medical Sciences and Guangdong General Hospital were collected, then were divided into a laparoscopy-assisted radical gastrectomy (LAG group, n=40) and an open radical gastrectomy (OG group, n=106) according to the operative mode. The differences of intraoperative and postoperative situation, and the postoperative complications were analyzed between the LAG group and the OG group. Results ① The age, gender, body mass index, albumin, ASA grade, tumor location, differentiation degree, TNM stage, radical gastrectomy, and digestive tract anastomosis had no significant differences between the LAG group and the OG group (P>0.05). ② None of the patients died during the operative period and there was no significant difference in the mean number of retrieved lymph nodes between these two groups (P>0.05). In the aspects of the intraoperative blood loss, the first flatus time or the first feeding time, and the postoperative hospitalization stay in the LAG group were significantly less than those in the OG group (P<0.05). For the operative time, the OG group showed a distinctive advantage with a significantdifference than the LAG group (P<0.05). ③ The rate of postoperative complication in the LAG group and OG group was 10.0% (4/40) and 15.1% (16/106) respectively, and the difference was not significant (χ2=0.64, P=0.591), the grade of the Clavien-Dindo complications had no significant difference (χ2=0.63, P=0.592). ④ None of the patients died following operation in the LAG group and one case died in the OG group because of the respiratory and circulatory failure caused by the pulmonary embolism. Conclusion Preliminary results of limited cases in this study show that LAG in the elderly patients with gastric cancer could reduce intraoperative blood loss, shorten the first flatus time or the first feeding time, and postoperative hospitalization stay, could obtain same radical effect without increasing incidence of postoperative complications as compared with OG, so it is safety and feasible.
ObjectiveTo describe the research progress of long non-coding RNA (lncRNA) and gastric cancer in recent years, and to make reasonable prospect for future research direction.MethodWe collected a large amount of literatures on lncRNA and gastric cancer at home and abroad, and sort out various kinds of lncRNA, to make an in-depth interpretation of the relationship between lncRNA and gastric cancer and the mechanism of action, and then clarified the latest research progress.ResultsAt present, the molecular mechanism of the occurrence and development of gastric cancer had not been fully elucidated, but current studies had shown that lncRNA (H19, HOTTIP, UCA1, MEG3, MALAT1, HULC, HOTAIR, GAPLINC, and so on) had regulatory effects at multiple levels such as epigenetics, transcription, translation, chemoresistance, and more and more lncRNA had been discovered closely related to gastric cancer.ConclusionlncRNA is closely related to the occurrence and development of gastric cancer and may be a key target for the treatment of gastric cancer in the future.
ObjectiveTo compare the clinical recovery and immune response between laparoscopic-assisted and open D2 gastrectomy for advanced gastric cancer. MethodsThe clinical data of 53 patients with advanced gastric cancer from January 2012 to October 2013 were studied prospectively. According to random number table, patients were randomly divided into laparoscopic-assisted group(LA group, n=27) and open operation group(OO group, n=26). Operative time, blood loss, time to passage of flatus, time to resume soft diet, after bed time, postoperative hospital stay, and number of retrieved lymph nodes were compared respectively between the two groups. The changes in CD3, CD4+, CD8+, IgG, IgA, IgM, and CRP were examined respectively by using flow cytometry and immunoturbidimetric assays on the preoperative day 1, and on the postoperative day 1 and 7. ResultsThe operative time was longer significantly in LA group than that in OO group(P < 0.05). The mean blood loss, the first flatus time, after bed time, and postoperative hospital stay in the two groups were all different statistically(P < 0.05), and all were better in LA group. However, the mean number of retrieved lymph nodes and the time to resume soft diet were not significantly different in the two groups(P > 0.05). On the day 1 and 7 after operation, the CD3, CD4+, and CD8+ significantly decreased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). On the day 1 after operation, the levels of IgG, IgA, and IgM significantly decreased as compared with those preoperatively in two groups(P < 0.05). Those immunoglobulin in LA group recovered to close to the level before surgery, but in OO group sustained lower level(P < 0.05). On the day 1 and 7 after operation, CRP level significantly increased as compared with those preoperatively in two groups(P < 0.01, P < 0.05). Those changes of above index were not significantly different between the LA group and OO group on the day 1 after operation(P > 0.05). All index recovered gradually in the two groups on the day 7 after operation and were better in LA group(P < 0.05, except IgA). ConclusionLaparoscopic radical gastrectomy for advanced gastric cancer resulted in a quicker clinical recovery and a lesser depression to the perioperative cellular and humoral immune function.
ObjectiveTo investigate the clinical characteristics of thoracic esophageal-gastric cancer (TEGC) and the safety and effectiveness of secondary reconstruction of thoracic and gastrointestinal tract after esophageal and preventriculus cancer (esophagogastric junction) surgery.MethodsThe clinical data of 353 patients with esophageal and preventriculus cancer who underwent endoscopic review from July 2007 to December 2019 were retrospectively analyzed. A total of 31 (8.78%) patients with relapsed or recurrent TEGC were found, including 24 males and 7 females with a mean age of 58.5 years (range: 42 to 68 years). There were 18 (58.06%) patients of adenocarcinoma and 13 (41.94%) squamous cell carcinoma. All patients underwent TEGC resection and secondary reconstruction of thoracic gastrointestinal tract. Thoracoabdominal computed tomography (CT) and upper gastrointestinal imaging (GI) were performed during follow-up, and gastroscopy was performed for suspected patients. All the patients were followed-up till death or December 30, 2019. The survival rate was calculated by Kaplan-Meier method, and the survival was analyzed using the log-rank test. ResultsThirty-one patients underwent thoracic esophagectomy and gastric cancer resection, and then reconstruction of the thoracic and gastrointestinal tract. Eight patients underwent residual gastroesophageal thoracic anastomosis, 13 patients colon esophagectomy, 6 patients jejunal esophagectomy (1 patient esophago-jejunal Roux-en-Y anastomosis), and 4 patients cervical esophagogastric anastomosis. The mean operation time and intraoperative blood loss were 404.8 (340-475) min and 378.4 (180-620) mL. The postoperative complications ocurred in 4 patients, including 3 patients of pulmonary infection and 1 patient of cervical incision infection. The mean hospital stay was 17.1 (14-21) d. All patients were followed up, the median survival time of 11 patients in stage Ⅰ-ⅡA was 25 (19.8-35.0) months and 20 patients in stage ⅡB-ⅢA was 16 (12.5-19.5) months. There was a significant difference between the two groups (χ2=7.840 8, P<0.01).ConclusionPostoperative relapsed and recurrent TEGC occurs after the surgery for esophageal and preventriculus cancers, most of which are caused by metachronous gastric cancer or residual esophageal carcinoma recurrence which leads to invasion of the thoracic and gastric wall. Regular endoscopic review is the main method after operation. It is technically safe and feasible to reconstruct the thoracic and esophageal digestive tract in patients with TEGC after reoperation, which can benefit the survival of patients.
Objective To detect the expression of copine 1 (CPNE1) in the gastric cancer (GC) and investigate its association with prognosis. MethodsThe clinicopathologic data of 121 patients who underwent radical gastrectomy in the Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army from March 2017 to December 2018 were retrospectively collected. The protein expression of CPNE1 in the GC tissues was detected by immunohistochemical (IHC) staining, and its association with prognosis was analyzed. GC tissues and adjacent tissues samples from 16 patients in the same time were prospectively collected, and the mRNA and protein expressions of CPNE1 were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Multivariate Cox proportional hazards regression model was used to analyze the prognostic factors of GC patients. ResultsIHC staining results showed that the CPNE1 was mainly expressed in the cell membrane and cytoplasm of gastric epithelial cells, and the color showed different degrees of brown. Among the 121 patients, 70 (57.9%) had high CPNE1 protein expression and 51 (42.1%) had low CPNE1 protein expression. The RT-qPCR and WB results of 16 pairs of fresh tissue specimens showed that the expression levels of CPNE1 mRNA and protein in the GC tissues were higher than those in the corresponding adjacent tissues (CPNE1 mRNA mean value: 1.451 vs. 1.100, P=0.048; CPNE1 protein mean value: 0.995 vs. 0.521, P=0.001). The multivariate Cox proportional hazards regression analysis showed that the high protein expression of CPNE1 [HR (95%CI)=1.931 (1.123, 3.321), P=0.017] was the risk factor affecting the prognosis of the patients with GC. ConclusionCPNE1 highly expresses in GC tissues and is associated with a poor prognosis in patients with GC, and it may be a potential tumor biomarker.
ObjectiveTo describe the research status of programmed death receptor protein 1 (PD-1) and its ligand(PD-L1) inhibitors in advanced gastric cancer and to understand the key issues of PD/PD-L1 inhibitors in order to provide atheoretical basis for future research.MethodThe classical and up to date literatures on the immunotherapy, especially thePD-1/PD-L1 inhibitors in the advanced gastric cancer were reviewed.ResultsThe PD-1/PD-L1 inhibitors were the hot spot in the current research of tumor immunotherapy. The pembrolizumab and nivolumab were the commonly immunosuppressive agents in the current clinical research, which had also achieved the great success in the clinical research of gastriccancer since it was shown the good results in the malignant melanoma and hematological malignancies. In some clinical studies, the PD-1/PD-L1 inhibitors treatment showed the longer overall survival than the conventional chemotherapy, especially in the patient with positive PD-1. However the study still had some issues to be solved, such as no accurate prediction for the beneficiary population, the tumor hyperprogression and so on. It was gratifying that the current research on the basic research of tumor immunity was increasing, then it provided a theoretical support for solving these problems.ConclusionsTumor immunosuppressive therapy such as PD-1/PD-L1 inhibitors brings a new idea in treatment of patients with advanced gastric cancer. Although there are still many problems need to be solved in clinical research, it is believed that PD-1/PD-L1 inhibitors will become one of key players in treatment of patients with advanced gastric cancer in the further study.