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Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.
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Objective:To explore the risk factors of lymph node metastasis (LNM) in early gastric cancer (ECG), and establish a risk-prediction model based on LNM.Method:Four hundred and twenty-seven EGC patients undergoing curative radical gastrectomy were enrolled in this study. The risk factors for LNM of ECG were analyzed with Logistic regression. LNM risk was stratified and risk-predicting model was established. The risk-predicting model was measured by area under ROC curve. According to the same standard, clinical data of 133 patients with EGC who underwent radical surgery were selected for external verification of the model.Results:The frequency of LNM was 13.3% (32/427) in EGC patients. The LNM ratio of intramucosal carcinoma and submucosal carcinoma was 1.3% (3/237), 15.3% (29/190) respectively. Ulcer presence, tumor size >2 cm, undifferentiated tumor, submucosal invasion, neural invasion, and vascular tumor thrombus were significantly associated with LNM in EGC patients ( χ2=3.408, 16.379, 4.808, 29.804, 25.305, 47.120, respectively P<0.05). Multivariate analysis suggested that ulcer presence, tumor size >2 cm, depth of invasion, neural invasion, and vascular tumor thrombus were independent predictors of LNM in EGC patients, ( OR=0.326, 2.924, 11.824, 13.047, 7.756, respectively P<0.05). LNM predicting model is established, P=e
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Objective:To investigate the expression of KLF11 in gastric cancer tissues and cell lines as well as its effect on proliferation and apoptosis of human gastric cancer cells BGC823.Methods:Sixty pairs gastric cancer tissues and corresponding adjacent tissues were collected. The expression of KLF11 mRNA in gastric cancer tissues and their adjacent tissues was detected by RT-PCR. The expression of KLF11 was detected in gastric cancer cells. KLF11 expression was silenced. The proliferation of cells were detected by using MTT assay. Flow cytometry was used to detect the cell cycle and cell apoptosis rate. Western bloting was used to examine the changes of concentration of proteins associated with cell cycle,cell apoptosis and Wnt/β-catenin signaling pathway related proteins. The activity of Caspase3 enzyme was detected by spectrophotometry.Results:The relative expression of KLF11 mRNA in gastric carcinoma tissues was significantly higher than that of the adjacent tissues ( t=11.38, P<0.05). Its expression was related to tumor size, depth of invasion, lymph node metastasis and TNM clinical stage (all P<0.05). The proliferation of BGC823 cells was significantly suppressed after KLF11 silencing ( F=19.56, P<0.05), and the cell cycle was arrested in G 0/G 1 phase [(41.40%±0.98%) vs. (66.53%±1.01%), F=32.69, P<0.05]. Meanwhile, the apoptosis rate was significantly increased by KFL11 silencing [(41.44%±1.59%) vs. (15.42%±0.86%), F=35.35, P<0.05]. The results of Western blotting revealed that the expression of Bax and Cleaved Caspase3 was significantly increased ( F=23.33, 33.63; both P<0.05), wheras that of β-catenin, Bcl-2, CyclinD1and CyclinE was significantly reduced ( F=22.21, 16.24, 26.75, 33.42; all P<0.05). The activity of Caspase3 enzyme was enhanced ( F=16.56, P<0.05). Conclusion:KLF11 was highly-expressed in gastric cancer tissues and cells, KFL11 silencing could inhibit gastric cancer cells proliferation and induce cell apoptosis via Wnt/β-catenin signaling pathway.
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Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.
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Objective:To investigate the clinically relevant factors of progressive disease (PD) after neoadjuvant therapy for locally advanced gastric cancer.Methods:From Jun 2011 to Mar 2016, 569 patients with locally advanced gastric cancer(cT3/4N0/+ M0) admitted to the Fourth Hospital of Hebei Medical University were retrospectively analyzed .Results:All 569 patients completed neoadjuvant therapy, 59 patients (10.4%) had PD. Univariate analysis showed that tumor size (χ 2=10.091, P=0.001), pathological type (χ 2=4.110, P=0.043), Borrmann type (χ 2=91.941, P=0.001), pre-treatment cT stage (χ 2=7.980, P=0.005) were associated with PD after neoadjuvant therapy for gastric cancer. The results of multi-factor regression analysis showed that pathological type, Borrmann type, pre-treatment cT stage were independent factors influencing the occurrence of PD after neoadjuvant therapy for advanced gastric cancer. The overall survival and progression-free suruival time of patients with PD is significantly shorter than that of patients without PD . Conclusion:The pathological type, Borrmann typing and pre-treatment cT stage are the influencing factors for the occurrence of PD after neoadjuvant treatment in advanced gastric cancer, and the prognosis of PD patients is poor.
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Objective@#To explore the clinical significance of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of patients with locally advanced gastric cancer.@*Methods@#Inclusion criteria: (1) cancer confirmed by gastroscopy and pathology without preoperative anti-tumor treatment; (2) no distant metastases found in preoperative imaging examinations; (3) patients without surgical contraindications and being tolerant to surgery; (4) patients were willing to undergo laparoscopic exploration and abdominal exfoliative cytology examination, and signed informed consent. A retrospective cohort study method was used to collect and analyze the clinicopathological data of 225 patients with advanced gastric cancer based on the above inclusion criteria from a prospective, multicenter, open, randomized controlled phase III clinical trial (registration No. NCT01516944) conducted between February 2012 and December 2018 in The Fourth Hospital of Hebei Medical University, including 162 males and 63 females with age ranged from 23 to 78 years old. Forty-five patients (20.0%) were classified as Borrmann type I to II, and 180 (80.0%) were classified as type III to IV. All the patients underwent laparoscopy and peritoneal lavage cytology under general anesthesia. Laparoscopic exploration sequence: left and right diaphragm→liver and spleen→parietal peritoneum→pelvic cavity→greater omentum, small intestine, mesentery→transverse colon mesentery →stomach. Contents of exploration: (1) with or without ascites; (2) whether metastatic lesions existed in the peritoneum, mesentery, omentum and Douglas pouch; (3) whether metastasis existed on the liver surface; (4) whether the gastric lymph nodes were swollen; (5) whether infiltration occurred on the gastric serosa surface; (6) whether gastric wall was stiff. The left and right subphrenic, the abdominal and pelvic peritoneum, and the mesentery were rinsed with 500 ml of sterilized normal saline. Position of the reverse Trendelenburg was used in the Douglas pouch. The peritoneal lavage fluid under the liver and spleen fossa was collected. Cytological examination was carried out for exfoliative tumor cells. Evaluation criteria: (1) peritoneal metastasis (P): P0 meant no peritoneal metastasis, P1 meant peritoneal metastasis; (2) free peritoneal cancer cells (CY): CY0 meant no cancer cells in peritoneal lavage fluid cytology, CY1 meant cancer cells in peritoneal lavage fluid cytology. The results of patients undergoing laparoscopic exploration combined with abdominal exfoliative cytology, treatment options and prognosis were analyzed. Kaplan-Meier method was used to calculate the survival rate and a survival curve was drawn. Log-rank test was used for survival analysis.@*Results@#After laparoscopic exploration in 225 patients, clinical staging was corrected in 68 (30.2%) patients, of whom 7 (3.1%) downstaged and 61 (27.1%) increased in staging. Of 164 patients evaluated as P0CY0 after the first laparoscopy and peritoneal cytology examination, 126 underwent radical D2 surgery, and the other 38 patients were found to have later local lesions or extensive fusion of local lymph nodes, so then received neoadjuvant chemotherapy. Twenty-nine patients evaluated as P1CY0 or P1CY1 and 32 patients as P0CY1 underwent intraperitoneal hyperthermic chemotherapy+conversion therapy, and then a second laparoscopic exploration was performed to determine the treatment plan. In total, the original treatment regimens were changed after laparoscopic exploration in 99(44.0%) cases. The follow-up period ended in January 2019. The overall 2-year survival rate of 225 patients was 64.0%. As for those who were evaluated as P0CY0, P0CY1 and P1CY0-1 after the first laparoscopic exploration, the 2-year overall survival rate was 70.7%, 65.6% and 24.1%, respectively (P=0.002). The stratified analysis showed that among 180 patients with stage III tumor, after laparoscopic exploration combined with abdominal exfoliative cytology, 125 patients were found to be P0CY0, 28 were P0CY1, and 27 were P1CY0-1, whose 2-year overall survival rates were 70.4%, 64.3%, and 29.6% respectively, and the difference among these 3 groups was statistically significant (P=0.009).@*Conclusion@#Laparoscopic exploration combined with abdominal exfoliative cytology in patients with locally advanced gastric cancer has important clinical guiding significance in improving accurate staging, treatment options and prognosis evaluation, and can avoid non-therapeutic open-close abdominal surgery.
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Objective:To evaluate multislices helical CT (MSCT) on the efficacy and prognosis of preoperative treatment for locally advanced gastric stromal tumors(GIST).Methods:From Oct 2012 to Oct 2014 at the Fourth Hospital of Hebei Medical University 30 patients received MSCT before and after preoperative imatinib treatment to measure the changes of the GIST longest diameter, CT value and tumor volume of the primary lesion. The correlation of Choi score, tumor volume reduction rate and histological efficacy evaluation were analyzed. ROC curve was drew. Kaplan-Meier method was used to draw survival curves, and the overall survival rates under the new classification were calculated.Results:The median time for preoperative treatment was 8 (4 to 14) months. Postoperative pathology showed 4 cases (13%) with mild effects and 3 cases (10%) with low effects. Seventeen cases (57%) with moderate effect and 6 cases (20%) with high effect. Choi score was moderately correlated with histological efficacy evaluation ( R=0.512, P<0.05), and tumor volume reduction rate was strongly correlated with histological efficacy evaluation results ( R=0.620, P<0.05). When the tumor volume reduction rate of 45.83% was used as the effective threshold, the AUC under the ROC curve was the largest, and the sensitivity and specificity were 87.0% and 85.7%, respectively. The 5-year overall survival rate of 30 patients was 87%. According to the new volume grading standard, the 5-year survival rates of the effective group and the ineffective group were 95% and 67% ( P<0.05) , respectively . Conclusion:MSCT measurement of Choi score and tumor volume reduction rate can evaluate the efficacy of preoperative treatment in patients with locally advanced GIST, and tumor volume measurement standards also have certain value in prognosis perdiction.
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Objective:To explore the exfoliative value of multi-slice CT (MSCT) on conversion therapy of gastric cancer patients with positive evaluation cytology (P 0CY 1) . Methods:A total of 36 P 0CY 1 gastric cancer patients receiving conversion therapy in a prospective, single-center, phase Ⅱ clinical trial were enrolled. MSCT examinations were performed before and after conversion therapy. Its solid tumor efficacy evaluation criteria (response evaluation criteria in solid tumors, Recist) 1.1 score and tumor volume reduction rate were evaluated. The Spearman correlation test was used to analyze the correlation between Recist 1.1 score and tumor volume reduction rate and the results of conversion therapy. The ROC curve was used to determine the defined value of the volume reduction rate to identify the effectiveness of conversion therapy, and formulate new grading standards. Results:According to the conversion of free cancer cells in the abdominal cavity , 15 of 36 patients had successful conversion therapy and 21 had failed. The rate of tumor volume reduction in the successful and failed conversion groups was 44.38%±37.86% and -54.96%±156.92%, respectively( P=0.016). The Recist 1.1 score was moderate correlated with the results of conversion therapy ( R=0.540, P=0.001), and the rate of tumor volume reduction was significantly correlated with the results of conversion therapy ( R=0.657, P<0.001). When the tumor volume reduction rate of 26.27% was used as the effective threshold for evaluating conversion therapy, the AUC under the ROC curve was the largest, and the sensitivity and specificity were 80.0% and 85.7%, respectively. Conclusion:Both the MSCT-measured Recist 1.1 score and the tumor volume reduction rate can be used to evaluate the efficacy of conversion therapy in patients with pure exfoliated cytology-positive gastric cancer, and CT tumor volume measurement significantly correlates with conversion therapy results.
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Objective@#To evaluate the efficacy of chemotherapy and estimate the prognosis of patients with progressive gastric cancer.@*Methods@#A total of 116 patients from a prospective, multicenter, open-label, and randomized phase Ⅲ clinical trial were enrolled in the Fourth Hospital of Hebei Medical University from Dec 2012 to Jun 2015. Pre- and two weeks after neoadjuvant chemotherapy, multi-slice spiral CT was performed to calculate the percentage change of the longest diameter and tumor volume to evaluate the Recist score and tumor volume reduction rate. Spearman correlation test was used to analyze the correlation of post-volume reduction rate, Recist 1.1 score, and tumor regression grade. The ROC curve was used to find a defined value for the volume reduction rate that identifies the effectiveness of chemotherapy and assign a new grading standard. The survival curve was drawn by Kaplan-Meier method, and the relationship between the effective survival group and the ineffective group under the new grading standard was observed.@*Results@#The Recist score was moderately correlated with the pathological tumor regression scale, and the volume reduction rate after chemotherapy was strongly correlated with the pathological regression scale (R=0.579). When the tumor volume reduction rate was 12.5% as an effective threshold for evaluating neoadjuvant chemotherapy, the AUC under the ROC curve was the largest, with sensitivity and specificity of 81.1% and 75.9%, respectively. The median survival time of the effective and ineffective groups was 25 months and 18 months, respectively, and the 2-year survival rate was 73.3% and 51.2%. The total survival time of patients with effective chemotherapy was significantly longer than those with ineffective chemotherapy (P=0.003 6).@*Conclusion@#The volume measurement grading standard can predict the pathological regression of neoadjuvant chemotherapy patients, and it is superior to the Recist score in the evaluation of efficacy and prognosis.
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Objective To evaluate the efficacy of chemotherapy and estimate the prognosis of patients with progressive gastric cancer.Methods A total of 116 patients from a prospective,multicenter,open-label,and randomized phase Ⅲ clinical trial were enrolled in the Fourth Hospital of Hebei Medical University from Dec 2012 to Jun 2015.Pre-and two weeks after neoadjuvant chemotherapy,multi-slice spiral CT was performed to calculate the percentage change of the longest diameter and tumor volume to evaluate the Recist score and tumor volume reduction rate.Spearman correlation test was used to analyze the correlation of post-volume reduction rate,Recist 1.1 score,and tumor regression grade.The ROC curve was used to find a defined value for the volume reduction rate that identifies the effectiveness of chemotherapy and assign a new grading standard.The survival curve was drawn by Kaplan-Meier method,and the relationship between the effective survival group and the ineffective group under the new grading standard was observed.Results The Recist score was moderately correlated with the pathological tumor regression scale,and the volume reduction rate after chemotherapy was strongly correlated with the pathological regression scale (R =0.579).When the tumor volume reduction rate was 12.5％ as an effective threshold for evaluating neoadjuvant chemotherapy,the AUC under the ROC curve was the largest,with sensitivity and specificity of 81.1％ and 75.9％,respectively.The median survival time of the effective and ineffective groups was 25 months and 18 months,respectively,and the 2-year survival rate was 73.3％ and 51.2％.The total survival time of patients with effective chemotherapy was significantly longer than those with ineffective chemotherapy (P =0.003 6).Conclusion The volume measurement grading standard can predict the pathological regression of neoadjuvant chemotherapy patients,and it is superior to the Recist score in the evaluation of efficacy and prognosis.
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Objective To investigate the expression of TIP 30 protein in gastric cancer tissues,and effect of TIP30 over-expression on migration and invasion of gastric cancer cell line SGC7901.Methods Immunohistochemistry streptavid-in-peroxidase (SP) methods were used to detect the expression levels of TIP30 in 93 cases of gastric cancer tissues.Previously constructed pcDNA3.1-TIP30 plasmid were transiently transfected into SGC7901 cells.The proliferation of cells were detected by using MTT assay when TIP30 was overexpressed.Transwell assay to determine migration and invasion ability of SGC7901.Western blot was used to examine the changes of concentration of E-cadherin,N-cadherin and MMP9.Results The positive expression rate of TIP30 was 39％ significantly lower in gastric cancer tissues than 92％ in normal gastric mucosa tissues (x2 =32.68,P ＜ 0.05),there was a significant correlation between reduced expression of TIP30 and depth of infiltration,including nodal metastasis,TNM stage (x2 =3.535,7.421,6.754,all P ＜ 0.05);MTT showed that the proliferation of SGC7901 cells in the pcDNA3.1-TIP30 transfected group significantly decreased when TIP30 was overexpressed at respective time of 72,96 hours (t =6.528,7.249,both P ＜ 0.05),Transwell assay showed that overexpression of TIP30 significantly decreased migratory and invasive numbers of SGC7901 cells (t =5.769,P ＜ 0.05;t =7.886,P ＜ 0.05);the expression level of MMP-9 and N-cadherin in TIP30 overexpressing cells group significantly decreased (t =9.811,10.362,both P ＜ 0.05),mean while E-cadherin expression was significantly higher than before (t =6.137,P ＜ 0.05).Conclusion TIP30 protein is low expressed in gastric cancer and the overexpression of TIP30 inhibits the proliferation,migration and invasion of gastric cell line SGC7901.
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Objective@#To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC).@*Methods@#71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated.@*Results@#The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group (P<0.05). The resting energy expenditure (REE) of the research group after surgery was lower than that before operation. The levels of prealbumin, albumin and lymphocyte count were higher in research group than the controls at the 7th day after surgery whereas the opposite was true for the creatinine, urea nitrogen, C-reactive protein and procalcitonin (P<0.05). Similarly, the rate of malnutrition and nutritional risk became lower in the research group (P<0.05). The gastrointestinal function recovery of patients in the research group was comparable to that of the control group (P>0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group (P<0.05). For patients with or without nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group.@*Conclusion@#Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.
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Objective To explore the relationship of pokemon gene expression and drug sensitivity and drug resistance gene in gastric cancer cells.Methods We collected the paraffin specimen of gastric cancer and para-carcinoma tissues from 60 patients with gastric cancer,detected the protein expressions of pokemon,drug resistance-associated protein P-glycoprotein (P-gp),multidrug resistance-associated protein 1 (MRP1),lung resistance protein (LRP) and survivin with immunohistochemistry (IHC) and analyzed the relationship between pokemon protein and other 4 proteins.Sulphorhodamine B (SRB) protein staining assay was performed to detect the inhibition effect of 5-fluorouracil (5-FU),cisplatin (DDP) and oxaliplatin (L-OHP) on gastric cancer cell line SGC7901,multidrug-resistant gastric carcinoma cell line SGC7901/ADR and gastric epithelial cell line GES-1,and qPCR and Western blotting were used to test expression of pokemon and drug resistance genes in the cells.Pokemon-siRNA was established and transfected into SGC7901/ADR cells,and the drug sensitivity and drug resistance genes were analyzed.Results Positive rates of pokemon,P-gp,MRP1,LRP and survivin proteins were significantly higher in gastric cancer tissues than those in para-carcinoma tissues (P＜0.05).The protein expression of pokemon was positively correlated with P-gp and survivin (r=0.385 2,P=0.002;r=0.342 4,P=0.007).Protein expressions of pokemon,P-gp,MRP1,and survivin were higher in SGC27901/ ADR cells than those in SGC7901 and GES-1 cells.The drug resistance of SGC7901/ADR cells was the strongest,followed by SGC7901,and that of GES-1 was the weakest (P＜0.01).After SGC7901/ADR cells was transfected with pokemonsiRNA,pokemon mRNA expression was significantly inhibited,mRNA and protein expressions of P-gp and survivin were decreased and the inhibitory effect of chemotherapy agents on SGC7901/ADR cells was increased (P＜0.05).Conclusion The pokemon is involved in drug resistance of gastric cancer by mutual regulation with P-gp and survivin,and pokemon may be a candidate gene for gastric cancer targeted treatment.
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<p><b>OBJECTIVE</b>To screen and identify the proteins related with tumor metastasis of gastric cancer in a nude mouse model bearing orthotopic transplanted tumor.</p><p><b>METHODS</b>Zinc finger protein 139 (ZNF139)-specific siRNA was synthesized and transfected into gastric cancer cell line SGC7901, which was then screened by G418. ZNF139-siRNA-transfected cells, negative plasmid-transfected cells and untreated SGC7901 cells were orthotopically transplanted separately on the stomach wall of BALB/c nude mice. The primary tumors and metastatic lymph nodes were harvested to separate the proteins by 2-D fluorescence difference gel electrophoresis (2-D DIGE); after gel digestion, the differential proteins were subjected to liquid chromatography-mass spectrometry (LC-MS) for identification and their functions were analyzed. Western blotting was performed to verify the identified proteins.</p><p><b>RESULTS</b>ZNF139 expression was effectively inhibited in siRNA-transfected SGC7901 cells. ZNF139-siRNA-transfected cells showed obviously suppressed tumor growth with a lowered lymph node metastasis rate in nude mice compared with untreated cells and the negative control cells (P<0.05). Proteomic study with 2-D DIGE showed that fascin and hnRNPA2/B1 were down-regulated while ANXA1 was up-regulated in the primary tumors, and ANXA5 was down-regulated in the metastatic lymph nodes in ZNF139-siRNA-transfected group. Western blotting confirmed the results of proteomic analysis.</p><p><b>CONCLUSION</b>ZNF139 gene may promote lymph node metastasis of gastric cancer by regulating fascin, hnRNPA2/B1, ANXA1, and ANXA5.</p>
Subject(s)
Animals , Humans , Mice , Annexins , Metabolism , Blotting, Western , Cell Line, Tumor , Chromatography, Liquid , Electrophoresis, Gel, Two-Dimensional , Heterogeneous-Nuclear Ribonucleoprotein Group A-B , Metabolism , Kruppel-Like Transcription Factors , Metabolism , Lymphatic Metastasis , Mice, Nude , Neoplasm Proteins , Metabolism , Neoplasm Transplantation , Proteomics , RNA, Small Interfering , Stomach Neoplasms , Pathology , TransfectionABSTRACT
<p><b>OBJECTIVE</b>The purpose of this study was to investigate the effect and mechanism of Vav3 gene on the proliferation of human gastric cancer cell line SGC7901.</p><p><b>METHODS</b>The expressions of Vav3 proten in gastric cancer tissue, tumor-adjacent tissue, human gastric cancer cell line SGC7901 and gastric epithelial cell line GES-1 cells were tested by Western blot. Vav3-siRNA was transfected into the SGC7901 cells. The proliferation of SGC7901 cells in vitro was measured by MTT assay. Cell cycle of SGC7901 cells was determined by flow cytometry.The expressions of proliferation-related genes PCNA, p16, cyclin D1, Rb were determined by qPCR and Western blot assay. Orthotopic transplantation nude mouse models of gastric cancer were prepared, and the tumor growth and expressions of PCNA, P16, cyclin D1, and Rb proteins were examined.</p><p><b>RESULTS</b>The relative expressions of Vav3 in the gastric cancer and peritumoral tissue were 0.910±0.242 and 0.243±0.045, respectively; the relative expressions of Vav3 in SGC7901 and GSE-1 cells were 0.925±0.127 and 0.277±0.038, respevtively (both P<0.05). The expression of Vav3 protein in SGC7901 cells was effectively inhibited by Vav3-siRNA. Proliferation of SGC7901 cells was inhibited by (83.43±10.17)% after 80 nmol/L Vav3-siRNA transfection (P<0.05). The ratio of SGC7901 cells in G0/G1 phase was increased, and in S phase decreased after Vav3-siRNA transfection (both P<0.05). The expressions of PCNA and cyclin D1 were decreased in cells after Vav3-siRNA transfection, and expressions of p16 and Rb were increased after Vav3-siRNA transfection (P<0.05 for all). The tumor growth in the Vav3-siRNA group was much slower than that in the other 2 control groups of nude mouse models. Compared with the two control groups, expressions of PCNA and cyclin D1 were significantly lower in the Vav3-siRNA group, while expressions of p16 and Rb were increased (P<0.05 for all).</p><p><b>CONCLUSION</b>Vav3 can promote the proliferation of gastric cancer cells by regulating proliferation-related genes.</p>
Subject(s)
Animals , Humans , Mice , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cyclin D1 , Metabolism , Mice, Nude , Proto-Oncogene Proteins c-vav , Metabolism , RNA, Small Interfering , Stomach Neoplasms , Metabolism , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To discuss the effect of modified double tracks anastomosis in patients with type Siewert II-III( adenocarcinoma of the esophagogastric junction(AEG) treated with radical gastrectomy.</p><p><b>METHODS</b>Clinical data of 763 patients with type Siewert II-III AEG undergoing radical operation in our department from January 2004 to December 2008 were analyzed retrospectively. Patients were randomized into 3 groups according to the different procedures modes: radical proximal gastrectomy with modified double tracks anastomosis(266 cases), radical proximal gastrectomy with esophageal gastric stump end-to-side anastomosis(252 cases), and radical total gastrectomy with esophageal jejunum Roux-en-Y anastomosis(245 cases). There were no significant differences in general information and biological characteristics among the 3 groups(all P>0.05). Radical degree, safety, quality of life and prognosis were compared among 3 groups.</p><p><b>RESULTS</b>There were no significant differences in postoperative complications among the three groups(P>0.05). Six months after operation, in modified double tracks anastomosis group, food intake recovery percentage was superior to the other two groups, and the Visick scores and endoscopic grading were better than esophageal gastric stump end-to-side anastomosis group(all P<0.05). There was no significant difference in recurrent rate of gastric stump between modified double tracks anastomosis group and esophageal gastric stump end-to-side anastomosis group(P>0.05). The 5-year overall survival rate of these 3 groups was 48.7%, 46.3% and 50.2% respectively, and no significant difference was found(all P>0.05).</p><p><b>CONCLUSION</b>Modified double tracks anastomosis is an ideal surgical method for type II-III AEG.</p>
Subject(s)
Humans , Adenocarcinoma , Anastomosis, Roux-en-Y , Esophageal Neoplasms , Esophagogastric Junction , Gastrectomy , Gastric Stump , Postoperative Complications , Quality of Life , Retrospective Studies , Stomach Neoplasms , Survival RateABSTRACT
Background and purpose:Recently, it was reported that tanshinoneⅡA (TanⅡA) could inhibit proliferation, induce differentiation and apoptosis of human cancer cells. Previous studies also indicated that TanⅡA could inhibit the migration and invasion of osteosarcoma. However, the effects of TanⅡA on the migration and invasion of gastric cancer and the mechanism remains unclear. The aim of this study was to investigate the effect of TanⅡA on gastric cancer cell SGC7901 migration and invasion of in vitro. Methods:After different concentrations (0.5, 1, 2, and 4μg/mL) of TanⅡA treatment for 24, 48, and 72 h respectively, MTT assay were developed to detect the cell proliferation of SGC7901. The wound healing assay and 3D-transwell assay were used to observe the migration and invasion of SGC7901 cells, respectively. Expression of intercellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase 2 (TIMP-2) mRNA and protein were measured with real-time PCR and Western blot. Results: 1, 2, and 4 μg/mL Tan ⅡA showed a dose-and time-dependent growth inhibition on SGC7901 cells. 2μg/mL TanⅡA showed a time-dependent migration inhibition of SGC7901 cells. 1, 2, and 4μg/mL TanⅡA could inhibit the invasion of SGC7901 cells. Real-time PCR and Western blot showed a reduction in expression of ICAM-1, MMP-2, and MMP-9, as well as an increase in expression of TIMP-2 (P<0.05).Conclusion:TanⅡA inhibits human gastric cancer SGC7901 cell migration and invasion in vitro. TIMP-2 upregulation and, ICAM-1, MMP-2, MMP-9 downregulation might be one of the mechanisms of anti-tumor of TanⅡA.
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Background and purpose:It was reported that zinc ifnger protein 139 (ZNF139) was expressed aberrantly in gastric cancer. But the relationship between ZNF139 and multidrug resistance (MDR) of gastric cancer is still not clear. The purpose of this research was to investigate the expressions and signiifcance of ZNF139, MRP-1, MDR1/P-gp, GST-π in human gastric carcinoma cell lines SGC7901 and SGC7901/ADR. Methods: The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere determined with RT-PCR and Western blot in SGC7901 and SGC7901/ADR cell lines. Then siRNA recombinant plasmid of targeting ZNF139 gene was constructed and imported into gastric cancer cell line SGC7901/ADR, and the expressions of MRP-1, MDR1/P-gp, GST-πwere tested simultaneously. Results:The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere higher in SGC7901/ADR than in SGC7901(P<0.05). ZNF139 was inhibited obviously after siRNA-ZNF139 was transfected into SGC7901/ADR, and expression of MRP-1, MDR1/P-gp, GST-πdecreased(P<0.05). Conclusion:ZNF139 may be invovled in multidrug resistance (MDR) of gastric cancer by up-regulating MRP-1, MDR1/P-gp and GST-π.
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Objective To evaluate the role of renal cell apoptosis in acute kidney injury (AKI) induced by sepsis in mice. Methods Forty-five male C57BL/6 mice were randomly assigned into 3 groups ( n = 15 each):sham operation group (group S), cecum ligation and puncture group (group CLP) and CLP + caspase-3 inhibitor Ac-DEVD-CHO group (group CI). Intra-abdominal infection was induced by CLP. Ac-DEVD-CHO 4 μg/g was infused subcutaneously 30 min before CLP in group CI. Five mice in each group were sacrificed after collection of blood samples at 6, 12 and 24 h after CLP. The levels of serum blood urea nitrogen (BUN) and creatinine (Cr)were detected. The apoptosis rate and expression of caspase-3 protein and caspase-3 mRNA were determined.Pathological changes in renal tissues were observed with light microscope. Results The serum BUN and Cr concentratiors, apoptosis rate and expression of caspase-3 mRNA and caspase-3 protein were significantly higher in group CLP than in group S, but lower in group CI than in group CLP ( P ＜ 0.05). Light microscopic examination showed that the pathologic changes induced by Ac-DEVD-CHO were less severe in group CI than in group CLP.Conclusion The renal cell apoptosis is one of the mechanism of AKI induced by sepsis.
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Objective: To investigate the relationship between chemosensitivity to L-OHP and expressions of multidrug resistance (MDR) associated factors in lymph node metastases (LNMs) of gastric carcinoma. Methods: The chemosensitivity to L-OHP was measured by MIT assay, and the expressions of P-gp, GST-π, P53, Survivin and Bcl-2 were determined by immunohistochemistry in 54 paired primary tumor (PT) and LNMs of gastric carcinoma. Results: The inhibition rates of LNMs cells for L-OHP were lower than those of PT (P<0.05). The expressions of P-gp, GST-π and Bcl-2 were higher in LNMs than in PT (P<0.05), and no signifi-cant difference was found in the expression of P53 and Survivin between LNMs and PT (P>0.05). Positive cor-relations among P-gp, P53 and Bcl-2 were found in PT and LNMs (r=0.3424, 0.7123, 0.4548, P<0.05). There was no significant difference in the expression of GST-π and Survivin between PT and LNMs (P>0.05). There was statistically negative correlation between inhibition rates and expression of P-gp, GST-π, and Survivin in PT (P<0.05). In LNMs, only Survivin was negatively correlated with inhibition rates of L-OHP (P<0.05). Conclu-sion: The LNMs of gastric carcinoma are heterogeneous with PT in respect to chemosensitivity to L-OHP and expression of multidrug resistance associated factors. The main factors that affect chemosensitivity to L-OHP are also significantly different between PT and LNMs. Effective adjuvant chemotherapy after surgery and re-version to multidrug resistance (MDR) of gastric carcinoma depend on targeting the metastatic lesions of gas-tric carcinoma.