Objective By observing the effectiveness of epidermal growth factor(EGF)combined with 5-flauouracil(5-FU)in the treatment of human colorectal cancer,to explore the anti-tumor effects of EGF.Methods MTT assay was used to evaluate the effects of EGF and 5-FU alone or combined use on the growth of tumor cells.The effects of EGF on PCNA expression were detected by Western blot,and flow cytometry was done to measure the changes in cell cycle.Results EGF could induce proliferation of tumor cells.With the increase in concentration of EGF,the number of cells in G0 phase was significantly reduced,and the expression of PCNA obviously increased.There was significant difference between 100 or 1 000 ng/mL EGF groups and control group(P＜0.05).The combined use of EGF and 5-FU could more significantly inhibited the growth of tumor cells than 5-FU alone(P＜0.05).Conclusion EGF can enhance the sensitivity of colorectal cancer cell Caco-2 to 5-FU,which might be related to the induction of proliferation of quiescent colorectal cancer cells.

Objective To evaluate the histological response and the clinical value in laparescopic colorectal surgery combined with preoperative regional intra-arterial chemotherapy(PRAC). Methods In cases of rectal cancer and fiver metastases selective regional intra-arterial chemotherapy and iodinated oil embolism was carried out in 23 cases of colorectal carcinoma. After 1 to 11 days laparoseopic radical resection was done, specimens were sent for histopathological examination. We analyzed the correlation between tumor differentiation and TNM stage, compared the effect of PRAC with PRAC + embolism by the criteria of histological response of chemotherapy. χ2-test was used to compare interclass correlation.Results The histological effect in the 23 cases of PRAC level 0 was in 2 cases, level Ⅰ in 7 cases, level Ⅱ in 10 cases, and level Ⅲ in 2 cases. The overall effective rate was 91% (21/23). In the 15 cases with lymph node metastases, the effective rate was 87% (13/15). There was no significant statistic correlation between tumor differentiation or TNM stage and histological response. PRAC associated embolism had a better histological response compared to PRAC alone. Conclusions Preoperative regional intra-arterial chemotherapy had marked therapeutic effect on histological response to the colorectal carcinoma patients of various tumor differentiations and TNM stage, especially combining with the embolism to rectal cancer could improve the efficacy.

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

OBJECTIVETo evaluate and compare the value of Modified NIH criteria and AFIP criteria for the risk classification of gastrointestinal stromal tumors (GIST).

METHODSClinicopathological and follow-up data of 539 patients diagnosed as primary GIST with or without irregular tyrosine kinase inhibitors in the Nanfang Hospital(n=143), Sun Yat-sen University Cancer Center (n=138), Guangdong Provincial People's Hospital (n=102) and Wuhan Union Hospital (n=156) from January 2012 to December 2015 were retrospectively analyzed. Recurrence risks of these 539 patients were classified by the modified NIH criteria and AFIP criteria. Overall survival and tumor-free survival of patients with different risks were compared by Log-rank test and the accuracy of the two criteria in predicting postoperative recurrence was compared by receiver operating characteristic(ROC) curves.

RESULTSOf 539 GIST patients, 283 were male and 256 were female; the age was (56.5±12.5) years old; tumors of 390 cases (72.4%) located in the stomach; tumor diameter of 178 cases (33.0%) was more than 5 cm; nuclear division number of 164 cases(30.4%) was more than 5/50 high magnification. The mean follow-up time was (37.5±13.6) months. According to the modified NIH criteria, the mean overall survival time of patients with very low, low, intermediate, and high risk was 52.0, 57.0, 56.9 and 53.6 months respectively (P=0.002), and the mean tumor-free survival time was 56.0, 58.1, 58.2 and 51.2 months respectively (P=0.000). According to the AFIP criteria, the mean overall survival time of patients with very low, low, intermediate, and high risk was 54.1, 57.8, 55.5 and 52.0 months respectively(P=0.015), and the mean tumor-free survival time was 57.3, 56.6, 54.9 and 50.4 months respectively(P=0.000). While predicting the risk of postoperative recurrence, the ROC curve of AFIP criteria has a larger area under the curve compared to the curve of the modified NIH criteria(0.689 vs 0.641, P<0.05).

CONCLUSIONCompared with the modified NIH criteria, AFIP criteria predicts the risk postoperative recurrence more accurately in GIST patients.

The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both and Of interest, CLDN3 undergoes -palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3 Moreover, the deprivation of -palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis Thus, our work reveals -palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 -palmitoylation might be a potential strategy for ovarian cancer therapy.

OBJECTIVETo retrospectively analyze the clinicopathology of patients with gastric gastrointestinal stromal tumor(gGIST) who underwent radical excision within 18 years in 10 domestic medical centers in order to understand the status of domestic surgical treatment of gGIST.

METHODSClinicopathological data of gGIST patients undergoing radical excision in 10 medical centers from January 1998 to January 2016 were collected, and their operational conditions, postoperative adjuvant therapy, gene detection and survival were analyzed retrospectively.

RESULTSA total of 1 846 cases were recruited in this study, including 246 cases from Guangdong General Hospital, 331 cases from Sun Yat-sen University Cancer Center, 374 cases from Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 342 cases from Nanfang Hospital of Southern Medical University, 265 cases from Fujian Medical University Union Hospital, 148 cases from Fudan University Shanghai Cancer Center, 49 cases from West China Hospital of Sichuan University, 43 cases from Peking University Cancer Hospital and Institute, 28 cases from the 81st Hospital of Pepole's Liberation Army(PLA), 20 cases from Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute. There were 918 male (49.7%) and 928 female patients (50.3%) with median onset age of 59(18 to 95) years old. Fundus(735 cases, 39.8%) and body (781 cases, 42.3%) of stomach were the common sites of lesions. The average size of tumor was (5.3±4.6) cm. There were 1 421 cases with mitotic count ≤5(77.0%). According to the operation procedure, 924 cases (50.1%) underwent laparoscopic surgery, 759 cases (41.1%) laparotomy, 120 cases (6.5%) endoscopic surgery, and 20 cases (1.1%) laparoscopic combined with endoscopic surgery, 6 cases (0.3%) laparoscopic excision surgery through gastric wall and cavity, and 17 cases (0.9%) laparoscopy and then were transferred to laparotomy. Wedge excision were performed in 1 308 cases (70.9%), proximal gastric excision in 226 cases(12.2%), distal gastric excision in 92 cases (5.0%), total gastrectomy in 94 cases (5.1%), and local gastrectomy in 126 cases(6.8%). Multi-visceral excision was performed in 138 cases, and the splenectomy was performed in 83 cases(60.1%)with the highest ratio. According to modified NIH classification, 399 cases(21.6%) were extreme low risk, 580 cases(31.4%) were low risk, 424 cases(23.0%) were moderate risk, 443 cases (24.0%) were high risk. A total of 461 cases received postoperative imatinib adjuvant therapy, accounting for 53.2%(461/867) of patients with moderate and high risk. Among 1 846 cases, 1 402 cases (75.9%) had complete follow-up data and the median follow-up time was 33.6 (0.1 to 158) months. The 5-year survival rates of extreme low risk, low risk, moderate risk and high risk were 100%, 98.5%, 92.5%, and 79.2% with significant difference(P=0.000).

CONCLUSIONSGastric GIST occurs mostly in fundus and body of stomach in China. Wedge excision is the main operational procedure and laparoscopic operation is over 50%. General prognosis of gastric GIST is quite good.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; China ; Combined Modality Therapy ; Female ; Gastrectomy ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; pathology ; surgery ; Humans ; Imatinib Mesylate ; therapeutic use ; Laparoscopy ; Laparotomy ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Retrospective Studies ; Splenectomy ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate ; Young Adult