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The clinical application of immune checkpoint inhibitor (ICI) offers novel treatment modality for locally advanced gastric cancer (LAGC) and adenocarcinoma of the gastroesophageal junction (AGEJ), with the crucial benefit of providing higher cure rates. These agents have become part of standard treatments in the perioperative setting for selected cases, such as tumor with MSI-H/dMMR, high expression of CPS (≥5) or EBV (+), MSI-H and MSS/TP53+ according to tumor immunohistochemical, genetic testing or molecular characterization. An in-depth understanding of the immune response mechanisms in "cold" and "hot" tumors enables us to better identify ICI beneficiary and further provide a rationale for converting nonresponsive "cold" tumors into responsive "hot" tumors, subsequently allowing nonresponders to benefit from ICI immunotherapy. Several recent clinical trials clearly demonstrated a synergistic and complementary effect of combining ICI with chemotherapy or chemoradiotherapy, as well as combining ICI with anti-HER2 or anti-VEGF/VEGFR and chemotherapy. Compared with chemotherapy alone, the combination treatment can significantly improve pCR, MRR or ypT0N0, and is expected to improve the prognosis. This article reviews the results of a series of clinical trials in recent years in the field of perioperative application of ICI with other modalities in LAGC/AGEJ, aiming at expanding upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC/AGEJ and exploring the feasibility of new perioperative combined immunotherapy in the future.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P >0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P <0.001), smaller maximum tumor diameter ( t =3.969, P <0.001), less number of metastatic lymph nodes ( t =1.343, P <0.001), lower ratio of vessel invasion (χ(2)=11.897, P =0.001) and nerve invasion (χ(2)=12.338, P <0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P =0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P =0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P <0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P <0.05); patients over 45 years of age ( P <0.05) and with normal body mass ( P <0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly ( P <0.05); patients with signet ring cell carcinoma benefited little ( P >0.05); tumors in the gastric body and gastric antrum benefited more significantly ( P <0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Local advanced gastric cancer (LAGC) accounts for a large proportion of annual newly diagnosed gastric cancer patients in China. There is a general consensus for D2 radical gastrectomy followed by postoperative adjuvant chemotherapy for LAGC patients, and this therapeutic strategy has been confirmed by a series of clinical trials to obviously improve the patients' prognosis; however, the recurrence rate is still high (about 50%-80% in advanced stage), which makes it difficult to further improve the long-term survival. Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve the efficacy of patients with LAGC, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing curative resection rate by downstaging tumor, eliminating micrometastases, and autologously testing of anti-cancer drug sensitivity etc. However, there are still some controversy whether LAGC patients could gain survival benefit from NAT and also lack of general consensus for this issue. In this paper, the author reviews and analyzes the current situation of perioperative therapies for LAGC patients, especially emphasize the results of neoadjuvant chemotherapy or chemoradiotherapy reported by various high-level clinical studies. The preliminary effect of perioperative chemotherapy combined with molecular targeted or immunotherapy has also aroused great interest and attention. While we continue to carry out NAT and look forward to more new high-level evidence trials on NAT, we must emphasize again that R0 gastrectomy remains the most important therapeutic modality for the patients with LAGC.

Objective: To explore the diagnostic value of laparoscopy in the postoperative recurrence of peritoneal metastasis in gastric cancer, and to investigate the efficacy of bidirectional intraperitoneal and systemic (BIPS) chemotherapy for the recurrence. Methods: The descriptive case series study was conducted. Case inclusion criteria: (1) gastric cancer patients without synchronous distant metastasis received D2 radical gastrectomy; (2) postoperative adjuvant chemotherapy was administered; (3) no other distant metastasis except recurrence of peritoneal metastasis; (4) age of 18-75 years; (5) Eastern Cooperative Oncology Group (ECOG) performance-status score≤2; (6) pretreatment evaluation suggested that surgery and chemotherapy could be tolerated. Eight consecutive gastric cancer patients with postoperative recurrence of peritoneal metastasis who met the above criteria at Department of Gastrointestinal Surgery of Ruijin Hospital from September 2015 to September 2016 were enrolled into the study. There were 6 males and 2 females with the median age of 52 (38-68) years. They received laparoscopy or laparotomy first, and then were evaluated with reference to the Sugarbaker peritoneal cancer index (PCI) and the peritoneal metastasis classification of gastric cancer developed by the Japanese Gastric Cancer Research Association. A peritoneal access port was implanted in the subcutaneous space of the lower abdomen and the patients received chemotherapy for 21 days as a course of treatment. All the patients received intraperitoneal 20 mg/m(2) of paclitaxel (PTX) via implanted subcutaneous peritoneal access ports and intravenous 50 mg/m(2) of PTX at day 1 and day 8, meanwhile 80 mg/m(2) of Tigio was orally administered per day for 14 consecutive days, followed by 7 days of interval. Follow-up ended on December 15, 2019. Results: Of these 8 patients with recurrence of peritoneal metastasis after gastric cancer surgery, 1 case underwent laparotomy and loop stoma of terminal ileum because of complete colonic obstruction, and the remaining 7 cases underwent laparoscopy successfully and the recurrence of peritoneal metastasis was clearly diagnosed. Two patients with ovarian metastasis underwent laparoscopic bilateral adnexectomy. The median follow-up time was 17.5 (1.5 to 39.0) months, the median number of BIPS chemotherapy course was 11 (1 to 30), and the median survival time (MST) after BIPS chemotherapy was 17.0 months. The major adverse reaction in BIPS treatment was mainly myelosuppression, of which grade 3/4 leukopenia and neutropenia developed in 1 and 2 cases respectively. No BIPS-related death occurred. The MST of gastric cancer after radical gastrectomy was 40.0 months. Conclusions: Laparoscopy is a safe and feasible method for diagnosing the recurrence of peritoneal metastasis of gastric cancer. BIPS chemotherapy is effective and safe for its treatment and deserves further study.

Translational medicine refers to translating basic research achievements into the clinical application for diagnosis and treatment. There are still many issues of gastric cancer to be solved in clinical diagnosis and treatment. We need to focus on clinical questions, by means of basic research and multidisciplinary intersection approach, to further improve the overall efficacy of gastric cancer. Based on Ruijin Hospital's translational research experiences, in this paper, the authors describe the future direction in the field of translational research, such as the etiology and pathogenesis of gastric cancer, tumor markers for early diagnosis, prediction of recurrence and metastasis, classification criteria, evaluation of chemotherapy, tumor heterogeneity, targeted therapy, immunotherapy and research platform establishment. In addition, here we share our perspective of the research on serum biomarkers, specific antibodies and improvement of drug delivery for gastric cancer.

Perioperative whole-process management (WPM) for patients with advanced gastric cancer (AGC) mainly focuses on some clinical issues which are easily neglected or underappreciated. WPM is helpful in making a scientific and rational therapeutic plan, and avoiding inadequate communication in multi-disciplinary participation, so that the diagnosis, treatment and rehabilitation for AGC patients can be integrated organically. Based on the current clinical practice for AGC patients, eight key issues in WPM should be emphasized.(1) Preoperative clinical staging. An accurate preoperative staging by endoscopy and imaging technique is helpful in setting up a rational therapeutic plan, and is also a prerequisite to start WPM. (2) Indications and value of diagnostic laparoscopy. Laparoscopic exploration is beneficial to find intraperitoneal micro-metastases so as to avoid unnecessary laparotomy. For cases of AGC infiltrating serosal layer or suspected of peritoneal metastasis, preoperative laparoscopic exploration should be routinely performed. (3) Neoadjuvant therapy. Multiple RCT studies have shown that neoadjuvant chemotherapy can benefit a majority of patients with AGC, improving prognosis and prolonging their overall survival. Therefore, neoadjuvant therapy should be considered first for stage III and IVA AGC patients. (4) Prediction of efficacy in neoadjuvant chemotherapy. Endoscopy, MDCT scan, PET-CT and liquid biopsy have certain predictive value individually, which can be used together or separately to improve the accuracy of prediction. (5) Effective prevention of postoperative peritoneal metastasis. Extensive intraoperative peritoneal lavage (EIPL), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) have been shown to be of various efficacy in preventing peritoneal metastases. (6) Prediction of postoperative prognosis of AGC patients. The key pathological indicators are tumor regression grade (TRG) and ypTNM staging, especially if there is lymph node metastasis. Usually for AGC patients who received neoajuvant chemotherapy with TRG 0 or ypN0, their prognosis was comparable to that of patients with cTNM stage I.(7) Postoperative adjuvant chemotherapy. Postoperative adjuvant therapy is always an important part of the WPM management of AGC patients. Several recent RCT studies have shown that duplet chemotherapy can significantly reduce the risk of death after D2 radical gastrectomy compared to singlet chemotherapy, especially for stage III patients. (8) Perioperative nutritional support. Due to different degrees of malnutrition in AGC patients, enhanced nutritional treatment in the perioperative period can not only reduce surgical complications, but also enable patients to complete necessary course of chemotherapy, and ultimately further improve their survival rate.

Objective: To investigate the differences of clinicopathological features, diagnosis, treatment and prognosis between patients with extra-gastrointestinal stromal tumors (EGIST) and duodenal gastrointestinal stromal tumors (DGIST). Methods: A retrospective case - control study was performed. Case inclusion criteria: (1) tumor confirmed by histology and pathology; (2) primary tumor locating in the extra - gastrointestinal tract or duodenum; (3) without other synchronous tumors; (4) complete clinical and pathological data. Clinical data of 20 EGIST patients and 32 DGIST patients from March 2011 to September 2016 at Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were retrospectively collected and analyzed. The observational parameters included clinicopathological characteristics, treatment and prognosis conditions. Continuous data of abnormal distribution were expressed as median (range) and compared using the Mann-Whitney U -test. Survival curves were drawn by the Kaplan-Meier method and compared with the Log-rank test. Results: Of the 20 EGIST patients, 8 were males and 12 were females with age of 61.0 (30.0 to 86.0) years and of the 32 DGIST patients, 12 were males and 20 were females with age of 55.5 (27.0 to 70.0) years. Compared with DGIST patients, EGIST patients were older ( U =188.000, P =0.012], had larger tumor size [10.0 (3.0 to 29.0) cm vs. 4.0 (1.5 to 10.0) cm, U =98.500, P <0.001] and higher ratio of high risk classification [85.0% (17/20) vs. 12.5% (4/32), χ(2)=26.870, P <0.001]. Among the 20 EGIST patients, 5 were diagnosed with distal metastasis and received imatinib (400 mg/d), and the other 15 patients underwent radical resection who were included in survival analysis. All the 32 DGIST patients underwent radical resection. The median follow-up of whole group was 43 (14 to 76) months. The 3-year recurrence/metastasis-free survival rate of 15 cases undergoing radical resection in the EGIST group was 85.6%, which was lower than that of the DGIST group (88.6%), and the difference was not statistically significant ( P =0.745). There was no significant difference in the 3-year overall survival rate between the EGIST group (92.9%) and the DGIST group (100%) ( P =0.271). Conclusions: As compared to DGIST, EGIST mostly occurs in those with older age, larger tumor size and higher risk grade. The prognosis of EGIST patients after radical resection is similar to that of DGIST patients.

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

Objective: This study aimed to identify clinicopathological factors predictive of lymph node metastasis in patients with the poorly differentiated early gastric cancer (EGC) to assess the feasibility of using endoscopic submucosal dissection (ESD). Methods: The records of patients with poorly differentiated early gastric cancer undergoing gastric radical resection between January 2012 and December 2016 were reviewed in Ruijin hospital. Those with distant metastasis, two or more malignant tumors, remnant gastric cancer, neo adjuvant therapy, previous history of gastric surgery or clear history of perigastric lymphadenectomy, and mixed tumors were excluded. Age, sex, presence of ulcerous lesion, tumor size, tumor location, depth of invasion, type of differentiation, lymphatic vessel invasion, vascular invasion, nerve invasion and HER2 expression were collected. Univariate and multivariate stepwise logistic regression analyses were used to identify the independent risk factors of perigastric lymph node metastasis.According to the Guidelines for the Treatment of Gastric Cancer (2018 edition) of the Chinese Society of Clinical Oncology (CSCO), the expanded indications of ESD for EGC are as follows: (1)no ulcerative lesions, the maximum diameter of lesions >2 cm of differentiated intramucosal cancer; (2)ulcerative lesions, the maximum diameter of lesions ≤3 cm of differentiated intramucosal cancer; (3)no ulcerative lesions, undifferentiated intramucosal carcinoma with diameter ≤2 cm. The relationship between clinicopathological factors and lymph node metastasis was analyzed. Results: A total of 517 patients, aged 21-83 (57.1±11.7), including 307 males and 210 females, were enrolled in the study. Among them, 114 (22.0%) patients had lymph node metastasis. Univariate analysis showed that ulcerative lesion ( P =0.042), tumor diameter ( P =0.048), depth of invasion ( P <0.001), location of tumors ( P <0.001), lymphatic vessel invasion ( P =0.009), vascular invasion ( P <0.001) and nerve invasion ( P =0.028) were related to lymph node metastasis after radical resection of poorly differentiated early adenocarcinoma. Age, sex, type of differentiation and HER2 expression were not significantly correlated to lymph node metastasis ( P >0.05). Multivariate analysis showed that tumor size (OR=1.61, 95% CI: 1.03-2.52, P =0.037), depth of invasion (OR=2.77, 95% CI:1.66-4.63, P <0.001), lymphatic duct invasion (OR=14.74, 95% CI:1.58-137.36, P =0.018) were independent risk factors for lymph node metastasis in poorly differentiated EGC, and ulcerative lesion was not a risk factor for lymph node metastasis (OR=0.82, 95% CI:0.56-1.18, P =0.285). A total of 119 patients with poorly differentiated EGC fully complied with the relative indications of ESD recommended by the Japanese Statute and the criteria for radical resection after ESD. Among them, 14 (11.8%) still had perigastric lymph node metastasis, while the gender, tumor diameter, location, differentiation and HER2 expression were not associated with lymph node metastasis ( P >0.05). Conclusion: For patients with poorly differentiated EGC, the application of ESD should be carefully weighed with precise assessment of tumor diameter, depth of invasion, and lymphatic duct invasion.

A more differentiated therapy regimen for gastric carcinoma requires more precise preoperative staging. In patients with early gastric cancer (EGC), especially mucosa, endoscopic resection (ER) should be performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer (AGC), neoadjuvant treatments have been investigated. Clinical staging of gastric cancer has been greatly improved by advance in imaging techniques such as endoscopic ultrasonography (EUS), transabdominal ultrasonography (TAUS), multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI), positron emission tomography (PET), combined PET-CT scans, and laparoscopic staging. This review is to summarize the clinical application and the value of preoperative staging in gastric cancer.

Objective: To identify novel multi-drug resistance-related genes, and to explore the mechanisms of multi-drug resistance., Methods: Multi-drug resistant cell line Lovo/5-FU was established by incubation with increasing dose of 5-FU. The sensitivity to 5-FU and cis-diaminodichloroplatinum (CDDP) was measured by MTT assay. Two dimensional electrophoresis plus mass spectrum(2-DE/MS) was used to identify the differentially expressed protein between Lovo and Lovo/5-FU. The identified protein was then verified by Western blot analysis., Results: The IC50 concentrations of Lovo/5-FU to 5-FU and CDDP were increased by 31 and 3 times, compared with Lovo (both P<0.01). 2DE-MS showed that CAP-G and RhoGDI2 were up-regulated, whereas 6-PGL, DCI, Prdx-6 and Maspin were down-regulated in Lovo/5-FU. Western blot analysis confirmed that the expression levels of RhoGDI2 and CAP-G in Lovo/5-FU were increased by 6.14 and 2.98 fold respectively (both P<0.01), whereas Maspin was decreased to 5.2% of Lovo(P<0.01)., Conclusions: Multi-gene and multi-pathway are involved in the development of multi-drug resistance of colorectal cancer cells. CAP-G, RhoGDI2 and Maspin are potential multi-drug resistant genes.

Objective: To evaluate the effects of Bevacizumab on the tumor growth, proliferation and apoptosis of gastric cancer xenograft, and the impacts on the VEGF and Sp1 expression., Methods: Gastric cancer xenografts in nude mice were established using SGC-7901 gastric cancer cell line. The nude mice were randomly divided into two groups, Bevacizumab treatment group and PBS group. The tumor sizes were measured for tumor growth curve. The proliferation and angiogenesis were evaluated by immunohistochemistry (IHC) staining of Ki67 and CD34. TUNEL assay was used for apoptosis evaluation. The expression of VEGF and Sp1 in tumor cells were detected by IHC and Western blot., Results: Compared to the PBS group, the tumor growth decreased significantly (P<0.05), the proliferation of tumor cells and angiogenesis decreased, and apoptosis index increased significantly [(5.3 ± 1.8)% vs. (16.7 ± 6.7)%, P<0.01] in Bevacizumab group. The results of IHC and Western blot demonstrated that the expression of VEGF and the microvessel density (MVD) was decreased (4.0 ± 1.0 vs. 16.3 ± 1.5, P<0.001) in Bevacizumab treatment group. No obvious changes of Sp1 expression were observed in Bevacizumab treatment group., Conclusions: Bevacizumab can inhibit the growth of gastric cancer xenografts in nude mice, decrease the VEGF expression and MVD. However, the compensatory up-regulation of transcription factor Sp1 is not affected by Bevacizumab.

Objective: To explore the interaction between SerpinB5 and MAFbx in gastric cancer cell and to identify the interaction sites., Methods: The interaction between SerpinB5 and MAFbx was screened and validated by yeast two-hybrid screening and co-immunoprecipitation. The expression of MAFbx was analyzed after SerpinB5 expression being modified by RNA interference and pGBKT7-SerpinB5 transfection. The impact of SerpinB5 on the expression of MAFbx was studied in gastric cancer cell line SUN-16. A model of MAFbx was constructed by homology modeling. The related residues for interaction were analyzed by Autodock4.0., Results: The interaction between SerpinB5 and MAFbx was validated. The expression of MAFbx changed along with SerpinB5 expression. Amino acids including PRO261, ASN361, and LYS362 were key residue in the interaction of SerpinB5 and MAFbx., Conclusion: SerpinB5 interacts with MAFbx in gastric cancer cell. Amino acids including PRO261, ASN361, and LYS362 are potential binding sites.

Objective: To evaluate laparoscopic radical gastrectomy for early gastric cancer., Methods: A total of 204 patients with early gastric cancer undergoing laparoscopic-assisted radical gastrectomy or open radical gastrectomy between October 2004 and December 2009 were retrospectively reviewed and analyzed. Patients were divided into laparoscopic group(LAP, n=78) and open group (OPEN, n=126). Operative time, blood loss, time to passage of flatus, postoperative hospital stay, complications and pathologic findings were compared between the two groups., Results: Compared to the OPEN group, operative time in the LAP group was significantly shorter[(202.9±45.6) min vs.(219.8±45.2) min, P<0.05], blood loss was less[(144.5±146.5) ml vs. (245.0±146.4) ml, P<0.05], time to passage of flatus was shorter[(3.1±1.1) d vs.(4.5±1.6) d, P<0.05], postoperative hospital stay was shorter[(10.8±1.2) d vs. (12.4±3.8) d, P<0.05]. However, the two groups were comparable with regard to postoperative complication rate(10.3% vs. 12.7%, P>0.05), proximal resection margin[(4.0±1.9) cm vs. (4.2±1.7) cm, P>0.05], distal resection margin [(3.6±1.7) cm vs. (3.5±1.8) cm, P>0.05], number of harvested lymph node(13.1±6.5 vs. 14.5±8.2, P>0.05). The median follow up was 22(2-64) months. There were no tumor recurrences or metastases in the LAP group. In the OPEN group, only 1 patient died from peritoneal metastasis. Total hospital costs between the two groups were similar(P>0.05)., Conclusion: Laparoscopic radical gastrectomy is a safe, feasible, effective, and less invasive surgery for early gastric cancer.

Objective: To clone core promoter regions of iroquois homeobox gene 1 (IRX1) gene and evaluate the regulatory mechanism of IRX1 transcription., Methods: Upstream sequence from transcriptional start site was predicted using bioinformatics methods. Serial deleted fragments from IRX1 promoter sequences were amplified by PCR and luciferase reporter plasmids were constructed. The luciferase intensity was analyzed after transferring reporters into GES-1 gastric mucosa cell line., Results: The promoter of IRX1 was predicted to be within 700 bp from the 5'-flanking region of IRX1 gene. Eight serial deleted luciferase reporter plasmids were constructed. The transcriptional activity of different fragments was expressed as following: p-416>p-584>p-715>p-350>p-687>p-320>p-188>p-92. Except p-320 and p-188, the transcriptional activity of other 6 fragments was higher than that of PGL3-basic plasmid. The transcriptional activity was the highest in p-416 and decreased sharply from p-320 to p-188., Conclusions: The fragment p-416 shows the strongest promoter activity. The sequence from -320 bp to -188 bp is identified as core promoter region, which is focused as key sequence for further regulatory analysis, since some binding sites for important transcriptional factors such as Sp1 and TFII D are predicted.

Objective: To assess the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the treatment of advanced gastric adenocarcinoma., Methods: A total of 30 patients were recruited to receive DOX regimen (docetaxel 75 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, and capecitabine 1000 mg/m(2) bid d1-14, repeated every 3 weeks). Only those who completed at least 2 cycles were assessed., Results: The number of patients with complete response, partial response, stable disease and progressive disease were 1, 2, 25 and 2, respectively. The objective response rate was 10.0%(3/30) and the disease control rate was 93.3%(28/30). After a median follow-up of 261 days, the median progression free survival and overall survival time were 197 days and 466 days, respectively. The most common grade III to IV toxicity was hematologic toxicity. The percentage of patients with grade III to IV leucopenia, neutropenia and febrile neutropenia were 60.0%, 43.3% and 30.0%, respectively. The most common grade III to IV non-hematologic toxicity was fatigue, nausea, vomiting, anorexia, diarrhea, and hand-foot syndrome., Conclusions: DOX regimen demonstrates promising efficacy in the treatment of advanced gastric adenocarcinoma. The associated toxicity can be well tolerated and controlled. Large scale clinical trial is necessary to obtain further evidence.

Objective: To investigate the value of multidetector-row computed tomography (MDCT) in preoperatively predicting peritoneal metastasis of gastric cancer and to evaluate the indication for laparoscopic staging of gastric cancer on the basis of MDCT features., Methods: Six hundred and forty gastric cancer patients underwent preoperative MDCT examination, and the results of MDCT were compared with surgical and pathological findings. In addition, the relationship between MDCT features (depth of invasion, lymph node metastasis status, tumor size, and thickness of tumor) and peritoneal metastasis of gastric cancer was analyzed., Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT in predicting peritoneal metastasis of gastric cancer were 51.0% (25/49), 99.3% (587/591), 86.2% (25/29), 96.1% (587/611), and 95.6% (612/640), respectively. Univariable analysis showed that all the four MDCT features (depth of invasion, lymph node metastasis status, tumor size, and tumor thickness) of gastric cancer were significantly correlated with the peritoneal metastasis of gastric cancer. None of the patients diagnosed with stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer by MDCT were found to have peritoneal metastasis. Receiver operating characteristic (ROC) analysis showed that the accuracy of the tumor size and thickness of gastric cancer in determining peritoneal metastasis was high(area under ROC curve was 0.83 and 0.75, respectively). Multivariable analysis showed that only tumor size was significantly correlated with the peritoneal metastasis from gastric cancer., Conclusions: The clinical value of MDCT in preoperative prediction of peritoneal metastasis from gastric cancer is favorable. Laparoscopy can be avoided in patients with small tumor size or stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer diagnosed by MDCT due to lower incidence of peritoneal metastasis.

Objective: To compare the efficacy of modified D(2) radical total gastrectomy with spleen-preserving and D(2) radical total gastrectomy with splenectomy in patients with gastric cancer located in the upper third, upper and middle third and entire stomach., Methods: One hundred and twelve patients with gastric cancer in the upper third, upper and middle third, or entire stomach underwent radical total gastrectomy between January 1989 and December 1994. Modified D(2) total radical gastrectomy with spleen-preserving (spleen-preservation group) was performed in 61 patients, and 51 underwent D(2) total radical gastrectomy with splenectomy (splenectomy group). The differences in clinicopathological characteristics,5-year survival rate, incidence of postoperative complication and hospital stay between the two groups were analyzed retrospectively., Results: There were no significant differences between the spleen-preservation group and the splenectomy group in gender, age, tumor size, T stage, N stage and TNM stage. The overall 5-year survival rate was 41.0% in the spleen-preservation group and 39.2% in the splenectomy group (P>0.05). The 5-year survival rates of patients with stage I, II, III and IIII were 100%, 66.7%, 27.8% and 17.4% in the spleen-preservation group, respectively, and were 100%, 70.0%, 26.7% and 5.6% in the splenectomy group, respectively (all P>0.05). The incidence of postoperative complication was lower in the spleen-preservation group (11.5% vs 27.5%, P<0.05). The mean hospital stay was longer in the splenectomy group (27.3 d vs 20.3 d, P=0.057)., Conclusion: The efficacy of modified D(2) radical total gastrectomy with spleen-preserving for patients with gastric cancer in the upper third, upper and middle third or entire stomach is similar to that of D(2) radical total gastrectomy with splenectomy, and the spleen-preserving procedure is associated with decreased postoperative complication and improved survival.

Objective: To investigate the effect of Hedgehog (HH) pathway on proliferation and in vitro tumorigenicity of gastric cancer cell lines., Methods: The expression of SHH, PTCH, SMO, SUFU and GLI1 in seven cell lines were tested by RT-PCR. siRNA targeting GLI1 mRNA was transfected into MKN28 cells. Cell proliferation and in vitro tumorigenicity were examined by CCK8 and soft agar colony formation test., Results: SHH in six gastric cancer cell lines was up-regulated. Expression of PTCH in KATOIII cell lines and expression of SUFU in MKN28 and KATOIII were reduced. GLI1 siRNA significantly inhibited the expression of GLI1 in MKN28 cell line. Growth rate and colony formation rate of MKN28 cells treated with GLI1 siRNA were significantly lower than those of control cells (all P <0.001)., Conclusions: HH signaling pathway is widely activated in gastric cancer cell lines. The activation of HH signaling pathway promotes the growth of MKN28 cells.

Objective: To evaluate the value of using nasogastric tube for patients after gastrectomy., Methods: One hundred and eight patients undergone gastrectomy were divided randomizely into nasogastric decompression group(n=53) and non-nasogastric decompression group (n=55). Gastrointestinal function and postoperative complications were compared between the two groups., Results: Between nasogastric decompression group and non-nasogastric decompression group, no significant differences in postoperative complications (20.8% vs 23.6%, P=0.719), postoperative time of flatus [(3.2+/-0.9) d vs (3.0+/-0.7) d, P=0.192], recovery time of drinking [(5.9+/-3.4) d vs (5.1+/-1.6) d, P=0.143], eating time of fluid food [(7.8+/-3.6) d vs (6.8+/-1.8) d, P=0.085] and eating time of semi-fluid food [(9.8+/-3.5) d vs (8.8+/-1.9) d, P=0.081] were found. While the recovery time of bowl sound [(1.8+/-0.7) d vs (2.2+/-0.9) d, (P=0.013)] and hospital stay [(10.2+/-2.1) d vs (11.7+/-4.3) d, (P=0.021)] were shorter in non-nasogastric decompression group., Conclusion: It is not necessary to use nasogastric decompression for patients after gastrectomy.

Objective: To screen differential expression genes and proteins at transcriptome and proteome levels between human gastric cancer tissue and corresponding normal mucosa., Methods: Fresh-frozen gastric cancers were collected from patients treated at Ruijin Hospital. A total of 22 pairs of gastric cancer tissues and the corresponding noncancerous mucosa were analyzed. Commercially available cDNA microarray with 14 592 genes/ESTs was used. Genes were considered to be up-or down-regulated when the intensity ratio Cy3/Cy5 was > or = 2 or < or = 0.5 in over 50% samples (P<0.05). Immobilized pH gradient(IPG)-based 2-DE was applied to separate the total proteins of gastric cancer tissue and paired normal tissue. After staining and analysis by software,the differential expression proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) or MALDI-TOF-TOF-MS., Results: As compared with corresponding noncancerous tissue, there were totally 149 up-regulating genes/ESTs and 238 down-regulating genes/ESTs in gastric cancer, including 29 genes with 3-fold over-expression ratio and 21 genes with 5-fold under-expression. Fifteen protein spots were identified successfully, among whom there were ten over-expressed and five under-expressed proteins in gastric cancer tissue compared with normal tissue. Most of over-expressed genes and proteins were related to cell motility, cell proliferation, signal transduction, while those under-expressed genes and proteins were related to defense response, toxoid metabolism., Conclusion: Studying gastric cancer at transcriptome and proteome levels can help demonstrate tumorigenesis and biological characteristics of gastric cancer comprehensively and provide powerful tools to find new biomarkers associated with gastric cancer and therapy targets.

Objective: To investigate the relationship between vascular endothelial growth factor D (VEGF-D) and metastasis of lymphatic vessel in gastric carcinoma., Methods: The human VEGF-D cDNA was amplified from total RNA isolated from human normal gastric tissue, then it was inserted into T-A clone plasmid and subcloned into pEGFP eukaryotic expression vector. After the full-length sequence expected was confirmed by enzymatic digestion and sequencing,the human gastric carcinoma cell line SGC7901, which expressed a low level of VEGF-D, was transfected with the pEGFP/VEGF-D expression vector. Stable SGC7901 clones with high expression of VEGF-D were selected in vitro with G418, which were then combined and subcutaneously injected into nude mice to observe the density and morphology of lymphatic vessel. The outcomes were later compared with those of SGC7901 cells transfected with null vector(pEGFP) by immunostaining with a specific antibody LYVE-1., Results: The average weight of tumors in the pEGFP group (1.13+/-0.40) g at day 35, was significantly lower than that in the pEGFP/VEGF-D group (2.24+/-0.82)g (P<0.05). The lymphatic vessel density (LVD) in the pEGFP group (2.89+/-1.32) was significantly lower than that in the pEGFP/VEGF-D group (5.74+/-1.30)(P<0.01). There were dilated functional lymphatic vessels around the tumor margin., Conclusion: VEGF-D may promote the growth and metastasis of tumor in gastric carcinoma by increasing the growth of lymphatic vessels.

Objective: To study the relationship of mesorectum with fasciae and nerves in the pelvic cavity and to specify the proper planes of dissection in total mesorectal excision., Methods: Twenty-four pelvises (12 males and 12 females) harvested from cadavers were studied by dissection., Results: There were three planes surrounding the rectum as the visceral fascia, vesicohypogastric fascia and parietal fascia. The pelvic plexus and its branches situated between the visceral fascia and the vesicohypogastric fascia. Pelvic splanchnic nerves and hypogastric nerves were observed between the visceral fascia and the parietal fascia., Conclusions: The posterior plane of total mesorectal excision lies between the visceral fascia and the parietal fascia. The lateral dissection should be conducted in a plane between the visceral fascia and the vesicohypogastric fascia. The proper planes for posterior and lateral resection can be identified by the hypogastric nerve and the pelvic plexus respectively.

Objective: To study the expression and intracellular localization of FRZB gene in gastric cancer tissue, and to explore its significance in gastric cancer., Methods: The expression of FRZB in tumor tissues from 90 patients with gastric cancer and in normal gastric mucous as control were analyzed by immunohistochemistry in tissue array. FRZB expression in gastric cancer cell lines and immortalized gastric epithelial cell line GES-1 were detected by quantitative real-time PCR(Q-PCR) and Western blot. The intracellular localization of FRZB was observed by immunofluorescence staining., Results: The positive expression rate of FRZB in gastric cancer was 92.2%. FRZB expressed in gastric cancer with well differentiation was higher than that with poor differentiation.The positive rate in normal gastric mucous was 10.0% (one out of ten). By confocal microscope, FRZB localized both in cytoplasma and nucleus, especially on the nuclear membrane. The Q-PCR and Western blot results also showed that the expression of FRZB in gastric cancer cell lines was higher than that in GES-1., Conclusions: The expression of FRZB in gastric cancer is correlated with tumor cell differentiation and tumor Lauren classification. The nuclear localization of FRZB may contribute to its function in gastric cancer formation and progression.

Objective: To evaluate the prognostic significance of metastatic lymph nodes ratio in patients with T(2)~T(3) stage gastric cancer., Methods: Clinical data of 238 patients with T(2)-T(3) stage gastric cancer undergone radical gastrectomy and D(2) lymphadenectomy, at least 15 lymph nodes was dissected per patient, were analyzed retrospectively. Spearman correlation analysis was used to determine the correlation coefficient. Survival was determined by the Kaplan-Meier method and differences were assessed by the Log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients 5 years postoperatively and that of metastatic lymph nodes number., Results: The metastatic lymph nodes ratio didn't correlate with the total number of dissected lymph nodes, whereas metastatic lymph nodes number did. Kaplan-Meier survival analysis demonstrated the metastatic lymph nodes ratio significantly influenced the postoperative survival time and Cox proportional hazard regression model analysis showed the metastatic lymph nodes ratio was an independent poor prognostic factor. There was no significant difference between the area under the receiver working characteristic curve of metastatic lymph nodes ratio and metastatic lymph nodes number in predicting the death of patients 5 years postoperatively., Conclusions: The metastatic lymph nodes ratio in T(2)-T(3) stage gastric cancer patients is not correlated with the total number of dissected lymph nodes if at least 15 lymph nodes are dissected. The metastatic lymph nodes ratio is a major independent poor prognostic factor of the patients of T(2)-T(3) stage gastric cancer. The ability of the metastatic lymph nodes ratio in predicting the death of T(2)-T(3) stage gastric cancer patients 5 years postoperatively is the same as that of metastatic lymph nodes number.

Objective: To evaluate the value of routine haematoxylin-eosin(HE) stain for submucosal lymphatic vessel infiltration in early gastric cancer., Methods: Four thousand four hundred and twenty early gastric cancer patients underwent D2 operation. Submucosal lymphatic vessel was detected by routine HE stain. The results were compared with pathological lymph node metastasis., Results: In early gastric cancer, the sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV) of routine HE stain for submucosal lymphatic vessel infiltration were 54.5%, 82.0%, 78.9%, 27.4%, and 93.5% respectively. In early gastric cancer limited in mucosa, these indexes were 14.5%, 98.0%, 95.8%, 15.8%, and 97.8% respectively. In early gastric cancer infiltrated to submucosa, they were 60.3%, 57.8%, 58.3%, 28.1%, and 84.2% respectively. There were significant differences of submucosal lymphatic vessel infiltration with lymph node metastasis (P< 0.001), but no significant difference with survival rate. The 5-year survival rates of submucosal lymphatic vessel infiltration positive and negative group were 84.4% and 87.3%, median survival time was 6998 d and 7237 d, and mean survival time was 6163.9 d and 6042.6 d respectively (P=0.2495)., Conclusion: The accuracy of routine HE stain is too low, thus it is not suitable for diagnosing submucosal lymphatic vessel infiltration in early gastric cancer.

Objective: To identify genetic abnormalities in primary gastric carcinoma., Methods: Comparative genomic hybridization (CGH) was used in screening DNA copy number changes along all chromosomes in 23 cases of primary gastric cancer., Results: Twenty-one out of 23 cases showed chromosomal losses and gains for at least one of the chromosomal arms in primary gastric cancer. The mean number of chromosomal alterations was 7.52. Chromosomal gains predominated over chromosomal losses in a ratio of 5.38:2.14. The most often involved chromosomal gains were observed in 8q (9/21, 42.9%), 20q (9/21, 42.9%), 17q (8/21, 38.1%), 3q (7/21, 33.3%), 7q (7/21, 33.3%), 11q (6/21, 28.6%), 13q (6/21, 28.6%), 1q (5/21, 23.8%) and 20p (5/21, 23.8%). The chromosomal arms with frequent losses were 17p (7/21, 33.3%), 18q (6/21, 28.6%), 5q (5/21, 23.8%), 8p (5/21, 23.8%), and 9p (5/21, 23.8%)., Conclusions: The phenomenon of gain and loss of chromosomal regions is observed in primary gastric cancer, which may induce the amplification of oncogenes and the loss of tumor suppressor genes to regulate the development and progression of gastric cancer.

Objective: To investigate the expression of Runt-related transcription factor gene 3(RUNX3) in gastric cancer and its impact on the outcome of gastric cancer patients., Methods: By using immunohistochemistry staining and western blot assay, the expression of RUNX3 protein in 66 cases of gastric cancer with various clinicopathologic characteristics were detected, and the effects of RUNX3 protein expression on the outcome of patients undergone surgical resection were evaluated., Results: (1) The expression rate of RUNX3 protein in gastric cancer lesions was 60.6% (40/66), and RUNX3 protein was mainly expressed in the cytoplasm of cancer cells. RUNX3 protein expression in tumor tissues was significantly higher than that in non-tumor tissues. (2) RUNX3 protein expression was correlated with tumor differentiation (P=0.025) and Lauren's classification (P=0.034), but had no relationship with the TNM stage (P=0.085). (3) In sharp contrast, the median survival time of patients who had tumors with negative and positive RUNX3 protein expression were 2478 and 2187 days respectively (P=0.016)., Conclusions: RUNX3 protein influences the differentiation of gastric cancer. The role of RUNX3 protein as a tumor-suppressor in tumorigenesis and differentiation of gastric carcinoma need to be further evaluated.

Objective: To identify the expression of polo like kinase 1 (plk1) and to discuss its relationship with the clinicopathological parameters and prognosis in gastric carcinoma., Methods: Plk1 protein expression levels in 89 cases of resected gastric carcinomas were detected by immunohistochemistry method, the relations between plk1 expression levels and the survival periods were estimated by Kaplan-Meier curve., Results: The positive rate of plk1 expression in gastric cancer tissues was 42.7% (38/89), significantly higher than that (13.5%) in the adjacent noncancerous tissues (12/89) (P<0.01). The expression levels of plk1 were closely related to tumor differentiation, invasion and TNM stage (P<0.05). Patients with plk1-positive expression had worse prognosis than those with plk1-negative expression in gastric cancer patients (P<0.05)., Conclusions: Plk1 may promote carcinogenesis and gastric cancer development, its overexpression can be a novel marker for diagnosing certain biological behaviours and predicting prognosis in gastric cancer.

Objective: To investigate the expression of Ezrin in gastric cancer, its role in tumor metastasis., Methods: Ezrin expression in tumor tissues from 90 gastric cancer cases and in normal gastric mucosa from 12 cases with benign disease was examined by immunohistochemical staining. Ezrin expression in gastric cancer cell lines was also detected by Western blot, and in vitro invasion assay was used to examine the invasive ability of the cell lines., Results: The expression rate of Ezrin was significantly higher in gastric cancer tissues than that in normal tissues (P< 0.05), and significantly correlated with lymph node metastasis (P< 0.05). Western blot showed that MKN-45 cell line had the highest expression of Ezrin among 5 gastric cancer cells. MKN-45 possessed highest invasion ability., Conclusion: Ezrin expression is up-regulated, and may be associated with lymph node metastasis in gastric cancer.

Objective: To observe the effect of inhibition of serine/threonine kinase15 (STK15) gene expression on apoptosis induction in gastric cancer cell line-MKN45 and discuss the role of STK15 in viability of gastric cancer cells., Methods: The STK15 expression was inhibited by chemically synthesized siRNA. The STK15 mRNA and protein level were respectively measured by real-time quantitative PCR and western blotting,the change of cell cycle distribution and apoptosis rate were detected by flow-cytometry, cell morphological change was observed by Hoechst staining,and pro-caspase 3 level was also detected by western blot., Results: After treatment by siRNA targeting STK15 after 48 h, STK15 mRNA and protein level decreased obviously. More MKN45 cells accumulated at G(2)/M phase (P< 0.05). The apoptosis rate of STK15 siRNA treated MKN45 cells was higher than that of control cells(P< 0.05) with the pro-caspase 3 level decreased., Conclusions: Inhibition of STK15 gene expression may induce apoptosis in MKN45 cells through the pathway of caspase3. STK15 gene play a key role in proliferation and viability of MKN45 cells.

Objective: To investigate the application of proteomics in the field of serology,and to screen the differential expression proteins related with poorly differentiated gastric carcinoma., Methods: Two-dimensional electrophoresis (2-DE) was applied to segregate the total proteins in the serum form gastric cancer patients and health volunteers. After staining,the differential expression proteins were analyzed using PDQuest software,and identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS)., Results: Electrophoresis figures with high resolution and reproducibility were obtained. Six differential expression proteins were found only in the serum from gastric cancer patients, while four other proteins from healthy volunteers., Conclusions: Protein expression is differential in the serum from the gastric cancer patients and health volunteers. It is hopeful to find the biomarkers related with poorly differentiated gastric carcinoma using proteomics.

Objective: To investigate the immunotherapy efficacy of both helper T lymphocytes (Th) and cytotoxic T lymphocytes (CTL) epitopes augmented dendritic cells (DCs) tumor vaccine on gastric cancer., Methods: Naïve spleen T cells were stimulated by mixed peptides (a mixture of Th epitope MAGE-3 (22-36)) primed DCs per week in vitro. After 4 cycles of restimulation, peptide specific T cells were harvested and subgroups of which were determined with flow cytometry. Cytokines secreting profiles by CD4+ T cells and cytotoxicities of CD8+ T cells on tumor cells were assessed. The protective immunity by referred DCs tumor vaccines was also monitored., Results: Both Th and CTL epitopes primed DCs could elicit both CD4+ T cells and CD8+ T cells in vitro,of which CD4+ T cells released high amount of Th1 type cytokines (IFN-gamma, IL-2) on recognizing specific antigen, as well as CD8+ T cells exhibited efficient tumor-killing capacity. The effects induced by DCs pulsed with single epitope (Th or CTL epitope) in vivo were less effective than those induced by DCs pulsed with mixture epitopes., Conclusions: Both Th and CTL epitopes augmented DCs tumor vaccine can induce CD4+ Th1 and CD8+ CTL mediated immune responses to eradicate gastric cancer cells.

Objective: To investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC)., Methods: A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared., Results: For prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC., Conclusion: IPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.

Objective: To observe the effect of inhibition of polo like kinase1 (plk1) gene expression on apoptosis induction in gastric cancer cell line-MKN45 and discuss the vital role of plk1 proliferation and viability of gastric cancer cells., Methods: The plk1 expression was inhibited by chemically synthesized siRNA. The plk1 mRNA and protein level were respectively measured by real-time quantitative PCR and Western blotting. The spindle morphological change was observed by immunofluorescence staining and confocal microscopy. The change of cell cycle distribution and apoptosis rate was detected by flow-cytometry. Pro caspase3 level was also detected by western blotting., Results: After treatment by siRNA targeting plk1, plk1 mRNA and protein level decreased obviously, the cell mitotic spindle became obscure and lost cohesiveness, more MKN45 cells accumulated at G(2)/M phase (P< 0.05), apoptosis rate of plk1 siRNA treated MKN45 cells was higher than that of control cells at 48 h and 72 h (P< 0.05) with pro-caspase3 level decreasing at 72 h., Conclusions: Inhibition of plk1 gene expression induces apoptosis in MKN45 cells through the pathway of caspase3. Plk1 gene play a key role in viability of MKN45 cells.

Objective: To investigate the expression of cancer-related gene MPS-1 in gastric cancer and to evaluate its significance in clinical diagnosis and therapy., Methods: The mRNA expression of MPS-1 was determined by polymerase chain reaction after reverse transcription (RT-PCR) in cancer tissues and adjacent non-cancerous tissues from 42 cases with gastric cancer. The expression levels of MPS-1 in 6 gastric cancer cell lines (AGS, MKN-45, SGC 7901, KATO III, N-87 and SNU-1) were also determined by RT-PCR and Western blot., Results: The MPS-1 mRNA was expressed in all tissues and cell lines. The mRNA expression level of MPS-1 in cancer tissues were 1.37+/- 0.87, significantly higher than 0.99+/- 0.67 in adjacent normal gastric mucous tissues (P< 0.01). The expression of MPS-1 was correlated with TNM stage (P< 0.05), but not with age, gender, tumor size and differentiation. The expression level of MPS-1 mRNA in the primary lesions was hig her in the patients with TNM stages III, IV than those with TNM stages I, II. Meanwhile, RT-PCR and Western blot showed the same results that MPS-1 expression was higher in the six gastric cancer cell lines as compared with that in the normal gastric cell line GES-1., Conclusion: The high expression of MPS-1 in gastric cancer indicates that MPS-1 might play an important role in gastric carcinogenesis,which may provide a new target in immunotherapy for gastric cancer.

Objective: To investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) in human gastric cancer, the relationship between their expression and the clinicopathological features,as well as the relationship between these two parameter expression and lymphangiogenesis and lymph node metastasis., Methods: COX-2 and VEGF-C expressions were detected in 63 gastric cancer samples by immunostaining. Lymphangiogenesis was evaluated by immunostaining with the specific antibody LYVE-1., Results: The expression rates of COX-2 and VEGF-C were 66.7% (42/63), 52.4% (33/63), respectively in 63 gastric cancer specimens. LYVE-1 was positive in 35 cases (35/63), which indicated lymphangiogenesis in the tumors. The expression of COX-2 was significantly correlated with the expression of VEGF-C, tumor lymphangiogenesis and lymphatic metastasis (P< 0.05), however not gender, tumor size, tumor location, Lauren classification and serosa invasion (P< 0.05)., Conclusions: In gastric cancer, the expression of COX-2 is significantly associated with VEGF-C expression, lymphangiogenesis and lymphatic metastasis. COX-2 may up-regulate the expression of VEGF-C, which induces lymphangiogenesis and accordingly contributes to lymphatic metastasis.

Objective: To detect the variation of gene expression profile of G1/S transition and elucidate the role of related genes regulating cell cycle from G1 to S phase in gastric cancer., Methods: Nocodazole-thymidine and double thymidine methods were used to synchronize gastric cells at G2/M and G1/S point, cDNA microarray chips was applied to examine the gene expression profile at G1 early and late phase, S early and late phase during the cell cycle, hierarchy analysis was conducted by a professional software package., Results: A total of 2001 genes were detected available, 959 genes appeared to be upregulated or downregulated, including 147 genes upregulated at G1 late phase. These 147 genes are involved in DNA metabolism, transcription and translation,posttranslational modification, ubiquitination, signal transduction etc, which all affected cell cycle from different aspects., Conclusion: Complex multiple gene processes, such as DNA metabolism, transcription and translation, posttranslational modification, ubiquitination, signal transduction etc,are implicated in and also essential for G1/S transition during gastric cancer cell cycle, part of these genes are significantly associate with overproliferation in gastric cancer.

Objective: To compare the expression and activities of urokinase type plasminogen activator (uPA) among different gastric cancer cell lines and investigate their relations with peritoneal metastatic potency., Methods: The uPA expression in 4 gastric cancer cell lines (AGS, SGC7901, MKN45, MKMN28) was detected using ELISA and Western blot methods. uPA activity was detected simultaneously using uPA activity kit. The gastric cancer cells were cultured with confluent mesothelial cells in 24-well plates or Boyden chambers for different times. The adhesive cells were counted directly under a microscope. The motility and invasion of gastric cancer cells were determined by MTT assay., Results: Among four gastric cancer lines,the highest expression of uPA was found in SGC7901 and the highest uPA activity in MKN45, while the lowest expression and activity of uPA in AGS. Compared with the other three lines, MKN45 had stronger adhesion than MKMN28 (P< 0.05), SGC7901 (P< 0.05), and AGS (P< 0.01), but there were no significant differences in motility and invasion among MKN45, MKN28 and SGC7901. The adhesion,motility and invasion of AGS were weaker compared with those of the other three cell lines., Conclusion: The uPA expression and activity are significantly different among 4 gastric cancer cell lines, and positively correlated with their peritoneal metastatic potency.

Objective: To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma., Methods: Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody., Results: The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01)., Conclusion: TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.

Objective: To observe the hepatic injury following stop- flow chemotherapy and investigate the potential mechanisms., Methods: Twelve healthy hybrid female pigs were randomly divided into two groups as stop- flow group (SF) and stop- flow chemotherapy (SFC) group. The expression of IL- 8 and ICAM- 1 mRNA in hepatic biopsies was detected by RT- PCR, and the expression of NF- kappa B P65 subunit in nuclei was assessed by Western blot analysis. The levels of ALT and AST, and histopathologic alterations were examined to evaluate the hepatic function at different time before and after stop- flow procedure., Results: The expression of NF- kappa B P65 subunit, IL- 8 and ICAM- 1mRNA increased at 30 min after stop- flow procedure, and gradually decreased at 3 h and 6 h after stop- flow procedure. The levels of ALT and AST decreased after reaching the peak at 24 h after stop- flow procedure, but removed one week after stop- flow procedure. Cytoplasmic microvascular steatosis developed with appreciable neutrophils infiltration after early stop- flow procedure without significant destroy occurred in the structure of hepatic lobule. No significant difference of various parameters above occurred between SF and SFC groups., Conclusion: The hepatic injury following stop- flow procedure was self-limited and reversible. There is no severe destroy of hepatic structure and disfunction during stop- flow chemotherapy.

Objective: To investigate amplification of zinc finger protein 217(ZNF217) and its association with clinicopathologic parameters in primary gastric carcinoma., Methods: Semiquantitative polymerase chain reaction (PCR) was used to determine DNA copies of ZNF217 in the specimens from forty- seven cases with primary gastric carcinoma., Results: There was no difference in DNA copies between tumor specimens and paratumor normal tissues. The incidence of ZNF217 amplification was 11.36% in gastric cancer. The amplification of ZNF217 was significantly associated with tumor size(P< 0.01) and intestinal type of stomach cancer(P< 0.05)., Conclusion: Oncogene ZNF217 may play a role in specific tumor types or subtypes of gastric cancer. There may be other oncogenes associated with gastric carcinoma in 20(q)13.