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Chylous ascites (CA) presents a challenge as a relatively common postoperative complication in gastric cancer (GC). Primary conservative therapy involved total parenteral nutrition, continuous low-pressure drainage, somatostatin, and a low-fat diet. Drainage tube (DT) clamping has been presented as a potential alternative conservative treatment for GC patients with CA.To propose novel conservative treatment strategies for CA following GC surgery.The data of patients with CA after GC surgery performed at the Fudan University Shanghai Cancer Center between 2006 and 2021 were evaluated retrospectively.53 patients underwent surgery for GC and exhibited postoperative CA during the study period. Postoperative hospitalization and time of DT removal showed a significant positive association (Infection and antibiotic usage were vital independent factors that influenced delayed DT removal in patients with CA. Appropriate standards for DT removal can significantly reduce the duration of hospitalization. Furthermore, DT clamping might be a recommended option for conservative treatment of postoperative CA.

// RenCui Quan 1, * , JiaXing Huang 1, * , HongTao Chen 2, * , YiFeng Liao 1 , WeiZe Lv 1 , Nan Chen 1 , JianJun Liu 3, 4 , HongYu Zhang 1 , DaZhi Xu 3, 4 1 Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People’s Republic of China 2 Department of Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, Guangdong Province, People’s Republic of China 3 Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China 4 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, China * These authors have contributed equally to this work Correspondence to: HongYu Zhang, email: zdwyzhy@163.com DaZhi Xu, email: xudzh@sysucc.org.cn Keywords: adjuvant chemotherapy, radically resected, gastric cancer Received: February 20, 2016 Accepted: August 09, 2016 Published: September 01, 2016 ABSTRACT Background: We conducted the retrospective study to compare the efficacy of monotherapies versus two-drug regimens as postoperative chemotherapy for patients with radically resected gastric cancer. Result: At a median follow-up of 5.3 years, no significant difference in terms of OS was observed between two groups, neither before nor after matching. After matching, median DFS was statistically significant between group A and B (median, 67.5 vs 101.0 months, respectively; hazard ratio [HR], 0.65; 95% CI, 0.45 to 0.95; P =0.027), which meant doublets prolonged DFS. In subgroup analysis, the patients of stage III receiving doublet achieved better OS than those receiving monotherapy. People who received doublet and were less than 65 years old, or male patients, or in T4 stage, or in N2 stage, or receiving subtotal gastrectomy had better DFS than those with monotherapy. Method: A data set including 501 patients (monotherapy, n=107; doublet, n=394) was matched between the two groups (n=107 patients per group) using the propensity-matched study. The primary and secondary endpoint was overall survival(OS) and disease-free survival(DFS), respectively. Survival data was compared using the Kaplan-Meier method and Cox proportion hazards models for univariate and multivariate analyses. Conclusion: The dual regimens seemed not to add overall survival benefits to patients receiving curative gastrectomy, compared with single-agent fluoropyrimidine as postoperative chemotherapy. However, dual regimens showed better disease-free survival.

Background: Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles and clinical significance of PLEK2 in gastric cancer are still unknown. Methods: We aimed to illustrate the function of PLEK2 in gastric cancer. Pearson's correlation analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. Loss-of-function approaches were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Immunoblotting and bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. Results: In gastric cancer tissue samples examined by western blot and real-time PCR, there was an increased level of PLEK2 compared with that in matched non-tumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival (p=0.0028) compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and pro-invasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT concomitantly with a reduction in E-cadherin and an elevation in Vimentin. Conclusions: Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may act as a prognostic factor for gastric cancer. Citation Format: Bo Sun, Jian-Bin Xiang, Yi Xuan, Zong-You Chen, Xiao-Dong Gu, Da-Zhi Xu. Pleckstrin-2 as a prognostic factor and mediator of gastric cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 361.

BackgroundLong non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown.MethodsReal-time PCR analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells.ResultslncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted.ConclusionslncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients.

BACKGROUND AND OBJECTIVE Although surgery is the only possible means to cure gastric cancer, the prognosis is often discrepant. The American Joint Committee on Cancer / International Union against Cancer (AJCC/UICC) published the TNM classification of Malignant Tumors (seventh edition) for gastric cancer recently. This study aimed to use this new edition staging system to investigate the prognostic factors for gastric cancer. METHODS The clinicopathologic data of 980 patients with gastric cancer treated by surgical resection in our hospital between January 2000 and December 2006 were analyzed retrospectively. The overall survival rate was determined by using Kaplan-Meier method and log-rank test was used to determine significance. The prognosis was analyzed using univariate analysis and multivariate analysis with the Cox proportional hazards model. The 6th and 7th edition AJCC/UICC TNM staging systems were used to compare the survival outcomes for the cohort of patients. RESULTS The overall 1-, 3-, 5-year survival rates for the whole group were 82.5%, 58.7%, and 52.6%. The 5-year survival rates for patients with pTNM stage I, II, III, and IV disease classified by the 7th edition staging system were 93.2%, 72.4%, 39.1%, and 5.2%, respectively. In both univariate analysis and Cox multivariate analysis, age, tumor site, tumor size, histological type, resection type, radical resection, lymphatic/venous invasion, depth of invasion, nodal status, metastasis, retrieved lymph nodes, metastatic lymph node ratio, and adjuvant chemotherapy were prognostic factors with these patients. CONCLUSION Compared with the 6th edition system, the new edition of TNM staging system for gastric cancer can accurately predict the survival after operation.

The purpose of this study was to clarify the outcome of the ratio between metastatic and examined lymph nodes (N ratio) in gastric cancer patients with ≤15 examined lymph nodes after D2 lymphadenectomy. A retrospective study was performed in 906 patients with gastric cancer who had undergone D2 resection. Patients with ≤15 examined lymph nodes (group 1, n = 729) and those with >15 lymph nodes (group 2, n = 177) were analyzed separately. N ratio categories were identified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; N ratio 3, >25%. Univariate analysis found that both the tumor, node, metastasis system (N staging system) and N ratio system well classified patients with significantly different prognosis. By multivariate analysis, only the N ratio classification was retained as an independent prognostic factor in both group 1 and 2 compared with the N stage system. Furthermore, when patients were divided into four groups according to the number of lymph nodes examined (1 to 3, 4 to 7, 8 to 11, and 12 to 15), the 5-year survival rates remained similar between groups according to the same N ratio (p > .05). Positive N ratio classification is a better prognostic tool compared with N staging system after D2 resection in patients with gastric cancer. It can prevent stage migration and can be used regardless of the examined number of lymph nodes.

The homing ability of hematopoietic stem cells (HSCs) was a critical step for transplantation and subsequent hematopoiesis. Although the HSC transplantation was widely used for many diseases, the mechanism by which HSC homing was regulated remained poorly understood. F-box protein S-phase kinase associated protein2 (Skp2), a component of the Skp2-SCF E3 ligase complex, was regarded as a cell cycle regulator by controlling the level of p21 and p27 through ubiquitination. We recently reported an important role of Skp2 in maintaining HSC pool size, quiescent stage and self-renewal ability. In this current study, we showed that Skp2 was a novel and critical regulator for maintaining the homing of HSCs as well as their residence in the endosteal niche. Microarray analysis together with biochemical validations revealed that Skp2 deficiency profoundly reduced the expression of β-catenin and its target genes. Knockdown of β-catenin mimicked the decline of HSC homing upon Skp2 deficiency, suggesting that Skp2 may regulate β-catenin and its target gene expression to orchestrate HSC homing. Our study not only identified Skp2 as a new regulator for maintaining β-catenin expression and HSC homing, but also suggested that Skp2 may serve as a predictive marker for monitoring the transplantation efficiency.

This study analyzed the time-varying pattern of the recurrence risk for gastric cancer after surgery. A total of 1,222 gastric patients undergoing D2 resection surgery were studied retrospectively. The annual recurrence hazard curve for all of the populations showed one early peak and a late rise within 10 years after the surgery. The first major recurrence peak covers the first 3 years after the surgery, rising to a maximum at 1.5 years after surgery, followed by a decline until 7.5 years after the surgery, at which point the curve began to rise again. A subgroup analysis of this pattern also revealed that the curves of the patients with bigger tumors, poorly differentiated/undifferentiated adenocarcinomas, lymphatic/venous invasion, T3 and T4, node positive or with fewer lymph nodes retrieved were steeper. Chemotherapy can reduce the hazard rate for recurrence of gastric cancer. Our study confirms the time-varying pattern of the recurrence risk for gastric cancer, and it further supports the hypothesis of tumor dormancy after surgery. To effectively reduce the recurrence risk, new adjuvant therapies beyond chemotherapy may be needed.

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

Background Beclin 1 is a main actor of autophagy. The expression of Beclin 1 and its prognostic role in gastric cancer is largely unexplored. The purpose of the present study is to investigate the expression of beclin 1 in gastric cancer cells, tissues and its relationship with prognosis. Methods The expression of Beclin 1 was detected in 271 specimens of lymph-node positive gastric cancer patients by immunohistochemistry. The correlation of Beclin 1 expression to clinicopathologic features and survival of gastric cancer was studied. Beclin-1 expression in gastric cancer cell lines and clinical specimens is also detected using reverse transcription-PCR and Western blotting. Results Beclin 1 is up-regulated at both mRNA and protein levels in six gastric cancer cell lines compared with those in normal gastric mucosa cell line (GES-1). The expression of Beclin-1 in gastric clinical specimens is also higher than those in the adjacent noncancerous tissues. Of the 271 patients, 229 (84.5%) were Beclin 1 high expression tumors by immunohistochemistry. Beclin 1 expression is closely associated with intravascular embolus. Kaplan-Meier analysis showed high beclin 1 expression was associated with longer overall survival. Both univariate analysis and multivariate analysis revealed that Beclin 1 expression were independent prognostic factors in the patients with node-positive gastric cancer. Conclusions Our findings strongly suggest that Beclin 1 has a potential role in tumorigenesis of gastric cancer and could be a promising biomarker for predicting the prognosis of patients with lymph node-positive gastric cancer. It might also serve as a novel therapeutic target for gastric cancer treatment.

To evaluate the influence of two different types of digestive tract reconstruction on the life quality, nutritional status and tolerance to adjuvant chemotherapy after total gastrectomy in patients with gastric carcinoma.The clinical data of a total of 107 patients treated in our department from January 2005 to december 2008 were analyzed retrospectively. Among them, 49 patients underwent digestive tract reconstruction with functional jejunal interposition (FJI group) and 58 patients underwent Roux en-Y jejunal P-type anastomosis (PR group) after total gastrectomy. 79 of 107 (73.8%) patients received postoperative adjuvant chemotherapy with XELOX regimen. The digestive complications and tolerance to chemotherapy were assessed respectively.Neither severe complications nor surgery-related or chemotherapy-related death were observed among the 107 patients. There were statistical differences in the incidence rate of emaciation, dumping syndrome and retention syndrome between the FJI and PR groups (P0.05), but no significant statistical difference in incidence rate of reflux esophagitis (P0.05). 28 of 40 (70.0%) patients in the FJI group completed all six cycles of chemotherapy, while 12 (30.0%) patients interrupted the treatment due to chemotherapy-related toxicity. 39 patients in the PR group received chemotherapy, 19 (48.7%) of them completed 6 cycles of chemotherapy but 20 (51.3%) patients interrupted. There was a significant difference in the incidence rate of grade III/IV chemotherapeutic toxicity and completion rate of chemotherapy (P0.05).Both functional jejunal interposition and Roux-Y operation are reasonable and safe procedures of digestive tract reconstruction. The incidence rates of emaciation, dumping syndrome and retention syndrome are lower in the patients with FJI, showing a better tolerance to adjuvant chemotherapy than Roux en-Y jejunal p type anastomosis.

To evaluate the effect of 2 regimens of postoperative combination chemotherapies on the prognosis of early stage gastric cancer patients.A total of 268 patients with stage II gastric cancer underwent D2 resection in our Cancer Center between January 1990 and December 2006 were recruited. Among them, 34 patients received the FAM regimen (5-fluorouracil [5-FU] 600 mg/m(2) intravenous [IV] drip on days 1, 8, 29, and 36; doxorubicin 30 mg/m(2) IV bolus injection on days 1 and 29; and mitomycin-C 10 mg/m(2) IV bolus injection on day 1; repeated every 8 weeks) and 81 patients received the FOLFOX regimen (oxaliplatin 100 mg/m(2) IV drip on days 1 and 15; leucovorin 400 mg/m(2) IV drip on days 1 and 15; 5-FU 400 mg/m(2) IV bolus injection; 5-FU 2.4/3.0 mg/m(2) continuous IV infusion for 48 hours on day 1, 2, 15, and 16; repeated every 4 weeks for at least 4 cycles). Patients were followed-up until December 2008. The Kaplan-Meier method was used to compare survival rates between treatment groups.The 1-, 3-, 5-, and 10-year survival rates for the patients who received postoperative chemotherapy versus the patients who underwent surgery only were 98%, 84%, 58%, 18% versus 96%, 78%, 59%, 22%, respectively (P0.05). Furthermore, the survival rates for patients who received the FAM and FOLFOX regimens were not significantly different (P0.05).Postoperative adjuvant chemotherapy did not produce survival benefits for the patients with stage II gastric cancer. Randomized controlled clinical trials are demanded to confirm the finding from this study.

Background Aimed to assess the relationship between H.Pylori and the clinicopathological features and prognosis of gastric cancer by quantitative detection of H.Pylori. Methods 157 patients were enrolled, all patients had a record of clinicopathological parameters. Specimens including the tumor and non-neoplastic were detected for H.Pylori by Real-Time PCR and analyzed clinical data retrospectively. Variables independently affecting prognosis were investigated by means of multivariate analysis using the Cox proportional hazards model. Results H.Pylori infection was greater in non-neoplastic tissue than the tumor tissue (p < 0.05), H.Pylori infection and its copies were related to the tumor site and N staging (p < 0.05). Overall survival (OS) in all 157 patients has no correlation with the H.Pylori infection status (p = 0.715). As to the patients who underwent a curative surgery, relapse-free survival (RFS) has no correlation with the H.Pylori infection status (p = 0.639). Among the H.Pylori positive patients, OS and RFS of those with higher copies were longer than in patients with low copies, but there was no significant statistical difference. Conclusions H.Pylori infection status and its copies were related to N staging. The OS and RFS in patients with positive H.Pylori status has no significant difference from the patients with negative H.Pylori status.

To explore the relationship between the lymph node count and prognosis in stage II gastric cancer.Retrospective analysis was performed for the 268 cases with gastric cancer who underwent parallel D(2) dissection between January 1990 and December 2006 in the Sun Yat-Sen Cancer Center. The Japanese Gastric Cancer Association(JGCA) 13th edition of pathological staging system was used to define stage II gastric cancer. Patients were followed up until December 2008. The Kaplan-Meier method and chi-square test were used for data analysis. All the data were analyzed using SPSS16.0 for Windows.The average number of detected lymph nodes was 17.3+/-1.2. There were 109 patients with detected lymph node15. The 1-, 3-, and 5-year survival rates were 92.7%, 67.8%, and 50.9%, respectively. The number of detected lymph node wasor =15 in 159 cases, and the 1-, 3-, and 5-year survival rates were 96.9 %, 81.0%, and 66.4%, respectively. The difference between two groups was statistically significant (P=0.003). Further analysis of the 199 cases with no lymph node metastasis (pN(0) group) showed that there were 95 cases with lymph nodes15, and the 1-, 3-, and 5-year survival rates were 92.6%, 70.4%, and 55.9%, respectively. There were 104 patients withor =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 97.1%, 84.4%, and 66.8%, respectively. The difference was also statistically significant (P=0.049). There were 69 cases with lymph node metastasis (PN(1) group), and the 1-, 3-, and 5-year survival rates of 14 patients with lymph nodes15 were 92.9%,57.1%, and 34.3%, respectively. Comparing two groups, the survival rate was significantly different (P=0.034). There were 55 patients withor =15 lymph nodes, and the 1-, 3-, and 5-year survival rates were 96.4%, 73.4%, and 63.8%. The difference was statistically significant (P=0.036).In patients with stage II gastric cancer as defined by the JGCA 13th edition, the survival rate is better in patients with more than 15 detected lymph nodes as compared to those with less than 15.

To explore the reason, features and preventive measures of residual carcinoma at incisal edge after gastric cancer operation.Clinical data of 108 cases with positive incisal margin(6.47%) from December 1964 to December 2004 in Cancer Center of Sun Yat-sen were summarized and analyzed retrospectively.Positive incisal margin patients accounted for 6.5%(108/1670) of total gastric carcinoma cases during above period. There were 62 men and 46 women with median age of 54 years(ranged from 23 to 82). The residual carcinoma rates of incisal edge were 3.6%(48/1333) in radical resection group and 17.8%(60/337) in palliative resection group respectively(P=0.000). Also, the residual carcinoma rates were 2.3%(3/129) in early group, 6.8(105/1541) in advanced group(P=0.046), 4.5%(37/815) in distal gastrectomy group and 8.0%(55/689) in proximal group respectively(P=0.000). Residual carcinomas were related with pTNM stage, Borrmann type, tumor size, differentiation and invasion depth(P0.05).Superior gastric carcinoma, Borrmann III(, IIII( type advanced cancer, tumor diameteror =5 cm, poor differentiation or undifferentiated type and serosa invaded easily result in residual carcinoma at incisal edge. The radical preventive measure is to ensure that incisal edge ought to exceed 5 cm apart from the tumor.

Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5%) were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%). Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.

Mitotic Aurora kinases are essential for accurate chromosome segregation during cell division. Forced overexpression of Aurora kinase results in centrosome amplification and multipolar spindles, causing aneuploidy, a hallmark of cancer. ZM447439 (ZM), an Aurora selective ATP-competitive inhibitor, interferes with the spindle integrity checkpoint and chromosome segregation. Here, we showed that inhibition of Aurora kinase by ZM reduced histone H3 phosphorylation at Ser10 in Hep2 carcinoma cells. Multipolar spindles were induced in these ZM-treated G(2)/M-arrested cells with accumulation of 4N/8N DNA, similar to cells with genetically suppressed Aurora-B. Cells subsequently underwent apoptosis, as assessed by cleavage of critical apoptotic associated protein PARP. Hep2 cells formed a tumor-like cell mass in 3-dimensional matrix culture; inhibition of Aurora kinase by ZM either destructed the preformed cell mass or prevented its formation, by inducing apoptotic cell death as stained for cleaved caspase-3. Lastly, ZM inhibition of Aurora kinase was potently in association with decrease of Akt phosphorylation at Ser473 and its substrates GSK3alpha/beta phosphorylation at Ser21 and Ser9. Together, we demonstrated that Aurora kinase served as a potential molecular target of ZM for more selective therapeutic cancer treatment.

Mitotic Aurora-A kinase was found to be required for formation of bipolar spindle, ensuring accurate chromosome segregation in mitosis. Recently, Aurora-A was shown to promote Ran-GTP-induced spindle formation and astral microtubule development. Here, by selective immunodepletion, we showed that Aurora-A was required for centrosome- but not Ran-GTP-induced astral microtubule formation in Xenopus egg extracts. Aurora-A enhanced microtubule polymerization in both centrosome- and Ran-GTP-induced aster assemblies: shortening the timing of aster assembly and increasing the aster size. Indeed, adding of Aurora-A protein alone induced microtubule clustering, which was abrogated by Aurora kinase inhibitory small molecule ZM447439. In addition, we showed that Aurora-A was indispensable for Ran-GTP-induced bipolar spindle formation. Inhibition of Aurora-A activity by adding of kinase inactive dominant mutant led to spindle collapse and formation of monopolar spindle whereas minus-end motor protein dynein/dynactin inhibitor p50/dynamitin rescued the bipolar structure. Lastly, we revealed that Aurora-A was necessary for microtubule poleward flux and this requirement depended on kinase activity. Thus, we showed that Aurora-A promoted microtubule polymerization and maintained microtubule flux in ensuring proper bipolar spindle assembly.

To compare the clinical characteristics of gastric cancer between young and elderly patients,and bring forward corresponding countermeasures.Clinical characteristics, treatment and prognosis between 79 young (or= 45 years old) and 120 elderly (or= 65 years old) patients were compared.The constituent ratio of gender between young and elderly group was not significantly different (P=0.226). There was no particularity of early symptom in young patients, but they had shorter course of disease (165 d vs 400 d, P=0.029) and more frequent inferior part of cancer (49.4% vs 41.7%, P=0.038) as compared to elderly patients. There was significant difference between two groups in pathological stage ratio (P=0.027). The median total survival time of young and elderly patients was 1006 d and 530 d respectively, which was not significantly different (P=0.108). Furthermore, median survival time of young and elderly patients after radical resection were 1197 d and 919 d respectively, and the difference was not significant as well (P=0.242).Characteristics of young patients with gastric cancer are lower incidence, larvaceous symptoms, more malignancy and quick development, which still remain general features of gastric cancer. By correct therapy, the efficacy of above young patients is similar to elderly patients. The key to improve prognosis is to further fortify cognition for gastric cancer and elevate early diagnostic rate.

Most results from clinical trials of neoadjuvant chemotherapy for gastric carcinoma are certain. Meanwhile, microsatellite instability (MSI) is thought to be a new mechanism of cell canceration. This study was to investigate the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma.Two microsatellite loci D2S123 and D3S1298 in tumor samples from 48 patients with gastric carcinoma, received preoperative chemotherapy of 5-fluorouracil (5-FU) and leucovorin (CF), were analyzed by polymerase chain reaction (PCR), electrophoresis on 8% denatured polyacrylamide gel, and silver staining. The microsatellite statuses of preoperative and postoperative specimens were compared. Chi-square test was used to analyze the influence of neoadjuvant chemotherapy on MSI in gastric carcinoma.The detection rate of MSI was significantly higher in preoperative samples than in postoperative samples (31.3% vs. 12.5%, P=0.026). After neoadjuvant chemotherapy, 9 cases changed from MSI-positive to MSI-negative, while no MSI-negative cases became MSI-positive.The neoadjuvant chemotherapy regimen of 5-FU/CF can induce some MSI-positive gastric carcinoma change to MSI-negative, but has no effect on MSI-negative cases.

To investigate the approaches to improve therapeutic effect of stomach cancer by analysis of the long-term results of surgical treatment of this disease.Prognostic factors of stomach cancer were analyzed by Cox multivariate regression model based on clinical data of 2561 stomach cancer cases who underwent surgical treatment from 1964 to 2004 at Sun Yat-sen University Cancer Center. Survival rates were calculated by life table method.Gastrectomy was performed for 1950 cases with resectability of 76.1%, among which there were 1192 cases of curative resection (46.5%) and 758 cases of non-curative resection (29.6%). The other 611 cases of palliative operation included bypass procedures and laparotomy. Operative mortality of all cases was 0.8% and morbidity was 5.1%. For all cases the 1-, 3- and 5-year survival rate was 52.4%, 38.6% and 35.5%, respectively. The stage-specific 5-year survival rate was 86.8% (Stage I), 58.7% (Stage II), 28.4% (Stage III) and 7.6% (Stage IV), respectively. The 5-year survival after curative resection in the period of 40 years was 45.5%, and increased to 52.7% in the last two decades and 61.8% in recent decade. Stage-specific case proportion during the earlier two decades was 1.4% (Stage I), 10.6% (Stage II), 23.1% (Stage III) and 64.9% (Stage IV), respectively, and that during the recent two decades was 9.3%, 18.5%, 35.3% and 36.8%, respectively. The 5-year survival rate of cases during the earlier two decades was 18.0% and increased to 37.5% during the recent two decades. Multivariate analysis indicated that main prognostic factors of stomach cancer included TNM staging, curative resection and multidisciplinary treatment.Early detection and curative resection were the most important measures to improve therapeutic effect of stomach cancer. A surgery-predominant multidisciplinary treatment individualizing biological characteristics of tumor, staging of disease and tumor site will contribute to improvement of therapeutic effect of stomach cancer.

The resection boundary for gastric cancer is controversial. The study was designed to investigate gastric wall infiltration length of gastric cancer.A total of 105 patients with gastric cancer who underwent gastrectomy at Cancer Center of Sun Yat-sen University from Apr. 2002 to Feb. 2004 were eligible. During gastrectomy, gastric wall lengths of 18 patients before traction (L1), after traction (L2), and after isolation (L3) were measured. Longitudinal specimen along the center of gastric cancer was fixed to measure the lengths of proximal and distal margins to the cancer. Giant section was observed under microscope to calculate the true infiltration length in proximal and distal margins according to the principle of the length changing uniformity.In the 18 specimens, L2 was significantly longer than L1 and L3 (P0.05); no significant difference was showed between L1 and L3 (P0.05). The infiltration length of localized gastric cancer, including early stage cancer, Borrmann I type cancer, and Borrmann II type cancer, was less than 2 cmû that of invasive gastric cancer, including Borrmann III type cancer and Borrmann IV type cancer, was less than 5 cm.The resection length for localized gastric cancer is at least 2 cm to tumor margin, and for invasive gastric cancer is at least 5 cm to tumor margin.

Whether received radical operation is an important prognostic factor of gastric carcinoma. But the long-term efficacies of radical operation on different patients are not the same. This study was to investigate prognostic factors of gastric carcinoma.Clinical data of 405 patients with gastric carcinoma, received radical operation from Jan. 1985 to Dec. 1995 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. Life table method was used to analyze survival rate, Wilcoxon test was used for statistical comparison, and Cox regression model was used for multivariate analysis.The 5-year overall survival rate was 43.4%. The 5-year survival rates of patients in pathologic TNM (pTNM) stage I, II, III, and IV were 75.6%, 58.7%, 28.0%, and 18.4%, respectively (P0.01). The 5- year survival rates of patients with tumor sizes of less than 2.0 cm, 2.0-3.9 cm, 4.0-5.9 cm, 6.0-7.9 cm, and no less than 8.0 cm were 82.0%, 57.4%, 43.7%, 38.7%, and 26.9%, respectively (P0.05). In addition, the 5-year survival rate was higher in patients with perioperative chemotherapy than in patients without perioperative chemotherapy (47.2% vs. 37.8%, P0.05). Univariate analysis showed that perioperative chemotherapy, Borrmann type, tumor size, pathologic type, and pTNM stage were prognostic factors of gastric carcinoma. Multivariate analysis showed that pTNM stage, tumor size, and perioperative chemotherapy were independent prognostic factors of gastric carcinoma.pTNM stage, tumor size, and perioperative chemotherapy are the most significant factors influencing prognosis of gastric carcinoma patients after radical operation. Perioperative chemotherapy contributes to enhance survival rate of gastric carcinoma patients.

Gastric cancer has the highest incidence rate and mortality rate among gastrointestinal malignancies. Twenty percent of the patients with dissectable gastric cancer cannot be cured simply by surgery due to local infiltration and distant metastasis. To evaluate the therapeutic effectiveness and safety of oxaliplatin combined with 5-fluorouracil and leucovorin on the patients with gastric carcinoma after palliative gastric resection, we analyzed all of the cases of gastric adenocarcinoma undergone palliative gastric resection in our Cancer Center in recent years.A total of 41 patients who underwent palliative gastric resection from Jan. 2000 to May 2004 in our Cancer Center were evaluated. Chemotherapy was given 8-18 days post-surgically with oxaliplatin (130 mg/m(2), intravenus infusion) on day 1, leukovorin (200 mg/m(2)) on day 1, 5-FU (500 mg/m(2), infusion) on day 1 followed by (5-FU 2600 mg/m(2), continuous infusion) for 48 h, the cycle was repeated every 4 weeks. Primary evaluation was performed after 3 cycles of chemotherapy. The chemotherapy was terminated in the patients without response to the treatment. In the patients with response to the treatment, the chemotherapy continued until 6-8 cycles for further analyses.None of the patients died from surgery or chemotherapy. Complete response occurred in 2 cases, partial response occurred in 19 cases, stable disease in 8 cases, and progressive disease in 12 cases. The total response rate was 52.5%. The 1-year, 2-year, and 3-year survival rates were 71%, 43%, and 32%, respectively. The side effects included neuropathy, nausea, vomiting, and myelosuppression. No grade 3 or 4 myelosuppression was observed.Palliative surgery in late stage gastric cancer followed by combination chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin is a safe therapeutic modality with promising short-term effectiveness and mild side effects.

AIM: To assess the efficacy and safety of intraperitoneal chemotherapy in patients undergoing curative resection for gastric cancer through literature review. METHODS: Medline (PubMed) (1980-2003/1), Embase (1980-2003/1), Cancerlit Database (1983-2003/1) and Chinese Biomedicine Database (1990-2003/1) were searched. Language was restricted to Chinese and English. The statistical analysis was performed by RevMan4.2 software provided by the Cochrane Collaboration. The results were expressed with odds ratio for the categorical variables. RESULTS: Eleven trials involving 1161 cases were included. The pooled odds ratio was 0.51, with a 95% confidence interval (0.40-0.65). Intraperitoneal chemotherapy may benefit the patients after curative resection for locally advanced gastric cancer, and the combination of intraperitoneal chemotherapy with hyperthermia or activated carbon particles may provide more benefits to patients due to the enhanced antitumor activity of drugs. Sensitivity analysis and fail-safe number suggested that the result was comparatively reliable. However, of 11 trials, only 3 studies were of high quality. CONCLUSION: Intraperitoneal chemotherapy after curative resection for locally advanced gastric cancer may be beneficial to patients. Continuous multicenter, randomized, double blind, rigorously designed trials should be conducted to draw definitive conclusions.

We study the light absorption and energy transferring in a donor-acceptor system with a bionic structure. In the optimal case with uniform couplings, it is found that the quantum dynamics of this seemingly complicated system is reduced as a three-level system of $\Lambda$-type. With this observation, we show that the dark state based electromagnetically-induced transparency (EIT) effect could enhance the energy transfer efficiency, through a quantum interference effect suppressing the excited population of the donors. We estimate the optimal parameters of the system to achieve the maximum output power. The splitting behavior of maximum power may be used to explain the phenomenon that the photosynthesis systems mainly absorb two colors of light.

Background The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer. Methods The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines. Results Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53. Conclusions In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.

Aim To evaluate the prognostic efficacy of the 7th edition tumor–node–metastasis (TNM) classification compared with the 6th edition in gastric cancer patients. Methods A total of 1,503 gastric cancer patients undergoing surgical resection were staged using the 6th and 7th edition staging systems. Homogeneity, discriminatory ability, and monotonicity of gradients of the two systems were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. Results Significant differences in 5-year survival rates were observed for the T, N, and M subgroups using the 7th edition system, except for stage N2 and N3 patients in the 6th edition system. There were no significant differences in survival between IB and IIA in the 7th edition system. Patients with stage IV disease due to T4/N3 in the 6th edition system who were downstaged to stage III in the 7th edition system had significantly better survival than those who remained at stage IV. The 7th edition system had higher linear trend and likelihood ratio χ2 scores, and smaller AIC values compared with those for the 6th edition, which represented the optimum prognostic stratification. Conclusions Our study suggests that the 7th edition system performs better than the 6th edition in several aspects.