High-throughput proteomics profiling-derived signature associated with chemotherapy response and survival for stage II/III colorectal cancer.

Adjuvant chemotherapy (ACT) is usually used to reduce the risk of disease relapse and improve survival for stage II/III colorectal cancer (CRC). However, only a subset of patients could benefit from ACT. Thus, there is an urgent need to identify improved biomarkers to predict survival and stratify patients to refine the selection of ACT. We used high-throughput proteomics to analyze tumor and adjacent normal tissues of stage II/III CRC patients with /without relapse to identify potential markers for predicting prognosis and benefit from ACT. The machine learning approach was applied to identify relapse-specific markers. Then the artificial intelligence (AI)-assisted multiplex IHC was performed to validate the prognostic value of the relapse-specific markers and construct a proteomic-derived classifier for stage II/III CRC using 3 markers, including FHL3, GGA1, TGFBI. The proteomics profiling-derived signature for stage II/III CRC (PS) not only shows good accuracy to classify patients into high and low risk of relapse and mortality in all three cohorts, but also works independently of clinicopathologic features. ACT was associated with improved disease-free survival (DFS) and overall survival (OS) in stage II (pN0) patients with high PS and pN2 patients with high PS. This study demonstrated the clinical significance of proteomic features, which serve as a valuable source for potential biomarkers. The PS classifier provides prognostic value for identifying patients at high risk of relapse and mortality and optimizes individualized treatment strategy by detecting patients who may benefit from ACT for survival.

[Effect of MicroRNA-199 on Proliferation and Migration of Gastric Carcinoma Cells].

Objective To detect the expression of microRNA(miR)-199 in gastric carcinoma tissues and cell lines, and further explore the effect and molecular mechanism of miR-199 on the proliferation and migration of gastric carcinoma cell lines. Methods Reverse transcriptase-polymerse chain reaction was used to detect the expression of miR-199 in gastric carcinoma and adjacent normal tissue obtained from 51 patients and in gastric carcinoma cell lines and human gastric epithelial cell line GES-1. The gastric carcinoma cell lines over-expressing and low-expressing miR-199 were established to detect their proliferation and migration abilities. Dual-luciferase reporter assay was performed to detect the regulatory effect of miR-199 on the 3'untranslated region of TBL1XR1. Western blot was used to explore the miR-199-related mechanism. Results The relative expression of miR-199 in gastric carcinoma tissues was significantly lower than that in the adjacent normal tissue (0.2635±0.0303 vs. 1.6700±0.9613, t=13.95, P<0.001). The relative expressions of miR-199 in gastric carcinoma cell lines AGS (0.81, t=9.13, P<0.001), SGC-7901 (0.83, t=8.88, P<0.001), MKN28 (0.58, t=10.80, P<0.001), KATO-3 (0.60, t=10.31, P<0.001), MKN-45 (0.27, t=13.10, P<0.001) were significantly lower than that in the normal gastric cell line GES-1 (2.1). In miR-199 over-expressed cell lines, the cell proliferation and migration significantly decreased as compared with the control group of gastric carcinoma cells (731±13 vs. 345±18, t=24.90, P<0.001), and in miR-199 low-expressed group, the cell proliferation and migration increased compared with the control group of gastric carcinoma cells (257±16 vs. 657±8, t=32.59, P<0.001). Dual-luciferase reporter assay proved that miR-199 directly targeted on the 3' untranslated region of TBL1XR1. Western blot analysis showed that miR-199 inhibited the expression of TBL1XR1. Conclusion The over-expression of miR-199 in gastric carcinoma is associated with the decreased ability of proliferation and migration of gastric carcinoma cells by targeting TBL1XR1.

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. METHODS: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.

The efficacy of tranexamic acid in reducing blood loss in total shoulder arthroplasty: A meta-analysis.

BACKGROUND: The purpose of this meta-analysis is to compare the efficacy of tranexamic acid (TXA) versus placebo after a total shoulder arthroplasty (TSA). METHODS: In April 2017, a systematic computer-based search was conducted in the databases of PubMed, Embase, Web of Science, Cochrane Library, and Google. Studies comparing TXA versus placebo in reducing blood loss after TSA were included. The endpoints were the need for transfusion, blood loss in drainage, hemoglobin drop, and total blood loss. Stata 12.0 software was used for the meta-analysis. RESULTS: Six studies involving a total of 637 patients met the inclusion criteria. The meta-analysis revealed that, compared with control groups, treatment with TXA could decrease the need for transfusion (P < .00001), blood loss in drainage (P = .000), hemoglobin drop (P = .001), and total blood loss (P = .000). CONCLUSION: TXA can decrease the need for transfusion as well as total blood loss in TSA patients. There was a negative correlation between the TXA dose and the need for transfusion and blood loss in drainage. Because the administration route and the dose of TXA were different, more studies are needed in order to identify the optimal dose and route.

Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

BACKGROUND: The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue. METHODS: We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes. RESULTS: Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs <22; group B: HLNs≥22). The intraoperative and postoperative characteristics, including operative blood loss (P=0.096), operation time (P=0.430), postoperative hospital stay (P=0.142), complications (P=0.552), rate of reoperation (P=0.966) and postoperative mortality (P=1.000), were comparable between the two groups. T-stage-stratified Kaplan-Meier analyses revealed that the 5-year survival rate of patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis. CONCLUSIONS: Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.

The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival.

BACKGROUND: The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer. METHODS: We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study. RESULTS: We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival. CONCLUSIONS: For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells.

S100A6 is involved in regulating the progression of cancer. S100A6 can regulate the dynamics of cytoskeletal constituents, cell growth and differentiation by interacting with binding or target proteins. The present study investigated whether S100A6 affects cell proliferation in gastric cancer cells by stimulating several downstream factors. Firstly, the expression and localization of S100A6 were investigated using immunohistochemical staining, an immunoelectron microscopy and laser confocal scanning. A ChIP-Chip assay was performed to determine the downstream factors of S100A6 using promoter Chip analysis, including approximately the -800 to +200 regions around the transcription starting point. Polymerase chain reaction analysis was performed to confirm this. It was found that the intensity of S100A6 staining was markedly higher in the cytoplasm and nucleus, and its expression level correlated with that of the Ki67 protein. The overexpression of S100A6 also promoted cell proliferation in AGS and BGC823 cell lines, detected using a Cell Counting-Kit 8 assay. In cells overexpressing S100A6, the expression levels of interleukin (IL)-8, cyclin-dependent kinase (CDK)5, CDK4, minichromosome maintenance complex component 7 (MCM7) and B-cell lymphoma 2 (Bcl2) were noticeably increased. In conclusion, the increased expression of S100A6 promoted cell proliferation by regulating the expression levels of IL-8, CDK5, CDK4, MCM7 and Bcl2 in gastric cancer cells.

Paclitaxel enhances tumoricidal potential of TRAIL via inhibition of MAPK in resistant gastric cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy due to its unique capacity to selectively trigger apoptosis in cancer cells. However, TRAIL therapy is greatly hampered by its resistance. A preclinical successful strategy is to identify combination treatments that sensitize resistant cancers to TRAIL. In the present study, we fully assessed TRAIL sensitivity in 9 gastric cancer cell lines. We found combined administration of paclitaxel (PTX) markedly enhanced TRAIL-induced apoptosis in resistant cancer cells both in vitro and in vivo. The sensitization to TRAIL was accompanied by activation of mitochondrial apoptotic pathway, upregulation of TRAIL receptors and downregulation of anti-apoptotic proteins including C-IAP1, C-IAP2, Livin and Mcl-1. Noticeably, we found PTX could suppress the activation of mitogen-activated protein kinases (MAPKs). Inhibition of MAPKs using specific inhibitors (ERK inhibitor U0126, JNK inhibitor SP600125 and P38 inhibitor SB202190) facilitated TRAIL-mediated apoptosis and cytotoxicity. Additionally, SP600125 upregulated TRAL receptors as well as downregulated C-IAP2 and Mcl-1 suggesting the anti-apoptotic role of JNK. Thus, PTX-induced suppression of MAPKs may contribute to restoring TRAIL senstitivity. Collectively, our comprehensive analyses gave new insight into the role of PTX on enhancing TRAIL sensitivity, and provided theoretical references on the development of combination treatment in TRAIL-resistant gastric cancer.

Trichostatin A potentiates TRAIL-induced antitumor effects via inhibition of ERK/FOXM1 pathway in gastric cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal apoptosis inducer and believed to have promise in cancer therapy, yet part of cancer cells exhibit resistance to TRAIL-mediated apoptosis. This necessitates the exploration of agents that resensitizes cancer cells to TRAIL. In our study, we found that Trichostatin A (TSA), an histone deacetylase (HDAC) inhibitor, augmented TRAIL-induced apoptosis in gastric cancer cells in a caspase-dependent manner. Besides, upregulation of DR5 and downregulation of anti-apoptotic proteins including XIAP, Mcl-1, Bcl-2 and Survivin also contributed to this synergism. Noticeably, TSA treatment inhibited Forkhead boxM1 (FOXM1), which expression level showed negative correlation with TRAIL sensitivity. Similarly, silencing of FOXM1 by small interfering RNA (siRNA) resensitized cancer cells to TRAIL and strengthened the TRAIL-augmenting effect of TSA. In addition, we demonstrated the depletion of FOXM1 was a consequence of the inactivation of ERK mediated by TSA. Collectively, it was first shown that TSA potentiated TRAIL sensitivity via ERK/FOXM1 pathway in gastric cancer cells. FOXM1 might serve as a biomarker for predicting sensitivity to TRAIL.

Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor survival in patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. METHODS: Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays). RESULTS: In the 129 patients, a copy number gain of three chromosome regions-namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator. CONCLUSIONS: Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.

Neoadjuvant chemoradiation therapy for resectable esophago-gastric adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor. METHODS: We systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR). RESULTS: Seven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63-0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant. CONCLUSION: Patients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.

High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer.

BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.

High-level SAE2 promotes malignant phenotype and predicts outcome in gastric cancer.

BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.

[Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer].

OBJECTIVE: To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer. METHODS: Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively. RESULTS: Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05). CONCLUSION: S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.

[Expression of CCAAT/enhancer binding protein beta in human gastric carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis. METHODS: CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed. RESULTS: The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P<0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021). CONCLUSION: Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.

[Prognostic biomarkers and targeted therapies for gastric cancer].

Gastric cancer patients with the same clinical stage may vary greatly in prognosis, which makes the improvement of current staging-based treatment imperative. The systematic biology approaches are the solution for systematic identification of biomarkers for prognostic evaluation and targeted therapy. These markers will be applied to classify the patients by molecular traits and then to guide the individualized medication. Although HER-2 antibody is currently the only targeted drug in guideline, more drugs are now addressed in early phases of clinical trials and parts of them will be eventually approved.

[Application of perioperative imatinib mesylate therapy in initial resectable primary local advanced gastrointestinal stromal tumor at intermediate or high risk].

OBJECTIVE: To evaluate the effect of perioperative imatinib mesylate (IM) therapy for patients with initial resectable primary local advanced gastrointestinal stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the prognosis. METHODS: Forty-eight above GIST patients between December 2001 and February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and post-operation IM therapy) and adjuvant group (33 cases, post-operative IM therapy). R0 resection rate, complication rate, disease-free survival (DFS) and overall survival (OS) were analyzed and compared between the two groups. RESULTS: The maximal tumor diameter and average tumor diameter were larger in neoadjuvant group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2 cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was 13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3-year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in neoadjuvant and adjuvant group respectively. CONCLUSIONS: Resectable primary local advanced GIST at intermediate or high risk with larger tumor diameter receiving perioperative IM therapy can achieve the same R0 resection rate, complication rate, DFS and OS as the GIST with smaller diameter receiving operation first. Perioperative IM therapy has potential advantage.

[Application of matrix assisted laser desorption ionization-time of flight-mass spectrometry in detecting K-ras gene mutation of colorectal cancer].

OBJECTIVE: To investigate the clinical value of matrix assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) in detecting K-ras gene mutation. METHODS: Sixty-one paraffin-embeded specimens of colorectal cancer were selected. MALDI-TOF-MS and regular sequencing were used to test the mutation of codon 12 and 13 in K-ras exon 2. RESULTS: Only 47 specimens could be detected successfully in regular sequencing, while all the specimens were tested successfully in MALDI-TOF-MS. Fourteen specimens had K-ras mutation in regular sequencing (30.0%), while 22 specimens had mutation in MALDI-TOF-MS (36.1%). Six specimens with mutation were found in MALDI-TOF-MS but were wild-type in regular sequencing. Same mutation types from 14 specimens were confirmed by both regular sequencing and MALDI-TOF-MS. MALDI-TOF-MS was able to detect the mutation in 2 specimens that was not identified in regular sequencing. CONCLUSIONS: MALDI-TOF-MS is a feasible approach of K-ras gene mutation testing in colorectal cancer, which is less demanding in terms of specimen quality and is more sensitive as compared to regular sequencing.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination.

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19-71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS + HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1-18.9 months) but was only 10.4 months (95 % CI 8.5-12.2 months) in the CRS group (P = 0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS + HIPEC was significantly higher than that for the patients treated with CRS alone (P = 0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P = 0.141). A multivariate analysis revealed that CRS + HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.

[Clinical significance of S100A8 and S100A9 expression in gastric cancer].

OBJECTIVE: To explore the expressions of S100A8 and S100A9 in gastric cancer. METHODS: A total of 176 patients with gastric cancer, including 124 males and 52 females, were recruit from 1998 to 2004, average age 57(26-80)years. The expressions of S100A8 (n = 125) , S100A9 (n = 176) and S100A8/A9 heterodimer (calprotectin) in gastric tissue samples were assessed by immunohistochemistry and immunofluorescence. The co-localization of S100A9 and its dimerization partner S100A8 and heterodimer S100A8/A9 were examined by laser confocal scanning.Receiver operator characteristic (ROC) curve was used in determining the cut-off value of S100A9 and S100A8-positive inflammatory cell counts in evaluating the pathological TNM stage. To obtain associations between S100A9 or S100A8 cell counts and clinicopathologic variables, the data were cross-tabulated and χ(2)-test was performed. Cumulative survival was estimated by the Kaplan-Meier method. RESULTS: ROC curves using the S100A9 and S100A8-positive inflammatory cell counts were 0.623 and 0.522 for pathological TNM stages respectively. The cutoff values were 200 and 65 per 200× magnification field with a sensitivity of 61.48% and 51.09% and a specificity of 64.29% and 51.52% respectively. Patients with S100A9 positive expression (n = 77) had better overall survival than negative expression(n = 99) ((35.1 ± 10.8) vs (20.3 ± 3.0) months, P = 0.021). There was no statistical significance between S100A8 positive expression(n = 62) and negative expression(n = 63) ((26.4 ± 2.8) vs (29.5 ± 2.9) months, P = 0.145).In gastric cancer tissues, both S100A9 and S100A8 proteins were detected in tumor-infiltrating inflammatory cells while no case of S100A8/A9 heterodimer was found. In addition, S100A9 and S100A8 proteins were detected in inflammatory cells in chronic gastritis. Distribution of these two proteins also partly overlapped. CONCLUSIONS: S100A9 positive expression in gastric cancer tissues is associated with an excellent prognosis. But S100A8 positive expression has no prognostic association. Calprotectin expression differs between gastric cancer and gastritis.Further explorations are warranted.