Yan Shi

Third Military Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (47)80.01 Total impact

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    ABSTRACT: MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastasis. Recently, miR-203 was reported as a tumor suppressor microRNA silenced in different malignancies including hepatocellular carcinoma, prostate cancer, oral cancer, breast cancer, and hematopoietic malignancy, whereas its role in the carcinogenesis of gastric carcinoma (GC) has not been evaluated. Here, we analyzed the levels of miR-203 and Slug in the GC specimen and studied their correlation. We analyzed the binding of miR-203 to the 3'-UTR of Slug messenger RNA (mRNA) and its effects on Slug translation by bioinformatics analysis and by luciferase-reporter assay, respectively. We modified miR-203 levels in GC cells and studied their effects on the cell invasiveness in transwell cell migration assay. We found that in GC, miR-203 levels were significantly decreased and Slug levels were significantly increased. miR-203 and Slug inversely correlated in patients' specimen. Bioinformatic analysis predicted that miR-203 may target the 3'-UTR of Slug mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-203 inhibited Slug and cell invasiveness, while depletion of miR-203 increased Slug and cell invasiveness. These data suggest that miR-203 suppression in GC promotes Slug-mediated cancer metastasis.
    Tumor Biology 07/2015; DOI:10.1007/s13277-015-3765-8 · 3.61 Impact Factor
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    ABSTRACT: The Clavien-Dindo classification for postoperative complications has been established as a standardized system and applied in many fields of surgery. The aim of our study was to assess the complications after total gastrectomy using the Clavien-Dindo classification and identify risk factors related to them. Four hundred and fifteen patients who underwent total gastrectomy for gastric cancer between April 2009 and September 2014 were enrolled in this study. Postoperative complications were graded, and possible risk factors related to complications were analyzed. The overall complication rate was 13.3 %, with the severe complications classified as grade III or above accounting for 3.1 %. Age of 65 years old or more, higher TNM staging, and open surgery were identified as independent risk factors for overall complications. Age of 65 years old or more, ASA score of 3 or more, multiorgan resection, and retrieved lymph nodes of 30 or more were identified as independent risk factors for severe complications. The Clavien-Dindo system has a broad applicability and facilitates the assessment on the incidence and severity of complications. Large-scaled, prospective clinical trials using the classification are necessary to evaluate the postoperative complications of total gastrectomy for gastric cancer.
    Medical Oncology 04/2015; 32(4):573. DOI:10.1007/s12032-015-0573-3 · 2.06 Impact Factor
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    ABSTRACT: A characteristic immunopathology of human cancers is the induction of tumor antigen-specific T lymphocyte responses within solid tumor tissues. Current strategies for immune monitoring focus on the quantification of the density and differentiation status of tumor-infiltrating T lymphocytes; however, properties of the TCR repertoire ‒ including antigen specificity, clonality, as well as its prognostic significance ‒ remain elusive. In this study, we enrolled 28 gastric cancer patients and collected tumor tissues, adjacent normal mucosal tissues, and peripheral blood samples to study the landscape and compartmentalization of these patients’ TCR β repertoire by deep sequencing analyses. Our results illustrated antigen-driven expansion within the tumor compartment and the contracted size of shared clonotypes in mucosa and peripheral blood. Most importantly, the diversity of mucosal T lymphocytes could independently predict prognosis, which strongly underscores critical roles of resident mucosal T-cells in executing post-surgery immunosurveillance against tumor relapse.
    OncoImmunology 01/2015; 4(4):e1001230. DOI:10.1080/2162402X.2014.1001230 · 6.28 Impact Factor
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    ABSTRACT: Background The purpose of this study was to determine the learning curve for robot-assisted gastrectomy using the Cumulative Summation (CUSUM) technique.Methods Two series of consecutive robotic gastrectomy were retrospective analyzed. Patient demographics, surgical performance, and short-term outcomes were examined and data of operation time were abstracted for the learning curve analysis.ResultsSimilar processes occurred in the two surgeons. Each of their learning curves of robotic gastrectomy was best modeled as a third-order polynomial, with equation CUSUMOT in minutes equal to 0.0495 case number 3 − 4.217 case number2 + 91.206 case number − 100.11(R2 = 0.8731) for surgeon A and 0.0314 case number 3 − 2.4106 case number2 + 33.682 case number + 315.28(R2 = 0.8816) for surgeon B. They both included three unique phases: an initial phase, a well-developed phase, and a mastery phase after the accumulation of additional experience.Conclusion The CUSUM method is a useful tool for objective evaluation of practical skills for surgeons during the learning phase of robotic surgery training. The robotic gastrectomy is found to have a short learning curve for experienced laparoscopic surgeons and the popularity of this new technology won't reduce because of its difficulty to learn. J. Surg. Oncol. 2014;9999:1–8. © 2015 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 01/2015; 111(6). DOI:10.1002/jso.23876 · 2.84 Impact Factor
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    ABSTRACT: The mechanisms underlying immune evasion by gastric cancer have not been well described due to a lack of gastric tumor models in immunocompetent mice. In the current study, we found that supernatants from MFC cells, a murine gastric cancer line, inhibited the LPS-induced maturation and cross-presentation of BMDCs. Moreover, MFC tumor-derived factors markedly altered the cytokine profiles of BMDCs, leading to a trend of increased levels of IL4, IL6, IL23 and TGFβ, as well as decreased levels of TNFα. qPCR and ELISA revealed that MFC cells expressed a high level of VEGF. Downregulating VEGF expression abrogated the inhibitory effect of MFC-derived factors on the maturation and cross-presentation of BMDCs. In addition, VEGF knockdown greatly impaired the tumorigenicity of MFC cells in immunocompetent mice. Compared with parental MFC tumors, VEGF-low MFC tumors grew much more slowly and the survival of tumor-inoculated mice was significantly improved. More importantly, mice rejecting inoculated VEGF-low MFC tumor cells gained resistance to re-challenged parental tumors, which was attributed to an antitumor immunity response against parental MFC tumors. These results reveal an immunosuppressive role for VEGF in murine gastric cancer.This article is protected by copyright. All rights reserved.
    FEBS Journal 07/2014; 281(17). DOI:10.1111/febs.12923 · 3.99 Impact Factor
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    ABSTRACT: Poultry intake has been inconsistently associated with incidence or mortality of colorectal cancer (CRC) in epidemiologic studies. The purpose of this study was to assess their relationships by performing a dose-response meta-analysis. We conducted a search of PubMed database between January 1966 and July 2013 for prospective studies that reported relative risks (RRs) with 95 % confidence interval (CIs) of CRC for at least three categories of poultry intake. Dose-response relationships were examined with the generalized least-squares trend estimation. Study-specific results were pooled with a random-effects model. Subgroup, sensitivity, and meta-regression analyses were also conducted to explore heterogeneity. Sixteen studies on poultry intake and CRC incidence, and four studies regarding poultry intake and CRC mortality were identified. These studies involved a total of 13,949 incident CRC cases and 983 CRC deaths. The RRs of CRC for higher compared with lower intake of poultry were reported in these studies, and the reported levels of poultry intake varied substantially. Results of the dose-response meta-analysis conferred a RR of 0.89 (95 % CI 0.81-0.97) for an increase in poultry intake of 50 g/day. The results were not sensitive to any individual studies and were similar for colon and rectal cancer. Poultry intake was not associated with CRC mortality (RR for 50 g/day = 0.97, 95 % CI 0.79-1.20). This meta-analysis indicates that poultry intake may be moderately associated with reduced incidence of CRC.
    European Journal of Nutrition 05/2014; 54(2). DOI:10.1007/s00394-014-0705-0 · 3.84 Impact Factor
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    ABSTRACT: To assess the effect of radical laparoscopy-assisted gastrectomy(LG) for patients with chronic obstructive pulmonary disease (COPD). Clinical data of 340 gastric cancer patients with COPD undergoing radical gastrectomy with lymphadenectomy at Southwest Hospital, Third Military Medical University between January 2010 and October 2013 were analyzed retrospectively. The clinical outcomes for the 262 patients with COPD who underwent LG(LG group) were compared with those of 78 patients with COPD who underwent open gastrectomy(OG group). During LG, pneumoperitoneum was maintained at an insuffiation pressure of 8 mmHg to 10 mmHg. The primary endpoint was postoperative pulmonary complication(PPC). To predict factors related to PPC, univariate and multivariate logistic analyses were carried out. Intraoperative blood loss was significantly less in the LG group [(131.2±14.7) ml] than in the OG group [(246.7±49.0) ml; t=-13.445, P=0.000], but operation time was significantly longer [(220.4±19.1) min vs. (194.2±31.5) min; t=6.877, P=0.000]. The findings showed PPC to be significantly less frequent in the LG group(5.3%,14/262) than in the OG group (15.4%, 12/78)(χ(2)=8.581, P=0.003). The severity of COPD was independent risk factor for PPC(P=0.031, HR=1.456, 95%CI:1.306-1.789). No independent predictor of PPCs was found in type of operative approach (open vs laparoscopic; P=0.126). The LG procedure with insuffiation pressure of pneumoperitoneum is tolerated for gastric cancer patients with mild or moderate COPD.
    Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 04/2014; 17(4):365-8.
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    ABSTRACT: This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed.
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    ABSTRACT: Early identification of treatment failure (TF) of nosocomial pneumonia (NP) remains a major challenge. To test whether use of procalcitonin (PCT) kinetics could assess the clinical efficacy in older critically ill patients with NP. A prospective observational study was conducted in 60 patients (≥65 years) admitted to the intensive care unit with severe NP. Serum PCT was measured on day 0, day 3, day 7 and at the end of treatment (EOT). The PCT time course was analyzed according to the therapeutic efficacy. PCT were elevated in all patients (n=60) on day 0 and the median levels (range) were 2.5 ( 0.85-42.7) μg/L. There were no differences between the improvement patients (n=41) and those without improvement ( n=19) in PCT on day 0 ( p>0.05). However, lower PCT on days 3, 7 and at the EOT (all p<0.05) as well as greater rate of PCT decline between day 0 and day 3( ΔPCTD3% ) (29.5 ± 10.8% vs 15.1 ± 5.9%, p = 0.009) were found in the improvement patients than in those without improvement. ΔPCTD3% was the best single predictor of efficacy (area under the curve [AUC], 0.791, p < 0.001) and had a sensitivity of 75.7% and a specificity of 72.0% with threshold of 26.2%. By comparison, traditional parameters and absolute PCT failed to predict treatment response ( p>0.05). Indeed, the combination of ΔPCTD3% > 26.2% and modified clinical pulmonary infection score (mCPIS) < 6 points could improve the predictive value (AUC, 0.890; sensitivity, 81.3%; specificity, 86.5% ). PCT levels were not influenced by aging and PCT kinetics might help to identify TF. ΔPCTD3% combined with CPIS have been shown to be an marker of clinical efficacy at an earlier stage.
    12/2013; 59(8). DOI:10.4187/respcare.02364
  • Yan Shi, Xi Rui
    Intensive Care Medicine 09/2013; 39(12). DOI:10.1007/s00134-013-3103-9 · 7.21 Impact Factor
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    ABSTRACT: The process of peritoneal metastasis involves the diapedesis of intra-abdominal exfoliated gastric cancer cells through the mesothelial cell monolayers; however, the related molecular mechanisms for this process are still unclear. Heterocellular gap-junctional intercellular communication (GJIC) between gastric cancer cells and mesothelial cells may play an active role during diapedesis. In this study we detected the expression of connexin 43 (Cx43) in primary gastric cancer tissues, intra-abdominal exfoliated cancer cells, and matched metastatic peritoneal tissues. We found that the expression of Cx43 in primary gastric cancer tissues was significantly decreased; the intra-abdominal exfoliated cancer cells and matched metastatic peritoneal tissues exhibited increasing expression compared with primary gastric cancer tissues. BGC-823 and SGC-7901 human gastric cancer cells were engineered to express Cx43 or Cx43T154A (a mutant protein that only couples gap junctions but provides no intercellular communication) and were co-cultured with human peritoneal mesothelial cells (HPMCs). Heterocellular GJIC and diapedesis through HPMC monolayers on matrigel-coated coverslips were investigated. We found that BGC-823 and SGC-7901 gastric cancer cells expressing Cx43 formed functional heterocellular gap junctions with HPMC monolayers within one hour. A significant increase in diapedesis was observed in engineered Cx43-expressing cells compared with Cx43T154A and control group cells, which suggested that the observed upregulation of diapedesis in Cx43-expressing cells required heterocellular GJIC. Further study revealed that the gastric cancer cells transmigrated through the intercellular space between the mesothelial cells via a paracellular route. Our results suggest that the abnormal expression of Cx43 plays an essential role in peritoneal metastasis and that Cx43-mediated heterocellular GJIC between gastric cancer cells and mesothelial cells may be an important regulatory step during metastasis. Finally, we observed that the diapedesis of exfoliated gastric cancer cells through mesothelial barriers is a viable route of paracellular migration.
    PLoS ONE 09/2013; 8(9):e74527. DOI:10.1371/journal.pone.0074527 · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Rapid detection of bacteremia is important for critically ill patients. Procalcitonin (PCT) has emerged as a marker of sepsis, but its characterization for predicting bacteremia is still unclear. This study aimed to investigate the role of change of PCT within 6 to 12 hours after new fever in predicting bacteremia. METHODS: An observational study was conducted in the ICU of our hospital from January 2009 to March 2010. Adult patients with new fever were included and grouped as bacteremia and non bacteremia group. Serum PCT concentration was measured at admission and within 6 to12 hours after new fever (designated PCT0 and PCT1). Other results of laboratory tests and therapeutic interventions were recorded. Multivariate Logistic regression analysis was used to identify the risk factors of bacteremia. The area under the ROC curve (AUC) was constructed to evaluate the discriminative power of variables to predict bacteremia. RESULTS: Totally 106 patients were enrolled, 60 of whom had bacteremia and 46 did not have bacteremia,. The acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were 13.1 ± 7.8 and 5.0 ± 2.2 at admission, respectively. There was no significant difference in PCT0 between the bacteremia group and nonbacteremia group; 1.27 µg/L (range, 0.10 - 33.3) vs. 0.98µg/L (range, 0.08 - 25.7), (P = 0.157). However, the PCT1 and the rate of change of PCT were significantly higher in bacteremia group; PCT1 was 6.73 µg/L (1.13 - 120.10) vs. 1.17 µg/L (0.10 - 12.10) (P = 0.001), and the rate of change was 5.62 times (1.05 - 120.6) vs. 0.07 times (-0.03 - 0.18) (P < 0.001). The area under the ROC curve (AUC; 95% confdence interval) of the rate of change of PCT was better for predicting bacteremia than that of PCT1; 0.864 (range, 0.801 - 0.927) vs. 0.715 (range, 0.628 - 0.801), (P < 0.05). The AUCs of PCT0 and other parameters (such as WBC count, granulocyte percentage and temperature) were not significantly different (all P > 0.05). The best cut-off value for the rate of change was 3.54 times, with a sensitivity of 88.5% and a specificity of 98.0%. It was also an independent predictor of bacteremia (odds ratio 29.7, P < 0.0001) and wasn't correlated with the presence or absence of co-infection, neutropenia or immunodefciency (P > 0.05). CONCLUSION: The rate of change of PCT is useful for early detection of bacteremia during new fever and superior to the PCT absolute value and other parameters in non-selected ICU patients.
    Chinese medical journal 05/2013; 126(10):1832-1837. · 1.02 Impact Factor
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    ABSTRACT: To investigate the feasibility and safety of da Vinci robotic surgical system in rectal cancer radical operation, and to summarize its short-term efficacy and clinical experience. Data of 101 cases undergoing da Vinci robotic surgical system for rectal cancer radical operation from March 2010 to September 2012 were retrospectively analyzed. Evaluation was focused on operative procedure, complication, recovery and pathology. All the 101 cases underwent operation successfully and safely without conversion to open procedure. Rectal cancer radical operation with da Vinci robotic surgical system included 73 low anterior resections and 28 abdominoperineal resections. The average operative time was (210.3±47.2) min. The average blood lose was (60.5±28.7) ml without transfusion. Lymphadenectomy harvest was 17.3±5.4. Passage of first flatus was (2.7±0.7) d. Distal margin was (5.3±2.3) cm without residual cancer cells. The complication rate was 6.9%, including anastomotic leakage(n=2), perineum incision infection(n=2), pulmonary infection (n=2), urinary retention (n=1). There was no postoperative death. The mean follow-up time was(12.9±8.0) months. No local recurrence was found except 2 cases with distant metastasis. Application of da Vinci robotic surgical system in rectal cancer radical operation is safe and patients recover quickly The short-term efficacy is satisfactory.
    Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 05/2013; 16(5):451-4.
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    ABSTRACT: To explore the effects of diagnostic protocols on etiology and outcome in immunocompromised host (ICH) with pulmonary infiltrate. For this historic control study, ICH with acute respiratory failure (ARF) were eligible as study group (n = 65) in 2009 while another ICH cohort was selected as control group (n = 45) in 2007. The protocol consisted of four parts: judgment possible site, determining probable etiology, checking and feedbacks on laboratory test in 12 hours and reassessment and adjustment treatment in 48-72 hours. The etiologies included infection, noninfection and unknown causes. Their average age was 45.3 years (range: 22 - 71). Causes of immune suppression were autoimmune disease (n = 69), hematological disorders (n = 21), solid cancers (n = 10) and others (n = 10). When two groups were compared, basic diseases, organ function and disease severity showed no significant difference, but etiologic diagnoses rate (73.8% vs 57.8%), time from ICU admission to diagnosis (4.0 vs 6.8 days) and 28-day mortality (38.5% vs 62.2%) had significant difference (P < 0.05). Implementation of clinical protocol in ICH with ARF is associated with improved etiologic diagnoses and decreased mortality.
    Zhonghua yi xue za zhi 03/2013; 93(9):684-9. DOI:10.3760/cma.j.issn.0376-2491.2013.09.013
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    ABSTRACT: Background/aims:Peritoneal implantation metastasis of gastric cancer cells is associated with poor prognosis. Peritoneal macrophages are the most important immune cells in the abdominal cavity to control tumor metastasis. In the present study, the immunosuppressive effects of mouse forestomach cells on macrophages were examined. Materials and Methods:Conditioned medium from mouse forestomach cell cultures were used to treat isolated peritoneal macrophages. A colorimetry-based phagocytosis assay was performed to investigate the functional change of macrophages. The alternation in cytokine secretion by macrophages was measured by enzyme-linked immunosorbent assay. Specific markers of macrophage polarization were analyzed by real-time reverse transcription polymerase chain reaction. The transforming growth factor-β1 signaling was evaluated by Western blotting. Neutralization experiments were performed by using transforming growth factor-β1 antibody. Results: The conditioned medium reduced the phagocytotic capability of macrophages. Lower tumor necrosis factor-αand interleukin-1βlevels and higher interleukin-10 and vascular endothelial growth factor levels were observed. Real-time reverse transcription polymerase chain reaction showed increased mRNA levels of M2 macrophage markers. Further study revealed that transforming growth factor-β1 was significantly elevated in the conditioned medium and transforming growth factor-β1 signaling was activated in the macrophages with treatment with conditioned medium. Neutralization of transforming growth factor-β1 reversed the immunosuppressive effects on macrophages. Conclusions: Immunosuppressive macrophages can be induced by conditioned medium from mouse forestomach cell cultures. These effects seemed to be through the production of transforming growth factor-β1 by the tumor cells. Targeting transforming growth factor-β1 intervention might help in the control of peritoneal metastasis of gastric cancers.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2012; 23(6):658-65. · 0.47 Impact Factor
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    ABSTRACT: Oxaliplatin is included in a number of effective combination regimens used as first and subsequent lines of therapy for metastatic colorectal cancer. Accumulating evidence indicates that autophagy plays a significant role in response to cancer therapy. However, the role of autophagy in oxaliplatin-induced cell death remains to be clarified. In this study, we showed that oxaliplatin induced cell death and autophagy in Caco-2 colorectal cancer cells. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (ATG5 or Beclin1) enhanced the cell death and reactive oxygen species (ROS) production induced by oxaliplatin in Caco-2 cells. Blocking oxaliplatin-induced ROS production by using ROS scavengers (NAC or Tiron) decreased autophagy. Furthermore, numerous dilated endoplasmic reticula (ER) were present in oxaliplatin-treated Caco-2 cells, and blocking ER stress by RNA interference against candidate of metastasis-1 (P8) and C/EBP-homologous protein (CHOP) decreased autophagy and ROS production. Taken together, these data indicate that oxaliplatin activates autophagy as a cytoprotective response via ER stress and ROS in human colorectal cancer cells.
    PLoS ONE 11/2012; 7(11):e51076. DOI:10.1371/journal.pone.0051076 · 3.53 Impact Factor
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    ABSTRACT: To explore the effects of cefoperazone-sulbactam (C/S) plus minocycline on extensively drug resistant Acinetobacter baumannii (XDRAB) infections in critically ill patients. For this prospective and single-center trial, a total of 101 patients with infection due to XDRAB received the primary therapy of C/S plus minocycline. Combined use of imipenem-cilastatin was considered when primary therapy failed. Among them, 77 patients were evaluated. There were 49 males and 28 females with a mean age of (69 ± 20) years. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15 ± 5. Among whom 61 had hospital-acquired pneumonia (n = 61), primary bacteremia (n = 5), intra-abdominal infection (n = 3), skin and soft tissue infection (SSTI)(n = 2) and multiple sites infection (n = 6). Twenty-three patients had mixed bacterial infections. Combined use of imipenem-cilastatin therapy was administered in 7 patients. The treatment duration was (16 ± 4) days. The outcomes were cure (n = 21), marked improvement (n = 27), improvement (n = 26) and ineffectiveness (n = 3). The overall effective rate was 62.3% (48/77) and the microbiological clearance rate 46.8% (36/77). The independent factors of decreased efficacy were underlying co-morbidity of impaired ability for infection control (OR = 5.3, P = 0.020), prolonged infection (OR = 3.8, P = 0.029), co-infecting organism (OR = 3.5, P = 0.032) and septic shock (OR = 2.5, P = 0.037). The combined regimen of C/S and minocycline is efficacious in the treatment of infections caused by XDRAB. But it has a lower rate of microbiological eradication.
    Zhonghua yi xue za zhi 10/2012; 92(40):2847-50.
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    ABSTRACT: To study the effect of different CO2 pneumoperitoneum pressures on the expression of adhesion molecules of human gastric cancer cell line MNK-45. MKN-45 cells in the experimental groups were exposed to simulated CO2 environment maintained at different pressures (1.2, 1.6, 2.0 kPa) for 4 hours. Control groups were exposed to room air. At the 0, 24, 48, 72, 96 hours after treatment, CD44v6, ICAM-1 and E-cadherin were detected by flow cytometry method. CD44v6 and ICAM-1 expressions showed pattern of firstly elevating, then descending to normal under the pressures of 1.2 kPa and 1.6 kPa. The expressions were different from control group significantly at 24 and 48 hours (P<0.01), while the 72 hours expression showed no difference compared with the controls (P>0.05). E-cadherin expression decreased significantly right after treatment compared to the control (P<0.01), but recovered to the level of control at 48 hours (P>0.05). In the 2.0 kPa group the expression changes of CD44v6, ICAM-1 and E-cadherin were more remarkable. CD44v6 and ICAM-1 expressions were increased significantly compared to control right after treatment (P<0.05). E-cadherin expression was significantly decreased even at 48 hours compared to the controls (P<0.01). In vitro CO2 pneumoperitoneum pressures have transient influence on the adhesion molecules expression of gastric cancer cell MKN-45, then those expressions can recover in a short-time.
    Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 08/2012; 15(8):830-3.
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    ABSTRACT: CD8(+) T cells that produce interleukin (IL)-17 (Tc17 cells) promote inflammation and have been identified in tumors. We investigated their role in the pathogenesis of gastric cancer. We used flow cytometry analyses to determine levels and phenotype of Tc17 cells in blood and tumor samples from 103 patients with gastric cancer. We performed multivariate analysis to identify factors associated with overall survival using the Cox proportional hazards model. CD8(+) T cells and monocytes were isolated and cocultured in an assay for induction of Tc17 cells. Tumor cells and myeloid-derived suppressor cells (MDSCs) were isolated and used in assays of Tc17 cell function. Tc17 cells with distinct cytokine and functional profiles were found in gastric tumor samples from patients. The percentage of Tc17 cells increased with tumor progression and was associated with overall survival time. Tumor-activated monocytes secreted IL-6, IL-1β, and IL-23, which promoted development of Tc17 cell populations. Supernatants from cultured Tc17 cells induced production of the chemokine CXCL12 by tumor cells; this promoted CXCR4-dependent migration of MDSCs and impaired functions of anti-tumor CD8(+) cytotoxic T cells via a cell contact-dependent mechanism. Percentages of Tc17 cells in gastric tumors are associated with survival times of patients. These cells promote chemotaxis of MDSCs, which might promote tumor progression.
    Gastroenterology 06/2012; 143(4):951-962.e8. DOI:10.1053/j.gastro.2012.06.010 · 13.93 Impact Factor
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    ABSTRACT: Peritoneal implantation metastasis of gastric cancer cells is associated with poor prognosis. Peritoneal macrophages are the most important immune cells in the abdominal cavity to control tumor metastasis. In the present study, the immunosuppressive effects of mouse forestomach cells on macrophages were examined. Conditioned medium from mouse forestomach cell cultures were used to treat isolated peritoneal macrophages. A colorimetry-based phagocytosis assay was performed to investigate the functional change of macrophages. The alteration of cytokine secretion by macrophages was measured by ELISA assay. Specific markers of macrophage polarization were analyzed by real-time RT-PCR. TGF-β1 signaling was evaluated by western blotting. Neutralization experiments were performed using an anti-TGF-β1 antibody. Conditioned medium reduced the phagocytotic capability of macrophages. Lower TNF-α and IL-1β levels and higher IL-10 and VEGF levels were observed. Real-time RT-PCR showed increased mRNA levels of M2 macrophage markers. Further study revealed that TGF-β1 was significantly elevated in the conditioned medium and TGF-β1 signaling was activated in the macrophages by the treatment of conditioned medium. Neutralization of TGF-β1 reversed the immunosuppressive effects on macrophages. Immunosuppressive macrophages can be induced by conditioned medium from mouse forestomach cell cultures. These effects appeared to occur through the production of TGF-β1 by the tumor cells. Targeted TGF-β1 intervention may help to control peritoneal metastasis of gastric cancers.
    Molecular Medicine Reports 04/2012; 5(4):988-92. DOI:10.3892/mmr.2012.777 · 1.48 Impact Factor

Publication Stats

144 Citations
80.01 Total Impact Points

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Institutions

  • 2005–2015
    • Third Military Medical University
      • Southwest Hospital
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2014
    • Southwest Hospital
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2013
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2009–2013
    • Peking Union Medical College Hospital
      Peping, Beijing, China