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Hangzhou, China

Lu Q.,PLA Fourth Military Medical University | Lu S.,Xian Central Hospital | Huang L.,PLA Fourth Military Medical University | Wang T.,PLA Fourth Military Medical University | And 5 more authors.
Diagnostic Pathology | Year: 2013

Objective: This article aims to investigate the expression of vacuolar-H + -ATPase (V-ATPase) in non-small cell lung cancer (NSCLC) and its variations with pathological type and grade. Furthermore, to evaluate the chemotherapy drug sensitivity of different cancer tissues as well as its correlation with V-ATPase expression in NSCLC.Methods: V-ATPase expression was examined in 92 NSCLC tissue samples using the immunohistochemical Envision method and immunofluorescence assay. The location of V-ATPase expression was observed by confocal laser scanning microscopy and the difference of its expression rate was evaluated. The sensitivity of cancer tissues to chemotherapy drug was examined using MTT assay and its correlation with the V-ATPase expression was tested in NSCLC by Spearman rank correlation analysis.Results: V-ATPase expression was mainly localized in the cell membrane and cytoplasm. The expression rate of V-ATPase was 71.43% in squamous cell lung cancer, significantly lower than that of the lung adenocarcinoma (83.72%, P = 0.000). In different pathological grades of squamous cell lung cancer, the expression rate of V-ATPase was 58.33% in grade II, significantly lower than that of the grade III (84.00%, P = 0.014). The expression rate of V-ATPase in grade II lung adenocarcinoma was 76.67%, significantly lower than that of the grade ΙΙΙ adenocarcinoma (100.0%, P = 0.012). Correlation analysis showed that the sensitivity of NSCLC tissues to cyclophosphamide, gemcitabine, doxorubicin, paclitaxel and cisplatin was significantly correlated with the V-ATPase expression rate (P < 0.05).Conclusions: V-ATPase was overexpressed in NSCLC. The expression of V-ATPase was related to the pathological type and grade of cancer and was likely associated with chemotherapy drug resistance in NSCLC.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7515811511020000. © 2013 Lu et al.; licensee BioMed Central Ltd. Source


Chen Q.-Y.,117th Hospital of PLA
Chinese Journal of Oncology | Year: 2012

Objective: To explore the expression of ezrin protein in human non-small cell lung cancer (NSCLC) tissues and lung cancer cell lines, and the association between the expression of ezrin protein and the expression of E-cadherin and CD44V6 proteins. Methods: The expression of ezrin protein and mRNA in lung cancer cell lines was detected by RT-PCR and Western blotting. Ezrin, E-cadherin and CD44V6 were detected by immunohistochemical SP staining in tumor tissues from 150 lung cancer cases and in adjacent normal lung tissues from 30 patients. Furthermore, the expression of ezrin in 30 freshly-taken NSCLC tissues was also detected by Western blot. Results: The expression of ezrin protein and mRNA was up-regulated in highly metastatic human lung cancer. The positive rate of ezrin, E-cadherin and CD44V6 expression in the lung cancer was 61.3%, 54.0% and 58.7%, respectively. The up-regulation of ezrin expression was significantly correlated with lymph node metastasis, but not correlated with age, sex, tumor size, histological type, clinical TNM system and pathological grade. Western blot analysis showed that the level of ezrin in the NSCLC tissues was significantly higher than that in the normal tissues (t = 5.013, P < 0.01). Survival analysis showed that the 5-year survival rate of patients with negative ezrin expression was 29.3%, significantly higher than that of patients with positive ezrin expression (15.2%, χ2 = 4.128, P = 0.042). Multivariate Cox regression analysis showed that ezrin expression (RR = 3.012, P = 0.047) and lymph node metastasis (RR = 4.827, P = 0.035) were significantly independent prognostic factors for patients with lung cancer. Furthermore, a negative correlation was observed between the expressions of ezrin and E-cadherin in lung cancer, and a positive correlation between the expressions of ezrin and CD44V6 in lung cancer. Conclusions: Ezrin, E-cadherin and CD44V6 play an important role in the regulation of growth and meastasis of lung cancer. Combined detection of ezrin, E-cadherin and CD44V6 expression is helpful in evaluating the metastasis and prognosis of non-small cell lung cancer. Source


Chen Q.-Y.,117th Hospital of PLA | Xu L.-Q.,117th Hospital of PLA | Jiao D.-M.,117th Hospital of PLA | Yao Q.-H.,Zhejiang Chinese Medical University | And 5 more authors.
International Journal of Molecular Medicine | Year: 2011

Rac1, an intracellular signal transducer, regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac1 has been reported in several human cancers. However, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of Rac1 as an appropriate molecular target for cancer gene therapy. The expression of Rac1 in 150 primary non-small cell lung cancer tissues (NSCLC) and 30 normal paraneoplastic lung tissues was determined by immunohistochemical staining, and the correlation of Rac1 overexpression with clinicopathological factors was evaluated. Overexpression of Rac1 was detected in 94 of 150 lung cancer specimens, the incidence rate being higher than that in normal lung tissue specimens. In addition, overexpression of Rac1 was also associated with poor differentiation, high TNM stage, and lymph node metastasis in NSCLC patients. Moreover, RNAi-mediated suppression of Rac1 expression reduced lamellipodia formation, migration and invasion potential of a lung cancer cell carcinoma cell line, 801D. Down-regulation of Rac1 expression also reduced the expression of Pak1. NSC23766, an inhibitor of Rac1 activity, could also inhibit lung cancer cell migration, invasion and induce rearrangements of the actin cytoskeleton. Furthermore, the suppression of Rac1 expression also sensitized cells to antitumor drugs. These results indicate that the overexpression of Rac1 is tightly associated with an aggressive phenotype of lung cancer cells. Therefore, we proposed that Rac1 could be a potential molecular target of gene therapy by RNAi-targeting in lung cancer cells. Source


Chen J.,117th Hospital of PLA | Song D.,117th Hospital of PLA
Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology | Year: 2014

Background: Researches indicated that etiology and epidemiology of pertussis toxin (PTX)-dependent experimental autoimmune uveoretinitis (EAU) model are very different with human uveoretinitis owing to the influence of PTX on immune. Our previous study has established lipopolysaccharide (LPS), an endotoxin, which instesad of PTX, mediated EAU model. However, the exact roles of LPS and PTX in EAU still remained unclear. Objective: This study was to investigate the roles of LPS and PTX in EAU model. Methods: Twenty SPF C57BL/6(H-2b) mice were assigned to 0 d-PTX-EAU group, 7 d-PTX-EAU group, 0 d-LPS-EAU group and 7 d-LPS-EAU group using random number table method. The mice were immunized with interphotoreceptor retinoid-binding protein 1-20(IRBP 1-20) emulsified in complete Freund adjuvant (CFA), and concurrently with or on day 7 postimmunization, LPS or PTX was injected in the footpad or intraperitoneally respectively. Delayed-type hypersensitivity (DTH) of the mice was evaluated by measuring the ear thickness 48 hours after IRBP was injected into the ear pinna, and lymphocyte proliferation was assessed by tritiated thymidine uptake. Retinal histopathological examination was performed and scored based on criteria of Caspi. The use and care of experimental animals complied with Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results: Serious infiltration of inflammatory cells, disorder of entire retinal structure and retinal folds were seen in the mice of the 0 d-PTX-EAU group and 7 d-LPS-EAU group on 21 days after injection of PTX or 14 days after injection of LPS, and severe vitritis and a few granuloma-like lesions were found in the 0 d-PTX-EAU group. However, only mild vasodilatation or less retinal folds were found in the 7 d-PTX-EAU group and 0 d-LPS-EAU group. The pathological scores in the mice of the 0 d-PTX-EAU group and 7 d-LPS-EAU group were higher than those of the 7 d-PTX-EAU group and 0 d-LPS-EAU group (all at P < 0.05). The ear thickness was (62.600 ± 3.362) μm, (60.000 ± 2.345) μm, (30.400 ± 1.817) μm and (32.800 ± 1.643) μm in the 0 d-PTX-EAU group, 7 d-PTX-EAU group, 0 d-LPS-EAU group and 7 d-LPS-EAU group, showing a significantly difference among the 4 groups (Fgroup = 259.751, P= 0.000), and the ear thicknesses of 0 d-PTX-EAU group and 7 d-PTX-EAU group were significantly higher than those of the 0 d-LPS-EAU group and 7 d-LPS-EAU group (all at P < 0.05). The lymphocyte proliferation was strongly enhanced in PTX-EAU groups, and the radiation count per minute (cpm) was (16150.000 ± 799.218)/min and (16120.000 ± 729.383)/min in the 0 d-PTX EAU group and 7 d-PTX EAU group, and (8348.000 ± 258.979)/min and (8540.000 ± 81.548)/min in the 0 d-LPS EAU group and 7 d-LPS EAU group respectively, with a significant difference among the PTX-EAU groups and LPS-EAU groups (Fgroup =316.978, P= 0.000). Conclusions: LPS and PTX play different roles during the EAU formation. LPS may be involved in the breakdown of blood-retina barriers (BRB). Copyright © 2014 by the Chinese Medical Association. Source


Chen J.,117th Hospital of PLA | Song D.,117th Hospital of PLA
Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology | Year: 2014

Background: The pathogenesis and management of human autoimmunity uveoretinitis is a focus in ophthalmology. For decades, a traditional experimental autoimmunity uveoretinitis (EAU) induced by pertussis toxin (PTX) was used for the basic investigation, which was thought to have a large deviation from the natural course of human autoimmunity uveoretinitis. Objective: This study was to establish a new mice model of autoimmunity uveoretinitis which mimics the human autoimmunity uveoretinitis pathogenesis and offer a basis for the investigation and treatment of uveoretinitis. Methods: Twenty 6-8 weeks old specific pathogen-free female C57BL/6(H-2) mice were randomized into normal control group, only endotoxin (lipopolysaccharide, LPS) induced uveitis group (endotoxin induced uveitis [EIU]group), interphotoreceptor retinoid-binding protein (IRBP1-20)+complete Freund adjuvant (CFA) induced uveoretinitis group (EAU group) and IRBP + CFA + LPS induced uveoretinitis group (LPS-EAU group). The mice of the EAU were only immunized with IRBP emulsified in CFA, and LPS-EAU group firstly were immunized with IRBP emulsified in CFA and then LPS was injected in the footpad of the mice on 7 days following immunization. The ocular pathological examination, histopathological scoring, delayed-type hypersensitivity and specific lymphocyte proliferating response were evaluated and compared with the EIU models, traditional EAU models without PTX and LPS-EAU models. The use and care of experimental animals complied with Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results: No inflammatory response was found in the iris, cilliary body and retina of mice in the normal control group. However, mild blood vessels dilation and fibrin exudation were seen in the iris and cilliary body of mice in the EIU group. In the EAU group, mild vasculitis and swelling of nerve fiber layer were exhibited in the retinas; while in the LPS-EAU group, severe disorder of retinal structure, infiltration of inflammatory cells and damage of photoreceptor were found under the optical microscope. The pathological score was 0 in the models of the normal control group and EIU group, 0.5 score in the EAU group and 3.0 scores in the LPS-EAU group, with a significant difference in the pathological scores between the EAU group and the LPS-EAU group (U=16.246, P=0.001). The earthickness of the mice was (35.60 ± 0.55) μm in the LPS-EAU group, and this value was significantly higher than (12.60 ± 0.55) μm of the EIU group (q=23.003, P<0.01), but closed to (34.80 ± 0.84) μm of the EAU group (t=0.820, P>0.05). The obvious cloning were seen and theradiation count per minute was (8540.00 ± 54.77)/min in the model mice of the LPS-EAU group, and that in the EAU group was (8484.00 ± 47.75)/min, without significant difference between them (q=56.634, P=0.069). Compared with the β particle number (2 050.00 ± 50.00)/min in the EIU group, that of the LPS-EAU group was significantly elevated (q=195.683, P=0.000). Conclusions: LPS injection can induce EAU in mice, and this model can better imitate the pathogenesis of human autoimmunity uveoretinitis. Copyright © 2014 by the Chinese Medical Association. Source

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