Xie L.-B.,University of Sichuan |
Zeng D.-Y.,University of Sichuan |
Wang X.-D.,University of Sichuan |
Lin T.,University of Sichuan |
And 3 more authors.
Transplantation Proceedings | Year: 2014
Objective The objective of this study was to compare the protease inhibitor gabexate with widely used inosine for reducing renal ischemia-reperfusion injury. Method A total of 48 rats were divided into 4 groups of 12 and administered gabexate, inosine, normal saline (NS), or nothing by injection through the vena dorsalis of the penis. Then all rats were subjected to right nephrectomy and 30-minute warm ischemia of the left kidney. At 24 and 48 hours after reperfusion, blood samples were collected from the inferior vena cava and serum creatinine (SCr) was assayed. Left kidney tissue was homogenized and used to assay malondialdehyde (MDA) and superoxide dismutase (SOD). The tissue was also analyzed using hematoxylin-eosin (HE) staining, TUNEL staining, and NF-κB immunohistochemistry. Results SCr level decreased after reperfusion more in the gabexate group than in the other groups. Reperfused kidney tissue in the gabexate group showed lower MDA levels but higher SOD activity than did tissue in the inosine and saline groups, as well as lower pathology scores based on HE staining, lower necrosis index, and lower levels of NF-κB expression (all P <.05). Tissue in the inosine and saline groups showed similar necrosis index and NF-κB expression (P >.05). Conclusion Preconditioning with gabexate is superior to preconditioning with inosine for ameliorating rat renal ischemia-reperfusion injury. Future studies are needed to verify the effects of gabexate in the clinic, especially for kidney transplantation. © 2014 by Elsevier Inc. All rights reserved.
Zhao S.,University of Sichuan |
Qiu Z.-X.,University of Sichuan |
Zhang L.,Key Laboratory of Transplant Engineering and Immunology |
Li W.-M.,University of Sichuan
Tumor Biology | Year: 2015
The extracellular-regulated kinase (ERK) 1/2, as a member of the mitogen-activated protein kinase family, plays a crucial role in the development of cancer. However, little is known about the prognostic value of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in non-small cell lung cancer (NSCLC). Thus, we investigated their prognostic values and analyzed the associations between their expressions and clinicopathological features in NSCLC patients. We examined ERK1/2 and p-ERK1/2 expressions via immunohistochemistry in 183 NSCLC samples. The prognostic significances of protein expression were evaluated with univariate and multivariate survival analysis. Of the specimens, 44.8 and 44.3 % revealed positive staining for ERK1/2 and p-ERK1/2, respectively. There were 24.6 % specimens with both ERK1/2 and p-ERK1/2-positive expression. The results showed p-ERK1/2-positive expression was an independent prognostic factor for poor overall survival (OS) in NSCLC patients on both univariate analysis (p < 0.0001) and multivariate analysis (p = 0.0000). Meanwhile, the positive expression of both proteins was also associated with poor OS (p = 0.002). With respect to clinicopathological features, the tumor differentiation was significantly associated with the positivity of ERK1/2, p-ERK1/2, and both proteins, while histological type was only related to ERK1/2. However, there were no significant differences between the expressions and other clinical features, such as gender, age, smoking, tumor–node–metastasis (TNM) stage, lymph node metastasis, and treatments. The p-ERK1/2-positive expression was associated with adverse outcomes, and the positive expression of both ERK1/2 and p-ERK1/2 proteins was also related to poor OS. Therefore, the positivity of p-ERK1/2 expression may serve as a vital biomarker in the development of NSCLC. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Xiao H.,Shanghai JiaoTong University |
Ding J.,Tianjin Medicine Union Center |
Gao S.,Shanghai JiaoTong University |
Yang S.,University of Sichuan |
And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2011
It is well-known that tobacco smoke is a definite causative agent important for human health. Epidemiological research has proven that smoking is a cause of various serious and fatal diseases. However, never-smokers comprise a high proportion of non-small-cell lung cancer (NSCLC) patients. To determine whether lung cancer patients in never smokers have different genetic mutations from their counterparts in smokers, we comprehensively searched the Cochrane Library, Medline and EMbase from 1966 to Jun 2010 for the following terms: ("non-smoker" or "never-smoker") and ("lung cancer") and ("gene") limited to English and clinical trials. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different molecular pathway of malignant formation, including EGFR gene mutation, P53 mutation and metabolic gene CYP1AIIle462Val polymorphism. These genes will help doctors to separate never-smoker lung cancer from smokers, and may present promising targets for therapy of never-smoker lung cancers. Future efforts should focus on further delineation of underlying biologic differences, identifying potential non-tobacco-related risk factors, and refining treatment strategies for different groups of lung cancerpatients.
Li J.,University of Sichuan |
Zhao Z.,University of Sichuan |
Liu J.,University of Sichuan |
Huang N.,University of Sichuan |
And 4 more authors.
Cell Proliferation | Year: 2010
Objectives: This study was carried out to reveal functions and mechanisms of MEK/ERK and p38 pathways in chondrogenesis of rat bone marrow mesenchymal stem cells (BMSCs), and to investigate further any interactions between the mitogen-activated protein kinase (MAPK) and transforming growth factor-β1 (TGF-β1)/Smads pathway in the process. Materials and methods: Chondrogenic differentiation of rat BMSCs was initiated in micromass culture, in the presence of TGF-β1, for 2 weeks. ERK1/2 and p38 kinase activities were investigated by Western Blot analysis. Specific MAPK inhibitors PD98059 and SB20350 were employed to investigate regulatory effects of MEK/ERK and p38 signals on gene expression of chondrocyte-specific markers, and TGF-β1 downstream pathways of Smad2/3. Results: ERK1/2 was phosphorylated in a rapid but transient manner, whereas p38 was activated in a slow and sustained way. The two MAPK subtypes played opposing roles in mediating transcription of cartilage-specific genes for Col2α and aggrecan. TGF-β1-stimulated gene expression of chondrogenic regulators, Sox9, Runx2 and Ihh, was also affected by activity of PD98059 and SB203580, to different degrees. However, influences of MAPK inhibitors on gene expression were relatively minor when not treated with TGF-β1. In addition, gene transcription of Smad2/3 was significantly upregulated by TGF-β1, but was regulated more subtly by treatment with MAPK inhibitors. Conclusions: MAPK subtypes seemed to regulate chondrogenesis with a delicate balance, interacting with the TGF-β1/Smads signalling pathway. © 2010 Blackwell Publishing Ltd.
Cheng L.,Key Laboratory of Transplant Engineering and Immunology |
Ye F.,Key Laboratory of Transplant Engineering and Immunology |
Yang R.,Key Laboratory of Transplant Engineering and Immunology |
Lu X.,Key Laboratory of Transplant Engineering and Immunology |
And 5 more authors.
Acta Biomaterialia | Year: 2010
Many studies have shown that calcium phosphate ceramics can induce bone formation in non-osseous sites without the application of any osteoinductive biomolecules, but the mechanisms of this phenomenon (intrinsic osteoinduction of bioceramics) remain unclear. In this study, we compared the intrinsic osteoinduction of porous hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) implanted in mice at different sites. In 30 mice the left fibula was fractured and the right fibula was kept intact. A porous HA/β-TCP cylinder was implanted into both the left (group 1) and right (group 2) leg muscles of each animal. In addition, two HA/β-TCP cylinders were bilaterally implanted into leg subcutaneous pockets (group 3) in each of the remaining 15 mice. New bone formation was studied in the three groups by histology, histomorphometry and immunostaining. In group 1 new bone was observed at week 6 and bone marrow appeared at week 12. In group 2 new bone was observed at week 8 and bone marrow appeared at week 12. The new bone area percentage in group 1 was significantly higher than in group 2 at both weeks 8 and 12. In contrast, group 3 did not show any new bone within the period studied. These differences were explained based on the location of the implants and thus their proximity to the osteogenic environment of fracture healing. The results support the hypothesis that intrinsic osteoinduction by calcium phosphate ceramics is the result of adsorption of osteoinductive substances on the surface. © 2009 Acta Materialia Inc.