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Chen H.,Peoples Hospital of Yixing City | Xie L.,Nanjing University | Liu B.,Nanjing University
Chinese-German Journal of Clinical Oncology | Year: 2012

MDM2 (the product of murine double minute 2 gene) is one of the most important negative regulators of p53, which can binds to p53 and initiates ubiquitin-mediated degradation. Besides, MDM2 also controls the activity of several cell-cycle regulators, e.g. pRB, p21, E2F1, independently of p53. The important role of MDM2 in cell-cycle regulation indicates it to be a point of interest in cancer research. In recent years, studies revealed that MDM2 participated in the genesis and development of human tumors. The expression levels and activity of MDM2 was associated with the invasion, metastasis, prognosis and more practical, chemosensitivity. MDM2 is becoming a novel biomarker in cancer prognosis and chemosensitivity prediction. © 2012 Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg. Source

Lu Y.,Nanjing University | Lu Y.,Jiangsu University | Liu Y.,Jiangsu Institute of Cancer Research | Jiang J.,Peoples Hospital of Yixing City | And 5 more authors.
Oncology Reports | Year: 2014

A hallmark of small cell lung cancer (SCLC) is frequent relapse characterized by newfound resistance to formerly efficacious chemotherapies. The prognosis for SCLC patients is particularly unfavorable. Aurora kinase A (AURKA), a member of the serine/threonine kinase family, is overexpressed across many types of human tumors. Recent studies have identified AURKA as an important factor in tumorigenesis, but little is known regarding its specific roles in SCLC. The aim of the present study was to establish the roles of AURKA in the molecular pathogenesis of human SCLC. In the present study, we constructed a lentiviral vector to express siRNA against AURKA (LV-AURKA siRNA). As we expected, the viral construct effectively suppressed the expression of the AURKA gene and protein in H446 and H1688 cell lines. Additionally, RNA interference of AURKA inhibited the colony formation and subsequent growth of H446 and H1688 cell lines by increasing the incidence of cell cycle arrest in the G2/M phase. Furthermore, suppression of AURKA by LV-AURKA siRNA also increased apoptosis of SCLC cells. A potential mechanism for the increase of apoptosis is the downregulation of Bcl-2 and upregulation of Bax. AURKA gene suppression may provide a novel, effective therapy for SCLC patients by inhibiting cell division and increasing the rate of apoptosis of SCLC cells. Source

Qian W.,Shanghai University | Chen G.,Peoples Hospital of Yixing City | Zhang Y.,Shanghai University | Zhu W.,Shanghai University | And 2 more authors.
Chinese Journal of Cancer Biotherapy | Year: 2014

Objective: To systematically evaluate the efficacy and safety of the concurrent use of anti-VEGF and anti-EGFR antibodies in patients with metastatic colorectal cancer. Methods: PubMed/MEDLINE,Ovid/EMBASE, Cochrane and some other databases together with related meeting abstracts were searched for randomized controlled trials on this topic by two independent researchers. Data were extracted from the included studies and analyzed using Review Manager 5.0.23. Results: A total of 2059 patients in five studies were included in this Meta-analysis. Compared with the control treatment involving an anti-VEGF or anti-EGFR antibody alone, the concurrent use of anti-VEGF and anti-EGFR antibodies decreased the progression-free survival (RR=1.12, 95% CI: 1.05-1.19) as. Patients in the two treatment groups did not differ significantly in either overall survival (RR=1.17, 95% CI: 0.98-1.40) or overall response rate (RR=0.97, 95% CI: 0.89-1.07). There were significant differences between the two groups in grade 3/4 adverse cutaneous events (RR=12.62, 95% CI: 1.90-83.84), grade 3/4 infection (RR=1.53, 95% CI: 1.13-2.08), grade 3/4 hypertension (RR=0.61, 95% CI: 0.42-0.87), and grade 3/4 adverse events of nervous system (RR=0.54, 95% CI: 0.37-0.80) but not in grade 3/4 adverse gastrointestinal events (RR=1.48, 95% CI: 0.79-2.77) and grade 3/4 venous thrombosis (RR=1.18, 95% CI: 0.84-1.65). Conclusion: The concurrent use of anti-VEGF and anti-EGFR antibodies offer no additional benefits for patients with metastatic colorectal cancer as compared with the use of theses antibodies each alone and therefore should not be recommended in clinics. Source

Chen X.,Nantong University | Liu L.,Peoples Hospital of Yixing City | Qian R.,Nantong University | Liu J.,Nantong University | And 5 more authors.
Cellular and Molecular Neurobiology | Year: 2016

Src-associated in mitosis (Sam68; 68 kDa) is a novel RNA-binding protein that belongs to the signal transduction and activation of RNA family involved in various biological processes. However, the expression and roles of Sam68 in the central nervous system remain unknown. In the present study, we performed a spinal cord injury (SCI) model in adult rats and found a significant increase of Sam68 protein levels in this model, which reached a peak at day 3 and then gradually returned to normal levels at day 14 after SCI. We use immunohistochemistry analysis revealing a widespread distribution of Sam68 in the spinal cord. In addition, double-immunofluorescence staining showed that Sam68 immunoreactivity was found predominantly in neurons and astrocytes. Moreover, colocalization of Sam68/active caspase-3 has been respectively detected in neuronal nuclei, and colocalization of Sam68/PCNA has been detected in glial fibrillary acidic protein. In vitro, we found that depletion of Sam68 by short interfering RNA inhibits neuronal apoptosis and astrocyte proliferation and decreases cyclin D1 protein levels. In conclusion, this is the first study to find the Sam68 expression in SCI. Our results suggest that Sam68 might be illustrated in the apoptosis of neurons and proliferation of astrocytes after SCI. This research will provide new drug targets for clinical treatment of SCI. © 2016 Springer Science+Business Media New York Source

Jiang Z.,Suzhou University | Jiang J.,Peoples Hospital of Yixing City | Yang H.,Suzhou University | Ge Z.,Peoples Hospital of Yixing City | And 4 more authors.
Oncology Reports | Year: 2014

The overexpression of Aurora kinase A (AURKA), a member of serine/threonine kinase family, has been observed in various types of human cancers. However, the role of AURKA in osteosarcoma (OS), the most common type of primary malignancy arising from bone, has not been clarified. We used AURKA-specific lentivirus-delivered short hairpin RNA (shRNA) to significantly and sustainably silence the endogenous AURKA expression in human OS cells SAOS-2 and U2OS. We found that AURKA downregulation in OS cells prominently decreased colony formation ability in vitro and tumorigenesis ability in vivo. We further evaluated the effect of AURKA silence on cell viability by MTT assay, cell apoptosis and cell cycle by .ow cytometer detection. The results showed that AURKA silence inhibited cell viability by inducing cell apoptosis and G2/M cell cycle arrest in OS cells. Taken together, our findings indicate that AURKA plays a crucial role on OS growth by inhibiting cell apoptosis and propelling cell cycle. Inhibition of AURKA by lentivirus-delivered specific shRNA showed the therapeutic potential in treatment of osteosarcoma. Source

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