分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Zhang, Junjie
Zhu, Lining
Lu, Xiaolu
Wang, Yi
Gao, Shou-jiang
Feng, Pinghui
Feldman, Emily R.
Keyes, Lisa R.
Tibbetts, Scott A.
Fan, Hui
Feng, Hao
Xia, Zanxian
Xia, Zanxian
Sun, Jiya
Jiang, Taijiao
Sun, Jiya
Jiang, Taijiao
Sun, Jiya
Jiang, Taijiao
Jiang, Taijiao
摘要： Human gamma herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are capable of inducing tumors, particularly in in immune-compromised individuals. Due to the stringent host tropism, rodents are resistant to infection by human gamma herpesviruses, creating a significant barrier for the in vivo study of viral genes that contribute to tumorigenesis. The closely-related murine gamma herpesvirus 68 (gamma HV68) efficiently infects laboratory mouse strains and establishes robust persistent infection without causing apparent disease. Here, we report that a recombinant gamma HV68 carrying the KSHV G protein-coupled receptor (kGPCR) in place of its murine counterpart induces angiogenic tumors in infected mice. Although viral GPCRs are conserved in all gamma herpesviruses, kGPCR potently activated downstream signaling and induced tumor formation in nude mouse, whereas gamma HV68 GPCR failed to do so. Recombinant gamma HV68 carrying kGPCR demonstrated more robust lytic replication ex vivo than wild-type gamma HV68, although both viruses underwent similar acute and latent infection in vivo. Infection of immunosuppressed mice with gamma HV68 carrying kGPCR, but not wild-type gamma HV68, induced tumors in mice that exhibited angiogenic and inflammatory features shared with human Kaposi's sarcoma. Immunohistochemistry staining identified abundant latently-infected cells and a small number of cells supporting lytic replication in tumor tissue. Thus, mouse infection with a recombinant gamma HV68 carrying kGPCR provides a useful small animal model for tumorigenesis induced by a human gamma herpesvirus gene in the setting of a natural course of infection.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-05
Zhang, Junjie
Guo, Fei
Wang, Lei
Zhao, Wei
Zhang, Da
Yang, Heying
Wang, Jiaxiang
Hu, Qian
Yu, Jiekai
Zheng, Shu
Niu, Lili
Yang, Fuquan
摘要： Wilms' tumors are one of the most common malignant, solid intra-abdominal tumors observed in children. Although potential tumor markers have been found, inflammatory cytokines interfere with the process of specific protein identification. The present study was undertaken to identify post-traumatic stress-related factors of Wilms' tumors and to verify the accuracy of early-stage tumor-specific serum protein markers. Serum samples were screened for differentially-expressed proteins using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Potential markers were isolated and purified using solid-phase extraction (SPE) and SDS-PAGE. Following enzymatic digestion of the protein samples, the peptide fragments were detected with high performance liquid chromatography-mass spectrometry. The obtained peptide mass fingerprint was searched in the Swiss-Prot protein sequence database via the Mascot search engine. Differentially-expressed proteins were verified using western blot analysis. Differentially-expressed proteins with a mass/charge of 5,816 were screened out using SELDI-TOF-MS, and significant differences between the tumor and control groups, and the trauma and control groups were observed. Target proteins were isolated and purified using SPE and SDS-PAGE. Thioredoxin 1 (Trx1) was found to be differentially expressed. In the serum of children with Wilms' tumors, there was an increase in the level of the post-traumatic stress-related inflammatory factor, Trx1, as compared with the normal control group. Thus, the results of this study indicate that Trx1 presents a potential post-traumatic stress-related factor of Wilms' tumors.
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