Xuexian Yan

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (6)27.05 Total impact

  • Xiaoling Yin · Xuexian Yan · Qinan Yang · Hui Cao · Houjie Liang
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    ABSTRACT: This study was designed to establish an interleukin-12 (IL-12)-expressing murine Lewis lung carcinoma (LLC) cell vaccine (LLC/murine IL-12 [mIL-12]) and assess its antitumor efficacy and mechanism in vivo. The recombinant IL-12 plasmid was transfected into LLC cells and screened by G418, and positive clones were obtained. C57BL/6 tumor-bearing mouse model was established and tumor-bearing mice were randomly divided into three groups (n = 20), that is, treated with an intratumoral injection of phosphate-buffered solution, blank plasmid, or LLC/mIL-12 vaccine, respectively, at days 0, 7, and 14. Tumor size was measured before and after treatment. Tumor growth curve was plotted, cytolytic T lymphocyte (CTL) activity assay and natural killer (NK) cell activity assay were performed, CD4(+) and CD8(+) T lymphocyte were quantitated using flow cytometry, and the expression of interferon-gamma (IFN-gamma), IL-12, and interferon-inducible protein-10 (IP-10) in serum was detected by ELISA. Microvessel density was determined by immunohistochemistry after all mice were euthanized at day 21. The study revealed suppressed tumor growth, elevated levels of IFN-gamma, IP-10, and IL-12, augmented NK and CTL cell activities, and decreased microvessel density of tumor tissues. There were abundant CD4(+) and CD8(+) T lymphocyte infiltration in the vaccine group. This study demonstrated that the antitumor mechanism of LLC/mIL-12 vaccine was to promote IFN-gamma and IL-12 secretion, augment the NK and CTL cell activities, and decrease the microvessel density of tumors.
    No preview · Article · Jun 2010 · Cancer Biotherapy & Radiopharmaceuticals
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    ABSTRACT: This study was designed to determine the antitumor effects of iodine-131 labeled monoclonal antibody LC-1 ((131)I-LC-1), interleukin-12 (IL-12) vaccine, or the combination of both on C57BL/6 mice bearing Lewis lung carcinoma (LLC) tumors. Tumor-bearing mice models were randomly divided into 4 groups that were respectively injected intratumorally with phosphate buffered solution (PBS), IL-12 vaccine gene therapy (GT), (131)I-LC-1 radioimmuno-therapy (RIT), or GT+RIT. Tumor volumes were measured before and after treatment. ELISA and RT-PCR determined the expression of IL-l2. LC-1 monoclonal antibody (Mab) was labeled with Na(131)I. Cytolytic T lymphocyte (CTL) activity assay, Natural Killer cell (NK) activity assay and apoptosis analysis were performed. Intratumoral (131)I-LC-1 injection leads to higher delivery of the antibody to the tumor. Tumor apoptosis occurred in the GT, RIT and GT+RIT groups. Tumor growth was inhibited in the GT, RIT and GT+RIT groups. Compared with other groups, the combination of GT+RIT up-regulated the expression of IL-l2 gene and inhibited the tumor growth more effectively than either GT or RIT alone (p<0.05). These results suggest that GT+RIT have the synergistic antitumor effects on tumor-bearing mice.
    No preview · Article · Nov 2009 · International immunopharmacology
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    ABSTRACT: The collagen IV binding receptor integrin alpha1beta1 has been shown to regulate lung cancer due to its proangiogenic properties; however, it is unclear whether this receptor also plays a direct role in promoting primary lung tumors. To investigate this possibility, integrin alpha1-null mice were crossed with KrasLA2 mice that carry an oncogenic mutation of the Kras gene (G12D) and develop spontaneous primary tumors with features of non-small cell lung cancer. We provide evidence that KrasLA2/alpha1-null mice have a decreased incidence of primary lung tumors and longer survival compared with KrasLA2/alpha1 wild-type controls. Tumors from KrasLA2/alpha1-null mice were also smaller, less vascularized, and exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end staining, respectively. Moreover, tumors from the KrasLA2/alpha1-null mice showed diminished extracellular signal-regulated kinase (ERK) but enhanced p38 mitogen-activated protein kinase activation. Primary lung tumor epithelial cells isolated from KrasLA2/alpha1-null mice showed a significant decrease in anchorage-independent colony formation, collagen-mediated cell proliferation, ERK activation, and, most importantly, tumorigenicity when injected into nude mice compared with KrasLA2/alpha1 wild-type tumor cells. These results indicate that loss of the integrin alpha1 subunit decreases the incidence and growth of lung epithelial tumors initiated by oncogenic Kras, suggesting that both Kras and integrin alpha1beta1 cooperate to drive the growth of non-small cell lung cancer in vivo.
    Preview · Article · Sep 2008 · Cancer Research
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    ABSTRACT: Produced by dietary fiber, butyrate is a potential chemopreventive agent against colon cancer. It stimulates proliferation of normal colonic epithelial cells but induces growth inhibition, differentiation, apoptosis, or a combination of effects in colon carcinoma cells. In this study, we used cDNA membrane arrays and real-time reverse transcriptase-polymerase chain reaction to identify stress genes that were differentially regulated by sodium butyrate (NaB) in HT 29 human colon carcinoma cells. The results indicated that a group of heat shock protein (hsp) genes were upregulated by 3 mM NaB within the first 24 hours of exposure. Because the transcription of hsp genes is under the control of heat shock factors (HSFs), we measured the effects of overexpressed HSF-1 on the responses of HT 29 cells to NaB. Overexpression of HSF-1 inhibited NaB-induced differentiation as measured by alkaline phosphatase activity and carcinoembryonic antigen expression. These results suggest that increased expression of HSFs and Hsps might render colon carcinoma cells resistant to the chemopreventive effects of butyrate.
    Full-text · Article · Feb 2006 · Cell Stress and Chaperones
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    ABSTRACT: This study provides evidence that in mammary epithelial cells the pluripotent cytokine TGF-beta1 repressed expression of multiple genes involved in Phase II detoxification. GCLC, the gene that encodes the catalytic subunit of the enzyme glutamate cysteine ligase, the rate-limiting enzyme in the biosynthesis of glutathione, was used as a molecular surrogate for investigating the mechanisms by which TGF-beta suppressed Phase II gene expression. TGF-beta was found to suppress luciferase reporter activity mediated by the human GCLC proximal promoter, as well as reporter activity mediated by the GCLC antioxidant response element, ARE4. TGF-beta downregulated expression of endogenous GCLC mRNA and GCLC protein. TGF-beta suppression of the Phase II genes correlated with a decrease in cellular glutathione and an increase in cellular reactive oxygen species. Ectopic expression of constitutively active Smad3E was sufficient to inhibit both reporters in the absence of TGF-beta, whereas dominant negative Smad3A blocked TGF-beta suppression. Smad3E suppressed Nrf2-mediated activation of the GCLC reporter. We demonstrate that TGF-beta increased ATF3 protein levels, as did transient overexpression of Smad3E. Ectopic expression of ATF3 was sufficient to suppress the GCLC reporter activity, as well as endogenous GCLC expression. These results demonstrate that Smad3-ATF3 signaling mediates TGF-beta repression of ARE-dependent Phase II gene expression and potentially provide critical insight into mechanisms underlying TGF-beta1 function in carcinogenesis, tissue repair, and fibrosis.
    Full-text · Article · Mar 2005 · Free Radical Biology and Medicine
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    ABSTRACT: Cyclooxygenase (COX) and its prostanoid metabolites have been implicated in the control of cell survival; however, their role as mitogens remains undefined. To better understand the role of prostanoids on cell growth, we used mouse colon adenocarcinoma (CT26) cells to investigate the role of prostaglandin E2 (PGE2) in cell proliferation. CT26 cells express both COX1 and COX2 and metabolize arachidonic acid to PGE2. Treatment with indomethacin, or COX-selective inhibitors, prevents PGE2 biosynthesis and CT26 cell proliferation. The anti-proliferative effects of COX inhibition are rescued specifically by treatment with PGE2 or the EP4 receptor-selective agonist PGE1-OH via phosphatidylinositol 3-kinase/extracellular signal-regulated kinase (ERK) activation, thus providing a functional link between PGE2-induced cell proliferation and EP4-mediated ERK signaling. Indomethacin or COX2 inhibitors, but not COX1 inhibitors, reduced the size and number of CT26-derived tumors in vivo. These inhibitory effects are paralleled by marked declines in the levels of tumor PGE2, suggesting that their anti-tumor effects are directly associated with the inhibition of COX2 enzymatic activity. The described anti-tumor effects of indomethacin are evident whether it is administered at the time of, or 7 days after, tumor cell injection, suggesting that it has tumor preventive and therapeutic actions. Furthermore, the observation that indomethacin increases the survival rates of tumor-bearing mice, even after withdrawal of the drug, indicates that its effects are long lasting and that it may be potentially useful for the prevention and the clinical management of human cancers.
    Preview · Article · Aug 2004 · Journal of Biological Chemistry