Browsing by Subject "Xenografts"

Now showing 1 - 3 of 3
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    ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature
    (Impact Journals, 2014-09-30) Roy, Lynn; Samyesudhas, Serene J.; Carrasco, Martin; Joseph, Stancy; Dahl, Richard; Cowden Dahl, Karen D.; Biochemistry & Molecular Biology, School of Medicine
    Ovarian cancer is the most deadly gynecological malignancy since most patients have metastatic disease at the time of diagnosis. Therefore, identification of critical pathways that contribute to ovarian cancer progression is necessary to yield novel therapeutic targets. Recently we reported that the DNA binding protein ARID3B is overexpressed in human ovarian tumors. To determine if ARID3B has oncogenic functions in vivo, ovarian cancer cell lines stably expressing ARID3B were injected intraperitoneally into nude mice. Overexpression of ARID3B increased tumor burden and decreased survival. To assess how ARID3B contributes to the increased tumor growth in vivo, we identified ARID3B induced genes in tumor ascites cells. ARID3B induced expression of genes associated with metastasis and cancer stem cells (CD44, LGR5, PROM1 (CD133), and Notch2). Moreover, ARID3B increased the number of CD133+ (a cancer stem cell marker) cells compared to control cells. The increase in CD133+ cells resulting from ARID3B expression was accompanied by enhanced paclitaxel resistance. Our data demonstrate that ARID3B boosts production CD133+ cells and increases ovarian cancer progression in vivo.
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    Axolotl Xenografts Improve Regeneration of Xenopus Hind Limbs
    (Office of the Vice Chancellor for Research, 2013-04-05) Chen, Xiaoping; Stocum, David L.
    Axolotls regenerate perfect copies of amputated limbs, whereas Xenopus froglet limbs regenerate only a spike of cartilage. We asked whether axolotl muscle and cartilage xenografted from normal or GFP-labeled limbs to amputated froglet limbs, with or without treatment with cyclosporin A (CSA) and/or retinoic acid (RA), would improve Xenopus limb regeneration via the release of regeneration-promoting factors into the host limb tissue. The grafted froglet limbs were allowed to regenerate for three months to two years. We detected initial symptoms of graft vs. host disease with or without CSA treatment that subsequently disappeared. The grafted limbs first formed a spike that subsequently grew wider at the tip and after three months began to separate into 2-5 digit-like structures that continued to grow. CSA and low-dose RA treatment decreased the time at which digit formation could be detected but were not necessary for digit formation. The digit pattern was not asymmetric, thus individual digits were not identifiable. Immature muscle was detected in the regenerated limbs by trichrome and MF-20 antibody staining, and nerve fibers were detected by Luxol Fast Blue staining. In one limb with a GFP graft, a few axolotl cells were detected around the base of the digits that may have stimulated digit separation. Although the mechanism of digit formation remains obscure, we conclude that factors released by degraded axolotl tissue or surviving axolotl cells can stimulate complex tissue regeneration and initiate the first step of digital anterior-posterior pattern formation in regenerating Xenopus hind limbs. These results have significance for the possibility of stimulating the regeneration of complex mammalian structures that have been injured by trauma or disease.
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    Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo
    (Taylor & Francis, 2019-02) Fu, Yuanyuan; Hong, Liang; Xu, Jiecheng; Zhong, Guoping; Gu, Qiong; Gu, Qianqian; Guan, Yanping; Zheng, Xueping; Dai, Qi; Luo, Xia; Liu, Cui; Huang, Zhiying; Yin, Xiao-Ming; Liu, Peiqing; Li, Min; Pathology and Laboratory Medicine, School of Medicine
    Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated in silico screening and in vitro assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.