To block NuRD complex activity, we treated HuH7 cells with HDAC inhibitors (SBHA and SAHA) or a PARP inhibitor (AG-014699) to identify the reduction of the EpCAM+ CSCs population, suggesting that NuRD participates in the maintenance of stemness and chemoresistance of EpCAM+ CSCs. Combination therapy of SBHA and AG-014699 successfully inhibited HCC growth in vivo in a mouse xenograft model. Conclusion: The NuRD complex mediates the maintenance of stemness and chemoresistance of EpCAM+ CSCs through interaction with
HDAC and PARP. Combination therapy of HDAC and PARP inhibitors may offer novel therapeutic ICG-001 possibilities to patients with advanced HCC. Disclosures: Mariko Yoshida – Grant/Research Support: Bayer Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Kouki Nio, Taro Yamashita, Mitsumasa Kondo, Hikari Okada, Tomoyuki Hayashi, Takehiro Hayashi, Yoshimoto Nomura, Yasumasa
Hara, Naoki Oishi, Hajime Dabrafenib price Sunagozaka, Hajime Takatori, Masao Honda Human biliary tree stem/progenitor cells (hBTSCs), obtained from human adult biliary tree tissue are multipotent endodermalderived epithelial stem cells, able to differentiate
in vitro and in vivo towards hepatocytes, cholangiocytes or pancreatic islets. They reside in peribiliary MCE公司 glands (PBGs) of large intrahepatic and extrahepatic bile ducts and furnish maturational lineages within the bile duct walls sustaining tissue renewal. The ability of stem cells to control T-cells immune-response was recently described for mesenchymal stem cells and dental pulp stem cells. So far this property has never been investigated for adult endodermal-derived cell populations. AIM. To evaluate whether hBTSCs are able to modulate immune response via activating the Fas/Fas ligand (FasL) apoptosis signaling pathway in human lymphocytes. The in vitro interaction between hBTSC primary cultures and human lymphocytes isolated from different donors has been evaluated. Fluorescence-activated cell sorting analysis of T-cells co-cultured with hBTSCs through different time points indicated that hBTSCs induce apoptosis in activated CD4+ and CD8+ T-cell populations. Moreover, Fas receptor appeared to be more expressed in T-cells co-cultured with hBTSCs with respect to resting T-cells. Western blot data demonstrated that hBTSCs constitutively express high levels of FasL that markedly increased after co-culture with T-cells. Confocal microscopy carried out on the first cell seeding (after isolation) demonstrates that FasL was expressed only by epithelial cells and not by fibroblast-like cell population.