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Browsing by Author "Cai, Q."
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Item Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells(Nature Publishing Group, 2015-06) Cai, Q.; Yan, L.; Xu, Y.; Department of Microbiology & Immunology, IU School of MedicineHigh-grade serous ovarian cancer is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells.Item Combinations of antioxidants and/or of epigenetic enzyme inhibitors allow for enhanced collection of mouse bone marrow hematopoietic stem cells in ambient air(Elsevier, 2018-07) Cai, Q.; Capitano, M.; Huang, X.; Guo, B.; Cooper, S.; Broxmeyer, H.E.; Microbiology and Immunology, School of MedicineHematopoietic cell transplantation (HCT) is a treatment for malignant and non-malignant disorders. However, sometimes the numbers of donor hematopoietic stem cells (HSC) are limiting, which can compromise the success of HCT. We recently published that collection and processing of mouse bone marrow (BM) and human cord blood cells in a hypoxic atmosphere of 3% O2 or in ambient air (~21% O2) in the presence of cyclosporine A yields increased numbers of HSC. We now show that collection and processing of mouse BM cells in ambient air in the presence of specific combinations of anti-oxidants and/or inhibitors of epigenetic enzymes can also enhance the collection of HSC, information of potential relevance for enhanced efficacy of HCT.