Multi-layer polymeric implants for sustained release of chemopreventives |
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Authors: | Farrukh Aqil Jeyaprakash Jeyabalan Hina Kausar Shyam S Bansal Ram J Sharma Inder P Singh Manicka V Vadhanam Ramesh C Gupta |
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Affiliation: | a Department of Hematology, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, China b Department of Hematology and Oncology, Shanghai Jiaotong University School of Medicine, China |
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Abstract: | The polycomb group (PcG) protein BMI1 plays a critical role in regulating self renewal capacity of both normal and leukemic stem cells. BMI1 is frequently overexpressed in several types of cancer, which is associated with poor prognosis. However, there are few researches on BMI1 in myelodysplastic syndromes (MDS). In this study, we reported that overexpression of BMI1 protein was detected in MDS patients, and inversely correlated with the apoptosis of CD34+ cells. In vitro overexpression of BMI1 facilitated proliferation and inhibited apoptosis of MDS-L cells. The overexpression of BMI1 could downregulate apoptosis sensitivity to cytotoxic agents in MDS-L cells; on the contrary, MDS-L cells could be rendered apoptosis-sensitive by BMI1 knockdown. Overexpression of BMI1 antagonised apoptosis by downregulating several apoptosis-related proteins, such as p16INK4a, phospho-p53 (Ser46) and caspase 3/9. In addition, overexpression of BMI1 was correlated with an elevated IPSS score and a shorter survival. Collectively, overexpression of BMI1 induces resistance to apoptosis and contributes to adverse prognosis in MDS. BMI1 could serve as a therapeutic target for patients with MDS. |
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Keywords: | Myelodysplastic syndrome BMI1 Overexpression CD34 Apoptosis resistance |
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