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Pharmacokinetics, Biodistribution, and Therapeutic Applications of Recently Developed siRNA and DNA Repair Genes Recurrence
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Survivin is an inhibitor of programmed cell death (apoptosis), expressed in various types of malignant tumor cells, especially in drug-resistant cells [53]. Survivin was initially identified as an inhibitor of caspase-9 and also found to be involved in the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis and chemo resistance [54]. Therefore, siRNA targeting survivin is pursued as a way of potentiating the activity of chemotherapeutics. Another main cause of failure in chemotherapy is MDR-related P-glycoprotein (Pgp). Pgp, a typical ATP-binding cassette membrane transporter, causes efflux of a broad range of drugs from a cell, reducing effective accumulation of the drugs in the cell [55]. Overexpression of Pgp, also known as MDR 1 protein 1 (MDR-1), and upregulation of its functional activity in cancer cells lead to reduced sensitivity to chemotherapy, thus making an attractive target for siRNA therapy [56].
Uniqueness, Advantages, Challenges, Solutions, and Perspectives in Therapeutics Applying RNA Nanotechnology
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Peixuan Guo, Farzin Haque, Brent Hallahan, Randall Reif, Hui Li
Cleavage of the HBV mRNA was nearly complete in vitro and HBV replication was inhibited in vivo by this chimeric pRNA (Hoeprich et al., 2003). The antiapoptosis factor, survivin, regulates tumor development and progression. A chimeric pRNA containing a hammerhead ribozyme designed to target survivin mRNA was shown to suppress survivin gene expression and initiate apoptosis in cell cultures (Liu et al., 2007). It was shown that the HBV ribozyme can also cleave the poly(A) signal from HBV mRNA after being incorporated into the 3WJ nanoparticles (Figure 10.4) (Liu et al., 2007; Shu et al., 2011a).
The Role of Nanotechnology in the Treatment of Drug Resistance Cancer
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Sandipan Dasgupta, Anup Kumar Das, Paulami Pal, Subhabrata Ray, Bhaskar Mazumder
It is well known that surviving, which is a negative regulator of apoptosis, generally shows high expression levels in MDR cancer cells. Therefore, inhibition of survivin expression can be considered as an effective means in increasing apoptosis in cancer cells (Kanwar et al., 2011).
Improved mechanical properties by modifying fibrin scaffold with PCL and its biocompatibility evaluation
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Lei Yang, Xiafei Li, Dongmei Wang, Songfeng Mu, Wenhao Lv, Yongwei Hao, Xiaosheng Lu, Guojiang Zhang, Wenbin Nan, Hongli Chen, Liqin Xie, Yongjun Zhang, Yuzhen Dong, Qiqing Zhang, Liang Zhao
MSCs proliferation were the better state of MSCs when it was synthesized. In the composition of the extracellular matrix (ECM), the secretion and growth of MSCs are also very important to it, for example, degraded scaffolds are replaced by collagen. Since then, when MSCs do not proliferate or contractile, it is beneficial to vasoconstriction state. Hence, we monitored the specificity of MSCs and ECM markers in 6 days. After MSCs were cocultured with PCL/fibrin scaffold extract for 3 days, the expression of collagen, survivin and CD105 genes decreased obviously (Figure 4(C)). However, there was no significant difference in MSCs gene expression at day 6 compared to control group (Figure 4(C)). Collagen was the main component of ECM, which plays an important role in cell growth [32]. However, the low expression of collagen in PCL/fibrin scaffolds was attributable to the fact that PCL hindered the secretion of ECM. Survivin belongs to inhibitor of apoptosis protein, which can regulate cell proliferation and anti-apoptosis. In addition, survivin gene can be fully expressed in MSCs. Vimentin is one of key structure genes of MSCs, which maintains the integrity and stability of the cytoskeleton. CD105 was commonly one of MSCs upper surface markers. The expression of CD105 in MSCs cultured with scaffolds showed that not only the cells had good compatibility with scaffolds, but also the immunophenotype of MSC was maintained in scaffold culture.
Immunotherapy approach with recombinant survivin adjuvanted with alum and MIP suppresses tumor growth in murine model of breast cancer
Published in Preparative Biochemistry and Biotechnology, 2018
Himani Garg, Jagdish C. Gupta, G. P. Talwar, Shweta Dubey
Survivin is a tumor protein belonging to member of inhibitor of apoptosis (IAP) family of proteins with a single Baculovirus IAP repeat domain.[1] Survivin is overexpressed by a large number of cancer cells but is not present in normal cells.[234] Survivin is the smallest member of IAP family of proteins and is involved in various processes contributing to survival of cancer cells such as inhibition of apoptosis and regulation of cell cycle.[5] Expression of survivin in tumors also correlates with resistance to chemotherapy and aggressiveness of tumors.[345] Survivin is specifically expressed on tumor cells and is a safe and attractive target for development of cancer therapeutics. Various approaches have been explored using survivin as tumor antigen such as survivin-derived peptides, DNA vaccine encoding survivin, or viral vectored vaccine approach.[6,7] These approaches, are however, not easy to translate for human therapeutic use.[8,9] Recombinant protein approach is a feasible way to produce vaccine antigens,[10,11] however, there are no reports describing application of full-length recombinant survivin protein for tumor immunotherapy.