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Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Abstract 4360: Validation of phosphodiesterase 10A as a cancer target
Phosphodiesterase 10A (PDE10) is a cAMP and cGMP degrading PDE isozyme that is highly expressed in the brain striatum where it plays an important role in cognition and psychomotor activity. PDE10 inhibitors are being developed for the treatment of schizophrenia and Huntington's disease and are generally well tolerated, likely because of low expression levels in peripheral tissues. We recently reported high levels of PDE10 in tumors and that genetic silencing by siRNA inhibits tumor cell growth with a high degree of selectivity over normal cells (Li et al., Oncogene 2014). These observations suggest that PDE10 may have an u...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lee, K., Li, N., Chen, X., Zhu, B., Yet, L., Madeira da Silva, L., Russo, S., Keeton, A. B., Boyd, M. R., Piazza, G. A. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 1762: Phosphodiesterase 10, a novel target for colorectal cancer therapeutics
Phosphodiesterase 10 (PDE10) is a newly characterized PDE isozyme that is expressed in regions of the brain affecting cognition and psychomotor activity. Inhibitors are currently being developed for the treatment of schizophrenia and Huntington's disease, one of which, Pf-2545920 (MP-10), is in clinical trials. Although PDE10 is not expressed in most peripheral tissues, we recently found high levels in colon tumor cells compared with normal colonocytes and that genetic silencing by siRNA selectively suppressed colon tumor cell growth. These observations suggest that PDE10 may represent a novel anticancer target. Pf-2545920...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lee, K. J., Li, N., Chen, X., Zhu, B., Yet, L., Piazza, G. Tags: Experimental and Molecular Therapeutics Source Type: research

Knockdown of HIP1 expression promotes ligand ‑induced endocytosis of EGFR in HeLa cells.
In this study, the effects of HIP1 on the degradation of EGFR, which have important roles in carcinogenesis after EGF stimulation, were examined. After screening 17 cell lines, the coexpression of HIP1 and EGFR was detected in HeLa cells. Accordingly, the expression of HIP1 was knocked down in HeLa cells using various HIP1 siRNA sequences. The endocytosis of EGFR and localization of clathrin in HeLa cells were examined after stimulation by EGF at various concentrations (i.e., 1.5 and 100 ng/ml). After HIP1 expression was blocked by siRNAs, EGFR endocytosis was accelerated and this effect was dependent on the EGF concentra...
Source: Oncology Reports - October 20, 2017 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research