WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Citation - WoS: 13Citation - Scopus: 18Stimuli Responsive Polymer-Based Strategies for Polynucleotide Delivery(Cambridge University Press, 2017) Uz, Metin; Alsoy Altınkaya, Sacide; Mallapragada, Surya K.In recent years, stimuli responsive polymer based gene delivery vehicle design for cancer treatment and treatment of other genetic disorders has received extensive attention. Early studies focusing on DNA delivery have been facilitated by functional polymers and this area has seen further growth spurred by recent gene silencing strategies developed for small RNA [i.e., small interfering RNA (siRNA) or micro RNA (miRNA)] delivery. DNA and small RNAs possess analogous properties; however, their explicit differences define the specific challenges associated with the delivery route and the design of functional materials to overcome distinct challenges. Apart from classical gene delivery, the recent advances in genome editing have revealed the necessity of new delivery devices for genome editing tools. A system involving CRISPR (clustered, regularly interspaced, short palindromic repeats) and an endonuclease CRISPR-associated protein 9 (Cas9) coupled with a short, single-guide RNA (sgRNA) has emerged as a promising tool for genome editing along with functional delivery systems. For all these nucleic acid based treatments, the internal or external physiochemical changes in the biological tissue/cells play a major role in the design of stimuli responsive delivery materials for both in vitro and in vivo applications. This review emphasizes the recent advances in the use of pH, temperature, and redox potential-responsive polymers overcoming hurdles for delivery of gene and gene editing tools for both in vitro and in vivo applications. Specifically the chapter focuses on recently proposed delivery strategies, types of delivery systems, and polymer synthesis/modification methods. The recent advances in CRISPR/Cas9-sgRNA technology and delivery are also described in a separate section. The review ends with current clinical trials, concluding remarks, and future perspectives.Article Citation - WoS: 108Citation - Scopus: 119Sphingosine Kinase-1 and Sphingosine 1-Phosphate Receptor 2 Mediate Bcr-Abl1 Stability and Drug Resistance by Modulation of Protein Phosphatase 2a(American Society of Hematology, 2011) Salas, Arelis; Ponnusamy, Suriyan; Senkal, Can E.; Meyers-Needham, Marisa; Selvam, Shanmugam Panneer; Saddoughi, Sahar A.; Apohan, Elif; Sentelle, R. David; Smith, Charles; Gault, Christopher R.; Obeid, Lina M.; El-Shewy, Hesham M.; Oaks, Joshua; Santhanam, Ramasamy; Marcucci, Guido; Baran, Yusuf; Mahajan, Sandeep; Fernandes, Daniel; Stuart, Robert; Perrotti, Danilo; Öğretmen, BesimThe mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1-/- MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib- or nilotinib-induced growth inhibition in primary CD34+ mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, expressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1-derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type- or mutant-Bcr-Abl1 thereby overcoming drug resistance. © 2011 by The American Society of Hematology.Article Citation - WoS: 106Citation - Scopus: 114Msrb1 (methionine-R Reductase 1) Knock-Out Mice: Roles of Msrb1 in Redox Regulation and Identification of a Novel Selenoprotein Form(American Society for Biochemistry and Molecular Biology, 2009) Fomenko, Dmitri E.; Novoselov, Sergey V.; Natarajan, Sathish Kumar; Lee, Byung Cheon; Koç, Ahmet; Carlson, Bradley A.; Lee, Tae- Hyung; Kim, Hwa-Young; Hatfield, Dolph L.; Gladyshev, Vadim N.Protein oxidation has been linked to accelerated aging and is a contributing factor to many diseases. Methionine residues are particularly susceptible to oxidation, but the resulting mixture of methionine R-sulfoxide (Met-RO) and methionine S-sulfoxide (Met-SO) can be repaired by thioredoxin-dependent enzymes MsrB and MsrA, respectively. Here, we describe a knock-out mouse deficient in selenoprotein MsrB1, the main mammalian MsrB located in the cytosol and nucleus. In these mice, in addition to the deletion of 14-kDa MsrB1, a 5-kDa selenoprotein form was specifically removed. Further studies revealed that the 5-kDa protein occurred in both mouse tissues and human HEK 293 cells; was down-regulated by MsrB1 small interfering RNA, selenium deficiency, and selenocysteine tRNA mutations; and was immunoprecipitated and recognized by MsrB1 antibodies. Specific labeling with 75Se and mass spectrometry analyses revealed that the 5-kDa selenoprotein corresponded to the C-terminal sequence of MsrB1. The MsrB1 knock-out mice lacked both 5- and 14-kDa MsrB1 forms and showed reduced MsrB activity, with the strongest effect seen in liver and kidney. In addition, MsrA activity was decreased by MsrB1 deficiency. Liver and kidney of the MsrB1 knock-out mice also showed increased levels of malondialdehyde, protein carbonyls, protein methionine sulfoxide, and oxidized glutathione as well as reduced levels of free and protein thiols, whereas these parameters were little changed in other organs examined. Overall, this study established an important contribution of MsrB1 to the redox control in mouse liver and kidney and identified a novel form of this protein.Article Citation - WoS: 18Citation - Scopus: 16Suppression of Stat5a Increases Chemotherapeutic Sensitivity in Imatinib-Resistant and Imatinib-Sensitive K562 Cells(Informa Healthcare, 2010) Kosova, Buket; Tezcanlı, Burçin; Ekiz, Hüseyin Atakan; Çakır, Zeynep; Selvi, Nur; Dalmızrak, Ayşegül; Yandım, Melis Kartal; Gündüz, Ufuk; Baran, YusufSTAT proteins are cytoplasmic transcription factors that are involved in the regulation of numerous cellular activities such as cell growth, differentiation, and survival. In this study, we aimed to identify the expression pattern of STAT genes in imatinib-sensitive and-resistant K562 cells, and further, to reveal the effects of STAT5A siRNA knockdown on cell growth and apoptosis induction. The XTT cell proliferation assay showed that both sensitive and resistant K562 cells were sensitized to imatinib upon transfection with STAT5A siRNA. Caspase-3 enzyme activity was increased significantly in both cells. These results may open up new opportunities to overcome chemotherapeutic resistance in leukemia. © 2010 Informa UK, Ltd.