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Resistance Mechanisms of Tumor Cells
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
In the hematopoietic system, other proteins are also able to exhibit these features. The EGR1 transcription factor (as well as EGR2 or EGR3) allows stem cells to go into homeostasis or dormancy to maintain them (Min et al., 2008; reviewed in Kühn et al., 2016). EGR1 has initially identified as activator of p21 and as gatekeeper of the TP53 (Krones-Herzig et al., 2003). Cells (over)expressing EGR1 protein can potentially escape treatment, and are presumably one of the reasons for relapses. A dormant cell needs only to switch back from this dormant state to the normal growth program. Recently, it has been shown that CDK4 but mainly overexpressed CDK6 (under certain stress conditions) re-activates dormant stem cells and causes tumor cell formation (Scheicher et al., 2015). Similarly, other factors have been described, such as HOXB4 (an OCT4 and GATA2 downstream target gene; Huang et al., 2016), which is capable of inducing sufficient amounts of the RUNX1 transcription factor to maintain hematopoietic stem cells (Teichweyde et al., 2017).
Natural Polymeric Scaffolds for Tissue Engineering Applications
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Moving forward, Dehghan—Baniani et al. [221] synthesized novel kartogenin (KGN)-loaded chitosan-based thermosensitive hydrogels having desirable characteristics of shear modulus, gelation time and temperature as well as swelling coefficient. KGN biomolecule was incorporated because of the need to address the challenge of poor regenerative ability of cartilage as it could promote chondrogenesis of stem cells. This is because research has earlier on demonstrated that KGN can release core-binding factor b (CBFb) which has the ability to bind to RUNX1, - a DNA-binding transcription factor present in the nucleus [222,223]. Anyway, administering KGN in high dosages can be harmful to tendon-bone junctions [224]. In particular, the influence of N- (β-maleimidopropyloxy) succinimide ester (βMPS), β-Glycerophosphate (β-GP) and chitosan concentration on the swelling and rheological properties of the hydrogels were examined. In other words, chitosan was chemically modified with βMPS to resolve the challenge of its’ poor mechanical properties for cartilage repairs [222], while β-GP was incorporated to induce hydrogel thermosensitivity. The optimized KGN-loaded hydrogel-based drug delivery system (DDS) could enhance the chondrogenesis of stem cells when compared to pure KGN because of several reasons. First, the DDS was cytocompatible with human adipose mesenchymal stem cells (hAMSCs). Next, the DDS displayed a high shear modulus capacity of 18 ± 5KPa, close to the 50-250KPa earlier reported for human articular cartilage [225]. Consequently, this shear modulus has been shown to depend on its’ depth from surface, for articular cartilage [226]. Moreover, it was possible to sustain the release of KGN from its’ surface for approximately 40 days for the enhanced chondrogenic differentiation of hAMSCs which could remove the need of multiple KGN injections while improving the drug efficacy. This improved chondrogenic differentiation of hAMSCs was as a result of the increase of hydrogel solubility and therapeutic efficacy because of the sustained and controlled release of KGN. Besides, adding KGN and β-GP into chitosan-modified βMPS is similarly an effective alternative. In brief, the novel thermo-responsive hydrogel can be suitable for applications in cartilage tissue engineering, involving repairs and regeneration.