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Engineered Extracellular Vesicle-Based Therapeutics for Liver Cancer
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
HCC is remarkably heterogeneous and can be related to alterations in several signaling pathways (Breuhahn, Longerich, and Schirmacher 2006). Several genetic alterations have been described in HCC. Among the most commonly encountered mutations in HCC are those associated with the β-catenin gene and the activation of Wnt/β-catenin pathway. This pathway plays an important role in tumor proliferation, maintenance of tumor initiating cells and metastasis (Thompson and Monga 2007; Anastas and Moon 2013). Aberrant activation of Wnt signaling has been associated with carcinogenesis. Mutations in genes encoding for β-catenin or CTNNB1 (Gao et al. 2018; de La Coste et al. 1998) occur in up to 40% of HCCs. The presence of CTNNB1 mutations is related to aberrant β-catenin signaling and tumor aggressiveness (Cieply et al. 2009). Specific therapy targeting β-catenin could therefore be beneficial for a subset of HCC or other types of cancers that are characterized by mutations or aberrant activations in this pathway. However, there are no current therapeutic agents that can directly target this pathway. We have developed and reported the use of a therapeutic approach based on delivery of β-catenin siRNA to tumor cells using MNV as a biological nanoparticle delivery carrier (Matsuda and Patel 2018). The therapeutic MNV (tMNV) were generated by loading MNV with β-catenin siRNA using lipid-based transfection. The use of tMNV provides an efficient and effective means of hepatic delivery of RNA-based therapeutics (Table 38.1).
Anti-Cancer and Anti-Angiogenic Properties of Nano-Diamino-Tetrac, A Thyroid Hormone Derivative
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2020
Paul J. Davis, Shaker A. Mousa
Catenins are proteins involved in cell-cell adhesion. β-Catenin also has transcriptional functions in the nucleus. Mutation and overexpression of β-catenin occurs in a variety of tumors, including colorectal carcinoma, breast and ovarian cancer [71, 72]. Nanotetrac increases transcription of the CBY1 gene [18], the gene product of which is an inhibitor of nuclear functions of β-catenins. From the standpoint of anti-tumor activity, this is a desirable effect of Nanotetrac at αvβ3 in cancer cells. The action would be deleterious in non-cancer cells, but the latter when not undergoing cell division express little αvβ3 or little activated αvβ3. Like β-catenins, integrin αvβ3 participates in cellular adhesion complexes and the αv monomer has functions in specific gene transcription [73].
Anti-Cancer and Anti-Angiogenic Properties of Nano-Diamino-Tetrac, A Thyroid Hormone Derivative
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2019
Paul J. Davis, Shaker A. Mousa
Catenins are proteins involved in cell-cell adhesion. β-Catenin also has transcriptional functions in the nucleus. Mutation and overexpression of β-catenin occurs in a variety of tumors, including colorectal carcinoma, breast and ovarian cancer [71, 72]. Nanotetrac increases transcription of the CBY1 gene [18], the gene product of which is an inhibitor of nuclear functions of β-catenins. From the standpoint of anti-tumor activity, this is a desirable effect of Nanotetrac at αvβ3 in cancer cells. The action would be deleterious in non-cancer cells, but the latter when not undergoing cell division express little αvβ3 or little activated αvβ3. Like β-catenins, integrin αvβ3 participates in cellular adhesion complexes and the αv monomer has functions in specific gene transcription [73].
Regulation of stem cell fate and function by using bioactive materials with nanoarchitectonics for regenerative medicine
Published in Science and Technology of Advanced Materials, 2022
Wei Hu, Jiaming Shi, Wenyan Lv, Xiaofang Jia, Katsuhiko Ariga
For commonly used covalently crosslinked hydrogels, the dynamic mechanical properties are often derived from cell-mediated degradation. Khetan et al. encapsulated human mesenchymal stem cells (hMSCs) in covalently crosslinked hyaluronic acid hydrogels subjected to a multi-step crosslinking protocol, from cell–mediated–degradable to non-degradable [126]. They demonstrate that the differentiation of hMSCs is directed by the generation of traction force mediated through cellular degradation of matrix. Furthermore, their work emphasizes the type of hydrogel underlying the mechanism by which stem cells respond to biophysical cues. Heilshorn et al. demonstrate that the maintenance of neural progenitor cell (NPC) stemness in 3D hydrogels is dependent on matrix degradability but interestingly is independent of cytoskeletal tension and integrin-binding ligand clustering [127]. According to their work, the underlying mechanism is increased cadherin-mediated cell–cell contact and activating β-catenin signalling. Moreover, they demonstrate that NPC proliferation and differentiation also require increased degradability. Following this study, they further clarify the role of matrix remodelling on NPC differentiation and maturation [128]. Permitting 7-day matrix remodelling prior to induction of differentiation, NPCs can differentiate into astrocytes or mature functional neurons. It is attributed to up-regulating YAP expression via cadherin-mediated cell–cell contact.
Histopathologic and physiologic effect of overlapping vs single coronary stents: impact of stent evolution
Published in Expert Review of Medical Devices, 2018
Atsushi Sakamoto, Sho Torii, Hiroyuki Jinnouchi, Renu Virmani, Aloke V. Finn
Endothelial cells play a pivotal role in the regulation of permeability by cell-to-cell adhesions and also maintaining vascular homeostasis by liberating both antithrombotic and prothrombotic molecules (Figure 5(c and d)). The importance of a sustained balance between these functions has been shown in the initiation and progression of atherosclerosis. Vascular endothelial cadherin (VE-cad)-based adherens junction regulates vascular permeability via interaction with intracellular protein p120 catenin. Our group previously reported that DES-loaded sirolimus is primarily the cause of increased endothelial permeability at implanted segment by activation of protein kinase C-α and downstream disruption of the p120/VE-cad interaction in vascular endothelium [63]. Although direct correlation between vascular permeability and subsequent neoatherosclerotic formation at the site of DES implantation has not been proven, we propose that the anatomic integrity and functional recovery of endothelial cells govern the early development of neoatherosclesosis. To achieve functional integrity of endothelial cells may be related to drug continuing to leach from permanent polymer for a longer period as compared to bioabsorbable-polymer DES because the drug is impregnated into the polymer, and therefore, when the polymer is fully degraded, the drug is no longer available, and the endothelial cells proliferate and able to be fully functional.
Callyspongia samarensis (Porifera) extracts exhibit anticancer activity and induce bleaching in Porites cylindrica (Scleractinia)
Published in Chemistry and Ecology, 2018
Miguel Azcuna, Jortan O. Tun, Helen T. Yap, Gisela P. Concepcion
Coral and human proteomes have common cell signalling pathways, like Wnt/β-catenin and NF-κβ-STAT pathways [23]. The Wnt/β-catenin pathway impacts cell processes like cell proliferation, fate determination, morphology, polarity, and motility. Wnts also regulate stem cell proliferation and may control the fate of cancer stem cells [24]. The NF-κβ protein complex is involved in the transcription of DNA and activates the expression of genes, such as anti-apoptotic and mitogenic genes [25]. In cancer cells, these signalling pathways may become misregulated or overexpressed, and several anticancer compounds from marine organisms have demonstrated an ability to act on such pathways [26]. Therefore, compounds in HPLC fraction 8 may act on the Wnt/β-catenin and NF-κβ-STAT pathways to induce necrosis in coral cells or inhibit growth in cancer cell lines. Furthermore, due to the symbiotic association of coral and dinoflagellates (the zooxanthellae), the latter, which are responsible for the photosynthetic machinery of the coral, will perish as a result of tissue necrosis in the coral. This can explain the lower MQY in nubbins that were exposed to experimental gels with HPLC fraction 8.