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Advantages and Limitations of RNAi Delivery for Cancer Biological Therapeutics Imaging
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
The siRNA-loaded lipid nanoparticles (Atu027) have been applied clinically to suppress the expression of protein kinase N3 (PKN3) [63]. PKN3 is an effector of PI3K pathway related to the modulation of cell growth, differentiation, survival, motility, and adhesion as well as immune cell and glucose transport function. Chronic activation of PI3K pathway could prevent various human cancers and inhibit the growth of malignant cells [64]. Although numerous signaling molecules can be considered as therapeutic candidates to mediate the PI3K pathway, their upstream inhibition could trigger signal cascades with undesirable signal regulation of normal cells associated with various side effects. For this reason, PKN3 is considered to be a proper effector to adjust the growth of metastatic cancer cells with activated PI3K [65]. The results from animal studies indicate that Atu027 could effectively knock down the expression of PKN3 gene in the vascular endothelium to inhibit tumor growth and metastasis [63]. In clinical study of Atu027, no interferon response or activation of cytokines was observed, which may be due to liposomal encapsulation of siRNA with enhanced safety while avoiding triggering side reactions during circulation [66]. Thus, Atu027 was well tolerated, and no dose-dependent toxicity was observed. Recent study of using Atu027 to treat advanced solid tumors has found that up to 41% of patients exhibited no further progression of tumors after eight weeks of treatment [67]. Since Atu027 targets tumor stroma instead of tumor cells, it is expected that this treatment will be effective for all type of vascularized metastatic cancers.
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Phosphatidylinositol 3-kinase (PI3K) is the major signaling component in the downstream of growth factor receptor tyrosine kinases (RTKs) [167–170]. The heterodimeric lipid kinase PI3K, composed of regulatory and catalytic subunits, catalyzes production of the lipid second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) found on the cell membrane [171–175]. The PI3K pathway regulates various cellular processes, such as proliferation, growth, apoptosis, and cytoskeletal rearrangement.
Core genes in lung adenocarcinoma identified by integrated bioinformatic analysis
Published in International Journal of Environmental Health Research, 2023
Liu Yang, Qi Yu, Yonghang Zhu, Manthar Ali Mallah, Wei Wang, Feifei Feng, Qiao Zhang
The PI3K-AKT pathway is one of the key signaling pathways involved in proliferation, migration and invasion of lung cancer cells (Jiang et al. 2020). It has been noted that aberrant activation of PI3K-AKT pathway is related to cancer tumorigenesis and progression (Mayer and Arteaga 2016). We found that six genes (ANGPT1, TEK, COL1A1, SPP1, THBS2 and VWF) involved in PI3K-AKT pathway (Figure 8). COL1A1, SPP1, THBS2 and VWF in extracellular matrix (ECM) activate focal adhesion kinase (FAK) by binding to integrin (ITGA and ITGB), which activates the PI3K/AKT signaling in turn. As a growth factor, ANGPT1 activates the PI3K/AKT and MEK/ERK signaling pathways by combining with TEK receptor tyrosine kinase. Club cell secretory protein (CC16) is encoded by the SCGB1A1 gene (Almuntashiri et al. 2020). Studies have showed that SPARCL1 (Ma et al. 2018) and CC16 (Zhou et al. 2019) can inhibit the transduction of mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑related kinase (ERK) signaling. Previous studies demonstrated that hepatic stellate cells (HSCs)-derived cartilage oligomeric matrix protein (COMP) collaborated with CD36 and subsequently activate MEK/ERK and PI3K/AKT signaling pathways (Li et al. 2018). Stromal cell-derived factor 1 (SDF-1) could induce PECAM-1 through Src family tyrosine kinases to enhance the chemotactic signaling pathway involving PI3K/AKT/mTORC1 (Umezawa et al. 2017). Core genes could affect cell survival, migration, proliferation and metabolism by activating or inhibiting the PI3K-AKT signaling pathway. Taken together, we speculated that core genes may modulate LUAD through PI3K-AKT pathway.
Analysis of long non-coding RNA profiled following MC-LR-induced hepatotoxicity using high-throughput sequencing
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Cong Wen, Shu Yang, Shuilin Zheng, Xiangling Feng, Jihua Chen, Fei Yang
The phosphoinositide 3-kinase (PI3K)/AKT pathway is most frequently activated in human cancer progression involving cellular transformation, tumorigenesis and drug resistance (Mayer and Arteaga 2016). It is of interest that Miao et al. (2016) suggested that activation of PI3K/AKT by MC-LR induced matrix metalloproteinase-13 (MMP-13) overexpression resulting in the migration and invasion of colorectal cancer DLD-1 cells and HT-29 cells. Chen et al (2017, 2018) noted that MC-LR-mediated activation of PI3K/AKT pathway produced male reproductive dysfunction. In our study, target genes of differentially expressed lncRNA induced by MC-LR also activated the PI3K/AKT pathway, suggesting the observed liver damage may also be associated with PI3K/AKT pathway stimulation.
6-(2-Morpholinoethyl)-thiazolo[3,2-a]pyrimidin-5-one: A novel scaffold for the synthesis of potential PI3kα inhibitors
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Ahmed R. Ali, Eman R. El-Bendary, Mariam A. Ghaly, Ihsan A. Shehata
The phosphoinositide 3-kinase (PI3K) pathway is an intracellular signaling pathway that has regulatory roles in cell survival, proliferation, and differentiation, and a critical role in tumorigenesis [8,9] . In cancer, multiple studies have investigated the therapeutic targeting of the PI3K pathway, and multiple inhibitors targeting PI3K and its isoforms, protein kinase B/AKT, and mammalian target of rapamycin (mTOR), have been developed [8]. A US patent reported thiazolopyrimidine compounds, substituted with a morpholine ring, of formulae I and II, with anticancer activity, and more specifically with PI3 kinase inhibitory activity. The compounds may inhibit tumor growth in mammals and may be useful for treating human cancer patients [10].