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Emerging Trends in Nanotechnology for Diagnosis and Therapy of Lung Cancer
Published in Alok Dhawan, Sanjay Singh, Ashutosh Kumar, Rishi Shanker, Nanobiotechnology, 2018
Nanda Rohra, Manish Gore, Sathish Dyawanapelly, Mahesh Tambe, Ankit Gautam, Meghna Suvarna, Ratnesh Jain, Prajakta Dandekar
Receptor tyrosine kinases (RTKs) and nonreceptor tyrosine kinases (non-RTKs) are essential to facilitate signaling pathways used for cell cycle regulation, migration, cell proliferation, angiogenesis, and differentiation (Imai and Takaoka 2006). Many such RTKs and non-RTKs are released during formation of cancerous tissue. Small molecule inhibitors are organic molecules of low molecular weight (<900 Da), with a size on the order of 10−9 m. These therapeutic actives work by targeting the kinases, thereby creating direct impact on the growth of tumor cells (Imai and Takaoka 2006). Small molecule inhibitors do not trigger any immune response. Moreover, owing to their small size, they are capable of permeating through the plasma membrane and interacting with the cytoplasmic domain of cell-surface receptors and intracellular signaling molecules. Gefitinib (Iressa) and Erlotinib (Tarceva) are small molecule agents that selectively inhibit EGFR expressed in NSCLC (Imai and Takaoka 2006). Crizotinib (Xalkori), another small molecule inhibitor, also selectively inhibits HGFR expressed in NSCLC (Lavanya et al. 2014).
Small-Molecule Inhibitors Targeting Receptor Tyrosine Kinases in Cancer
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Mohammad Hojjat-Farsangi, Gholamreza Khamisipour
Receptor tyrosine kinases are consisted of three major domains, including extracellular (binds to ligand/s), transmembrane and intracellular domain. Intracellular region has special amino acid residues that are necessary for kinase activity of the RTK and will be phosphorylated for activation of the enzyme. EGFR, vascular endothelial growth factor receptor (VEGFR), insulin receptor (InsR), and platelet-derived growth factor receptor (PDGFR) families are examples of RTKs (Jimenez et al., 2012).
The emergence of nanoporous materials in lung cancer therapy
Published in Science and Technology of Advanced Materials, 2022
Deepika Radhakrishnan, Shan Mohanan, Goeun Choi, Jin-Ho Choy, Steffi Tiburcius, Hoang Trung Trinh, Shankar Bolan, Nikki Verrills, Pradeep Tanwar, Ajay Karakoti, Ajayan Vinu
Using short interference RNAs (siRNA), targeted therapy for various pathways has been studied with different nanoparticles such as polymers, inorganic and organic nanoparticles. Challenges, including poor conjugation, reduced stability, and ineffective release to the cytoplasm, must be overcome before a successful translation of siRNA-based nanomedicines. To overcome these challenges, Suresh et al. developed gelatin nanoparticles functionalised with antibodies [287]. Gelatin is another natural molecule made up of collagen and is used for reducing systemic immune response during drug delivery. Gelatin was synthesised with two-step desolvation process with glutaraldehyde as a crosslinker. To reduce the toxicity of the gelatin arising from the aldehyde groups on gelatin, excess glutaraldehyde was quenched with tris glycine. The modified gelatin was functionalised with cetuximab (anti-AXL antibody) by EDC/sulfo-NHS chemistry. AXL (Ark or UFO) is a member of TAM family of receptor tyrosine kinase, which is highly expressed in cancers. The gene silencing efficacy was analysed by western blotting in EGFR mutant H820 cells. The H820 cells were incubated with the gelatin-antibody for 72 hours, and it was estimated that >25 nM of transfected-siRNA was required for ~70% knock-down of AXL protein. Thus, high transfection efficiency with minimal toxicity can be achieved by utilizing porous gelatin hydrogels. Similar studies are reported in other cancers such as breast and colon cancers [288].
Plant mediated green synthesis and nanoencapsulation of MgO nanoparticle from Calotropis gigantea: Characterisation and kinetic release studies
Published in Inorganic and Nano-Metal Chemistry, 2018
Yiik Siang Hii, Jaison Jeevanandam, Yen San Chan
The US Centers for Diseases Control and National Center for Chronic Disease Prevention and Health Promotion stated that in 2011, there were roughly 25.8 million Americans suffered from diabetes and most of them had type 2 diabetes.[1] Type 2 diabetes is caused by combination of insulin resistance, insulin deficiency and incretin dysfunction. Insulin deficiency is related to failure in secreting sufficient amount of insulin for breaking of glucose. Insulin resistance occurred mainly by the inhibition of receptor tyrosine kinase activity and the reduction in the number of insulin receptors on the surface of insulin-sensitive cells. Numerous studies showed that magnesium deficiency also causes insulin resistance and increases the risk for Type 2 diabetes.[2] Besides, incretion dysfunction is demonstrated by dys-sychronization between food intake and insulin response.[1]
A critical review of developmental exposure to particulate matter, autism spectrum disorder, and attention deficit hyperactivity disorder
Published in Journal of Environmental Science and Health, Part A, 2018
Tiffani A. Fordyce, Megan J. Leonhard, Ellen T. Chang
Volk et al.[126] studied the association of ASD with air pollution exposure after stratifying by a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. This analysis was motivated by toxicological findings of altered brain MET expression in mice after prenatal exposure to a model air pollutant. The authors reported a significant relationship between PM10 and ASD for both MET rs1858830 genotypes by quartiles of exposure, with a somewhat stronger association for CC carriers (CC genotype:[OR: 3.2 95% CI: 1.3–9.1]; CG/GG genotypes:[OR: 2.1; 95% CI: 1.2–3.9]), divided at the top 20% of the exposure distribution (CC genotype:[OR: 2.74 95% CI: 1.10–7.87]; CG/GG genotypes:[OR: 1.99; 95% CI: 1.05–3.98]), and at the top quartile of PM10 exposure for combined analysis (OR: 2.5; 95% CI: 1.6–4.3).[126]