China
Africa
Explore chapters and articles related to this topic
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Marveh Rahmati, Saeid Amanpour, Hadiseh Mohammadpour
When cells are infected by viruses, the perforin/granzyme apoptosis pathway is initiated by cytotoxic lymphocytes to remove the infected cells. Perforin, also known as cytoplasmic granule toxin, is a kind of protein with a pore-forming ability in mitochondrial membrane. Granzyme is a serine protease protein, which contains cytotoxic granules of cytotoxic lymphocytes (CLs). Although, Granzyme is required for triggering apoptosis, it should be delivered appropriately by perforin. In humans, there are numerous granzymes including A, B, H, K, and M, but the Granzymes A and B are the most abundant enzymes that are involved in apoptosis. This pathway is initiated when granzymes could enter into target cells. This internalization is facilitated by perforin. Granzyme B activates pro-apoptotic BH3-interacting domain death agonist Bid, leading to the activation of CASP-3. Activated CASP-3 is subsequently able to proceed with executive apoptosis. Granzyme B can also inactivate MCL-1, which is a member of the anti-apoptotic BCL-2 family [36]. The granzyme A pathway is also involved in apoptosis via activating a parallel, caspase-independent cell death pathway through single-stranded DNA damage [37].
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Zelphati et al. (2001) developed a lipid-mediated delivery system composed of trifluoroacetylated lipopolyamine (TFA-DODAPL) and dioleoyl phosphatidylethanolamine (DOPE) able of successfully delivering β-galactosidase (β-Gal) and caspase 3 (CP3), caspase 8 (CP8), and granzyme B into cultured cell lines as demonstrated by intracellular fluorescence intensity measurements. In order to prove the functionality of their delivery system, the authors tested the ability of TFA-DODAPL:DOPE to deliver functional granzyme B into primary human AML cells by using a fluorogenic cell permeable substrate, CaspaTag, and measured the activation of endogenous caspases by flow cytometry. Similarly, CP3, CP8 and granzyme B activity was evaluated in Jurkat cells. Granzyme B and CP3 induced apoptosis in ~60% of Ki-Ras 267β1 cells.
Preclinical Characterization of Engineered Nanoparticles Intended for Cancer Therapeutics
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Anil K. Patri, Marina A. Dobrovolskaia, Stephan T. Stern, Scott E. McNeil
Apoptosis in mammalian cells can be initiated by four potential pathways: (1) mitochondrial pathway, (2) Death receptor-mediated pathway, (3) ER-mediated pathway, and (4) Granzyme B-mediated pathway.114 Our laboratory has focused on caspase-3 activation in liver and kidney cells as a biomarker of apoptosis, since this a downstream event in all the classical apoptotic signaling pathways and can be measured using a fluorometric protease assay. This assay quantifies caspase-3 activation in vitro by measuring the cleavage of DEVD-7-amino-4-trifluoromethyl coumarin (AFC) to free AFC that emits a yellow-green fluorescence (λmax = 505 nm).115 This initial apoptosis screen can then be followed by additional analysis, as cellular morphology studies using nuclear staining techniques to detect perinuclear chromatin, or agarose gel electrophoresis to detect DNA laddering.116
A mathematical model of cytotoxic and helper T cell interactions in a tumour microenvironment
Published in Letters in Biomathematics, 2018
Heidi Dritschel, Sarah L. Waters, Andreas Roller, Helen M. Byrne
While immunosurveillance should, in theory, rid the body of pre-cancerous and/or cancerous cells, in practice this does not always occur. If, for example, immunogeneic cells are removed by the immune system then a poorly immunogeneic and antigenic population of tumour cells remains (DuPage et al., 2012; Pardoll, 2003; Vicari et al., 2002). As these tumour cells proliferate, they mutate, creating cells that present low levels of tumour antigen and, consequently, evade recognition by T cells (Vesely and Schreiber, 2013). Cancer cells also manipulate the local microenvironment by producing immunosuppressive cytokines such as TGF- and IL-10 that promote differentiation of helper T cells to a regulatory phenotype (Kawamura et al., 2002). Cancer cells may also produce cytolytic molecules such as Granzyme B that induce apoptosis of immune cells (Igney and Krammer, 2002).