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Recent Progress in Cancer Thermal Therapy Using Gold Nanoparticles *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Nardine S. Abadeer, Catherine J. Murphy
Chen et al. [102] monitored cancer cells in real-time to better understand changes in cellular morphology that occur during photothermal heating. Gold nanorods (AR 3.9, λmax = 800 nm) were functionalized with the negatively charged polyelectrolyte polystyrenesulfonate to enhance nanorod biocompatibility. EMT-6 breast cancer cells were incubated with gold nanorods overnight to facilitate cellular uptake into the endosomes or lysosomes. Endocytosis resulted in the uptake of a few hundred to a few thousand nanorods per cell. Irradiation with a femtosecond pulsed laser (790 nm, 0.5 ms) seemed to explode the lysosomes in the cells, but interestingly, cell death was not immediate. Photothermal treatment caused a great amount of cell damage due to the formation of 10 µM cavities and then led to rupture of the plasma membrane. Subsequent intracellular responses eventually resulted in death of the cells within 4 min of laser irradiation at 185 and 222 W/cm2 (Fig. 3.9). The authors proposed that cell death was mainly the result of oncosis (ischemic cell death) due to sudden swelling [102].
Normal and Abnormal Intestinal Absorption by Humans
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
David W. Hobson, Valerie L. Hobson Balldin
Clostridium perfringens type A produces a 35 kDa enterotoxin (CPE) that is an important cause of food poisoning, human non-foodborne GI disease, and some veterinary GI diseases. CPE action involves formation of complexes in mammalian plasma membranes. One such complex of approximately 155 kDa is responsible for plasma membrane permeability alterations, which result in enterotoxin-treated mammalian cell death. Such membrane permeability changes also damage the epithelium, allowing the enterotoxin to interact with the tight junction (TJ) protein occludin. CPE:occludin interacts to form an approximately 200 kDa CPE complex and the internalization of occludin into the cytoplasm. Removal of occludin (and possibly other proteins) damages TJs and disrupts the normal paracellular permeability barrier of the intestinal epithelium, which may contribute to CPE-induced diarrhea. Low CPE doses kill mammalian cells by inducing a classic apoptotic pathway involving mitochondrial membrane depolarization, cytochrome C release, and caspase 3/7 activation. High enterotoxin doses, however, induce oncosis, which is a proinflammatory event. CPE is a unique, multifunctional toxin with cytotoxic, TJ-damaging, and potentially significant proinflammatory action [74].
Apoptosis and Cell Death
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Necroptosis primarily appears to occur when caspases are inhibited, and one reason why apoptosis normally takes precedence over necroptosis is because active caspase 8 can cleave RIPK1 and RIPK3.9 Viral infection is a situation that can result in necroptosis because viruses inhibit caspases. Where tumour cells have become apoptosis resistant (perhaps through similar mechanisms to viral infection) necroptosis might be a useful way to eliminate tumour cells, although the consequences of the induction of inflammation to the tumour microenvironment will have to be considered.12, 13 While microscopically necroptosis appears as a swollen cell with formation of a balloon-like structure, known as oncosis, methods to identify necroptosis currently involve biochemical and fluorogenic assays on lysates or living cells, use of genetically modified mice or cells with RIPK3 or MLKL knockdown, or use of necrostatin and other more specific RIPK1 inhibitors to block the process.13
Induction of hepatic portal fibrosis, mitochondria damage, and extracellular vesicle formation in Sprague-Dawley rats exposed to copper, manganese, and mercury, alone and in combination
Published in Ultrastructural Pathology, 2020
Priyanka Dhanraj, Chantelle Venter, Megan Jean Bester, Hester Magdalena Oberholzer
In all groups exposed to Cu, Mn, or Hg, alone or in combination, minor morphological changes were observed and these were sinusoidal dilation and hydropic swelling. Hydropic swelling or hydropic degeneration has been identified as the first stage of liver injury and is characterized by vacuolization and cellular swelling.25 This is a reversible change that is most often caused by water and sodium accumulation due to membrane disturbances that reduce the ability of a cell to maintain fluid and ionic homeostasis.25 These features are consistent with cells undergoing oncosis, a pre-lethal phase following cell injury due to subsequent exposure to drugs or chemicals.26 Characteristics of oncosis include cellular and organelle swelling, dilation of the endoplasmic reticulum and Golgi apparatus, mitochondrial and chromatin condensation and formation of cytoplasmic blebs or blisters which is associated energy depletion which interferes with the membrane ion pumps.27,28
Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside
Published in OncoImmunology, 2018
S. Faraj, M. Bahri, S. Fougeray, A. El Roz, J. Fleurence, J. Véziers, M. D. Leclair, E. Thébaud, F. Paris, S. Birklé
We went on to investigate the mechanism by which mAb 8B6 sensitizes neuroblastoma cells to topotecan. It was proven that anti-ganglioside mAbs could induce an alternative form of programmed cell death through oncosis.17,18 Features of oncosis include cell swelling, membrane damage associated with increased cell permeability, and cell death.19-21 In our previous work, we observed under light microscopy that tumor cells treated with mAb 8B6 aggregated and underwent morphologic changes, which was followed by cell death.12 Based on this evidence, we investigated here an oncosis-like mechanism as the probable mAb 8B6 mode of action in tumor cell sensitization to topotecan. Thus, we examined the cell surface of neuroblastoma cells for structural changes after mAb treatment with scanning electron microscopy (Fig. 3). Strikingly, neuroblastoma cell plasma membranes displayed numerous pores in the presence of anti-OAcGD2 mAb 8B6 (Fig. 3). These effects were not seen when the cell were treated with the control antibody (Fig. 3). Next, we carried out a flow cytometry assay to study topotecan incorporation in the mAb-treated cells. Remarkably, the analysis of MFI ratios of intracellular topotecan fluorescence indicated that topotecan uptake was significantly greater in the mAb 8B6-treated neuroblastoma cells than in the control cells (Fig. 4A, and Fig. S2). Taken together, these data indicate that mAb 8B6-treated cells display cell membrane injuries that result in increased cell permeability to topotecan. In parallel, we conducted immunoblots analysis to study the cleaved caspase-3 level in the tumor cells treated with both mAb 8B6 and topotecan (Fig. 4B). As shown in Fig. 4B, the increased intracellular topotecan uptake induced by mAb 8B6 correlated with a gain of cleaved caspase-3 level in all studied neuroblastoma cell lines, indicating a more profound cell death. These findings suggest that alteration of the tumor cell plasma membrane permeability as a mechanism for the synergism between mAb 8B6 and topotecan combination.