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Immune RNA and Tumor Immunity*
Published in Edward P. Cohen, A. Arthur Gottlieb, Immune RNA, 2020
In 14 of the 35 patients treated with I-RNA, peripheral blood lymphocytes, from serial bleedings obtained prior to and weekly during I-RNA therapy, were tested for cytotoxic effects against allogeneic target cells of the same histologic type. Of five patients in whom a significant increase in cytotoxic effects was noted, four evidenced stability or possible benefit in their clinical course. One was a treatment failure. Of eight patients in whom no change in lymphocyte-mediated cytotoxicity was noted, four evidenced stability or possible benefit, while four failed treatment. In one patient, a decrease in lymphocyte cytotoxic effect was noted, and this patient was a treatment failure. Table 4 presents a correlation between changes in lymphocyte-mediated cytotoxic responses assessed in vitro and clinical response. A possible correlation between increases in lymphocyte-mediated cytotoxicity, assessed in vitro, and clinical response is apparent.
Disruption of Cellular Growth Control and Signal Transduction Mechanisms as a Target for Cancer Chemotherapy
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
The major objective of cancer chemotherapy has been to poison cells with cytotoxic chemicals. There now exist many types of agents, treatments, and conditions that can injure or kill cancer cells, and an enormous amount of research effort has been invested in determining the underlying mechanisms of cytotoxicity. If one considers a cell as a collection of organelles and molecular assemblies, it seems reasonable that any of these targets could be susceptible to attack by cytotoxic agents. To some extent, this prediction has proven true — all aspects of cellular metabolism and physiology have known poisons and inhibitors. What is incomplete in the picture, however, is a link between the knowledge of a biochemical target for a drug and a molecular explanation of why a cell dies when this target is disrupted. If dihydrofolate reductase is inhibited, for example, is this inhibtion of an important enzyme itself responsible for cell death, or does the lack of products of the enzyme have additional metabolic repercussions that are the key event in cell death? Considering another locus for cytotoxicity, does physical breakage of DNA damage the ability of a cell to reproduce, or does DNA damage couple to other cellular regulatory mechanisms which are the central lethal events following exposure to DNA-damaging drugs? A related problem can also be stated: is DNA or enzyme damage the cause or the consequence of cytotoxicity?
Cytotoxicology Studies of 2-D Nanomaterials
Published in Suresh C. Pillai, Yvonne Lang, Toxicity of Nanomaterials, 2019
Priyanka Ganguly, Ailish Breen, Suresh C. Pillai
The rise in the use of 2D NMs in various applications demands the necessity to understand their health and environmental effects. The physicochemical properties of these materials govern the nature of their cytosolic interaction. In this chapter, the role of the surface and morphological parameters is discussed in detail by highlighting several recent studies. The mode of intake is also a domain of particular interest as it dictates the targeted delivery and nanotoxicity. It is of paramount interest to understand that the cytotoxicity of the material cannot be governed or categorized by any set of precise factors; as explained earlier, a minute change in the biological or physiological parameter of the material or the environment can totally change the toxicity profile. The 2D NMs are still a very new class of materials, which still require several combinations of characterization to evaluate the prime cause of toxicity. Careful in vivo assays to substantiate the results obtained from the in vitro analysis are yet to be developed for 2D NMs. The need for interdisciplinary collaboration for the formation of libraries detailing the ever-changing profiles of the NMs and also a possible theoretical model enabled to predict the toxicity impact is highly desirable. These steps can ensure the structuring of the mitigation process to define a safer world for NM use.
Iron oxide nanoparticles cause surface coating- and core chemistry-dependent endothelial cell ferroptosis
Published in Nanotoxicology, 2022
Xue Zhang, Fei Kong, Tian Wang, Xin Huang, Wanqing Li, Meichen Zhang, Tao Wen, Jian Liu, Yu Zhang, Jie Meng, Haiyan Xu
Iron oxide nanoparticles (IONPs) have been intensively investigated for biomedical applications due to their unique physical properties. Some comprehensive review articles have summarized representative applications of IONPS including intravenous iron supplements, contrasts of magnetic resonance imaging (MRI), tumor therapeutics agents, drug or gene delivery systems and biomedical detection agents (Dadfar et al. 2019; Zhao et al. 2020; Israel et al. 2020; Hu et al. 2018; Bell et al. 2019). Although IONPs are initially considered none or low toxic because they are biodegradable and iron ions are the necessary for human physiological need (Zhang et al. 2020; Paik et al. 2015; Nosrati et al. 2019),the intravenous iron supplements ferumoxytol is warned on the label due to possible serious hypersensitivity reactions when it was approved by Food and Drug Administration in 2015 (Varallyay et al. 2017). In recent years, some studies have reported that IONPs were able to cause certain degrees of cytotoxic effects, inflammatory reactions, oxidative stress, ion channels activity change, and genotoxicity (Abakumov et al. 2018; Arami et al. 2015; Malhotra et al. 2020; Laffon et al. 2018). The mechanism of IONPs cytotoxicity awaits further investigations. Moreover, the development of effective therapeutics rescuing the cytotoxicity is a desiderate research problem.
Olaparib@human serum albumin nanoparticles as sustained drug-releasing tumour-targeting nanomedicine to inhibit growth and metastasis in the mouse model of triple-negative breast cancer
Published in Journal of Drug Targeting, 2022
Nageswara Rao Vysyaraju, Milan Paul, Sanjay Ch, Balaram Ghosh, Swati Biswas
As shown in Figure 9A, the growth of the OLA@HSA NPs treated spheroids significantly reduced than the free olaparib group. Over time, an increment in the diameter of untreated spheroids (size reached up to about 925 µm) was observed, which was significantly bigger in volume than the spheroids treated with OLA@HSA NPs and free olaparib. The average diameter was found to be 925.23 ± 22.61, 514.15 ± 23.52 and 352.20 ± 10.61 µm in control, free olaparib and OLA@HSA NPs treated spheroids, respectively, on day 4. Live/dead cell assay was performed to estimate the treatment-induced cytotoxicity. The spheroids treated with OLA@HSA NPs showed intense red fluorescence compared to the spheroids with free olaparib treatment, suggesting the presence of a higher number of dead cells population (Figure 9B). The Z-stacked images of spheroids treated with OLA@HSA-Rh NPs showed red fluorescence in the centre slices (50–70 µm) after 4 h, indicating time-dependent spheroid uptake (Figure 9C).
New Multi-Walled carbon nanotube of industrial interest induce cell death in murine fibroblast cells
Published in Toxicology Mechanisms and Methods, 2021
Krissia Franco de Godoy, Joice Margareth de Almeida Rodolpho, Patricia Brassolatti, Bruna Dias de Lima Fragelli, Cynthia Aparecida de Castro, Marcelo Assis, Juliana Cancino Bernardi, Ricardo de Oliveira Correia, Yulli Roxenne Albuquerque, Carlos Speglich, Elson Longo, Fernanda de Freitas Anibal
In turn, cytotoxicity is related to the interaction of CNTs in the cellular environment, which in this case occurs in different ways (endocytosis, phagocytosis or needle-shaped penetration), which can trigger changes in cell cycle signaling and regulation (Aschberger et al. 2010; Firme and Bandaru 2010). The penetration of CNTs through the cell lipid bilayer membrane induces oxidative stress, free radical production, damage to proteins, impairment of genetic material and inflammation (Clichici et al. 2012; Mohanta et al. 2019; Prajapati et al. 2020). In addition, from a physicochemical point of view, this cytotoxicity is directly influenced by the type of nanoparticle, size, composition, surface charge, morphology, porosity, aggregation and solubility (Holsapple et al. 2005; Khan et al. 2019).