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Hormesis
Published in T. D. Luckey, Radiation Hormesis, 2020
An attractive generalization suggests that unusual cell reactions arise following cell stress from radiation, oxidations, oncogenic viruses, heat, and a wide variety of chemical poisons.473,801 This oxidation stress leads to the production and accumulation of hyperphosphorylated nucleotides, e.g., adenine-P-P-P-P-adenine (AppppA). Such compounds, called “alarmones”, are produced in large quantities by “heat shock” proteins.801 Production of these proteins may be a cell response to general stress. The alarmones alert cells to the onset of the need for drastically changed priorities. The modified cell, or organism, becomes more resistant to harm from many agents.
Alteration in Cell Cycle Control Factors and the Induction of Oxygen-Regulated Proteins by Hypoxic Stress
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Harold C. Smith, Robert L. Howell, John W. Ludlow
The data and discussions presented here indicate the need for more molecular analyses in the area of cell cycle progression in hypoxic cells. The prediction from the data is that each tissue and cell type evaluated in this manner will express generic as well as cell type specific or nongeneric responses to ischemic stress. Understanding ischemic cell stress response at the level of the pathways affected is essential for the development of rational interventions for either enhancing the killing of cells (in the case of cancer) or preserving their integrity (in the case of organ transplantation or ischemia-related diseases). A recurring theme at this workshop was that the pathophysiology of the stressed cell may actually be protective. Attempts to rapidly return the cell’s extracellular and intracellular microenvironment to that characteristic of normoxic cell physiology may actually exacerbate cell survival.
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
An intrinsic pathway is initiated in response to cell stress caused by DNA damage or growth factor deficiency. It is mediated by changes in permeability of the mitochondrial outer membrane which is regulated through interactions between pro- and anti-apoptotic members of the Bcl-2 family of proteins. This results in release of mitochondrial factors, most importantly cytochrome C, leading to loss of mitochondrial functions and initiation of a cascade of caspase protease activities and cell death, reviewed in Elmore (50); Noy (51); Tait and Green (52).
CD80 expression is upregulated by TP53 activation in human cancer epithelial cells
Published in OncoImmunology, 2021
Melania Scarpa, Chiara Marchiori, Marco Scarpa, Ignazio Castagliuolo
Tumor cells employ several immune-suppressive strategies to overcome antitumor immunity. One such method is the modulation on the tumor cell surface of the expression of T cell cosignaling molecules, which are required for effective T cell activation and consequently a successful elimination of cancer cells.5 CD80 is recognized as one of the most potent costimulatory molecules by which immune cells limit malignant growth.6 It is upregulated upon cell stress and it is critical for efficacious immune surveillance during carcinogenesis.7–9 Low surface expression of CD80 was reported as an immune escape mechanism of colon carcinoma;10 on the other hand, its expression resulted enhanced in high-frequency microsatellite instability (MSI) colorectal cancers, a CRC subtype which is highly immunogenic and associated with a better prognosis.11 Both in vivo and in vitro studies showed that the upregulation of CD80 on tumor cell surface successfully activates anti-tumor immune responses, while its expression is frequently lost during tumor progression probably due to selective pressure by the immune system.7,12–14 Thus, to develop effective approaches for cancer immunotherapy, strategies for enhancing CD80 expression in tumors are urgently required.15 However, the current understanding of the regulation of CD80 expression is limited.
Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report
Published in International Journal of Hyperthermia, 2020
Rolf D. Issels, Lars H. Lindner, Michael von Bergwelt-Baildon, Peter Lang, Christoph Rischpler, Heinz Diem, Barbara Mosetter, Judith Eckl, Dolores J. Schendel, Christoph Salat, Oliver Stötzer, Stefan Burdach, Irene von Luettichau-Teichert, Rupert Handgretinger, Jens Neumann, Thomas Kirchner, Katja Steiger, Melanie Boxberg, Ulrich Mansmann, Gabriele Multhoff, Elfriede Noessner
Alveolar rhabdomyosarcoma (ARMS) with PAX3–FKHR translocation is an aggressive subtype of rhabdomyosarcoma in childhood with dismal prognosis [1]. Regional hyperthermia is a noninvasive cancer treatment targeting heat (range 41–43 °C) to the region of the localized tumor without an increase of the systemic body temperature. In a randomized phase III trial comparing regional hyperthermia combined with chemotherapy to chemotherapy alone, the addition of heat improved local tumor control in patients with high-risk soft tissue sarcoma [2]. After long-term follow-up, survival was improved also in the subgroup of patients with extremity tumors who usually die of metastases, suggesting immune effects outside of the heated target [3]. Cell stress provides critical cues for activating and targeting the immune system to recognize cancer cells [4]. Up-regulation of the MHC class I chain-related protein family (MICA, MICB) and induction of heat shock protein 70 (HSP70) by heat-stress have been identified as triggers to activate innate immunity and to bridge toward adaptive immunity [5]. NK cells as well as cytotoxic CD8+ and subsets of CD4+ T cells express the lectin-like natural-killer group 2 D (NKG2D) activating receptor and thereby can receive co-stimulation through stress-induced NKG2D ligands, like MICA/B and HSP70, and thereby support their capacity to kill tumor cells [6]. Furthermore, NK cells recognize and target cells with an incomplete or incompatible expression of MHC class I molecules (KIR-ligand mismatch) [7].
The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes
Published in Expert Review of Proteomics, 2019
Ernesto S. Nakayasu, Wei-Jun Qian, Carmella Evans-Molina, Raghavendra G. Mirmira, Decio L. Eizirik, Thomas O. Metz
Most clinical trials in T1D have been initiated at the onset of Stage 3 T1D. As the success of this approach has been modest, an alternative is to intervene earlier in the disease process, at a time when greater β-cell mass remains. While the presence of multiple autoantibodies signifies a future risk of developing T1D, the time-frame of disease development is unclear based on the measurement of autoantibody status alone. Furthermore, the determination of these autoantibodies neither allows evaluation of progressive cell death nor of the potential impact of novel therapies to protect them. Thus, the idea of developing biomarkers of β-cell stress and death is attractive and offers the potential of both targeting the individuals at highest risk and evaluating the effects of intervention therapies. However, a major challenge is to discriminate the signals emitted from insulitis and the dying β cells, as β cells comprise only 1–2% of the pancreas mass (1–2 g total in humans), from signals emitted by other tissues. Moreover, T1D poses a unique challenge owing to the relative inaccessibility of the target organ for interrogation by imaging or biopsy in living individuals.