Ataxia-Telangiectasia (A-T): An Emerging Dimension of Premature Ageing.

Ataxia-Telangiectasia (A-T): An Emerging Dimension of Premature Ageing. Ageing Res Rev. 2016 May 12; Authors: Shiloh Y, Lederman HM Abstract A-T is a prototype genome instability syndrome and a multifaceted disease. A-T leads to neurodegeneration - primarily cerebellar atrophy, immunodeficiency, oculocutaneous telangiectasia (dilated blood vessels), vestigial thymus and gonads, endocrine abnormalities, cancer predisposition and varying sensitivity to DNA damaging agents, particularly those that induce DNA double-strand breaks. With the recent increase in life expectancy of A-T patients, the premature ageing component of this disease is gaining greater awareness. The complex A-T phenotype reflects the ever growing number of functions assigned to the protein encoded by the responsible gene - the homeostatic protein kinase, ATM. The quest to thoroughly understand the complex A-T phenotype may reveal yet elusive ATM functions. PMID: 27181190 [PubMed - as supplied by publisher]
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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Clin Immunol. 2021 Jul 20:108802. doi: 10.1016/j.clim.2021.108802. Online ahead of print.ABSTRACTAtaxia-telangiectasia (A-T) is a multisystem disorder caused by biallelic pathogenic variants in the gene encoding A-T mutated (ATM) kinase, a master regulator of the DNA damage response (DDR) pathway. Most A-T patients show cellular and/or humoral immunodeficiency that has been associated with cancer risk and reduced survival, but NK cells have not been thoroughly studied. Here we investigated NK cells of A-T patients with a special focus on the NKG2D receptor that triggers cytotoxicity upon engagement by its ligands (NKG2DLs)...
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
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Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Source Type: research
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
Paul Nghiem Metastatic cancers resistant to immunotherapy require novel management strategies. DNA damage response (DDR) proteins, including ATR (ataxia telangiectasia and Rad3-related), ATM (ataxia telangiectasia mutated) and DNA-PK (DNA-dependent protein kinase), have been promising therapeutic targets for decades. Specific, potent DDR inhibitors (DDRi) recently entered clinical trials. Surprisingly, preclinical studies have now indicated that DDRi may stimulate anti-tumor immunity to augment immunotherapy. The mechanisms governing how DDRi could promote anti-tumor immunity are not well understood; however, early evi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
J Radiat Res. 2021 Jul 1:rrab050. doi: 10.1093/jrr/rrab050. Online ahead of print.ABSTRACTProgrammed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that ...
Source: Cell Research - Category: Cytology Authors: Source Type: research
a Ataxia telangiectasia (AT) is characterized by extreme sensitivity to ionizing radiation. The gene mutated in AT, Ataxia Telangiectasia Mutated (ATM), has serine/threonine protein kinase activity and mediates the activation of multiple signal transduction pathways involved in the processing of DNA double-strand breaks. Reactive oxygen species (ROS) created as a byproduct of the mitochondria’s oxidative phosphorylation (OXPHOS) has been proposed to be the source of intracellular ROS. Mitochondria are uniquely vulnerable to ROS because they are the sites of ROS generation. ROS-induced mitochondrial mutations lead...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ien Hoffmann Jenifer Saffi Despite the ample improvements of CRC molecular landscape, the therapeutic options still rely on conventional chemotherapy-based regimens for early disease, and few targeted agents are recommended for clinical use in the metastatic setting. Moreover, the impact of cytotoxic, targeted agents, and immunotherapy combinations in the metastatic scenario is not fully satisfactory, especially the outcomes for patients who develop resistance to these treatments need to be improved. Here, we examine the opportunity to consider therapeutic agents targeting DNA repair and DNA replication stress respon...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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