scholarly journals The NLRP3 inflammasome affects DNA damage responses after oxidative and genotoxic stress in dendritic cells

2013 ◽  
Vol 43 (8) ◽  
pp. 2126-2137 ◽  
Author(s):  
Ginevra Licandro ◽  
Hwei Ling Khor ◽  
Ottavio Beretta ◽  
Junyun Lai ◽  
Heidi Derks ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dendritic Cells ◽  
Nlrp3 Inflammasome ◽  
Genotoxic Stress ◽  
Dna Damage Responses

Temporal Telomere and DNA Damage Responses in the Space Radiation Environment

2020 ◽  
Author(s):  
Jared J. Luxton ◽  
Miles J. McKenna ◽  
Lynn E. Taylor ◽  
Kerry A. George ◽  
Sara Zwart ◽  
...  
Keyword(s):  
Dna Damage ◽  
Space Radiation ◽  
Radiation Environment ◽  
Dna Damage Responses ◽  
Space Radiation Environment

A novel NGR-conjugated peptide targets DNA damage responses for radiosensitization

2015 ◽  
Vol 15 (6) ◽  
pp. 533-541 ◽  
Author(s):  
Jinlu Ma ◽  
Dan Zhang ◽  
Xia Ying ◽  
Ying Zhao ◽  
Chenchen He ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Responses

scholarly journals PRL3 induces polypoid giant cancer cells eliminated by PRL3-zumab to reduce tumor relapse

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Min Thura ◽  
Zu Ye ◽  
Abdul Qader Al-Aidaroos ◽  
Qiancheng Xiong ◽  
Jun Yi Ong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cancer Cells ◽  
Embryonic Stem ◽  
Genotoxic Stress ◽  
Stem Cell Markers ◽  
Tumor Removal ◽  
Primary Tumors ◽  
Tumor Relapse ◽  
Dna Damage Signaling

AbstractPRL3, a unique oncotarget, is specifically overexpressed in 80.6% of cancers. In 2003, we reported that PRL3 promotes cell migration, invasion, and metastasis. Herein, firstly, we show that PRL3 induces Polyploid Giant Cancer Cells (PGCCs) formation. PGCCs constitute stem cell-like pools to facilitate cell survival, chemo-resistance, and tumor relapse. The correlations between PRL3 overexpression and PGCCs attributes raised possibilities that PRL3 could be involved in PGCCs formation. Secondly, we show that PRL3+ PGCCs co-express the embryonic stem cell markers SOX2 and OCT4 and arise mainly due to incomplete cytokinesis despite extensive DNA damage. Thirdly, we reveal that PRL3+ PGCCs tolerate prolonged chemotherapy-induced genotoxic stress via suppression of the pro-apoptotic ATM DNA damage-signaling pathway. Fourthly, we demonstrated PRL3-zumab, a First-in-Class humanized antibody drug against PRL3 oncotarget, could reduce tumor relapse in ‘tumor removal’ animal model. Finally, we confirmed that PGCCs were enriched in relapse tumors versus primary tumors. PRL3-zumab has been approved for Phase 2 clinical trials in Singapore, US, and China to block all solid tumors. This study further showed PRL3-zumab could potentially serve an ‘Adjuvant Immunotherapy’ after tumor removal surgery to eliminate PRL3+ PGCC stem-like cells, preventing metastasis and relapse.

scholarly journals Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Munetoshi Maeda ◽  
Masanori Tomita ◽  
Mika Maeda ◽  
Hideki Matsumoto ◽  
Noriko Usami ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Ataxia Telangiectasia ◽  
Kinase Inhibitor ◽  
Surrogate Marker ◽  
X Rays ◽  
Ataxia Telangiectasia Mutated ◽  
Whole Cell ◽  
X Ray ◽  
Dna Damage Responses

AbstractWe recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

scholarly journals Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1289 ◽  
Author(s):  
Xing Bian ◽  
Wenchu Lin
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Repair ◽  
Predictive Biomarkers ◽  
Replication Stress ◽  
Genotoxic Stress ◽  
Repair System ◽  
Damage Repair ◽  
Repair Pathways

Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies are urgently needed to improve clinical outcomes. Replication stress is a hallmark of SCLC due to several intrinsic factors. As a consequence, constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system is involved in counteracting this genotoxic stress. Therefore, therapeutic targeting of such RSR and DNA damage repair pathways will be likely to kill SCLC cells preferentially and may be exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions. Here, we summarize potentially valuable targets involved in the RSR and DNA damage repair pathways, rationales for targeting them in SCLC treatment and ongoing clinical trials, as well as possible predictive biomarkers for patient selection in the management of SCLC.

scholarly journals Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4

2010 ◽  
Vol 29 (18) ◽  
pp. 3130-3139 ◽  
Author(s):  
Sophie E Polo ◽  
Abderrahmane Kaidi ◽  
Linda Baskcomb ◽  
Yaron Galanty ◽  
Stephen P Jackson
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Chromatin Remodelling ◽  
Cycle Progression ◽  
Dna Damage Responses

scholarly journals Methotrexate enhances antigen presentation and maturation of tumour antigen-loaded dendritic cells through NLRP3 inflammasome activation: a strategy for dendritic cell-based cancer vaccine

2021 ◽  
Vol 13 ◽  
pp. 175883592098705
Author(s):  
Gao-Na Shi ◽  
Min Hu ◽  
Chengjuan Chen ◽  
Junmin Fu ◽  
Shuai Shao ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Nlrp3 Inflammasome ◽  
Tumour Antigen ◽  
Inflammasome Activation ◽  
Antigen Uptake ◽  
Nlrp3 Inflammasome Activation ◽  
Dc Maturation

Background: Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in adaptive cell-mediated immunity by priming and activating T cells against specific tumour and pathogenic antigens. Methotrexate (MTX), a folate derivative, functions as an immunoregulatory agent. However, the possible effect of MTX on tumour antigen-loaded DCs has not yet been investigated. Methods: We analysed the effect of MTX on the maturation and function of DCs along with tumour cell lysates (TCLs). Using bone marrow-derived DCs, we investigated the effect of MTX combined TCL-loaded DCs on T cells priming and proliferation. We also tested the anti-tumour immune effect on DCs when treated with MTX and/or TCL in vivo. Results: MTX combined with TCL not only enhanced DC maturation and stimulated cytokine release but also promoted CD8+ T cell activation and proliferation. The latter was associated with increased tumour antigen uptake and cross-presentation to T cells. Mechanistically, DC maturation and antigen presentation were partly modulated by NLRP3 inflammasome activation. Furthermore, immunisation of mice with MTX and TCL-pulsed DCs before a tumour challenge significantly delayed tumour onset and retarded its growth. This protective effect was due to priming of IFN-γ releasing CD8+ T cells and enhanced killing of tumour cells by cytotoxic T lymphocytes isolated from these immunised mice. Conclusion: MTX can function as a potent adjuvant in DC vaccines by increasing antigen presentation and T cell priming. Our findings provide a new strategy for the application of DC-based anti-tumour immunotherapy.

scholarly journals 570 The AHR-p27 axis modulates DNA damage responses in UV-irradiated keratinocytes in vitro and in vivo

2016 ◽  
Vol 136 (5) ◽  
pp. S101 ◽  
Author(s):  
S. Shaik ◽  
M. Pollet ◽  
J. Krutmann ◽  
T. Haarmann-Stemmann
Keyword(s):  
Dna Damage ◽  
Dna Damage Responses
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