Effects of silver nanoparticles on oxidative DNA damage-repair as a function of p38 MAPK status: A comparative approach using human Jurkat T cells and the nematodeCaenorhabditis elegans

2013 ◽  
Vol 55 (2) ◽  
pp. 122-133 ◽  
Author(s):  
Nivedita Chatterjee ◽  
Hyun Jeong Eom ◽  
Jinhee Choi
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
T Cells ◽  
P38 Mapk ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Comparative Approach ◽  
Jurkat T Cells ◽  
Damage Repair

RECQL5 mutations as a potential efficacious predictor of immunotherapy in melanoma patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21547-e21547
Author(s):  
Yun Zhao ◽  
Dandan Fan ◽  
Xiaochun Huang ◽  
Mengli Huang ◽  
Yaoxu Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
Immune Cells ◽  
Statistical Significance ◽  
Dna Damage Repair ◽  
Objective Response ◽  
Wilcoxon Test ◽  
Durable Response ◽  
Damage Repair ◽  
Melanoma Patients

e21547 Background: Gene mutations in DNA damage repair (DDR) pathway were reported to affect the clinical response to immune checkpoint inhibitors (ICIs) by driving mutagenicity. Previous studies showed that RECQL5 is involved in RAD51-mediated strand invasion for homologous recombination DNA damage repair (HR-DDR). RECQL5 encoding RecQ protein-like 5 (RECQL5) is a member of RecQ helicase family and was discovered to play a tumor-suppressive or oncogenic role in various cancers. However, the association between RECQL5 mutation and ICI efficacy has not been revealed. Methods: Data of nine publicly independent cohorts of NSCLC, melanoma, and pan-cancer were retrieved (Rizvi, MSKCC, OAK/POPLAR, Van Allen, Hugo, Synder, Miao and Samstein cohorts) to investigate the correlation between RECQL5 mutations and clinical events including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). Wilcoxon test was used for comparing tumor mutational burden (TMB) between RECQL5-mutated patients and their wild-type counterparts. In addition, the correlation between infiltration of immune cells and RECQL5 mutation status was also analyzed by QUANTISEO using data of SKCM cohort (n=466) from TCGA database. Statistical significance was set at P = 0.05. Results: RECQL5 mutations were most commonly seen in melanoma patients and the detection rate was 4%-8% in melanoma patients from cohort Van Allen, Hugo, Synder, and Miao. RECQL5 mutation was not detected in other cancers except for one lung cancer case. In the three melanoma cohorts (Van Allen, Synder, Miao) with OS data available, the OS of the RECQL5-mutated patients was 2 to 3 times longer than that of the RECQL5-wt patients. In Synder cohort, the difference in OS between these two subsets was statistically significant (53.9 months vs 25.0 months, P = 0.045). In addition, the occurrence of RECQL5 mutations was correlated with higher CBR both in Miao ( P = 0.017) and Synder cohorts ( P = 0.011). No difference was observed in the PFS or ORR between these two subsets. Notably, RECQL5 mutations were associated with higher TMB levels both in Miao (32.6 mut/Mb vs 7.9 mut/Mb, P = 0.016) and Synder cohorts (1124 mut/Mb vs 358 mut/Mb, P = 0.033). Moreover, RECQL5 mutations were found to be correlated with increased infiltration of CD4+ T cells (no-regulatory) ( P = 0.037), B cells ( P = 0.13) and decreased infiltration of regulatory CD4+ T cells ( P = 0.02) in RECQL5-mutated tumors over RECQL5-wt tumors. Conclusions: RECQL5 mutations can serve as a potential predictor for a durable response to ICIs in melanoma. Moreover, the occurrence of RECQL5 mutations was correlated with higher TMB level as well as infiltration of immune cells, indicating the underlying mechanism of its predictive effect.

Mechanism of oxidative DNA damage repair and relevance to human pathology

2008 ◽  
Vol 659 (1-2) ◽  
pp. 4-14 ◽  
Author(s):  
M DERRICO ◽  
E PARLANTI ◽  
E DOGLIOTTI
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Human Pathology

Oxidative DNA damage repair products as molecular markers of cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e13525-e13525
Author(s):  
Krzysztof Roszkowski ◽  
Piotr Blaszczyk ◽  
Anna Mucha-Malecka ◽  
Anna Bak ◽  
Gabriela Karczewska ◽  
...  
Keyword(s):  
Dna Damage ◽  
Molecular Markers ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Damage Repair

An association selected polymorphisms of XRCC1, OGG1 and MUTYH gene and the level of efficiency oxidative DNA damage repair with a risk of colorectal cancer

2013 ◽  
Vol 745-746 ◽  
pp. 6-15 ◽  
Author(s):  
Karolina Przybylowska ◽  
Jacek Kabzinski ◽  
Andrzej Sygut ◽  
Lukasz Dziki ◽  
Adam Dziki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Mutyh Gene

scholarly journals The function of cux1 in oxidative dna damage repair is needed to prevent premature senescence of mouse embryo fibroblasts

Oncotarget ◽  
2015 ◽  
Vol 6 (6) ◽  
pp. 3613-3626 ◽  
Author(s):  
Zubaidah M. Ramdzan ◽  
Ranjana Pal ◽  
Simran Kaur ◽  
Lam Leduy ◽  
Ginette Bérubé ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mouse Embryo ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Premature Senescence ◽  
Mouse Embryo Fibroblasts ◽  
Damage Repair ◽  
Embryo Fibroblasts

Ezh2 Is An Essential Regulator Of T-Cell Development and Oncogenic Transformation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3729-3729
Author(s):  
Camille Simon ◽  
Jalila Chagraoui ◽  
Jana Krosl ◽  
Josee Hebert ◽  
Guy Sauvageau
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
Cell Division ◽  
Dna Replication ◽  
T Cell ◽  
Dna Damage Repair ◽  
Conditional Knockout ◽  
Functional Study ◽  
Wild Type ◽  
Damage Repair

Abstract Enhancer of zeste homolog 2 (EZH2) catalyzes di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) and establishes chromatin marks associated with gene silencing. We and others have recently shown that Ezh2 and its partners act as tumour suppressor genes in mouse and likely human lymphoblastic leukemia. Moreover some studies also suggest that Ezh2 is strongly required during B and T cell differentiation. However, the function of EZH2 during these processes remains unclear. For functional study we exploited an Ezh2 conditional knockout mouse model. The Cre-mediated deletion generates a mutated Ezh2Δ allele and abrogates production of EZH2 protein. Upon gene inactivation we monitored T-cell maturation and cancer development. We found that Ezh2 inactivation induces a block at the DN3-DN4 transition of TCRab+T-cells while TCRγδ T-cells were increased by 5 fold compared to wild type animals. Cell cycle analysis revealed increase in the proportions of TCRγδ+T-cells in the G2 phase compared to TCRβ+T-cells and wild type controls. This observation suggested a possibility of G2/M checkpoint activation resulting from either improper DNA replication, or a non-repaired DNA damage. Moreover we found that the Ezh2 deficient TCRγδ+ leukemia were prone to genomic instability. A majority of leukemias analyzed were aneuploid, and ∼50% were near-tetraploid. These observations were confirmed by Spectral Karyotyping (SKY), which also enabled detection of several chromosomal rearrangements. Consistent with these observations, analysis of global gene expression data from various RNA-Seq-derived datasets revealed that the genes having the highest correlation factor with Ezh2 are involved in cell division, DNA replication and DNA damage repair. Together, these studies show that Ezh2 is an essential regulator of the TCRγδ T-cell state, and prevents T-cell transformation, likely through regulation of DNA replication, cell division or DNA damage repair. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G 2 /M arrest and multinucleation

2008 ◽  
Vol 29 (4) ◽  
pp. 722-728 ◽  
Author(s):  
Yali Xie ◽  
Hanjing Yang ◽  
Jeffrey H. Miller ◽  
Diana M. Shih ◽  
Geoffrey G. Hicks ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Repair Genes
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