Biliary Tract Cancer: State of the Art and potential role of DNA Damage Repair

2018 ◽  
Vol 70 ◽  
pp. 168-177 ◽  
Author(s):  
Angela Lamarca ◽  
Jorge Barriuso ◽  
Mairéad G. McNamara ◽  
Juan W. Valle
Keyword(s):  
Dna Damage ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Potential Role ◽  
State Of The Art ◽  
Dna Damage Repair ◽  
Tract Cancer ◽  
Damage Repair

scholarly journals The DNA damage repair (DDR) pathway in biliary tract cancer (BTC): a new Pandora’s box?

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e001042 ◽  
Author(s):  
Angela Dalia Ricci ◽  
Alessandro Rizzo ◽  
Giovanni Brandi
Keyword(s):  
Dna Damage ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Dna Damage Repair ◽  
Tract Cancer ◽  
Damage Repair

scholarly journals Metabolomics Reveals Aging-associated Attenuation of Noninvasive Radiation Biomarkers in Mice: Potential Role of Polyamine Catabolism and Incoherent DNA Damage-repair

2013 ◽  
Vol 12 (5) ◽  
pp. 2269-2281 ◽  
Author(s):  
Soumen K. Manna ◽  
Kristopher W. Krausz ◽  
Jessica A. Bonzo ◽  
Jeffrey R. Idle ◽  
Frank J. Gonzalez
Keyword(s):  
Dna Damage ◽  
Potential Role ◽  
Dna Damage Repair ◽  
Polyamine Catabolism ◽  
Damage Repair

Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer.

2021 ◽  
Author(s):  
Satoshi Nara ◽  
Minoru Esaki ◽  
Daisuke Ban ◽  
Takeshi Takamoto ◽  
Takahiro Mizui ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tract Cancer ◽  
Adjuvant And Neoadjuvant Therapy

Investigating the Role of SF3B1 Mutations in DNA Damage Repair in Myeloid Malignancies

2017 ◽  
Vol 55 ◽  
pp. S159-S160
Author(s):  
K. Lappin ◽  
F. Liberante ◽  
K. Savage ◽  
K. Mills
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Myeloid Malignancies ◽  
Damage Repair

Abstract 2039: The role of HORMAD1 in DNA damage repair in squamous cell carcinomas

2021 ◽  
Author(s):  
Jennifer Gantchev ◽  
Amelia Martinez Villarreal ◽  
Brandon Ramchatesingh ◽  
Ivan V. Litvinov
Keyword(s):  
Dna Damage ◽  
Squamous Cell ◽  
Dna Damage Repair ◽  
Squamous Cell Carcinomas ◽  
Damage Repair

Prognostic value of dickkopf-1 and ß-catenin expression according to the antitumor immunity of CD8-positive tumor-infiltrating lymphocytes in biliary tract cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16172-e16172
Author(s):  
Seoree Kim ◽  
Yoon Ho Ko ◽  
Hye Sung Won ◽  
Ji Hyun Yang ◽  
Der Sheng Sun ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Research Network ◽  
Antigen Retrieval ◽  
Tract Cancer ◽  
Tissue Sections ◽  
Dkk1 Expression

e16172 Background: Despite recent advancements in the understanding of the molecular biology of biliary tract cancer (BTC), target therapy and immunotherapy have demonstrated only limited efficacy, with cytotoxic systemic therapy still being the most effective treatment in BTC, except for surgery. Thus, this study aimed to analyze the role of DKK1 or β-catenin as a prognostic factor in BTC and determine the clinical association of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocyte (TIL). Methods: We used data in The Cancer Genome Atlas (TCGA) Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, and whole tissue sections of representative tumor samples were used for antigen retrieval. Results: CD8+TIL expression was a significant predictor of favorable overall survival (OS) and recurrence-free survival (RFS) (median OS, 34.9months in TIL-high, 16.7months in TIL-low, P < 0.0001 respectively; median RFS, 27.1months in TIL-high, 10months in TIL-low, P < 0.0001 respectively). Positive ß-catenin expression and high DKK1 expression was also associated with a shorter OS (median OS, 23.95months in positive ß-catenin, 26.1months in negative ß-catenin, P = 0.1009 respectively; median OS, 19.4months in high DKK1, 31.65months in Low DKK1, P = 0.0093 respectively), but not RFS (p = 0.1466, at ß-catenin respectively; p = 0.2924, in DKK1 respectively). In the CD8+TIL-high BTC group, the tumor expression of β-catenin and DKK1 had a significant negative impact on either OS or RFS (p = 0.0146 and p = 0.0112, at ß-catenin respectively; p = 0.0950 and p = 0.3904, in DKK1 respectively). However, in the TIL-low BTC group, there were no differences in OS or RFS according to ß-catenin and DKK1 expression (p = 0.5108 and p = 0.8431, at ß-catenin respectively; p = 0.1127 and p = 0.1095, in DKK1 respectively). Cox regression multivariate analysis demonstrated that CD8+ TIL (hazard ratio [HR], 0.490; 95% confidence interval (CI), 0.303-0.791; p = 0.004) and β-catenin (HR, 1.652; 95% CI, 1.035-2.639; p = 0.036) retained significant association with OS after adjustment for all variables. Conclusions: Among patients with resected BTC, β-catenin and DKK1 protein levels are associated with poor clinical outcomes, whereas high CD8+ TIL levels are associated with good clinical outcomes. This confirms the differential clinical role of Wnt/β-catenin and DKK1 proteins according to TIL expression in BTC.

scholarly journals SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair

2019 ◽  
Vol 5 (3) ◽  
pp. eaav1118 ◽  
Author(s):  
Ming Tang ◽  
Zhiming Li ◽  
Chaohua Zhang ◽  
Xiaopeng Lu ◽  
Bo Tu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Class Iii ◽  
Ataxia Telangiectasia Mutated ◽  
Damage Repair ◽  
Damage Response ◽  
Late Stages

The activation of ataxia-telangiectasia mutated (ATM) upon DNA damage involves a cascade of reactions, including acetylation by TIP60 and autophosphorylation. However, how ATM is progressively deactivated after completing DNA damage repair remains obscure. Here, we report that sirtuin 7 (SIRT7)–mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. In response to DNA damage, SIRT7 is mobilized onto chromatin and deacetylates ATM during the late stages of DNA damage response, when ATM is being gradually deactivated. Deacetylation of ATM by SIRT7 is prerequisite for its dephosphorylation by its phosphatase WIP1. Consequently, depletion of SIRT7 or acetylation-mimic mutation of ATM induces persistent ATM phosphorylation and activation, thus leading to impaired DNA damage repair. Together, our findings reveal a previously unidentified role of SIRT7 in regulating ATM activity and DNA damage repair.

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