Genomic instability in chronic airway inflammatory diseases

Bao, Zhengqiang; Xiong, Juan; Li, Wen; Chen, Zhihua; Shen, Huahao; Ying, Songmin

doi:10.4103/2319-4170.143478

Cited by 16 publications

(7 citation statements)

References 78 publications

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“…Indeed, PARPis lead to genotoxic effects in vitro. Yet, considerations on in vivo relevance of these studies and possible indirect protection from oxidative response-induced DNA damage make the picture more complex [157,158]. Although safety studies required for oncological drugs are "lighter" than for other diseases, clinically relevant PARPis passed safety studies and their potential side effects should be compared with currently available therapies for the considered diseases (for instance methotrexate in autoimmunity), none of which devoid of relevant side effects.…”

Section: Therapy Of Non-cancer Diseasesmentioning

confidence: 99%

Multifaceted Role of PARP-1 in DNA Repair and Inflammation: Pathological and Therapeutic Implications in Cancer and Non-Cancer Diseases

Pazzaglia

Pioli

2019

Cells

158

135

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PARP-1 (poly(ADP-ribose)-polymerase 1), mainly known for its protective role in DNA repair, also regulates inflammatory processes. Notably, defects in DNA repair and chronic inflammation may both predispose to cancer development. On the other hand, inhibition of DNA repair and inflammatory responses can be beneficial in cancer therapy and PARP inhibitors are currently used for their lethal effects on tumor cells. Furthermore, excess of PARP-1 activity has been associated with many tumors and inflammation-related clinical conditions, including asthma, sepsis, arthritis, atherosclerosis, and neurodegenerative diseases, to name a few. Activation and inhibition of PARP represent, therefore, a double-edged sword that can be exploited for therapeutic purposes. In our review, we will discuss recent findings highlighting the composite multifaceted role of PARP-1 in cancer and inflammation-related diseases.

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Section: Therapy Of Non-cancer Diseasesmentioning

confidence: 99%

Multifaceted Role of PARP-1 in DNA Repair and Inflammation: Pathological and Therapeutic Implications in Cancer and Non-Cancer Diseases

Pazzaglia

Pioli

2019

Cells

158

135

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“…As PARK2 deficiency results in both increased inflammation and genomic instability [37–39], we assessed a potential role of PARK2 in lung cancer and COPD through a comprehensive validation study of 114 informative single nucleotide polymorphism (SNP) variants of PARK2 (Supplementary Table S2) in 2,484 cases and controls with well-defined lung cancer (LC) and COPD phenotypes (Table 1). For specific comparisons, we assigned the four groups into the six models as follows: Model 1: LC+COPD+ vs. LC-COPD- (cases with both compared to controls with neither); Model 2: LC+COPD- vs. LC-COPD- (cases with LC compared to controls with neither); Model 3: LC-COPD+ vs. LC-COPD- (cases with COPD compared to controls with neither); Model 4: LC+COPD+ vs. LC-COPD+ (cases with both compared to controls with COPD); Model 5: LC+ vs. LC- (LC cases compared to LC-free controls, adjusting for COPD and other covariates including age, sex, and smoking history); and Model 6: COPD+ vs. COPD- (COPD cases compared to COPD-free controls, adjusting for LC and other covariates including age, sex, and smoking history).…”

Section: Resultsmentioning

confidence: 99%

Multiple-level validation identifiesPARK2in the development of lung cancer and chronic obstructive pulmonary disease

et al. 2016

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An important precursor to lung cancer development is chronic obstructive pulmonary disease (COPD), independent of exposure to tobacco smoke. Both diseases are associated with increased host susceptibility, inflammation, and genomic instability. However, validation of the candidate genes and functional confirmation to test shared genetic contribution and cellular mechanisms to the development of lung cancer in patients with COPD remains underexplored. Here, we show that loss of PARK2 (encoding Parkin) increases the expression of proinflammation factors as well as nuclear NF-κB localization, suggesting a role of PARK2 loss in inflammation. Additional exploration showed that PARK2 deficiency promotes genomic instability and cell transformation. This role of PARK2 in inflammation and chromosome instability provides a potential link among Parkin, COPD and lung cancer. A further comprehensive validation of 114 informative single nucleotide polymorphism (SNP) variants of PARK2, in 2,484 cases and controls with well-defined lung cancer and COPD phenotypes, found rs577876, rs6455728 and rs9346917 (p<0.01) to be significantly associated with lung cancer development in people with COPD. Our findings support the evidence that PARK2 might have a tumor suppressor role in the development of COPD and lung cancer.

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“…The situation in vivo is more complex and there is a possibility of indirect protection against DNA damage caused by oxidative reactions. 14 , 104 , 110 This issue undoubtedly requires further research.…”

Section: Parp Inhibitors – Opportunities and Threatsmentioning

confidence: 99%

PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis

Wasyluk¹,

Zwolak²

2021

JIR

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Genomic instability in chronic airway inflammatory diseases

Cited by 16 publications

References 78 publications

Multifaceted Role of PARP-1 in DNA Repair and Inflammation: Pathological and Therapeutic Implications in Cancer and Non-Cancer Diseases

Multifaceted Role of PARP-1 in DNA Repair and Inflammation: Pathological and Therapeutic Implications in Cancer and Non-Cancer Diseases

Multiple-level validation identifiesPARK2in the development of lung cancer and chronic obstructive pulmonary disease

PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis

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