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Frontiers in Immunology 2022As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several...
As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several cytoplasm pattern recognition receptors exist to sense the attacks from either foreign or host origins, triggering the immune response to battle with the infections. Among them, cGAS-STING is the major pathway that mainly responds to microbial DNA, DNA virus infections, or self-DNA, which mainly comes from genome instability by-product or released DNA from the mitochondria. cGAS was initially found functional in the cytoplasm, although intriguing evidence indicates that cGAS exists in the nucleus where it is involved in the DNA damage repair process. Because the close connection between DNA damage response and immune response and cGAS recognizes DNA in length-dependent but DNA sequence-independent manners, it is urgent to clear the function balance of cGAS in the nucleus versus cytoplasm and how it is shielded from recognizing the host origin DNA. Here, we outline the current conception of immune response and the regulation mechanism of cGAS in the nucleus. Furthermore, we will shed light on the potential mechanisms that are restricted to be taken away from self-DNA recognition, especially how post-translational modification regulates cGAS functions.
Topics: Signal Transduction; Immunity, Innate; Nucleotidyltransferases; DNA; DNA Damage
PubMed: 36591232
DOI: 10.3389/fimmu.2022.1076784 -
Critical Reviews in Oncology/hematology Sep 2020Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical... (Review)
Review
BACKGROUND
Current research that combines radiation with targeted therapy may dramatically improve prognosis of pancreatic ductal adenocarcinoma (PDAC). We investigated preclinical outcomes of DNA repair inhibitor targeted therapy associated with radiotherapy.
METHODS
We searched Pubmed database to identify publications assessing DNA damage targeted therapies in preclinical models of PDACin vitro and in vivo. Standard enhancement ratio, median survival and growth delay were extracted.
RESULTS
We identified fourteen publications using DNA repair targeted therapies in preclinical models of PDAC. Ten publications comprising twenty-eight experiments evaluated radiosensitization with different DNA repair inhibitors in vitro and displayed cell killing by a factor of 1.35 ± 0.047. Moreover, 86 % (24/28) of in vitro experiments showed radiosensitization with DNA damage response inhibitor. However, only 60 % (9/15) of the in vivo experiments presented radiosensitization effects.
CONCLUSION
DNA repair targeted therapies use promising radiosensitizers for PDAC and could successfully be translated into clinical trials.
Topics: Carcinoma, Pancreatic Ductal; DNA Damage; DNA Repair; Humans; Pancreatic Neoplasms; Radiation-Sensitizing Agents
PubMed: 32707435
DOI: 10.1016/j.critrevonc.2020.103060 -
Journal of Dietary Supplements 2021Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities and . There...
Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities and . There is growing commercial interest in the application of astaxanthin in nutraceuticals and cosmeceuticals, due to its purported photoprotective, DNA repair, antioxidant, and anti-inflammatory benefits. This systematic review therefore aimed to summarize current clinical evidence on the effects of astaxanthin supplementation on skin health. Using the following combinations of broad Major Exploded Subject Headings (MesH) terms or text words [astaxanthin OR AST OR ASX OR carotenoid OR xanthophyll] AND [skin OR derm*], a comprehensive search of PubMed, EMBASE, Medline, Clinicaltrials.gov, and Google Scholar databases found a total of eleven clinical studies. There were six randomized, placebo-controlled, double-blind trials, while the rest were prospective, open-label studies. In many of the randomized, controlled trials reviewed, AST supplementation improved skin texture, appearance (wrinkles), and moisture content at the end of the study period. AST also appeared to protect against UV-induced skin damage. No serious adverse events were reported in any of the studies. However, most available studies had a relatively small sample size and were conducted on healthy Japanese females. Many of the studies were also funded by commercial entities, with potential conflicts of interests. This was difficult to account for in our analyses. Overall, there is some clinical data to support the benefits of astaxanthin supplementation (in the range of 3 to 6 mg/d) on skin health, especially for photoaged skin.
Topics: Dietary Supplements; Female; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Skin; Xanthophylls
PubMed: 32202443
DOI: 10.1080/19390211.2020.1739187 -
Critical Reviews in Oncology/hematology Oct 2013The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the deficiency in mismatch repair (MMR) genes and prognosis in women with endometrial cancer is unclear. Here we report a systematic review and meta-analysis exploring this association.
METHODS
We searched literature databases (MEDLINE, EMBASE, and Cochrane) from 1980 until December 2011 to identify studies evaluating the association between MMR status and clinical outcome in endometrial cancer. The main outcome measures were overall survival (OS) and disease-free survival (DFS).
RESULTS
Twenty-three studies met the inclusion criteria. The median sample size of studies was 112, 74% were retrospective case-series and 70% performed microsatellite instability (MSI) analysis to evaluate the status of MMR. Only 22% of studies used the panel of five microsatellite markers recommended by the National Cancer Institute. Seven studies used immunohistochemistry to define MMR deficiency, but only two of them determined the expression of all four MMR proteins. Overall, significant associations between MMR and outcome were observed in 32% of studies. There was marked inter-study heterogeneity for estimates of OS and DFS. Pooled analysis did not show any significant association between deficiency in MMR and worse OS (6 studies, hazard ratio [HR] 2.0, p=0.11) or DFS (4 studies, HR ratio 1.31, p=0.66).
CONCLUSION
There is no definitive evidence of a significant association between MMR status and detrimental survival in endometrial cancer.
Topics: DNA Mismatch Repair; DNA-Binding Proteins; Endometrial Neoplasms; Female; Humans; Microsatellite Instability; Patient Outcome Assessment; Prognosis; Proportional Hazards Models
PubMed: 23562498
DOI: 10.1016/j.critrevonc.2013.03.002 -
Frontiers in Endocrinology 2023In the complex and dynamic processes of replication, transcription, and translation of DNA molecules, a large number of replication errors or damage can occur which lead... (Review)
Review
In the complex and dynamic processes of replication, transcription, and translation of DNA molecules, a large number of replication errors or damage can occur which lead to obstacles in the development process of germ cells and result in a decreased reproductive rate. DNA damage repair has attracted widespread attention due to its important role in the maintenance and regulation of germ cells. This study reports on a systematic review of the role and mechanism of DNA damage repair in germline development. First, the causes, detection methods, and repair methods of DNA damage, and the mechanism of DNA damage repair are summarized. Second, a summary of the causes of abnormal DNA damage repair in germ cells is introduced along with common examples, and the relevant effects of germ cell damage. Third, we introduce the application of drugs related to DNA damage repair in the treatment of reproductive diseases and related surgical treatment of abnormal DNA damage, and summarize various applications of DNA damage repair in germ cells. Finally, a summary and discussion is given of the current deficiencies in DNA damage repair during germ cell development and future research development. The purpose of this paper is to provide researchers engaged in relevant fields with a further systematic understanding of the relevant applications of DNA damage repair in germ cells and to gain inspiration from it to provide new research ideas for related fields.
Topics: DNA Repair; DNA Damage; Reproduction; Germ Cells; Cell Differentiation
PubMed: 37529603
DOI: 10.3389/fendo.2023.1234280 -
Bulletin Du Cancer Apr 2015The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility, and a large amount studies have examined the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility, and a large amount studies have examined the association of the rs861539 in XRCC3 (Thr241Met) with lung cancer risk in various populations. However, the results remain inconclusive.
METHODS
The electronic database of PubMed, Medline, Embase and CNKI (China National Knowledge Infrastructure) were searched for case-control studies published up to December 05, 2013. A systematic review and meta-analysis was performed to evaluate the relationship between XRCC3 Thr241Met polymorphism and lung cancer risk. Data were extracted and pooled odds ratio (OR) with its 95% confidence intervals (CI) were calculated.
RESULTS
Total 21 studies, including 6880 lung cancer cases and 8329 controls, were available for meta-analysis. Overall, our results showed that the XRCC3 Thr241Met polymorphism was not associated with risk of lung cancer in all genetic contrast models (P>0.05). Stratified analyses by ethnicity (Asians, Caucasians and mixed population) showed similar results. Additionally, no evidence of publication bias was observed by using the funnel plot.
CONCLUSIONS
There is no clear evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk in total population and stratified analysis by ethnicity. However, studies assessing the gene-gene interactions should be considered to further estimate this gene variant in lung cancer risk.
Topics: Case-Control Studies; Confidence Intervals; DNA Repair; DNA-Binding Proteins; Humans; Lung Neoplasms; Polymorphism, Genetic
PubMed: 25794597
DOI: 10.1016/j.bulcan.2015.02.003 -
Radiation Research Jun 2024This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which...
This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which currently includes 285 DNA DSB repair experiments utilizing both photons and ions, we investigate the impact of distinct experimental parameters on the kinetics of DNA DSB repair. Methodological differences and inconsistencies in reporting make the comparison of data generated by different research groups challenging. Nevertheless, by implementing filtering criteria, we can compare repair kinetics obtained with normal and tumor cells derived from human or animal tissues, as well as cells exposed to photons or ions ranging from hydrogen to iron ions. In addition, several repair curves of repair deficient cell lines were included. The study aims to provide researchers with a comprehensive overview of experimental factors that may confound results and emphasize the importance of precise reporting of experimental parameters. Moreover, we identify gaps in the literature that require attention in future studies, aiming to address clinically relevant questions related to radiotherapy. The database can be freely accessed at: https://github.com/weradstake/DRDNA.
Topics: DNA Breaks, Double-Stranded; Humans; Photons; DNA Repair; Kinetics; Animals; Ions
PubMed: 38376467
DOI: 10.1667/RADE-23-00190.1 -
Clinical Oncology (Royal College of... Jul 2024ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both... (Meta-Analysis)
Meta-Analysis
AIMS
ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer.
MATERIALS AND METHODS
SNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate.
RESULTS
A total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001).
CONCLUSION
Genetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription.
Topics: Humans; Radiation Pneumonitis; Lung Neoplasms; DNA Repair; Polymorphism, Single Nucleotide; Xeroderma Pigmentosum Group D Protein; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Carcinoma, Non-Small-Cell Lung
PubMed: 38653664
DOI: 10.1016/j.clon.2024.03.019 -
Asian Pacific Journal of Cancer... Feb 2017Objective: Although there are a few studies investigating the relation between X-Ray Repair Cross Complementing 3 (XRCC3) gene rs861539 polymorphism and osteosarcoma...
Objective: Although there are a few studies investigating the relation between X-Ray Repair Cross Complementing 3 (XRCC3) gene rs861539 polymorphism and osteosarcoma (OSA), the results are inconsistent. Therefore, we performed this systematic review and meta-analysis to clarify the associations between XRCC3 rs861539 polymorphism and OSA risk. Methods: We have retrieved published literature from PubMed, Google scholar, and ISI Web of Knowledge up to 25 January 2017. Odds ratios were pooled using either fixed-effects or random effects models. Overall and subgroup analyses were performed. Statistical analysis was performed running comprehensive meta-analysis (CMA) 2.0 software. Results: A total of four studies with 515 cases and 1,109 controls were identified in order to investigate the association between XRCC3 rs861539 polymorphism and OSA risk. The results showed that XRCC3 rs861539 polymorphism was associated with OSA in allelic (T vs. C: OR= 1.563, 95% CI: 1.244-1.963, p= <0.001), homozygote (TT vs. CC: OR= 2.574, 95% CI: 1.573-4.212, p= <0.001), dominant (TT+TC vs. CC: OR= 1.255, 95% CI: 1.011-1.558, p= 0.039), and recessive (TT vs. TC+CC: OR= 2.224, 95% CI: 1.393-3.552, p= 0.001), but not with heterozygote (TC vs. CC: OR= 1.361, 95% CI: 0.982-1.885, p= 0.064). The XRCC3 rs861539 polymorphism conferred susceptibility to OSA in Asians, but not in Caucasians. Additionally, we observed no evidence of publication bias. Conclusion: To the best of our knowledge, this is the first meta-analysis investigating the association between XRCC3 rs861539 polymorphism and OSA risk. Our results revealed a significant association between the XRCC3 rs861539 polymorphism and risk of OSA, especially in Asian populations. Future more comprehensive and well-designed case control studies with larger sample size are needed to warrant these findings.
PubMed: 28345844
DOI: 10.22034/APJCP.2017.18.2.549 -
Clinical and Translational... Jul 2017Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower...
OBJECTIVES
Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations in these genes are associated with high-penetrance CRC syndromes such as Lynch syndrome. However, the association of low-penetrance polymorphisms of DNA repair genes with CRC risk remains unclear.
METHODS
A systematic literature review of PubMed, Embase, and HuGENet databases was conducted. Pre-specified criteria determined study inclusion/exclusion. Per-allele, pooled odds ratios disclosed the risk attributed to each variant. Heterogeneity was investigated by subgroup analyses for ethnicity and tumor location; funnel plots and Egger's test assessed publication bias.
RESULTS
Sixty-one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses for 22 polymorphisms in 17 genes revealed that six polymorphisms were significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5, XPC), double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup analyses revealed significant association of OGG1 rs1052133 with rectal cancer risk. Egger's test revealed no publication bias.
CONCLUSIONS
Low-penetrance polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies should therefore analyze whole-genome polymorphisms and any synergistic effects on CRC risk.Translational impact:This knowledge may enhance CRC risk assessment and facilitate a more personalized approach to cancer prevention.
PubMed: 28749454
DOI: 10.1038/ctg.2017.35