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Cancers Nov 2021Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of... (Review)
Review
Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34-1.76, < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10-1.21, < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03-1.08, < 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28-1.49, < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10-1.33, = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29-3.45, = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94-5.58, < 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.
PubMed: 34830749
DOI: 10.3390/cancers13225594 -
Frontiers in Endocrinology 2021Several studies have explored the relationship among traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM); however,... (Meta-Analysis)
Meta-Analysis
Several studies have explored the relationship among traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM); however, the findings remain controversial. Hence, we conducted a meta-analysis to explore the relationship among traditional semen parameters, SDF, and unexplained RM. Multiple databases, including PubMed, Google Scholar, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI), were searched to identify relevant publications. From the eligible publications, data were extracted independently by two researchers. A total of 280 publications were identified using the search strategy. According to the inclusion/exclusion criteria, 19 publications were eligible. A total of 1182 couples with unexplained RM and 1231 couples without RM were included in this meta-analysis to assess the relationship among traditional semen parameters, SDF, and unexplained RM. Our results showed that couples with unexplained RM had significantly increased levels of SDF and significantly decreased levels of total motility and progressive motility compared with couples without RM, although significant differences were not observed in the semen volume, sperm concentration, and total sperm count between couples with and without RM. The SDF assay may be considered for inclusion in evaluations of couples with unexplained RM.
Topics: Abortion, Habitual; DNA Fragmentation; Female; Humans; Male; Semen; Semen Analysis; Spermatozoa
PubMed: 35058886
DOI: 10.3389/fendo.2021.802632 -
The World Journal of Men's Health Jul 2021The advent of intracytoplasmic sperm injection (ICSI) has changed the human reproduction landscape by overcoming several limitations related to both male and female... (Review)
Review
The advent of intracytoplasmic sperm injection (ICSI) has changed the human reproduction landscape by overcoming several limitations related to both male and female infertility factors. However, despite the development of new technologies, the live-birth rate with ICSI has not exceeded 30%. In order to improve assisted reproductive technology outcomes, advanced sperm function analysis have gained increased attention and the effects of sperm DNA fragmentation (SDF) on assisted reproduction success are being extensively studied. Utilizing ejaculated sperm with an elevated SDF has been found to result in poor ICSI outcomes. Furthermore, studies have reported that testicular sperm has lower SDF level, when compared to ejaculated sperm. This has led a number of clinicians world-wide to offer testicular sperm retrieval for ICSI in non-azoospermic males with high SDF. This practice has remained controversial due to lack of high quality evidence.
PubMed: 32648379
DOI: 10.5534/wjmh.200084 -
Frontiers in Aging Neuroscience 2021Other than its direct impact on cardiopulmonary health, Coronavirus Disease 2019 (COVID-19) infection affects additional body systems, especially in older adults....
Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories.
Other than its direct impact on cardiopulmonary health, Coronavirus Disease 2019 (COVID-19) infection affects additional body systems, especially in older adults. Several studies have reported acute neurological symptoms that present at onset or develop during hospitalisation, with associated neural injuries. Whilst the acute neurological phase is widely documented, the long-term consequences of COVID-19 infection on neurocognitive functioning remain unknown. Although an evidence-based framework describing the disease chronic phase is premature, it is important to lay the foundations for future data-driven models. This systematic review aimed at summarising the literature on neuroimaging and neuropathological findings in older over-60 patients with COVID-19 following a cognitive neuroscientific perspective, to clarify the most vulnerable brain areas and speculate on the possible cognitive consequences. PubMed and Web of Science databases were searched to identify relevant manuscripts published between 1st March 2020 and 31th December 2020. Outputs were screened and selected by two assessors. Relevant studies not detected by literature search were added manually. Ninety studies, mainly single cases and case series, were included. Several neuroimaging and neuropathological findings in older patients with COVID-19 emerged from these studies, with cerebrovascular damage having a prominent role. Abnormalities (hyperintensities, hypoperfusion, inflammation, and cellular damage) were reported in most brain areas. The most consistent cross-aetiology findings were in white matter, brainstem and fronto-temporal areas. Viral DNA was detected mainly in olfactory, orbitofrontal and brainstem areas. Studies on COVID-19 related neural damage are rich and diverse, but limited to description of hospitalised patients with fatal outcome (i.e., in neuropathological studies) or severe symptoms (i.e., in neuroimaging studies). The damage seen in this population indicates acute and largely irreversible dysfunction to neural regions involved in major functional networks that support normal cognitive and behavioural functioning. It is still unknown whether the long-term impact of the virus will be limited to chronic evolution of acute events, whether sub-clinical pathological processes will be exacerbated or whether novel mechanisms will emerge. Based on current literature, future theoretical frameworks describing the long-term impact of COVID-19 infection on mental abilities will have to factor in major trends of aetiological and topographic heterogeneity.
PubMed: 34149394
DOI: 10.3389/fnagi.2021.646908 -
Brazilian Oral Research 2023Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and... (Meta-Analysis)
Meta-Analysis
Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30-1.18), GSTT1 (OR: 1.18; 95%CI:0.49-2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18-3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47-1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers.
Topics: Humans; Nicotiana; Carcinoma, Squamous Cell; Genotype; Polymorphism, Genetic; Squamous Cell Carcinoma of Head and Neck; Genetic Predisposition to Disease; Non-Smokers; Mouth Neoplasms; Head and Neck Neoplasms; DNA
PubMed: 36629591
DOI: 10.1590/1807-3107bor-2023.vol37.0008 -
European Urology Open Science Jul 2020Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and... (Review)
Review
CONTEXT
Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain.
OBJECTIVE
To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study.
EVIDENCE ACQUISITION
We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment.
EVIDENCE SYNTHESIS
We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue () loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours.
CONCLUSIONS
Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets.
PATIENT SUMMARY
Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.
PubMed: 33000006
DOI: 10.1016/j.euros.2020.06.006 -
International Journal of Oncology Sep 2019Several ongoing international prostate cancer (PC) clinical trials are exploring therapies that target the DNA damage response (DDR) pathway. This systematic review...
Several ongoing international prostate cancer (PC) clinical trials are exploring therapies that target the DNA damage response (DDR) pathway. This systematic review summarizes the prevalence of DDR mutation carriers in the unselected (general) PC and familial PC populations. A total of 11 electronic databases, 10 conference proceedings, and grey literature sources were searched from their inception to December 2017. Studies reporting the prevalence of somatic and/or germline DDR mutations were summarized. Metastatic PC (mPC), castration‑resistant PC (CRPC) and metastatic CRPC (mCRPC) subgroups were included. A total of 11,648 records were retrieved, and 80 studies (103 records) across all PC populations were included; 59 records were of unselected PC and 13 records of familial PC. Most data were available for DDR panels (n=12 studies), ataxia telangiectasia mutated (ATM; n=13), breast cancer susceptibility gene (BRCA)1 (n=14) and BRCA2 (n=20). ATM, BRCA2 and partner and localizer of BRCA2 (PALB2) had the highest mutation rates (≥4%). Median prevalence rates for DDR germline mutations were 18.6% in PC (range, 17.2‑19%; three studies, n=1,712), 11.6% in mPC (range, 11.4‑11.8%; two studies, n=1,261) and 8.3% in mCRPC (range, 7.5‑9.1%; two studies, n=738). Median prevalence rates for DDR somatic mutations were 10.7% in PC (range, 4.9‑22%; three studies, n=680), 13.2% in mPC (range, 10‑16.4%; two studies, n=105) and not reported (NR) in mCRPC. The prevalence of DDR germline and/or somatic mutations was 27% in PC (one study, n=221), 22.67% in mCRPC (one study, n=150) and NR in mPC. In familial PC, median mutation prevalence was 12.1% (range, 7.3‑16.9%) for germline DDR (two studies, n=315) and 3.7% (range, 1.3‑7.9%) for BRCA2 (six studies, n=945). In total, 88% of studies were at a high risk of bias. The prevalence of DDR gene mutations in PC varied widely within somatic subgroups depending on study size, genetic screening techniques, DDR mutation definition and PC diagnosis; somatic and/or germline DDR mutation prevalence was in the range of 23‑27% in PC. These findings support DDR mutation testing for all patients with PC (including those with mCRPC). With the advent of the latest clinical practice PC guidelines highlighting the importance of DDR mutation screening, and ongoing mCRPC clinical trials evaluating DDR mutation‑targeted drugs, future larger epidemiological studies are warranted to further quantify the international burden of DDR mutations in PC.
Topics: Ataxia Telangiectasia Mutated Proteins; BRCA1 Protein; BRCA2 Protein; DNA Damage; DNA Repair; Fanconi Anemia Complementation Group N Protein; Gene Regulatory Networks; Germ-Line Mutation; Humans; Male; Mutation; Mutation Rate; Prevalence; Prostatic Neoplasms
PubMed: 31322208
DOI: 10.3892/ijo.2019.4842 -
Clinical and Translational Radiation... Nov 2023Pain is the most common acute symptom following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of RT-induced pain makes it highly... (Review)
Review
BACKGROUND/OBJECTIVE
Pain is the most common acute symptom following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of RT-induced pain makes it highly challenging to manage. Multiple studies were conducted to identify genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this review, we summarize the potential mechanisms of acute pain after RT in HNC and identify genetic variants associated with RT-induced acute pain and relevant acute toxicities.
METHODS
A comprehensive search of Ovid Medline, EMBASE and Web of Science databases using terms including "Variants", "Polymorphisms", "Radiotherapy", "Acute pain", "Acute toxicity" published up to February 28, 2022, was performed by two reviewers. Review articles and citations were reviewed manually. The identified SNPs associated with RT-induced acute pain and toxicities were reported, and the molecular functions of the associated genes were described based on genetic annotation using The Human Gene Database; GeneCards.
RESULTS
A total of 386 articles were identified electronically and 8 more articles were included after manual search. 21 articles were finally included. 32 variants in 27 genes, of which 25% in inflammatory/immune response, 20% had function in DNA damage response and repair, 20% in cell death or cell cycle, were associated with RT-inflammatory pain and acute oral mucositis or dermatitis. 4 variants in 4 genes were associated with neuropathy and neuropathic pain. 5 variants in 4 genes were associated with RT-induced mixed types of post-RT-throat/neck pain.
CONCLUSION
Different types of pain develop after RT in HNC, including inflammatory pain; neuropathic pain; nociceptive pain; and mixed oral pain. Genetic variants involved in DNA damage response and repair, cell death, inflammation and neuropathic pathways may affect pain presentation post-RT. These variants could be used for personalized pain management in HNC patients receiving RT.
PubMed: 37954025
DOI: 10.1016/j.ctro.2023.100669 -
OncoTargets and Therapy 2021Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review... (Review)
Review
PURPOSE
Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC.
METHODS
Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail.
RESULTS
A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways.
CONCLUSION
LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.
PubMed: 33500626
DOI: 10.2147/OTT.S294378 -
Ecotoxicology and Environmental Safety Jan 2023It has been demonstrated that human exposure to environmental chemicals may have sperm genotoxic potentiality. Among the different classes, Polycyclic Aromatic... (Review)
Review
It has been demonstrated that human exposure to environmental chemicals may have sperm genotoxic potentiality. Among the different classes, Polycyclic Aromatic Hydrocarbons (PAHs) have been receiving attention in recent years due to reports of sperm geno-toxicity, a series of reproductive defects and male infertility. This review aims to substantiate the effects of PAHs exposure on male infertility, with focus on the sperm characteristics (count, concentration, volume, motility, DNA damage, and morphology). To this end, international databases such as Cochrane Library, PubMed, Web of Science, Embase Ovid, Scopus, and Google Scholar were used to conduct a systematic search for papers on the subject, based on PRISMA guidelines, published up to 24 March 2022. The Newcastle-Ottawa Scale was subsequently used to assess the quality of the studies. The results showed that there is a significant negative relationship between PAHs metabolites and sperm volume, concentration, motility, morphology, as well as an observed DNA degeneration. Also, the CYP1A1 genotype polymorphisms were considered as a representative of PAHs exposure to infertility; the review highlights that polymorphisms of this genotype were more common in the infertile people. In overall, this work provides a solid summary of the existing works correlating PAHs exposure and male infertility, which could impulse further protective measures and informative campaigns on users, workers, and general population.
Topics: Humans; Male; Polycyclic Aromatic Hydrocarbons; Semen; Infertility, Male; Semen Analysis; Spermatozoa
PubMed: 36608572
DOI: 10.1016/j.ecoenv.2022.114485