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Frontiers in Oncology 2023The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm...
OBJECTIVE
The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.
METHODS
After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.
RESULTS
Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I = 65%) and for those after non-PtCh (HR=0.87; I = 0%), the presence of DDRm did not show a significant association with longer OS.
CONCLUSION
1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.
PubMed: 37954082
DOI: 10.3389/fonc.2023.1267577 -
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 -
Journal of Personalized Medicine Dec 2021Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. (Review)
Review
UNLABELLED
Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated.
OBJECTIVES
The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors.
METHODS
Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle-Ottawa Scale for the randomized and non-randomized trials, respectively.
RESULTS
From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; = 0.003).
CONCLUSIONS
Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.
PubMed: 35055323
DOI: 10.3390/jpm12010008 -
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 -
BMJ Open Feb 2023To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out.
OBJECTIVE
To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out.
METHODS
We identified studies of occupational seroprevalence from a living systematic review (PROSPERO CRD42020183634). Electronic databases, grey literature and news media were searched for studies published during January-December 2020. Seroprevalence estimates and a free-text description of the occupation were extracted and classified according to the Standard Occupational Classification (SOC) 2010 system using a machine-learning algorithm. Due to heterogeneity, results were synthesised narratively.
RESULTS
We identified 196 studies including 591 940 participants from 38 countries. Most studies (n=162; 83%) were conducted locally versus regionally or nationally. Sample sizes were generally small (median=220 participants per occupation) and 135 studies (69%) were at a high risk of bias. One or more estimates were available for 21/23 major SOC occupation groups, but over half of the estimates identified (n=359/600) were for healthcare-related occupations. 'Personal Care and Service Occupations' (median 22% (IQR 9-28%); n=14) had the highest median seroprevalence.
CONCLUSIONS
Many seroprevalence studies covering a broad range of occupations were published in the first year of the pandemic. Results suggest considerable differences in seroprevalence between occupations, although few large, high-quality studies were done. Well-designed studies are required to improve our understanding of the occupational risk of SARS-CoV-2 and should be considered as an element of pandemic preparedness for future respiratory pathogens.
Topics: Humans; COVID-19; SARS-CoV-2; Seroepidemiologic Studies; Algorithms; Occupations
PubMed: 36854599
DOI: 10.1136/bmjopen-2022-063771 -
The Eurasian Journal of Medicine Oct 2020The use of some agents as radioprotectors has been evaluated for protection against normal tissue toxicity following exposure to ionizing radiation. Resveratrol, a... (Review)
Review
The use of some agents as radioprotectors has been evaluated for protection against normal tissue toxicity following exposure to ionizing radiation. Resveratrol, a natural flavonoid, with antioxidant and anti-inflammatory properties has attracted research interests for its radioprotective potential. This study systematically evaluates existing studies to examine the radioprotective effectiveness of resveratrol. A literature search of the electronic databases, including PubMed, Scopus, and Embase was conducted to retrieve articles investigating the protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. The search timeframe ranged from the inception of each database to January 2020. From an initial search of 231 articles, and after the removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 33 articles were finally included for this systematic review. Results showed promising protective effect of resveratrol against ionizing radiation-induced damage to normal tissues. Furthermore, no adverse effect was observed after administering resveratrol. Resveratrol showed the potential to protect against ionizing radiation-induced damage to normal tissue cells via notable mechanisms, including anti-apoptotic and anti-inflammatory effects. However, further studies on the efficacy of clinical translation of resveratrol would open up more insights, while other gray areas such as the optimal radioprotective dosage of resveratrol requires further investigation. Overall, resveratrol is a potential double-edged sword in cancer therapy while protecting healthy tissues.
PubMed: 33209085
DOI: 10.5152/eurasianjmed.2020.20143 -
Antioxidants (Basel, Switzerland) Jul 2023Bioactive compounds in berries may scavenge reactive oxygen and nitrogen species by donating electrons to free radicals, thereby protecting DNA, proteins, and lipids... (Review)
Review
Bioactive compounds in berries may scavenge reactive oxygen and nitrogen species by donating electrons to free radicals, thereby protecting DNA, proteins, and lipids from oxidative damage. Evidence shows that berry consumption has beneficial health effects, though it remains unclear whether berries exert a significant impact on oxidative stress in humans. Thus, we performed a systematic review of randomized controlled trials (RCT) to examine the effects of non-acute (more than a single dose and ≥7 days) berry consumption on biomarkers of oxidative stress. Searches were conducted in PubMed, Cochrane Library, and Scopus; results were imported into Covidence for screening and data extraction. The literature search identified 622 studies that were screened, and 131 full-text studies assessed for eligibility. Ultimately, 28 RCTs met the eligibility criteria. Common biomarkers of oxidative stress (antioxidants, DNA damage, isoprostanes, malondialdehyde, and oxidized LDL) were systematically reviewed, and results were reported narratively. Of the approximate 56 oxidative stress biomarkers evaluated in the 28 RCTs, 32% of the biomarkers were reported to have statistically significant beneficial results and 68% of the biomarkers were reported as having no statistically significant differences. More well-designed and longer-term berry RCTs are needed to evaluate biomarkers of oxidative stress.
PubMed: 37507981
DOI: 10.3390/antiox12071443 -
Toxics Mar 2022Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive... (Review)
Review
Oxidative stress has been associated with various inflammation-related human diseases. It is defined as an imbalance between the production and elimination of reactive oxygen species (ROS). ROS can oxidize proteins, lipids, and DNA, and some of these oxidized products are excreted in urine, such as malondialdehyde (MDA), which is considered a biomarker for oxidative damage of lipids. To interpret changes of this biomarker as a measure of oxidative species overproduction in humans, a background range for urinary MDA concentration in the general population is needed. We sought to establish urinary MDA concentration ranges for healthy adult populations based on reported values in the available scientific literature. We conducted a systematic review and meta-analysis using the standardized protocol registered in PROSPERO (CRD42020146623). EMBASE, PubMed, Web of Science, and Cochrane library databases were searched from journal inception up to October 2020. We included 35 studies (divided into 47 subgroups for the quantitative analysis). Only studies that measured creatinine-corrected urinary MDA with high-performance liquid chromatography (HPLC) with mass spectrometry (MS), fluorescence detection, or UV photometry were included. The geometric mean (GM) of urinary MDA concentration was 0.10 mg/g creatinine and 95% percentile confidence interval (CI) 0.07-0.12. Age, geographical location but not sex, and smoking status had a significant effect on urinary MDA concentrations. There was a significant increasing trend of urinary MDA concentrations with age. These urinary MDA values should be considered preliminary, as they are based on mostly moderate to some low-quality evidence studies. Although urinary MDA can reliably reflect excessive oxidative stress in a population, the influence of physiological parameters that affect its meaning needs to be addressed as well as harmonizing the chemical analytical methods.
PubMed: 35448421
DOI: 10.3390/toxics10040160 -
Mutation Research. Reviews in Mutation... 2020The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a... (Meta-Analysis)
Meta-Analysis
The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a large part of our society at increased risk for diseases, such as cancer, cardiovascular diseases and cognitive impairment. Especially the development of type 2 diabetes and overweight/obesity could theoretically be prevented. The loss of DNA and genome stability is associated with the above-mentioned metabolic diseases. Insulin resistance, high blood glucose levels or increased body fat are linked to a chronically elevated inflammatory state. This amplifies oxidative stress, might lead to oxidative DNA damage, impairs the cellular proliferation process and results in mutations; all of which increase the possibility for the development of dysfunctional cells, tissue and organs. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this systematic review and meta-analysis is to collect and analyse the current literature of diabetic, obese and overweight patients and their link to cellular mutations measured by the CBMN assay. A clear trend towards increased genome damage in these metabolic diseases was observed. Significantly increased frequencies of chromosomal aberrations were seen in type 2 diabetic subjects (micronuclei frequency: SMD: 1.18, 95% CI: 0.76, 1.60; I = 84%). In both, type 1 and type 2 diabetics, disease progression as well as medical quality and quantity were linked to further elevated genome instability. In type 1 diabetic and overweight/obese subjects the number of studies is small and for valid and reliable results more data are needed. Besides the traditionally used material for this method, PBMCs, we extended our analysis to buccal cells in order to qualitatively compare the two cell types. Finally, we discuss knowledge as well as technical/methodical gaps of the CBMN cytome assay and its usability for clinical practice in these metabolic diseases.
Topics: Cell Proliferation; Chromosome Aberrations; Cognitive Dysfunction; Cytokinesis; DNA Damage; Diabetes Mellitus, Type 2; Humans; Micronuclei, Chromosome-Defective; Micronucleus Tests; Obesity; Oxidative Stress
PubMed: 33339574
DOI: 10.1016/j.mrrev.2020.108343