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International Journal of Cancer Nov 2022Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative... (Meta-Analysis)
Meta-Analysis
Ovarian cancer (OC) is the least survivable gynecological malignancy and presents late. Five-year survival for OC is around 45% increasing the need for innovative treatments. Checkpoint inhibitors have shown significant clinical efficacy in mismatch repair deficient (MMRd) cancers and could be a powerful treatment in OC. However, their application in OC is limited due to the lack of data on the prevalence of MMRd. The aim of our study was to conduct a systematic review of the literature and meta-analysis to provide an accurate estimate of the prevalence of MMRd in OC. We followed PRISMA guidelines throughout. Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science followed by citation searching. Studies not written in English were excluded. All studies were reviewed by at least two independent reviewers. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I score was used to assess heterogeneity across studies. In total 54 studies were included with 17 532 analyzed for MMRd. The overall proportions of MMRd by immunohistochemistry and microsatellite instability analysis were 6.7% and 10.4%, respectively. MMRd was reported in all histotypes of epithelial OC but was most common in endometrioid OC. We estimate that on average 46.7% (95% CI: 28.8-65.4) of ovarian carcinomas showing MMRd by IHC had a germline path_MMR variant identified. OC in those with Lynch syndrome seems to present at an earlier age and stage. Studies however were generally of low quality and there was a high degree of heterogeneity. A significant minority (up to 16%) of OC displays MMRd and, therefore, could be amenable to checkpoint inhibition therapy. However, the current literature base is of limited quality and therefore high-quality prospective studies exploring MMRd in OC with the use of multimodal testing are required. In addition, trials researching efficacy of checkpoint inhibition in MMRd OC are needed.
Topics: Brain Neoplasms; Carcinoma, Ovarian Epithelial; Colorectal Neoplasms; DNA Mismatch Repair; Female; Humans; Microsatellite Instability; Neoplastic Syndromes, Hereditary; Ovarian Neoplasms; Prevalence; Prospective Studies
PubMed: 35792468
DOI: 10.1002/ijc.34165 -
Food Science & Nutrition Jul 2023This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid...
This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.
PubMed: 37457145
DOI: 10.1002/fsn3.3420 -
Archives of Gynecology and Obstetrics Jun 2021The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking.
OBJECTIVE
To provide a clinical characterization of the ProMisE groups of EC.
METHODS
A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated.
RESULTS
Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%.
CONCLUSION
The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.
Topics: Aged; Biomarkers, Tumor; DNA Polymerase II; Endometrial Neoplasms; Female; Genes, p53; Humans; Middle Aged; Mutation; PTEN Phosphohydrolase; Phenotype; Poly-ADP-Ribose Binding Proteins; Prognosis; Risk Assessment; Tumor Suppressor Protein p53
PubMed: 33754186
DOI: 10.1007/s00404-021-06028-4 -
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 -
BMC Cancer Jan 2021Ataxia telangiectasia-mutated (ATM) gene contributes to repair damaged DNA and to regulate cell cycle; therefore, ATM variants seem to increase breast cancer risk;... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ataxia telangiectasia-mutated (ATM) gene contributes to repair damaged DNA and to regulate cell cycle; therefore, ATM variants seem to increase breast cancer risk; however, the results are controversial. So we conducted a systematic review and meta-analysis to clarify the pooled association between various ATM variants and the risk of breast cancer.
METHODS
The relevant studies were searched through Scopus, Web of Science, PubMed and Cochrane. Stratified and subgroup analyses were performed to explore heterogeneity between studies and assess effects of study quality. The pooled estimates logarithm with standard error logarithm of odds ratio and relative risk with confidence interval were calculated.
RESULTS
This study revealed that there is association between ATM variants and the risk of breast cancer; according to the seven adjusted case-control studies, OR of this association was estimated as 1.67 (95%CI: 0.73-3.82), according to nine unadjusted case-control studies, the crude OR was 2.27 (95% CI: 1.17-4.40) and according to two cohorts, the RR was estimated as 1.68 (95% CI: 1.17-2.40).
CONCLUSIONS
The ATM variants are associated with an increased risk of breast cancer that ATM V2424G mutation is detected as the most predisposing factor while ATM D1853V, L546V, and S707P variants have the least predictive ability.
Topics: Ataxia Telangiectasia Mutated Proteins; Breast Neoplasms; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Prognosis
PubMed: 33402103
DOI: 10.1186/s12885-020-07749-6 -
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 -
The World Journal of Men's Health Jan 2023Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and...
PURPOSE
Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.
MATERIALS AND METHODS
Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.
RESULTS
We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.
CONCLUSIONS
The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.
PubMed: 36102104
DOI: 10.5534/wjmh.220067 -
Journal of Clinical Medicine Nov 2020Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered an independent risk factor for cardiovascular disease. The exact mechanism of... (Review)
Review
Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease and is considered an independent risk factor for cardiovascular disease. The exact mechanism of cardiovascular complications (CVC) development as a complication of OSA is not entirely understood. Oxidative stress is suspected to be the essential factor in initiating various comorbidities in OSA. Biomarkers of nonenzymatic lipid and protein peroxidation, DNA repair and antioxidant capabilities measured in serum, plasma and urine are frequently used to assess the presence of oxidative stress. We conducted a systematic review and quality assessment of available observational analytic studies to determine whether there is an association between oxidative stress and OSA in patients with prevalent CV disease compared to (a) patients with prevalent CV disease but no OSA, (b) patients with prevalent CV disease and less severe OSA and (c) patients with OSA and no overt CV disease. This systematic review demonstrated that, while oxidative stress is associated with OSA, there was no clear difference in the severity of oxidative stress between OSA patients with or without cardiovascular complications.
PubMed: 33233796
DOI: 10.3390/jcm9113734 -
JCO Precision Oncology 2021With the broad use of next-generation sequencing assays, it has become clear that mutations in DNA repair genes are more commonly found than previously reported. In...
PURPOSE
With the broad use of next-generation sequencing assays, it has become clear that mutations in DNA repair genes are more commonly found than previously reported. In advanced prostate cancer patients with 1/2 or mutations, poly (ADP-ribose) polymerase inhibition (PARPi) causes an increased overall survival advantage compared with patients without these mutations. This review explores the advantages and limitations of PARPi treatment and its use beyond 1/2-altered tumors. Furthermore, it discusses the benefits of current biomarkers and what role functional biomarkers and organoids may play in addressing the involvement of homologous recombination repair mutations in tumor development and progression.
METHODS
A systematic review was conducted in MEDLINE, National Library of Medicine, and ClinicalTrials.gov to identify studies published between January 1, 2016, and August 31, 2021. The search strategy incorporated terms for PARPi, BRCA, DNA damage, homologous recombination, organoids, patient-derived organoids, biomarker AND prostate cancer, breast cancer, ovarian cancer.
RESULTS
A total of 261 records remained after duplicate removal, 69 of which were included in the qualitative synthesis.
CONCLUSION
To improve the outcome of targeted therapy and increase sensitivity of tumor detection, patients should be repeatedly screened for DNA repair gene alterations and biomarkers. Future clinical studies should explore the use of PARPi beyond 1/2 mutations and focus on finding new synthetically lethal interactions.
Topics: DNA Damage; Humans; Male; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Recombinational DNA Repair
PubMed: 34712892
DOI: 10.1200/PO.21.00152 -
International Journal of Molecular... Feb 2022Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) is receiving more attention as a biomarker for eligibility for immune checkpoint inhibitors in... (Review)
Review
Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) is receiving more attention as a biomarker for eligibility for immune checkpoint inhibitors in advanced diseases. However, due to high costs and resource limitations, MSI/dMMR testing is not widely performed. Some attempts are in progress to predict MSI/dMMR status through histomorphological features on H&E slides using artificial intelligence (AI) technology. In this study, the potential predictive role of this new methodology was reviewed through a systematic review. Studies up to September 2021 were searched through PubMed and Embase database searches. The design and results of each study were summarized, and the risk of bias for each study was evaluated. For colorectal cancer, AI-based systems showed excellent performance with the highest standard of 0.972; for gastric and endometrial cancers they showed a relatively low but satisfactory performance, with the highest standard of 0.81 and 0.82, respectively. However, analyzing the risk of bias, most studies were evaluated at high-risk. AI-based systems showed a high potential in predicting the MSI/dMMR status of different cancer types, and particularly of colorectal cancers. Therefore, a confirmation test should be required only for the results that are positive in the AI test.
Topics: Artificial Intelligence; Colorectal Neoplasms; DNA Mismatch Repair; Endometrial Neoplasms; Female; Humans; Microsatellite Instability
PubMed: 35269607
DOI: 10.3390/ijms23052462