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International Journal of Molecular... Aug 2023PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure...
PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.
Topics: Humans; Male; DNA Repair; Medical Oncology; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Radiation Oncology
PubMed: 37629155
DOI: 10.3390/ijms241612978 -
The Science of the Total Environment Dec 2023Road traffic is a major contributor to air pollution through aerosols both from exhaust emissions (EE) and non-exhaust emissions (NEE). NEE result from mechanical... (Review)
Review
Road traffic is a major contributor to air pollution through aerosols both from exhaust emissions (EE) and non-exhaust emissions (NEE). NEE result from mechanical abrasion of brakes and tires, erosion of road surfaces and resuspension of road dust into the atmosphere by passing traffic. EE have been thoroughly studied and have decreased over time due to a stricter control. On the other hand, NEE have not received such attention and there is currently no legislation to specifically reduce NEE particles. Consequently, NEE relative part has become prevalent, potentially making of these emissions a major human health concern. The aim of this systematic review was to provide an overview of the current state of knowledge on the biological effects of brake wear particles, a type of NEE. To this end, we conducted a bibliographic search of two databases (PubMed and Web of Science) on June 1, 2023, focusing on the toxicological effects of brake wear particles induced in vitro and in vivo. We excluded reviews (no original experimental data), papers not written in English, studies performed in non-mammalian models and papers where no toxicity data were reported. Of the 291 papers, 19 were found to be relevant and included in our analysis, confirming that the assessment of the brake wear particles toxicity in mammalian models is still limited. This review also reports that brake wear particles can induce oxidative stress, proinflammatory response and DNA damage. Finally, some perspectives for further research and measures to mitigate the risk of brake wear emissions are discussed.
Topics: Animals; Humans; Air Pollutants; Environmental Monitoring; Air Pollution; Dust; Vehicle Emissions; Particulate Matter; Mammals
PubMed: 37741409
DOI: 10.1016/j.scitotenv.2023.167266 -
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 -
Chemosphere Mar 2024Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical... (Review)
Review
Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage" and "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage" as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.
Topics: Humans; Durapatite; Biocompatible Materials; Hydroxyapatites; DNA Damage; Mutagens
PubMed: 38360416
DOI: 10.1016/j.chemosphere.2024.141383 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2024The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens and young adults, being advertised as a less harmful alternative to... (Review)
Review
BACKGROUND
The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens and young adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitro and in vivo studies have evidenced a variable quantity of potentially harmful components and some recognized carcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes may play active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapid review aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentially malignant disorders (OPMD) and oral cancer.
MATERIAL AND METHODS
A systematic search for English language articles published was performed in PubMed (MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelve clinical studies about OPMD and oral cancer risk in e-cigarette users.
RESULTS
The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes, DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However, results were inconsistent compared to tobacco smokers and control groups.
CONCLUSIONS
the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes as a risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsibly about the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designed clinical studies are needed.
Topics: Adolescent; Humans; Young Adult; Electronic Nicotine Delivery Systems; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; Risk Factors
PubMed: 37992145
DOI: 10.4317/medoral.26042 -
BMJ Open Jul 2023Charcoal production and utilisation are linked to various health issues and occupational hazards. However, to our knowledge, no systematic review has primarily focused...
UNLABELLED
Charcoal production and utilisation are linked to various health issues and occupational hazards. However, to our knowledge, no systematic review has primarily focused on the health implications of charcoal production and its use while distinguishing charcoal from other solid fuels such as wood and coal.
OBJECTIVES
This systematic review presents a synthesis of the evidence on the health risks associated with producing and using charcoal across the world.
DESIGN
Systematic review using a systematic narrative synthesis approach.
DATA SOURCES
MEDLINE (through Ovid interface), CINAHL, Embase, Web of Science, PsycINFO, Cochrane Library and SCOPUS, from inception to 26 February 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Peer-reviewed journal articles reporting empirical findings on the associations between charcoal usage/production and health parameters.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data and assessed the quality of primary studies.
RESULTS
Our findings showed that charcoal production and usage are linked with specific adverse health outcomes, including respiratory diseases (n=21), cardiorespiratory and neurological diseases (n=1), cancer (n=3), DNA damage (n=3), carbon monoxide (CO) poisoning (n=2), physical injury (n=2), sick house syndrome (n=1), unintentional weight loss and body mass index (BMI) reduction (n=2), increase in blood pressure (n=1) and CO death (n=1). Among the included articles that reported respiratory diseases (n=21), there was one case of asthma and tuberculosis and two cases of chronic obstructive pulmonary disease.
CONCLUSIONS
This review links charcoal production/usage and some associated human health risks. These include respiratory diseases and other non-respiratory illnesses such as sick-building syndrome, cardiovascular diseases, DNA damage, CO poisoning and death, unintentional weight loss and BMI reduction, and physical injuries.
Topics: Humans; Charcoal; Asthma; Blood Pressure; Carbon Monoxide; Carbon Monoxide Poisoning
PubMed: 37487686
DOI: 10.1136/bmjopen-2022-065914 -
Mutation Research. Genetic Toxicology... Oct 2023Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and... (Meta-Analysis)
Meta-Analysis Review
Can human peripheral blood cells be used as a surrogate for bone marrow cells, in evaluating the genotoxic effects of stressors? We searched the Pubmed/Medline and PubChem databases to identify publications relevant to this question. Micronucleus formation was the genotoxicity endpoint. Three publications comparing exposed vs. non-exposed individuals are included in this analysis; the exposures were to ethylene oxide or ionising radiation (atomic bomb, thorotrast, or radioiodine therapy). Information was extracted on the types of exposure, the numbers of participants, and the micronucleus frequencies. Relative differences (odds ratios) and absolute differences (risk differences) in the numbers of micronuclei between exposed and non-exposed persons were calculated separately for individual cell types (peripheral blood and bone marrow). Random effects meta-analyses for the relative differences in cell abnormalities were performed. The results showed very small differences in the frequencies of micronuclei between exposed and non-exposed individuals, as measured in either peripheral blood or bone marrow cell populations, on both absolute and relative scales. No definite conclusion concerning the relative sensitivities of bone marrow and peripheral blood cells can be made, based on these publications.
Topics: Humans; Bone Marrow; Iodine Radioisotopes; Micronucleus Tests; Blood Cells; Bone Marrow Cells; DNA Damage; Micronuclei, Chromosome-Defective
PubMed: 37770146
DOI: 10.1016/j.mrgentox.2023.503689 -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003 -
Cancers Feb 2024Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in an individual's DNA sequences. SNPs can occur in both coding and non-coding... (Review)
Review
Single Nucleotide Polymorphisms as Biomarker Predictors of Oral Mucositis Severity in Head and Neck Cancer Patients Submitted to Combined Radiation Therapy and Chemotherapy: A Systematic Review.
Single Nucleotide Polymorphisms (SNPs) are the most common type of genetic variation found in an individual's DNA sequences. SNPs can occur in both coding and non-coding regions of the genome and can affect gene expression, protein function, and disease susceptibility. In this systematic review, we evaluate the potential of SNPs as biomarkers in the assessment of oral mucositis (OM) severity in head and neck cancer (HNC) patients treated with concomitant chemoradiation (CRT). The study selection process involved screening 66 articles from different platforms, and after removing duplicates and excluding articles that did not meet the eligibility criteria, 23 articles were included for full-text evaluation. Among them, genes from several pathways were analyzed. The DNA damage repair pathways had the highest number of genes studied. The most frequently analyzed gene was . The proinflammatory cytokine pathways evaluated were TNF, with three articles, and NF-κB, with one article. Most included studies showed a potential association between certain SNPs and high-grade mucositis. We conclude that SNPs can be used as possible biomarkers for the assessment of OM intensity in HNC patients, and further research is needed to explore the potential of SNPs in personalized medicine for HNC treatment.
PubMed: 38473311
DOI: 10.3390/cancers16050949 -
Iranian Journal of Basic Medical... 2024Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits... (Review)
Review
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular " and "obesity" in title/abstract. Data were collected from 2000 until 2021 (up to April). Only papers published in the English language were included. Forty-six full-text articles out of 1016 retrieved papers were reviewed and underwent quality assessment by investigators. Anti-obesity activity of apigenin is mainly through attenuating adipocyte differentiation by suppressing the mitotic clonal expansion and the adipogenesis-related factors. Its anti-diabetic effects can be exerted through inhibition of protein tyrosine phosphatase1B expression, maintaining the activity of anti-oxidant enzymes, reducing intracellular ROS production, cellular DNA damage, protein carbonylation, and attenuating β-cell apoptosis. Moreover, apigenin could attenuate dyslipidemia and subsequent atherosclerotic conditions through down-regulating sterol regulatory element-binding proteins (SREBP)-1c, SREBP-2, stearyl-CoA desaturase-1, and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Apigenin as a dietary bioactive compound would be a promising candidate for improving MetS and its components.
PubMed: 38629096
DOI: 10.22038/IJBMS.2024.71539.15558