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Cancers Dec 2022Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore,... (Review)
Review
Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and CCA, focusing on tumorigenesis and prognosis. A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane database for the association between SNPs and CCA, including literature published between January 2000 and April 2022. This systematic review compiles 43 SNPs in 32 genes associated with CCA risk, metastatic progression and overall prognosis based on 34 studies. Susceptibility to CCA was associated with SNPs in genes related to inflammation (PTGS2/COX2, IL6, IFNG/IFN-γ, TNF/TNF-α), DNA repair (ERCC1, MTHFR, MUTYH, XRCC1, OGG1), detoxification (NAT1, NAT2 and ABCC2), enzymes (SERPINA1, GSTO1, APOBEC3A, APOBEC3B), RNA (HOTAIR) and membrane-based proteins (EGFR, GAB1, KLRK1/NKG2D). Overall oncological prognosis was also related to SNPs in eight genes (GNB3, NFE2L2/NRF2, GALNT14, EGFR, XRCC1, EZH2, GNAS, CXCR1). Our findings indicate that multiple SNPs play different roles at various stages of CCA and might serve as biomarkers guiding treatment and allowing oncological risk assessment. Considering the differences in SNP detection methods, patient ethnicity and corresponding environmental factors, more large-scale multicentric investigations are needed to fully determine the potential of SNP analysis for CCA susceptibility prediction and prognostication.
PubMed: 36497451
DOI: 10.3390/cancers14235969 -
The Journal of Urology Apr 2021To characterize the global epidemiology of metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC) and...
PURPOSE
To characterize the global epidemiology of metastatic castration-sensitive prostate cancer (mCSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC). Additionally, to assess the prevalence of homologous recombination repair gene alterations (HRRm) and their prognostic impact in advanced disease setting.
MATERIALS AND METHODS
A systematic literature review of real-world evidence published from January 2009 through May 2019 was conducted to assess global epidemiology and clinical practice trends for mCSPC, nmCRPC, mCRPC and HRRm; 4,732 papers were systematically screened for inclusion. Ten conference proceedings from 2014 through 2019 were reviewed.
RESULTS
Of the screened articles 22 relevant publications were identified for this paper. Six publications reported global epidemiology of advanced prostate cancer. The prevalence of nmCRPC was estimated as 1.1% to 12.3% of prostate cancer cases and for mCRPC 1.2% to 2.1% of prostate cancer cases. No mCSPC prevalence was captured. Sixteen publications investigated HRRm prevalence in advanced prostate cancer with the majority conducted in mCRPC assessed using next-generation sequencing of tissue and germline samples. In mCRPC, the highest prevalence HRRm in both germline (3.3%-6.0%) and somatic (5.0%-15.1%) was . Five publications reported the prognostic impact of HRRm in advanced prostate cancer.
CONCLUSIONS
Published real-world evidence quantifying the prevalence of advanced prostate cancer and HRRm beyond mCRPC is sparse. Published data on HRRm, specifically , are consistent with published clinical trial data for poly (ADP-ribose) polymerase inhibitors in mCRPC. In mCRPC, real-world evidence suggests that patients with HRRm have different clinical outcomes to noncarriers. More data are needed to better understand real-world patient segmentation and clinical outcomes for biomarkers given increasing interest in profiling.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; DNA Mutational Analysis; Disease Progression; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Neoplasm Metastasis; Prevalence; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Recombinational DNA Repair
PubMed: 33332152
DOI: 10.1097/JU.0000000000001570 -
La Clinica Terapeutica 2023Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is... (Review)
Review
BACKGROUND
Cancer, a potentially fatal condition, is one of the leading causes of death worldwide. Among males aged 20 to 35, the most common cancer in healthy individuals is testicular cancer, accounting for 1% to 2% of all cancers in men.
METHODS
Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources.
RESULTS
The onset and spread of testicular cancer are significantly influenced by genetic changes, including mutations in oncogenes, tu-mor suppressor genes, and DNA repair genes. As a result of identifying these specific genetic mutations in cancers, targeted medications have been developed to disrupt the signaling pathways affected by these genetic changes. To improve the diagnosis and treatment of this disease, it is crucial to understand its natural and clinical histories.
CONCLUSIONS
In order to comprehend cancer better and to discover new biomarkers and therapeutic targets, oncologists are increasingly employing omics methods, such as genomics, transcriptomics, proteomics, and metabolomics. Targeted medications that focus on specific genetic pathways and mutations hold promise for advancing the diagnosis and management of this disease.
Topics: Humans; Male; Testicular Neoplasms; Precision Medicine; Genomics; Proteomics
PubMed: 37994745
DOI: 10.7417/CT.2023.2468 -
Fertility and Sterility Dec 2011To perform a literature search on the association between varicocele and sperm DNA fragmentation. (Review)
Review
OBJECTIVE
To perform a literature search on the association between varicocele and sperm DNA fragmentation.
DESIGN
Systematic review.
PATIENT(S)
Men with a varicocele and infertility.
INTERVENTION(S)
Varicocele repair.
MAIN OUTCOME MEASURE(S)
Does the presence of a varicocele increase seminal oxidative stress and sperm DNA fragmentation?
RESULT(S)
In men with a varicocele increased levels of reactive oxygen species and sperm DNA damage can be found. This is probably related to defective spermatogenesis in these patients. Seminal oxidative stress is believed to be the source of sperm DNA damage. Patients with a varicocele and oligospermia may also have a diminished seminal antioxidant capacity. After varicocele repair sperm DNA fragmentation decreases.
CONCLUSION(S)
Varicocele is associated with sperm DNA damage, and this sperm pathology may be secondary to varicocele-mediated oxidative stress. The beneficial effect of varicocelectomy on sperm DNA damage further supports the premise that varicocele may impair sperm DNA integrity.
Topics: DNA; DNA Damage; DNA Fragmentation; Humans; Infertility, Male; Male; Oxidative Stress; Spermatozoa; Varicocele
PubMed: 22035729
DOI: 10.1016/j.fertnstert.2011.10.016 -
Cancer Treatment Reviews Dec 2015Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation... (Review)
Review
BACKGROUND
Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response.
OBJECTIVE
Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events.
METHOD
We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way.
RESULTS
Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results.
CONCLUSION
This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Docetaxel; Gastrointestinal Diseases; Hematologic Diseases; Humans; Neurotoxicity Syndromes; Paclitaxel; Pharmacogenetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, EphA5; Receptor, EphA6; Taxoids; Tubulin
PubMed: 26585358
DOI: 10.1016/j.ctrv.2015.10.010 -
Asian Pacific Journal of Cancer... 2016Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk... (Meta-Analysis)
Meta-Analysis Review
Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk assessment. The aim of this meta-analysis was to investigate the role of XRCC1 polymorphisms (Arg194Trp, Arg280His and Arg399Gln) for risk of breast cancer among different population and categories of menopausal status. PubMed, Medline, Web of Science, and PubMed Central were systematically searched to identify studies evaluating association between breast cancer and XRCC1 gene polymorphisms (Arg194Trp, Arg280His and Arg399Gln). Two authors independently extracted required information. Odds Ratios were pooled for four genetic inheritance models using both fixed and the DerSimonian and Laird random-effect models. Egger's test and contour-enhanced funnel plot were used to evaluate publication bias and small study effect. Additional subgroup analysis was performed for menopausal status, ethnicity, and source of controls. After evaluation and applying inclusion criteria on extracted studies, fifty three studies were included in this meta-analysis. For polymorphisms of Arg194Trp and Arg280His, no significant association was observed in all genetic models. Arg194Trp had a protective effect in post-menopausal status only in homozygote model (OR=0.57 [0.37-0.88]). Arg399Gln showed significant association with breast cancer in homozygote (OR=1.21 [1.10-1.34]), dominant (OR=1.09 [1.03-1.15]) and recessive (OR=1.21 [1.09-1.35]) models. Arg399Gln was associated with higher risk in post-menopausal status for homozygote and heterozygote models. Our findings suggest that XRCC1 gene polymorphisms modify breast cancer risk in different populations and different categories of menopausal status.
Topics: Breast Neoplasms; Case-Control Studies; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Prognosis; Risk Factors; X-ray Repair Cross Complementing Protein 1
PubMed: 27165246
DOI: 10.7314/apjcp.2016.17.s3.323 -
International Journal of Hyperthermia :... 2022Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation...
Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation oncologist. Dose escalation or combination of RT with systemic therapies is used to improve tumor control in patients with unfavorable prostate cancer, at the risk of increasing rates and severity of treatment-related toxicities. Elevation of temperature to a supra-physiological level has been shown to both increase tumor oxygenation and reduce DNA repair capabilities. Thus, hyperthermia (HT) combined with RT represents a compelling treatment strategy to improve the therapeutic ratio in prostate cancer patients. The aim of the present systematic review is to report on preclinical and clinical evidence supporting the combination of HT and RT for prostate cancer, discussing future applications and developments of this combined treatment.
Topics: Combined Modality Therapy; Humans; Hyperthermia; Hyperthermia, Induced; Male; Prostatic Neoplasms
PubMed: 35313781
DOI: 10.1080/02656736.2022.2053212 -
Journal of Receptor and Signal... Apr 2017Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption,... (Review)
Review
CONTEXT
Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury.
METHODS
In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details.
RESULTS AND CONCLUSION
Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.
Topics: Cell Death; Chemical Warfare Agents; DNA Damage; DNA Repair; Inflammation; Interleukin-17; Mustard Gas; Oxidative Stress; Signal Transduction
PubMed: 27485024
DOI: 10.1080/10799893.2016.1212374 -
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 -
Biological Reviews of the Cambridge... Dec 2023Various biological attributes associated with individual fitness in animals change predictably over the lifespan of an organism. Therefore, the study of animal ecology... (Meta-Analysis)
Meta-Analysis
Various biological attributes associated with individual fitness in animals change predictably over the lifespan of an organism. Therefore, the study of animal ecology and the work of conservationists frequently relies upon the ability to assign animals to functionally relevant age classes to model population fitness. Several approaches have been applied to determining individual age and, while these methods have proved useful, they are not without limitations and often lack standardisation or are only applicable to specific species. For these reasons, scientists have explored the potential use of biological clocks towards creating a universal age-determination method. Two biological clocks, tooth layer annulation and otolith layering have found universal appeal. Both methods are highly invasive and most appropriate for post-mortem age-at-death estimation. More recently, attributes of cellular ageing previously explored in humans have been adapted to studying ageing in animals for the use of less-invasive molecular methods for determining age. Here, we review two such methods, assessment of methylation and telomere length, describing (i) what they are, (ii) how they change with age, and providing (iii) a summary and meta-analysis of studies that have explored their utility in animal age determination. We found that both attributes have been studied across multiple vertebrate classes, however, telomere studies were used before methylation studies and telomere length has been modelled in nearly twice as many studies. Telomere length studies included in the review often related changes to stress responses and illustrated that telomere length is sensitive to environmental and social stressors and, in the absence of repair mechanisms such as telomerase or alternative lengthening modes, lacks the ability to recover. Methylation studies, however, while also detecting sensitivity to stressors and toxins, illustrated the ability to recover from such stresses after a period of accelerated ageing, likely due to constitutive expression or reactivation of repair enzymes such as DNA methyl transferases. We also found that both studied attributes have parentally heritable features, but the mode of inheritance differs among taxa and may relate to heterogamy. Our meta-analysis included more than 40 species in common for methylation and telomere length, although both analyses included at least 60 age-estimation models. We found that methylation outperforms telomere length in terms of predictive power evidenced from effect sizes (more than double that observed for telomeres) and smaller prediction intervals. Both methods produced age correlation models using similar sample sizes and were able to classify individuals into young, middle, or old age classes with high accuracy. Our review and meta-analysis illustrate that both methods are well suited to studying age in animals and do not suffer significantly from variation due to differences in the lifespan of the species, genome size, karyotype, or tissue type but rather that quantitative method, patterns of inheritance, and environmental factors should be the main considerations. Thus, provided that complex factors affecting the measured trait can be accounted for, both methylation and telomere length are promising targets to develop as biomarkers for age determination in animals.
Topics: Humans; Animals; Aging; Biological Clocks; Ecology; Karyotyping
PubMed: 37356823
DOI: 10.1111/brv.12992