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Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
Frontiers in Cardiovascular Medicine 2022Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and...
Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and prevent adverse cardiovascular events. Cardiac repair after myocardial infarction can effectively remove necrotic tissue, induce neovascularization, and ultimately replace granulation tissue. Cardiac inflammation is the primary determinant of whether beneficial cardiac repair occurs after myocardial infarction. Immune cells mediate inflammatory responses and play a dual role in injury and protection during cardiac repair. After myocardial infarction, genetic ablation or blocking of anti-inflammatory pathways is often harmful. However, enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways may improve cardiac repair after myocardial infarction. A deficiency of neutrophils or monocytes does not improve overall cardiac function after myocardial infarction but worsens it and aggravates cardiac fibrosis. Several factors are critical in regulating inflammatory genes and immune cells' phenotypes, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, strict control and timely suppression of the inflammatory response, finding a balance between inflammatory cells, preventing excessive tissue degradation, and avoiding infarct expansion can effectively reduce the occurrence of adverse cardiovascular events after myocardial infarction. This article reviews the involvement of neutrophils, monocytes, macrophages, and regulatory T cells in cardiac repair after myocardial infarction. After myocardial infarction, neutrophils are the first to be recruited to the damaged site to engulf necrotic cell debris and secrete chemokines that enhance monocyte recruitment. Monocytes then infiltrate the infarct site and differentiate into macrophages and they release proteases and cytokines that are harmful to surviving myocardial cells in the pre-infarct period. As time progresses, apoptotic neutrophils are cleared, the recruitment of anti-inflammatory monocyte subsets, the polarization of macrophages toward the repair phenotype, and infiltration of regulatory T cells, which secrete anti-inflammatory factors that stimulate angiogenesis and granulation tissue formation for cardiac repair. We also explored how epigenetic modifications regulate the phenotype of inflammatory genes and immune cells to promote cardiac repair after myocardial infarction. This paper also elucidates the roles of alarmin S100A8/A9, secreted frizzled-related protein 1, and podoplanin in the inflammatory response and cardiac repair after myocardial infarction.
PubMed: 36698953
DOI: 10.3389/fcvm.2022.1077290 -
Life (Basel, Switzerland) Dec 2022The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate... (Review)
Review
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.
PubMed: 36676004
DOI: 10.3390/life13010055 -
Reports of Practical Oncology and... 2022Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests... (Review)
Review
BACKGROUND
Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs.
MATERIALS AND METHODS
This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases.
RESULTS
Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: null, null, *4, Arg194Trp and Arg399Gln, C8092A, Lys751Gln, Thr241Met, codon 72 and C677T polymorphisms.
CONCLUSION
Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.
PubMed: 36632298
DOI: 10.5603/RPOR.a2022.0115 -
HGG Advances Jan 2023To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics,...
To identify Lynch syndrome (LS) carriers, DNA mismatch repair (MMR) immunohistochemistry (IHC) is performed on colorectal cancers (CRCs). Upon subsequent LS diagnostics, MMR deficiency (MMRd) sometimes remains unexplained (UMMRd). Recently, the importance of complete LS diagnostics to explain UMMRd, involving MMR methylation, germline, and somatic analyses, was stressed. To explore why some MMRd CRCs remain unsolved, we performed a systematic review of the literature and mapped patients with UMMRd diagnosed in our center. A systematic literature search was performed in Ovid Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar for articles on UMMRd CRCs after complete LS diagnostics published until December 15, 2021. Additionally, UMMRd CRCs diagnosed in our center since 1993 were mapped. Of 754 identified articles, 17 were included, covering 74 patients with UMMRd. Five CRCs were microsatellite stable. Upon complete diagnostics, 39 patients had single somatic MMR hits, and six an MMR germline variant of unknown significance (VUS). Ten had somatic pathogenic variants (PVs) in , , , and . The remaining 14 patients were the only identifiable cases in the literature without a plausible identified cause of the UMMRd. Of those, nine were suspected to have LS. In our center, complete LS diagnostics in approximately 5,000 CRCs left seven MMRd CRCs unexplained. All had a somatic MMR hit or MMR germline VUS, indicative of a missed second MMR hit. In vitually all patients with UMMRd, complete LS diagnostics suggest MMR gene involvement. Optimizing detection of currently undetectable PVs and VUS interpretation might explain all UMMRd CRCs, considering UMMRd a case closed.
Topics: Humans; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Colorectal Neoplasms, Hereditary Nonpolyposis; Brain Neoplasms
PubMed: 36624813
DOI: 10.1016/j.xhgg.2022.100167 -
Frontiers in Immunology 2022As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several...
As the first barrier of host defense, innate immunity sets up the parclose to keep out external microbial or virus attacks. Depending on the type of pathogens, several cytoplasm pattern recognition receptors exist to sense the attacks from either foreign or host origins, triggering the immune response to battle with the infections. Among them, cGAS-STING is the major pathway that mainly responds to microbial DNA, DNA virus infections, or self-DNA, which mainly comes from genome instability by-product or released DNA from the mitochondria. cGAS was initially found functional in the cytoplasm, although intriguing evidence indicates that cGAS exists in the nucleus where it is involved in the DNA damage repair process. Because the close connection between DNA damage response and immune response and cGAS recognizes DNA in length-dependent but DNA sequence-independent manners, it is urgent to clear the function balance of cGAS in the nucleus versus cytoplasm and how it is shielded from recognizing the host origin DNA. Here, we outline the current conception of immune response and the regulation mechanism of cGAS in the nucleus. Furthermore, we will shed light on the potential mechanisms that are restricted to be taken away from self-DNA recognition, especially how post-translational modification regulates cGAS functions.
Topics: Signal Transduction; Immunity, Innate; Nucleotidyltransferases; DNA; DNA Damage
PubMed: 36591232
DOI: 10.3389/fimmu.2022.1076784 -
Cancer Reports (Hoboken, N.J.) Mar 2023The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not.
RECENT FINDINGS
Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models.
OBJECTIVE
The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not.
METHODS
A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05.
RESULTS
Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, p = .032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, p = .119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, p = .021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, p = .119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models.
CONCLUSION
Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.
Topics: Humans; DNA-Binding Proteins; X-ray Repair Cross Complementing Protein 1; Squamous Cell Carcinoma of Head and Neck; Genetic Predisposition to Disease; Mouth Neoplasms; Head and Neck Neoplasms
PubMed: 36573562
DOI: 10.1002/cnr2.1776 -
European Journal of Medical Research Dec 2022Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle... (Review)
Review
BACKGROUND
Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle therapy for prostate cancer are extremely limited. The aim of this study was to comprehensively investigate the biological effects of charged particles on prostate cancer from the perspective of in vitro studies.
METHODS
We conducted a systematic review by searching EMBASE (OVID), Medline (OVID), and Web of Science databases to identify the publications assessing the radiobiological effects of charged particle irradiation on prostate cancer cells. The data of relative biological effectiveness (RBE), surviving fraction (SF), standard enhancement ratio (SER) and oxygen enhancement ratio (OER) were extracted.
RESULTS
We found 12 studies met the eligible criteria. The relative biological effectiveness values of proton and carbon ion irradiation ranged from 0.94 to 1.52, and 1.67 to 3.7, respectively. Surviving fraction of 2 Gy were 0.17 ± 0.12, 0.55 ± 0.20 and 0.53 ± 0.16 in carbon ion, proton, and photon irradiation, respectively. PNKP inhibitor and gold nanoparticles were favorable sensitizing agents, while it was presented poorer performance in GANT61. The oxygen enhancement ratio values of photon and carbon ion irradiation were 2.32 ± 0.04, and 1.77 ± 0.13, respectively. Charged particle irradiation induced more G0-/G1- or G2-/M-phase arrest, more expression of γ-H2AX, more apoptosis, and lower motility and/or migration ability than photon irradiation.
CONCLUSIONS
Both carbon ion and proton irradiation have advantages over photon irradiation in radiobiological effects on prostate cancer cell lines. Carbon ion irradiation seems to have further advantages over proton irradiation.
Topics: Male; Humans; Protons; Gold; Dose-Response Relationship, Radiation; Metal Nanoparticles; Prostatic Neoplasms; Carbon; Oxygen; Phosphotransferases (Alcohol Group Acceptor); DNA Repair Enzymes
PubMed: 36572945
DOI: 10.1186/s40001-022-00942-2 -
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 -
Frontiers in Genetics 2022Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and...
Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and rRNAs that participate in mRNA processing and translation. In addition, there are small RNAs with a regulatory role, such as siRNAs, miRNAs, and piRNAs. Finally, the long non-coding RNAs (lncRNAs) are transcripts of more than 200 bp that can positively and negatively regulate gene expression (both in cis and trans), serve as a scaffold for protein recruitment, and control nuclear architecture, among other functions. An essential process regulated by lncRNAs is genome stability. LncRNAs regulate genes associated with DNA repair and chromosome segregation; they are also directly involved in the maintenance of telomeres and have recently been associated with the activity of the centromeres. In cancer, many alterations in lncRNAs have been found to promote genomic instability, which is a hallmark of cancer and is associated with resistance to chemotherapy. In this review, we analyze the most recent findings of lncRNA alterations in cancer, their relevance in genomic instability, and their impact on the resistance of tumor cells to anticancer therapy.
PubMed: 36479250
DOI: 10.3389/fgene.2022.984329