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Virology Journal Dec 2021Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of...
BACKGROUND
Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of yet. DNA-based immunization is a promising modality to generate cellular and humoral immune responses. The objective of this study is to provide a systematic review of HCV DNA vaccines and investigate and discuss the strategies employed to optimize their efficacies.
METHODS
MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and databases in persian language including the Regional Information Centre for Science & Technology (RICeST), the Scientific Information Database and the Iranian Research Institute for Information Science and Technology (IranDoc) were examined to identify studies pertaining to HCV nucleic acid vaccine development from 2000 to 2020.
RESULTS
Twenty-seven articles were included. Studies related to HCV RNA vaccines were yet to be published. A variety of strategies were identified with the potential to optimize HCV DNA vaccines such as incorporating multiple viral proteins and molecular tags such as HBsAg and Immunoglobulin Fc, multi-epitope expression, co-expression plasmid utilization, recombinant subunit immunogens, heterologous prime-boosting, incorporating NS3 mutants in DNA vaccines, utilization of adjuvants, employment of less explored methods such as Gene Electro Transfer, construction of multi- CTL epitopes, utilizing co/post translational modifications and polycistronic genes, among others. The effectiveness of the aforementioned strategies in boosting immune response and improving vaccine potency was assessed.
CONCLUSIONS
The recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.
Topics: Animals; Hepacivirus; Hepatitis C; Humans; Iran; Mice; Mice, Inbred BALB C; Vaccines, DNA; Viral Hepatitis Vaccines
PubMed: 34903252
DOI: 10.1186/s12985-021-01716-8 -
Neuropathology and Applied Neurobiology Jun 2022Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for... (Meta-Analysis)
Meta-Analysis Review
Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH-mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost-effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real-time PCR, multiplex ligation-dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next-generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR-based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost-effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations.
Topics: Brain Neoplasms; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Oligodendroglioma
PubMed: 34958131
DOI: 10.1111/nan.12790 -
The Cochrane Database of Systematic... Nov 2018Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second...
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.
OBJECTIVES
The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries,Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 19 July 2018.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 30480767
DOI: 10.1002/14651858.CD007652.pub6 -
Nutrition and Metabolic Insights 2023The present study aimed to evaluate the effect of Mangifera indica (mango) on dental caries. The entire plant, including the leaves, fruit, roots, and flowers, has... (Review)
Review
The present study aimed to evaluate the effect of Mangifera indica (mango) on dental caries. The entire plant, including the leaves, fruit, roots, and flowers, has various therapeutic characteristics used for centuries to cure various illnesses. This systematic review aimed to identify an inexpensive, simple, and effective method of preventing and controlling dental caries. The search was performed among the studies written in English, the database of abstracts concentrating on the effects of Mangifera indica (Mango) on dental caries detected in Pubmed, Scopus, Google Scholar, and Central. In total, we find 37 articles. The relevant English language articles published up to August 2022 were collected, screened, and reviewed. Search words contained "Mangifera indica" and "dental caries" or "Streptococcus mutans" or "tooth demineralization." For our systematic review analysis, we included 3 randomized controlled trial studies studying a total of 130 people, of whom 110 were children aged 8 to 14 and 20 were adults aged 20 to 25. These experiments all employed mouthwash containing an extract from Mangifera indica. In conclusion, it has been proven in 2 separate studies that saliva's PH will increase significantly. In addition, a reduction of S. mutants has been observed in another research. Overall, it was concluded that mango extract mouthwash is highly effective in decreasing the bacteria that can cause dental caries. however, we firmly believe that conduction of more detailed in vivo studies regarding Mangifera indica implications in dental caries treatment is essentially needed for further confirmation.
PubMed: 38024868
DOI: 10.1177/11786388231204200 -
Medicine Aug 2020Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment.
METHOD
The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS.
RESULT
A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028).
CONCLUSION
Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.
Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cigarette Smoking; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pneumonia; Progression-Free Survival; Survival Rate
PubMed: 32846826
DOI: 10.1097/MD.0000000000021826 -
Journal of Translational Medicine Aug 2023Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate...
BACKGROUND
Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings.
METHODS
Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets.
RESULTS
Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1 neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome.
CONCLUSION
This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.
Topics: Humans; Glioblastoma; Isocitrate Dehydrogenase; Brain Neoplasms; Prognosis; Nomograms; Methyltransferases
PubMed: 37553713
DOI: 10.1186/s12967-023-04382-2 -
Frontiers in Pharmacology 2022Epidermal growth factor receptor (EGFR) mutations are common in patients with non-small-cell lung cancer (NSCLC), particularly in Asian populations. Tyrosine kinase...
Epidermal growth factor receptor (EGFR) mutations are common in patients with non-small-cell lung cancer (NSCLC), particularly in Asian populations. Tyrosine kinase inhibitors (TKIs) are a first-line treatment in patients with mutant EGFR, but their use is often accompanied by drug resistance, which leads to disease progression. Chemotherapy and immunotherapy are the main treatment options after progression. The efficacy of immune checkpoint inhibitors (ICIs) and their combination therapy in patients with EGFR-TKI resistant is not clear. It is thus necessary to evaluate the efficacy of ICIs and ICI-based combination therapies in patients with EGFR-TKI-resistant NSCLC. We searched for randomized controlled trials (RCTs) comparing ICI therapy alone or in combination versus other therapies using PubMed, the Cochrane Library, Web of Science, EMBASE, MEDLINE, ClinicalTrials.gov, and several international conference databases, from database inception to 10 March 2022. The hazard ratio (HR) and 95% confidence interval (95% CI) for median overall survival (OS) and median progression-free survival (PFS) were evaluated. Odds ratio (OR), risk ratio (RR), and 95% CI were used as effect indicators for objective response rate (ORR) and safety data. Seven eligible RCTs were included in the present meta-analysis. The results showed that neither ICIs nor combination therapy prolonged median OS in EGFR-TKI resistant NSCLC patients (HR = 1.04, 95% CI: 0.84-1.29, = 0.73). However, compared with the control group, the patients treated with ICI-based combination therapy had better PFS (HR = 0.62, 95% CI: 0.45-0.86, = 0.004) and ORR (OR = 1.84, 95% CI: 1.28-2.66, = 0.001). ICI monotherapy did not improve the OS or PFS of NSCLC patients previously treated with EGFR-TKIs, whereas patients treated with ICI-based combination therapy had better PFS compared with those receiving conventional chemotherapy, indicating that this therapy could be offered to patients with EGFR-mutant NSCLC after progression following TKI treatment. There was no significant difference in all-grade treatment-related adverse events (TRAEs) between the combination therapy group and the control group. However, a higher incidence of discontinuation due to TRAEs was observed; this requires attention in future studies. The results of this meta-analysis provide a reference for clinical practice and future trial design. CRD42021282207.
PubMed: 36071838
DOI: 10.3389/fphar.2022.926890 -
Genetics and Molecular Research : GMR Dec 2015The germline R337H mutation of the TP53 gene has been associated with the development of many tumor types. This systematic review of literature investigated the... (Meta-Analysis)
Meta-Analysis Review
The germline R337H mutation of the TP53 gene has been associated with the development of many tumor types. This systematic review of literature investigated the association between the R337H mutation and the patients' family history and its predictive and prognostic value in cancer. Data were collected from articles archived in the PubMed, LILACS, MEDLINE, IBECS, and SciELO databases. The systematic review of literature was performed on 12 selected articles, describing a total of 175,462 individuals tested for the R337H mutation, including 1548 individuals with cancer and 118 individuals with a family history of Li-Fraumeni and Li-Fraumeni-like syndrome. Eight studies showed an association between the mutation and a family history of cancer in 411 patients, including 390 cases of cancer among family members. Patients with the homozygous mutant genotype experienced cancer recurrence, progressive disease, secondary cancer, and a short survival rate. Heterozygous patients showed a better response to treatment and increased survival rates than did patients with the homozygous mutant genotype from newborns to adult patients. In conclusion, the R337H mutation has significant predictive and prognostic value and is associated with tumorigenesis of the adrenal cortex.
Topics: Alleles; Amino Acid Substitution; Biomarkers, Tumor; Codon; Female; Gene Frequency; Genes, p53; Genotype; Germ-Line Mutation; Humans; Li-Fraumeni Syndrome; Male; Mutation; Neoplasms; Odds Ratio; Prognosis
PubMed: 26681051
DOI: 10.4238/2015.December.16.4 -
Surgical Neurology International 2020Gliosarcoma (GS) is classified as an IDH-wild-type variant of glioblastoma (GBM). While GS is already an unusual presentation of GBM, IDH1-mutant cases are especially...
BACKGROUND
Gliosarcoma (GS) is classified as an IDH-wild-type variant of glioblastoma (GBM). While GS is already an unusual presentation of GBM, IDH1-mutant cases are especially rare. We present an IDH1-mutant primary intraventricular GS case report and a systematic review of the molecular profile in GS correlating to the prognostic and pathogenesis of IDH1/2 mutations.
CASE DESCRIPTION
A 44-years-old man presented with ongoing fatigue symptoms and a new-onset intense occipital headache. The patient complained of memory loss, dyscalculia, and concentration difficulties. An MRI revealed a bihemispheric intraventricular mass crossing the midline through the corpus callosum and infiltrating the trigone of the lateral ventricles, hypointense, and hyperintense on the T1- and T2-weighted image. We performed a microsurgical resection with a transparietal transsulcal approach; however, the contralateral mass was attached to vascular structures and we decided to reoperate the patient in another moment. The histopathological study showed a Grade IV tumor and the immunohistochemistry confirmed the diagnosis of GS. The patient presented progressive neurologic decline and died 45 days after the surgical approach.
CONCLUSION
We did two systematic reviews studies from PubMed, EMBASE, MEDLINE, Cochrane, and SCOPUS databases, and included molecular and intraventricular studies of GS. We performed further meta-analysis using OpenMetaAnalyst™ software. We conducted a forest plot with the molecular profile of GS. When correlated IDH1 mutation versus tp53 mutation, we found an odds ratio (OR) of 0.018 (0.005-0.064) and < 0.001. Moreover, we compared IDH1 mutation versus MGMT methylation ( = 0.006; OR = 0.138 [0.034-0.562]). The studies evaluating the molecular profile in GS prognostics are often extended from all GBMs despite specifics GBM variants (i.e., GS). We found a correlation between IDH1 mutation expression with tp53 and MGMT expression in GS, and future studies exploring this molecular profile in GS are strongly encouraged.
PubMed: 33408906
DOI: 10.25259/SNI_586_2020 -
Orphanet Journal of Rare Diseases May 2020Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a... (Review)
Review
BACKGROUND
Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1-related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics.
METHODS
We conducted a comprehensive scoping review of scientific literature pertaining to RYR1-RM and MH preclinical model systems in accordance with the PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O'Malley. Two major electronic databases (PubMed and EMBASE) were searched without language restriction for articles and abstracts published between January 1, 1990 and July 3, 2019.
RESULTS
Our search yielded 5049 publications from which 262 were included in this review. A majority of variants tested in RYR1 preclinical models were localized to established MH/central core disease (MH/CCD) hot spots. A total of 250 unique RYR1 variations were reported in human/rodent/porcine models with 95% being missense substitutions. The most frequently reported RYR1 variant was R614C/R615C (human/porcine total n = 39), followed by Y523S/Y524S (rabbit/mouse total n = 30), I4898T/I4897T/I4895T (human/rabbit/mouse total n = 20), and R163C/R165C (human/mouse total n = 18). The dyspedic mouse was utilized by 47% of publications in the rodent category and its RyR1-null (1B5) myotubes were transfected in 23% of publications in the cellular model category. In studies of transfected HEK-293 cells, 57% of RYR1 variations affected the RyR1 channel and activation core domain. A total of 15 RYR1 mutant mouse strains were identified of which ten were heterozygous, three were compound heterozygous, and a further two were knockout. Porcine, avian, zebrafish, C. elegans, canine, equine, and drosophila model systems were also reported.
CONCLUSIONS
Over the past 30 years, there were 262 publications on MH and RYR1-RM preclinical model systems featuring more than 200 unique RYR1 variations tested in a broad range of species. Findings from these studies have set the foundation for therapeutic development for MH and RYR1-RM.
Topics: Animals; Caenorhabditis elegans; Dogs; HEK293 Cells; Horses; Humans; Hyperthermia; Malignant Hyperthermia; Mice; Muscular Diseases; Mutation; Rabbits; Ryanodine Receptor Calcium Release Channel; Swine; Zebrafish
PubMed: 32381029
DOI: 10.1186/s13023-020-01384-x