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Diagnostics (Basel, Switzerland) Mar 2023Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type.... (Review)
Review
Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.
PubMed: 36980495
DOI: 10.3390/diagnostics13061187 -
Cancer Medicine Oct 2014There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR) of... (Meta-Analysis)
Meta-Analysis Review
There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR) of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are conflicting. We performed a review and meta-analysis in an attempt to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or estimated from each manuscript. Log HRs and log CIs were combined across studies using the inverse-variance weight to calculate fixed- and random-effects summary estimates and corresponding 95% CIs for overall and progression-free survival. We did not observe any significant association between overall or progression-free survival, neither when considering all colorectal cancer patients nor for subgroup analyses (metastatic, anti-EGFR [epidermal growth factor receptor] treatment, or KRAS wild type). There was substantial heterogeneity across studies, overall and among subgroups analyzed. We have found no clear evidence to support an association between the KRAS-LCS6 genotype and overall or progression-free survival among colorectal cancer patients, even after conducting subgroup analyses by stage and anti-EGFR treatment status. This information helps to clarify the confusing body of literature regarding the clinical implications of the KRAS-LCS6 genetic variant on colorectal cancer outcomes, indicating that it should not be used at the present time to personalize therapeutic strategies (PROSPERO registration number: CRD42013005325).
Topics: 3' Untranslated Regions; Binding Sites; Colorectal Neoplasms; Humans; MicroRNAs; Patient Outcome Assessment; Proportional Hazards Models; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins
PubMed: 24890702
DOI: 10.1002/cam4.279 -
Medicina (Kaunas, Lithuania) Mar 2023Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of... (Review)
Review
Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.
Topics: Humans; Becaplermin; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Intercellular Signaling Peptides and Proteins; Furcation Defects
PubMed: 37109634
DOI: 10.3390/medicina59040676 -
Cardiovascular Research Sep 2016The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide... (Review)
Review
The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cyclin-Dependent Kinases; Genetic Predisposition to Disease; Humans; MicroRNAs; Proto-Oncogene Mas; Risk
PubMed: 27357636
DOI: 10.1093/cvr/cvw174 -
Arquivos Brasileiros de Cirurgia... 2019Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial.
AIM
To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk.
METHODS
The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR.
RESULTS
A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall.
CONCLUSIONS
The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.
Topics: Genetic Predisposition to Disease; Hirschsprung Disease; Humans; Polymorphism, Genetic; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Sensitivity and Specificity
PubMed: 31644668
DOI: 10.1590/0102-672020190001e1448 -
The Oncologist Nov 2023A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically...
PURPOSE
A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC).
DESIGN
Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC.
RESULTS
A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm.
CONCLUSION
Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Prevalence; Colorectal Neoplasms; Neoplasm Recurrence, Local; Mutation; Lung Neoplasms
PubMed: 37432264
DOI: 10.1093/oncolo/oyad138 -
Oncotarget Feb 2017The genetic alterations of papillary thyroid carcinoma (PTC) have been reported to change over the past few decades. We performed this systematic review to further... (Review)
Review
BACKGROUND
The genetic alterations of papillary thyroid carcinoma (PTC) have been reported to change over the past few decades. We performed this systematic review to further examine the trends and modifications of patient demographic, clinicopathological features and molecular profiles of PTC over time.
METHODS
A literature search was performed within six electronic databases to identify relevant articles. The inclusion criteria were published studies investigating BRAF mutations, RET/PTC rearrangements or RAS mutations in PTCs or classical PTCs. Two teams of reviewers independently screened titles and abstracts of all articles. Full texts of potential articles were read and extracted data were listed and stratified into an excel file according to country, city, institution, and surgical time period. Student t test and Pearson Chi-square were used to analyze the trends of demographic and clinicopathological features of PTC patients and the prevalence of each genetic alteration in individual institutions.
RESULTS
From 3139 articles, we included 16 articles for final analysis. Our results showed an increasing trend of BRAF and a decreasing trend of RET/PTC prevalence over time in PTCs and classical PTCs, accompanied by an older age of PTC patients, an increase in proportion of PTMC and less aggressive behaviours of tumours.
CONCLUSIONS
The demographic and clinicopathological characteristics and molecular profile of PTCs have been changing over the past few decades. These modifications suggest changes in etiologies and risk factors of thyroid cancer that influence the tumorigenesis of PTCs.
Topics: Adult; Biomarkers, Tumor; Carcinoma, Papillary; Chi-Square Distribution; Female; Gene Rearrangement; Genes, ras; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Phenotype; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-ret; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Time Factors; Transcriptome
PubMed: 27793009
DOI: 10.18632/oncotarget.12885 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0 -
BioMed Research International 2022Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost... (Meta-Analysis)
Meta-Analysis
Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost mutually exclusively involved in the pathogenesis of CRC. Both are major culprits in treatment failure and poor prognosis for CRC. . A systematic review and meta-analysis of various research was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This trial is registered with PROSPERO CRD42021256452. The initial search included 646 articles; after the removal of noneligible studies, a total of 88 studies was finally selected. Data analysis was carried out using OpenMeta Analyst and Comprehensive Meta-Analysis 3.0 (CMA 3.0) software to investigate the prevalence of KRAS and BRAF mutations among patients with CRC in Asia. . The meta-analysis comprises of 25,525 sample sizes from Asia with most being male 15,743/25525 (61.7%). Overall prevalence of KRAS mutations was (59/88) 36.3% (95% CI: 34.5-38.2) with = 85.54% ( value < 0.001). In 43/59 studies, frequency of KRAS mutations was majorly in codon 12 (76.6% (95% CI: 74.2-78.0)) and less in codon 13 (21.0% (95% CI: 19.1-23.0)). Overall prevalence of BRAF mutations was 5.6% (95% CI: 3.9-8.0) with = 94.00% ( value < 0.001). When stratified according to location, a higher prevalence was observed in Indonesia (71.8%) while Pakistan has the lowest (13.5%). . Total prevalence of KRAS and BRAF mutations in CRC was 36.6% and 5.6%, respectively, and the results conformed with several published studies on KRAS and BRAF mutations.
Topics: Biomarkers; Codon; Colorectal Neoplasms; Female; Humans; Male; Mutation; Pakistan; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 35782059
DOI: 10.1155/2022/5824183 -
International Journal of Molecular... Jun 2023Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to... (Review)
Review
Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.
Topics: Humans; MAP Kinase Signaling System; Proto-Oncogene Proteins c-akt; Pituitary Neoplasms; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases; Mitogen-Activated Protein Kinase Kinases; Carcinogenesis
PubMed: 37446128
DOI: 10.3390/ijms241310952