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Modern Pathology : An Official Journal... Oct 2022Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic...
Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.
Topics: Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; ErbB Receptors; Humans; In Situ Hybridization, Fluorescence; Nuclear Proteins; Proto-Oncogene Proteins p21(ras); Salivary Gland Neoplasms; Trans-Activators; Transcription Factors
PubMed: 35871081
DOI: 10.1038/s41379-022-01100-z -
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 -
Clinical & Translational Oncology :... Feb 2024The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available.
METHODS
The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs).
RESULTS
There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events.
CONCLUSION
TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.
Topics: Humans; Trifluridine; Uracil; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); Colonic Neoplasms; Rectal Neoplasms; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Thymine
PubMed: 37414979
DOI: 10.1007/s12094-023-03268-5 -
Critical Reviews in Oncology/hematology Nov 2021Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common mutations with tumour budding.
METHODS
A systematic review of studies relating to tumour budding and genetic mutation in CRC was performed. The relationship between mutational status and tumour budding was evaluated using meta-analysis.
RESULTS
A total of 6153 patients from 17 articles were included. According to the meta-analysis, high-grade tumour budding was significantly associated with KRAS mutation (OR = 1.52, 95 %CI: 1.13-2.02, P = 0.005) and MSS/pMMR (OR = 2.06, 95 %CI: 1.42-2.97, P = 0.0001).
CONCLUSION
The significant association between high-grade tumour budding and mutated KRAS or MSS/pMMR may suggest a role of these mutations in the development of the tumour budding phenotype and be useful for stratifying patient outcome in CRC.
Topics: Colorectal Neoplasms; Humans; Mutation; Phenotype; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34619332
DOI: 10.1016/j.critrevonc.2021.103490 -
World Journal of Clinical Oncology Jan 2020Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different...
BACKGROUND
Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.
AIM
To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors.
METHODS
An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed.
RESULTS
Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E.
CONCLUSION
The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
PubMed: 31976308
DOI: 10.5306/wjco.v11.i1.31 -
Phytomedicine : International Journal... Nov 2022Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Securinine is an alkaloid identified from the roots and leaves of the shrub Flueggea suffruticosa (Pall.) Baill. The molecular structure of securinine consists of four rings, including three chiral centers. It has been suggested that securinine can be chemically synthesized from tyrosine and lysine. Securinine has long been used to treat central nervous system diseases. In recent years, more and more evidence shows that securinine also has anticancer activity, which has not been systematically discussed and analyzed.
PURPOSE
This study aims to propose an overall framework to describe the molecular targets of securinine in different signal pathways, and discuss the current status and prospects of each pathway, so as to provide a theoretical basis for the development securinine as an effective anticancer drug.
METHODS
The research databases on the anticancer activity of securinine from PubMed, Scopus, Web of Science and ScienceDirect to 2021 were systematically searched. This paper follows the Preferred Reporting Items and Meta-Analysis guidelines.
RESULTS
Securinine has the ability to kill a variety of human cancer cells, including, leukemia as well as prostate, cervical, breast, lung, and colon cancer cells. It can regulate the signal pathways of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, Wnt and Janus kinase-signal transducer and activator of transcription, promote cancer cell apoptosis and autophagy, and inhibit cancer cell metastasis. Securinine also has the activity of inducing leukemia cell differentiation.
CONCLUSION
Although there has been some experimental evidence indicating the anticancer effect of securinine and its possible pharmacology, in order to design more effective anticancer drugs, it is necessary to study the synergy of intracellular signaling pathways. More in vivo experiments and even clinical studies are needed, and the synergy between securinine and other drugs is also worth studying.
Topics: Alkaloids; Azepines; Cell Line, Tumor; Heterocyclic Compounds, Bridged-Ring; Humans; Janus Kinases; Lactones; Leukemia; Lysine; Male; Phosphatidylinositols; Piperidines; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Tyrosine
PubMed: 36063584
DOI: 10.1016/j.phymed.2022.154417 -
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 -
Critical Reviews in Oncology/hematology Jan 2022This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Humans; Mutation; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras)
PubMed: 34843928
DOI: 10.1016/j.critrevonc.2021.103548 -
Journal of Lower Genital Tract Disease Jan 2023Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they...
OBJECTIVES
Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important.
MATERIALS AND METHODS
Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included.
RESULTS
Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway.
CONCLUSIONS
Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.
Topics: Female; Humans; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Melanoma; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36083687
DOI: 10.1097/LGT.0000000000000701