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BMC Cancer Apr 2016Brain metastases (BM) from colorectal cancer (CRC) are a rare event. However, the implications for affected patients are severe, and the incidence has been reported to... (Review)
Review
BACKGROUND
Brain metastases (BM) from colorectal cancer (CRC) are a rare event. However, the implications for affected patients are severe, and the incidence has been reported to be increasing. For clinicians, knowledge about the characteristics associated with BM is important and could lead to earlier diagnosis and improved survival.
METHOD
In this paper, we describe the incidence as well as characteristics associated with BM based on a systematic review of the current literature, following the PRISMA guidelines.
RESULTS
We show that the incidence of BM in CRC patients ranges from 0.6 to 3.2%. BM are a late stage phenomenon, and young age, rectal primary and lung metastases are associated with increased risk of developing BM. Molecular markers such as KRAS, BRAF, NRAS mutation as well as an increase in CEA and CA19.9 levels are suggested predictors of brain involvement. However, only KRAS mutations are reasonably well investigated and associated with an increased risk of BM.
CONCLUSION
The incidence of BM from CRC is 0.6 to 3.2% and did not seem to increase over time. Development of BM is associated with young age, lung metastases, rectal primary and KRAS mutation. Increased awareness of brain involvement in patients with these characteristics is necessary.
Topics: Age Factors; Brain Neoplasms; Colorectal Neoplasms; Female; GTP Phosphohydrolases; Genetic Association Studies; Humans; Lung Neoplasms; Male; Membrane Proteins; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Risk Factors
PubMed: 27037031
DOI: 10.1186/s12885-016-2290-5 -
Lung Cancer (Amsterdam, Netherlands) Jul 2021Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients.
RESULTS
We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis. For ALK+ NSCLC, the pooled OR was 2.00 (95% CI: 1.60-2.50) for total TE (TTE) by random-effects model, 2.10 (95% CI: 1.70-2.60) for venous thromboembolism (VTE), and 1.24 (95% CI: 0.80-1.91) for arterial thromboembolism (ATE). For ROS1+ NSCLC, the pooled OR was 3.08 (95% CI: 1.95-4.86) for TTE, and 3.15 (95% CI: 1.83-5.43) for VTE. Six studies (739 ALK+, 137 ROS1+, 561 EGFR+, 714 "wildtype" NSCLC patients) were included in the time-to-event analysis. The TTE incidence rate was 17.4 (95% CI: 15.3-19.5) per 100 pateint-years for ALK+ NSCLC, and 32.1 (95% CI: 24.6-39.6) per 100 patient-years for ROS1+ NSCLC with a 50 % cumulative incidence rate at year 3 of diagnosis. HR for TTE was 2.35 (95% CI: 1.90-2.92, p < 0.001) and 3.23 (95% CI: 2.40-4.34, p < 0.001) for ALK+ and ROS1+ NSCLC, respectively. Comparing ROS1+ NSCLC to ALK+ NSCLC, HR for TTE was 1.37 (95% CI: 1.05-1.79, p = 0.020).
CONCLUSIONS
ALK+ and ROS1+ NSCLC patients had an increased risk of TE. ROS1+ NSCLC had further increased risk of TE over ALK+ NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Gene Rearrangement; Humans; Lung Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases
PubMed: 34049720
DOI: 10.1016/j.lungcan.2021.05.019 -
Journal of Racial and Ethnic Health... Feb 2024Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and... (Meta-Analysis)
Meta-Analysis Review
Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.
Topics: Humans; Ameloblastoma; Proto-Oncogene Proteins B-raf; Jaw Neoplasms; Treatment Outcome; Mutation
PubMed: 36596981
DOI: 10.1007/s40615-022-01500-6 -
Recent Patents on Anti-cancer Drug... 2016Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC.
OBJECTIVE
The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC.
METHODS
A systematic review was performed using Pubmed and Google patents databases.
RESULTS
We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field.
CONCLUSION
Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.
Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Drug Design; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Proto-Oncogene Mas; Thyroid Neoplasms
PubMed: 27306881
DOI: 10.2174/1574892811666160614115356 -
PloS One 2014Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
METHODS
We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model.
RESULTS
25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation.
CONCLUSIONS
This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.
Topics: Colorectal Neoplasms; Genetic Association Studies; Genetic Markers; Humans; Mutation, Missense; Odds Ratio; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf
PubMed: 24594804
DOI: 10.1371/journal.pone.0090607 -
Journal of Diabetes and Its... 2014The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-β using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.
Topics: Becaplermin; Biomarkers; Diabetic Retinopathy; Humans; Proto-Oncogene Proteins c-sis; Receptor, Endothelin A; Receptor, Endothelin B; Transforming Growth Factor beta; Vitreous Body
PubMed: 24630762
DOI: 10.1016/j.jdiacomp.2013.09.010 -
Human Mutation Jun 2007Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental... (Review)
Review
Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental carcinogenic mechanisms involved in melanoma remain largely unknown. To this end, we systematically reviewed, extracted, and analyzed mutational data from the extant melanoma literature in an effort to gain more insight into its early pathogenic events. We searched PubMed (1966-January 2006) using the words "mutation" AND "melanoma" in the title or abstract. Out of 2,095 returned results, there were 203 eligible studies that were subsequently analyzed. We cataloged 8,201 somatic and cultured melanoma specimens and annotated 2,041 reported somatic sequence variants. The single BRAF c.1799T>A (p.Val600Glu) alteration is the most prevalent variant while other A:T>T:A transversions were uncommon. Four highly-recurrent, non-ultraviolet B (UVB) changes account for most of the NRAS and BRAF variants. CDKN2A, PTEN/MMAC1, and TP53 harbored statistically higher rates of UVB signature changes (64.2%, 52.4%, and 69.2%, respectively) than oncogenic loci (NRAS: 15.3% and BRAF: 2.4%). More specifically, cutaneous melanomas showed a significantly higher proportion of UVB signature mutations at both TP53 and CDKN2A when compared to non-skin cancers using data from their respective locus-specific databases. Superficial spreading and nodular melanomas had the highest rates of BRAF (53.4%) and NRAS (28.0%) mutations. In melanoma, there is sufficient mutational evidence to support a role for direct UVB participation, especially at TP53 and CDKN2A. For oncogenes, the role for UVB is less clear since functionally-activating changes are uncommon and are subject to sequence constraints.
Topics: DNA Mutational Analysis; Genes, Tumor Suppressor; Humans; Melanoma; Mutation; Neoplasms, Radiation-Induced; Proto-Oncogenes; Skin Neoplasms; Ultraviolet Rays; Uveal Neoplasms
PubMed: 17295241
DOI: 10.1002/humu.20481 -
Critical Reviews in Oncology/hematology Apr 2021A systematic review (SR) and meta-analysis were conducted to determine the prevalence of PI3K-AKT-mTOR signaling pathway mutations in patients with head and neck cancer... (Meta-Analysis)
Meta-Analysis Review
A systematic review (SR) and meta-analysis were conducted to determine the prevalence of PI3K-AKT-mTOR signaling pathway mutations in patients with head and neck cancer (HNC). Overall, 105 studies comprising 8630 patients and 1306 mutations were selected. The estimated mutations prevalence was 13 % for PIK3CA (95 % confidence interval [CI] = 11-14; I = 82 %; p < 0.0001), 4% for PTEN (95 % CI = 3-5; I = 55 %; p < 0.0001), 3% for MTOR (95 % CI = 2-4; I = 5%; p = 0.40), and 2% for AKT (95 % CI = 1-2; I = 50 %; p = 0.0001). We further stratified the available data of the participants according to risk factors and tumor characteristics, including HPV infection, tobacco use, alcohol exposure, TNM stage, and histological tumor differentiation, and performed subgroup analysis. We identified significant associations between PI3K-AKT-mTOR pathway-associated mutations and advanced TNM stage (odds ratio [OR] = 0.20; 95 % CI = 0.09-0.44; I² = 71 %; p = 0.0001) and oropharyngeal HPV-positive tumors and PIK3CA mutations (OR = 17.48; 95 % CI = 4.20-72.76; I² = 69 %; p < 0.0002). No associations were found between alcohol and tobacco exposure, and tumor differentiation grade. This SR demonstrated that the PI3K-AKT-mTOR pathway emerges as a potential prognostic factor and could offer a molecular basis for future studies on therapeutic targeting in HNC patients.
Topics: Head and Neck Neoplasms; Humans; Mutation; Phosphatidylinositol 3-Kinases; Prevalence; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases
PubMed: 33675910
DOI: 10.1016/j.critrevonc.2021.103284 -
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 -
Urologic Oncology Aug 2017The c-Met proto-oncogene pathway plays an important role in the progression of various cancers. However, the effect of the c-Met pathway on renal cell carcinoma (RCC)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
The c-Met proto-oncogene pathway plays an important role in the progression of various cancers. However, the effect of the c-Met pathway on renal cell carcinoma (RCC) remains controversial. We decided to clarify the role of c-Met in prognosis and clinicopathology of RCC.
METHODS
A total of 10 pairs of tumour and adjacent tissues were obtained from patients with primary RCC between 2013 and 2014 and tissue microarrays to assess c-Met expression in tumour tissues from 90 patients with RCC by Western blot and immunohistochemical staining. We also presented a meta-analysis to explore the correlation between c-Met and pathological grade and stage of RCC. The two-tailed Pearson's χ and Fischer exact tests were used to compare categorical variables. Multivariate analysis was performed using the multivariate Cox proportional hazards model.
RESULTS
C-Met protein levels were increased in 8 of 10 RCC tissue samples compared with their adjacent normal tissue and c-Met expression levels were positively associated with a high nuclear grade (P = 0.008) and pT stage (P = 0.002). Multivariate analysis showed that a high expression of c-Met was an independent predictor of disease-specific survival (P = 0.017). A meta-analysis found that increased c-Met expression in RCC tissues was closely correlated with high tumour grade (P<0.001) and high pT stage (P = 0.001). Most importantly, c-Met expression was significantly correlated with disease-specific survival (P<0.001).
CONCLUSIONS
Because c-Met is strongly associated with pathological grade, stage and disease-specific survival, c-Met levels may have potential to predict patient prognosis and to guide clinical diagnosis and treatment.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Prognosis; Proportional Hazards Models; Proto-Oncogene Mas; Proto-Oncogene Proteins c-met
PubMed: 28427859
DOI: 10.1016/j.urolonc.2017.03.027