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Cancer Feb 2013The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat... (Meta-Analysis)
Meta-Analysis Review
KRAS p.G13D mutation and codon 12 mutations are not created equal in predicting clinical outcomes of cetuximab in metastatic colorectal cancer: a systematic review and meta-analysis.
BACKGROUND
The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations.
METHODS
Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies.
RESULTS
Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54).
CONCLUSIONS
Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution.
Topics: Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aspartic Acid; Cetuximab; Codon; Colorectal Neoplasms; Disease-Free Survival; Female; Glycine; Humans; Male; Middle Aged; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Treatment Outcome; ras Proteins
PubMed: 22972628
DOI: 10.1002/cncr.27804 -
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 Clinical Laboratory Analysis Oct 2021Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers....
BACKGROUND
Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma.
METHODS
For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening.
RESULTS
Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks.
CONCLUSION
The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.
Topics: Human papillomavirus 16; Human papillomavirus 18; Humans; Papillomavirus Infections; Prevalence; Retinal Neoplasms; Retinoblastoma
PubMed: 34462972
DOI: 10.1002/jcla.23981 -
Scientific Reports Feb 2018Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of... (Meta-Analysis)
Meta-Analysis Review
Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47-0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53-0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30-2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62-0.98; HR: 0.60; 95% CI: 0.40-0.90; HR: 0.62; 95% CI: 0.41-0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; Humans; Magnesium; Neoplasm Metastasis; Panitumumab; Proto-Oncogene Proteins p21(ras); Randomized Controlled Trials as Topic; Survival Analysis
PubMed: 29391418
DOI: 10.1038/s41598-018-19835-8 -
The Journal of Maternal-fetal &... Dec 2023Previous studies evaluating the association between circulating neutrophil gelatinase-associated lipocalin (NGAL) and the risk of preeclampsia (PE) showed inconsistent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies evaluating the association between circulating neutrophil gelatinase-associated lipocalin (NGAL) and the risk of preeclampsia (PE) showed inconsistent results. A systematic review and meta-analysis was performed to summarize the relationship between circulating NGAL and PE.
METHODS
Studies comparing the circulating NGAL between pregnant women with PE and controls with no PE were found by searching Medline, Web of Science, Cochrane's Library, and Embase. Pooling results was performed using a random-effects model incorporating heterogeneity.
RESULTS
In the study, 1293 women with PE and 1773 healthy pregnant women were enrolled in 18 case-control studies, and the gestational age was matched between cases and controls. Pooled results showed that compared to controls, women with PE had a significantly higher blood level of NGAL (standardized mean difference [SMD]: 0.95, 95% confidence interval [CI]: 0.63-1.28, < .001; = 92%). Subgroup analyses showed consistent results in studies of NGAL measured at the first (SMD: 0.47, 95% CI: 0.15-0.80, = .004), the second (SMD: 0.87, 95% CI: 0.55-1.19, < .001), and the third trimester (SMD: 1.06, 95% CI: 0.63-1.24, < .001) of pregnancy. In addition, women with mild (SMD: 0.78, 95% CI: 0.13-1.44, = .02) and severe PE (SMD: 1.19, 95% CI: 0.40-1.97, = .003) both had higher circulating NGAL as compared to controls.
CONCLUSIONS
High circulating NGAL is associated with PE, which may be independent of the trimesters for blood sampling and the severity of PE.
Topics: Female; Humans; Pregnancy; Biomarkers; Lipocalin-2; Pre-Eclampsia; Pregnancy Trimester, Third; Pregnancy Trimesters
PubMed: 37282560
DOI: 10.1080/14767058.2023.2197100 -
Expert Opinion on Biological Therapy Jun 2008Kidney cancer is not a homogenous entity; it is comprised of many different tumor types, with different biologies and molecular mechanisms leading to disease and... (Review)
Review
BACKGROUND
Kidney cancer is not a homogenous entity; it is comprised of many different tumor types, with different biologies and molecular mechanisms leading to disease and therefore different treatment approaches.
OBJECTIVE
To describe the genetic basis and biochemical pathways underlying inherited forms of renal cancer, specifically in four described syndromes (von Hippel-Lindau [VHL], hereditary papillary renal cancer [HPRC], Birt-Hogg-Dubé [BHD] and hereditary leiomyomatosis renal cell carcinoma [HLRCC]), and to elucidate how the understanding of these diseases enables the possibility of disease-specific approaches to therapy.
METHODS
A systematic review of the published literature on inherited and sporadic forms of renal cancer was performed.
CONCLUSION
Understanding of the biology and mechanisms of different forms of kidney cancer provides an opportunity for development of new treatment options.
Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Drug Design; Fumarate Hydratase; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Humans; Kidney Neoplasms; Leiomyomatosis; Neoplasm Proteins; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-met; Proto-Oncogenes; Receptors, Growth Factor; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor A; Von Hippel-Lindau Tumor Suppressor Protein; von Hippel-Lindau Disease
PubMed: 18476789
DOI: 10.1517/14712598.8.6.779 -
Transplantation and Cellular Therapy Dec 2021Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic... (Meta-Analysis)
Meta-Analysis
Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation-A Systematic Review and Meta-Analysis.
BACKGROUND
Disease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic hematopoietic cell transplant (allo-HCT). Maintenance treatment with FLT3 inhibitors and hypomethylating agents (HMA) has been studied in various clinical trials with mixed results.
OBJECTIVE
To synthesize the current evidence on the efficacy and safety of FLT3 inhibitors and HMA for maintenance therapy after allo-HCT in AML and MDS.
METHODS
For this systematic review and meta-analysis Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to March 2021 for studies on maintenance therapies after allo-HCT in AML and MDS. Studies were excluded if they were reviews, commentaries, case series with <5 patients, or basic research articles, not published in English, not on post-allo-HCT maintenance with FLT3 inhibitors or HMA in AML or MDS, or if they were clinical trials without published results or duplicate publications from the same patient cohort. Studies with insufficient reporting of the primary endpoint (2-year overall survival [OS]) and studies using FLT3 inhibitors or HMA for pre-emptive treatment of imminent relapse based on positive measurable residual disease testing were excluded. Random-effects models were used to pool response rates for the primary outcome of 2-year OS. Hazard ratios (HR) for death and relapse were calculated for studies that included a control group. Rates of relapse-free survival (RFS), non-relapse mortality, and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Downs and Black checklist and risk of bias assessments were used to gauge the quality of individual studies. The study protocol has been registered on PROSPERO (CRD42020187298).
RESULTS
Our search strategy identified 5559 studies. Twenty-one studies with a total of 809 patients were included in the meta-analysis. The 2-year OS rates were 81.7% (95% confidence interval [CI], 73.8%-87.7%) and 65.7% (95% CI, 55.1%-74.9%) among patients treated with FLT3 inhibitors and HMA, respectively. In sensitivity analyses restricted to studies that included a control group, maintenance therapy with FLT3 inhibitors (HR for death = 0.41; 95% CI, 0.26-0.62) or HMA (HR = 0.45; 95% CI, 0.31-0.66) appeared superior to no maintenance therapy. The 2-year RFS rates were 79.8% (95% CI, 75.0%-83.9%) and 62.4% (95% CI, 50.6%-72.9%) among patients treated with FLT3 inhibitors and HMA, respectively. Rates of any grade acute and chronic GVHD were 33.1% (95% CI, 25.4%-41.8%; grade 3/4: 16.5%) and 42.5% (95% CI, 26.3%-60.4%) among FLT3 inhibitor and 42.7% (95% CI, 33.5%-52.4%; grade 3/4: 8.1%) and 41.5% (95% CI, 32.0%-51.6%) among HMA-treated patients, respectively.
CONCLUSION
Maintenance therapy with either FLT3 inhibitors or HMA after allo-HCT can lead to prolonged and improved OS and RFS with a favorable safety profile. Additional studies are needed to define the optimal duration of treatment, the role of measurable residual disease status, and transplant characteristics in patient selection.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Protein Kinase Inhibitors; fms-Like Tyrosine Kinase 3
PubMed: 34551341
DOI: 10.1016/j.jtct.2021.09.005 -
British Journal of Cancer Apr 2011The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.
METHODS
Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.
RESULTS
Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.
CONCLUSION
These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cyclin-Dependent Kinase Inhibitor p16; ErbB Receptors; Humans; Immunohistochemistry; Neoplasm Proteins; Pancreatic Neoplasms; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins c-bcl-2; Smad4 Protein; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; bcl-2-Associated X Protein
PubMed: 21448172
DOI: 10.1038/bjc.2011.110 -
Journal of Nephrology Nov 2022Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants.
METHOD
A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria.
RESULTS
We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58-89%), specificity of 76% (95% CI 57-88%) and AUC-SROC of 0.83 (95% CI 0.80-0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37-66%) with a positive test and decreased to 9% (95% CI 5-16%) with a negative test if the pre-test probability was 25%.
CONCLUSION
uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants.
Topics: Humans; Infant; Infant, Newborn; Lipocalin-2; Cystatin C; Creatinine; Osteopontin; Acute Kidney Injury; Biomarkers; Infant, Premature; EGF Family of Proteins
PubMed: 35384606
DOI: 10.1007/s40620-022-01307-y -
Osteoarthritis and Cartilage Mar 2023To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes. (Review)
Review
OBJECTIVE
To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes.
METHOD
PubMed, EMBASE and Web of Science databases were searched up to 19 September 2021 to identify in vitro studies exploring ultrasound to stimulate chondrocytes for osteoarthritis (OA) treatment. Study characteristics, ultrasound parameters, in vitro setup, and mechanotransduction pathways were collected. Risk of bias was judged using the Risk of Bias Assessment for Non-randomized Studies (RoBANS) tool.
RESULTS
Thirty-one studies were included comprising healthy and OA chondrocytes and explants. Most studies had high risk of performance, detection and pseudoreplication bias due to lack of temperature control, setup calibration, inadequate semi-quantitatively analyzes and independent experiments. Ultrasound was applied to the culture plate via acoustic gel, water bath or culture media. Regardless of the setup used, ultrasound stimulated the cartilage production and suppressed its degradation, although the effect size was nonsignificant. Ultrasound inhibited p38, c-Jun N-terminal kinases (JNK) and factor nuclear kappa B (NFκB) pathways in OA chondrocytes to reduce apoptosis, inflammation and matrix degradation, while triggered phosphoinositide-3-kinase/akt (PI3K/Akt), extracellular signal-regulated kinase (ERK), p38 and JNK pathways in healthy chondrocytes to promote matrix synthesis.
CONCLUSION
The included studies suggest that ultrasound application induces therapeutic effects on chondrocytes. However, these results should be interpreted with caution because high risk of performance, detection and pseudoreplication bias were identified. Future studies should explore the application of ultrasound on human OA chondrocytes cultures to potentiate the applicability of ultrasound towards cartilage regeneration of knee with OA.
Topics: Humans; Chondrocytes; Mechanotransduction, Cellular; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Cartilage, Articular; Osteoarthritis; Ultrasonic Therapy
PubMed: 36481451
DOI: 10.1016/j.joca.2022.07.014