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Cancers Aug 2023Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical... (Review)
Review
Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical meta-analysis was to assess the prevalence of other hematological adverse events (AEs) that occur during or after predominantly first-line treatment with TKIs. Data from seventy peer-reviewed, published studies were included in the analysis. Hematological AEs were assessed as a function of TKI drug type (dasatinib, imatinib, bosutinib, nilotinib) and CML phase (chronic, accelerated, blast). AE prevalence aggregated across all severities and phases was significantly different between each TKI ( < 0.05) for anemia-dasatinib (54.5%), bosutinib (44.0%), imatinib (32.8%), nilotinib (11.2%); neutropenia-dasatinib (51.2%), imatinib (29.8%), bosutinib (14.1%), nilotinib (14.1%); thrombocytopenia-dasatinib (62.2%), imatinib (30.4%), bosutinib (35.3%), nilotinib (22.3%). AE prevalence aggregated across all severities and TKIs was significantly ( < 0.05) different between CML phases for anemia-chronic (28.4%), accelerated (66.9%), blast (55.8%); neutropenia-chronic (26.7%), accelerated (63.8%), blast (36.4%); thrombocytopenia-chronic (33.3%), accelerated (65.6%), blast (37.9%). An odds ratio (OR) with 95% confidence interval was used to compare hematological AE prevalence of each TKI compared to the most common first-line TKI therapy, imatinib. For anemia, dasatinib OR = 1.65, [1.51, 1.83]; bosutinib OR = 1.34, [1.16, 1.54]; nilotinib OR = 0.34, [0.30, 0.39]. For neutropenia, dasatinib OR = 1.72, [1.53, 1.92]; bosutinib OR = 0.47, [0.38, 0.58]; nilotinib OR = 0.47, [0.42, 0.54]. For thrombocytopenia, dasatinib OR = 2.04, [1.82, 2.30]; bosutinib OR = 1.16, [0.97, 1.39]; nilotinib OR = 0.73, [0.65, 0.82]. Nilotinib had the greatest fraction of severe (grade 3/4) hematological AEs (30%). In conclusion, the overall prevalence of hematological AEs by TKI type was: dasatinib > bosutinib > imatinib > nilotinib. Study limitations include inability to normalize for dosage and treatment duration.
PubMed: 37686630
DOI: 10.3390/cancers15174354 -
Food and Chemical Toxicology : An... Aug 2023The prevalence of ochratoxin A (OTA) in meat, edible offal, and meat products (MOP) was assessed through systematic review and meta-analysis. Four electronic databases... (Meta-Analysis)
Meta-Analysis
The prevalence of ochratoxin A (OTA) in meat, edible offal, and meat products (MOP) was assessed through systematic review and meta-analysis. Four electronic databases were used to gather data from 1975 to September 15, 2022. Seventy-five articles comprising 8585 samples were identified and analyzed. The studies included in the analysis were conducted at a global level, with a predominant focus on Europe [72% (54/75)], Asia [13.33% (10/75)], Africa [13.33% (10/75)], and North America [1.33% (1/75)]. The overall prevalence of OTA in MOP was 39%. The highest and lowest prevalence percentages were recorded in Iraq (77%) and the USA (3%), respectively. Concerning food type, OTA prevalence was highest in the poultry gizzard (66%) and lowest in the cow liver (2%). The overall concentration of OTA in the MOP was 1.789 μg/kg. Poultry kidneys had the highest concentration of OTA (0.880-22.984 μg/kg), while pork had the lowest concentration (0.127-0.824 μg/kg). Conspicuous amounts of OTA contamination have been reported in fermented sausages. The lowest OTA concentration was found in Belgium (0.220 μg/kg) and the highest in Denmark (60.527μg/kg). These results can help food authorities minimize and control OTA in the MOP.
Topics: Animals; Female; Cattle; Food Contamination; Prevalence; Ochratoxins; Meat; Poultry
PubMed: 37390956
DOI: 10.1016/j.fct.2023.113921 -
Lung Cancer (Amsterdam, Netherlands) Nov 2023The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to...
INTRODUCTION
The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC.
METHODS
EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients. Meta-analyses were done to determine prevalence using a random effects model.
RESULTS
Fifty-five articles were included. EGFR and KRAS were the most prevalent genes with high heterogeneity across the countries. The overall mutation frequency for EGFR was 22%. The most frequent mutations in the EGFR gene were del19 (10%) and L858R (7%). The mean of KRAS mutation was a 14% prevalence. KRASG12C was the most frequent mutation with a 7% prevalence in an entire population. The overall frequency of ALK rearrangement was 5%. The mean frequency of ROS-1 rearrangement was 2%, and the frequencies of HER-2, MET, BRAF, RET, NTRK molecular alterations were 4%, 3%, 2%, 2%, and 1% respectively. Almost half of the cases were male, and 65.8% had a history of tobacco exposure. The most common clinical stage was IV.
CONCLUSIONS
The prevalence of driver mutations such as EGFR and KRAS in LA populations differs from what is reported in Asians and Europeans. In the present article, countries with a high proportion of Amerindian ancestry show a greater prevalence of EGFR in contrast to countries with a high proportion of Caucasians. Lack of information on some countries or studies with a small sample size affects the real prevalence data for the region.
PubMed: 37729688
DOI: 10.1016/j.lungcan.2023.107378 -
Journal of Oral Pathology & Medicine :... Nov 2023This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables.
METHODS
A comprehensive search was conducted using databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, Google Scholar and grey literature, without any limitation on start date or language up to 20 June 2023. A random effect meta-analysis was conducted and Metaregression analyses were performed based on available clinicopathological factors.
RESULTS
Fifteen studies met the criteria for meta-analysis of outcomes. There was no significant difference in overall recurrence rates between the two groups (risk difference = 0.001, p-value = 0.987). Increasing male:female ratio in the BRAFv600e+ group was associated with a lower reported recurrence, suggesting a higher recurrence rate in females. The odds of having mandibular lesion were four times higher in BRAFv600e+ cases compared to BRAFv600e- cases (confidence interval: 2.121-7.870, p < 0.001, I = 28.37%).
CONCLUSION
Within the BRAFv600e+ group, females showed a higher reported recurrence rate. This specific clinical group may benefit from BRAFv600e mutation investigation and potential upscaled surgical treatment and additional BRAF inhibitor therapy, which needs validation in future studies.
Topics: Humans; Male; Female; Ameloblastoma; Proto-Oncogene Proteins B-raf; Mutation; Molecular Targeted Therapy
PubMed: 37872712
DOI: 10.1111/jop.13494 -
International Archives of Occupational... Apr 2024Our aimed to conduct a meta-analysis of cohort studies on risk of genitourinary (GU) cancers in workers exposed to welding fumes (WF). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Our aimed to conduct a meta-analysis of cohort studies on risk of genitourinary (GU) cancers in workers exposed to welding fumes (WF).
METHODS
We performed a systematic review of studies published on Pubmed, Scopus and Embase following PRISMA criteria. Two researchers selected cohort studies on WF exposure. From 2582 articles, 7 non-overlapping studies were included. Quality of studies was scored according to CASP. We run a random effects meta-analysis to calculate the relative risk (RR) and 95% confidence intervals (CI) of GU cancer, overall and stratified by cancer, country, and quality score.
RESULTS
We included seven studies reporting results on GU cancers, including prostate, bladder and kidney cancer (PC, BC, and KC). The RR was 1.19 (95% CI = 1.07-1.32, 16 risk estimates) for GU cancer; 1.13 (95% CI = 0.90-1.42, 4 risk estimates) for PC; 1.26 (95% CI = 0.98-1.60, 7 risk estimates) for BC and 1.28 (95% CI = 1.12-1.47, 5 risk estimates) for KC. Heterogeneity was present in all meta-analyses (p < 0.001). The increased risk was more pronounced in North American than in European studies (respectively, OR = 1.35, 95% CI = 1.18-1.55; OR = 1.13, 95% CI = 1.01-1.27 p heterogeneity = 0.03). There was no heterogeneity according to quality score (p = 0.4). Data were insufficient to investigate associations by industry or welding type. Publication bias for each cancer was excluded.
CONCLUSION
This meta-analysis suggests increased risk of KC and BC, but not of PC, in workers exposed to WF. Confounding by other occupational and non-occupational risk factors could not be excluded. Data were not adequate to address the risk of specific exposure circumstances.
Topics: Male; Humans; Urinary Bladder; Welding; Occupational Exposure; Prostatic Neoplasms; Kidney
PubMed: 38231405
DOI: 10.1007/s00420-023-02040-0 -
Cancers Jul 2023Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related... (Review)
Review
Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related mortality rate. However, the aetiology of this disease is not yet fully understood. While human papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancers, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.
PubMed: 37568712
DOI: 10.3390/cancers15153897 -
Pathway Mutations as Predictive Biomarkers in Middle Eastern Colorectal Cancer: A Systematic Review.Clinical Medicine Insights. Oncology 2024This review article aims to investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations, and their... (Review)
Review
BACKGROUND
This review article aims to investigate the prevalence and spectrum of rat sarcoma (RAS) and V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations, and their connection with geographical location, clinicopathological features, and other relevant factors in colorectal cancer (CRC) patients in the Middle East.
METHODS
A systematic literature review, employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was conducted to investigate the association between the frequency of relevant mutations and the descriptive clinicopathological characteristics of CRC patients. Multiple electronic databases, including PubMed, Science Direct, Web of Science, Scopus, and Google Scholar, were searched to analyze the relevant literature.
RESULTS
A total of 19 eligible studies comprising 2960 patients with CRC were included in this review. A comprehensive analysis of the collected literature data as well as descriptive and methodological insights is provided. Men were predominant in reviewed studies for the region, accounting for 58.6%. Overall, RAS mutation prevalence was 38.1%. Kirsten RAS Viral Oncogene Homolog (KRAS) mutations were the most common, accounting for 37.1% of cases and distributed among different exons, with the G12D mutation being the most frequent in exon 2 (23.2%) followed by G12V (13.7%), G13D (10.1%), G12C (5.1%), G12A (5.04%), and G12S (3.6%). Neuroblastoma RAS Viral Oncogene Homolog (NRAS) mutations were identified in 3.3% of tumor samples, with the most common mutation site located in exons 2, 3, and 4, and codon 61 being the most common location for the region. The total mutation frequency in the BRAF gene was 2.6%, with the V600E mutation being the most common.
CONCLUSION
The distribution patterns of RAS and BRAF mutations among CRC patients exhibit notable variations across diverse ethnic groups. Our study sheds light on this phenomenon by demonstrating a higher prevalence of KRAS mutations in CRC patients from the Middle East, as compared with those from other regions. The identification of these mutations and geographical differences is important for personalized treatment planning and could potentially aid in the development of novel targeted therapies. The distinct distribution patterns of RAS and BRAF mutations among CRC patients across different ethnic groups, as well as the regional variability in mutation prevalence, highlight the need for further research in this area.
PubMed: 38798959
DOI: 10.1177/11795549241255651 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500 -
PloS One 2024Although milk and dairy products are almost complete food, they can contain toxic heavy elements with potential hazards for consumers. This review aims to provide a...
OBJECTIVE
Although milk and dairy products are almost complete food, they can contain toxic heavy elements with potential hazards for consumers. This review aims to provide a comprehensive report on the occurrence, concentration, and health risks of selected heavy metals in pasteurized and sterilized milk recorded worldwide.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to develop this systematic review. Databases included the Web of Knowledge, Scopus, Scientific Information Database, Google Scholar, and PubMed from inception until January 2023. Keywords related to the terms "Heavy metals", "Arsenic" and "Pasteurized and sterilized milk" and "Risk Assessment" were used. The potential health risks to human health from milk daily consumption were estimated using extracted data on heavy metals concentration based on metal estimated daily intake, target hazard quotient, and carcinogenic risk.
RESULTS
A total of 48 potentially relevant articles with data on 981 milk samples were included in the systematic review. Atomic Absorption Spectroscopy, atomic absorption spectroscopy, inductively coupled plasma-mass spectrometry, and inductively coupled plasma-optical emission spectrometry were the most common valid methods to measure heavy metals in milk samples. Following the initial evaluation, Cu, Cd, Zn, and Pb were the most contaminants, which exceeded the maximum permissible criteria in 94%, 67%, 62%, and 46% of the milk samples tested. Relying on target hazard quotient and carcinogenic risk results, milk consumers in 33(68.75%) and 7 (14.5%) studies were exposed to moderate to high levels of carcinogenic and non-carcinogenic risk, respectively. The highest level of risk is due to the consumption of pasteurized and sterilized milk detected in Pakistan, Brazil, Egypt, Slovakia, and Turkey.
CONCLUSION
The elevated levels of heavy metals in milk samples, especially Pb and Cd is a public health concern; therefore, maximum control and strict regulations must be adopted to decrease heavy metals contaminants in the dairy industry. Further studies are required to develop safe milk processing and handling methods for the decontamination of heavy metals in milk and its products.
Topics: Humans; Animals; Milk; Cadmium; Lead; Metals, Heavy; Risk Assessment; Carcinogens; Environmental Monitoring
PubMed: 38315713
DOI: 10.1371/journal.pone.0296649 -
International Journal of Molecular... Jul 2023In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options... (Review)
Review
In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. Recent advancements in our understanding of the intricate relationship between inflammation and oncogenesis, particularly involving the IL-1β/PD-1/PD-L1 pathway, have shed light on their application in lung cancer development and clinical outcomes of patients. Targeting these pathways in cancers like NSCLC holds immense potential to revolutionize cancer treatment, particularly for patients lacking targetable genetic mutations. However, despite these promising prospects, there remain certain aspects of this pathway that require further investigation, particularly regarding treatment resistance. Therefore, the objective of this review is to delve into the role of IL-1β in NSCLC, its participation in inflammatory pathways, and its intricate crosstalk with the PD-1/PD-L1 pathway. Additionally, we aim to explore the potential of IL-1β as a therapeutic target for NSCLC treatment.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Interleukin-1beta
PubMed: 37511306
DOI: 10.3390/ijms241411547