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Fundamental & Clinical Pharmacology Aug 2023Panax ginseng is a common natural product, which is well-known to have a wide range of pharmacological activities in cancer. Its metabolite, compound K (CK), has been... (Review)
Review
Panax ginseng is a common natural product, which is well-known to have a wide range of pharmacological activities in cancer. Its metabolite, compound K (CK), has been reported to have anticancer activity. We aimed to systematically review the literature for evidence of anticancer effects of CK. We conducted a systematic search in eight databases. We included all in vitro and in vivo studies investigating the anticancer effects of CK with no restrictions. Quality assessment was applied by ToxRTool. Fifty-four articles were included in our study. The purity of CK in our included studies was at least 95%. The in vitro studies reported that CK had a potential anticancer activity on several cell lines including human lung cancer cell lines (A549, PC-9), nasopharyngeal carcinoma cell line (Hk-1), liver cancer cell line (BEL 7402), and pediatric acute myeloid leukemia cell lines (Kasumi-1, MV4-11). The in vivo studies reported a significant decrease in tumor volume in mice treated with CK. CK is a potential supplementary treatment in cancer chemotherapies. The safety and further clinical trials of CK should be explored for future drug development.
Topics: Child; Humans; Animals; Mice; Cell Line; Ginsenosides
PubMed: 36691721
DOI: 10.1111/fcp.12874 -
PloS One 2016The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a... (Meta-Analysis)
Meta-Analysis Review
The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20-1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31-2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97-1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52-1.74), relapse risk (RR, 1.12; 95% CI, 0.90-1.41) or OS (RR, 1.03; 95% CI, 0.90-1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02-4.05), relapse risk (RR, 1.89; 95%CI: 1.51-2.37) and OS (RR, 2.26; 95%CI: 1.35-3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19-1.95) or OS (RR, 1.12; 95%CI: 0.90-1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings.
Topics: Animals; Core Binding Factors; Humans; Leukemia, Myeloid, Acute; Mutation; Prognosis
PubMed: 26771376
DOI: 10.1371/journal.pone.0146614 -
Pharmaceutics Mar 2022Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic... (Review)
Review
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.
PubMed: 35335935
DOI: 10.3390/pharmaceutics14030559 -
Systematic Reviews May 2020Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current studies have found that VEGF plays an important role in hematologic diseases including acute myeloid leukemia (AML). However, the circulating levels of VEGF in AML were still controversial among published studies.
METHODS
Three databases including PubMed, EMBASE, and Cochrane Library databases were searched up to February 2020. All articles included in the meta-analysis met our inclusion and exclusion criteria. Studies will be screened and data extracted by two independent investigators. The Newcastle-Ottawa Scale (NOS) and the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool were applied to evaluate the quality of the included studies. A random-effects model was applied to pool the standardized mean difference (SMD). Heterogeneity test was performed by the Q statistic and quantified using I. All statistical analysis was conducted in Stata 12.0 software.
RESULTS
Fourteen case-control studies were finally included in this systematic review and meta-analysis. Heterogeneity was high in our included studies (I = 91.1%, P < 0.001). Sensitivity analysis showed no significant change when any one study was excluded using random-effect methods (P > 0.05). Egger's linear regression test showed that no publication bias existed (P > 0.05). Patients with AML, mainly those newly diagnosed and untreated, have higher VEGF levels (SMD = 0.85, 95% CI 0.28-1.42). Moreover, AML patients in n ≥ 40 group, plasma group, Asia and Africa group, and age ≥ 45 group had higher circulating VEGF levels (all P < 0.05).
CONCLUSIONS
Compared to healthy controls, our meta-analysis shows a significantly higher level of circulating VEGF in AML patients, and it is associated with sample size, sample type, region, and age.
Topics: Africa; Asia; Humans; Leukemia, Myeloid, Acute; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 32375879
DOI: 10.1186/s13643-020-01368-9 -
Value in Health : the Journal of the... Dec 2023This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and... (Meta-Analysis)
Meta-Analysis
Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.
OBJECTIVES
This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy.
METHODS
A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective.
RESULTS
A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46).
CONCLUSIONS
VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.
Topics: Adult; Humans; Treatment Outcome; Azacitidine; Network Meta-Analysis; Bayes Theorem; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Leukemia, Myeloid, Acute
PubMed: 37741447
DOI: 10.1016/j.jval.2023.09.001 -
Frontiers in Pediatrics 2022The purpose of this systematic review was to explore the value of the expression level of the triggering receptor expressed on myeloid cell-1 (TREM-1) in the diagnosis...
OBJECTIVE
The purpose of this systematic review was to explore the value of the expression level of the triggering receptor expressed on myeloid cell-1 (TREM-1) in the diagnosis and prognosis of neonatal sepsis.
METHODS
A comprehensive search was performed to identify the diagnostic and prognostic predictive values of the TREM-1 expression level in neonatal sepsis. Based on the retrieval strategy, Cochrane Library, Embase, Ovid, ProQuest, PubMed, Scopus, and Web of Science databases were searched from inception to February 2022. Studies were included if they assessed the accuracy of TREM-1 expression in the diagnosis of neonatal sepsis and distinguished survival and death in neonatal sepsis. Two authors independently evaluated the study and extracted the data, including the first author of the literature, country, total study population, basic population characteristics of the study group and the control group, study design (observational studies), type of sample, sepsis onset, type of biomarker, assay method, cut-off, sensitivity, specificity, true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). A third party will be consulted if disputed. The accuracy of TREM-1 expression in the diagnosis and prognostic prediction of neonatal sepsis was evaluated by a bivariate mixed-effects model. The source of heterogeneity was explored through meta-regression analysis.
RESULTS
Thirteen articles that met the research criteria were included in qualitative analysis, and 11 of them were included in quantitative analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operator characteristic (SROC) curve of soluble TREM-1 (sTREM-1) were 0.94 (95% CI: 0.82, 0.98), 0.87 (95% CI: 0.70, 0.95), 7.36 (95% CI: 2.75, 19.74), 0.07 (95% CI: 0.02, 0.24), 111.71 (95% CI: 13.24, 942.92), and 0.96 (95% CI: 0.94, 0.98), respectively. Meta-regression and subgroup analysis were used to investigate the heterogeneity, owing to non-threshold effects caused by types of test sample and research design. sTREM-1 as a biomarker for distinguishing survival and death in neonates with sepsis had pooled sensitivity, specificity, area under the SROC curve, PLR, NLR, and DOR of 0.95 (95% CI: 0.83, 0.99), 0.98 (95% CI: 0.68, 1.00), 0.99 (95% CI: 0.97, 0.99), 39.28 (95% CI: 2.13, 723.99), 0.05 (95% CI: 0.01, 0.19), and 789.61 (95% CI: 17.53, 35,560.72), respectively.
CONCLUSION
The study showed that TREM-1 was a potential biomarker for the diagnosis and prognosis of neonatal sepsis. The biggest advantage of this study is that it is the first to comprehensively explore the role of TREM-1 expression in the diagnosis and prognosis of neonatal sepsis. However, there are some limitations in this study, such as the reduced number of clinical studies on TREM-1 expression as a biomarker of neonatal sepsis, regional bias, and differences in detection methods. Hence, more large-scale and high-quality studies are needed to improve diagnostic accuracy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022338041.
PubMed: 35935355
DOI: 10.3389/fped.2022.929665 -
EXCLI Journal 2023Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of... (Review)
Review
Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.
PubMed: 38234970
DOI: 10.17179/excli2023-6577 -
Leukemia Research Feb 2013The main objective of this systematic review is to quantify and to summarize all studies that have included health-related quality of life (HRQOL) or, any other type of... (Meta-Analysis)
Meta-Analysis Review
The main objective of this systematic review is to quantify and to summarize all studies that have included health-related quality of life (HRQOL) or, any other type of patient-reported outcomes (PROs), in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Nine papers were found and none of these were published before 2003. Overall, 3290 CML patients were enrolled in the studies reviewed. Four studies reported HRQOL data on patients treated with imatinib only. The most solid data in this area indicate that CML patients receiving TKIs have a worse HRQOL profile when compared to their peers, without cancer, in the general population and interventions to improve HRQOL outcomes are thus needed. Our review revealed the paucity of evidence-based data in this area. However, HRQOL assessment in these studies emphasize the unique information provided by the patient's perspective. Urgent efforts are needed to provide solid PROs data to complement current knowledge on clinical efficacy of TKIs.
Topics: Antineoplastic Agents; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Self Report; Surveys and Questionnaires; Treatment Outcome
PubMed: 23177797
DOI: 10.1016/j.leukres.2012.10.021 -
Asian Pacific Journal of Cancer... Apr 2022we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. (Meta-Analysis)
Meta-Analysis
Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
OBJECTIVES
we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk.
MATERIALS AND METHODS
The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR).
RESULTS
We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%).
CONCLUSION
Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.
Topics: Adult; Core Binding Factor Alpha 2 Subunit; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Splicing Factor U2AF
PubMed: 35485665
DOI: 10.31557/APJCP.2022.23.4.1107 -
Bone Marrow Transplantation Feb 2023The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation... (Meta-Analysis)
Meta-Analysis
Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.
The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.
Topics: Humans; Adult; Busulfan; Thiotepa; Bayes Theorem; Network Meta-Analysis; Transplantation, Homologous; Graft vs Host Disease; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Recurrence; Retrospective Studies; Transplantation Conditioning
PubMed: 36357773
DOI: 10.1038/s41409-022-01865-6