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International Journal of Molecular... Dec 2023Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was...
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the and genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, = 2.6 × 10; R = -0.21, = 0.015) and cg21886367 (R = -0.45, = 7.3 × 10; R = -0.24, = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated . To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.
Topics: Humans; Triple Negative Breast Neoplasms; Cell Line, Tumor; Epigenomics; Receptors, Leukotriene
PubMed: 38139172
DOI: 10.3390/ijms242417343 -
Journal of the College of Physicians... Sep 2023This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and pulmonary function in children with cough variant asthma (CVA). Five electronic databases were searched for studies about MKST+BUD therapy and BUD alone therapy on inflammation and pulmonary function in CVA children from inception to November 23, 2021. Twenty-two articles were included. The results showed that, compared with BUD alone, the combination treatment could achieve better improvement of pulmonary function and lower levels of inflammation (MKST+BUD group: FEV1: SMD = 2.77, 95% CI: 2.07, 3.46; FVC: SMD = 2.54, 95% CI: 1.82, 3.27; PEF: SMD = 2.27, 95% CI: 1.79, 2.75; IgE: SMD = -7.95, 95% CI: -9.66, -6.25; TNF-α: SMD = -4.67, 95% CI: -6.04, -3.31; IL-8: SMD = -8.18, 95% CI: -11.46, -4.90; BUD alone group: FEV1: SMD = 1.83, 95% CI: 1.34, 2.31; FVC: SMD = 1.39, 95% CI: 0.93, 1.84; PEF: SMD = 1.51, 95% CI: 1.13, 1.89; IgE: SMD = -4.93, 95% CI: -6.14, -3.72; TNF-α: SMD = -2.78, 95% CI: -3.76, -1.80; IL-8: SMD = -4.94, 95% CI: -7.10, -2.79). To conclude, compared with BUD alone, MKST+BUD therapy was found to be more effective in improving pulmonary function and reducing inflammation in CVA children. Key Words: Montelukast, Budesonide, Cough variant asthma, Children, Pulmonary function, Inflammatory markers, Meta-analysis.
Topics: Child; Humans; Budesonide; Cough; Interleukin-8; Tumor Necrosis Factor-alpha; Asthma; Inflammation; Immunoglobulin E
PubMed: 37691368
DOI: 10.29271/jcpsp.2023.09.1040 -
Children (Basel, Switzerland) Jul 2023Drug-induced neuropsychiatric effects are important for disease management. We aim to evaluate the neuropsychiatric effects of montelukast-levocetirizine combination...
Drug-induced neuropsychiatric effects are important for disease management. We aim to evaluate the neuropsychiatric effects of montelukast-levocetirizine combination therapy in children. This descriptive study was conducted with children aged 2-5 years, diagnosed with asthma and allergic rhinitis, who began to receive montelukast and levocetirizine combination therapy. The respiratory and asthma control test for children (TRACK), Rhino Conjunctivitis Scoring System (RCSS), and common neuropsychiatric effects (irritable behavior, hallucinations, headaches, nightmares, sleep disorders, behavioral and mood disorder, restlessness, depression) were ascertained by the questionnaire applied before and 4 weeks after the treatment. Parents answered on behalf of their children. The most common finding before and after treatment was irritable behavior. While irritable behavior was observed in 82.4% ( = 56) of children before the treatment, this percentage was 63.2% ( = 43) after the treatment ( = 0.004). The percentage of children who developed at least one neuropsychiatric symptom after treatment was 22.1% ( = 15). There was no significant effect of age, gender, RCSS, TRACK, or allergy test positivity on the development of neuropsychiatric symptoms ( > 0.05). According to the results, at least one neuropsychiatric finding developed in approximately one in five children. Identifying risk factors will enable more careful treatment or consideration of alternative treatments for children at higher risk in the clinical follow-up period.
PubMed: 37628300
DOI: 10.3390/children10081301 -
Luminescence : the Journal of... Dec 2023In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a...
A highly sensitive micelle-enhanced synchronous spectrofluorimetric determination of the recently approved co-formulated drugs, bilastine and montelukast in pharmaceuticals and human plasma at nanogram levels.
In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a quick, sensitive, environmentally friendly, and reasonably priced synchronous fluorescence spectroscopic approach for the first time. Enhancement of the method's sensitivity down to nanogram levels was achieved by the addition of sodium dodecyl sulfate (1.0% w/v) as a micellar system. According to the results, bilastine and montelukast's fluorescence was measured at 255.3 and 355.3 nm, respectively, using Δλ of 40.0 nm and distilled water as a green diluting solvent. With respect to the concentration ranges of bilastine (5.0-300.0 ng/ml) and montelukast (50.0-1000.0 ng/ml), the method showed excellent linearity (r ≥ 0.9998). The results showed that the suggested method is highly sensitive, with detection limits of 1.42 and 13.74 ng/ml for bilastine and montelukast, respectively. Within-run precisions (intra- and interday) per cent relative standard deviations (RSD) for both analytes were <0.59%. With high percentage recoveries and low percentage RSD values, the designed approach was successfully applied for the simultaneous estimation of the cited medications in their dosage form and human plasma samples. To evaluate the green profile of the suggested method, an analytical GREENNESS metric approach (AGREE) and green analytical procedure index (GAPI) metric tools were used. These two methods for evaluating greenness confirmed that the developed method met the highest number of green requirements, recommending its use as a green substitute for the routine analysis of the studied drugs. The proposed approach was validated according to ICHQ2 (R1) guidelines.
PubMed: 38044037
DOI: 10.1002/bio.4635 -
Cureus Oct 2023Background Cough is one of the most common presenting complaints for physicians across the world, with the potential to result in a significant influence on one's daily...
Background Cough is one of the most common presenting complaints for physicians across the world, with the potential to result in a significant influence on one's daily life. It is typically categorized into acute cough (<3 weeks), subacute cough (three to eight weeks), and chronic cough (>8 weeks). The lack of specific treatment guidelines and evidence-based recommendations for resolving cough creates reasonable controversy in the medical field. This retrospective study aims to identify the clinical features of cough and evaluate the comparative efficacy between different anti-asthmatic treatment modalities in the urban city of Dubai, United Arab Emirates. Methods A retrospective cross-sectional study was performed on patients presenting to pulmonology or respiratory outpatient clinics with complaints of cough in the absence of any known history of chronic respiratory illness (e.g., asthma). Analysis was conducted via chi-squared and analysis of variance (ANOVA) testing. Results A total of 308 patients were eligible for inclusion, with 273 patients presenting for follow-up. Overall, patients with acute, subacute, and chronic coughs had similar clinical presentations, with no statistically significant differences noted. However, patients with pets were more likely to develop an acute cough (p = 0.04). Moreover, the follow-up outcomes of acute, subacute, and chronic cough were similar, with no significant statistical difference noted. Furthermore, patients receiving dual therapy using budesonide and montelukast, and patients receiving triple therapy using budesonide, montelukast, and tiotropium/ipratropium were most likely to gain complete relief of their symptoms, although triple therapy treatment was also associated with the highest rate of null improvement (p = 0.012). Additionally, chronic cough patients were more likely to be subject to higher C-reactive protein (CRP) levels in comparison to other cohorts (p = 0.26). Conclusion The comparative superiority of dual therapy using budesonide and montelukast, and triple therapy using budesonide, montelukast, and tiotropium/ipratropium were highlighted in this study. In the sparseness of specific treatment guidelines and evidence-based recommendations for cough, the use of anti-asthmatic therapy for cough patients has shown favorable results. Moreover, the lack of clinical differences between acute, subacute, and chronic cough may result in difficulties with the treatment of cough patients. To arrive at a valid conclusion, further comprehensive studies with larger and more diversified sample populations are encouraged.
PubMed: 38021559
DOI: 10.7759/cureus.47377 -
Scientific Reports Feb 2024Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in...
Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast "repurposing" in cardiovascular diseases and in particular in myocardial infarction.
Topics: Mice; Animals; Female; Ventricular Remodeling; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38337010
DOI: 10.1038/s41598-024-53936-x -
The Journal of Dermatological Treatment Dec 2024There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
BACKGROUND
There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
METHODS
We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines.
RESULTS
Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria.
CONCLUSIONS
Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
Topics: Humans; Female; Middle Aged; Male; Hydroxychloroquine; Pilot Projects; Chronic Disease; Chronic Urticaria; Urticaria; Omalizumab; Histamine H1 Antagonists; Cyclosporine; Dapsone; Anti-Allergic Agents; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38508226
DOI: 10.1080/09546634.2024.2329784 -
Therapeutic Advances in Respiratory... 2024Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in... (Review)
Review
A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.
Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft--host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.
Topics: Humans; Leukotriene Antagonists; Bronchiolitis Obliterans; Bronchiolitis Obliterans Syndrome; Lung; Lung Transplantation; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Leukotrienes; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38504551
DOI: 10.1177/17534666241232284 -
PLoS Neglected Tropical Diseases Feb 2024Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with warning signs.
METHODS
This multicenter, randomized, double-blind, placebo-controlled trial enrolled adult participants with NS1 antigenemia in Thailand. The participants were randomly assigned to receive either oral montelukast (10 mg) or a placebo for 10 days or until all symptoms resolved.
RESULTS
Between January 2021 and June 2023, 358 participants were enrolled and randomly assigned (1:1) to receive either montelukast or placebo. The incidence rate of warning signs in the montelukast group and the placebo group were 9.5% and 7.8% per day, respectively. There was no difference between the two groups (HR 1.36; 95%CI 0.94-1.96, P = 0.105). No statistically significant differences were observed in the incidence rate of severe dengue, hemoconcentration, thrombocytopenia, admission, or recovery from dengue. Neither dengue shock, nor mortality occurred. The montelukast group exhibited a decreased incidence rate of transaminase elevations (0.7% vs 1.4% per day, HR: 0.48, 95%CI 0.25-0.90, P = 0.023).
CONCLUSION
Oral montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast.
CLINICAL TRIALS REGISTRATION
Clinicaltrials.gov, NCT04673422, registered on 9 December 2020.
Topics: Adult; Humans; Treatment Outcome; Acetates; Double-Blind Method; Severe Dengue; Transaminases; Cyclopropanes; Quinolines; Sulfides
PubMed: 38306389
DOI: 10.1371/journal.pntd.0011927 -
Targeted Oncology Nov 2023Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a...
BACKGROUND
Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few.
OBJECTIVE
In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders.
PATIENTS AND METHODS
A total of 189 patients diagnosed with MM or light chain amyloidosis were included in this retrospective study, and all subjects were daratumumab-naïve. Primary endpoint was safety of subcutaneous daratumumab, especially for infusion-related reaction (IRR) incidence and severity. All patients received premedication with dexamethasone, paracetamol, and antihistamine, with montelukast usage in 85% of cases.
RESULTS
Eight patients (4%) experienced IRRs, mainly of grade I-II, and other frequent toxicities were: hematological (thrombocytopenia, 4%; neutropenia, 5%; lymphopenia, 6%) and non-hematological (pneumonia, 4%; diarrhea, 2%; and cytomegalovirus reactivation, 0.5%). In our multicenter retrospective real-life experience, subcutaneous daratumumab was well-tolerated with an excellent safety profile with a very low (4%) IRR incidence, even in frailer MM patients with severe renal impairment or increased body weight.
CONCLUSIONS
Subcutaneous daratumumab was safe in a real-life setting including patients with severe renal failure and advanced disease. However, further studies on larger and prospective cohorts are required to confirm our real-life observations.
Topics: Humans; Retrospective Studies; Plasma Cells; Prospective Studies; Antineoplastic Agents; Multiple Myeloma; Antibodies, Monoclonal; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37747623
DOI: 10.1007/s11523-023-01001-4