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Cancer Medicine Mar 2020Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple...
Previous studies have shown that forkhead box P4 antisense RNA 1 (FOXP4-AS1) is dysregulated in tumor tissues and can serve as a prognostic indicator for multiple cancers. However, the clinical significance of FOXP4-AS1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The goal of this study is to recognize the possible clinical significance of long noncoding RNA FOXP4-AS1 in patients with early stage PDAC. A total of 112 patients from The Cancer Genome Atlas (TCGA) PDAC cohort, receiving RNA sequencing, were involved in the study. Survival analysis, functional mechanism, and potential small molecule drugs of target therapy of FOXP4-AS1 were performed in this study. Survival analysis in TCGA PDAC cohort suggested that patients with high FOXP4-AS1 expression had significantly augmented possibility of death than in PDAC patients with lower FOXP4-AS1 expression (adjusted P = .008; adjusted HR = 2.143, 95% CI = 1.221-3.760). In this study, a genome-wide RNA sequencing dataset was used to identify 927 genes co-expressing with FOXP4-AS1 in PDAC tumor tissues. A total of 676 differentially expressed genes were identified between different FOXP4-AS1 expression groups. Functional enrichment analysis of these genes and gene set enrichment analysis for PDAC genome-wide RNA sequencing dataset was done. We have found that FOXP4-AS1 may function in PDAC by participating in biological processes and pathways including oxidative phosphorylation, tricarboxylic acid cycle, classical tumor-related pathways such as NF-kappaB as well as Janus kinase/signal transducers in addition to activators of transcription, cell proliferation, and adhesion. In addition, we also screened two potential targeted therapeutic small molecule drugs (dimenhydrinate and metanephrine) for FOXP4-AS1 in PDAC. In conclusion, our present study demonstrated that higher expression of FOXP4-AS1 in PDAC tumor tissues were related with an inferior medical outcome. Through multiple genome-wide approaches, we identified the potential molecular mechanisms of FOXP4-AS1 in PDAC and two targeted therapeutic drugs for it.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Cell Proliferation; Citric Acid Cycle; Cohort Studies; Datasets as Topic; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Staging; Nomograms; Oxidative Phosphorylation; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; RNA, Long Noncoding; RNA-Seq; Survival Analysis
PubMed: 31991068
DOI: 10.1002/cam4.2818 -
The Annals of Otology, Rhinology, and... May 2020The aim of this study was to compare the effects of betahistine with dimenhydrinate on the resolution of residual dizziness (RD) of patients with benign paroxysmal...
The Impact of Betahistine versus Dimenhydrinate in the Resolution of Residual Dizziness in Patients with Benign Paroxysmal Positional Vertigo: A Randomized Clinical Trial.
OBJECTIVES
The aim of this study was to compare the effects of betahistine with dimenhydrinate on the resolution of residual dizziness (RD) of patients with benign paroxysmal positional vertigo (BPPV) after successful Epley maneuver.
METHODS
In this double-blind, randomized clinical trial, patients with posterior semicircular canal type of BPPV were included. After execution of the Epley maneuver, patients were assigned randomly to one group for 1 week: betahistine, dimenhydrinate or placebo. The primary outcomes were scores of the Dizziness Handicap Inventory (DHI) and the modified Berg balance scale (mBBS). All patients were asked to describe the characteristics of their subjective residual symptoms. Binary logistic regression analysis was performed to examine the predictors of improved RD. All analyses were conducted using SPSS 19.0.
RESULTS
In total, 117 patients (age range: 20-65 years) participated in this study. After the Epley maneuver, 88 participants had RD. After the intervention, 38 patients exhibited an improved RD. Less than 50% of participants in the three groups showed mild to moderate dizziness handicap. However, there was no significant difference between mBBS scores of groups before or after the intervention. Logistic regression was shown that patients with receiving betahistine were 3.18 times more likely to have no RD than the placebo group. Increasing age was associated with a decreased likelihood of improving RD ( = .05).
CONCLUSION
The analysis of data showed that the use of betahistine had more effect on improving RD symptoms. We recommended future studies using objective indicators of residual dizziness.
Topics: Adolescent; Adult; Aged; Benign Paroxysmal Positional Vertigo; Betahistine; Dimenhydrinate; Dizziness; Double-Blind Method; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vasodilator Agents; Young Adult
PubMed: 31810393
DOI: 10.1177/0003489419892285 -
Neurochemical Research Feb 2020Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict...
Motion sickness (MS) is the visceral discomfort caused due to contradicting visual and vestibular inputs to the brain leading to nausea and vomiting. Sensory conflict theory which proves histamine elevations as the primary reason for MS provides a path for an effective pharmaco-therapy. We aimed to evaluate the anti-MS effect of hesperidin (HSP) by modulating histamine and histamine receptor H1 (HRH1) expression. The inhibitory effect of HSP on histamine release was studied in KU812 cells treated with 10 µM calcium ionophore. The in vivo anti-MS effect of HSP was evaluated in Balb/c mice. Thirty six mice were divided into six groups namely, normal control (NC, no rotation), hesperidin at 80 mg/kg body weight control (HSP80, no rotation), motion sickness (MS, rotation induced), dimenhydrinate (Standard drug) at 20 mg/kg body weight + rotation (STD + MS), hesperidin at 40 mg/kg body weight + rotation (HSP40 + MS) and hesperidin at 80 mg/kg body weight + rotation (HSP80 + MS). Hypothalamus and brainstem samples were analysed for histamine levels and HRH1 expression by RT-PCR, Western blot and immunohistochemistry analysis. Calcium ionophore treated KU812 cells significantly increased histamine release when compared to control cells. Pre-treatment with HSP inhibited histamine, HRH1 mRNA and protein expression. Histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem samples of MS group increased significantly when compared to the NC group. Pre-treatment with HSP significantly reduced histamine, HRH1 mRNA and protein expression. Thus, indicating that HSP has a potent anti- MS effect by decreasing the elevated levels of histamine, HRH1 mRNA and protein expression in hypothalamus and brainstem regions.
Topics: Animals; Cell Line, Tumor; Female; Hesperidin; Histamine; Humans; Hypothalamus; Mice, Inbred BALB C; Motion Sickness; RNA, Messenger; Receptors, Histamine H1
PubMed: 31782104
DOI: 10.1007/s11064-019-02923-0 -
Indian Journal of Otolaryngology and... Nov 2019Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by...
Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by anti-vasoconstrictor activity, reducing blood viscosity and reducing nystagmus in labyrinth. Lack of adequate literature on clinical evidence of cinnarizine and its combination (dimenhydrinate) in vertigo management prompted this review. A specific MEDLINE literature search strategy was designed combining Medical Subject Headings, free-text keywords (like cinnarizine and vertigo) using Boolean operators (1970-2016) for clinical studies, clinical reviews and meta-analyses of cinnarizine. Analyses of studies validated cinnarizine's efficacy in peripheral and central vertigo versus placebo or other therapies, and was well-tolerated by the patients recruited across different studies. Cinnarizine and/ or its combinations are favorable in management of vestibular disorders wherein cinnarizine acts predominantly peripherally on labyrinth and dimenhydrinate acts centrally on vestibular nuclei and associated centers in brainstem. Combination therapy of cinnarizine and/ or its combinations demonstrated a better safety profile than either of the mono-components, offering a viable therapeutic option in vertigo management.
PubMed: 31750127
DOI: 10.1007/s12070-017-1120-7 -
BMC Cancer Nov 2019Chemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone... (Observational Study)
Observational Study
Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy - results of a non-interventional observation study.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone is used as antiemetic prophylaxis in pediatric patients undergoing emetogenic chemotherapy. However, dexamethasone is prohibited in different pediatric chemotherapy protocols. Currently, data on the use of ondansetron with the new antiemetic agent fosaprepitant without dexamethasone is not available for pediatric patients.
METHODS
In this non-interventional observation study, 79 pediatric patients with a median age of 8.0 years (range 0.5-17.9 years) who received a CINV prophylaxis regimen with either fosaprepitant (4 mg/kg; maximum 150 mg) and ondansetron (as 24-h continuous infusion) (n = 40; fosaprepitant group/FG) or ondansetron only (n = 39; control group/CG) during moderately or highly emetogenic chemotherapy were analyzed. The groups were analyzed and compared for frequency of vomiting, administered doses of on-demand antiemetic dimenhydrinate and adverse events during the acute (0-24 h after chemotherapy administration) and delayed (> 24 h-120 h) CINV phases.
RESULTS
A total of 112 and 116 chemotherapy blocks were analyzed in the fosaprepitant and the control group, respectively. The emetogenic potential of the administered chemotherapy did not significantly differ (p = 0.8812) between the two cohorts. In the acute CINV phase, the percentage of patients experiencing vomiting (n = 26 patients) and the vomiting events were significantly higher (p = 0.0005 and p < 0.0001, respectively) in the CG (n = 26 patients (66.7%); 88 events) compared with the FG (n = 10 patients (25.0%); 37 events). In the delayed CINV phase, the percentage of patients experiencing vomiting and the vomiting events were also significantly higher (p = 0.0017 and p < 0.0001, respectively) in the CG (n = 31 patients (79.5%); 164 events) compared with the FG (n = 17 patients (42.5%); 103 events). Additionally, significantly more dimenhydrinate doses were administered in the CG compared with the FG patients (n = 322/n = 198; p < 0.0001). The occurrence of adverse events did not significantly differ between the two groups (p > 0.05).
CONCLUSION
Fosaprepitant (4.0 mg/kg) in addition to ondansetron, without application of dexamethasone, was well tolerated, safe, effective and superior to ondansetron only as CINV prophylaxis in pediatric patients during moderately and highly emetogenic chemotherapy.
Topics: Adolescent; Antiemetics; Antineoplastic Agents; Case-Control Studies; Child; Child, Preschool; Feasibility Studies; Female; Humans; Infant; Male; Morpholines; Nausea; Neoplasms; Ondansetron; Patient Safety; Treatment Outcome; Vomiting
PubMed: 31730451
DOI: 10.1186/s12885-019-6252-6 -
Drug Design, Development and Therapy 2019Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic... (Observational Study)
Observational Study
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HTR-antagonists and NKR-antagonists. The NKR-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant.
METHODS
This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts.
RESULTS
Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%).
CONCLUSION
Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.
Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cohort Studies; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Morpholines; Nausea; Vomiting
PubMed: 31686784
DOI: 10.2147/DDDT.S214264 -
Clinical Drug Investigation Jan 2020
Topics: Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Humans; Prospective Studies; Vertigo
PubMed: 31679119
DOI: 10.1007/s40261-019-00872-8 -
Clinical Drug Investigation Jan 2020
Topics: Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Humans; Prospective Studies; Vertigo
PubMed: 31676932
DOI: 10.1007/s40261-019-00871-9 -
The Medical Letter on Drugs and... Oct 2019
Review
Topics: Acetazolamide; Altitude Sickness; Antiemetics; Carbonic Anhydrase Inhibitors; Central Nervous System Stimulants; Dexamethasone; Humans; Jet Lag Syndrome; Modafinil; Motion Sickness
PubMed: 31599874
DOI: No ID Found -
The Medical Letter on Drugs and... Oct 2019
Review
Topics: Animals; Antimalarials; Diarrhea; Humans; Insect Bites and Stings; Malaria; Travel; Travel-Related Illness
PubMed: 31599872
DOI: No ID Found