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Biomedicine & Pharmacotherapy =... Apr 2022Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Esomeprazole (ESO) has been shown to have anticancer...
Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Esomeprazole (ESO) has been shown to have anticancer activity by affecting cell growth and autophagy and its mechanism in gastric cancer cells is evident. The PI3K/AKT/FOXO3a pathway is central in cancers. 3-Methyladenine (3-MA), a dual inhibitor of PI3K and autophagy, plays a synergistic role in combination with antitumor agents. In this study, we assessed the role of ESO on the PI3K/AKT/FOXO3a pathway and the beneficial effects of ESO combined with 3-MA in gastric cancer cells. Cell viability, proliferation, invasion, migration, apoptosis, autophagy, and protein expression were detected by CCK-8, EdU, Transwell, flow cytometry, immunofluorescence assay, and western blot. ESO decreased cell viability in a concentration- and time-dependent manner and increased autophagy with upregulation of LC3II and P62. Additionally, ESO inhibited the proliferation, migration, and invasion and induced the apoptosis of gastric cancer cells in a concentration-dependent manner. ESO inhibited PI3K/AKT/FOXO3a signaling and EGFR and SKP2 expression concentration-dependent. 3-MA enhanced the antiproliferative activity of ESO and synergistically inhibited PI3K/FOXO3a signaling and the expression of EGFR but not SKP2. Furthermore, pretreatment with the EGFR inhibitor AG1478 enhanced the antiproliferative activity of ESO in gastric cancer cells. In conclusion, our results suggested that the PI3K inhibitor 3-MA promotes the antiproliferative activity of ESO in gastric cancer cells by synergistically downregulating EGFR via the PI3K/FOXO3a pathway.
Topics: Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; ErbB Receptors; Esomeprazole; Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Stomach Neoplasms
PubMed: 35228068
DOI: 10.1016/j.biopha.2022.112665 -
Journal of Enzyme Inhibition and... Dec 2022Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the...
Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this compound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cell Survival; Docetaxel; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esomeprazole; Molecular Structure; NF-kappa B; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 34986722
DOI: 10.1080/14756366.2021.2018684 -
Pediatric Rheumatology Online Journal Jun 2018Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO).
METHODS
Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly.
RESULTS
Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect.
CONCLUSION
NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT01544114 . Registered February 21, 2012.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child; Drug Therapy, Combination; Esomeprazole; Female; Follow-Up Studies; Humans; Male; Naproxen; Prospective Studies; Proton Pump Inhibitors; Treatment Outcome; United States
PubMed: 29941047
DOI: 10.1186/s12969-018-0260-y -
Scientific Reports Sep 2020Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI)... (Clinical Trial)
Clinical Trial
Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.
Topics: Adult; Aged; Biomarkers; Cytokines; Esomeprazole; Esophageal Mucosa; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Microbiome; Humans; Inflammation Mediators; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors
PubMed: 32938975
DOI: 10.1038/s41598-020-72082-8 -
Chinese Medical Journal Apr 2015Helicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Helicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.
METHODS
Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.
RESULTS
There were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).
CONCLUSIONS
Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.
Topics: Adolescent; Adult; Aged; Amoxicillin; Esomeprazole; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Tinidazole; Young Adult
PubMed: 25881589
DOI: 10.4103/0366-6999.155049 -
PloS One 2020Naproxen is a widely used non-steroidal anti-inflammatory drug for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with...
Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography-tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazole.
Naproxen is a widely used non-steroidal anti-inflammatory drug for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with esomeprazole has been widely studied and has yielded good results for the control of acute pain, even with the delayed absorption of naproxen owing to the presence of esomeprazole. To further understand the absorption, distribution, and metabolism of this drug alone and in combination with esomeprazole, we will analyze the pharmacokinetic parameters of naproxen and its major metabolite, 6-O-desmethylnaproxen, in saliva samples. A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometric method for the simultaneous determination of naproxen and 6-O-desmethylnaproxen in saliva will be developed and validated. Sequential saliva samples from six patients will be analyzed before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72, and 96 h after the ingestion of one naproxen tablet (500 mg) and esomeprazole-associated naproxen tablets (500 + 20 mg), at two different times. After liquid-liquid extraction with ethyl acetate and HCl, the samples will be analyzed using an 8040 Triple Quadrupole Mass Spectrometer (Shimadzu, Kyoto, Japan). Separation of naproxen and its major metabolic products will be performed using a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column (Shimadzu, Kyoto, Japan) at 40°C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v) with an injection flow of 0.3 mL/min. The total analytical run time will be 5 min. The detection and quantification of naproxen and its metabolite will be validated, which elucidate the pharmacokinetics of this drug, thereby contributing to its proper prescription for the medical and dental interventions that cause acute pain.
Topics: Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Combinations; Drug Monitoring; Esomeprazole; Female; Gastrointestinal Absorption; Humans; Male; Methanol; Middle Aged; Naproxen; Pain, Procedural; Reproducibility of Results; Saliva; Tablets; Tandem Mass Spectrometry; Young Adult
PubMed: 32780750
DOI: 10.1371/journal.pone.0236297 -
BMJ Open Nov 2020This study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review...
OBJECTIVES
This study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review of electronic medical records in a single-centred hospital.
DESIGN
All patients admitted to the outpatient department of Jinshan Hospital, Fudan University, Shanghai, between 1 January 2018 and 31 December 2018 were evaluated. Individuals aged 18 years or above and with at least one dispensing for PPIs were identified as PPI users. New PPI users were defined as a subject who did not receive any dispensing for PPIs in the year prior to the index date. Baseline characteristics of PPI users and their therapies were described by treatment indication, economic indicators and co-prescription, overall and separately.
SETTING
The prescription database was retrieved from the hospital information system of Jinshan Hospital, Fudan University.
RESULTS
Among 18 435 identified PPI users in 2018, 14 219 patients (aged 18 years or above) who had at least one dispensing PPIs were new users (77%), and among them, men accounted for 47%. The mean treatment duration was 23 days. Omeprazole was the most commonly prescribed drug. PPIs are inappropriately prescribed in 50% (13 589/25 850) of prescriptions. Prescription appropriateness analysis indicated that the unapproved indications for PPI new users accounted for 47%; among them, the proportion of gastritis diagnosis was 34%. The proportion of PPI new users with co-prescription of glucocorticosteroids (GCs) who have risk factors accounted for 24% and lower than other co-prescription. A majority of PPI users (73%) reported high-dose PPI prescription. The defined daily dose of oral pantoprazole was the highest, and injectable omeprazole had the highest defined daily cost. In contrast, only the drug utilisation index value of oral esomeprazole was less than 1.0.
CONCLUSION
The results indicate the challenge of PPI use was accompanied by unapproved indications, frequent inappropriate co-prescription with GCs and excessive dosages. Efforts should be paid to promote rational use and ensure the choice of suitable PPI therapy in the future.
Topics: Adolescent; Adult; Aged; China; Esomeprazole; Female; Humans; Inappropriate Prescribing; Male; Middle Aged; Practice Patterns, Physicians'; Proton Pump Inhibitors; Retrospective Studies; Young Adult
PubMed: 33243802
DOI: 10.1136/bmjopen-2020-040473 -
World Journal of Gastroenterology May 2013To analyze risk factors for refractoriness to proton pump inhibitors (PPIs) in patients with non-erosive reflux disease (NERD).
AIM
To analyze risk factors for refractoriness to proton pump inhibitors (PPIs) in patients with non-erosive reflux disease (NERD).
METHODS
A total of 256 NERD patients treated with the PPI esomeprazole were enrolled. They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia (QolRad) scale. All subjects completed questionnaires on psychological status (self-rating anxiety scale; self-rating depression scale) and quality of life scale (Short Form 36). Multivariate analysis was used to determine the predictive factors for PPI responses.
RESULTS
According to QolRad, 97 patients were confirmed to have residual reflux symptoms, and the remaining 159 patients were considered symptom free. There were no significant differences between the two groups in lifestyle factors (smoking and alcohol consumption), age, Helicobacter pylori infection, and hiatal hernia. There were significant differences between the two groups in relation to sex, psychological distress including anxiety and depression, body mass index (BMI), and irritable bowel syndrome (IBS) (P < 0.05). Logistic regression analysis found that BMI < 23, comorbid IBS, anxiety, and depression were major risk factors for PPI resistance. Symptomatic patients had a lower quality of life compared with symptom-free patients.
CONCLUSION
Some NERD patients are refractory to PPIs and have lower quality of life. Residual symptoms are associated with psychological distress, intestinal disorders, and low BMI.
Topics: Aged; Anxiety; Asian People; Body Mass Index; China; Comorbidity; Depression; Drug Resistance; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Irritable Bowel Syndrome; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Proton Pump Inhibitors; Quality of Life; Risk Factors; Sex Factors; Surveys and Questionnaires
PubMed: 23716993
DOI: 10.3748/wjg.v19.i20.3124 -
Alimentary Pharmacology & Therapeutics Feb 2001Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Omeprazole and lansoprazole are used to treat erosive oesophagitis in the respective daily doses of 20 and 30 mg.
AIM
To investigate, by meta-analysis, whether treatment with lansoprazole 30 mg increases erosive oesophagitis healing rates over omeprazole 20 mg.
METHODS
We searched for randomized, double-blind trials comparing omeprazole 20 mg and lansoprazole 30 mg in endoscopically diagnosed erosive oesophagitis. After assessing for homogeneity, non-heterogeneous trials were combined and pooled healing rates derived. We calculated the relative benefit increase, absolute benefit increase and number needed to treat.
RESULTS
Six trials without significant heterogeneity met predetermined inclusion criteria. By per protocol analysis, pooled healing rates for omeprazole 20 mg and lansoprazole 30 mg were, respectively, 74.7% and 77.7% after 4 weeks and 87.0% and 88.7% after 8 weeks. The corresponding figures by intention-to-treat analysis were 70.8% and 72.7% after 4 weeks and 81.8% and 83.3% after 8 weeks. In each analysis the absolute benefit increase for lansoprazole was small and its 95% confidence interval encompassed zero.
CONCLUSION
Lansoprazole 30 mg produces healing rates in erosive oesophagitis that are not statistically significantly different to those of omeprazole 20 mg.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Esophagitis; Humans; Lansoprazole; Omeprazole; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 11148442
DOI: 10.1046/j.1365-2036.2001.00904.x -
JPMA. the Journal of the Pakistan... Mar 2024To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection. (Randomized Controlled Trial)
Randomized Controlled Trial
Therapeutic efficacy and drug safety comparison of one-week Vonoprazan triple therapy with two-weeks Esomeprazole triple therapy in Helicobacter pylori infection: Findings from a single-centre randomized clinical trial in population of Pakistan.
OBJECTIVE
To compare the therapeutic efficacy and drug safety of Vonoprazan and Esomeprazole triple therapies in Helicobacter pylori infection.
METHODS
The randomised clinical trial was conducted from December 2022 to January 2023 at the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Gastroenterology Department of Pak Emirates Military Hospital, Rawalpindi, and comprised patients found positive for Helicobacter pylori by stool antigen test. They were randomly distributed into two groups. The EAL group received twoweek triple therapy with Esomeprazole 20mgand Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. The VAL group was prescribed one-week triple therapy with Vonoprazan 20mg and Amoxicillin 1000mg twice daily with Levofloxacin 500mg once daily. Eradication success was evaluated by stool antigen test 4 weeks after starting the treatment. Safety of the therapy was assessed by noting adverse effects at days 3 and 14 of the treatment. Data was analysed using SPSS 27.
RESULTS
Of the 122 patients, there were 61(50%) in each of the 2 groups; 30(49.2%) males and 31(50.8%) females with mean age 38.40±12.25 years in group EAL, and 35(57.4%) males and 26(42.6%) females with mean age 40.98±12.13 years in VAL group. In the EAL group, 57(93.4%) patients were found to be free of Helicobacter pylori infection compared to 58(95%) in the VAL group. Nausea 14(23%), bitter taste 41(67.2%), abdominal pain 16(26.2%) and headache 20(32.8%) were the adverse effects that were significantly more common in the EAL group compared to the VAL group B.
CONCLUSIONS
Vonoprazan-based triple therapy was found to be more effective with less reported adverse effects and potential benefits of better patient compliance due to shorter therapy duration.
CLINICAL TRIAL NUMBER
Iranian Registry of Clinical Trials: IRCT20221207056738N1.
Topics: Male; Female; Humans; Adult; Middle Aged; Helicobacter Infections; Esomeprazole; Levofloxacin; Anti-Bacterial Agents; Helicobacter pylori; Pakistan; Iran; Amoxicillin; Drug Therapy, Combination; Treatment Outcome; Clarithromycin; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 38591272
DOI: 10.47391/JPMA.9545