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Pharmacological Research Jun 2024Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6... (Review)
Review
Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.
Topics: Humans; Low Density Lipoprotein Receptor-Related Protein-6; Neoplasms; Animals; Antineoplastic Agents; Molecular Targeted Therapy; Wnt Signaling Pathway
PubMed: 38710241
DOI: 10.1016/j.phrs.2024.107200 -
Frontiers in Endocrinology 2024The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea... (Clinical Trial)
Clinical Trial
The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.
OBJECTIVE
The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy.
METHOD
We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases.
RESULTS
A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders.
CONCLUSIONS
In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.
Topics: Humans; Male; Female; Middle Aged; Antiemetics; Adult; Iodine Radioisotopes; Aged; Vomiting; Nausea; Young Adult; Adolescent; Thyroid Neoplasms; Ondansetron; Quality of Life
PubMed: 38706697
DOI: 10.3389/fendo.2024.1310223 -
BMC Medical Research Methodology May 2024During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies.
OBJECTIVE
To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring.
METHODS
REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022.
RESULTS
The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted.
CONCLUSION
Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.
Topics: Humans; COVID-19; Pantoprazole; SARS-CoV-2; Intensive Care Units; Pandemics; Female; Respiration, Artificial; Male; Clinical Protocols; Middle Aged; Gastrointestinal Hemorrhage; Anti-Ulcer Agents
PubMed: 38704520
DOI: 10.1186/s12874-024-02233-2 -
Gut Microbes 2024Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by...
Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing (ESBL-). The combination of inulin and pantoprazole (IP) significantly reduced ESBL- fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with or also reduced ESBL- fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant . The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.
Topics: Animals; Inulin; Mice; Gastrointestinal Microbiome; Escherichia coli; Feces; Amoxicillin; Pantoprazole; Drug Resistance, Multiple, Bacterial; beta-Lactamases; Dysbiosis; Anti-Bacterial Agents; Escherichia coli Infections; Female; Prebiotics
PubMed: 38685762
DOI: 10.1080/19490976.2024.2347021 -
Antibiotics (Basel, Switzerland) Apr 2024Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for () eradication. We compared...
Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for () eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 Pylera capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age ( = 0.27) and sex ( = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT ( = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively ( = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety.
PubMed: 38667024
DOI: 10.3390/antibiotics13040348 -
The Korean Journal of Gastroenterology... Apr 2024() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIMS
() is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for eradication. We aimed to compare the efficacy of two different regimens as first-line eradication regimens, in an area with high antibiotic resistance.
METHODS
In this RCT, we assigned 223 patients with infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). eradication was assessed eight weeks after the end of treatment.
RESULTS
eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001).
CONCLUSIONS
Twelve-day concomitant therapy seems to be an acceptable regimen for first-line eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Metronidazole; Pantoprazole; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38659251
DOI: 10.4166/kjg.2024.012 -
Inflammopharmacology Jun 2024Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the...
Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.
Topics: Animals; Oxidative Stress; Stomach Ulcer; Rats; Apoptosis; Pantoprazole; Inflammation; Mesenchymal Stem Cells; Male; Mesenchymal Stem Cell Transplantation; Rats, Wistar; Anti-Ulcer Agents; Adipose Tissue; Combined Modality Therapy
PubMed: 38652367
DOI: 10.1007/s10787-024-01469-0 -
Acta Medica Portuguesa Apr 2024
Topics: Humans; Pantoprazole; Diabetic Ketoacidosis; Chemical and Drug Induced Liver Injury, Chronic; Proton Pump Inhibitors; Diabetes Mellitus
PubMed: 38631049
DOI: 10.20344/amp.20928 -
Journal of Clinical Medicine Mar 2024Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently,... (Review)
Review
Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.
PubMed: 38610738
DOI: 10.3390/jcm13071970 -
F1000Research 2023Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the...
Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. The assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. : In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.
Topics: Pantoprazole; Drug Liberation; Excipients; Solubility; Tablets; Stomach
PubMed: 38596002
DOI: 10.12688/f1000research.140607.1