Objective : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC 50 radiation dose was determined. Dexamethasone dose (10 µM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTENmutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.
Objectives: As access to cancer care has improved throughout sub-Saharan Africa, treatment-associated infections have increased. Assessing healthcare worker knowledge of antimicrobial stewardship and identifying the barriers to infection management will inform the development of contextually appropriate antimicrobial stewardship programs, improving cancer outcomes in sub-Saharan Africa. Design: Cross-sectional survey. Setting: The Uganda Cancer Institute (UCI), a national cancer referral center in Kampala, Uganda. Participants: We surveyed 61 UCI staff: 29 nurses, 7 pharmacists, and 25 physicians. Methods: The survey contained 25 questions and 1 ranking exercise. We examined differences in responses by staff role. Results: All 60 respondents who answered the question had heard the term “antimicrobial resistance.” Only 44 (73%) had heard the term “antimicrobial stewardship.” Nurses were less likely than pharmacists or physicians to be familiar with either term. Also, 41 respondents (68%) felt that loss of antibiotic susceptibility is a major issue at UCI. Regarding barriers to diagnosing infections, 54 (93%) of 58 thought that it was difficult to obtain blood cultures and 48 (86%) of 56 thought that it was difficult to regularly measure temperatures. Conclusions: Although most recognized the term “antimicrobial resistance,” fewer were familiar with the term “antimicrobial stewardship.” Inappropriate antibiotic use was recognized as a contributor to antimicrobial resistance, but hand hygiene was underrecognized as a contributing factor. We identified numerous barriers to diagnosing infections, including the ability to obtain blood cultures and consistently monitor temperatures. Educating staff regarding antimicrobial selection, allocating resources for blood cultures, and implementing strategies to enhance fever detection will improve infection management.
Background As access to cancer treatment has increased in sub-Saharan Africa (sSA), infection-related complications are a growing concern. Little is known about infection management practices in this setting. Understanding the unique challenges to diagnosing and treating infections can inform the development of targeted strategies to improve infection management for cancer treatment programs throughout sSA. Methods We conducted a cross-sectional survey of doctors, nurses, and pharmacists at the Uganda Cancer Institute (UCI), a national cancer referral hospital in Kampala, Uganda. The 25-item survey was designed to assess staff knowledge of antimicrobial resistance and antimicrobial stewardship, investigate antibiotic decision-making practices, and identify barriers to diagnosing and treating infections. Results Of the 61 respondents, 25 (41%) were doctors, 7 (11%) were pharmacists, and 29 (48%) were nurses. In total, 98% (60/61) had heard of the term “antimicrobial resistance” and 84% (51/61) agreed that antimicrobial resistance is an important problem at UCI. Multiple factors were felt to contribute to antimicrobial resistance including the use of too many antibiotics, patient insistence on antibiotics, and poor patient adherence (Fig 1). While 72% (44/61) had heard of the term “antimicrobial stewardship”, only 25% (15/61) knew a lot about what it meant. Numerous factors were considered important to antibiotic decision-making including patient white blood cell count and severity of illness (Fig 2). Perceived barriers to infection diagnosis included the inability to obtain blood cultures and to regularly measure patient temperatures; perceived barriers to obtaining blood cultures included patient cost and availability of supplies (Fig 3). Figure 1. Factors that doctors, pharmacists, and nurses working at the Uganda Cancer Institute (UCI) perceive as contributing to antimicrobial resistance at the UCI. Percentages shown next to bars represent the combined total percentage of respondents reporting that the factor does not or usually does not contribute (left of bars, main chart), occasionally or frequently contributes (right of bars, main chart), or neither contributes nor does not contribute (right of neutral chart). Figure 2. Factors that doctors, pharmacists, and nurses working at the Uganda Cancer Institute consider to be important when choosing antibiotics to treat infections. Percentages shown next to bars represent the combined total percentage of respondents reporting that the factor is somewhat or very unimportant (left of bars, main chart), somewhat or very important (right of bars, main chart), or neither important nor unimportant (right of neutral chart). Figure 3. Factors that doctors, pharmacists, and nurses working at the Uganda Cancer Institute perceive as limiting the ability to diagnose infections and obtain blood cultures. Conclusion While most staff recognized the term “antimicrobial resistance” and identified this as a major local problem, fewer were familiar with the term “antimicrobial stewardship”. We identified numerous perceived barriers to infection diagnosis and treatment, including the ability to consistently measure temperatures and the cost of blood cultures. A multipronged approach is needed to improve staff knowledge of antimicrobial stewardship and to address the systematic barriers to infection management at UCI. Disclosures All Authors: No reported disclosures
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.