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The massive emergence of antimicrobial resistance in recent decades has rendered the use of a single-agent strategy ineffective. Consequently, the combination of different therapeutic agents has emerged as a promising new approach. The aim of the present study was to investigate the combined effect of Chlorella vulgaris methanol extract (CVME) and Origanum elongatum essential oil (OEEO) on methicillin-resistant Staphylococcus aureus (MRSA). Thus, the antibacterial activity of OEEO and CVME on Escherichia coli, Staphylococcus aureus, and MRSA was evaluated using the agar well diffusion and broth microdilution methods. The killing activity of CVME and OEEO, individually and in combination, on MRSA ATCC 43300 was tested using the time-kill assay. The synergistic effect was examined by determining the fractional inhibitory concentration index (FICI) using the checkerboard test. The results showed very significant antibacterial activity against all the bacteria tested, for both OEEO and CVME, with minimum inhibitory concentrations (MICs) ranging from 0.125 to 0.25% (v/v) for OEEO and from 3.12 to 6.25 mg mL-1 for CVME. Minimum bactericidal concentration (MBC) values for OEEO and CVME were in the range 0.125-0.5% (v/v) and 6.25-12.5 mg mL-1, respectively. The inhibition zones associated with OEEO were distinctly greater than those associated with CVME for all the bacteria examined. When used individually, the time-kill curves of OEEO and CVME revealed a dose-dependent effect on MRSA proliferation. Compared with controls, both agents were able to prolong the latent phase of growth curves and decelerate bacterial growth. The killing effect of OEEO on MRSA was considerably higher than that observed with CVME. OEEO prevented MRSA proliferation at only 1/2 of its MIC, while the CVME did so at 2 times its MIC. The combination of OEEO with CVME demonstrated a synergistic effect against MRSA, with a FIC index value of 0.49. The findings therefore suggest that the combination of C. vulgaris methanol extract and O. elongatum essential oil at very low doses may be promising anti-MRSA candidates. A search of the published literature revealed that, to our knowledge, no studies have yet been carried out on the antibacterial potential of combining essential oils and microalgae extracts in the fight against MRSA.
RESUMO
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.
RESUMO
INTRODUCTION: Glioblastoma and astrocytoma, grade 4, are the most common and aggressive brain tumors. Several biomarkers, such as the isocitrate dehydrogenase mutation (IDH-1), alpha-thalassemia/mental retardation, and the X-linked mutation (ATRX), enable more accurate glioma classification and facilitate patient management. This study aimed to determine the prognostic value of clinical and molecular factors (IDH, TP53, and ATRX mutations). We also studied the relationship between these molecular markers and the overall survival (OS) of 126 patients with grade 4 glioblastoma/astrocytoma. METHODS: The immunohistochemical study was conducted using antibodies namely, IDH1, R132H, p53, and ATRX. Statistical tests were used to investigate factors that might influence overall survival using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY). RESULTS: The median age at diagnosis was 51.5 years. Patients with a Karnofsky performance score (KPS) <70 presented less favorable survival outcomes compared to those with a KPS ≥70. The median OS for patients was found to be 11.17 months. Expression of IDH1 R132H was found in 13.5% of patients, p53 overexpression was identified in 55.6% of cases, and loss of ATRX expression was detected in 11.9%. The group of patients with IDH mutant/ATRX mutant/p53 wild-type had the best prognosis (OS = 27.393 months; p = 0.015). Our results were in line with previous studies. CONCLUSION: The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.