ABSTRACT
PURPOSE: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment. METHODS: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature. RESULTS: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection. CONCLUSION: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes.
Subject(s)
Brain Neoplasms , Glioblastoma , Protein Kinase Inhibitors , Receptors, Vascular Endothelial Growth Factor , Humans , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Receptors, Vascular Endothelial Growth Factor/metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacologyABSTRACT
Osteosarcoma (OS) is an aggressive primary bone malignancy that metastasizes rapidly. The standard of care has changed little over the previous four decades, and survival rates have plateaued. In this context, tyrosine kinase inhibitors (TKIs) emerge as potential treatments. A literature search was conducted to collect data related to receptor tyrosine kinase genetic alterations and expression in OS specimens. Gene amplification and protein expression of these receptors were linked to prognosis and tumor behavior. Relevant TKIs were evaluated as monotherapies and as parts of combination therapies. Certain TKIs, such as apatinib, regorafenib, and cabozantinib, present a potential therapeutic avenue for OS patients, especially when combined with chemotherapy. Producing long-lasting responses and enhancing quality of life remain key goals in OS treatment. To this effect, optimizing the use of TKIs by identifying biomarkers predictive of response and assessing promising TKIs in larger-scale trials to validate the efficacy and safety outcomes relative to these drugs reported in phase II clinical trials. To this effect, it is necessary to identify biomarkers predictive of response to TKIs in larger-scale trials and to validate the efficacy and safety of these drugs reported in phase II clinical trials.
ABSTRACT
A 5-year-old girl who presented with two episodes of meningitis, had a patchy red area and a small skin dimple in the midline of the occiput on physical examination. Imaging revealed a well-demarcated oval intradural lesion of the posterior fossa with restricted diffusion and peripheral enhancement, raising the possibility of an abscess. The 3D volume rendering of CT images of the inner surface of bone showed chronic bone remodeling and a tiny bone defect of the outer table. This detailed anatomical evaluation has an added value to MRI characteristics to orient for a preoperative diagnosis of an intradural dermoid cyst with a dermal sinus, that was confirmed by histopathological analysis after surgical excision.
ABSTRACT
Over 70 million individuals are infected with hepatitis C virus (HCV) worldwide. Yet most prevalence data are in the adult population, with little focus on paediatrics, partially due to the scarcity of public data. The objective of this paper is to examine HCV prevalence in children by estimating prevalence rates among women, given the assumption that most cases are vertically transmitted. Between 2001 and 2017, maternal HCV infection affected ~ 0.24% of all births, with prevalence increasing by at least 261%. On average, approximately 0.01% of the total number of live births were infected with HCV, with a 245% increase in the number of children born with the infection. HCV epidemiology has evolved, with women of childbearing age representing a greater proportion of infected individuals in the United States, and infants born to infected mothers being at risk. We therefore recommend a greater public health focus of HCV on the paediatric population.
Subject(s)
Hepatitis C , Pediatrics , Adult , Child , Female , Hepacivirus , Hepatitis C/epidemiology , Humans , Infant , Prevalence , United States/epidemiologyABSTRACT
Gyrase is a type II DNA topoisomerase that introduces negative supercoils into DNA in an ATP-dependent reaction. It consists of a topoisomerase core, formed by the N-terminal domains of the two GyrA subunits and by the two GyrB subunits, that catalyzes double-stranded DNA cleavage and passage of a second double-stranded DNA through the gap in the first. The C-terminal domains (CTDs) of the GyrA subunits form a ß-pinwheel and bind DNA around their positively charged perimeter. As a result, DNA is bound as a positive supercoil that is converted into a negative supercoil by strand passage. The CTDs contain a conserved 7-amino acid motif that connects blades 1 and 6 of the ß-pinwheel and is a hallmark feature of gyrases. Deletion of this so-called GyrA-box abrogates DNA bending by the CTDs and DNA-induced narrowing of the N-gate, affects T-segment presentation, reduces the coupling of DNA binding to ATP hydrolysis, and leads to supercoiling deficiency. Recently, a severe loss of supercoiling activity of Escherichia coli gyrase upon deletion of the non-conserved acidic C-terminal tail (C-tail) of the CTDs has been reported. We show here that, in contrast to E. coli gyrase, the C-tail is a very moderate negative regulator of Bacillus subtilis gyrase activity. The C-tail reduces the degree of DNA bending by the CTDs but has no effect on DNA-induced conformational changes of gyrase that precede strand passage and reduces DNA-stimulated ATPase and DNA supercoiling activities only 2-fold. Our results are in agreement with species-specific, differential regulatory effects of the C-tail in gyrases from different organisms.
Subject(s)
Bacillus subtilis/enzymology , Bacterial Proteins/metabolism , DNA Gyrase/metabolism , DNA, Superhelical/metabolism , Adenosine Triphosphate/metabolism , Amino Acid Motifs/genetics , Bacillus subtilis/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Binding Sites/genetics , DNA Gyrase/chemistry , DNA Gyrase/genetics , DNA, Superhelical/chemistry , DNA, Superhelical/genetics , Escherichia coli/enzymology , Escherichia coli/genetics , Fluorescence Polarization , Fluorescence Resonance Energy Transfer , Hydrolysis , Models, Molecular , Mutation , Protein Binding , Protein Structure, Tertiary , Protein Subunits/chemistry , Protein Subunits/genetics , Protein Subunits/metabolism , Species SpecificityABSTRACT
Linezolid is an important agent for the treatment of infections because of vancomycin-resistant Enterococcus (VRE). This study identified independent predictors for isolation of linezolid-resistant VRE (LZD-R-VRE) and analyzed outcomes associated with linezolid resistance. Immunosuppression, prior surgery, and previous exposure to ß-lactam antibiotics were independent predictors for isolation of LZD-R-VRE but not for LZD-susceptible-VRE. Prior exposure to linezolid was not a predictor for isolation of LZD-R-VRE.
