The latest medical research on Oncology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about oncology gathered by our medical AI research bot.
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In Vivo Functional Characterization of EGFR Variants Identifies Novel Drivers of Glioblastoma.Neuro-Oncology
Glioblastoma is the most common and aggressive primary brain tumor. Large scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.
We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased lipidomics screen.
Our screen identified A289I as the most potent EGFR variant, which has previously not been characterized. One of the mechanisms through with A289I promotes gliomagenesis is to alter cellular triacylglycerides through MTTP. Knockout of Mttp in mouse gliomas, reduces gliomagenesis in multiple models.
EGFR variants that differ by a single amino acid residue differentially promote gliomagenesis. Among the identified mechanism that drive glioma growth include lipid metabolism through MTTP. Understanding triacylglyceride accumulation may present a prospective therapeutic pathway for this deadly disease.
Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection.Antimicrobial Agents and Chemotherapy
Accumulating evidence suggests that drug repurposing has drawn attention as an anticipative strategy for controlling tuberculosis (TB), considering...
Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria among Children in Western Kenya, 2016 to 2017.Antimicrobial Agents and Chemotherapy
Antimalarial resistance threatens global malaria control efforts. The World Health Organization (WHO) recommends routine antimalarial efficacy moni...
Population Pharmacokinetic Meta-Analysis and Dosing Recommendation for Meropenem in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.Antimicrobial Agents and Chemotherapy
The optimal dosing regimen for meropenem in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains undefined due to...
Protontherapy for adult craniopharyngioma: experience of a single institution in 91 consecutive patients.Neuro-Oncology
Craniopharyngioma (CP) in adults is a rare benign tumor associated with many morbidities, with limited contemporary studies to define treatment, and follow-up guidelines.
A single-center retrospective study was conducted on patients aged ≥18-years from 2006-2018 with CP and who were treated with proton therapy (PT). Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS), local recurrence-free survival (LRFS), and toxicity were characterized using Kaplan-Meier and Cox regression analyses.
Ninety-one patients met the criteria, with a median age of 37-years (range 18-82y). PT was conducted after tumor resection in 88 patients (97%), in 64 patients (70.3%) as an adjuvant strategy and 27 (29.7%) after recurrent disease. Three patients received exclusive PT. A median MRI follow-up of 39 months revealed 35.2% complete response, 49.5% partial response, and 9.9% stable disease. Five patients developed local recurrence (LR). Pattern of failure study showed that these five LR were within the GTV volume. The 5-year LRFS was 92.0% [CI95%:84.90-99.60]. All the patients were alive at the end of the follow-up. Patients requiring treatment adaptation during PT tend to have a higher risk of LR (p=0.084). Endocrinopathy was the most frequent grade≥2 late toxicity. Among patients who were symptom-free before the start of treatment, none developed hearing toxicity but four (9.8%) developed visual disorders and 10 (11.3%) symptomatic memory impairment. Patients with large tumors had a higher risk of developing symptomatic memory impairment (p=0.029).
Adults with CP treated with PT have favorable survival outcomes, with acceptable late toxicity. Prospective quality-of-life and neurocognitive studies are needed to define late adverse effects better.
Oncofetal reprogramming in tumour development and progression.Nature Reviews Cancer
Embryonic development is characterized by rapidly dividing cells, cellular plasticity and a highly vascular microenvironment. These features are si...
National-level overall survival patterns for molecularly-defined diffuse glioma types in the United States.Neuro-Oncology
Molecularly-defined diffuse glioma types - including IDH-wildtype glioblastoma, IDH-mutant astrocytoma, IDH-mutant 1p/19q-codeleted oligodendroglioma, and H3 K27M-mutant diffuse midline glioma - were incorporated into U.S. cancer registry reporting for individuals with brain tumors beginning in 2018. We leveraged these new data to estimate the national-level overall survival (OS) patterns associated with glioma integrated diagnoses.
Individuals diagnosed with diffuse gliomas in 2018 and had brain molecular marker data were identified within the U.S. National Cancer Database. OS was estimated using Kaplan Meier methods and stratified by WHO CNS grade, age, sex, tumor size, treatment, extent of resection, and MGMT promoter methylation. Additionally, the effects of WHO CNS grade were examined among individuals with IDH-wildtype astrocytic gliomas.
8,651 individuals were identified. One-year OS was 53.7% for WHO grade 4 IDH-wildtype glioblastomas; 98.0%, 92.4%, and 76.3% for WHO grade 2, 3, and 4 IDH-mutant astrocytomas, respectively; 97.9% and 94.4% for WHO grade 2 and 3 IDH-mutant 1p/19q-codeleted oligodendrogliomas, respectively; and 55.9% for H3 K27M-mutant diffuse midline gliomas. Among IDH-wildtype glioblastomas, median OS was 17.1 months and 12.4 months for methylated and unmethylated MGMT promoters. Additionally, IDH-wildtype diffuse astrocytic gliomas reported as WHO grade 2 or 3 demonstrated longer OS compared to grade 4 tumors (both p<0.001).
Our findings provide the initial national OS estimates for molecularly-defined diffuse gliomas in the U.S. and illustrate the importance of incorporating such data into cancer registry reporting.
Mastering the use of cellular barcoding to explore cancer heterogeneity.Nature Reviews Cancer
Tumours are often composed of a multitude of malignant clones that are genomically unique, and only a few of them may have the ability to escape ca...
Repurposing the Ionophore, PBT2, for Treatment of Multidrug-Resistant Neisseria gonorrhoeae Infections.Antimicrobial Agents and Chemotherapy
Multidrug-resistant (MDR) N. gonorrhoeae is a current public health threat. New therapies are urgently needed. PBT2 is an ionophore that disrupts m...
Translational Significance of CDKN2A/B Homozygous Deletion in IDH-Mutant Astrocytoma.Neuro-Oncology
Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower g...
Docetaxel Targets Aggressive Methylation Profiles and Serves as a Radiosensitizer in High-Risk Meningiomas.Neuro-Oncology
Meningioma is the most common primary intracranial tumor in adults. A subset of these tumors recur and invade the brain, even after surgery and radiation, resulting in significant disability. There is currently no standard-of-care chemotherapy for meningiomas. As genomic DNA methylation profiling can prognostically stratify these lesions, we sought to determine whether any existing chemotherapies might be effective against meningiomas with high-risk methylation profiles.
A previously published dataset of meningioma methylation profiles was used to screen for clinically significant CpG methylation events and associated cellular pathways. Based on these results, patient-derived meningioma cell lines were used to test candidate drugs in vitro and in vivo, including efficacy in conjunction with radiotherapy.
We identified 981 genes for which methylation of mapped CpG sites was related to progression-free survival in meningiomas. Associated molecular pathways were cross-referenced with FDA-approved cancer drugs, which nominated Docetaxel as a promising candidate for further preclinical analyses. Docetaxel arrested growth in 17 meningioma cell sources, representing all tumor grades, with a clinically-favorable IC50 values ranging from 0.3 nM to 10.7 mM. The inhibitory effects of this medication scaled with tumor doubling time, with maximal benefit in fast-growing lesions. The combination of Docetaxel and radiation therapy increased markers of apoptosis and double-stranded DNA breaks, and extended the survival of mice engrafted with meningioma cells relative to either modality alone.
Global patterns of DNA methylation may be informative for the selection of chemotherapies against meningiomas, and existing drugs may enhance radiation sensitivity in high-risk cases.
Hepatosplenic T Cell Lymphoma: Diagnostic Conundrum.International Journal of Epidemiology
Hepatosplenic T cell lymphoma (HSTCL) is a very rare and aggressive peripheral T cell lymphoma that comprises less than 1% of Non-Hodgkin lymphomas...