Publications by authors named "B G Neel"
Background And Objectives: Three phase 3 trials demonstrated the efficacy and safety of atogepant in episodic migraine (EM) and chronic migraine (CM) across 12-week treatment periods. This analysis evaluates improvements in efficacy and functional outcomes in the first 4 weeks of treatment with the oral calcitonin gene-related peptide receptor antagonist, atogepant, for the preventive treatment of migraine.
Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo-controlled 12-week trials.
Article Synopsis
- Hypoxic cancer cells often resist treatments and can lead to cancer recurrence, with PTP1B deficiency promoting breast cancer cell death under low oxygen conditions via RNF213 activation.
- PTP1B and ABL1/2 interact to regulate RNF213 phosphorylation, promoting its role in degrading CYLD/SPATA2, which in turn activates NF-κB and the NLRP3 inflammasome, culminating in pyroptotic cell death.
- The findings reveal a novel PTP1B-RNF213-CYLD-SPATA2 pathway that plays a critical role in inflammatory cell death in hypoxic tumors, with broader implications for diseases like Moyamoya, inflammation, and autoimmune disorders.
The interaction between tumors and their microenvironment is complex and heterogeneous. Recent developments in high-dimensional multiplexed imaging have revealed the spatial organization of tumor tissues at the molecular level. However, the discovery and thorough characterization of the tumor microenvironment (TME) remains challenging due to the scale and complexity of the images.
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- Atogepant is an oral medication designed to prevent chronic migraines and was tested in a study involving participants with and without medication overuse.
- The study involved 755 adults and assessed the impact of two dosages of atogepant compared to a placebo over 12 weeks, measuring changes in headache and migraine days.
- Results showed significant reductions in migraine and headache days, along with reduced medication use, particularly in participants treated with atogepant, highlighting its effectiveness in managing chronic migraines.
Molecular basis for antibody recognition of multiple drug-peptide/MHC complexes.
Proc Natl Acad Sci U S A
May 2024
The HapImmune platform exploits covalent inhibitors as haptens for creating major histocompatibility complex (MHC)-presented tumor-specific neoantigens by design, combining targeted therapies with immunotherapy for the treatment of drug-resistant cancers. A HapImmune antibody, R023, recognizes multiple sotorasib-conjugated KRAS(G12C) peptides presented by different human leukocyte antigens (HLAs). This high specificity to sotorasib, coupled with broad HLA-binding capability, enables such antibodies, when reformatted as T cell engagers, to potently and selectively kill sotorasib-resistant KRAS(G12C) cancer cells expressing different HLAs upon sotorasib treatment.
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