Publications by authors named "C Noreen Hinrichs"
Mutations in the exonuclease domains of the replicative nuclear DNA polymerases POLD1 and POLE are associated with increased cancer incidence, elevated tumor mutation burden (TMB), and enhanced response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond, highlighting the need for a better understanding of how TMB affects tumor biology and subsequently immunotherapy response. To address this, we generated mice with germline and conditional mutations in the exonuclease domains of Pold1 and Pole.
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- Hypernatremia is a common and serious condition in ICU patients, linked to higher mortality and longer stays, prompting this study to compare sodium chloride 0.9% and glucose 5% solutions as intravenous drug diluents.
- The study analyzed 265 adult COVID-19 patients, observing sodium levels and severe hypernatremia over the first 8 days after ICU admission, finding that glucose 5% led to lower sodium levels and reduced occurrences of severe hypernatremia.
- The results suggest that switching to glucose 5% as the standard diluent can help prevent hypernatremia in ICU patients, indicating a potentially simple change in treatment protocols.
Background: Adoptive T-cell therapy has demonstrated clinical activity in B-cell malignancies, offering hope for its application to a broad spectrum of cancers. However, a significant portion of patients with solid tumors experience primary or secondary resistance to this treatment modality. Target antigen loss resulting either from non-uniform antigen expression or defects in antigen processing and presentation machinery is one well-characterized resistance mechanism.
View Article and Find Full Text PDFThe E6 and E7 oncoproteins of human papillomavirus (HPV) are considered promising targets for HPV-related cancers. In this study, we evaluated novel T cell receptor mimic (TCRm) nanobodies targeting the E6 peptide complexed with human leukocyte antigen (HLA)-A∗02:01 in the chimeric antigen receptor (CAR) format. We isolated two dromedary camel nanobodies, F5 and G9, through phage display screening.
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- CAR T cells are genetically engineered T lymphocytes designed to target and kill tumor cells, showing improved survival rates in patients with large B-cell lymphoma and multiple myeloma.
- Six CAR T-cell therapies are FDA-approved for various blood cancers, demonstrating better outcomes compared to traditional chemotherapy, particularly in large B-cell lymphoma and pediatric acute lymphoblastic leukemia.
- Despite high efficacy, CAR T-cell therapy can cause significant side effects, including cytokine release syndrome and neurologic issues; ongoing research aims to enhance effectiveness and reduce risks, with some progress in treating solid tumors.