Publications by authors named "Zachary Knotts"
IRES mediated translation initiation requires a different repertoire of factors than canonical cap-dependent translation. Treatments that inhibit the canonical translation factor EIF4G1 have little or no effect on the ability of the Insr and Igf1r cellular IRESes to promote translation. Transcripts for two cellular receptors contain RNA elements that facilitate translation initiation without intact EIF4G1.
View Article and Find Full Text PDFArticle Synopsis
- Solid tumors trigger an immune response, but this response often aids tumor growth instead of fighting it, mainly due to the presence of tumor-associated macrophages (TAMs).
- RP-182 is a synthetic compound that targets the mannose receptor on M2-like macrophages, reprogramming them from supporting tumors to an antitumor M1-like phenotype, which boosts immune activity.
- In various murine cancer models, RP-182 showed success in slowing tumor growth and enhancing survival, especially when used alongside traditional therapies, while also increasing the phagocytosis of cancer cells by the reprogrammed TAMs.
Article Synopsis
- Synthetic host defense peptides (HDP), like RP-182, are being developed as promising treatments to enhance anti-tumor immunity by targeting specific macrophages in tumors.
- A new sensitive method using liquid chromatography and mass spectrometry was created to measure RP-182 in complex biological samples, specifically mouse plasma and tissue homogenates.
- The method showed good accuracy and precision in detecting low concentrations of RP-182, and it was also applicable to other HDPs, indicating its potential for broader use in research.
Article Synopsis
- Metarrestin is a new small molecule that targets the perinucleolar compartment, specifically designed for treating metastatic cancer cells, and this study assesses its pharmacokinetic properties and how it affects cancer-related biological markers.
- The study involved administering different doses of metarrestin to mice with pancreatic tumors, revealing it has a good oral bioavailability and demonstrates significant tissue concentration in tumors, suggesting effective drug delivery.
- Results indicated that metarrestin achieves high levels in tumor tissues, with a strong correlation between dosage and drug concentration, alongside a favorable influence on certain mRNA expressions related to tumor biology.
Metastasis remains a leading cause of cancer mortality due to the lack of specific inhibitors against this complex process. To identify compounds selectively targeting the metastatic state, we used the perinucleolar compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds. Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects.
View Article and Find Full Text PDF