Publications by authors named "Ryan D Watkins"
Background And Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the biliary epithelium with limited therapeutic options and poor long-term survival rates. To address the limitations of CCA treatment, we investigated cell-targeted nanovesicles as a delivery platform for transcriptome-targeting therapeutics.
Approach And Results: Milk-derived nanovesicles were loaded with short interfering RNAs targeting Yes-associated protein (YAP), the downstream effector of the Hippo pathway; LCK, an upstream regulator of YAP; and tafazzin, a protein critical for the integrity of the inner mitochondrial membrane.
Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer-related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins.
View Article and Find Full Text PDFThe Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.
View Article and Find Full Text PDFBackground: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations.
View Article and Find Full Text PDFLow- and middle-income countries (LMICs) have adopted procedural skill simulation, with researchers increasingly investigating simulation efforts in resource-strained settings. We aim to summarize the current state of procedural skill simulation research in LMICs focusing on methodology, clinical area, types of outcomes and cost, cost-effectiveness, and overall sustainability. We performed a comprehensive literature review of original articles that assessed procedural skill simulation from database inception until April 2022.
View Article and Find Full Text PDFArticle Synopsis
- Researchers are targeting a protein called LCK as a potentially effective treatment for cholangiocarcinoma (CCA) by inhibiting its role in activating the oncogenic YAP protein.
- The new tyrosine kinase inhibitor, NTRC 0652-0, showed selectivity for inhibiting LCK and led to tumor cell death in various CCA models, including patient-derived organoids and xenografts.
- The study identifies CCA with FGFR2 fusions as a particularly promising subset for treatment with NTRC 0652-0, demonstrating significant reductions in tumor growth and YAP activity in preclinical tests.
Article Synopsis
- Disrupted liver regeneration after surgery is a major clinical challenge, linked to poor patient outcomes, and involves the role of Yes-associated protein (YAP) in the process.
- The study investigates the effects of a selective SHP1/SHP2 inhibitor, NSC-87877, on liver regeneration in mice, showing it promotes faster liver cell growth and reduces injury post-surgery, relying on YAP activity.
- Results also indicate that NSC-87877 improves survival in models of fatty liver disease and modifies gene activity related to fibrosis and cell survival, highlighting its potential in enhancing liver regeneration.
Article Synopsis
- The study explored how Behavioral Health Disorders (BHDs) impact outcomes for injured children aged 5-15, finding that a notable percentage of these kids had BHDs.
- Among the 69,305 injured children analyzed, those with BHDs were more likely to have severe injuries and suffer from intentional and penetrating trauma, including a higher incidence of gunshot wounds.
- Despite these factors, children with BHDs showed a lower risk of in-hospital mortality compared to those without, indicating a complex relationship between BHDs and trauma outcomes that requires further investigation, especially regarding prevention strategies.