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Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.
Clin Pharmacol Drug Dev
January 2025
Department of Pharmacometrics Modeling, A2-Ai LLC, Ann Arbor, MI, USA.
Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters.
View Article and Find Full Text PDFKRAS Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma.
JAMA Netw Open
January 2025
Huntsman Cancer Institute, University of Utah Health Care, Salt Lake City.
Importance: Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC.
Objective: To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations.
PLGA-Nano-Encapsulated Disulfiram Inhibits Cancer Stem Cells and Targets Non-Small Cell Lung Cancer In Vitro and In Vivo.
Biomolecules
December 2024
Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
Cancer stem cells (CSCs) play a key role in non-small cell lung cancer (NSCLC) chemoresistance and metastasis. In this study, we used two NSCLC cell lines to investigate the regulating effect of hypoxia in the induction and maintenance of CSC traits. Our study demonstrated hypoxia-induced stemness and chemoresistance at levels comparable to those in typical CSC sphere culture.
View Article and Find Full Text PDFCost-effectiveness analysis of first-line combination chemotherapy regimens for metastatic pancreatic cancer and evidence-based pricing strategy of liposomal irinotecan in China.
Front Pharmacol
December 2024
Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, China.
Background: The phase III NAPOLI-3 trial, which upgraded FOLFIRINOX (leucovorin, fluorouracil, irinotecan and oxaliplatin) to NALIRIFOX (liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil), demonstrated the superiority of NALIRIFOX over GEMNABP (gemcitabine and nab-paclitaxel) as the first-line treatment for metastatic pancreatic ductal adenocarcinoma. The purpose of this study was to assess the cost-effectiveness of NALIRIFOX, FOLFIRINOX, and GEMNABP, and to simulate the price of liposomal irinotecan at which NALIRIFOX could achieve cost-effectiveness.
Methods: A partitioned survival model was performed to evaluate the cost-effectiveness of NALIRIFOX, FOLFIRINOX and GEMNABP from the perspective of the Chinese healthcare system.
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