Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very poor prognosis, characterized by incidence rates very close to death rates. Despite the efforts of the scientific community, preclinical models that faithfully recreate the PDAC tumor microenvironment remain limited. Currently, the use of 3D bio-printing is an emerging and promising method for the development of cancer tumor models with reproducible heterogeneity and a precisely controlled structure. This study presents the development of a model using the extrusion 3D bio-printing technique. Initially, a model combining pancreatic cancer cells (Panc-1) and cancer-associated fibroblasts (CAFs) encapsulated in a sodium alginate and gelatin-based hydrogel to mimic the metastatic stage of PDAC was developed and comprehensively characterized. Subsequently, efforts were made to vascularize this model. This study demonstrates that the resulting tumors can maintain viability and proliferate, with cells self-organizing into aggregates with a heterogeneous composition. The utilization of 3D bio-printing in creating this tumor model opens avenues for reproducing tumor complexity in the future, offering a versatile platform for improving anti-cancer therapy models.
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http://dx.doi.org/10.3390/diseases12090206 | DOI Listing |
Gastro Hep Adv
August 2024
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida.
Background And Aims: Enzyme insufficiency (EPI) is common in chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and after pancreatic resection. 40%-50% of CP patients and 70%-80% of PDAC patients develop EPI. 1/3rd of these patients are prescribed Pancreatic enzyme replacement therapy (PERT), often at an inadequate dose, with evidence that this leads to increased morbidity and mortality.
View Article and Find Full Text PDFClin 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 PDFNat Cancer
January 2025
Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype.
View Article and Find Full Text PDFGut
January 2025
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
Background: The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells.
View Article and Find Full Text PDFArch Biochem Biophys
January 2025
Department of Biosciences, Biotechnologies, and Environment, University of Bari Aldo Moro, Italy. Electronic address:
Lysine-specific demethylase 1 (LSD1) is a key regulator in cancer epigenetic, and its activity is reliant on flavin adenine dinucleotide (FAD) as a cofactor. In this study, we investigated the correlation between LSD1 and FAD synthase isoform 2 (FADS2) protein levels in pancreatic ductal adenocarcinoma (PDAC) cell lines. We first assessed LSD1 protein and mRNA levels in mutant p53-expressing PANC-1 and MiaPaCa2 cells and p53-null AsPc-1 cells, compared to human pancreatic ductal epithelial (HPDE) controls.
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