Introduction: Extracellular vesicles (EVs) and their cargo may provide promising biomarkers for the early detection of pancreatic ductal adenocarcinoma (PDAC). Although blood-borne EVs are most frequently studied as cancer biomarkers, pancreatic juice (PJ) may represent a better biomarker source because it is in close contact with the ductal cells from which PDAC arises. It is, as yet, unknown whether PDAC results in a distinct type or increased number of particles in PJ and whether this has diagnostic value.
Methods: Secretin-stimulated PJ was collected from the duodenum of 54 cases and 117 nonmalignant controls under surveillance for PDAC. Serum was available for a subset of these individuals. The vesicular composition of these biofluids was analyzed with nanoparticle tracking analysis.
Results: The concentration of EVs did not differ between controls and PDAC cases. However, a higher number of large vesicles were found in PJ (but not serum) for patients with PDAC compared with controls.
Discussion: The composition of isolated EVs from PJ, but not serum, is altered in patients with PDAC. This suggests that PJ may carry disease-specific markers not present in serum and provides a valuable biomarker source for PDAC diagnosis. The nature of the larger particles in EV isolates from PJ of PDAC cases requires further investigation.
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http://dx.doi.org/10.14309/ctg.0000000000000465 | DOI Listing |
Nanomedicine (Lond)
January 2025
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Aim: To develop pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL) of CD40a to enhance anti-tumor activity in pancreatic cancer while reducing systemic toxicity.
Materials And Methods: A small library of nanoliposomes (NL) with various lipid compositions were synthesized to prepare pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL). Physical and functional characterization of pHTANL-CD40a was performed via dynamic light scattering (DLS), Transmission Electron Microscopy (TEM), confocal microscopy, and flow cytometry.
Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the PDAC microenvironment. The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP).
View Article and Find Full Text PDFBackground: Cachexia is defined by chronic loss of fat and muscle, is a frequent complication of pancreatic ductal adenocarcinoma (PDAC), and negatively impacts patient outcomes. Nutritional supplementation cannot fully reverse tissue wasting, and the mechanisms underlying this phenotype are unclear. This work aims to define the relative contributions of catabolism and anabolism to adipose wasting in PDAC-bearing mice.
View Article and Find Full Text PDFJ Gastrointest Cancer
January 2025
Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.
Methods: In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.
Nat Commun
January 2025
Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany.
Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment.
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