We apply spatial transcriptomics and proteomics to select pancreatic cancer surface receptor targets for molecular imaging and theranostics using an approach that can be applied to many cancers. Selected cancer surfaceome epithelial markers were spatially correlated and provided specific cancer localization, whereas the spatial correlation between cancer markers and immune- cell or fibroblast markers was low. While molecular imaging of cancer-associated fibroblasts and integrins has been proposed for pancreatic cancer, our data point to the tight junction protein claudin-4 as a theranostic target. Claudin-4 expression increased ∼16 fold in cancer as compared with normal pancreas, and the tight junction localization conferred low background for imaging in normal tissue. We developed a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to ∼25% injected activity per cc (IA/cc) in metastases and ∼18% IA/cc in tumors. Our work motivates a new approach for data-driven selection of molecular targets.
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http://dx.doi.org/10.1101/2024.01.07.574209 | DOI Listing |
Nat Commun
December 2024
Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated fibroblasts and integrins have been proposed as targets for imaging of pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics and proteomics of human surgical samples are applied to select PDAC targets. We find that selected cancer cell surface markers are spatially correlated and provide specific cancer localization, whereas the spatial correlation between cancer markers and immune-related or fibroblast markers is low.
View Article and Find Full Text PDFKaohsiung J Med Sci
December 2024
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
This study aimed to investigate whether activation of PPARγ regulates M1/M2 macrophage polarization to attenuate dextran sulfate sodium salt (DSS)-induced inflammatory bowel disease (IBD) via the STAT-1/STAT-6 pathway in vivo and in vitro. We first examined the effect of PPARγ on macrophage polarization in LPS/IFN-γ-treated M1 RAW264.7 cells and IL-4/IL-13-treated M2 RAW264.
View Article and Find Full Text PDFTherap Adv Gastroenterol
December 2024
Division of Gastroenterology & Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Perelman Center for Advanced Medicine, 750 South 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
Background: Esophagogastric junction outflow obstruction (EGJOO) is a manometric diagnosis based on Chicago Classification version 4.0 (CC4.0) that requires confirmatory testing for clinical relevancy.
View Article and Find Full Text PDFFront Nutr
December 2024
College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi, China.
Background: The use of enzymes within pig feed can reduce the challenges associated with antibiotic-free animal feeding. However, this enzymatic effect is often limited by the internal and external gut environment. This study aimed to improve diet quality and assess the impact of an enzymatically hydrolyzed diet (EHD) on growth performance, meat quality, and intestinal health in growing pigs.
View Article and Find Full Text PDFFASEB J
December 2024
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine Jilin University, Center of Infectious Diseases and Pathogen Biology, Department of Infectious Diseases, First Hospital of Jilin University, Changchun, China.
Salmonella enterica serovar Typhimurium (S. Typhimurium) poses a serious threat to human and animal health, and there is an urgent need to develop new therapeutic agents. In our in vivo study, ginsenoside Ro (Ro) reduced the mortality rate of S.
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