High Endothelial Venules and Pancreatic Ductal Adenocarcinoma: A potential game changer
| Autor: | Ser Yee Lee, Shu Ming Chai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Pathology medicine.medical_specialty Pancreatic ductal adenocarcinoma Paclitaxel High endothelial venules Antineoplastic Agents General Biochemistry Genetics and Molecular Biology Theranostic Nanomedicine Cell Line Mice Text mining Carcinoma Medicine Animals Humans Pancreatic carcinoma Molecular Targeted Therapy Neovascularization Pathologic business.industry General Medicine medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays Pancreatic Neoplasms Disease Models Animal Commentary Nanoparticles Female Lymph Nodes Endothelium Lymphatic business Biomarkers Carcinoma Pancreatic Ductal |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC.The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was more robust than non-conjugated NPs. Treatment with MECA79-Taxol-NPs augmented the delivery of Paclitaxel (Taxol) to the tumor site and significantly reduced the tumor size. This effect was associated with a higher apoptosis rate of PDAC cells and reduced vascularization within the tumor.Targeting the HEVs of PDAC using MECA79-NPs could lay the ground for the localized delivery of a wide variety of drugs including chemotherapeutic agents. FUND: National Institutes of Health (NIH) grants: T32-EB016652 (B·B.), NIH Cancer Core Grant CA034196 (L.D.S.), National Institute of Allergy and Infectious Diseases grants R01-AI126596 and R01-HL141815 (R.A.). |
| Databáze: | OpenAIRE |
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