FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2566888434> ?p ?o ?g. }

• W2566888434 abstract "Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in the United States. Most newly diagnosed patients have unresectable disease due to local spread or early aggressive metastasis and have a medial survival of 6 months. Cancer stem cells (CSC) have been found to be involved in the development of metastatic disease. CSC markers such as C-X-C chemokine receptor 4 (CXCR4) and CD133 are overexpressed on the invasive front of PDAC. In this study, we tested a CXCR4-targeted conditionally replicative adenovirus (CRAd) with fiber and hexon modifications toward systemic treatment of PDAC. Due to poor infectivity of CRAd to PDAC cells, our vector contains a modified chimeric fiber which incorporates adenovirus 5 shaft and adenovirus 3 knob (Ad5/3) in order to target PDAC cells via an alternative receptor. The CXCR-4 targeted CRAd with Ad5/3 fiber modification showed strong replication in CD133(+) primary cells isolated from human PDAC tumors. The virus copy number in CD133(+) cells was more than 5 times higher than in CD133(-) cells (p<0.0005). Virus replication capability as measured by luciferase expression from Ad major late promoter was more than double in CD133(+) cells (p<0.05). This data indicates Ad5/3 modified oncolytic adenovirus shows enhanced replication in CSC-rich CD133(+) population. To overcome the issue of adenoviral sequestration upon systemic injection by non-target organs (ie liver, lung), our vector was additionally modified by replacing the Ad5 hexon hypervariable regions 5 and 7 with those from Ad3. We assessed the hexon modified adenovirus in a human Ad replication-permissive model that is most frequently used in IND-directed distribution/toxicology studies, the Syrian hamster. When the virus copy number was assayed after systemic injection via the saphenous vein, the hexon modified virus showed decreased liver sequestration, while showing no difference in the lungs. On the other hand, the major late promoter driven luciferase expression showed much more significant reductions in both liver and lung. The difference between the assays may indicate more contribution of macrophages to the copy number. Next, antitumor effect of the fiber and hexon modified CRAd was assessed in patient-derived xenografts. After intratumoral administration, the fiber-modified CRAd showed antitumor effect compared to the untreated group regardless of the presence (AdCXCR4 E1 F5/3 H5/H3) or absence of (AdCXCR4 E1 F5/3) hexon modification (p<0.01 and 0.05, respectively). On the contrary, with intravenous infection, only the fiber and hexon modified CRAd (AdCXCR4 E1 F5/3 H5/H3) showed significant antitumor effect. We believe that our CXCR4-targeted chimeric fiber and hexon modified CRAd may be employed in advanced PDAC, and that hexon modification of oncolytic adenovirus can be advantageous with systemic administration in the clinical setting." @default.
• W2566888434 created "2017-01-06" @default.
• W2566888434 creator A5022987623 @default.
• W2566888434 creator A5027836042 @default.
• W2566888434 creator A5040066354 @default.
• W2566888434 creator A5040557156 @default.
• W2566888434 creator A5044954997 @default.
• W2566888434 creator A5048788127 @default.
• W2566888434 creator A5074689132 @default.
• W2566888434 date "2016-05-01" @default.
• W2566888434 modified "2023-09-26" @default.
• W2566888434 title "519. Intravenous Application of CXCR4 Targeted Conditionally Replicative Adenovirus with Fiber and Hexon Modifications to Pancreatic Cancer" @default.
• W2566888434 doi "https://doi.org/10.1016/s1525-0016(16)33328-7" @default.
• W2566888434 hasPublicationYear "2016" @default.
• W2566888434 type Work @default.
• W2566888434 sameAs 2566888434 @default.
• W2566888434 citedByCount "0" @default.
• W2566888434 crossrefType "journal-article" @default.
• W2566888434 hasAuthorship W2566888434A5022987623 @default.
• W2566888434 hasAuthorship W2566888434A5027836042 @default.
• W2566888434 hasAuthorship W2566888434A5040066354 @default.
• W2566888434 hasAuthorship W2566888434A5040557156 @default.
• W2566888434 hasAuthorship W2566888434A5044954997 @default.
• W2566888434 hasAuthorship W2566888434A5048788127 @default.
• W2566888434 hasAuthorship W2566888434A5074689132 @default.
• W2566888434 hasBestOaLocation W25668884341 @default.
• W2566888434 hasConcept C104317684 @default.
• W2566888434 hasConcept C121608353 @default.
• W2566888434 hasConcept C129470790 @default.
• W2566888434 hasConcept C13373296 @default.
• W2566888434 hasConcept C159047783 @default.
• W2566888434 hasConcept C203014093 @default.
• W2566888434 hasConcept C2522874641 @default.
• W2566888434 hasConcept C2776914184 @default.
• W2566888434 hasConcept C2777283488 @default.
• W2566888434 hasConcept C2779013556 @default.
• W2566888434 hasConcept C2780210213 @default.
• W2566888434 hasConcept C2908647359 @default.
• W2566888434 hasConcept C32470452 @default.
• W2566888434 hasConcept C40767141 @default.
• W2566888434 hasConcept C49744831 @default.
• W2566888434 hasConcept C502942594 @default.
• W2566888434 hasConcept C54355233 @default.
• W2566888434 hasConcept C55493867 @default.
• W2566888434 hasConcept C71924100 @default.
• W2566888434 hasConcept C82210918 @default.
• W2566888434 hasConcept C86803240 @default.
• W2566888434 hasConcept C99454951 @default.
• W2566888434 hasConceptScore W2566888434C104317684 @default.
• W2566888434 hasConceptScore W2566888434C121608353 @default.
• W2566888434 hasConceptScore W2566888434C129470790 @default.
• W2566888434 hasConceptScore W2566888434C13373296 @default.
• W2566888434 hasConceptScore W2566888434C159047783 @default.
• W2566888434 hasConceptScore W2566888434C203014093 @default.
• W2566888434 hasConceptScore W2566888434C2522874641 @default.
• W2566888434 hasConceptScore W2566888434C2776914184 @default.
• W2566888434 hasConceptScore W2566888434C2777283488 @default.
• W2566888434 hasConceptScore W2566888434C2779013556 @default.
• W2566888434 hasConceptScore W2566888434C2780210213 @default.
• W2566888434 hasConceptScore W2566888434C2908647359 @default.
• W2566888434 hasConceptScore W2566888434C32470452 @default.
• W2566888434 hasConceptScore W2566888434C40767141 @default.
• W2566888434 hasConceptScore W2566888434C49744831 @default.
• W2566888434 hasConceptScore W2566888434C502942594 @default.
• W2566888434 hasConceptScore W2566888434C54355233 @default.
• W2566888434 hasConceptScore W2566888434C55493867 @default.
• W2566888434 hasConceptScore W2566888434C71924100 @default.
• W2566888434 hasConceptScore W2566888434C82210918 @default.
• W2566888434 hasConceptScore W2566888434C86803240 @default.
• W2566888434 hasConceptScore W2566888434C99454951 @default.
• W2566888434 hasLocation W25668884341 @default.
• W2566888434 hasOpenAccess W2566888434 @default.
• W2566888434 hasPrimaryLocation W25668884341 @default.
• W2566888434 hasRelatedWork W1481569791 @default.
• W2566888434 hasRelatedWork W1545850408 @default.
• W2566888434 hasRelatedWork W1582673757 @default.
• W2566888434 hasRelatedWork W1963743961 @default.
• W2566888434 hasRelatedWork W1994784565 @default.
• W2566888434 hasRelatedWork W1995188322 @default.
• W2566888434 hasRelatedWork W2020222773 @default.
• W2566888434 hasRelatedWork W2026213690 @default.
• W2566888434 hasRelatedWork W2041243019 @default.
• W2566888434 hasRelatedWork W2055354508 @default.
• W2566888434 hasRelatedWork W2082024280 @default.
• W2566888434 hasRelatedWork W2095919287 @default.
• W2566888434 hasRelatedWork W2126613715 @default.
• W2566888434 hasRelatedWork W2141560715 @default.
• W2566888434 hasRelatedWork W2143113338 @default.
• W2566888434 hasRelatedWork W2152553659 @default.
• W2566888434 hasRelatedWork W2167188379 @default.
• W2566888434 hasRelatedWork W2395868980 @default.
• W2566888434 hasRelatedWork W2744851056 @default.
• W2566888434 hasRelatedWork W2768254930 @default.
• W2566888434 isParatext "false" @default.
• W2566888434 isRetracted "false" @default.
• W2566888434 magId "2566888434" @default.
• W2566888434 workType "article" @default.