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. 2021 Aug 31;13(17):4393. doi: 10.3390/cancers13174393

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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In vivo optCPE gene therapy in patient derived xenograft (PDX) models of PC. (A) Claudin3/4 expression analysis in 21 PC patient derived xenograft (PDX) models at mRNA and protein level (Figure S9). (B) Histopathology of primary and xenograft tissue show similar histological appearance in representative models (upper two rows). Representative images of Cldn3/4 expression (brown staining) in Panc9699, Panc9996, Panc10991, Panc11074 and Panc11495 PDX tumors (C) in optCPE non-viral jet-injection (performed 21 days after PDX derived cell injection) transfected Panc12536/eGFP-Luc-bearing mice significant antitumoral activity was observed. Significantly decreased tumor bioluminescence and (D) tumor growth was determined in optCPE-expressing tumors compared to empty vector control (VC). (E) In optCPE-transfected tumors reduced luminescence was measured compared to respective vector controls (VC), shown in representative images. (F) Significant reduction of viability in optCPE-transfected tumors, determined by quantification of ex vivo bioluminescence of tumors (representative bioluminescence images, lower panel). (G) The intratumoral optCPE gene transfer led to significantly reduced Ki67 reactivity within tumor tissue compared to VC treated tissue. (H) In optCPE-transfected Panc12536/eGFP-Luc PDX tumors the TUNEL assay revealed significantly increased number of TUNEL positive nuclei compared to VC-transfected tumors. (* p < 0.05; ** p < 0.01: *** p < 0.001).

In vivo optCPE gene therapy in patient derived xenograft (PDX) models of PC. (A) Claudin3/4 expression analysis in 21 PC patient derived xenograft (PDX) models at mRNA and protein level (Figure S9). (B) Histopathology of primary and xenograft tissue show similar histological appearance in representative models (upper two rows). Representative images of Cldn3/4 expression (brown staining) in Panc9699, Panc9996, Panc10991, Panc11074 and Panc11495 PDX tumors (C) in optCPE non-viral jet-injection (performed 21 days after PDX derived cell injection) transfected Panc12536/eGFP-Luc-bearing mice significant antitumoral activity was observed. Significantly decreased tumor bioluminescence and (D) tumor growth was determined in optCPE-expressing tumors compared to empty vector control (VC). (E) In optCPE-transfected tumors reduced luminescence was measured compared to respective vector controls (VC), shown in representative images. (F) Significant reduction of viability in optCPE-transfected tumors, determined by quantification of ex vivo bioluminescence of tumors (representative bioluminescence images, lower panel). (G) The intratumoral optCPE gene transfer led to significantly reduced Ki67 reactivity within tumor tissue compared to VC treated tissue. (H) In optCPE-transfected Panc12536/eGFP-Luc PDX tumors the TUNEL assay revealed significantly increased number of TUNEL positive nuclei compared to VC-transfected tumors. (* p < 0.05; ** p < 0.01: *** p < 0.001).