A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions

Yim, Joshua J.; Harmsen, Stefan; Flisikowski, Krzysztof; Flisikowska, Tatiana; Namkoong, Hong; Garland, Megan; Berg, Nynke S. van den; Vilches-Moure, José G.; Schnieke, Angelika; Saur, Dieter; Glasl, Sarah; Gorpas, Dimitris; Habtezion, Aida; Ntziachristos, Vasilis; Contag, Christopher H.; Gambhir, Sanjiv S.; Bogyo, Matthew; Rogalla, Stephan

doi:10.1073/pnas.2008072118

Cited by 49 publications

(42 citation statements)

References 33 publications

(42 reference statements)

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“…However, the complex interaction between p53 family members and YAP/Hippo pathway is still not fully understood. Recent studies have proven the importance of genetically engineered pigs as an animal model in oncology [67][68][69][70]. By using flTP53 R167H pigs, we identified the role of YAP1 in the progression of p53-dependent OS.…”

Section: Discussionmentioning

confidence: 99%

Allelic Expression Imbalance Analysis Identified YAP1 Amplification in p53- Dependent Osteosarcoma

Niu

Bak

Nusselt

et al. 2021

Cancers

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Osteosarcoma (OS) is a primary bone malignancy that mainly occurs during adolescent growth, suggesting that bone growth plays an important role in the aetiology of the disease. Genetic factors, such as heritable mutations of Rb1 and TP53, are associated with an increased risk of OS. Identifying driver mutations for OS has been challenging due to the complexity of bone growth-related pathways and the extensive intra-tumoral heterogeneity of this cancer. We previously generated pigs carrying a mutated TP53 gene, which develop OS at high frequency. RNA sequencing and allele expression imbalance (AEI) analysis of OS and matched healthy control samples revealed a highly significant AEI (p = 2.14 × 10−39) for SNPs in the BIRC3-YAP1 locus on pig chromosome 9. Analysis of copy number variation showed that YAP1 amplification is associated with the AEI and the progression of OS. Accordingly, the inactivation of YAP1 inhibits proliferation, migration, and invasion, and leads to the silencing of TP63 and reconstruction of p16 expression in p53-deficient porcine OS cells. Increased p16 mRNA expression correlated with lower methylation of its promoter. Altogether, our study provides molecular evidence for the role of YAP1 amplification in the progression of p53-dependent OS.

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Section: Discussionmentioning

confidence: 99%

Allelic Expression Imbalance Analysis Identified YAP1 Amplification in p53- Dependent Osteosarcoma

Niu

Bak

Nusselt

et al. 2021

Cancers

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“…Furthermore, some NIR imaging probes have received approval from the Food and Drug Administration (FDA) for clinical use [ 8 ]. Thus, new fluorescents probes are being tested for different diagnostic and theranostic procedures [ 31 , 32 , 33 , 34 , 35 ]. Fluorescence-guided surgery can provide real-time imaging during surgery, and it is much easier and reliable to perform [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

Arevalo

Castelli

Ibarra

et al. 2022

IJMS

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Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.

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“…Pancreatic cancer is one of the most lethal forms of cancer, with fewer than 20% of people surviving for longer than twelve months after diagnosis. The usefulness of large animal models for translational research and as pre-clinical models has been documented (31)(32)(33)(34)(35). Modelling PDAC in large animals was hampered by the lack of Cre-driver lines.…”

Section: Discussionmentioning

confidence: 99%

The Missing Link: Cre Pigs for Cancer Research

et al. 2021

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The Cre/loxP system is a powerful tool for the generation of animal models with precise spatial and temporal gene expression. It has proven indispensable in the generation of cancer models with tissue specific expression of oncogenes or the inactivation of tumor suppressor genes. Consequently, Cre-transgenic mice have become an essential prerequisite in basic cancer research. While it is unlikely that pigs will ever replace mice in basic research they are already providing powerful complementary resources for translational studies. But, although conditionally targeted onco-pigs have been generated, no Cre-driver lines exist for any of the major human cancers. To model human pancreatic cancer in pigs, Cre-driver lines were generated by CRISPR/Cas9-mediated insertion of codon-improved Cre (iCre) into the porcine PTF1A gene, thus guaranteeing tissue and cell type specific function which was proven using dual fluorescent reporter pigs. The method used can easily be adapted for the generation of other porcine Cre-driver lines, providing a missing tool for modeling human cancers in large animals.

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A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions

Cited by 49 publications

References 33 publications

Allelic Expression Imbalance Analysis Identified YAP1 Amplification in p53- Dependent Osteosarcoma

Allelic Expression Imbalance Analysis Identified YAP1 Amplification in p53- Dependent Osteosarcoma

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model

The Missing Link: Cre Pigs for Cancer Research

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