Elevated expression of p53 in early colon polyps in a pig model of human familial adenomatous polyposis

Sikorska, Agata; Flisikowska, Tatiana; Stachowiak, Monika; Kind, Alexander; Schnieke, Angelika; Flisikowski, Krzysztof; Świtoński, M.

doi:10.1007/s13353-018-0461-6

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Previously, Flisikowska et al created an APC mutated pig line, which develops dysplastic adenomas in the large intestine, similar to the precancerous lesions in human patients 78 . These pigs have contributed greatly to understanding CRC cellular mechanisms and improving diagnostics/therapeutics for human CRC patients in ways that previous mouse models could not 79–82 . Historically, colon cancer has been difficult to model completely in genetically modified mice due to the tendency of tumors to form in the small intestine instead of the colon 77 .…”

Section: Discussionmentioning

confidence: 99%

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

et al. 2023

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Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies lack a large animal model. This study validates ISC isolation in a new porcine Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5) reporter line and demonstrates the use of these pigs as a novel colorectal cancer (CRC) model. We applied histology, immunofluorescence, fluorescence-activated cell sorting, flow cytometry, gene expression quantification, and 3D organoid cultures to whole tissue and single cells from the duodenum, jejunum, ileum, and colon of LGR5-H2B-GFP and wild-type pigs. Ileum and colon LGR5-H2B-GFP, healthy human, and murine biopsies were compared by mRNA fluorescent in situ hybridization (FISH). To model CRC, adenomatous polyposis coli (APC) mutation was induced by CRISPR/Cas9 editing in porcine LGR5-H2B-GFP colonoids. Crypt-base, green fluorescent protein (GFP) expressing cells co-localized with ISC biomarkers. LGR5-H2B-GFP hi cells had significantly higher LGR5 expression (p < .01) and How to cite this article: Schaaf CR, Polkoff KM, Carter A, et al. A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.

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Section: Discussionmentioning

confidence: 99%

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

et al. 2023

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“…TP53 encodes tumor protein p53, a long-established tumor suppressor protein. Although p53 expression may be downregulated in colonic cancer, increased expression has been documented in relation to the progression of colorectal adenomas [28] and with high-grade dysplasia in adenomas [29,30]. In turn, no changes were detected for PCNA, PTGS2 (COX2), CEACAM5 (carcinoembryonic antigen cell adhesion molecule 5), or MKI67 (marker of proliferation Ki67).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of a Novel Submucosal Injection Solution for Resection of Gastrointestinal Lesions

Moles-Aranda

González-Pérez

Gallego-Rojo

et al. 2020

JCM

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Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are minimally invasive and efficient techniques for the removal of gastrointestinal (GI) mucosal polyps. In both techniques, submucosal injection solutions are necessary for complete effectiveness and safety during the intervention to be obtained. The main objective of this study was to evaluate the efficacy and safety of a new sterile submucosal injection solution for EMR/ESD used within a clinical protocol in patients with intestinal polyps. We carried out a prospective study between 2016 and 2017 with patients who attended the Endoscopy Consultation—Digestive Department of Primary Hospital. Patients were selected for EMR/ESD after the application of clinical protocols. Thirty-six patients were selected (≥ 66 years with comorbidities and risk factors). Lesions were located mainly in the colon. Our solution presented an intestinal lift ≥ 60 min in EMR/ESD and a high expansion of tissue, optimum viscosity, and subsequent complete resorption. The genes S100A9 and TP53 presented an expression increase in the distal regions. TP53 and PCNA were the only genes whose expression was increased in polyp specimens vs. the surrounding tissue at the mRNA level. In EMR/ESD, our solution presented a prolonged effect at the intestinal level during all times of the intervention. Thus, our solution seems be an effective and safe alternative in cases of flat lesions in both techniques.

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“…Growing evidence indicates that marked TP53 mutations are found in CRC cells and human samples. Abnormally mutated changes of the TP53 gene play a key role in advanced CRC [13]. Compared with non-cancer tissues, the methylation levels of microRNA-34a in TP53 PIN A1A1 and TP53 MSP GG genotypes in CRC tumors are clearly higher [14].…”

Section: Discussionmentioning

confidence: 99%

Anti-Colorectal Cancer Mechanisms of Formononetin Identified by Network Pharmacological Approach

et al. 2019

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This study is funded by the 2018 Innovation Project of Guangxi Graduate Education (No. YCBZ2018036) Background: The network pharmacological approach was used to identity the anti-colorectal cancer (CRC) targets of formononetin (FN) and the molecular mechanisms of FN against CRC. Material/Methods: A tool of the DisGeNET database was used for collection of CRC-based targets. Other tools of SuperPred, herbal ingredients target (HIT), and SwissTargetPrediction databases were applied in prediction of pharmacological targets of FN against cancer. A protein-protein interaction (PPI) network of FN against CRC was obtained by using a STRING database. All top biological functional processes and signaling pathways of FN against CRC were identified by using Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Omicshare cloud platform. Results: The most key anti-CRC targets of FN were identified as tumor protein p53 (TP53), cytochrome P450 3A4 (CYP3A4), ATP binding cassette subfamily G member 2 (ABCG2), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and cytochrome P450 1A1 (CYP1A1). In further assays, the treatment of CRC by FN was mainly involved in biological functional processes of reactive oxygen species metabolic process, positive regulation of transcription, DNA-templated, positive regulation of nucleic acid-templated transcription, and positive regulation of RNA metabolic process. anti-CRC by FN of signaling pathways were associated with amyotrophic lateral sclerosis (ALS), allograft rejection, cytokine-cytokine receptor interaction, asthma, mitogen-activated protein kinase (MAPK) signaling pathways, and others. Conclusions: The anti-CRC molecular mechanisms of FN are implicated in suppression of cellular proliferation and regulation of cancer-related metabolic pathways. Interestingly, 8 optimal biological targets may be used as potential molecular markers for predicting and treating CRC.

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Elevated expression of p53 in early colon polyps in a pig model of human familial adenomatous polyposis

Cited by 7 publications

References 32 publications

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

Efficacy and Safety of a Novel Submucosal Injection Solution for Resection of Gastrointestinal Lesions

Anti-Colorectal Cancer Mechanisms of Formononetin Identified by Network Pharmacological Approach

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