Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

Cáceres, Marta; Quesada, Rita; Iglesias, Mar; Real, Francisco X.; Villamonte, María; Villarreal, Jaime Martínez de; Pérez, M.E. Ruíz; Andaluz, Anna; Moll, Xavier; Berjano, Enrique; Dorcaratto, Dimitri; Sánchez-Velázquez, Patricia; Grande, Luís; Burdı́o, Fernando

doi:10.1038/s41598-020-74947-4

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…Among the big 4 driver mutations, KRAS plays a dominant role in the occurrence and development of PDAC in animals and humans ( (accessed on 1 August 2022)) [ 29 , 30 , 31 ]. Alterations in cyclin-dependent kinase inhibitors result in uncontrolled cancer cell growth by constitutive activation of cyclin-dependent kinases accelerating cell cycle progression from G1/S to G2/M through their checkpoints, which will give rise to strong proliferative phenotypes [ 32 ].…”

Section: Diagnosis Through Methods Other Than Dna Sequencingmentioning

confidence: 99%

Pancreatic Cancer Research beyond DNA Mutations

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in the early stages challenging. Therefore, the development of innovative therapeutic approaches is desirable. The key to overcoming PDAC is diagnosing it in the early stages. Therefore, recent studies have investigated the multifaced characteristics of PDAC, which includes cancer cell metabolism, mesenchymal cells including cancer-associated fibroblasts and immune cells, and metagenomics, which extend to characterize various biomolecules including RNAs and volatile organic compounds. Various alterations in the KRAS-dependent as well as KRAS-independent pathways are involved in the refractoriness of PDAC. The optimal combination of these new technologies is expected to help treat intractable pancreatic cancer.

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Section: Diagnosis Through Methods Other Than Dna Sequencingmentioning

confidence: 99%

Pancreatic Cancer Research beyond DNA Mutations

et al. 2022

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“…The expression of NUPR1 was determined to be upregulated in acute pancreatitis and, at even higher levels in pancreatic adenocarcinoma [ 155 ], NUPR1 can also interact with mut-KRas signaling in pancreatic cancer and other cells. Genetic studies indicated that in the absence of NUPR1 in a mouse model, mut-KRAS (G12D) did not result in the development of PanIns, which is a precursor of the high lethal PDAC [ 155 , 156 ]. NUPR1 protected the pancreatic cancer cells from apoptosis by a RelB-mediated non-canonical NF-κβ pathway which interacted with immediate early response 3 (IRE3) protein.…”

Section: Interactions Between Tp53 and The Stress-inducible Nupr1 Onc...mentioning

confidence: 99%

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression

McCubrey

Yang

Abrams

et al. 2022

Cells

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Approximately 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is the fourth leading cause of cancer death world-wide. Therapies for PDAC are largely ineffective due to the dense desmoplastic tumor microenvironment which prevents chemotherapeutic drugs and small molecule inhibitors from exerting effective anti-cancer effects. In this review, we will discuss the roles of TP53 and miRs on the PDAC tumor microenvironment and how loss of the normal functions of TP53 promote tumor progression. The TP53 gene is mutated in approximately 50% of pancreatic cancers. Often, these TP53 mutations are point mutations which confer additional functions for the TP53 proteins. These are called gain of function (GOF) mutations (mut). Another class of TP53 mutations are deletions which result in loss of the TP53 protein; these are referred to TP53-null mutations. We have organized this review into various components/properties of the PDAC microenvironment and how they may be altered in the presence of mutant TP53 and loss of certain miR expression.

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Optimal reproduction of a porcine benign biliary stricture model using endobiliary radiofrequency ablation

Kwon

Jang

Jeong

et al. 2022

Sci Rep

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The use of endobiliary radiofrequency ablation (RFA) to generate a benign biliary stricture (BBS) model has a significant reproducibility problem. The aims of this animal study were to create an optimal BBS model using endobiliary RFA and determine the best way to develop it. The first step was performed on the common bile duct (CBD) of 10 miniature pigs using endoscopic RFA with a target temperature-controlled mode (80 ℃, 7 W for 90 s). The second step was performed on the CBD of five miniature pigs to understand more about the time-dependent changes in BBS development and the causes of adverse events. Using the conditions and techniques identified in the previous steps, the third step was conducted to create an optimal BBS model in 12 miniature pigs. In the first trial, four out of 10 animals died (40%) after the procedure due to cholangitis-induced sepsis. Based on this, biliary obstruction was prevented in further steps by placing a biliary plastic stent after RFA application. Histologic examinations over time showed that a severe abscess developed at the RFA application site on the fifth day, followed by fibrosis on the tenth day, and completion on the twentieth day. In the third trial, 11 animals survived (91.7%), the average BBS fibrotic wall thickness was 1107.9 µm (763.1–1864.6 µm), and the degree of upstream biliary dilation was 14.4 mm (11.05–20.7 mm). In conclusion, endobiliary RFA combined with a biliary plastic stent resulted in a safe and reproducible BBS animal model.

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Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

Cited by 4 publications

References 51 publications

Pancreatic Cancer Research beyond DNA Mutations

Pancreatic Cancer Research beyond DNA Mutations

Effects of TP53 Mutations and miRs on Immune Responses in the Tumor Microenvironment Important in Pancreatic Cancer Progression

Optimal reproduction of a porcine benign biliary stricture model using endobiliary radiofrequency ablation

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