Evaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia

Rosa, Lorena; Lobos-González, Lorena; Muñoz‐Durango, Natalia; García, Patricia; Bizama, Carolina; Gómez, Natalia; González, Ximena; Wichmann, Ignacio A.; Saavedra, Nicolás; Guevara, Francisca; Villegas, Jaime; Arrese, Marco; Ferreccio, Catterina; Kalergis, Alexis M.; Miquel, Juan Francisco; Espinoza, Jaime A.; Roa, Juan Carlos

doi:10.1002/1878-0261.12766

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…Furthermore, animals fed a lithogenic diet evidenced fatty liver and higher plasma cholesterol levels than animals fed a normal diet in a similar manner to that observed in humans. More interestingly, those animals treated with a lithogenic diet had metaplastic and dysplastic architecture in gallbladder tissues, with no invasive features, but with a well-defined inflammatory component showing a predominance of lymphocytes and polymorphonuclear cells [116]. A similar study showed that mice treated with a lithogenic diet had epithelial hyperplasia along with the occurrence of acute and chronic inflammation characterized by the presence of eosinophils, neutrophils, and lymphocytes within the lamina propria [117].…”

Section: Nutritional and Lifestyle Aspects That Increase Susceptibili...mentioning

confidence: 90%

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Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer

Pérez-Moreno

Riquelme

García

et al. 2022

JPM

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Gallbladder cancer (GBC) is an aggressive neoplasm that in an early stage is generally asymptomatic and, in most cases, is diagnosed in advanced stages with a very low life expectancy because there is no curative treatment. Therefore, understanding the early carcinogenic mechanisms of this pathology is crucial to proposing preventive strategies for this cancer. The main risk factor is the presence of gallstones, which are associated with some environmental factors such as a sedentary lifestyle and a high-fat diet. Other risk factors such as autoimmune disorders and bacterial, parasitic and fungal infections have also been described. All these factors can generate a long-term inflammatory state characterized by the persistent activation of the immune system, the frequent release of pro-inflammatory cytokines, and the constant production of reactive oxygen species that result in a chronic damage/repair cycle, subsequently inducing the loss of the normal architecture of the gallbladder mucosa that leads to the development of GBC. This review addresses how the different risk factors could promote a chronic inflammatory state essential to the development of gallbladder carcinogenesis, which will make it possible to define some strategies such as anti-inflammatory drugs or public health proposals in the prevention of GBC.

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Section: Nutritional and Lifestyle Aspects That Increase Susceptibili...mentioning

confidence: 90%

“…Different animal models have been used to study gallstone formation and its effect on the development of preneoplastic lesions [114][115][116][117]. Our research group established an animal model of gallbladder preneoplasia through a lithogenic diet.…”

Section: Nutritional and Lifestyle Aspects That Increase Susceptibili...mentioning

confidence: 99%

Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer

Pérez-Moreno

Riquelme

García

et al. 2022

JPM

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“…In that context, Rosa and coworkers fed wild-type C57BL/6 mice with a high-cholesterol lithogenic diet. 106 The mice developed gallstones, and gallbladder metaplasia were detected within a month. Within 9 months, 60% of the animals evolved toward dysplasia.…”

Section: Animal Models For Studying Precursor Lesions Of Biliary Trac...mentioning

confidence: 99%

“…Nongenetic mouse models have the advantage of considerably facilitating the breeding of the animals. In that context, Rosa and coworkers fed wild-type C57BL/6 mice with a highcholesterol lithogenic diet 106 . The mice developed gallstones, and gallbladder metaplasia were detected within a month.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Biliary Tract Cancer: Molecular Biology of Precursor Lesions

Manzano-Núñez,

Prates Tiago Aguilar,

Sempoux

et al. 2023

Semin Liver Dis

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Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of the precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterize the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment. This review delves into the molecular mechanisms that initiate and promote the development of precursor lesions of intra- and extrahepatic cholangiocarcinoma and of gallbladder carcinoma. It addresses the genomic, epigenomic and transcriptomic landscape of these precursors, and provides an overview of animal and organoid models used to study them. In conclusion, this review summarizes the known molecular features of precancerous lesions in biliary tract cancer and highlights our fragmentary knowledge of the molecular pathogenesis of tumor initiation.

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“…Gallbladder stone, which can damage the gallbladder epithelium and initiate chronic inflammation, is the main cause of gallbladder cancer (GBC) ( Lammert et al, 2016 ). Previous observations have shown that ezetimibe could completely prevent the occurrence and development of chronic inflammation, metaplasia and dysplasia by reducing the level of interstitial macrophage and the infiltration of polymorphonuclear cell and CD8+T cell ( Rosa et al, 2020 ). In addition, estrogen is considered as a critical driver for gallstone formation in male prostate cancer patients who are treated with estrogen ( Henriksson et al, 1989 ).…”

Section: Anti-cancer Mechanisms Of Ezetimibementioning

confidence: 99%

Ezetimibe and Cancer: Is There a Connection?

Zhu

et al. 2022

Front. Pharmacol.

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The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.

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Evaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia

Cited by 9 publications

References 37 publications

Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer

Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer

Biliary Tract Cancer: Molecular Biology of Precursor Lesions

Ezetimibe and Cancer: Is There a Connection?

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