Effect of Nicotine and Cigarette Smoke on an Experimental Model of Intraepithelial Lesions and Pancreatic Adenocarcinoma Induced by 7,12-Dimethylbenzanthracene in Mice

Bersch, Vivian Pierri; Osvaldt, Alessandro Bersch; Edelweiss, Maria Isabel Albano; Schumacher, Rita de Cássia Alves; Wendt, Luiz Roberto Rigo; Abreu, Laís Pilau de; Blom, Carla Brauner; Abreu, Gabriela Pilau de; Costa, Leonardo; Piccinini, Pedro Salomão; Rohde, Luis Augusto

doi:10.1097/mpa.0b013e318184d330

Cited by 27 publications

(25 citation statements)

References 23 publications

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“…NIC and other nAChRs agonists in cigarette smoke appear to have an essential role in the pathogenesis of cancer and arteriosclerosis, which were previously believed to be caused primarily by other components of tobacco smoke (i.e. PAHs and nitrosamines) (Bersch et al, 2009;Wong et al, 2007;Egleton et al, 2008;Schuller, 2007Schuller, , 2008Cucina et al, 2008;Lau et al, 2006;Catanzaro et al, 2007;Knaapen et al, 2007;Ramos and Moorthy, 2005;Baird et al, 2005). Furthermore, recent genome-wide association studies have identified single nucleotide polymorphisms (SNP) in 15q24-25 locus (containing the genes for a3, a5 and b4 subunits of nAChRs), which are associated with the risk of lung cancer, arteriosclerosis, and NIC addiction (Thorgeirsson et al, 2008;Amos et al, 2008;Hung et al, 2008;Volkow et al, 2008).…”

Section: Pharmacology and Health Consequences Of Smokingmentioning

confidence: 99%

Smoking, nicotine and neuropsychiatric disorders

Döme

Lazáry

Kalapos³

et al. 2010

Neuroscience & Biobehavioral Reviews

200

140

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Section: Pharmacology and Health Consequences Of Smokingmentioning

confidence: 99%

Smoking, nicotine and neuropsychiatric disorders

Döme

Lazáry

Kalapos³

et al. 2010

Neuroscience & Biobehavioral Reviews

200

140

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“…But, the model used was relatively consistent with the histopathological features of human PDAC [32], [33]; PanIN grading and the formation of PDAC showed an increasing trend with the extension of DMBA induction time; and CTSE expression level was also gradually increased with the development of lesions. For the transgenic PDAC mouse model, the PDAC and PanINs often show multiple lesions and lack connective tissue hyperplasia; Some genes abnormally expressed in human PDAC are not expressed in the transgenic PDAC mouse model.…”

Section: Discussionmentioning

confidence: 74%

Monitoring Pancreatic Carcinogenesis by the Molecular Imaging of Cathepsin E In Vivo Using Confocal Laser Endomicroscopy

Cui

et al. 2014

PLoS ONE

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The monitoring of pancreatic ductal adenocarcinoma (PDAC) in high-risk populations is essential. Cathepsin E (CTSE) is specifically and highly expressed in PDAC and pancreatic intraepithelial neoplasias (PanINs), and its expression gradually increases along with disease progression. In this study, we first established an in situ 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced rat model for PanINs and PDAC and then confirmed that tumorigenesis properties in this model were consistent with those of human PDAC in that CTSE expression gradually increased with tumor development using histology and immunohistochemistry. Then, using in vivo imaging of heterotopically implanted tumors generated from CTSE- overexpressing cells (PANC-1-CTSE) in nude mice and in vitro imaging of PanINs and PDAC in DMBA-induced rats, the specificity of the synthesized CTSE-activatable probe was verified. Quantitative determination identified that the fluorescence signal ratio of pancreatic tumor to normal pancreas gradually increased in association with progressive pathological grades, with the exception of no significant difference between PanIN-II and PanIN-III grades. Finally, we monitored pancreatic carcinogenesis in vivo using confocal laser endomicroscopy (CLE) in combination with the CTSE-activatable probe. A prospective double-blind control study was performed to evaluate the accuracy of this method in diagnosing PDAC and PanINs of all grades (>82.7%). This allowed us to establish effective diagnostic criteria for CLE in PDAC and PanINs to facilitate the monitoring of PDAC in high-risk populations.

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“…Wisniewska et al (13), however, did not differentiate between the different types of pancreatic cells. Cigarette smoke was found not to promote 7,12-dimethylbenzanthracene-induced pancreatic carcinogenesis in mice (14). Cell proliferation was increased in the lung after short-term exposure to cigarette smoke in several studies (7,8,15,16).…”

Section: Discussionmentioning

confidence: 95%

Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation

et al. 2017

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Abstract. Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRas G12D ) in the pancreas as well as wild-type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure decreased cell proliferation in pancreatic ductal and acinar cells, and had no effect in islet cells. Cigarette smoke did not affect pancreatic protein levels of tumor necrosis factor (TNF)α, p53, or cyclin D 1 , but mutant Kras overexpression slightly decreased TNFα and p53 protein levels. Therefore, pancreatic cell proliferation in mice overexpressing mutant Kras is associated with the later development of pancreatic tumors, but effects of cigarette smoke on pancreatic cell proliferation do not provide a good model for human pancreatic carcinogenesis.

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Effect of Nicotine and Cigarette Smoke on an Experimental Model of Intraepithelial Lesions and Pancreatic Adenocarcinoma Induced by 7,12-Dimethylbenzanthracene in Mice

Abstract: Nicotine but not cigarette smoke promotes pancreatic DMBA carcinogenesis in mice. Pancreatic adenocarcinomas and PanINs have the same phenotypic appearance as those that occur in humans.

Cited by 27 publications

References 23 publications

Smoking, nicotine and neuropsychiatric disorders

Smoking, nicotine and neuropsychiatric disorders

Monitoring Pancreatic Carcinogenesis by the Molecular Imaging of Cathepsin E In Vivo Using Confocal Laser Endomicroscopy

Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation

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