Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

Raimondi, Sara; Lowenfels, Albert B.; Morselli-Labate, Antonio Maria; Maisonneuve, Patrick; Pezzilli, Raffaele

doi:10.1016/j.bpg.2010.02.007

Cited by 544 publications

(405 citation statements)

References 45 publications

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“…KPT mice infected with Lenti-Cre developed PanINs and PDAC 2-6 mo after tumor initiation ( Fig Table 1; data not shown). In many cases, Ad-Cre-induced and Lenti-Cre-induced tumors developed in the head of the pancreas and were accompanied by evidence of gallbladder obstruction and jaundice, a frequent end-stage complication of pancreatic cancer in patients (Supplemental Table 1 Chronic pancreatitis is associated with an increased incidence of PDAC in humans, and experimental evidence from mouse models suggests that adult cells may be refractory to transformation in the absence of pancreatic inflammation (Guerra et al 2007;Raimondi et al 2010). Therefore, we assessed whether retrograde ductal viral infection induces pancreatitis.…”

Section: Resultsmentioning

confidence: 99%

Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing

et al. 2015

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Pancreatic ductal adenocarcinoma (PDAC) is a genomically diverse, prevalent, and almost invariably fatal malignancy. Although conventional genetically engineered mouse models of human PDAC have been instrumental in understanding pancreatic cancer development, these models are much too labor-intensive, expensive, and slow to perform the extensive molecular analyses needed to adequately understand this disease. Here we demonstrate that retrograde pancreatic ductal injection of either adenoviral-Cre or lentiviral-Cre vectors allows titratable initiation of pancreatic neoplasias that progress into invasive and metastatic PDAC. To enable in vivo CRISPR/Cas9-mediated gene inactivation in the pancreas, we generated a Cre-regulated Cas9 allele and lentiviral vectors that express Cre and a single-guide RNA. CRISPR-mediated targeting of Lkb1 in combination with oncogenic Kras expression led to selection for inactivating genomic alterations, absence of Lkb1 protein, and rapid tumor growth that phenocopied Cre-mediated genetic deletion of Lkb1. This method will transform our ability to rapidly interrogate gene function during the development of this recalcitrant cancer.

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Section: Resultsmentioning

confidence: 99%

Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing

et al. 2015

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“…Indeed, inappropriate expression of SCF or c-Kit leads to a wide range of pancreatic diseases, ranging from chronic pancreatitis to pancreatic cancer [64]. It was reported that SCF-c-Kit interactions had an influential effect on mast cells, in which increased mast cell presence correlated with inflammation and fibrosis in chronic pancreatitis [65].…”

Section: C-kit In Pancreatic Disease and Other Metabolic Disordersmentioning

confidence: 99%

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

et al. 2015

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The interactions between c-Kit and its ligand, stem cell factor (SCF), play an important role in haematopoiesis, pigmentation and gametogenesis. c-Kit is also found in the pancreas, and recent studies have revealed that c-Kit marks a subpopulation of highly proliferative pancreatic endocrine cells that may harbour islet precursors. c-Kit governs and maintains pancreatic endocrine cell maturation and function via multiple signalling pathways. In this review we address the importance of c-Kit signalling within the pancreas, including its profound role in islet morphogenesis, islet vascularisation, and beta cell survival and function. We also discuss the impact of c-Kit signalling in pancreatic disease and the use of c-Kit as a potential target for the development of cell-based and novel drug therapies in the treatment of diabetes.

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“…Tobacco smoking,4, 5, 6 high age4, 7, 8 and heredity9, 10 seem to be the only truly validated risk factors for pancreatic cancer. Several other risk factors have been investigated, and numerous studies claim a significant impact of diabetes,11, 12, 13 pancreatitis,14, 15, 16 alcohol17, 18, 19, 20 and body mass index (BMI)13, 21, 22, 23; however, no consensus has yet been reached.…”

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confidence: 99%

Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study

Andersson

Borgquist

Jirström

2018

Intl Journal of Cancer

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The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.

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Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

Cited by 544 publications

References 45 publications

Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing

Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study

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