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

Li, Hui; Li, Yongdong; Cui, Lei; Wang, Biyuan; Cui, Weigang; Li, Minghua; Cheng, Ye

doi:10.1371/journal.pone.0106566

Cited by 21 publications

(13 citation statements)

References 34 publications

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“…These would be helpful for confirming our results, and for providing additional, similar insights into the natural history of PDAC for the development of viable screening technologies. Although pancreatic carcinomas in situ, or PanIN-3, are not detectable by currently available imaging and screening modalities, emerging technologies including molecular imaging, and serum biomarkers such as circulating tumor cells (CTCs) (23–25), may allow for the detection of pancreatic neoplasia at significantly earlier stages within their natural history.…”

Section: Discussionmentioning

confidence: 99%

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size

et al. 2016

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Objectives-Pancreatic Ductal AdenoCarcinoma (PDAC) has not experienced a meaningful mortality improvement over the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies.Methods-Early pancreatic ductal adenocarcinomas from the NCI SEER database (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) were analyzed. We stratified by size and included carcinomas-in-situ (Tis). Overall cancerspecific survival were calculated. A Cox-Proportional Hazards model was developed and the significance of key covariates for survival prediction was evaluated.Results-A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the CoxProportional Hazard analysis. Additional, relatively weaker predictors of worse survival included: older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy.Conclusions-For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

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Section: Discussionmentioning

confidence: 99%

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size

et al. 2016

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“…A number of imaging agents targeting cathepsin E activity have recently been developed to monitor PDAC status in vivo (Cruz-Monserrate et al, 2012; Keliher et al, 2013; Li et al, 2014). These imaging agents were designed to target the mature enzyme active site or be specifically cleaved by cathepsin E. In addition, Abd-Elgaliel and colleagues have developed a cathepsin E activated prodrug that is toxic to cells expressing cathepsin E (Abd-Elgaliel et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors

O’Donoghue

Ivry

Chaudhury

et al. 2016

Biological Chemistry

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The cathepsin family of lysosomal proteases is increasingly being recognized for their altered expression in cancer and role in facilitating tumor progression. The aspartyl protease cathepsin E is overexpressed in several cancers and has been investigated as a biomarker for pancreatic ductal adenocarcinoma (PDAC). Here we show that cathepsin E expression in mouse PDAC tumors is increased by more than 400-fold when compared to healthy pancreatic tissue. Cathepsin E accumulates over the course of disease progression and accounts for more than 3% of the tumor protein in mice with end-stage disease. Through immunoblot analysis we determined that only procathepsin E exists in mouse PDAC tumors and cell lines derived from these tumors. By decreasing the pH, this procathepsion E is converted to the mature form, resulting in an increase in proteolytic activity. Although active site inhibitors can bind procathepsin E, treatment of PDAC mice with the aspartyl protease inhibitor ritonavir did not decrease tumor burden. Lastly, we used multiplex substrate profiling by mass spectrometry to identify two synthetic peptides that are hydrolyzed by procathepsin E near neutral pH. This work represents a comprehensive analysis of procathepsin E in PDAC and could facilitate the development of improved biomarkers for disease detection.

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“…76 The cathepsin E sensitive fluorescent probe was not only able to detect specifically PDAC in human xenografts and genetically modified mouse model but was also able to detect pancreas with PanIN lesions in genetically engineered mouse model before tumor formation in an optical imaging systems. 65 In a genetically defined mouse model of PDAC, PanIN lesions were found to be detectable with the help of cathepsin (cathepsin B, H, L and S) activation by near infrared probe in a confocal fluorescence laser microscope.…”

Section: Cathepsins As Screening Probe For Pancreatic Cancermentioning

confidence: 99%

Roles of cathepsins in pancreatic cancer

Singh¹,

Saraya²

2016

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Pancreatic cancer is an aggressive disease with rapid invasion and metastasis. Extracellular matrix degrading enzymes play an important role in cancer cell invasion and migration. Cathepsins are a group of proteolytic enzymes, which are responsible for the matrix turnover. Among the cathepsins, more number of studies have focused upon cysteine cathepsins. The function and activities of these enzymes are interwoven and their interplay causes the activation of one another by following a proteolytic cascade. This review focuses on differential expression of cathepsins in different types of pancreatic cancer and controls, importance of cathepsins in various phenomena responsible for tumorigenesis and its spread in experimental and human studies. Thus, cathepsins and its expression in pancreatic cancer may be used as potential biomarkers and may prove to be important therapeutic targets if tested clinically.

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

Cited by 21 publications

References 34 publications

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size

Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors

Roles of cathepsins in pancreatic cancer

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