Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic...

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Bibliographic Details
Published in:Scientific reports 2014-03, Vol.4 (1), p.4410-4410, Article 4410
Main Authors: Cruz-Monserrate, Zobeida, Roland, Christina L., Deng, Defeng, Arumugam, Thiruvengadam, Moshnikova, Anna, Andreev, Oleg A., Reshetnyak, Yana K., Logsdon, Craig D.
Format: Article
Language:English
Subjects:
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631/67/2321
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Amino Acid Sequence
Animals
Carcinoma, Pancreatic Ductal - diagnosis
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - secondary
Cell Line, Tumor
Diagnostic Imaging - methods
Disease Models, Animal
Humanities and Social Sciences
Humans
Hydrogen-Ion Concentration
Mice
Mice, Nude
Molecular Sequence Data
multidisciplinary
Neoplasm Transplantation
Pancreatic Neoplasms - diagnosis
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Peptides - chemical synthesis
Peptides - metabolism
Peritoneal Neoplasms - diagnosis
Peritoneal Neoplasms - metabolism
Peritoneal Neoplasms - secondary
Prognosis
Science
Tumor Microenvironment
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep04410