This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (35)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Liver/ Biliary Tract/ Pancreatic Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Selwyn M. Vickers, MD; Lee Ann MacMillan-Crow, PhD; Mary Green, BA; Chris Ellis, BA; John A. Thompson, PhD

Arch Surg. 1999;134:245-251.

Background  Despite recognition of the devastating malignant potential of pancreatic cancer, the exact pathophysiological events contributing to tumor growth, vascular invasiveness, and hepatic metastasis remain to be elucidated.

Methods  Twelve human pancreatic adenocarcinomas were evaluated using immunohistochemical and in situ hybridization techniques for the appearance of the angiogenic and neurogenic growth factors, acidic fibroblast (FGF-1) and basic fibroblast growth factor (FGF-2), and their high-affinity receptors. Since FGF biological processes appear to be regulated by oxidant stress, tumors were examined further for the immunoappearance of inducible nitric oxide synthase (iNOS) and nitrotyrosine.

Results  Compared with normal human pancreatic tissue, tumor specimens exhibited varying levels of enhanced staining for FGF ligands and receptors. The increased appearance of FGF-1 and FGF-2 proteins was accompanied by increased detection of messenger RNA encoding each growth factor. In addition, these pancreatic tumors demonstrated the overexpression of iNOS and immunostaining of nitrotyrosine compared with normal pancreatic tissue.

Conclusions  The enhanced expression of FGF and FGF receptors suggests that these polypeptide mitogens may serve as important mediators of growth and of angiogenic and metastatic responses associated with pancreatic tumors, not seen in normal pancreatic tissue. Furthermore, we provide the first indication of increased expression of iNOS and protein tyrosine nitration, thereby predicting the potential involvement of oxidant stress during development and progression of pancreatic adenocarcinoma.

From the Department of Surgery, School of Medicine, University of Alabama at Birmingham.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Increased expression of inducible nitric oxide synthase (iNOS) in N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic carcinogenesis and prevention of cancer development by ONO-1714, an iNOS inhibitor
Takahashi et al.
Carcinogenesis 2008;29:1608-1613.
ABSTRACT | FULL TEXT  

Tumor Escape Mechanism Governed by Myeloid-Derived Suppressor Cells
Nagaraj and Gabrilovich
Cancer Res. 2008;68:2561-2563.
ABSTRACT | FULL TEXT  

Negative Association of Melanoma Differentiation-associated Gene (mda-7) and Inducible Nitric Oxide Synthase (iNOS) in Human Melanoma: MDA-7 Regulates iNOS Expression in Melanoma Cells
Ekmekcioglu et al.
Molecular Cancer Therapeutics 2003;2:9-17.
ABSTRACT | FULL TEXT  

Oxidative Stress and p53 Mutations in the Carcinogenesis of Iron Overload-Associated Hepatocellular Carcinoma
Marrogi et al.
JNCI J Natl Cancer Inst 2001;93:1652-1655.
FULL TEXT  

Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis
Jaiswal et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2001;281:G626-G634.
ABSTRACT | FULL TEXT  

Inducible Nitric Oxide Synthase and Nitrotyrosine in Human Metastatic Melanoma Tumors Correlate with Poor Survival
Ekmekcioglu et al.
Clin. Cancer Res. 2000;6:4768-4775.
ABSTRACT | FULL TEXT  

Selective Nitration of Histone Tyrosine Residues in Vivo in Mutatect Tumors
Haqqani et al.
J. Biol. Chem. 2002;277:3614-3621.
ABSTRACT | FULL TEXT