BACKGROUND: The stem cell marker nestin recently has been shown to be expressed in nascent blood vessels in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice. MATERIALS AND METHODS: In the present study, we visualized by dual-color fluorescence imaging tumor angiogenesis in the ND-GFP transgenic nude mice after orthotopic transplantation of the MIA PaCa-2 human pancreatic cancer line expressing red fluorescent protein. Mice were treated with gemcitabine at 150 mg/kg/dose on days 3, 6, 10, and 13 after tumor implantation. At day 14, mice were sacrificed and mean nascent blood vessel density and tumor volume were calculated and compared to control mice. RESULTS: Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that CD31 co-localized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. Gemcitabine significantly decreased the mean nascent blood vessel density in the tumor as well as decreased tumor volume. CONCLUSION: The dual-color model of the ND-GFP nude mouse orthotopically implanted with RFP-expressing pancreatic tumor cells enabled the simultaneous visualization and quantitation of tumor angiogenesis and tumor volume. These results demonstrated for the first time that gemcitabine is an inhibitor of angiogenesis as well as tumor growth in pancreatic cancer. The results have important implications for the clinical application of gemcitabine in this disease.
BACKGROUND: The stem cell marker nestin recently has been shown to be expressed in nascent blood vessels in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice. MATERIALS AND METHODS: In the present study, we visualized by dual-color fluorescence imaging tumor angiogenesis in the ND-GFP transgenic nude mice after orthotopic transplantation of the MIA PaCa-2 humanpancreatic cancer line expressing red fluorescent protein. Mice were treated with gemcitabine at 150 mg/kg/dose on days 3, 6, 10, and 13 after tumor implantation. At day 14, mice were sacrificed and mean nascent blood vessel density and tumor volume were calculated and compared to control mice. RESULTS: Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that CD31 co-localized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. Gemcitabine significantly decreased the mean nascent blood vessel density in the tumor as well as decreased tumor volume. CONCLUSION: The dual-color model of the ND-GFP nude mouse orthotopically implanted with RFP-expressing pancreatic tumor cells enabled the simultaneous visualization and quantitation of tumor angiogenesis and tumor volume. These results demonstrated for the first time that gemcitabine is an inhibitor of angiogenesis as well as tumor growth in pancreatic cancer. The results have important implications for the clinical application of gemcitabine in this disease.
Authors: Eric A Murphy; David J Shields; Konstantin Stoletov; Elena Dneprovskaia; Michele McElroy; Joshua I Greenberg; Jeff Lindquist; Lisette M Acevedo; Sudarshan Anand; Bharat Kumar Majeti; Igor Tsigelny; Adrian Saldanha; Breda Walsh; Robert M Hoffman; Michael Bouvet; Richard L Klemke; Peter K Vogt; Lee Arnold; Wolfgang Wrasidlo; David A Cheresh Journal: Proc Natl Acad Sci U S A Date: 2010-02-12 Impact factor: 11.205
Authors: Georg Feldmann; Surajit Dhara; Volker Fendrich; Djahida Bedja; Robert Beaty; Michael Mullendore; Collins Karikari; Hector Alvarez; Christine Iacobuzio-Donahue; Antonio Jimeno; Kathleen L Gabrielson; William Matsui; Anirban Maitra Journal: Cancer Res Date: 2007-03-01 Impact factor: 12.701
Authors: Hop S Tran Cao; Hiroaki Kimura; Sharmeela Kaushal; Cynthia S Snyder; Jose Reynoso; Robert M Hoffman; Michael Bouvet Journal: JOP Date: 2009-03-09
Authors: Michele K McElroy; Sharmeela Kaushal; Hop S Tran Cao; A R Moossa; Mark A Talamini; Robert M Hoffman; Michael Bouvet Journal: Mol Cancer Ther Date: 2009-07-07 Impact factor: 6.261