Target Therapy Using a Small Molecule Inhibitor against Angiogenic Receptors in Pancreatic Cancer

Büchler, Peter; Reber, Howard A.; Roth, Mendel; Shiroishi, Mark S.; Frieß, Helmut; Hines, Oscar J.

doi:10.1593/neo.06616

Cited by 32 publications

(26 citation statements)

References 43 publications

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“…28 The experimental protocol was approved by the Chancellor's Animal Research Committee of the University of Heidelberg (Heidelberg, Germany) in accordance with national guidelines for animal care and the use of laboratory animals. The poorly differentiated human pancreatic cancer cell line MIA-PaCa-2 was used for xenograft tumor induction.…”

Section: Evaluation Of Msc Differentiationmentioning

confidence: 99%

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

et al. 2008

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Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 mm h À1 was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.

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Section: Evaluation Of Msc Differentiationmentioning

confidence: 99%

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

et al. 2008

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“…By targeting both receptors, PD17304 should be both anti-angiogenic and anti-mitogenic, thereby potentially abrogating two critical pathways in tumor growth and metastasis [94]. Preclinical trials in orthotopic mouse models showed significant reduction in tumor growth, a lower incidence of metastatic spread, and a lower volume of ascites in PD173074-treated animals [95]. These data suggest that PD17304 may be a promising new treatment option for PDAC.…”

Section: Small-molecule Inhibitors Targeting Growth Factors And/or Thmentioning

confidence: 98%

Targeting angiogenesis in pancreatic cancer: rationale and pitfalls

Whipple

Korc

2008

Langenbecks Arch Surg

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“…The tumor size in the subcutaneous xenograft model was measured every 6 days using a vernier caliper, while in the two orthotopic xenograft models the size of the tumor was measured using an in vivo animal fluorescence imager (Carestream Health, Rochester, NY, USA) (excitation wavelength, 530 nm; emission wavelength, 600 nm). The average tumor volume (V) was calculated using the following equation: V = A x B 2 x 0.5 (A, long diameter; B, short diameter) (10). The tumor growth rate (U) was calculated using the equation U = V (mm 3 )/tumor-bearing time (days).…”

Section: Preparation Of Pancreatic Cells Stably Expressing Red Fluorementioning

confidence: 99%

Construction of orthotopic xenograft mouse models for human pancreatic cancer

Dai

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Animal models are indispensable for the study of tumorigenesis and the development of anti-cancer drugs for human pancreatic cancer. In the present study, two orthotopic xenograft mouse models were developed. AsPC-1 human pancreatic cancer cells were stably labeled with red fluorescent protein (RFP) and injected subcutaneously into nude mice. For the orthotopic tumor mass model, the formed subcutaneous tumors were cut into blocks and implanted into the pancreas of nude mice via laparotomy. For the Matrigel™ tumor block model, solidified Matrigel containing RFP-labeled AsPC-1 cells was cut into blocks and implanted into the pancreas of nude mice. A subcutaneous tumor xenograft model was used as a control. Tumor growth and metastasis were assessed using an in vivo fluorescence imaging system. Thirty-six days after implantation, all mice from the two orthotopic xenograft models (n=20 per group) and 55% of the subcutaneous xenograft mice (n=20) developed tumors. The tumor growth rate was significantly higher in the orthotopic models than that in the subcutaneous model (P<0.01). Metastasis to organs such as the liver was observed in the orthotopic tumor models. Histological examination showed that the tumors were poorly differentiated adenocarcinomas. In conclusion, two orthotopic xenograft mouse models of human pancreatic cancer were established; these exhibited greater tumor growth and metastasis than the subcutaneous xenograft mouse model.

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Target Therapy Using a Small Molecule Inhibitor against Angiogenic Receptors in Pancreatic Cancer

Abstract: These data highlight VEGF-RII and FGF-RI as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable pancreatic cancer patients.

Cited by 32 publications

References 43 publications

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer

Targeting angiogenesis in pancreatic cancer: rationale and pitfalls

Construction of orthotopic xenograft mouse models for human pancreatic cancer

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