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Autologous Stem Cell Transplantation: Leukapheresis Product has Anti-angiogenic Effects In Vivo Correlating with Neutrophil-derived VEGFR1
被引:0
|作者:
Luethy, Anita
[1
,2
]
Stenner, Frank
[3
]
Lohri, Corinne
[3
]
Muller, Christoph
[1
,2
]
Samaras, Panagiotis
[3
]
Steiner, Rudolf
[3
]
Van den Broek, Maries
[3
]
Mischo, Axel
[3
]
Renner, Christoph
[3
]
Knuth, Alexander
[3
]
Ruegg, Curzio
[4
]
Wenger, Roland H.
[1
,2
]
Zweifel, Martin
[3
]
机构:
[1] Univ Zurich, Inst Physiol, Zurich, Switzerland
[2] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland
[3] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland
[4] Univ Fribourg, Fac Sci, Dept Med, CH-1700 Fribourg, Switzerland
关键词:
Alternative splicing;
angiogenesis;
autologous stem cell transplantation;
chick chorioallantoic membrane assay;
high-dose chemotherapy;
placental growth factor;
vascular endothelial growth factor;
VEGFR1;
ENDOTHELIAL GROWTH-FACTOR;
BONE-MARROW-TRANSPLANTATION;
ACUTE MYOCARDIAL-INFARCTION;
PERIPHERAL-BLOOD;
PROGENITOR CELLS;
MULTIPLE-MYELOMA;
FACTOR RECEPTOR-1;
TYROSINE KINASE;
LIMB ISCHEMIA;
THERAPEUTIC ANGIOGENESIS;
D O I:
暂无
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Background: High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is used for the treatment of hemato-oncologic malignancies. In this study, we measured the effect of HDC/ASCT on plasma concentrations of antiangiogenic soluble vascular endothelial growth factor receptor I (sVEGFR1) and of leukapheresis products (LP) and patient serum on chick chorioallantoic (CAM) angiogenesis. Materials and Methods: VEGFR1- and CD34-expressing cells of leukapheresis products were analyzed by flow cytometry. Alternatively spliced isoforms of VEGFR1 mRNA were quantified using reverse transcription PCR. Results: Plasma concentrations of sVEGFR1 decreased after HDC, but significantly increased after ASCT. In the CAM assay, sera of patients elicited a proangiogenic effect before and after HDC, but a strong antiangiogenic response after ASCT, comparable to that of bevacizumab at therapeutic concentrations. LP contains high concentrations of sVEGFR1, and high density of VEGFR1(+) neutrophilic granulocytes, in which mRNA expression is shifted toward the soluble VEGFR1 isoform. Conclusion: Neutrophil-derived antiangiogenic sVEGFR1 within the LP may contribute to the therapeutic efficacy of ASCT.
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页码:3115 / 3124
页数:10
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