Regulation of Angiogenesis and Tumor Growth by Thrombospondin-1

2008 ◽  
pp. 401-415
Author(s):  
Karen O. Yee ◽  
Jack Lawler
Keyword(s):  
Tumor Growth ◽  
Thrombospondin 1

scholarly journals Expression of the Type-1 Repeats of Thrombospondin-1 Inhibits Tumor Growth Through Activation of Transforming Growth Factor-β

2004 ◽  
Vol 165 (2) ◽  
pp. 541-552 ◽  
Author(s):  
Karen O. Yee ◽  
Michael Streit ◽  
Thomas Hawighorst ◽  
Michael Detmar ◽  
Jack Lawler
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Thrombospondin 1

Thrombospondin-1 Mimetic Peptide Inhibitors of Angiogenesis and Tumor Growth:  Design, Synthesis, and Optimization of Pharmacokinetics and Biological Activities†

2005 ◽  
Vol 48 (8) ◽  
pp. 2838-2846 ◽  
Author(s):  
Fortuna Haviv ◽  
Michael F. Bradley ◽  
Douglas M. Kalvin ◽  
Andrew J. Schneider ◽  
Donald J. Davidson ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Biological Activities ◽  
Peptide Inhibitors ◽  
Design Synthesis ◽  
Mimetic Peptide ◽  
Thrombospondin 1

scholarly journals Abstract 198: The T3R domain of thrombospondin-1 delays tumor growth and improves tumor response to chemotherapy by remodeling the tumor vasculature

2019 ◽  
Author(s):  
Denise Pinessi ◽  
Andrea Resovi ◽  
Lavinia Morosi ◽  
Patrizia Borsotti ◽  
Alexander Berndt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Response ◽  
Tumor Vasculature ◽  
Response To Chemotherapy ◽  
Thrombospondin 1

scholarly journals Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent mechanism

2006 ◽  
Vol 5 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Karen O. Yee ◽  
Caitlin M. Connolly ◽  
Mark Pines ◽  
Jack Lawler
Keyword(s):  
Tumor Growth ◽  
T Antigen ◽  
Independent Mechanism ◽  
Thrombospondin 1 ◽  
Polyoma Middle T Antigen ◽  
Middle T Antigen

Phase II Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer: A Trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia

2008 ◽  
Vol 26 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Agustin A. Garcia ◽  
Hal Hirte ◽  
Gini Fleming ◽  
Dongyun Yang ◽  
Denice D. Tsao-Wei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Phase Ii ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Oral Cyclophosphamide ◽  
Frequent Administration ◽  
Thrombospondin 1 ◽  
Endothelial Growth Factor

PurposeVascular endothelial growth factor (VEGF) plays an important role in the biology of ovarian cancer (OC). Inhibitors of VEGF suppress tumor growth in OC models. Metronomic chemotherapy, defined as frequent administration of low doses of cytotoxic chemotherapy, suppresses tumor growth, possibly by inhibiting angiogenesis. A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC.Patients and MethodsPatients with measurable disease and prior treatment with a platinum-containing regimen were eligible. Up to two different regimens for recurrent disease were allowed. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d. The primary end point was progression-free survival at 6 months. Plasma levels of VEGF, E-selectin, and thrombospondin-1 were obtained serially.ResultsSeventy patients were enrolled. The probability of being alive and progression free at 6 months was 56% (± 6% SE). A partial response was achieved in 17 patients (24%). Median time to progression and survival were 7.2 and 16.9 months, respectively. The most common serious toxicities were hypertension, fatigue, and pain. Bevacizumab-related toxicities included four episodes of gastrointestinal perforation or fistula, two episodes each of CNS ischemia and pulmonary hypertension, and one episode each of gastrointestinal bleeding and wound healing complication. There were three treatment-related deaths. Levels of VEGF, E-selectin, and thrombospondin-1 were not associated with clinical outcome.ConclusionThe combination of bevacizumab and metronomic cyclophosphamide is active in recurrent OC. Further study of this combination is warranted.

scholarly journals Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis

Blood ◽  
2010 ◽  
Vol 115 (22) ◽  
pp. 4605-4613 ◽  
Author(s):  
Alexander Zaslavsky ◽  
Kwan-Hyuck Baek ◽  
Ryan C. Lynch ◽  
Sarah Short ◽  
Jenny Grillo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Angiogenesis Inhibitor ◽  
Negative Regulator ◽  
Mouse Tumor ◽  
Tumor Bearing ◽  
Potential Biomarker ◽  
Thrombospondin 1

Abstract The sequential events leading to tumor progression include a switch to the angiogenic phenotype, dependent on a shift in the balance between positive and negative angiogenic regulators produced by tumor and stromal cells. Although the biologic properties of many angiogenesis regulatory proteins have been studied in detail, the mechanisms of their transport and delivery in vivo during pathologic angiogenesis are not well understood. Here, we demonstrate that expression of one of the most potent angiogenesis inhibitors, thrombospondin-1, is up-regulated in the platelets of tumor-bearing mice. We establish that this up-regulation is a consequence of both increased levels of thrombospondin-1 mRNA in megakaryocytes, as well as increased numbers of megakaryocytes in the bone marrow of tumor-bearing mice. Through the use of mouse tumor models and bone marrow transplantations, we show that platelet-derived thrombospondin-1 is a critical negative regulator during the early stages of tumor angiogenesis. Collectively, our data suggest that the production and delivery of the endogenous angiogenesis inhibitor thrombospondin-1 by platelets may be a critical host response to suppress tumor growth through inhibiting tumor angiogenesis. Further, this work implicates the use of thrombospondin-1 levels in platelets as an indicator of tumor growth and regression.

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