References of "Struman, Ingrid"
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See detailNF-kappaB activation in endothelial cells is critical for the activity of angiostatic agents.
Tabruyn, Sébastien ULg; Memet, Sylvie; Ave, Patrick et al

in Molecular Cancer Therapeutics (2009), 8(9), 2645-54

In tumor cells, the transcription factor NF-kappaB has been described to be antiapoptotic and proproliferative and involved in the production of angiogenic factors such as vascular endothelial growth ... [more ▼]

In tumor cells, the transcription factor NF-kappaB has been described to be antiapoptotic and proproliferative and involved in the production of angiogenic factors such as vascular endothelial growth factor. From these data, a protumorigenic role of NF-kappaB has emerged. Here, we examined in endothelial cells whether NF-kappaB signaling pathway is involved in mediating the angiostatic properties of angiogenesis inhibitors. The current report describes that biochemically unrelated agents with direct angiostatic effect induced NF-kappaB activation in endothelial cells. Our data showed that endostatin, anginex, angiostatin, and the 16-kDa N-terminal fragment of human prolactin induced NF-kappaB activation in endothelial cells in both cultured human endothelial cells and in vivo in a mouse tumor model. It was also found that NF-kappaB activity was required for the angiostatic activity, because inhibition of NF-kappaB in endothelial cells impaired the ability of angiostatic agents to block sprouting of endothelial cells and to overcome endothelial cell anergy. Therefore, activation of NF-kappaB in endothelial cells can result in an unexpected antitumor outcome. Based on these data, the current approach of systemic treatment with NF-kappaB inhibitors may therefore be revisited because NF-kappaB activation specifically targeted to endothelial cells might represent an efficient strategy for the treatment of cancer. [less ▲]

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See detailAntiangiogenic liposomal gene therapy with 16K human prolactin efficiently reduces tumor growth.
Kinet, Virginie ULg; Nguyen, Ngoc-Quynh-Nhu ULg; Sabatel, Céline ULg et al

in Cancer Letters (2009), 284(2), 222-228

Human 16K PRL (16K hPRL) is a potent inhibitor of angiogenesis both in vitro and in vivo. It has been shown to prevent tumor growth in three xenograft mouse models. Here we have used a gene transfer ... [more ▼]

Human 16K PRL (16K hPRL) is a potent inhibitor of angiogenesis both in vitro and in vivo. It has been shown to prevent tumor growth in three xenograft mouse models. Here we have used a gene transfer method based on cationic liposomes to produce 16K hPRL and demonstrate that 16K hPRL inhibits tumor growth in a subcutaneous B16F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in the reduction of tumor vessel length and width, leading to a 57% reduction in average vessel size. We thus show, for the first time, that administration of the 16K hPRL gene complexed to cationic liposomes is effective to maintain antiangiogenic activities of 16K hPRL level. [less ▲]

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See detailNovel antiangiogenic peptide agents and their therapeutic and diagnostic use
Weiner, Richard I.; Martial, Joseph ULg; Struman, Ingrid ULg et al

Patent (2008)

The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormones, human placental lactogen ... [more ▼]

The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormones, human placental lactogen, human growth hormone variant hGH-V, and prolactin, and their use in inhibiting angiogenesis and in the diagnosis of diseases of human pregnancy involving abnormalities of placental vascularization. [less ▲]

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See detailStudy of the role of Sprouty1 in the regulation of angiogenesis
Sabatel, Céline; Tabruyn, Sébastien ULg; Cornet, Anne et al

Poster (2008, March 30)

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See detailAntiangiogenic peptides
Martial, Joseph ULg; Struman, Ingrid ULg; Nguyen, Ngoc-Quynh-Nhu ULg et al

Patent (2008)

The present invention refers to a pharmaceutical composition comprising an isolated antiangiogenic peptide or a recombinant protein comprising the antiangiogenic peptide, wherein the peptide is between 11 ... [more ▼]

The present invention refers to a pharmaceutical composition comprising an isolated antiangiogenic peptide or a recombinant protein comprising the antiangiogenic peptide, wherein the peptide is between 11 and 40 amino acids in length and having antiangiogenic activity, the peptide comprising the amino acid sequence: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14, wherein X1 is any amino acid residue comptabile with forming a helix; X2 is an amino acid redisue of : Leu, Ile, Val; X3 is an amino acid residue of: Arg, Lys, His, Ser, Thr; X4 is an amino acid residue of: Ile, Leu, Val; X5 is any amino acid residue compatible with forming a helix; X6 is an amino acid residue of: Leu, Ile, Val; X7 is an amino acid residue of: Leu, Ile, Val, Ser, Thr; X8 is any amino acid residue compatible with forming a helix; X9 is any amino acid residue compatible with forming a helix; X10 is an amino acid residue of: Gln, Glu, Asp, Arg, His, Lys, Asn; X11 is an amino acid residue of: Ser, Thr; X12 is an amino acid residue of: Trp, Tyr, Phe; X13 is an animo acid residue of Leu, Ile, Val, Asn, Gln; X14 is an amino acid residue of: Glu, Gln, Asp, Asn. [less ▲]

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See detailZebrafish Sox7 and Sox18 function together to control arterial-venous identity
Pendeville-Samain, Hélène ULg; Winandy, Marie ULg; Manfroid, Isabelle ULg et al

in Developmental Biology (2008), 317(2), 405-16

Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox18 are the underlying cause of ... [more ▼]

Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox18 are the underlying cause of the severe hypotrichosis-lymphedema-telangiectasia disorder characterized by vascular defects. However little is known about which vasculogenic processes Sox7 and Sox18 regulate in vivo. We cloned the orthologs of Sox7 and Sox18 in zebrafish, analysed their expression pattern and performed functional analyses. Both genes are expressed in the lateral plate mesoderm during somitogenesis. At later stages, Sox18 is expressed in all axial vessels whereas Sox7 expression is mainly restricted to the dorsal aorta. Knockdown of Sox7 or Sox18 alone failed to reveal any phenotype. In contrast, blocking the two genes simultaneously led to embryos displaying dysmorphogenesis of the proximal aorta and arteriovenous shunts, all of which can account for the lack of circulation observed in the trunk and tail. Gene expression analyses performed with general endothelial markers on double morphants revealed that Sox7 and Sox18 are dispensable for the initial specification and positioning of the major trunk vessels. However, morphants display ectopic expression of the venous Flt4 marker in the dorsal aorta and a concomitant reduction of the artery-specific markers EphrinB2a and Gridlock. The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest that Sox7 and Sox18 control arterial-venous identity by regulating Gridlock expression. [less ▲]

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See detailInhibition of tumor growth and metastasis establishment by adenovirus-mediated gene transfer delivery of the antiangiogenic factor 16K hPRL
Nguyen, Ngoc-Quynh-Nhu ULg; Cornet, Anne ULg; Blacher, Silvia ULg et al

in Molecular Therapy : The Journal of the American Society of Gene Therapy (2007), 15(12), 2094-2100

Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic ... [more ▼]

Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic therapy, therefore, holds potential as an attractive strategy for inhibiting metastasis development. Human 16K PRL (16K hPRL), a potent inhibitor of angiogenesis, has been demonstrated to prevent tumor growth in two xenograft mouse models, but whether it also affects tumor metastasis is unknown. In this study we will investigate the ability of 16K hPRL to prevent the establishment of metastasis. We demonstrate that 16K hPRL administered via adenovirus-mediated gene transfer, inhibits tumor growth by 86% in a subcutaneous (SC) B16-F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in a reduction of tumor-vessel length and width, leading to a 57% reduction of average vessel size. In a pre-established tumor model, moreover, 16K hPRL can significantly delay tumor development. Finally, for the first time, we provide evidence that 16K hPRL considerably reduces the establishment of B16-F10 metastasis in an experimental lung metastasis model. Both the number and size of metastases are reduced by 50% in 16K hPRL-treated mice. These results highlight a potential role for 16K hPRL in anticancer therapy for both primary tumors and metastases. [less ▲]

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See detailThe expression of prolactin and its cathepsin D-mediated cleavage in the bovine corpus luteum vary with the estrous cycle
Erdmann, S.; Ricken, A.; Merkwitz, C. et al

in American Journal of Physiology - Endocrinology and Metabolism (2007), 293(5), 1365-1377

In the corpus luteum (CL), blood vessels develop, stabilize, and regress. This process depends on the ratio of pro-and antiangiogenic factors, which change during the ovarian cycle. The present study ... [more ▼]

In the corpus luteum (CL), blood vessels develop, stabilize, and regress. This process depends on the ratio of pro-and antiangiogenic factors, which change during the ovarian cycle. The present study focuses on the possible roles of 23,000 (23K) prolactin (PRL) in the bovine CL and its antiangiogenic NH2-terminal fragments after extracellular cleavage by cathepsin D (Cath D). PRL RNA and protein were demonstrated in the CL tissue, in luteal endothelial cells, and in steroidogenic cells. Cath D was detected in CL tissue, cell extracts, and corresponding cell supernatants. In the intact CL, 23K PRL levels decreased gradually, whereas Cath D levels concomitantly increased between early and late luteal stages. In vitro, PRL cleavage occurred in the presence of acidified homogenates of CL tissue, cells, and corresponding cell supernatants. Similar fragments were obtained with purified Cath D, and their appearance was inhibited by pepstatin A. The aspartic protease specific substrate MOCAc-GKPILF similar to FRLK(Dnp)-D-R-NH2 was cleaved by CL cell supernatants, providing further evidence for Cath D activity. The 16,000 PRL inhibited proliferation of luteal endothelial cells accompanied by an increase in cleaved caspase-3. In conclusion, 1) the bovine CL is able to produce PRL and to process it into antiangiogenic fragments by Cath D activity and 2) PRL cleavage might mediate angioregression during luteolysis. [less ▲]

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See detailDetection of micro-RNA/gene interactions involved in angiogenesis using machine learning techniques
Huynh-Thu, Vân Anh ULg; Hiard, Samuel ULg; Geurts, Pierre ULg et al

Poster (2007, September)

Motivation: Angiogenesis is the process responsible for the growth of new blood vessels from existing ones. It is also associated with the development of cancer, as tumors need to be irrigated by blood ... [more ▼]

Motivation: Angiogenesis is the process responsible for the growth of new blood vessels from existing ones. It is also associated with the development of cancer, as tumors need to be irrigated by blood vessels for growing. New cancer therapies appear that exploit angiogenesis inhibitors, also called angiostatic agents, to asphyxiate and starve the tumors. Better understanding the regulatory mechanisms that control angiogenesis is thus fundamental. Recently, short non-coding RNA molecules, called micro-RNAs, have been discovered that are involved in post- transcriptional regulation of gene expressions. These molecules bind to RNA messengers following the base pairing rules, preventing them from being translated into proteins and/or tagging them for degradation. The main goal of this work is to use computational approaches to identify micro-RNAs involved in angiogenesis. Method: In order to identify genes involved in angiogenesis, bovine endothelial cells were treated by a known angiogenesis inhibitor [1], prolactin 16K, and their gene expression profile was compared to the profile of untreated cells. The genes were then divided into three classes: up-regulated, down-regulated, and unaffected genes. The 3'UTR regions of these genes were then analysed by machine learning techniques. Different approaches were considered. First, we described each gene by a vector of motif counts in their 3'UTR regions and used machine learning techniques to rank the motifs according to their relevance for separating the genes into the different classes. We considered successively motifs corresponding to the seeds of known micro- RNAs and also all possible motifs of a given length. To rank the motifs, we compared ensemble of decision trees and linear support vector machines. Second, we considered an approach called Segment and Combine that was proposed in [2]. Finally, we also carried out an exhaustive search of all motifs of a given length that satisfy some constraints on specificity and coverage with respect to a given gene category. Results: The ability of the different approaches at identifying relevant motifs was first assessed on genes predicted to be the target of some known miRNAs. In this simple setting, most methods were able to identify the micro-RNA seed. The results obtained on the genes regulated by prolactin 16K are also very encouraging. We were able to identify one micro-RNA already known to play a role in angiogenesis and several motifs are predicted by different approaches as very specific of up- or down-regulation by prolactin 16K. Their relationship with known micro-RNAs is certainly worth exploring. Conclusion: Machine learning approaches are promising techniques for the identification of micro-RNA/gene interactions. Future work will concern the application of the same kind of techniques on promoters for the identification of transcription factor binding sites. [less ▲]

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See detailAntiangiogenic peptides
Martial, Joseph ULg; Struman, Ingrid ULg; Nguyen, Ngoc-Quynh-Nhu ULg et al

Patent (2007)

The present invention refers to antiangiogenic peptides, especially to tilted peptides having antiangiogenic properties and peptides from the prolactin/growth hormone familiy having antiangiogenic ... [more ▼]

The present invention refers to antiangiogenic peptides, especially to tilted peptides having antiangiogenic properties and peptides from the prolactin/growth hormone familiy having antiangiogenic properties. [less ▲]

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See detailA cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy
Hilfiker-Kleiner, D.; Kaminski, K.; Podewski, E. et al

in Cell (2007), 128(3), 589-600

Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 ... [more ▼]

Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitior of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM. [less ▲]

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See detailEvaluation of the antitumor activity of 16K prolactin
Kinet, Virginie; Nguyen, Ngoc-Quynh-Nhu ULg; Cornet, Anne ULg et al

Poster (2007)

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See detailRecovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine
Hilfiker-Kleiner, D.; Meyer, G. P.; Schieffer, E. et al

in Journal of the American College of Cardiology (2007), 50(24), 2354-5

Detailed reference viewed: 43 (6 ULg)