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Université de Fribourg

The αVβ3/αVβ5 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model

Hagen, Timo L.M. ten ; Seynhaeve, Ann L.B. ; Wiel-Ambagtsheer, Gisela aan de ; Bruijn, Ernst A. de ; Tiel, Sandra T. van ; Rüegg, Curzio ; Meyring, Michael ; Grell, Matthias ; Goodman, Simon L. ; Eggermont, Alexander M.M.

In: International Journal of Cancer, 2012, p. -

Isolated limb perfusion (ILP) with melphalan and tumor necrosis factor (TNF)-α is used to treat bulky, locally advanced melanoma and sarcoma. However, TNF toxicity suggests a need for better-tolerated drugs. Cilengitide (EMD 121974), a novel cyclic inhibitor of alpha-V integrins, has both anti-angiogenic and direct anti-tumor effects and is a possible alternative to TNF in ILP. In this study,...

Université de Fribourg

New insights into the mechanisms of organ-specific breast cancer metastasis

Lorusso, Girieca ; Rüegg, Curzio

In: Seminars in Cancer Biology, 2012, p. -

Despite the substantial advances obtained in the treatment of localized malignancies, metastatic disease still lacks effective treatment and remains the primary cause of cancer mortality, including in breast cancer. Thus, in order to improve the survival of cancer patients it is necessary to effectively improve prevention or treatment of metastasis. To achieve this goal, complementary strategies...

Université de Fribourg

Concepts of metastasis in flux: the stromal progression model

Sleeman, Jonathan P. ; Christofori, Gerhard ; Fodde, Riccardo ; Collard, John G. ; Berx, Geert ; Decraene, Charles ; Rüegg, Curzio

In: Seminars in Cancer Biology, 2012, p. -

The ability of tumor cells to leave a primary tumor, to disseminate through the body, and to ultimately seed new secondary tumors is universally agreed to be the basis for metastasis formation. An accurate description of the cellular and molecular mechanisms that underlie this multistep process would greatly facilitate the rational development of therapies that effectively allow metastatic...

Université de Fribourg

Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axes

Xue, Gongda ; Restuccia, David F. ; Lan, Qiang ; Hynx, Debby ; Dirnhofer, Stephan ; Hess, Daniel ; Rüegg, Curzio ; Hemmings, Brian A.

In: Cancer Discovery, 2012, vol. 2, no. 3, p. 248-259

Metastatic breast tumor cells display an epithelial–mesenchymal transition (EMT) that increases cell motility, invasion, and dissemination. Although the transcription factor Twist1 has been shown to contribute to EMT and cancer metastasis, the signaling pathways regulating Twist1 activity are poorly understood. Here, we show that Twist1 is ubiquitously phosphorylated in 90% of 1,532 invasive...

Université de Fribourg

Radiation-induced modifications of the tumor microenvironment promote metastasis

Rüegg, Curzio ; Monnier, Yan ; Kuonen, François ; Imaizumi, Natsuko

In: Bulletin du Cancer, 2011, vol. 98, no. 6, p. 47-57

Radiotherapy is successfully used to treat cancer. Emerging evidence, however, indicates that recurrences after radiotherapy are associated with increased local invasion, metastatic spreading and poor prognosis. Radiation-induced modifications of the tumor microenvironment have been proposed to contribute to increased aggressive tumor behavior, an effect also referred to as tumor bed effect, but...

Université de Fribourg

68Ga-NODAGA-RGDyK for αvβ3 integrin PET imaging : Preclinical investigation and dosimetry

Buchegger, F. ; Viertl, D. ; Baechler, Sébastien ; Dunet, V. ; Kosinski, M. ; Poitry-Yamate, C. ; Rüegg, Curzio ; Prior, J. O.

In: Nuklearmedizin, 2011, vol. 50, no. 6, p. 221-246

Aim: To visualize neovasculature and/or tumour integrin αvβ3 we selected the binding moiety Arg-Gly-Asp-D-Tyr-Lys (RGDyK) coupled to NODAGA for labeling with 68Ga. Methods: NODAGA-RGDyK (ABX) was labeled with the 68Ga eluate from the 68Ge generator IGG100 using the processor unit PharmTracer. Biodistribution was measured in female Hsd mice sacrificed 10, 30, 60 and 90 min after i.v. injection...

Université de Fribourg

Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2 inhibitors in colorectal cancer cells

Zaric, J. ; Joseph, J.-M. ; Tercier, S. ; Sengstag, T. ; Ponsonnet, L. ; Delorenzi, M. ; Rüegg, Curzio

In: Oncogene, 2012, vol. 31, p. 48-59

Cyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and progression, in particular of the colon. The COXIB...

Université de Fribourg

MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells

Carrascosa, C. ; Obula, R. G. ; Missiaglia, E. ; Lehr, H.-A. ; Delorenzi, M. ; Frattini, M. ; Rüegg, Curzio ; Mariotti, Agnese

In: Oncogene, 2011, p. -

Milk fat globule-EGF factor 8 (MFG-E8) is a glycoprotein highly expressed in breast cancer that contributes to tumor progression through largely undefined mechanisms. By analyzing publicly available gene expression profiles of breast carcinomas, we found that MFG-E8 is highly expressed in primary and metastatic breast carcinomas, associated with absent estrogen receptor expression....

Université de Fribourg

Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism

Garrido-Urbani, Sarah ; Jemelin, Stephane ; Deffert, Christine ; Carnesecchi, Stéphanie ; Basset, Olivier ; Szyndralewiez, Cédric ; Heitz, Freddy ; Page, Patrick ; Montet, Xavier ; Michalik, Liliane ; Arbiser, Jack ; Rüegg, Curzio ; Krause, Karl Heinz ; Imhof, Beat A.

In: PLoS ONE, 2011, vol. 6, no. 2, p. e14665

Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired...

Université de Fribourg

Radiotherapy suppresses angiogenesis in mice through TGF-ßRI/ALK5-dependent inhibition of endothelial cell sprouting

Imaizumi, Natsuko ; Monnier, Yan ; Hegi, Monika ; Mirimanoff, René-Olivier ; Rüegg, Curzio

In: PLoS ONE, 2010, vol. 5, no. 6, p. e11084

Background: Radiotherapy is widely used to treat cancer. While rapidly dividing cancer cells are naturally considered the main target of radiotherapy, emerging evidence indicates that radiotherapy also affects endothelial cell functions, and possibly also their angiogenic capacity. In spite of its clinical relevance, such putative anti-angiogenic effect of radiotherapy has not been thoroughly...