References of "ANSIAUX, Reginald"
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See detailPotentiation of cyclophosphamide chemotherapy using the anti-angiogenic drug thalidomide: Importance of optimal scheduling to exploit the ‘normalization’ window of the tumor vasculature
SEGERS, Jerome; DI FAZIO, Vincent; ANSIAUX, Reginald et al

in Cancer Letters (2006), 244(1), 12935

The aim of this work was to study how administration schedule affects potentiation of cyclophosphamide, an alkylating agent, by thalidomide, an anti-angiogenic agent. Tumor oxygenation after thalidomide ... [more ▼]

The aim of this work was to study how administration schedule affects potentiation of cyclophosphamide, an alkylating agent, by thalidomide, an anti-angiogenic agent. Tumor oxygenation after thalidomide administration was determined over time by EPR oximetry. Such measurements provide a surrogate marker for determining the timing of ‘normalization’ of tumor vasculature. Re-growth delays were measured using different combinations and schedules of treatments. Additionally, the uptake of the metabolite of cyclophosphamide (hydroxycyclophosphamide or OH-CP) into tumors was determined by high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A significant increase in pO2 was observed after 2 and 3 days of treatment before eventually declining on day 4. Thalidomide potentiated the effect of cyclophosphamide only when cyclophosphamide was administered after 2 days of treatment with thalidomide (no significant benefit using other schedules). In this time frame, the HPLC/MS/MS measurements showed that the quantity of OH-CP penetrating into the tumor was about twice in mice treated by thalidomide compared to controls. In conclusion, the present study demonstrates that the benefit of combined therapy using an anti-angiogenic agent with a cytotoxic agent requires knowledge of the time window during which the vessels initially become normalized. [less ▲]

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See detailMechanism of tumor reoxygenation after anti-angiogenic therapy using SU5416 and its importance for guiding combined anti-tumor therapy
Ansiaux, Réginald; Cron, G-O; Crokart, N et al

in International Journal of Cancer Research (2006), (66(19)), 9698-9704

Emerging preclinical studies support the concept of a transient ‘‘normalization’’ of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated ... [more ▼]

Emerging preclinical studies support the concept of a transient ‘‘normalization’’ of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds. (Cancer Res 2006; 66(19): 9698-704 [less ▲]

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See detailMechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance for guiding combined antitumor therapy
ANSIAUX, Réginald; BAUDELET, Christine; JORDAN, Bénédicte et al

in Cancer Research (2006), 66(19), 9698704

Emerging preclinical studies support the concept of a transient "normalization" of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated ... [more ▼]

Emerging preclinical studies support the concept of a transient "normalization" of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds. [less ▲]

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See detailBotulinum toxin potentiates cancer radiotherapy and chemotherapy
ANSIAUX, Reginald; BAUDELET, Christine; CRON, Greg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2006), 12(4), 127683

PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer ... [more ▼]

PURPOSE: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation. <br /> <br />EXPERIMENTAL DESIGN: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells. <br /> <br />RESULTS: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature. <br /> <br />CONCLUSIONS: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy. [less ▲]

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See detailThalidomide radiosensitizes tumors through early changes in the tumor microenvironnement
Ansiaux, Réginald; Jordan, BF; Beghein, N et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2005)

ABSTRACT Purpose: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of ... [more ▼]

ABSTRACT Purpose: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible ‘‘normalization’’ of the tumor vasculature that could be exploited to improve radiotherapy. Experimental Design: Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO2) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrastenhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a ‘‘wick-inneedle’’ technique. Results: Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling. Conclusions: In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization. [less ▲]

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See detailThalidomide radiosensitizes tumors through early changes in the tumor microenvironment
ANSIAUX, Reginald; BAUDELET, Christine; JORDAN, Bénédicte et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2005), 15(11), 74350

Purpose: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers ... [more ▼]

Purpose: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible normalization of the tumor vasculature that could be exploited to improve radiotherapy. Experimental Design: Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO2) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a wick-in-needle technique. Results: Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling. Conclusions: In summary, the microenvironmental changes induced by thalidomide were sufficient to radio-sensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization. [less ▲]

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