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See detailPhase I/IIclinical trial of local GM-CSF application in patients with cervical HPV-associated low grade squamous intraepithelial lesions
Hubert, Pascale ULg; Doyen, Jean ULg; Chapelle, X. et al

Conference (2007)

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM ... [more ▼]

Background: Quantitative and functional alterations of professional antigen-presenting cells (APC) in SIL suggest that these lesions may have a diminished capacity to capture viral antigens. Moreover, GM-CSF (whose production is decreased in HPV-transformed keratinocytes) is an essential factor for the migration of APC in cervical (pre)neoplastic lesions formed in vitro and transplanted in vivo on mouse. In this study we performed a phase I/II clinical trial in order to determine whether a local application of GM-CSF on cervical low-grade squamous intraepithelial lesions (LSIL) might increase the recruitment of APC into the epithelium and indirectly the viral antigen presentation to the immune system. Methods: Fifteen patients with LSIL (10 GM-CSF and 5 placebo) were enrolled in this study. Patients received 4 GM-CSF applications (or placebo gel) and were followed during 6-7 months. APC infiltration was quantified by immunostaining with anti-CD1a mAb. Cellular immune response was evaluated by using an IFN-gamma intracellular staining on PBMC stimulated in vitro with the E7 HPV16 protein and L1 HPV16 Virus-like particles (VLP). Hybrid capture was performed to semi-quantify the viral DNA in cervical brush specimens. Results: GM-CSF applications were well tolerated in all patients. No difference in the cytological/histological and viral parameters assessed at 2 and 6 months after the last application was observed between the GM-CSF and the placebo group. An increased number of CD1a+ APC was observed in 6/10 patients treated by GM-CSF compared to 1/5 patient in the placebo group. There was an increased immune response against HPV in the GM-CSF group showed by NK and T cells producing IFN-gamma. [less ▲]

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See detailPhase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy.
Saura, Cristina; Bendell, Johanna; Jerusalem, Guy ULg et al

in Clinical cancer research : an official journal of the American Association for Cancer Research (2014), 20(7), 1935-45

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose ... [more ▼]

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose of this study was to determine the clinical activity of the PI3K inhibitor buparlisib (BKM120) in patients with HER2(+) advanced/metastatic breast cancer resistant to trastuzumab-based therapy. EXPERIMENTAL DESIGN: In the dose-escalation portion of this phase I/II study, patients with trastuzumab-resistant locally advanced or metastatic HER2(+) breast cancer were treated with daily oral doses of buparlisib and weekly intravenous trastuzumab (2 mg/kg). Dose escalation was guided by a Bayesian logistic regression model with overdose control. RESULTS: Of 18 enrolled patients, 17 received buparlisib. One dose-limiting toxicity of grade 3 general weakness was reported at the 100-mg/day dose level (the single-agent maximum tolerated dose) and this dose level was declared the recommended phase II dose (RP2D) of buparlisib in combination with trastuzumab. Common (>25%) adverse events included rash (39%), hyperglycemia (33%), and diarrhea (28%). The pharmacokinetic profile of buparlisib was not affected by its combination with trastuzumab. At the RP2D, there were two (17%) partial responses, 7 (58%) patients had stable disease (>/=6 weeks), and the disease control rate was 75%. Pharmacodynamic studies showed inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways. CONCLUSIONS: In this patient population, the combination of buparlisib and trastuzumab was well tolerated, and preliminary signs of clinical activity were observed. The phase II portion of this study will further explore the safety and efficacy of this combination at the RP2D. Clin Cancer Res; 20(7); 1935-45. (c)2014 AACR. [less ▲]

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See detailA phase II exploratory study of BIM23A760 in acromegalic patients : preliminary results of safety and efficacy after a single-dose administration
Lesage, C.; Seymour, C.; Urbanavicius, V. et al

in The Endocrine Society's 91st Annual Meeting : 10-13 juin 2009, Washington (2009)

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See detailPhase II study of docetaxel alternating with cisplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer
Mattson, Karin; Vansteenkiste, Johan; Stupp, Roger et al

in Anti-Cancer Drugs (2000), 11

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See detailA phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956)
Scagliotti, G. V.; Smit, E.; Bosquee, Léon ULg et al

in Lung Cancer (2005), 50(1), 91-96

Purpose: The incidence of bronchioloalveolar carcinoma (BAC) has risen steadily over the last decades along with the increasing frequency of adenocarcinomas. BAC is relatively resistant to commonly used ... [more ▼]

Purpose: The incidence of bronchioloalveolar carcinoma (BAC) has risen steadily over the last decades along with the increasing frequency of adenocarcinomas. BAC is relatively resistant to commonly used chemotherapy regimens. A phase 11 study with single agent pactitaxel in patients with stages IIIB, IV or recurrent BAC was performed. Experimental design: Patients with BAC with at least one target bidimensionally measurable lesion staged as unresectable stages IIIB, IV or recurrent disease, not previously irradiated; ECOG performance status 0-2; life expectancy greater than 3 months; age range between 18 and 75, received pactitaxel at a dose of 200 mg/m(2) i.v. as 3 h continuous infusion on day 1 every 21 days. Treatment was continued until progression or up to a maximum of six cycles. Results: Nineteen patients were eligible. Median number of cycles was 3 (range 0-6); 35% of patients received the planned six cycles of chemotherapy. One patient died of unrelated cause before the start of treatment. Both hematological and non-hematological toxicities were generally mild. Only one partial response (PR) was observed among the 18 eligible patients who started protocol treatment, with a response rate of 5.6% (95% Cl: 0.1-27.3%). After an independent review, two PR were confirmed, for a response rate of 11.1% (95% CI: 1.4-34.7%); nine patients had stable disease (50.0%), three patients had progressive disease (11.1%) and four patients were not assessable (22.2%). Median survival was 8.6 months (95% CI: 5.8-14.5) and 1-year survival was 35.0% (95% CI: 14.1-55.8). Median progression free survival for all patients was 2.2 months (95% CI: 1.5-6.0). The study was terminated due to the low response rate. Conclusions: Pactitaxel as single agent in stages IIIB-IV BAC was well tolerated and manageable but of limited efficacy. BAC should not be excluded from trials of new forms of chemotherapy. (c) 2005 Elsevier Ireland Ltd. All rights reserved. [less ▲]

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See detailA phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease.
Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjorn et al

in Breast cancer research and treatment (2014)

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study ... [more ▼]

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was -10.1 nmol bone collagen equivalents/mmol creatinine (-32.8 %; P = 0.0124); median bALP change was -16.7 ng/mL (-42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (>/=25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease. [less ▲]

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See detailPhase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy, followed by intensification and autologous transplantation in patients with nonmyeloid malignancies.
Andre, Marc; Baudoux, Etienne ULg; Bron, Dominique et al

in Transfusion (2003), 43(1), 50-7

BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic ... [more ▼]

BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit. [less ▲]

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See detailPhase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).
Ketterer, N.; Coiffier, B.; Thieblemont, C. et al

in Annals of Oncology (2013), 24/n°4

Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparaison with cyclophosphamide, doxorubicin, vincristin and prednisone ... [more ▼]

Background The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparaison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for Young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which évaluâtes the role of rituximab combined with ACVBP (R- ACVBP) in these patients. Patients and methods untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. Results a total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P=0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P=0.0205). Overall survival did not differ between the two groups with a 3-year estimâtes of 98% and 97%, respectively (P=0.686). Conclusion in Young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly Superior to ACVBP plus consolidation alone. [less ▲]

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See detailPhase ratio estimations from true color images
Pirard, Eric ULg; Tarquini, Simone

(1996)

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See detailPhase referencing in optical interferometry
Filho, Mercedes E; Garcia, Paulo; Duvert, Gilles et al

in Schöller, Markus; Danchi, William; Delplancke, Françoise (Eds.) Optical and Infrared Interferometry (2008, July 01)

One of the aims of next generation optical interferometric instrumentation is to be able to make use of information contained in the visibility phase to construct high dynamic range images. Radio and ... [more ▼]

One of the aims of next generation optical interferometric instrumentation is to be able to make use of information contained in the visibility phase to construct high dynamic range images. Radio and optical interferometry are at the two extremes of phase corruption by the atmosphere. While in radio it is possible to obtain calibrated phases for the science objects, in the optical this is currently not possible. Instead, optical interferometry has relied on closure phase techniques to produce images. Such techniques allow only to achieve modest dynamic ranges. However, with high contrast objects, for faint targets or when structure detail is needed, phase referencing techniques as used in radio interferometry, should theoretically achieve higher dynamic ranges for the same number of telescopes. Our approach is not to provide evidence either for or against the hypothesis that phase referenced imaging gives better dynamic range than closure phase imaging. Instead we wish to explore the potential of this technique for future optical interferometry and also because image reconstruction in the optical using phase referencing techniques has only been performed with limited success. We have generated simulated, noisy, complex visibility data, analogous to the signal produced in radio interferometers, using the VLTI as a template. We proceeded with image reconstruction using the radio image reconstruction algorithms contained in aips imagr (clean algorithm). Our results show that image reconstruction is successful in most of our science cases, yielding images with a 4 milliarcsecond resolution in K band. We have also investigated the number of target candidates for optical phase referencing. Using the 2MASS point source catalog, we show that there are several hundred objects with phase reference sources less than 30 arcseconds away, allowing to apply this technique. [less ▲]

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See detailPhase resolved X-ray spectroscopy of HDE 228766: Probing the wind of an extreme Of+/WNLha star
Rauw, Grégor ULg; Mahy, Laurent; Nazé, Yaël ULg et al

in Astronomy and Astrophysics (2014), 566

Context. HDE 228766 is a very massive binary system hosting a secondary component, which is probably in an intermediate evolutionary stage between an Of supergiant and an WN star. The wind of this star ... [more ▼]

Context. HDE 228766 is a very massive binary system hosting a secondary component, which is probably in an intermediate evolutionary stage between an Of supergiant and an WN star. The wind of this star collides with the wind of its O8 II companion, leading to relatively strong X-ray emission. <BR /> Aims: Measuring the orbital variations of the line-of-sight absorption toward the X-ray emission from the wind-wind interaction zone yields information on the wind densities of both stars. <BR /> Methods: X-ray spectra have been collected at three key orbital phases to probe the winds of both stars. Optical photometry has been gathered to set constraints on the orbital inclination of the system. <BR /> Results: The X-ray spectra reveal prominent variations of the intervening column density toward the X-ray emission zone, which are in line with the expectations for a wind-wind collision. We use a toy model to set constraints on the stellar wind parameters by attempting to reproduce the observed variations of the relative fluxes and wind optical depths at 1 keV. <BR /> Conclusions: The lack of strong optical eclipses sets an upper limit of ~ 68° on the orbital inclination. The analysis of the variations of the X-ray spectra suggests an inclination in the range 54-61° and indicates that the secondary wind momentum ratio exceeds that of the primary by at least a factor 5. Our models further suggest that the bulk of the X-ray emission arises from the innermost region of the wind interaction zone, which is from a region whose outer radius, as measured from the secondary star, lies between 0.5 and 1.5 times the orbital separation. Based on observations collected with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA member states and the USA (NASA), and on data collected at the San Pedro Mártir observatory (Mexico). [less ▲]

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See detailPhase resolved X-ray spectroscopy of HDE 228766: Probing the wind of an extreme Of+/WNLha star (Corrigendum)
Rauw, Grégor ULg; Mahy, Laurent; Nazé, Yaël ULg et al

in Astronomy and Astrophysics (2014), 569

Based on observations collected with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA member states and the USA (NASA), and on data collected at the San Pedro ... [more ▼]

Based on observations collected with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA member states and the USA (NASA), and on data collected at the San Pedro Mártir observatory (Mexico). Corrigendum [less ▲]

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See detailPhase resonance testing of nonlinear vibrating structures
Peeters, Maxime ULg; Kerschen, Gaëtan ULg; Golinval, Jean-Claude ULg

in 28th International Modal Analysis Conference, Jacksonville, 2010 (2011)

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See detailPhase retarders in liquid crystals polymers
Piron, Pierre ULg

Scientific conference (2012, March 12)

Liquid crystals polymers posses birefringent properties and they are locally orientable, they allow the realization of space variant optical retarders which creates non uniformly polarized beam. To ... [more ▼]

Liquid crystals polymers posses birefringent properties and they are locally orientable, they allow the realization of space variant optical retarders which creates non uniformly polarized beam. To realize a retarder, liquid crystals are exposed to a UV linearly polarized beam, the optical axis of the retarder will be parallel to the incident polarization. We shall present an innovative way to produce space-variant retarders without mechanical interaction polarization holography . Superposing several beams differently polarized, results in a non-uniformly polarized recording beam used to realize space variant retarders. We shall also present our research retarders for two applications based on this method polarization analysis and coronagraphy. [less ▲]

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See detailPhase segregation and avalanches in multispecies sandpiles
Vandewalle, Nicolas ULg

in Physica A: Statistical Mechanics and its Applications (1999), 272(3-4), 450-458

A stochastic lattice model for the simulation of sandpiles is presented. The model allows for the numerical investigation of the phase segregation phenomenon occurring when different granular species are ... [more ▼]

A stochastic lattice model for the simulation of sandpiles is presented. The model allows for the numerical investigation of the phase segregation phenomenon occurring when different granular species are initially mixed together before deposition. The model includes the collective motion of grains along the pile surface and produces the so-called landslides. The parameters of the model are discussed. The distribution of avalanche sizes is found to broaden when the number of grain types increases. This result raises new questions about previously reported experimental observations of avalanche size distributions. [less ▲]

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See detailPhase segregation in binary sandpiles on fractal bases
Vandewalle, Nicolas ULg; D'hulst, R.; Ausloos, Marcel ULg

in Physical Review. E : Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics (1999), 59(1), 631-635

We have built experimentally and have numerically studied sandpiles on a base having a prefractal perimeter. This type of perimeter induces the formation of quite complex pile shapes characterized by both ... [more ▼]

We have built experimentally and have numerically studied sandpiles on a base having a prefractal perimeter. This type of perimeter induces the formation of quite complex pile shapes characterized by both ridges and valleys. The effects of a fractal base on the phase segregation of a binary granular system have been investigated. Both demixing and self-stratification phenomena have been investigated. It is found that the demixing of binary granular piles is enhanced by the prefractal perimeter character. The concentration profiles are given. This is briefly discussed in terms of length scale selection. [less ▲]

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See detailPhase separation during silica gel formation followed by time-resolved SAXS
Gommes, Cédric ULg; Goderis, Bart; Pirard, Jean-Paul ULg et al

Poster (2004, August)

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