Glycerol and NEFA kinetics in long-term fasting king penguins: phase IIversusphase III

2002 ◽  
Vol 205 (17) ◽  
pp. 2745-2754 ◽  
Author(s):  
S. F. Bernard ◽  
C. Fayolle ◽  
J.-P. Robin ◽  
R. Groscolas
Keyword(s):  
Body Mass ◽  
Phase Ii ◽  
Fat Mass ◽  
Feeding Behaviour ◽  
Fold Increase ◽  
Phase Iii ◽  
Protein Catabolism ◽  
Body Protein ◽  
Fat Stores

SUMMARYIn spontaneously fasting birds such as penguins, below a body mass threshold corresponding to the phase II—phase III transition, a metabolic and hormonal shift occurs and feeding behaviour is stimulated(`refeeding signal'). The major aim of this study was to determine whether a decrease in non-esterified fatty acid (NEFA) release from adipose tissue could be a component of this signal. Lipolytic fluxes and primary triacylglycerol:fatty acid (TAG:FA) cycling were determined in vivoin breeding, fasting king penguins (Aptenodytes patagonicus) using continuous infusions of 2-[3H]glycerol and 1-[14C]palmitate under field conditions. In phase II (after approximately 8 days of fasting, large fat stores, body protein spared, N=8), the rate of appearance (Ra) of glycerol and of NEFA were 5.7±0.8 and 10.5±0.4 μmol kg-1min-1, respectively, and the percentage of primary TAG:FA cycling was 41±7%. In phase III (after approximately 25 days of fasting, fat stores reduced by fourfold, increased body protein catabolism, N=9), Ra glycerol kg-1 body mass remained unchanged,whereas Ra glycerol kg-1 fat mass and Ra NEFA kg-1 body mass were increased by 2.8-fold and 1.5-fold, respectively. Increased Ra glycerol kg-1 fat mass was possibly the result of a 3.5-fold increase in circulating glucagon, the increased Ra NEFA kg-1 body mass being attributable to decreased primary TAG:FA cycling. Thus, triggering of the refeeding signal that redirects the behavior of fasting, incubating penguins from incubation towards the search for food after entrance into phase III cannot be ascribed to a reduction in lipolytic fluxes and NEFA availability.

scholarly journals Blockade of fatty acid oxidation mimics phase II-phase III transition in a fasting bird, the king penguin

2002 ◽  
Vol 283 (1) ◽  
pp. R144-R152 ◽  
Author(s):  
Servane F. Bernard ◽  
Eliane Mioskowski ◽  
René Groscolas
Keyword(s):  
Fatty Acid ◽  
Phase Ii ◽  
Plasma Concentrations ◽  
Fold Increase ◽  
Phase Iii ◽  
Acid Oxidation ◽  
Body Protein ◽  
Nonesterified Fatty Acids ◽  
Protein Sparing

This study tests the hypothesis that the metabolic and endocrine shift characterizing the phase II-phase III transition during prolonged fasting is related to a decrease in fatty acid (FA) oxidation. Changes in plasma concentrations of various metabolites and hormones and in lipolytic fluxes, as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo in spontaneously fasting king penguins in the phase II status (large fat stores, protein sparing) before, during, and after treatment with mercaptoacetate (MA), an inhibitor of FA oxidation. MA induced a 7-fold decrease in plasma β-hydroxybutyrate and a 2- to 2.5-fold increase in plasma nonesterified fatty acids (NEFA), glycerol, and triacylglycerols. MA also stimulated lipolytic fluxes, increasing the rate of appearance of NEFA and glycerol by 60–90%. This stimulation might be partly mediated by a doubling of circulating glucagon, with plasma insulin remaining unchanged. Plasma glucose level was unaffected by MA treatment. Plasma uric acid increased 4-fold, indicating a marked acceleration of body protein breakdown, possibly mediated by a 2.5-fold increase in circulating corticosterone. Strong similarities between these changes and those observed at the phase II-phase III transition in fasting penguins support the view that entrance into phase III, and especially the end of protein sparing, is related to decreased FA oxidation, rather than reduced NEFA availability. MA could be therefore a useful tool for understanding mechanisms underlying the phase II-phase III transition in spontaneously fasting birds and the associated stimulation of feeding behavior.

Protein and lipid utilization during long-term fasting in emperor penguins

1988 ◽  
Vol 254 (1) ◽  
pp. R61-R68 ◽  
Author(s):  
J. P. Robin ◽  
M. Frain ◽  
C. Sardet ◽  
R. Groscolas ◽  
Y. Le Maho
Keyword(s):  
Uric Acid ◽  
Mass Loss ◽  
Body Mass ◽  
Phase Ii ◽  
Plasma Concentrations ◽  
The Body ◽  
Phase Iii ◽  
Body Mass Loss ◽  
Emperor Penguins

The body mass of male emperor penguins is approximately 38 kg at the beginning of the 4-mo winter fast connected with breeding, and it is an estimated approximately 18 kg in leanest birds at time of spontaneous refeeding. For a 38- to 18-kg range, we investigated the changes in the rate of body mass loss, body composition, and plasma concentrations of uric acid and urea. After the first few days (phase I) a steady state (phase II) was reached in the proportions of the energy derived from proteins and lipids with proteins accounting for a constant 4%, and the remaining 96% being from lipids. The same proportions were maintained until body mass had decreased to 24 kg. Below this value the proportion of energy derived from proteins increased progressively (phase III), being 14 times higher at 18 kg than during phase II. Rate of body mass loss and plasma uric acid and urea concentrations closely reflected the changes in protein utilization: being at a low and steady value throughout phase II and increasing during phase III. Emperor penguins also fast during the spring, but for periods of only 2-3 wk. We found a 2.5 times higher value for rate of body mass loss, uric acid, and urea during spring phase II, suggesting lower effectiveness in protein sparing at that time. It may be attributed to the lower initial lipid reserves of spring birds. Would these findings be generalized to the wide variety of birds and mammals that spontaneously fast under natural conditions?(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrogeological Characterization Based on Long Term Groundwater Pressure Monitoring

2010 ◽  
Author(s):  
Shuji Daimaru ◽  
Ryuji Takeuchi ◽  
Masaki Takeda ◽  
Masayuki Ishibashi
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Large Scale ◽  
Pumping Test ◽  
Phase Iii ◽  
Pressure Monitoring ◽  
Energy Agency ◽  
Hydrogeological Characteristics ◽  
Under Construction

The Mizunami Underground Research Laboratory (MIU) is now under construction by the Japan Atomic Energy Agency in the Tono area of central Japan. The MIU project is being implemented in three overlapping Phases: Surface-based Investigation (Phase I), Construction (Phase II) and Operation (Phase III). The changes of groundwater pressure due to shaft excavation can be considered analogous to a large-scale pumping test. Therefore, there is the possibility that the site scale groundwater field (several km square) can be approximated by the long-term groundwater pressure monitoring data from Phase II. Based on the monitoring observations, hydrogeological characteristics were estimated using the s-log(t/r2) plot based on the Cooper-Jacob straight line method. Results of the s-log(t/r2) plots are as follows. The groundwater flow field around the MIU construction site is separated into domains by an impermeable fault. In other words, the fault is a hydraulic barrier. Hydraulic conductivity calculated from s-log(t/r2) plots are in the order of 1.0E−7(m/s). The above results from the long term monitoring during Phase II are a verification of the hydrogeological characteristics determined in the Phase I investigations.

scholarly journals A 15-year record (2001–2015) of the ratio of nitrate to non-seasalt sulfate in precipitation over East Asia

2017 ◽  
Author(s):  
Syuichi Itahashi ◽  
Keiya Yumimoto ◽  
Itsushi Uno ◽  
Hiroshi Hayami ◽  
Shin-ichi Fujita ◽  
...  
Keyword(s):  
Phase I ◽  
East Asia ◽  
Phase Ii ◽  
Precipitation Amount ◽  
Phase Iii ◽  
So2 Emissions ◽  
So2 Emission ◽  
Deposition Amount ◽  
Long Term Trend

Abstract. Acidifying species in precipitation can cause severe impacts on ecosystem. The chemical concentration of precipitation is directly related to the precipitation amount, so it is partly difficult to identify the long-term variation from precipitation concentration. The ratio of nitrate (NO3−) to non-seasalt sulfate (nss-SO42−) concentration in precipitation on an equivalent basis (hereinafter, Ratio) will be a useful index. To identify the long-term record of acidifying species in precipitation over East Asia, where is the highest emission region in the world, we have compiled the ground-based observations of the chemical concentration of precipitation over China, Korea, and Japan from 2001 to 2015 based on the Acid Deposition Monitoring Network in East Asia (EANET). The period was partly limited but other monitoring data in Japan, southern China, and northern China around Beijing were additionally utilized. The analyzed period was categorized into three phases: Phase I (2001–2005), Phase II (2006–2010), and Phase III (2011–2015). The behavior of NO3− and nss-SO42− concentration, and hence Ratio in precipitation will be related to these precursors. The anthropogenic NOx and SO2 emission amount, and NOx/SO2 emission ratio are analyzed. Further, satellite observations of NO2 and SO2 column density to capture the variation in emission was applied. We found that the long-term trend of NO3− concentration in precipitation was not related to the variation in NOx emission and the NO2 column. In comparison, the nss-SO42− concentration in precipitation over China, Korea, and Japan was partly connected to the changes in SO2 emission from China, but the trends were not significant. The long-term trend of Ratio over China, Korea, and Japan were nearly flat during Phase I, increasing significantly during Phase II, and almost flat again during Phase III. These variations of Ratio in East Asia clearly corresponded to the NOx/SO2 emission ratio and the NO2/SO2 column ratio in China. The first flat trend during Phase I was due to both increases in NOx and SO2 emissions in China, the significant increasing trend during Phase II was triggered by the increase in NOx emission and decrease in SO2 emission in China, and the returned flat trend during Phase III was caused by both declines in NOx and SO2 emissions in China. This suggests that China’s emission has a significant impact not only on China but also on downwind precipitation chemistry during the analyzed 15–year period of 2001–2015. In terms of wet depositions, the NO3− wet deposition amount over China, Korea, and Japan has not changed dramatically, but the nss-SO42− wet deposition amount declined over China, Korea, and Japan from Phase II to III. These declines were caused by a strong decrease in nss-SO42− concentration in precipitation accompanied by a reduction in SO2 emission from China, which counteracted an increase in precipitation amount. It was indicated the decision on the acidity of precipitation would be shift from sulfur to nitrogen.

scholarly journals Activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction

2018 ◽  
Vol 96 (3) ◽  
pp. 308-312 ◽  
Author(s):  
Isabelle Côté ◽  
Sara M. Green ◽  
Drake Morgan ◽  
Christy S. Carter ◽  
Nihal Tümer ◽  
...  
Keyword(s):  
Food Intake ◽  
Mass Loss ◽  
Body Mass ◽  
Fat Mass ◽  
Control Level ◽  
Mass Ratio ◽  
Melanocortin System ◽  
Body Mass Loss ◽  
Fat Mass Ratio

Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

scholarly journals Long-Term Use of Coagulation Factor IX (Recombinant) Albumin Fusion Protein (rIX-FP) in Previously Treated Patients with Hemophilia B in the Prolong-9FP Program

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1096-1096
Author(s):  
Aaron Lubetsky ◽  
Uri Martinowitz ◽  
Toshko Lissitchkov ◽  
Christine Voigt ◽  
Denise Wolko ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Phase Ii ◽  
Clinical Studies ◽  
Hemophilia B ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
On Demand ◽  
Clinical Program ◽  
Over Time

Abstract A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) has been developed with an improved PK profile, improving hemophilia B treatment by allowing less frequent dosing than required with standard plasma-derived (pd) and recombinant (r) FIX products. The PROLONG-9FP clinical program has evaluated the use of rIX-FP for prophylaxis and on-demand treatment of bleeding in patients with severe hemophilia B. The clinical program is comprised of 5 clinical studies, including four completed studies (a Phase I pharmacokinetic (PK) study, a Phase II study, and two Phase III studies in adults and children), and an ongoing extension study, which includes previously untreated patients. Over 100 subjects from 42 hemophilia treatment centers in 12 countries have participated in the PROLONG-9FP clinical program. Here, we report on the long-term safety and efficacy of rIX-FP in 15 subjects who have continuously participated in 3 clinical studies (Phase II, Phase III and the on-going Phase III extension studies) over a period of 4 years. Subjects began either weekly prophylaxis treatment or on-demand treatment with rIX-FP in the Phase II 2004 study, and continued that treatment regimen in the Phase III 3001 study. The Phase III global study evaluated safety and efficacy of rIX-FP for prophylaxis treatment (PT) of every 7-, 10- and 14-days and on-demand treatment (ODT) of bleeding episodes. Subjects in the on-demand arm received only ODT for 6 months and then switched to 7-day PT. Subjects in the prophylaxis arm received 7-day PT for 6 months, and eligible subjects switched to 10- or 14-day PT interval. Upon completion of the 3001 study, subjects entered the on-going extension study 3003 and either continued the treatment regimen or switched to a longer prophylaxis interval of 10-, 14- or 21-days. Within subject comparisons of the annualized spontaneous bleeding rates (AsBR), total ABR over time and other efficacy parameters between regimens will be presented. Long-term use of rIX-FP is safe and well-tolerated. No subjects developed inhibitors to FIX or antibodies to rIX-FP during the 4 year treatment period, with a mean of 180 exposure days (EDs) for PT subjects and 125 EDs for ODT subjects. ABR decreased over time with rIX-FP prophylaxis, and longer treatment intervals were possible with no increase in consumption. Disclosures Lubetsky: CSL Behring: Consultancy. Martinowitz:CSL Behring: Honoraria, Speakers Bureau. Voigt:CSL Behring: Employment. Wolko:CSL Behring: Employment. Jacobs:CSL Behring: Employment. Santagostino:Biotest: Speakers Bureau; Kedrion: Speakers Bureau; Roche: Speakers Bureau; Octapharma: Speakers Bureau; Novo Nordisk: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Bayer: Speakers Bureau; Biogen/Sobi: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau.

Ceramic Stationary Gas Turbine Development Program: Third Annual Summary

1996 ◽  
Author(s):  
Mark van Roode ◽  
William D. Brentnall ◽  
Kenneth O. Smith ◽  
Bryan D. Edwards ◽  
Leslie J. Faulder ◽  
...  
Keyword(s):  
Silicon Nitride ◽  
Gas Turbine ◽  
Phase Ii ◽  
Development Program ◽  
Full Scale ◽  
Phase Iii ◽  
Ceramic Component ◽  
Ceramic Components ◽  
Engine Testing

The goal of the Ceramic Stationary Gas Turbine (CSGT) Development Program, under the sponsorship of the United States Department of Energy (DOE), Office of Industrial Technologies (OIT), is to improve the performance (fuel efficiency, output power, exhaust emissions) of stationary gas turbines in cogeneration through the selective replacement of hot section components with ceramic parts. The program, currently in Phase II focuses on detailed engine and component design, ceramic component fabrication and testing, establishment of a long term materials property data base, the development of supporting nondestructive evaluation (NDE) technologies, and the application of ceramic component life prediction. A 4000 hr engine field test is planned for Phase III of the program. This paper summarizes progress from January 1995 through January 1996. First generation designs of the primary ceramic components (first stage blades and nozzles, combustor liners) for the program engine, the Solar Centaur 50S, and of the secondary metallic components interfacing with the ceramic parts were completed. The fabrication of several components has been completed as well. These components were evaluated in rigs and the Centaur 50S test engine. NTI64 (Norton Advanced Ceramics) and GN-10 (AlliedSignal Ceramic Components) silicon nitride dovetail blades were cold and hot spin tested and engine tested at the baseline nominal turbine rotor inlet temperature (TRIT) of 1010°C. Full scale SiC/SiC continuous fiber-reinforced ceramic matrix composite (CFCC) liners (B.F. Goodrich Aerospace) were also rig tested and engine tested at the nominal baseline TRIT of 1010°C. One of the engine tests, incorporating both the GN-10 blades and the full scale SiC/SiC CFCC liners, was performed for 21.5 hrs (16 hrs at 100% load) with six start/stop cycles. A cumulative 24.5 hrs of engine testing was performed at the end of January, 1996. The ceramic components were in good condition following completion of the testing. Subscale Hexoloy® SA silicon carbide (Carborundum) and enhanced SiC/SiC CFCC (DuPont Lanxide Composites) and Al2O3/Al2O3 CFCC (Babcock & Wilcox) combustor liners were tested to evaluate mechanical attachment, durability and/or emissions reduction potential. The enhanced SiC/SiC CFCC of DuPont Lanxide Composites demonstrated superior durability in subscale combustor testing and this material was subsequently selected for the fabrication of full scale combustor liners for final engine rig testing in Phase II and field testing in Phase III of the program. Enhanced SiC/SiC CFCC liners also showed significantly reduced emissions of NOx and CO when compared with conventionally cooled subscale metallic liners. This observation is believed to apply generally to “hot wall” combustor substrates. The emissions results for the enhanced SiC/SiC CFCC liners were paralleled by similar emissions levels of NOx and CO monitored during engine testing with B.F. Goodrich Aerospace SiC/SiC CFCC combustor liners. NOx levels below 25 ppmv and CO levels below 10 ppmv were measured during the engine testing. Short term (1,000 hrs) creep testing of candidate ceramic materials under approximate nozzle “hot spot” conditions was completed and long term (5000–10,000 hrs) creep testing is in progress. The selected nozzle material, SN-88 silicon nitride, has survived over 5,500 hrs at 1288°C and 186 MPa stress at the end of January, 1996.

Behavioral changes in fasting emperor penguins: evidence for a “refeeding signal” linked to a metabolic shift

1998 ◽  
Vol 274 (3) ◽  
pp. R746-R753 ◽  
Author(s):  
Jean-Patrice Robin ◽  
Laurent Boucontet ◽  
Pascal Chillet ◽  
René Groscolas
Keyword(s):  
Uric Acid ◽  
Locomotor Activity ◽  
Mass Loss ◽  
Body Mass ◽  
Plasma Levels ◽  
Escape Behavior ◽  
Phase Iii ◽  
Body Mass Loss ◽  
Body Protein ◽  
Emperor Penguins

This study examines the relationships between metabolic status and behavior in spontaneously fasting birds in the context of long-term regulation of body mass and feeding. Locomotor activity, escape behavior, display songs, body mass, and metabolic and endocrine status of captive male emperor penguins were recorded during a breeding fast. We also examined whether body mass at the end of the fast affected further survival. The major part of the fast ( phase II) was characterized by the maintenance of a very low level of locomotor activity, with almost no attempt to escape, by an almost constant rate of body mass loss, and by steady plasma levels of uric acid, β-hydroxybutyrate, and corticosterone. This indicates behavioral and metabolic adjustments directed toward sparing energy and body protein. Below a body mass of ∼24 kg ( phase III), spontaneous locomotor activity and attempts to escape increased by up to 8- and 15-fold, respectively, and display songs were resumed. This probably reflected an increase in the drive to refeed. Simultaneously, daily body mass loss and plasma levels of uric acid and corticosterone increased, whereas plasma levels of β-hydroxybutyrate decreased. Some experimental birds were seen again in following years. These findings suggest that at a threshold of body mass, a metabolic and endocrine shift, possibly related to a limited availability of fat stores, acts as a “refeeding signal” that improves the survival of penguins to fasting.

Physiology and biochemistry of long-term fasting in birds

1988 ◽  
Vol 66 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Yves Cherel ◽  
Jean-Patrice Robin ◽  
Yvon Le Maho
Keyword(s):  
Energy Expenditure ◽  
Body Mass ◽  
Metabolic Response ◽  
Bird Species ◽  
Climatic Conditions ◽  
Phase Iii ◽  
Protein Catabolism ◽  
Minimum Level ◽  
Rapid Phase ◽  
Three Phases

Various bird species regularly fast in connection with breeding, migration, or drastic climatic conditions. The metabolic response of penguins and domestic geese to fasting has been studied in detail. These large birds, in contrast to small species, do not become torpid when they are fasting. Nevertheless, they reduce their rate of energy expenditure by decreasing both resting metabolic rate and locomotor activity. From changes in the loss of body mass, the fast of penguins and geese has been divided into three phases: I, the loss of body mass decreases; II, it remains at a minimum level; and III, it increases. These phases reflect metabolic adjustments. Phase I is a rapid phase of adaptation, marked by a decrease in protein catabolism and mobilization of lipids. Phase II is a phase of economy, during which more than 90% of the energy expenditure derives from lipids, while protein catabolism remains at a minimum level. In phase III there still are lipid reserves and this phase is reversible; it is, however, critical because proteins are no longer spared. Data in the literature suggest that these three phases may also be used to describe how a wide variety of wild and domestic birds adapt to fasting.

Overall survival benefit with masitinib mesylate in imatinib-naive, locally advanced, or metastatic gastrointestinal stromal tumor (GIST): 4-years follow-up of the French Sarcoma Group phase II trial.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 85-85 ◽  
Author(s):  
J. Blay ◽  
A. Le Cesne ◽  
N. Bin Bui ◽  
O. Bouche ◽  
A. Adenis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Locally Advanced ◽  
Phase Iii ◽  
Long Term Results ◽  
First Line ◽  
Juxtamembrane Region ◽  
Metastatic Gist

85 Background: Masitinib is a novel tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib (IM) against both wild-type KIT receptor and its mutated form in the juxtamembrane region (IC 50=100 nM versus 200 nM for IM, 3 nM versus 27nM and 40 nM versus 120nM, respectively, for exons 9,11, and 13). This multicenter phase II study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Methods: IM-naïve patients with inoperable, locally advanced or metastatic GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Efficacy variables included response rate, best response (RECIST), progression-free survival (PFS) and overall survival (OS). Initial results were previously reported in EJC 2010. We present here the same series with updated PFS and OS (median follow up of 48 months). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. At the cut-off date (31 august 2010), 9 patients are still under treatment with a median treatment duration of 41 months (min=33, max=52). Two additional progressions have been reported for a total of 14 events (13 progressions and 1 death). Updated median PFS is 41 months (95% CI: [17.5; NR]) with PFS rates of 60% [39; 77], 56% [35; 73] and 45% [24; 64] respectively at 2, 3 and 4 years. With 8 patients dead, median OS is not yet reached with OS rates of 90% [72; 97], 87% [68; 95] and 74% [52; 87], respectively, at 2, 3, and 4 years. The main frequent relevant grade 3 toxicities were: rash (10%), neutropenia (7%) and abdominal pain (7%) with one patient presented a grade 4 skin exfoliation. No other relevant long-term toxicities were reported and no more patients discontinued treatment due to suspected toxicity. Conclusions: The long term results observed with masitinib confirm a very interesting activity with prolonged PFS and OS. These results support the head to head comparison with imatinib in the currently ongoing phase III randomized clinical trial in first line locally advanced or metastatic GIST patients. [Table: see text]

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