Institute Regional du Cancer
Institute Regional du Cancer
Chavanieu A.,Montpellier University |
Pugniere M.,Institute Of Recherche En Cancerologie Of Montpellier |
Pugniere M.,Montpellier University |
Pugniere M.,Institute Regional du Cancer
Expert Opinion on Drug Discovery | Year: 2016
Introduction: Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps.Areas covered: In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes.Expert opinion: The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Bernard P.,Montpellier University |
Bernard P.,Challenge for the Change of Behaviour Group |
Bernard P.,Laval University |
Bernard P.,University Laval |
And 16 more authors.
Health Education and Behavior | Year: 2017
A meta-analysis of randomized controlled trials (RCTs) has recently showed that theory-based interventions designed to promote physical activity (PA) significantly increased PA behavior. The objective of the present study was to investigate the moderators of the efficacy of these theory-based interventions. Seventy-seven RCTs evaluating theory-based interventions were systematically identified. Sample, intervention, methodology, and theory implementation characteristics were extracted, coded by three duos of independent investigators, and tested as moderators of interventions effect in a multiple–meta-regression model. Three moderators were negatively associated with the efficacy of theory-based interventions on PA behavior: intervention length (≥14 weeks; β = −.22, p =.004), number of experimental patients (β = −.10, p =.002), and global methodological quality score (β = −.08, p =.04). Our findings suggest that the efficacy of theory-based interventions to promote PA could be overestimated consequently due to methodological weaknesses of RCTs and that interventions shorter than 14 weeks could maximize the increase of PA behavior. © 2016, © 2016 Society for Public Health Education.
Bellocq J.-P.,CHRU |
Luporsi E.,Institute Of Cancerologie Of Lorraine |
Barriere J.,Center Antoine Lacassagne |
Bonastre J.,Institute Gustave Roussy |
And 12 more authors.
Annales de Pathologie | Year: 2014
Context and aims: Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint®, in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOEI according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions. Methods: The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence. Conclusions: Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint® prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint®, new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking. © 2014.
Lamy P.-J.,Institute Regional Du Cancer Of Montpellier |
Montels F.,Institute Regional Du Cancer Of Montpellier |
Tosi D.,Institute Regional Du Cancer Of Montpellier |
Leizour B.,Clinique Beausoleil |
And 5 more authors.
Annales de Biologie Clinique | Year: 2013
The analytical and clinical validation of newbiomarkers for the early detection of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to calculate a standardized PHI index linked to a higher probability of a positive biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for prostate cancer diagnosis. The purpose of this study is to validate the analytical performance of the (-2)proPSA and to determine the predictive value of PHI for the early detection of prostate cancer. Analytical performances are correct. It is not necessary to dilute samples before analysis. The stability of (-2)proPSA is good until at least 3 hours at room temperature before centrifugation. The study of thePSAT, PSAL, (-2)proPSA and PHI values in a population of patients consulting for an early prostate cancer diagnosis shows that the index PHI is the most powerful predictive marker of cancer with an area under ROC curve of 0.70, whereas it is only 0.56 for total PSA.
Eberst L.,Center Leon Berard |
Eberst L.,University Claude Bernard Lyon 1 |
Cropet C.,Center Leon Berard |
Le Cesne A.,Institute Gustave Roussy |
And 21 more authors.
BMC Cancer | Year: 2014
Background: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs. Methods: Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice. Results: From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n = 48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n = 39, receiving sorafenib in 79%), and angiosarcoma (n =18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95% CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC 95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively. Conclusion: Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials. © 2014 Eberst et al.
Sgarbura O.,Carol Davila University of Medicine and Pharmacy |
Sgarbura O.,Institute Regional du Cancer |
Tomulescu V.,Carol Davila University of Medicine and Pharmacy |
Tomulescu V.,Fundeni Clinical Institute |
And 2 more authors.
International Journal of Medical Robotics and Computer Assisted Surgery | Year: 2016
Background: While there is little doubt that robotic interventions have already opened new horizons in surgery due to its inherent complexity, there is still an unmet need for tools allowing center-to-center performance comparisons. A complexity score could be a valuable instrument for further research. Methods: The items of the robotic oncologic complexity score (ROCS) were based on risk factors identified in previous studies. We attempt to build the score and validate it on 400 consecutive cases of robotic oncologic surgery. The primary endpoint is to assess the value of ROCS in predicting major complications. Results: The mean ROCS in the group was 3.3(+/−1.4). Different correlations were calculated: the score and the complications (r=0.38), the major complications (r=0.42), Clavien grade (r=0.5), the operating time (r=0.35), and the length of stay (r=0.47). On the ROC-curve a score >4 has the best specificity and sensibility for predicting major complications (P<0.05). Conclusion: ROCS has potential in predicting complications and hospital length of stay, as well as a role in classifying oncologic robotic surgical interventions. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Lamy P.-J.,Institute regional du Cancer |
Durigova A.,Hopitaux Universitaires Of Geneva |
Jacot W.,Institute regional du Cancer
Clinica Chimica Acta | Year: 2014
Iron plays a fundamental role in cell life and its concentration in living organisms is precisely regulated. Different molecules for iron storage and transport are used to maintain its intracellular homeostasis which is often altered in cancer cells. Specifically, recent studies have demonstrated that in breast cancer cells, the expression/activity of several iron-related proteins, such as ferritin, hepcidin and ferroportin, is deregulated and that these alterations may have a prognostic impact in patients with breast cancer. Moreover, molecules that regulate iron metabolism could become therapeutic targets. This review focuses on recent findings on iron metabolism particularly in breast cancer and on the development of new biomarkers that may be used in the clinical routine for the diagnosis, prognosis and management of cancer-associated anemia as well as for monitoring personalized treatments. © 2014 Elsevier B.V.
Bortolon C.,Montpellier University |
Krikorian A.,Montpellier University |
Krikorian A.,Pontifical Bolivarian University |
Carayol M.,Montpellier University |
And 4 more authors.
Psycho-Oncology | Year: 2014
Objective The aim of this study is to examine factors contributing to cancer-related fatigue (CRF) in breast cancer patients who have undergone surgery. Methods Sixty women (mean age: 50.0) completed self-rated questionnaires assessing components of CRF, muscular and cognitive functions. Also, physiological and subjective data were gathered. Data were analyzed using partial least squares variance-based structural equation modeling in order to examine factors contributing to CRF after breast surgery. Results The tested model was robust in terms of its measurement quality (reliability and validity). According to the structural model results, emotional distress (β = 0.59; p < 0.001), pain (β = 0.23; p < 0.05), and altered vigilance (β = 0.30; p < 0.05) were associated with CRF, accounting for 61% of the explained variance. Also, emotional distress (β = 0.41; p < 0.05) and pain (β = 0.40; p < 0.05) were related to low physical function and accounted for 41% of the explained variance. However, the relationship between low physical function and CRF was weak and nonsignificant (β = 0.01; p > 0.05). Conclusion Emotional distress, altered vigilance capacity, and pain are associated with CRF in postsurgical breast cancer. In addition, emotional distress and pain are related to diminished physical function, which, in turn, has no significant impact on CRF. The current model should be examined in subsequent phases of the treatment (chemotherapy and/or radiotherapy) when side effects are more pronounced and may lead to increased intensity of CRF and low physical function. Copyright © 2013 John Wiley & Sons, Ltd.
PubMed | Hopitaux Universitaires Of Geneva and Institute regional du Cancer
Type: | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2014
Iron plays a fundamental role in cell life and its concentration in living organisms is precisely regulated. Different molecules for iron storage and transport are used to maintain its intracellular homeostasis which is often altered in cancer cells. Specifically, recent studies have demonstrated that in breast cancer cells, the expression/activity of several iron-related proteins, such as ferritin, hepcidin and ferroportin, is deregulated and that these alterations may have a prognostic impact in patients with breast cancer. Moreover, molecules that regulate iron metabolism could become therapeutic targets. This review focuses on recent findings on iron metabolism particularly in breast cancer and on the development of new biomarkers that may be used in the clinical routine for the diagnosis, prognosis and management of cancer-associated anemia as well as for monitoring personalized treatments.
PubMed | Institute Hartmann, Clinique Courlancy, Marseille University Hospital Center, Institute regional du cancer and 7 more.
Type: | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016
In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5Gy in 16 fractions, or 41.6Gy en 13 or 40Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy.