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See detailMyoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer
Blomme, Arnaud; Costanza, Brunella ULg; De Tullio, Pascal ULg et al

in Oncogene (2016)

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as ... [more ▼]

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients. [less ▲]

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See detailInfluence d'un programme de revalidation multidisciplinaire post-cancer du sein sur la fonction physique
Leclerc, Anne-France ULg; Foidart-Dessalle, Marguerite ULg; BURY, Thierry ULg et al

in 9ème Congrès commun SFMES - SFTS : Abstract book (2016, September 22)

Objectif : Le cancer du sein ainsi que ses traitements sont à l'origine de nombreux effets secondaires indésirables, notamment sur la fonction physique. Cette étude a pour objectif de déterminer les ... [more ▼]

Objectif : Le cancer du sein ainsi que ses traitements sont à l'origine de nombreux effets secondaires indésirables, notamment sur la fonction physique. Cette étude a pour objectif de déterminer les bénéfices éventuels d’un programme de revalidation multidisciplinaire sur la santé physique des femmes ayant été traitées pour un cancer du sein et d'évaluer l'influence de certaines caractéristiques individuelles initiales sur la réponse du groupe expérimental au programme de revalidation. Matériel et méthodes : L'étude constitue un essai clinique contrôlé non-randomisé évaluant une population totale de 209 patientes, recrutées sur base du volontariat et réparties en deux groupes, soit un groupe contrôle (n = 106) et un groupe expérimental (n = 103). Ce dernier a bénéficié d’une revalidation de trois mois comprenant un entraînement physique supervisé à raison de trois séances par semaine et diverses sessions psycho-éducatives. Pour l'ensemble des participantes, des évaluations constituées d'une part de mesures physiques et fonctionnelles et d'autre part de mesures de composition corporelle ont été programmées à 0 et 3 mois. Celles-ci ont inclus un test de souplesse ("Sit and Reach"), un test d'effort maximal sur bicyclette ergométrique avec suivi cardio-respiratoire, un test de marche de six minutes et la mesure de l'indice de masse corporelle et du pourcentage de graisse corporelle. Afin d'affiner l'analyse, trois groupes ont également été constitués au sein du groupe expérimental à partir des caractéristiques individuelles de thérapie adjuvante (présence de chimiothérapie ou non), de chirurgie (mastectomie ou tumorectomie) et de délai de fin de traitement (délai ≤ 4 mois ou ≥ 8 mois). Résultats : Initialement, toutes les patientes présentent un état de déconditionnement physique, non influencé par le délai de fin de traitement ou par le type de chirurgie, mais bien influencé par la présence d'une chimiothérapie puisque la VO2max apparaît significativement plus faible dans ce cas. Au terme des trois mois, la souplesse (p < 0,0001), la consommation maximale d'oxygène (p < 0,0001), la puissance maximale aérobie (p < 0,0001) et la distance de marche en six minutes (p < 0,0001) s’améliorent significativement au sein du groupe expérimental. Au sein du groupe contrôle, aucune amélioration n'est constatée, excepté pour la distance de marche (p = 0,0031). Par ailleurs, une augmentation significative de l'indice de masse corporelle (p = 0,034) et du pourcentage de graisse corporelle (p = 0,034) est observée au sein du groupe contrôle alors que ce paramètre diminue significativement au sein du groupe expérimental (p = 0,037). Enfin, toutes les patientes du groupe expérimental présentent un même profil de progression quelles que soient leurs caractéristiques individuelles initiales. Conclusion : Cette étude démontre ainsi les effets bénéfiques, tant sur le plan physique que de la composition corporelle, d’une prise en charge multidisciplinaire chez des femmes ayant été traitées pour le cancer du sein. [less ▲]

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See detailEtude pilote auprès de patientes atteintes d'un cancer du sein: Apport des méthodes alternatives.
Bragard, Isabelle ULg; Etienne, Anne-Marie ULg; Faymonville, Marie-Elisabeth ULg et al

in Etienne, Anne-Marie; Bragard, Isabelle (Eds.) Evolutions Sociales, Innovations et Politiques: nouvelles questions et nouveaux enjeux pour la psychologie de la santé. (2016)

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See detailCirculating microRNA-based screening tool for breast cancer
Freres, Pierre ULg; Wenric, Stéphane ULg; Boukerroucha, Meriem et al

in Oncotarget (2015)

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative ... [more ▼]

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis. A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women. A diagnostic model was designed based on the expression of 8 miRNAs measured first in a profiling cohort composed of 41 primary breast cancers and 45 controls, and further validated in diverse cohorts composed of 108 primary breast cancers, 88 controls, 35 breast cancers in remission, 31 metastatic breast cancers and 30 gynecologic tumors. A receiver operating characteristic curve derived from the 8-miRNA random forest based diagnostic tool exhibited an area under the curve of 0.81. The accuracy of the diagnostic tool remained unchanged considering age and tumor stage. The miRNA signature correctly identified patients with metastatic breast cancer. The use of the classification model on cohorts of patients with breast cancers in remission and with gynecologic cancers yielded prediction distributions similar to that of the control group. Using a multivariate supervised learning method and a set of 8 circulating miRNAs, we designed an accurate, minimally invasive screening tool for breast cancer. [less ▲]

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See detailPsychological benefits of a multidisciplinary rehabilitation program after breast cancer
Leclerc, Anne-France ULg; FOIDART-DESSALLE, Marguerite ULg; Bury, Thierry ULg et al

in European Cancer Congress : Abstract book (2015, September 27)

Background : Breast cancer is the most frequent cancer in women, affecting 8 women out of 100. With early detection and improved treatments, the number of deaths linked to this disease has declined ... [more ▼]

Background : Breast cancer is the most frequent cancer in women, affecting 8 women out of 100. With early detection and improved treatments, the number of deaths linked to this disease has declined. However, the disease and its treatments are at the origin of many undesirable side effects such as fatigue, anxiety, weight gain and sleep disorders. The objective of this study is to determine the psychological benefits of a multidisciplinary rehabilitation program among women treated for breast cancer (on average six months after the end of the adjuvant radiotherapy or chimiotherapy). Material and methods : 122 patients were included into a control group (n = 61) and a treated group (n = 61). All participants were submitted to evaluations before the beginning of the trial and after three months. These evaluations included different questionnaires exploring the quality of life, anxiety, depression and various functions and other symptoms related to cancer (EORTC QLQ-C30, EQ-5D, STAI, HADS) and functional assessments. The control group has received no intervention unlike the treated group that received a three-month rehabilitation including supervised physical training (90 min) with three times a week and various psycho-educational sessions (120 min) once a week. Results : After three months, the health status (quality of life) (p < 0,0001), the functional role (p = 0,031), emotional state (p < 0,0001) and physical (p = 0,0045), cognitive (p = 0,0027) and social functions (p = 0,0018) improve significantly in the treated group. This observation also applies to symptoms of fatigue (p < 0,0001), insomnia (p < 0,0001), pain (p = 0,002), dyspnea (p = 0,009), loss of appetite (p = 0,04), anxiety (p < 0,0001) and depression (p < 0,0001) as well as physical parameters obtained through functional assessments. In the control group, these improvements do not appear. Conclusions : This study shows the feasibility and psychological benefits of such a multidisciplinary oncological rehabilitation program in women after their treatments for breast cancer. Additional studies are needed to know the optimal time of beginning (during treatments or after them) and the optimal management time for this support. [less ▲]

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See detailPhysical benefits of a multidisciplinary rehabilitation program after breast cancer
Leclerc, Anne-France ULg; FOIDART-DESSALLE, Marguerite ULg; Bury, Thierry ULg et al

Poster (2015, September 26)

Background : Breast cancer is the most frequent cancer in women, affecting 8 women out of 100. With early detection and improved treatments, the number of deaths linked to this disease has declined ... [more ▼]

Background : Breast cancer is the most frequent cancer in women, affecting 8 women out of 100. With early detection and improved treatments, the number of deaths linked to this disease has declined. However, the disease and its treatments are at the origin of many undesirable side effects such as fatigue, anxiety, weight gain and decreased physical fitness. The objective of this study is to determine the physical benefits of a multidisciplinary rehabilitation program among women treated for breast cancer (on average six months after the end of the adjuvant radiotherapy or chimiotherapy). Material and methods : 122 patients were included into a control group (n = 61) and a treated group (n = 61). All participants were submitted to evaluations before the beginning of the trial and after three months. These evaluations included functional assessments (a maximal incremental exercise protocol on a cycle ergometer, flexibility by Sit and Reach Test and walking distance by Six-Minute Walk Test), anthropometric and body composition measurements (Body Mass Index and body fat percentage) and different questionnaires on quality of life, anxiety and other symptoms related to cancer. The control group has received no intervention unlike the treated group that received a three-month rehabilitation including supervised physical training (90 min) with three times a week and various psycho-educational sessions (120 min) once a week. Results : After three months, maximal oxygen consumption (p < 0,0001), maximal aerobic power (p < 0,0001), peak of ventilation (p < 0,0001) and time to exhaustion (p = 0,0055) during the maximal incremental exercise protocol improve significantly in the treated group. This observation also applies to flexibility (p < 0,0001), walking distance in six minutes (p < 0,0001) and different physical and psychological parameters obtained through questionnaires. In the control group, these improvements do not appear and a significant increase in body mass index (p = 0,032) and body fat percentage (p = 0,034) is observed while these data remain constant in the treated group. Conclusions : This study shows the feasibility and physical benefits of such a multidisciplinary oncological rehabilitation program in women after their treatments for breast cancer. Additional studies are needed to know the optimal time of beginning (during treatments or after them) and the optimal management time for this support. [less ▲]

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See detailRetour au travail après un cancer du sein
Mairiaux, Philippe ULg; Schippers, Nathalie ULg; DESREUX, Joëlle ULg et al

Conference (2015, April 23)

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See detailOncological and surgical outcome after oncoplastic breast surgery
NIZET, Jean-Luc ULg; MAWEJA, Sylvie ULg; LAKOSI, Ferenc ULg et al

in Acta Chirurgica Belgica (2015), 115

BACKGROUND: Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the ... [more ▼]

BACKGROUND: Oncoplastic surgery combines breast-conserving treatment and plastic surgery techniques. The aim of the study was to identify breast and tumor-related characteristics that contribute to the rate of complications and recurrence. METHODS: This retrospective study included 72 patients with a median follow-up of 32 months. For each patient, a comprehensive set of data was collected, including epidemiology, tumor characteristics, preoperative information, detailed pathology reports, radiotherapy treatment and type of surgical technique. The rate of complications, recurrence and survival were studied. RESULTS: Complete tumor removal was performed with clear margins in all patients but in 25 of them margins were less than 2 mm. One patient had local recurrence and another developed distant metastases. The study showed that the size of the margin was not predictive of recurrence as long as not positive; the greater the resection volume, the larger the excision margin. The resection size was the only factor influencing complications and no specific tumor-related factor significantly increased the complication rate. Surgical complications did not delay the initiation of chemotherapy and radiotherapy. CONCLUSIONS: This is the first oncoplastic study where both tumor and breast characteristics were analyzed using the most recent criteria of the literature. Oncoplastic surgery can be considered as oncologically safe. The resection size was the sole significant risk factor for postoperative complications. Complications after oncoplastic breast surgery did not differ neoadjuvant therapy. Long-term event-free survival was excellent (96% at 7 years). [less ▲]

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See detailPrise en charge d'un cancer du sein chez une femme porteuse de prothèses mammaires
REMACLE, Sarah; LIFRANGE, Eric ULg; NIZET, Jean-Luc ULg

in Revue Médicale de Liège (2015), 70

The incidence of breast cancer, currently one woman on eight, also concerns patients who underwent augmentation surgery. Breast implants have already been the subject of numerous publications concerning ... [more ▼]

The incidence of breast cancer, currently one woman on eight, also concerns patients who underwent augmentation surgery. Breast implants have already been the subject of numerous publications concerning the risk of inducing breast cancer or delaying the diagnosis, however, no significant causal relationship has been established. The purpose of this article is to assess the diagnostic and therapeutic consequences when breast cancer is identified in a patient with breast implants. [less ▲]

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See detailAsporin Is a Fibroblast-Derived TGF-beta1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
Maris, Pamela; Blomme, Arnaud; Palacios, Ana Perez et al

in PLoS medicine (2015), 12(9), 1001871

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key ... [more ▼]

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1beta, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-beta1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-beta1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy. [less ▲]

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See detailMyoferlin is a key regulator of EGFR activity in breast cancer.
Turtoi, Andrei ULg; Blomme, Arnaud ULg; Bellahcene, Akeila ULg et al

in Cancer Research (2013), 73

Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its ... [more ▼]

Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its expression in and contributions to cancer are not well established. In this study, we show that myoferlin is overexpressed in human breast cancers and that it is has a critical role in controlling degradation of the EGFR after its activation and internalization in breast cancer cells. Myoferlin depletion blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both effects were induced as a result of impaired degradation of phosphorylated EGFR via dysfunctional plasma membrane caveolae and alteration of caveolin homooligomerization. In parallel, myoferlin depletion reduced tumor development in a chicken chorioallantoic membrane xenograft model of human breast cancer. Considering the therapeutic significance of EGFR targeting, our findings identify myoferlin as an novel candidate function to target for future drug development. [less ▲]

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See detailShould we individualize breast cancer screening?
DESREUX, Joëlle ULg; BLERET, Valerie ULg; LIFRANGE, Eric ULg

in Maturitas (2012), 73

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See detailEuropean inter-institutional impact study of MammaPrint
CUSUMANO, Giuseppe ULg; Generali, D; Ciruelos, E et al

Poster (2012)

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See detailNovel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues
Turtoi, Andrei ULg; Dumont, Bruno ULg; Greffe, Yannick et al

in Journal of Proteome Research (2011), 10(7), 3160-82

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a ... [more ▼]

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer lesions. Due to the fact that our technology is applicable to any type of tissue biopsy, it bears the ability to accelerate the discovery of new relevant biomarkers in a broad spectrum of pathologies. [less ▲]

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See detailTechniques de prélèvements cytologiques en pathologie mammaire
LAMBERT, Chantal ULg; Colin; Delvenne, Philippe ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 261-4

Mammary cytology is part of the breast cancer test. Its accuracy depends on both the sample quality and the cyto-pathologist’s competence. Extracting cells in a liquid environment allows obtaining smears ... [more ▼]

Mammary cytology is part of the breast cancer test. Its accuracy depends on both the sample quality and the cyto-pathologist’s competence. Extracting cells in a liquid environment allows obtaining smears in less hemorrhagic thin layers, containing more cells and with less interference with the fixation artefact. This technique keeps materiel for further immunocytochemistry and cell biology studies if needed. It will be especially useful in automated analysis. [less ▲]

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