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See detailMesenchymal stem cells shed amphiregulin at the surface of lung carcinoma cells in a juxtacrine manner .
Carnet, Oriane ULg; Lecomte, Julie; Masset, Anne et al

in Neoplasia : An International Journal for Oncology Research (in press)

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See detailBRCA1 germline mutation and glioblastoma development: report of cases
Boukerroucha, Meriem ULg; Josse, Claire ULg; SEGERS, Karin ULg et al

in BMC Cancer (2015), 15

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma ... [more ▼]

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma (GBM). Cases presentation Two patients diagnosed with triple negative breast cancer (TNBC) were screened for BRCA1 germline mutation. They both carried a pathogenic mutation introducing a premature STOP codon in the exon 11 of the BRCA1 gene. Few years later, both patients developed a glioblastoma and a second breast cancer. In an attempt to clarify the role played by a mutated BRCA1 allele in the GBM development, we investigated the BRCA1 mRNA and protein expression in breast and glioblastoma tumours for both patients. The promoter methylation status of this gene was also tested by methylation specific PCR as BRCA1 expression is also known to be lost by this mechanism in some sporadic breast cancers. Conclusion Our data show that BRCA1 expression is maintained in glioblastoma at the protein and the mRNA levels, suggesting that loss of heterozygosity (LOH) did not occur in these cases. The protein expression is tenfold higher in the glioblastoma of patient 1 than in her first breast carcinoma, and twice higher in patient 2. In agreement with the high protein expression level in the GBM, BRCA1 promoter methylation was not observed in these tumours. In these two cases, despite of a BRCA1 pathogenic germline mutation, the tumour-suppressor protein expression is maintained in GBM, suggesting that the BRCA1 mutation is not instrumental for the GBM development. [less ▲]

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See detailMetabolomic, proteomic and preclinical imaging of patient-derived tumor xenografts for improving treatment of liver metastases patients
Perez Palacios, A; Blomme, A; Boutry, S et al

in Acta Gastro-Enterologica Belgica (2015, March), 78(1), 134

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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 detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULg; Blomme, Benoît ULg; Freres, Pierre ULg et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

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See detailEACVI/HFA Cardiac Oncology Toxicity Registry in breast cancer patients: rationale, study design, and methodology (EACVI/HFA COT Registry)-EURObservational Research Program of the European Society of Cardiology.
Lancellotti, Patrizio ULg; Anker, Stefan D.; Donal, Erwan et al

in European Heart Journal - Cardiovascular Imaging (2015)

The goal of adjuvant anti-cancer therapies is cure with limited or no side effects, in particular long-term side effects with negative impact on quality of life. In the palliative setting disease control ... [more ▼]

The goal of adjuvant anti-cancer therapies is cure with limited or no side effects, in particular long-term side effects with negative impact on quality of life. In the palliative setting disease control, quality of life and overall survival are important end points. Partly due to improvements in treatment, the population of cancer survivors is large and growing. However, anti-cancer drug-related cardiotoxicity (ADRC) is the leading cause of treatment-associated mortality in cancer survivors. It is one of the most common post-treatment problems among 5- to 10-year survivors of adult cancer. This is particularly true for breast cancer, the most common cancer in women. The EACVI/HFA COT registry is designed for comprehensive data collection and evaluation of the current European practice in terms of diagnosis and management of ADRC in breast cancer patients. The COT registry will be carried out in two continuing phases, the pilot study phase involving 13 countries followed by the long-term registry in which all the 56 ESC countries will be invited to participate. With the COT registry, several critical information will be obtained: on predisposing factors for the development of ADRC, the rate of subclinical LV dysfunction and its transition to overt heart failure, the clinical impact and outcome of ADRC. [less ▲]

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See detailPrise en charge de la neutropénie fébrile chez le patient cancéreux
FRERES, Pierre ULg; GONNE, Elodie ULg; COLLIGNON, Joëlle ULg et al

in Revue Médicale de Liège (2015), 70(4), 195-200

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, médecins généralistes, urgentistes, hématologues et oncologues se trouvent régulièrement ... [more ▼]

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, médecins généralistes, urgentistes, hématologues et oncologues se trouvent régulièrement confrontés à un effet secondaire sévère des traitements cytotoxiques, le neutropénie fébrile (NF). La NF est une complication gravissime de la chimiothérapie, car elle peut être rapidement mortelle et provoque un arrêt temporaire, voire définitif, des traitements. Dans cet article, nous résumons les dernières recommandations quant à la prise en charge thérapeutique des patients présentant une NF sous traitements anti-cancéreux. [less ▲]

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See detailCancer du sein : de la thérapie ciblée à la médecine personnalisée
JERUSALEM, Guy ULg; COLLIGNON, Joëlle ULg; Josse, Claire ULg et al

in Revue Médicale de Liège (2015), 70(5-6), 269-276

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce ... [more ▼]

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce traitement est-il individualisé ? Les nouvelles technologies permettent une analyse détaillée des anomalies génomiques au niveau des cellules cancéreuses. Malheureusement, nous n'avons pas encore compris comment utiliser au mieux ces données au bénéfice du patient. La majorité des modifications du génome sont des évènements relativement rares compliquant le développement de nouveaux médicaments dans le cadre d'une médecine de précision. De plus, les tumeurs présentent une grande hétérogénéité temporelle et spatiale dont il faudra tenir compte lors de ce développement. Une collaboration internationale intensive est en cours pour tenter de confirmer que la médecine de précision permet d'optimiser les résultats du traitement systémique dans le cancer du sein. [less ▲]

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See detailA network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.
Generali, Daniele; Venturini, Sergio; Rognoni, Carla et al

in Breast cancer research and treatment (2015), 152(1), 95-117

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods ... [more ▼]

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances. [less ▲]

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See detailChemotherapy options for patients suffering from heavily pretreated metastatic breast cancer.
Jerusalem, Guy ULg; RORIVE, Andrée ULg; COLLIGNON, Joëlle ULg

in Future oncology (London, England) (2015), 11(12), 1775-89

ABSTRACT The identification of additional chemotherapy agents for anthracycline- and taxane-pretreated advanced breast cancer (ABC) is an urgent medical need. Single agent chemotherapy is most times ... [more ▼]

ABSTRACT The identification of additional chemotherapy agents for anthracycline- and taxane-pretreated advanced breast cancer (ABC) is an urgent medical need. Single agent chemotherapy is most times administered because combined therapy is only associated with modest, if any, improvement in median progression-free survival. Randomized trials failed to show overall survival benefit compared with single agent chemotherapy. We hope to modify the natural history of ABC by the consecutive use of treatments with documented activity in heavily pretreated patients. Quality of life remains an important end point as cure is in general not possible. We first review the activity of the approved and the most frequently used agents in heavily pretreated ABC. Thereafter, the potential role and safety profile of etirinotecan pegol is discussed given the results recently released of a Phase III trial comparing this agent to Treatment of Physician's Choice. [less ▲]

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See detailCancer du sein: intérêt du bilan d’extension par imagerie lors du diagnostic initial et du suivi les trois premières années après le diagnostic
SCHROEDER, Hélène ULg; Hanocq, Florence ULg; COLLIGNON, Joëlle ULg et al

in Revue Médicale de Liège (2015), 70(3), 140-147

In our region, repeated tumor staging by radiological procedures aiming to detect relapses and/or metastases from breast cancer is frequently performed. However, these procedures are not recommended by ... [more ▼]

In our region, repeated tumor staging by radiological procedures aiming to detect relapses and/or metastases from breast cancer is frequently performed. However, these procedures are not recommended by current international guidelines. We retrospectively analyzed the charts from 818 patients with a new diagnosis of breast cancer seen at CHU Liege between 2005 and 2009. We assessed the role of staging procedures at initial diagnosis and during follow-up the first 3 years after the diagnosis of breast cancer. Twenty-six patients presented with metastatic disease at diagnosis and 55 patients developed loco-regional relapses or metastases during follow-up. For asymptomatic patients, imaging procedures only detected tumor metastases or relapse without elevated tumor markers in 9 patients at initial diagnosis and 10 patients during follow-up. The diagnosis of an asymptomatic relapse and/or metastases had no positive impact on progression-free or overall survival. The anatomic extension identified patients at high risk for presenting distant metastases already at the time of initial diagnosis and the biological aggressiveness evaluated by Ki-67 was an important prognostic factor for early relapse. In view of these results, we do not recommend staging and searching for metastatic disease in asymptomatic patients presenting early stage breast cancer with low expression of the Ki-67 at the time of initial diagnosis. We also do not recommend repeated staging and searching for metastases by imaging in asymptomatic patients during routine follow-up. Staging should only be performed if a relapse is suspected during follow-up. [less ▲]

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See detailTrebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer: A phase 2 randomized study.
Dieras, Veronique; Wildiers, Hans; Jassem, Jacek et al

in Breast (Edinburgh, Scotland) (2015), 24

INTRODUCTION: This phase 2 randomized study evaluated trebananib (AMG 386), a peptide-Fc fusion protein that inhibits angiogenesis by neutralizing the interaction of angiopoietin-1 and -2 with Tie2, in ... [more ▼]

INTRODUCTION: This phase 2 randomized study evaluated trebananib (AMG 386), a peptide-Fc fusion protein that inhibits angiogenesis by neutralizing the interaction of angiopoietin-1 and -2 with Tie2, in combination with paclitaxel with or without bevacizumab in previously untreated patients with HER2-negative locally recurrent/metastatic breast cancer. METHODS: Patients received paclitaxel 90 mg/m2 once weekly (3-weeks-on/1-week-off) and were randomly assigned 1:1:1:1 to also receive blinded bevacizumab 10 mg/kg once every 2 weeks plus either trebananib 10 mg/kg once weekly (Arm A) or 3 mg/kg once weekly (Arm B), or placebo (Arm C); or open-label trebananib 10 mg/kg once a week (Arm D). Progression-free survival was the primary endpoint. RESULTS: In total, 228 patients were randomized. Median estimated progression-free survival for Arms A, B, C, and D was 11.3, 9.2, 12.2, and 10 months, respectively. Hazard ratios (95% CI) for Arms A, B, and D versus Arm C were 0.98 (0.61-1.59), 1.12 (0.70-1.80), and 1.28 (0.79-2.09), respectively. The objective response rate was 71% in Arm A, 51% in Arm B, 60% in Arm C, and 46% in Arm D. The incidence of grade 3/4/5 adverse events was 71/9/4%, 61/14/5%, 62/16/3%, and 52/4/7% in Arms A/B/C/D. In Arm D, median progression-free survival was 12.8 and 7.4 months for those with high and low trebananib exposure (AUCss >/= 8.4 versus < 8.4 mg.h/mL), respectively. CONCLUSIONS: There was no apparent prolongation of estimated progression-free survival with the addition of trebananib to paclitaxel and bevacizumab at the doses tested. Toxicity was manageable. Exposure-response analyses support evaluation of combinations incorporating trebananib at doses > 10 mg/kg in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00511459. [less ▲]

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See detailLe regard (peu optimiste) du soignant sur la personne âgée
Schroyen, Sarah ULg; Missotten, Pierre ULg; Marquet, Manon ULg et al

in Medi-Sphere (2015), 469

L’âgisme (c’est-à-dire l’ensemble de nos stéréotypes liés à l’avancée en âge) a de nombreuses conséquences négatives tant pour le patient lui-même qu’au sein de la relation entre le patient et le ... [more ▼]

L’âgisme (c’est-à-dire l’ensemble de nos stéréotypes liés à l’avancée en âge) a de nombreuses conséquences négatives tant pour le patient lui-même qu’au sein de la relation entre le patient et le personnel soignant. Au cours de cet article, nous illustrerons les représentations du vieillissement prévalentes chez les soignants et aborderons brièvement les conséquences de l’âgisme sur leurs attitudes de soins. [less ▲]

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See detailVISMODEGIB ET CARCINOMES BASOCELLULAIRES LOCALEMENT AVANCES
LEBAS, Eglantine ULg; RORIVE, Andrée ULg; EL HAYDERI, Lara ULg et al

in Revue Médicale de Liège (2015)

Basal cell carcinoma is the most frequent skin cancer. Even though metastases are exceptional, these cancers may be locally highly aggressive. The Hedgehog signaling pathway plays a significant role in ... [more ▼]

Basal cell carcinoma is the most frequent skin cancer. Even though metastases are exceptional, these cancers may be locally highly aggressive. The Hedgehog signaling pathway plays a significant role in the pathogenesis of basal cell carcinoma. Vismodegib is a selective inhibitor of this pathway and may be administered orally. Its main indication is locally advanced basal cell carcinoma, when other therapeutic options have failed or are contra-indicated. Vismodegib can also be used as prophylactic therapy in the Gorlin syndrome or basal cell nevomatosis. Its principal adverse effects are muscle spasms, alopecia and altered taste. They are frequent, but often moderate in intensity; they sometimes restrict continuation of treatment. Two clinical cases are presented, relating the efficacity and tolerance of this new therapeutic option. [less ▲]

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See detailAgeism and its clinical impact in oncogeriatry: state of knowledge and therapeutic leads
Schroyen, Sarah ULg; Adam, Stéphane ULg; JERUSALEM, Guy ULg et al

in Clinical Interventions in Aging (2015), 10

Cancer is a major health problem that is widespread in elderly people. Paradoxically, older people suffering from cancer are often excluded from clinical trials and are undertreated when compared to ... [more ▼]

Cancer is a major health problem that is widespread in elderly people. Paradoxically, older people suffering from cancer are often excluded from clinical trials and are undertreated when compared to younger patients. One explanation for these observations is age stigma (ie, stereotypes linked to age, and thus ageism). These stigmas can result in deleterious consequences for elderly people’s mental and physical health in “normal” aging. What, then, is the impact in a pathological context, such as oncology? Moreover, health care professionals’ attitudes can be tainted with ageism, thus leading to undesirable consequences for patients. To counter these stigmas, we can apply some possible interventions emerging from research on normal aging and from social psychology, such as intergenerational contact, activation of positive stereotypes, self-affirmation, and so on; these tools can improve opinions of aging among the elderly people themselves, as well as health care professionals, thus affecting patients’ mental and physical health. [less ▲]

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See detailPersonnel soignant et âgisme: quelles conséquences cliniques ?
Schroyen, Sarah ULg; Missotten, Pierre ULg; JERUSALEM, Guy ULg et al

Conference (2014, December 16)

Introduction : Le cancer est un problème de santé majeur dont l’âge constitue un facteur de risque avéré1. Paradoxalement, les personnes âgées souffrant d’un cancer sont souvent exclues des essais ... [more ▼]

Introduction : Le cancer est un problème de santé majeur dont l’âge constitue un facteur de risque avéré1. Paradoxalement, les personnes âgées souffrant d’un cancer sont souvent exclues des essais cliniques et sous-traitées comparativement à des patients plus jeunes1. Un élément explicateur de ces constats est la stigmatisation liée à l’âge² (c.à.d. nos stéréotypes liés à l’âge, et donc l’âgisme). Méthodologie : Nous avons interrogé 76 infirmiers (-ères) travaillant en oncologie. A l’aide de fiches cli-niques, nous leur avons demandé s’ils encourageraient à des patients un traitement expérimental (40 vs 70 ans), une chimiothérapie ou une reconstruction mammaire (35, 55 ou 75 ans), tout paramètres cliniques étant équivalents par ailleurs. Résultats : L’encouragement d’un traitement expérimental est moins fréquente pour une personne de 70 ans comparativement à une personne de 40 ans (p<.001). De plus, le personnel soignant encourage moins fréquemment une chimiothérapie pour une personne de 75 ans comparativement aux per-sonnes de 55 et 35 ans (p<.001). Au niveau de la reconstruction mammaire, une différence est vi-sible dès 55 ans : la reconstruction mammaire est moins encouragée pour une personne de cet âge par rapport à une personne de 35 ans (p=.02) et encore moins encouragée pour une personne de 75 ans comparativement à une personne de 55 ans (p<.001). L’âge des infirmiers (M = 35.8) a une influence sur ces encouragement : plus ils sont âgés, plus ils encouragent le traitement chimiothérapeutique d’une per-sonne de 75 ans (p = .005) de même que le traitement expérimental pour une personne de 70 ans (p = .01). Conclusion : A l’instar d’autres études3, 4, nous confirmons que tant du point de vue esthétique que cura-tif, le personnel médical encourage moins fréquemment un traitement aux patients plus âgés compa-rativement aux plus jeunes. 1. Hurria, A., et al. (2012). J Natl Compr Canc Netw, 10, 162-209. 2. Penson, R. T., et al. (2004). The Oncologist, 9, 343-352. 3. Madan, A. K., et al. (2001). Acad Med, 76, 282-284. 4. Protière, C., et al. (2010). Crit Rev Oncol Hematol, 75, 138-150. [less ▲]

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