Publications of Pierre FOIDART
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See detailDiagnostic différentiel de l’anémie dans la cirrhose éthylique
Delmotte, Valentine ULiege; Foidart, Pierre ULiege; DE VOEGHT, Adrien ULiege et al

in Revue Médicale de Liège (2019), 74(10), 527-534

We report here the case of a 62-year-old patient with Child-Pugh stage C ethylic cirrhosis associated with severe macrocytic anaemia, refractory to iterative transfusions and withdrawal. After a ... [more ▼]

We report here the case of a 62-year-old patient with Child-Pugh stage C ethylic cirrhosis associated with severe macrocytic anaemia, refractory to iterative transfusions and withdrawal. After a haemorrhagic, deficiency-related, or sideroblastic etiology was ruled out, haemolytic anaemia was suspected. A blood smear allowed diagnosis of haemolytic anaemia with acanthocytes. This offers the opportunity to discuss anaemia in patients with alcoholic cirrhosis, a frequent complication spanning a broad severity range and having the potential to be life-threatening. Its origin can be multifactorial : acute haemorrhage, dilution, haemolysis (here due to acanthocytosis), marrow insufficiency caused by direct alcohol toxicity, malnutrition, iron deficiency, vitamin B9 or B12 deficiency, chronic inflammation, splenic sequestration induced by portal hypertension...Nous rapportons le cas d’une patiente de 62 ans atteinte d’une cirrhose éthylique de stade Child-Pugh C associée à une anémie macrocytaire sévère, réfractaire aux transfusions itératives et au sevrage. Après avoir exclu les étiologies hémorragiques, carentielles et sidéroblastiques, une anémie hémolytique (AH) est suspectée. La réalisation d’un frottis sanguin a permis le diagnostic d’une anémie hémolytique à acanthocytes. L’opportunité nous est donnée de discuter de l’anémie chez le patient cirrhotique alcoolique, complication fréquente recouvrant un large spectre de gravité et pouvant menacer la survie. Elle peut être multifactorielle : hémorragie aiguë, dilution, hémolyse (dans le cas particulier, liée à une acanthocytose), insuffisance médullaire par toxicité directe de l’alcool, malnutrition, carence martiale, déficit en vitamine B9 ou B12, inflammation chronique, séquestration splénique induite par l’hypertension portale…. [less ▲]

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See detailCapecitabine efficacy is correlated with TYMP and RB expression in PDX established from triple-negative breast cancers.
Marangoni, Elisabetta; Laurent, Cecile; Coussy, Florence et al

in Clinical Cancer Research (2018)

PURPOSE: triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to ... [more ▼]

PURPOSE: triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to identify efficient chemotherapies and predictive biomarkers in a context of resistance to anthracyclines and taxanes-based treatments. EXPERIMENTAL DESIGN: PDX were established from residual tumors of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were treated by anthracyclines, taxanes, platins and capecitabine. Predictive biomarkers were identified by transcriptomic and immunohistological analysis. Downregulation of RB1 was performed by siRNA in a cell line established from a PDX. RESULTS: residual TNBC PDX were characterized by a high tumor take, a short latency and a poor prognosis of the corresponding patients. With the exception of BRCA1/2 mutated models, residual PDX were resistant to anthracyclines, taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly efficient in 60% of PDX with two models showing complete responses. Prior treatment of a responder PDX with 5-FU increased expression of thymidylate synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses of 32 TNBC PDX, including both residual tumors and treatment-naive derived tumors, identified RB and TYMP proteins as predictive biomarkers for capecitabine response. Finally, RB1 knockdown in a cell line established from a capecitabine-responder PDX decreased sensitivity to 5-FU treatment. CONCLUSIONS: we identified capecitabine as efficient chemotherapy in TNBC PDX models established from residual disease and resistant to anthracyclines, taxanes and platins. RB positivity and high expression of TYMP were significantly associated with capecitabine response. [less ▲]

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See detailMT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib.
Yip, Cassandre ULiege; Foidart, Pierre ULiege; Somja, Joan ULiege et al

in British Journal of Cancer (2017)

BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a ... [more ▼]

BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. METHODS: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. RESULTS: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. CONCLUSIONS: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs.British Journal of Cancer advance online publication 14 February 2017; doi:10.1038/bjc.2017.23 www.bjcancer.com. [less ▲]

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