E. Maubec

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (89)236.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by co-administration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate, eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect epidermis thickness but co-application of clobetasol and spironolactone limited significantly clobetasol-induced atrophy and was well tolerated. Altogether these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.Journal of Investigative Dermatology accepted article preview online, 10 February 2015. doi:10.1038/jid.2015.44.
    The Journal of investigative dermatology. 02/2015;
  • Annales de Dermatologie et de Vénéréologie 11/2014; · 0.67 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 11/2014; · 0.67 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 11/2014; · 0.67 Impact Factor
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    ABSTRACT: Cutaneous head and neck tumors mainly comprise malignant melanoma, squamous cell carcinoma, trichoblastic carcinoma, Merkel cell carcinoma, adnexal carcinoma, dermatofibrosarcoma protuberans, sclerodermiform basalioma and angiosarcoma. Adapted management requires an experienced team with good knowledge of the various parameters relating to health status, histology, location and extension: risk factors for aggression, extension assessment, resection margin requirements, indications for specific procedures, such as lateral temporal bone resection, orbital exenteration, resection of the calvarium and meningeal envelopes, neck dissection and muscle resection. Copyright © 2014. Published by Elsevier Masson SAS.
    European Annals of Otorhinolaryngology, Head and Neck Diseases 11/2014; 131(6):375-383.
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    ABSTRACT: Objectifs La Société française d’otorhinolaryngologie (SFORL) a organisé un groupe de travail chargé de la rédaction de recommandations pour la prise en charge des patients immunodéprimés atteints de tumeurs de la tête et du cou de point de départ cutané. Ces recommandations abordent la prise en charge diagnostique et thérapeutique ainsi que les mesures de prévention des tumeurs de la tête et du cou à point de départ cutané survenant chez les immunodéprimés, en particulier les transplantés et les patients infectés par le VIH. Matériels et méthodes L’élaboration de ces recommandations repose sur une lecture critique multidisciplinaire de la littérature. L’immunosuppression et les différents types d’immunosuppression ont été définis. Les facteurs de risque habituels des tumeurs cutanées et ceux spécifiques à l’immunodéprimé sont présentés. La prévention, le bilan et la prise en charge des carcinomes cutanés, du mélanome, de la maladie de Kaposi et des lymphomes sont traités. Le niveau de preuve des études a été estimé, permettant de grader le niveau des recommandations. Le cas échéant, des avis d’experts ont été proposés. Résultats Les immunodéprimés ont un risque accru de développer des tumeurs cutanées de l’extrémité cervico-céphalique. Le risque de développer ces tumeurs varie en fonction du type d’immunosuppression ; il existe un risque particulièrement élevé de carcinomes épidermoïdes chez les transplantés et de maladie de Kaposi chez les patients séropositifs pour le VIH. Différents virus sont associés à ces cancers cutanés. Les tumeurs cutanées de l’immunodéprimé sont souvent caractérisées par leur évolutivité justifiant une prise en charge thérapeutique rapide. La prise en charge spécifique, en général similaire à celle du sujet immunocompétent, doit être discutée en RCP. La modulation de l’immunosuppression doit être envisagée. Chez le transplanté d’organe, la seule classe d’immunosuppresseurs ayant un effet anti-tumoral documenté est celle des inhibiteurs de mTOR en particulier pour les carcinomes épidermoïdes cutanés. La fréquence de la surveillance clinique doit être adaptée au risque de récidive. Des mesures de prévention doivent être proposées. Conclusion Les tumeurs cutanées de l’immunodéprimé sont souvent caractérisées par leur évolutivité justifiant une prise en charge thérapeutique la plus précoce possible. Une modulation de l’immunosuppression doit être discutée. En raison d’un risque souvent élevé de récidive, une surveillance attentive doit être proposée. Les mesures de prévention doivent également être respectées.
    Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale. 04/2014; 131(2):107–116.
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    ABSTRACT: Objectives The French ENT Society (SFORL) created a workgroup to draw up guidelines for the management of immunodeficient patients with head and neck cancer of cutaneous origin. The present guidelines cover diagnostic and therapeutic management and prevention of head and neck cancer of cutaneous origin in immunodeficient patients, and in particular in transplant patients and those with HIV infection. Materials and methods The present guidelines were based on a critical multidisciplinary reading of the literature. Immunosuppression and its varieties are defined. The usual risk factors for skin cancer and those specific to immunodeficiency are presented. The prevention, assessment and management of cutaneous carcinoma, melanoma, Kaposi's sarcoma and lymphoma are dealt with. The level of evidence of the source studies was assessed so as to grade the various guidelines. When need be, expert opinions are put forward. Results Immunodeficient patients are at higher risk of head and neck skin tumors. The level of risk depends on the type of deficiency; there is an especially high risk of squamous cell carcinoma in transplant patients and of Kaposi's sarcoma in HIV-positive subjects. Various viruses are associated with skin cancers. Skin tumors are often evolutive in case of immunodeficiency, requiring rapid treatment. Management is generally the same as in immunocompetent subjects and should be discussed in a multidisciplinary team meeting. Immunosuppression may need to be modulated. In organ transplant patients, the only class of immunosuppressants with proven antitumoral efficacy are mTOR inhibitors, particularly in cutaneous squamous cell carcinoma. The rhythm of clinical surveillance should be adapted according to the risk of recurrence. Preventive measures should be undertaken. Conclusion Skin cancers in immunodeficiency are highly evolutive, requiring the earliest possible treatment. Immunosuppression may need modulating. As the risk of recurrence may be elevated, careful surveillance should be implemented. Preventive measures should also be undertaken.
    European Annals of Otorhinolaryngology, Head and Neck Diseases 04/2014;
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    ABSTRACT: IMPORTANCE Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), occurs in elderly patients and has been considered as a lymphoma with a poor prognosis, with estimated 5-year specific survival rates of approximately 50%. The hypothesis of an improvement in prognosis over time has not been studied. OBJECTIVES To evaluate this hypothesis in a large series of patients and investigate factors associated with prognosis as well as improvement in the prognosis. DESIGN, SETTING, AND PARTICIPANTS A retrospective multicenter study was conducted including dermatology departments belonging to the French Study Group on Cutaneous Lymphoma. Participants were 115 patients with PCDLBCL-LT diagnosed between 1988 and 2003 (period 1) or between 2004 and 2010 (period 2). MAIN OUTCOMES AND MEASURES Age, sex, period of diagnosis, number of skin lesions, tumor stage, tumor location (leg vs nonleg), lactate dehydrogenase level, type of therapy (with or without a combination of rituximab and polychemotherapy [PCT]), and outcome were recorded. Baseline characteristics and outcome were compared according to period of diagnosis and type of therapy. Prognosis factors were identified by univariate and multivariate survival analyses. RESULTS The mean age of the patients was 76.9 years, and 47% of the patients were older than 80 years. The 3- and 5-year specific survival rates improved between period 1 and period 2, from 55% to 74% and from 46% to 66%, respectively (P = .01). Patients had similar baseline characteristics during both periods, but rituximab-PCT regimens were administered to 88.5% of the patients in period 2 vs 16.7% in period 1 (P < .001). The 3- and 5-year specific survival rates were 80% and 74%, respectively, in patients who received a rituximab-PCT regimen compared with 48% and 38% in those who received less-intensive therapies. No significant difference was observed between both groups in age and baseline prognostic factors. In multivariate analysis, treatment without rituximab-PCT was the only adverse prognostic factor (odds ratio, 4.6 [95% CI, 2.4-9.1]; P < .001), whereas the number of skin lesions (P = .06) and location on the leg (P = .07) had only borderline significance. CONCLUSIONS AND RELEVANCE A major improvement in the survival of patients with PCDLBCL-LT has occurred over time in France, mainly as a result of the use of intensive rituximab-PCT regimens in most patients, including very elderly ones. Until further prospective clinical trials are conducted, such regimens should be considered as the standard of care in these patients.
    JAMA dermatology. 03/2014;
  • Claudia Bejar, Eve Maubec
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    ABSTRACT: Advanced unresectable squamous cell carcinoma of the skin (SCCS) is a rare condition, which is difficult to treat. Because of its rarity, few therapeutic trials are available. Moreover, SCCS often occur in elderly. Conventional treatment options for advanced SCCS are chemotherapy mainly with cisplatin-based regimens. Immunotherapy with interferon alpha and retinoids combination was also shown to be efficient. Toxicity of these treatments limits, however, their use in elderly patients and an initial work up for a global assessment is needed in order to adapt the choice. More recently, epithelial growth factor receptor (EGFR) targeted therapies have been developed and induced interesting response rates in small series of patients with unresectable SCCS. Their efficacy in SCCS must be confirmed by larger phase III trials and the identification of predictive biological factors of response is warranted. New therapeutic approaches combining EGFR inhibitors either with IGFR inhibitors, or immunomodulators or inhibitors of the PI3K/AKT/mTOR pathway are currently under evaluation in head and neck carcinomas and might represent valuable therapeutic approaches for unresectable SCCS. Moreover, there are several new molecular candidate treatment targets for unresectable SCCS including somatic NOTCH1 or NOTCH2 inactivating mutations, ALK1, which could be a good candidate for antiangiogenic therapy and matrix metallopeptidase 7, which enhances proliferation, migration, and invasion of cancer cells. Organ transplant recipients often develop SCCS and in some patients, SCCS are rapidly progressing. Management of SCCS in this subgroup of patients includes both carcinologic treatment and modification of immunosuppression. Specific treatment is generally the same as in immunocompetent patients. Switching from calcineurin inhibitors to sirolimus or reducing immunosuppression has to be considered.
    Current Treatment Options in Oncology 03/2014; 15(2). · 2.42 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2013; 138(12):A96–A97. · 0.67 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2013; 140(12):S413. · 0.67 Impact Factor
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    ABSTRACT: Melanomas are characterized by high metastatic potential, with regional lymph node (LN) representing the most frequent site of early dissemination in this disease. These regional LN also represent the primary site for differentiation of natural killer cells (NK cells). While blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic LN (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in melanoma patients. Here we report that M-LN contain 0.5-11% of CD56bright NK cells among CD45+ hematopoietic cells present and that this cell population surrounded tumor cell clusters in M-MN. This NK cell population was characterized by expression of CD62L, chemokine receptors and high levels of natural cytotoxicity receptors (NCRs), NKG2D and DNAM-1. Expression of NCR-NKp30 and NKG2D correlated negatively with percentages of tumor cells in M-LN. Interestingly, M-LN contained a unique subset of mature CD56brightCD16+ NK cells displaying co-regulated expression of NCR and NKG2D activating receptors. Ex vivo analyses suggested that M-LN-derived NK cells were inactive but could be activated by appropriate cytokine signals (IL-2 or IL-15), could lyse metastatic melanoma cells in a highly efficient manner compared to blood-derived NK cells. Taken together, the results offer evidence that adjuvant immunotherapy that targets NK cells in M-LN for activation may improve treatment of sentinel LN-positive melanoma patients.
    Cancer Research 11/2013; · 9.28 Impact Factor
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    ABSTRACT: IMPORTANCE Curative treatment of aggressive Kaposi sarcoma (KS) with conventional chemotherapy in human immunodeficiency virus (HIV)-infected patients remains difficult. The administration of thalidomide, an immunomodulatory drug with antiangiogenic effects, is limited by its toxicity. This engenders interest in evaluating thalidomide analogues such as lenalidomide with better toxicity profiles. To our knowledge, we describe for the first time a patient with visceral KS successfully treated with lenalidomide. OBSERVATIONS A man with advanced visceral HIV-related KS progressing after 11 months of highly active antiretroviral therapy (HAART) and 2 lines of conventional chemotherapy (pegylated liposomal doxorubicin and docetaxel) was treated with lenalidomide on a compassionate use basis. He showed a rapid partial response without any substantial adverse effect but experienced relapse after 5 months of treatment, in a context of virologic failure. CONCLUSIONS AND RELEVANCE Similar to our observation, good partial response without toxic effects has been reported in 3 patients with only skin involvement. Because immune reconstitution syndrome may occur in HIV-infected patients with KS undergoing HAART, KS improvement may be partly explained by immune recovery. An ongoing US phase 1/2 trial will better evaluate the efficacy and tolerance of lenalidomide in patients with HIV-related KS with and without visceral involvement.
    JAMA dermatology (Chicago, Ill.). 10/2013;
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    ABSTRACT: BACKGROUND: Genital and anorectal mucosal melanomas (GAMM) are rare, compared to cutaneous melanoma (CM). Many epidemiological and genetic studies have been carried out in CM. In contrast, the genetic and environmental risk factors for GAMM have been poorly documented up to now. OBJECTIVE: The aim of the study was to compare the distribution of pigmentation and nevus phenotypes, sun exposure and family history of melanoma between GAMM and CM patients. METHODS: For that purpose, we compared two series of 81 GAMM and 293 CM patients. RESULTS: GAMM and CM patients did not show significant differences for phenotypic risk factors. However, GAMM patients tend to display red hair (10.8% vs 5.5%, P = 0.08) and a poor tanning ability (22.2% vs 13.3%, P = 0.06) at a higher frequency than CM patients.A family history of melanoma was significantly more frequent in the GAMM than in the CM series (18.2% vs 7.5%, P = 0.005). Apart from the GAMM index case, affected relatives had CM except in one family. The frequency of multiple primary melanomas (MPM) was similar in GAMM and CM series (6.5% vs 5.3%, P=0.43). All GAMM patients with MPM had only one GAMM primary while the other primary was cutanaeous. No CDKN2A germline mutation was detected in GAMM patients. CONCLUSIONS: This study shows that GAMM and CM may occur in the same patient and GAMM may develop in a familial setting. The association of both GAMM and CM in patients and families suggests shared genetic factors by these two types of melanoma. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 05/2013; · 3.76 Impact Factor
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    ABSTRACT: INTRODUCTION: Blastic plasmacytoid Dentritic Cell Neoplasm (BPDCN) is, as defined in the new 2008 World health Organized (WHO) classification of tumors of hematopoietic and lymphoid tissue, a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is mostly revealed and diagnosed on cutaneous spreading associated d'emblée or not with a leukaemic component .The prognosis is very poor. We herein studied a large cohort of 90 patients with BPDCN and try to define additional clues to coin earlier the correct diagnosis and manage such patients accordingly. MATERIALS AND METHOD: We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma (GFELC) database from November 1995 to January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging, and outcome were recorded. RESULTS: The studied group contained 62 male and 28 female patients (sex ratio 2.2). Age ranged from 8 to 103 years at the time of diagnosis (mean age: 67.2 years).Three major different clinical presentations were identified: Sixty six patients (73.2%) presented with nodular lesions only, 11 patients with "bruise-like» patches (12.2%).The remaining 13 ones showed disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (5.6%) The median survival in patients with BPDCN was at 12 months . CONCLUSIONS: We here distinct three different clinical presentation of BPDCN. Nodular pattern is actually a more common feature than the originally reported "bruise-like" pattern. Despite the fact that BPDCN may initially appear as a localized skin tumor an aggressive management including allogenic bone marrow transplantation should be considered d'emblée since it is so far the only one option associated with long term survival. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 05/2013; · 3.76 Impact Factor
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    ABSTRACT: BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.
    Journal of the European Academy of Dermatology and Venereology 02/2013; · 2.69 Impact Factor
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    ABSTRACT: Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.
    PLoS ONE 01/2013; 8(10):e76928. · 3.53 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2012; 139(12):B52. · 0.67 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2012; 139(12):B84. · 0.67 Impact Factor
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Publication Stats

817 Citations
236.92 Total Impact Points

Institutions

  • 2007–2014
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2008–2013
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2006–2011
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      • Service de Dermatologie
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2003–2007
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
  • 2001–2004
    • Hôpital Henri Mondor (Hôpitaux Universitaires Henri Mondor)
      • Service de Dermatologie
      Créteil, Île-de-France, France