Publications by authors named "Philippe Bahadoran"

60 Publications

Ingenol mebutate to treat lentigo maligna of the head (face and scalp): A prospective, multicenter, single-arm phase 2 trial indicates no benefit.

J Am Acad Dermatol 2020 03 17;82(3):731-733. Epub 2019 Jul 17.

Department of Dermatology, Archet Hospital, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France; Team 12, Centre Méditerranéen de Médecine Moléculaire, INSERM, U1065, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France.

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http://dx.doi.org/10.1016/j.jaad.2019.07.035DOI Listing
March 2020

Evaluation of the glycemic effect of methotrexate in psoriatic arthritis patients with metabolic syndrome: A pilot study.

Dermatol Reports 2019 Jan 9;11(1):7965. Epub 2019 May 9.

Medical Institute of Ministry of Interior (MVR), Department of Dermatology, Venereology and Dermatologic Surgery, Sofia, Bulgaria.

Methotrexate (MTX) is a systemic immunosuppressant drug used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis, hypertension, eventuating into metabolic syndrome. This study aimed at exploring the glycemic effects of MTX in psoriatic arthritis (PsA) patients. In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indices. Blood indicators including HbA1c, erythrocyte sedimentation rate, fasting blood sugar, total cholesterol, high-density lipoprotein, triglycerides, and C-reactive protein were examined before and 12 weeks after MTX therapy. There were no significant changes between HbA1c levels before and after MTX therapy in both genders (men: P=0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506). MTX in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabetes.
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http://dx.doi.org/10.4081/dr.2019.7965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547029PMC
January 2019

Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells.

Oncogene 2019 02 25;38(8):1282-1295. Epub 2018 Sep 25.

Team 1, Biology and Pathologies of Melanocytes, Equipe labellisée ARC 2015, Université Côte d'Azur, Inserm U1065, C3M, Nice, France.

Phenotypic plasticity and subsequent generation of intratumoral heterogeneity underly key traits in malignant melanoma such as drug resistance and metastasis. Melanoma plasticity promotes a switch between proliferative and invasive phenotypes characterized by different transcriptional programs of which MITF is a critical regulator. Here, we show that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK signaling cascade. In line with that, human melanoma biopsies revealed heterogeneous staining of ASAH1 and low ASAH1 expression at the melanoma invasive front. We also identified ASAH1 as a new target of MITF, thereby involving MITF in the regulation of sphingolipid metabolism. Together, our findings provide new cues to the mechanisms underlying the phenotypic plasticity of melanoma cells and identify new anti-metastatic targets.
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http://dx.doi.org/10.1038/s41388-018-0500-0DOI Listing
February 2019

Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: Results of a multicenter case-control study by the International Dermoscopy Society.

J Am Acad Dermatol 2019 Jun 20;80(6):1585-1593. Epub 2018 Sep 20.

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1.

Objectives: We sought to describe the clinical and dermoscopic features of BIMTs.

Methods: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients.

Results: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively).

Limitations: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs.

Conclusions: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.
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http://dx.doi.org/10.1016/j.jaad.2018.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426687PMC
June 2019

Dermoscopy of eccrine angiomatous hamartoma: The spitzoid pattern.

JAAD Case Rep 2018 Sep 18;4(8):835-836. Epub 2018 Sep 18.

Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Service de Dermatologie, Nice, France.

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http://dx.doi.org/10.1016/j.jdcr.2018.06.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143715PMC
September 2018

[Reflectance confocal microscopy : what future for dermatology ?]

Rev Med Suisse 2016 Oct;12(534):1724-1728

Service de dermatologie, CHU de Nice, voie Romaine 30, 06000 Nice, France.

Reflectance confocal microscopy is a non invasive imaging technique which provides in vivo and real time images of different skin tissues with a resolution close to histology, however with a depth limited to superficial dermis.The first lesions that were morphologically analyzed are melanocytic lesions. Reflectance confocal microscopy has been used for about ten years in dermatology. Its progressive improvement over the years has allowed it to be an efficient tool for diagnosing cutaneous tumors. It has been developed for inflammatory dermatosis, cutaneous infections, angiomas, cosmetology. Furthermore, it is also used to delimit the edges of lesions or the area to biopsy. This cutaneous imaging technique represents a major innovation and has its place in dermatological practice.
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October 2016

Fractionated bipolar radiofrequency and bipolar radiofrequency potentiated by infrared light for treating striae: A prospective randomized, comparative trial with objective evaluation.

Lasers Surg Med 2016 Mar 12;48(3):245-53. Epub 2016 Jan 12.

Department of Dermatology, University Hospital of Nice, Nice, France.

Background And Objective: Very few treatments for striae are based on prospective randomized trials. The objective of this study was to assess the efficacy of bipolar fractional radiofrequency and bipolar radiofrequency potentiated with infrared light, alone or combined, for treating abdominal stretch marks.

Study Design/materials And Methods: Bicentric prospective interventional randomized controlled trial in the department of Dermatology of University Hospital of Nice and Aesthetics Laser Center of Bordeaux, France. Men and women of age 18 years or above, who presented for the treatment of mature or immature abdominal striae were included. The patients' abdomens were divided into four equal quadrants. Bipolar radiofrequency potentiated with infrared light and fractional bipolar radiofrequency were applied, alone or combined, and compared to the remaining untreated quadrant. The main criterion of evaluation was the measurement of depth of striae, using 3D photography at 6 months follow-up. A global assessment was also rated by the physician performing the treatment and by the patients. Histological analysis and confocal laser microscopy were additionally performed.

Results: A total of 22 patients were enrolled, and 384 striae were measured. In per protocol analysis mean striae depth was decreased by 21.64%, observed at 6 months follow-up with the combined approach, compared to an increase of 1.73% in the control group (P < 0.0001). No significant difference in striae width was observed between the treated or control quadrants. Global assessment by the physician who performed the treatment and by the patient both showed greater improved with the combination treatment compared to control areas (P = 0.004 and P = 0.01, respectively). A more homogeneous interlacing pattern and thicker collagen fibers with a decreased proportion of elastic fibers was observed after treatment.

Conclusion: Fractional bipolar radiofrequency, combined with bipolar radiofrequency potentiated by infrared light, is an effective treatment of both immature and mature striae of the abdomen.
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http://dx.doi.org/10.1002/lsm.22458DOI Listing
March 2016

High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

Cancer Med 2016 06 6;5(6):1022-30. Epub 2016 Mar 6.

Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.

Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.
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http://dx.doi.org/10.1002/cam4.661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924359PMC
June 2016

Comparative Methods for Improving Transepidermal Methylaminolevulinate Delivery: A Randomized Clinical Trial.

JAMA Dermatol 2015 Dec;151(12):1371-1373

Department of Dermatology, University Hospital of Nice, Nice, France4Institut National de la Santé Et de la Recherche Médicale U1065, Team 12, C3M, University Hospital of Nice, Nice, France.

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http://dx.doi.org/10.1001/jamadermatol.2015.2234DOI Listing
December 2015

Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.

J Invest Dermatol 2015 Dec 26;135(12):3096-3104. Epub 2015 Aug 26.

C3M, INSERM U1065, team 12, Nice, France; Department of Dermatology, University Hospital Center of Nice, Nice, France. Electronic address:

Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.
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http://dx.doi.org/10.1038/jid.2015.332DOI Listing
December 2015

Copper Bromide Laser vs Triple-Combination Cream for the Treatment of Melasma: A Randomized Clinical Trial.

JAMA Dermatol 2015 Jul;151(7):791-2

Department of Dermatology, University Hospital of Nice, Nice, France3INSERM U1065, Team 12, C3M, Nice, France.

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http://dx.doi.org/10.1001/jamadermatol.2014.5580DOI Listing
July 2015

Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma.

J Am Acad Dermatol 2015 May 7;72(5):786-93. Epub 2015 Feb 7.

Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France. Electronic address:

Background: It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors.

Objective: We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma.

Methods: We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing.

Results: Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity.

Limitations: Limitations include retrospective design and lack of multicenter interobserver reproducibility.

Conclusion: The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
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http://dx.doi.org/10.1016/j.jaad.2015.01.012DOI Listing
May 2015

Maintenance therapy of adult vitiligo with 0.1% tacrolimus ointment: a randomized, double blind, placebo-controlled study.

J Invest Dermatol 2015 Apr 18;135(4):970-974. Epub 2014 Dec 18.

Department of Dermatology, University Hospital Center of Nice, Nice, France; C3M, INSERM U1065, team 12, Nice, France. Electronic address:

The risk of relapse after successful repigmentation in vitiligo is estimated to 40% within the first year. It has been shown in atopic dermatitis that continuous low-level use of topical corticosteroids and calcineurin inhibitors in previously affected skin can prevent new flares. We hypothesized that a twice-weekly application of 0.1% tacrolimus ointment might be effective for maintaining repigmentation in therapeutically repigmented lesions of vitiligo patients. After randomization, sixteen patients with 31 patches were assigned to the placebo group and 19 patients with 41 patches were assigned to the tacrolimus group. In the intention-to-treat analysis, 48.4% of lesions showed depigmentation in the placebo group, whereas 26.8% did in the tacrolimus group (P=0.059). The intention-to-treat results did not remain significant after adjustment for within-patient clustering, odds ratio (OR) 2.55; 95% confidence interval (CI; 0.65-9.97); P=0.1765. The per-protocol analysis (n=56) showed that 40% of lesions had some depigmentation in the placebo group, whereas only 9.7% did in the tacrolimus group (P=0.0075). The per-protocol results remained significant after adjustment for within-patient clustering: OR 6.22; 95% CI (1.48-26.12); P=0.0299. Our study shows that twice-weekly application of 0.1% tacrolimus ointment is effective in preventing the depigmentation of vitiligo patches that have been previously successfully repigmented.
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http://dx.doi.org/10.1038/jid.2014.527DOI Listing
April 2015

Treatment of keloids with laser-assisted topical steroid delivery: a retrospective study of 23 cases.

Dermatol Ther 2015 Mar-Apr;28(2):74-8. Epub 2014 Dec 4.

Department of Dermatology, University Hospital of Nice, Nice, France.

Topical or intralesional corticosteroids are referred to as gold standard treatments for keloids. Recent studies showed that ablative fractional laser (AFL) treatment facilitates delivery of topical drug deeply into the skin by creating vertical channels. The objective of the present study was to assess the ablative erbium laser in fractionated mode, combined with topical high potent corticosteroid cream for treating resistant keloid scars. We conducted a retrospective study in the laser center of the Department of Dermatology (University Hospital of Nice, France), from January 2010 to June 2012, on patients with keloids who were resistant to a first-line of treatment. A 2940-nm ablative fractional erbium laser was used. Topical betamethasone cream was applied twice a day under occlusion with transparent film dressings. A total of 23 patients with 70 keloids were treated from January 2010 to June 2012. The median percentage of improvement was 50% (range -43 to 84). The mean follow-up was 8 months (range 3-18), and a recurrence was observed for eight lesions (22%). Although this observation warrants a prospective comparative evaluation, it supports the interest of the laser-assisted delivery of steroids for treating keloids scars.
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http://dx.doi.org/10.1111/dth.12187DOI Listing
May 2016

Trichoblastoma with dermoscopic features of a malignant tumor: three cases.

J Am Acad Dermatol 2014 Sep;71(3):e63-4

Department of Dermatology, University Hospital of Nice, Archet 2 Hospital, Nice, France; Clinical Research Centre, University Hospital of Nice, Nice, France.

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http://dx.doi.org/10.1016/j.jaad.2013.12.033DOI Listing
September 2014

CD271 is an imperfect marker for melanoma initiating cells.

Oncotarget 2014 Jul;5(14):5272-83

INSERM U1065, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome, Equipe labellisée Ligue 2013, Centre Méditerranéen de Médecine Moléculaire, Nice, France; Université de Nice Sophia-Antipolis, UFR Médecine, Nice, France; CHU Nice, Service de Dermatologie, Nice, France.

Understanding the molecular and cellular processes underlying melanoma plasticity and heterogeneity is of paramount importance to improve the efficiency of current treatment and to overcome resistance to chemotherapy drugs. The notion of plasticity and heterogeneity implies the existence of melanoma cell populations with different phenotypic and tumorigenic properties. Using melanoma cell lines and melanoma cells freshly isolated from patient biopsies, we investigated the relationship between ABCB5+, CD271+ and low-MITF, expressing populations that were reported to display melanoma initiating cell properties. Here, we showed that ABCB5+ and CD271+ populations poorly overlap. However, we found that the CD271+ population is enriched in low-MITF cells and expresses a higher level of stemness genes, such as OCT4, NANOG and NES. These features could explain the increased tumorigenicity of the CD271+ cells. The rapid conversion of CD271+ to CD271- cells in vitro demonstrates the plasticity ability of melanoma cells. Finally, we observed that the transient slow-growing population contains only CD271+ cells that are highly tumorigenic. However, the fast growing/CD271+ population exhibits a poor tumorigenic ability. Taking together, our data show that CD271 is an imperfect marker for melanoma initiating cells, but may be useful to identify melanoma cells with an increased stemness and tumorigenic potential.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170612PMC
http://dx.doi.org/10.18632/oncotarget.1967DOI Listing
July 2014

Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata.

JAMA Dermatol 2014 Jul;150(7):748-51

Department of Dermatology, University Hospital of Nice, Nice, France5Institut National de la Santé et de la Récherche Médicale (INSERM) U1065, Team 12, Mediterranean Centre of Molecular Medicine, Nice, France.

Importance: An impaired inhibitory function of circulating CD4+CD25+ regulatory T (Treg) cells was reported to play a key role in alopecia areata (AA). We report the first use to our knowledge of low-dose interleukin 2 for treating severe AA by promoting the recruitment of Treg cells.

Observations: We conducted a prospective open pilot study in 5 patients with severe AA resistant to previous systemic treatments. Subcutaneous interleukin 2 (1.5 million IU/d) was administered during 5 days, followed by three 5-day courses of 3 million IU/d at weeks 3, 6, and 9. The primary outcome was the evolution of the Severity of Alopecia Tool (SALT) score, evaluated by 2 independent investigators on standardized photographs. Lesional skin biopsy specimens and peripheral blood lymphocyte phenotype were analyzed. The median SALT score went from 82 (range, 63-100) at baseline to 69 (range, 28-100) at 6 months. Immunochemical analysis revealed the appearance or a notable increase in Treg cell count in 4 of 5 patients at the end of the treatment compared with baseline. No serious adverse event was reported.

Conclusions And Relevance: The partial regrowth achieved in 4 of 5 patients and the recruitment of Treg cells in lesional skin support the interest of promoting Treg cells for treating AA. Further investigations are now required to confirm and to optimize the design in order to enhance the Treg cell response.

Trial Registration: clinicaltrials.gov Identifier: NCT01840046.
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http://dx.doi.org/10.1001/jamadermatol.2014.504DOI Listing
July 2014

Diagnosis and treatment monitoring of toenail onychomycosis by reflectance confocal microscopy: prospective cohort study in 58 patients.

J Am Acad Dermatol 2014 Jul 29;71(1):56-61. Epub 2014 Apr 29.

Dermatology Department, Centre Hospitalier Universitaire de Nice, Nice, France; Clinical Research Center (CRC), Centre Hospitalier Universitaire de Nice, Nice, France; INSERM U 1065, Team 1, Nice, France; Groupe Imagerie Cutanée Non Invasive de la Société Française de Dermatologie. Electronic address:

Background: The clinical presentation of onychomycosis is often nonspecific and can lead to inappropriate antifungal therapy. Available mycologic tests share many drawbacks.

Objective: We sought to evaluate the accuracy of reflectance confocal microscopy (RCM) for the diagnosis of onychomycosis compared with standard mycologic tests.

Methods: In all, 58 patients with suspected onychomycosis were enrolled prospectively. RCM, potassium hydroxide preparation, and fungal culture were performed at baseline and after treatment in patients with confirmed onychomycosis. RCM diagnosis of onychomycosis was based on the presence of filamentous and/or roundish structures in the nail plate, corresponding respectively to septate hyphae and/or arthroconidia.

Results: Of patients, 46 of 58 were correctly classified by RCM, with a diagnosis yield of 79.3%, sensitivity of 52.9%, specificity of 90.2%, positive predictive value of 69.2%, and negative predictive value of 82.2%. The use of a handheld RCM imager permitted a faster examination with the same accuracy. RCM performed after treatment in 9 patients showed a normal nail plate, and healing was confirmed by mycologic tests or by follow-up.

Limitations: Existing RCM scanner heads are not intended for nail examination.

Conclusion: RCM has excellent specificity and can be used as a rapid, office-based test to strengthen the prescription of antifungal therapy and for follow-up. Technical improvement could aid sensitivity.
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http://dx.doi.org/10.1016/j.jaad.2014.02.020DOI Listing
July 2014

SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human melanoma cells.

Oncotarget 2014 Apr;5(8):2085-95

INSERM, U1065 (équipe 1), Equipe labélisée Ligue Contre le Cancer, C3M, Nice, France.

SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the cell context. Whether SIRT1 plays a role in melanoma biology remained poorly elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma cell proliferation. SIRT1 suppression by genetic or pharmacological approaches induces cell cycle arrest and a senescence-like phenotype. Gain and loss of function experiments show that M-MITF regulates SIRT1 expression, thereby revealing a melanocyte-specific control of SIRT1. SIRT1 over-expression relieves the senescence-like phenotype and the proliferation arrest caused by MITF suppression, demonstrating that SIRT1 is an effector of MITF-induced proliferation in melanoma cells. Interestingly, SIRT1 level and activity are enhanced in the PLX4032-resistant BRAF(V600E)-mutated melanoma cells compared with their sensitive counterpart. SIRT1 inhibition decreases melanoma cell growth and rescues the sensibility to PLX4032 of PLX4032-resistant BRAF(V600E)-mutated melanoma cells. In conclusion, we provide the first evidence that inhibition of SIRT1 warrants consideration as an anti-melanoma therapeutic option.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039147PMC
http://dx.doi.org/10.18632/oncotarget.1791DOI Listing
April 2014

Macular eruption revealing hypomelanotic cutaneous melanoma metastases: diagnostic role of dermoscopy.

J Am Acad Dermatol 2014 Jan;70(1):e7-9

Department of Dermatology, University Hospital of Nice, Nice, France; INSERM U 1065, Team 1, University Hospital of Nice, Nice, France; Clinical Research Centre, University Hospital of Nice, Nice, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2013.09.004DOI Listing
January 2014

Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype.

Oncotarget 2013 Dec;4(12):2212-24

Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Equipe 1, Biologie et pathologies des mélanocytes: de la pigmentation cutanée au mélanome. Equipe labellisée Ligue 2013, Nice, F-06204, France.

Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naïve melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926821PMC
http://dx.doi.org/10.18632/oncotarget.1143DOI Listing
December 2013

A new KIT mutation (N505I) in acral melanoma confers constitutive signaling, favors tumorigenic properties, and is sensitive to imatinib.

J Invest Dermatol 2014 May 6;134(5):1473-1476. Epub 2013 Dec 6.

Equipe Labellisée par la Ligue Contre le Cancer, Biology and Pathologies of Melanocytes, Equipe 1, Centre Méditerranéen de Médecine Moléculaire (C3M), INSERM U1065, Nice, France; Department of Dermatology, CHU Nice, Nice, France; UFR Médecine, Université de Nice-Sophia Antipolis, Nice, France. Electronic address:

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http://dx.doi.org/10.1038/jid.2013.525DOI Listing
May 2014

Recurrent BRAF kinase fusions in melanocytic tumors offer an opportunity for targeted therapy.

Pigment Cell Melanoma Res 2013 Nov 19;26(6):845-51. Epub 2013 Aug 19.

Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

BRAF is the most prevalent oncogene and an important therapeutic target in melanoma. In some cancers, BRAF is activated by rearrangements that fuse its kinase domain to 5' partner genes. We examined 848 comparative genomic hybridization profiles of melanocytic tumors and found copy number transitions within BRAF in 10 tumors, of which six could be further characterized by sequencing. In all, the BRAF kinase domain was fused in-frame to six N-terminal partners. No other mutations were identified in melanoma oncogenes. One of the seven melanoma cell lines without known oncogenic mutations harbored a similar BRAF fusion, which constitutively activated the MAP kinase pathway. Sorafenib, but not vemurafenib, could block MAP kinase pathway activation and proliferation of the cell line at clinically relevant concentrations, whereas BRAF(V) (600E) mutant melanoma cell lines were significantly more sensitive to vemurafenib. The patient from whom the cell line was derived showed a durable clinical response to sorafenib.
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http://dx.doi.org/10.1111/pcmr.12148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808507PMC
November 2013

Reflectance confocal microscopy features of Degos disease.

JAMA Dermatol 2014 Jan;150(1):96-7

Department of Dermatology, University Hospital of Nice, Nice, France3INSERM U1065 C3M Team 1, Nice, France4Cliniacal Research Center, University Hospital of Nice, Nice, France.

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http://dx.doi.org/10.1001/jamadermatol.2013.4662DOI Listing
January 2014

Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner.

Mol Cancer Ther 2013 Aug 5;12(8):1605-15. Epub 2013 Jun 5.

Equipe Biologie et Pathologie des cellulesmelanocytaire: de la pigmentation cutanee au melanome, Centre Mediterraneen de Medecine Moleculaire (C3M), INSERM, U1065.

Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without affecting cell migration and independently of antiproliferation action. This inhibition is correlated with modulation of expression of proteins involved in epithelial-mesenchymal transition such as Slug, Snail, SPARC, fibronectin, and N-cadherin and with inhibition of MMP-2 and MMP-9 activation. Furthermore, our data indicate that this process is dependent on activation of AMPK and tumor suppressor protein p53. Finally, we showed that metformin inhibits melanoma metastasis development in mice using extravasation and metastasis models. The presented data reinforce the fact that metformin might be a good candidate for clinical trial in melanoma treatment.
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http://dx.doi.org/10.1158/1535-7163.MCT-12-1226-TDOI Listing
August 2013

Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma.

J Clin Oncol 2013 Jul 28;31(19):e324-6. Epub 2013 May 28.

Department of Dermatology, Archet Hospital-Centre Hospitalier Universitaire de Nice, Nice cedex 03, France.

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http://dx.doi.org/10.1200/JCO.2012.46.1061DOI Listing
July 2013