32 research outputs found

    MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma

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    MicroRNAs usually regulate gene expression negatively, and aberrant expression has been involved in the development of several types of cancers. Microarray profiling of microRNA expression was performed to define a microRNA signature in a series of mycosis fungoides tumor stage (MFt, n=21) and CD30+ primary cutaneous anaplastic large cell lymphoma (CD30+ cALCL, n=11) samples in comparison with inflammatory dermatoses (ID, n=5). Supervised clustering confirmed a distinctive microRNA profile for cutaneous T-cell lymphoma (CTCL) with respect to ID. A 40 microRNA signature was found in MFt including upregulated onco-microRNAs (miR-146a, miR-142-3p/5p, miR-21, miR-181a/b, and miR-155) and downregulated tumor-suppressor microRNAs (miR-200ab/429 cluster, miR-10b, miR-193b, miR-141/200c, and miR-23b/27b). Regarding CD30+ cALCL, 39 differentially expressed microRNAs were identified. Particularly, overexpression of miR-155, miR-21, or miR-142-3p/5p and downregulation of the miR-141/200c clusters were observed. DNA methylation in microRNA gene promoters, as expression regulatory mechanism for deregulated microRNAs, was analyzed using Infinium 450K array and approximately one-third of the differentially expressed microRNAs showed significant DNA methylation differences. Two different microRNA methylation signatures for MFt and CD30+ cALCL were found. Correlation analysis showed an inverse relationship for microRNA promoter methylation and microRNA expression. These results reveal a subgroup-specific epigenetically regulated microRNA signatures for MFt and CD30+ cALCL patients

    Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene

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    Importance: hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: to analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: this case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: these results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile

    Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry

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    [Background] Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited.[Objectives] To evaluate the response and tolerance of BV in a cohort of patients with CTCL.[Methods] We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP).[Results] Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2.[Conclusions] These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.The Spanish Primary Cutaneous Lymphoma Registry (RELCP) is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which received an unrestricted grant support from Kyowa Kirin.Peer reviewe

    Ecology and resistance to UV light and antibiotics of microbial communities on UV cabins in the dermatology service of a Spanish hospital

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    Abstract Microorganisms colonize all possible ecological habitats, including those subjected to harsh stressors such as UV radiation. Hospitals, in particular the UV cabins used in phototherapy units, constitute an environment in which microbes are intermittently subjected to UV irradiation. This selective pressure, in addition to the frequent use of antibiotics by patients, may represent a threat in the context of the increasing problem of antimicrobial resistance. In this work, a collection of microorganisms has been established in order to study the microbiota associated to the inner and outer surfaces of UV cabins and to assess their resistance to UV light and the antibiotics frequently used in the Dermatology Service of a Spanish hospital. Our results show that UV cabins harbor a relatively diverse biocenosis dominated by typically UV-resistant microorganisms commonly found in sun-irradiated environments, such as Kocuria, Micrococcus or Deinococcus spp., but also clinically relevant taxa, such as Staphylococcus or Pseudomonas spp. The UV-radiation assays revealed that, although some isolates displayed some resistance, UV is not a major factor shaping the biocenosis living on the cabins, since a similar pool of resistant microorganisms was identified on the external surface of the cabins. Interestingly, some Staphylococcus spp. displayed resistance to one or more antibiotics, although the hospital reported no cases of antibiotic-resistance infections of the patients using the cabins. Finally, no association between UV and antibiotic resistances was found

    Impact of negative pressure wound therapy and nanocrystalline silver dressings on the quality of life of patients with chronic non-healing ulcers: a preliminary study

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    Therapeutic measures should be primarily directed to promote healing, but also to improve or at least to maintain HRQoL. This prospective randomized pilot study was conducted to assess the impact on HRQoL of negative pressure wound therapy (NPWT) combined with nanocrystalline silver dressings in outpatients with chronic nonhealing ulcers. A total of 17 patients were included in the study, 10 of which were treated with the combined method and 7 with NPWT only. Patients were followed for 6 weeks. The 36-item short-form (SF-36) questionnaire was administered to at baseline and at the end of treatment. Patients included in the study had multiple concomitant pathological conditions and a mean age of 70 years. Significant changes in different domains of the SF-36 questionnaire, including physical functioning, role limitations (physical), vitality, mental health, social functioning, bodily pain, and general health, before and after treatment were not found. The mean (standard deviation, SD) score of social functioning was 53.1 (31.8) before treatment and 66.3 (23.6) after treatment (P = 0.09). The application of NPWT with nanocrystalline silver dressings or NPWT alone for 6 weeks was effective in wound healing promotion. The impact on HRQoL was non-significant except for somewhat better benefits in the social domain in patients treated with NPWT and silver dressings. The present preliminary data could be the basis for the design of future, more robust clinical studies
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