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1.
Artículo en Inglés | MEDLINE | ID: mdl-38661511

RESUMEN

BACKGROUND: There are conflicting data on a potential association between obesity and atopic dermatitis (AD). The purpose of this study was to investigate the relationship between obesity and AD disease severity. METHODS: Patients from the TREATgermany registry cohort were divided into three groups according to their body mass index (BMI). Due to low numbers, underweight patients (BMI <18.5 kg/m2) were excluded from the analysis. Physician- and patient-reported disease severity scores as well as additional phenotypic characteristics were evaluated for association with BMI. Generalized linear mixed models and multinomial logit models, respectively, were applied to investigate the association of BMI, age, sex and current systemic AD treatment with disease severity. RESULTS: This study encompassed 1416 patients, of which 234 (16.5%) were obese (BMI ≥30 kg/m2). Obesity was associated with lower educational background and smoking. Otherwise, obese and non-obese AD patients had similar baseline characteristics. Increased BMI was associated with higher oSCORAD (adjusted ß: 1.24, 95% CI: 1.05-1.46, p = 0.013) and Patient-oriented eczema measure (POEM) (adjusted ß: 1.09, 95% CI: 1.01-1.17, p = 0.038). However, the absolute difference in the overall oSCORAD was small between obese and non-obese AD patients (Δ oSCORAD = 2.5). Allergic comorbidity was comparable between all three groups, with the exception of asthma which was more pronounced in obese patients (p < 0.001). DISCUSSION: In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance. The overall prevalence of obesity among the German AD patients was lower than in studies on other AD cohorts from different countries, which confirms previous research on the German population and suggests regional differences in the interdependence of AD and obesity prevalence.

3.
J Am Acad Dermatol ; 52(2 Suppl 1): 20-3, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15692506

RESUMEN

BACKGROUND: Angiosarcoma of the scalp is a rare but highly aggressive malignant tumor that differentiates toward vascular endothelial cells and shows a tendency for diffuse, often clinically occult spread. OBSERVATIONS: A 65-year-old Caucasian man presented with multiple erythematous skin lesions at the right scalp hemisphere and a prominent forehead edema that had developed during a period of 2 months. The clinical diagnosis of angiosarcoma was confirmed by histopathology. Because of the advanced local progression of the tumor and the unilateral localization on the right side of the scalp, we initiated an intra-arterial chemotherapy using pegylated liposomal doxorubicin (Caelyx) (8 mg/cycle every 4 weeks by an A. carotis externa port system). In addition, the patient received pegylated interferon alfa (50 microg/wk) by a percutaneous intralesional injection route. After 2 months, the tumor showed a marked regression; after 4 months, only one nodule located at the margins of the area perfused by the A. carotis externa persisted but regressed after focal irradiation. At 30 months after diagnosis, the patient shows no recurrence of tumor growth. CONCLUSIONS: In combination with intralesional interferon alfa, intra-arterial doxorubicin may be a promising innovative therapeutic option for localized scalp angiosarcoma, a hitherto poorly manageable and aggressive malignant tumor.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Hemangiosarcoma/tratamiento farmacológico , Cuero Cabelludo , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Arteria Carótida Externa , Doxorrubicina/administración & dosificación , Humanos , Infusiones Intraarteriales , Inyecciones Intralesiones , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Liposomas , Masculino , Polietilenglicoles , Proteínas Recombinantes
4.
J Invest Dermatol ; 122(5): 1266-76, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15140231

RESUMEN

Bypassing molecular mechanisms of apoptosis deficiency may be of great utility for the successful treatment of malignant tumors. We have discovered that imiquimod, a small-molecule immunomodulator, exerts rather tumor-selective direct pro-apoptotic activity in vivo and in vitro towards cutaneous metastases of malignant melanoma, an aggressive skin tumor. This pro-apoptotic activity was not detectable with resiquimod, a closely related structural analogue whose pro-inflammatory activity is even greater than that of imiquimod. Unresponsiveness of some melanoma metastases to imiquimod in vivo corresponded to resistance towards imiquimod-induced apoptosis in vivo and in vitro. At the molecular level, the pro-apoptotic activity of imiquimod was independent of membrane-bound death receptors, but depended on Bcl-2 expression as demonstrated by overexpression of Bcl-2 in melanoma cells. Imiquimod is the first topical compound with the potential to bypass molecular mechanisms of apoptosis deficiency, a concept that may be relevant for other tumors as well.


Asunto(s)
Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Aminoquinolinas/farmacología , Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis , Biopsia , Línea Celular Tumoral/citología , Línea Celular Tumoral/efectos de los fármacos , Humanos , Imidazoles/farmacología , Imiquimod , Melanocitos/citología , Melanocitos/efectos de los fármacos , Melanoma/inmunología , Melanoma/secundario , Glicoproteínas de Membrana/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Ligando Inductor de Apoptosis Relacionado con TNF , Factor de Necrosis Tumoral alfa/metabolismo , Receptor fas/metabolismo
5.
J Natl Cancer Inst ; 95(15): 1138-49, 2003 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-12902443

RESUMEN

BACKGROUND: The incidence of nonmelanoma skin cancer, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) is increasing, representing a major medical and economic problem. Imiquimod, a topical small-molecule immune response modifier, has shown efficacy toward BCC and actinic keratoses in clinical trials. Imiquimod acts both indirectly, via cytokine-mediated stimulation of cellular immune responses, and directly, through unknown mechanisms against tumor cells. We examined the mechanism by which imiquimod induces apoptosis in cancer cells. METHODS: Apoptosis was assessed by enzyme-linked immunosorbent assay, western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays in five SCC cell lines, HaCaT cells (a spontaneously immortalized human keratinocyte cell line), and normal keratinocytes treated with imiquimod, with its analog resiquimod, or with neither. Expression of death receptors, caspases, and cytochrome c in the apoptotic signaling cascade was analyzed using western blot and flow cytometric analyses. The functional relevance of imiquimod-induced cytochrome c release was assessed by transfection of HaCaT cells with Bcl-2. Apoptosis in BCCs in vivo was assessed by TUNEL assays of imiquimod-treated and untreated tumors from three patients. Differences between treated and untreated cells and tumors were determined using a two-tailed Student's t test. RESULTS: Imiquimod, but not resiquimod, induced apoptosis in all SCC cell lines and HaCaT cells. This induction involved activation of several caspases and Bcl-2-dependent cytosolic translocation of cytochrome c but was independent of the membrane-bound death receptors Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-R1-R4 receptors, and tumor necrosis factor-R1 and -R2 receptors. Topical application of imiquimod to BCC tumors in vivo induced apoptosis. CONCLUSION: Imiquimod has the potential to induce apoptosis in skin cancer cells, possibly by circumventing mechanisms developed by malignant tumors to resist apoptotic signals.


Asunto(s)
Aminoquinolinas/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Imidazoles/farmacología , Factores Inmunológicos/farmacología , Western Blotting , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/inmunología , Carcinoma de Células Escamosas/metabolismo , Caspasa 3 , Caspasas/efectos de los fármacos , Grupo Citocromo c/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imiquimod , Etiquetado Corte-Fin in Situ , Queratinocitos/efectos de los fármacos , Queratinocitos/inmunología , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Receptores del Factor de Necrosis Tumoral/efectos de los fármacos , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacos
6.
Dermatology ; 205(2): 135-8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12218228

RESUMEN

BACKGROUND: Imiquimod 5% cream (Aldara, a novel topical immune response modifier, has been approved for the topical treatment of anogenital HPV-induced warts. In addition, several studies have demonstrated antitumoral activity in solar keratoses, superficial basal cell carcinomas and Bowen's disease. AIM: Given the convincing therapeutic results of imiquimod when used for treating selected types of epithelial skin cancer, we became interested to study imiquimod as an adjuvant for treating cutaneous metastases of malignant melanoma. METHODS: Three patients with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant melanoma in unilateral localization on the leg were treated topically with imiquimod 5% cream. RESULTS: Twice daily application under occlusive conditions for a period of 21-28 weeks resulted in >90% regression of cutaneous metastases in 2 patients. The third patient showed marked response only when topical imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for 2 weeks. Unwanted side effects were mild in all patients. CONCLUSION: Overall, imiquimod as a single agent or in combination with intralesional IL-2 may be a promising immunomodulatory compound for the adjuvant topical treatment of patients with multiple cutaneous metastases of malignant melanoma.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imiquimod , Inyecciones Intralesiones , Interleucina-2/administración & dosificación , Masculino , Melanoma/secundario , Neoplasias Cutáneas/secundario
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