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Luz , Luz Solar/efectos adversos , Urticaria/diagnóstico , Adulto , Femenino , Humanos , Urticaria/etiologíaRESUMEN
Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.
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Carcinoma Hepatocelular/secundario , Neoplasias Hepáticas/patología , Neoplasias Nasales/secundario , Neoplasias Cutáneas/secundario , Biomarcadores de Tumor , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Bexarotene is the first synthetic retinoid X receptor-selective retinoid (rexinoid) approved for the treatment of cutaneous T-cell lymphoma (CTCL). However, little is known about the signalling pathways by which it exerts its anticarcinogenic effect. OBJECTIVES: To characterize the effects of bexarotene in CTCL cell lines and elucidate the underlying molecular pathways of its antineoplastic effect. METHODS: The cell lines Hut-78, HH and MJ were used. Cell viability was assessed with the XTT assay. The self-renewal potential of cells after bexarotene treatment was studied with the methylcellulose clonogenic assay. Flow cytometry was used to analyse the effects on cell cycle, Ki-67 expression and apoptosis induction. Cell cycle and apoptosis-related protein expression were determined by Western blot and immunofluorescence. RESULTS: Bexarotene induced a loss of viability and more pronounced inhibition of clonogenic proliferation in HH and Hut-78 cells, whereas the MJ line exhibited resistance. Bexarotene upregulated and activated Bax in sensitive lines, although not enough to signal significant apoptosis. Instead, all data point to the inhibition of proliferation, rather than apoptosis, as the main mechanistic action of the rexinoid. Bexarotene signals both G(1) and G(2)/M arrest by the modulation of critical checkpoint proteins. We further found that bexarotene activates p53 by phosphorylation at Ser15, which influences the binding of p53 to promoters for cell cycle arrest, induces p73 upregulation, and, in concordance, also modulates some p53/p73 downstream target genes, such as p21, Bax, survivin and cdc2. Bexarotene-mediated ataxia telangiectasia mutated protein (ATM) activation in all studied lines suggests that ATM is likely to be the p53/p73 upstream activator. CONCLUSIONS: Our data indicate for the first time that bexarotene exerts its effect in CTCL mainly by triggering the p53/p73-dependent cell cycle inhibition pathway, probably by upstream ATM activation. Therefore, bexarotene-modulated genes represent potential biomarkers to assess the response to treatment of patients with CTCL.
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Anticarcinógenos/farmacología , Proteínas de Unión al ADN/metabolismo , Linfoma Cutáneo de Células T/patología , Proteínas Nucleares/metabolismo , Neoplasias Cutáneas/patología , Tetrahidronaftalenos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Apoptosis/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada , Bexaroteno , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión al ADN/efectos de los fármacos , Humanos , Linfoma Cutáneo de Células T/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Proteínas Nucleares/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/metabolismo , Células Tumorales Cultivadas , Proteína Tumoral p73 , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteínas Supresoras de Tumor/efectos de los fármacosRESUMEN
Generalized guttate morphea is a very uncommon clinical entity, and few reports are available in the literature. We report the case of a 7-year-old boy who first attended our clinic in 1990 with guttate morphea on the trunk and upper limbs. These lesions were associated with plaque morphea on his right foot. Twelve years later, lesions with a different appearance to the previous ones were observed in the right pectoral region. Clinically and histopathologically, they resembled lichen sclerosus et atrophicus. Given that morphea and lichen sclerosus et atrophicus share certain clinical and pathologic characteristics, some authors believe that these entities may be related or even different presentations of the same disease. The most noteworthy aspect of our case is the type of morphea, as we were unable to find equivalent examples in the literature.
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Liquen Escleroso y Atrófico/diagnóstico , Esclerodermia Localizada/diagnóstico , Brazo , Dorso , Niño , Progresión de la Enfermedad , Estudios de Seguimiento , Dermatosis del Pie/diagnóstico , Dermatosis del Pie/patología , Humanos , Liquen Escleroso y Atrófico/clasificación , Liquen Escleroso y Atrófico/patología , Masculino , Esclerodermia Localizada/clasificación , Esclerodermia Localizada/patología , TóraxRESUMEN
Efalizumab (Raptiva) is one of the biological agents approved recently for the treatment of patients with moderate-severe psoriasis who have not responded to conventional treatments. It is a humanized IgG1 monoclonal antibody which, due to its anti-D11 effect, is capable of blocking the endothelial migration and T cell activation on the skin, fundamental processes in the etiopathogeny of psoriasis. We present the experience we have had in our hospital over the last two years with 23 patients who have initiated treatment with efalizumab.
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Anticuerpos Monoclonales/uso terapéutico , Productos Biológicos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Psoriasis/terapia , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Productos Biológicos/efectos adversos , Terapia Combinada , Ciclosporina/uso terapéutico , Dermatitis Exfoliativa/etiología , Fármacos Dermatológicos/efectos adversos , Femenino , Hospitales Urbanos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Terapia PUVA , Psoriasis/tratamiento farmacológico , Estudios Retrospectivos , Trombocitopenia/etiología , Resultado del TratamientoRESUMEN
We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene.
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Antineoplásicos/uso terapéutico , Micosis Fungoide/cirugía , Trasplante de Células Madre de Sangre Periférica , Tetrahidronaftalenos/uso terapéutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bexaroteno , Busulfano/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Mecloretamina/administración & dosificación , Metilprednisolona/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/patología , Micosis Fungoide/radioterapia , Terapia PUVA , Prednisona/administración & dosificación , Proteínas Recombinantes , Inducción de Remisión , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
Adalimumab is a fully human monoclonal antibody targeted toward tumor necrosis factor alpha (TNF-alpha). TNF-alpha is proinflammatory cytokine involved in the pathogenesis of many inflammatory diseases, as the psoriasis. The production process of adalimumab is complex and it is based in the called phague display technology.
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Antiinflamatorios/síntesis química , Anticuerpos Monoclonales/biosíntesis , Bacteriófagos/metabolismo , Adalimumab , Anticuerpos Monoclonales Humanizados , Biotecnología/métodos , HumanosAsunto(s)
Acrospiroma/diagnóstico , Dedos , Pigmentación de la Piel , Neoplasias de las Glándulas Sudoríparas/diagnóstico , Acrospiroma/patología , Acrospiroma/cirugía , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias de las Glándulas Sudoríparas/patología , Neoplasias de las Glándulas Sudoríparas/cirugíaRESUMEN
Adalimumab es un anticuerpo monoclonal totalmente humano y dirigido contra el factor de necrosis tumoral alfa (TNF-α). El TNF-α es una citocina proinflamatoria, implicada en la Etiopatogenia de múltiples entidades, entre ellas la psoriasis. El mecanismo de obtención de adalimumab es complejo y se basa en la denominada técnica de selección mediante presentación en fagos (AU)
Adalimumab is a fully human monoclonal antibody targeted toward tumor necrosis factor alpha (TNF-α). El TNF-α is proinflammatory cytokine envolved in the patogenesis of many inflammatory diseases, as the psoriasis. The production process of adalimumab is complex and it is based in the called phague display technology (AU)
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Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Psoriasis/tratamiento farmacológico , Bacteriófagos , Bacteriófagos/metabolismo , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/tendenciasRESUMEN
INTRODUCTION: Eruptive pseudoangiomatosis consists in the acute development of small vascular lesions in the face and extremities that resolve in several weeks without scarring. Lesions are described as 3-4 mm asymptomatic macules and papules with peripheral whitish halo that blanch upon pressure. Initially it was considered a disease limited to children but it has also been described in adults. It overlaps with the entity known in Japan as <
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Eritema/diagnóstico , Adulto , Anciano , Animales , Biopsia , Culex , Diagnóstico Diferencial , Eritema/etiología , Eritema/patología , Extremidades , Dermatosis Facial/diagnóstico , Dermatosis Facial/etiología , Dermatosis Facial/patología , Estudios de Seguimiento , Hemangioma/diagnóstico , Humanos , Mordeduras y Picaduras de Insectos/diagnóstico , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/diagnósticoRESUMEN
OBJECTIVE: To report our 12-year experience with Merkel cell carcinomas (MCCs) from a clinical and pathological point of view. SUBJECTS AND SETTING: Eleven MCCs were diagnosed at our institution between 1991 and 2002. METHODS: A retrospective clinical, histopathological and immunohistochemical study was performed. Age, gender, location, size, stage, treatment and follow-up data were collected. Histopathological pattern and immunohistochemical study with CAM 5.2, cytokeratin 20 (CK20), CK7, Ber EP4, neurofilaments, synaptophysin, chromogranin, S100 protein, p53 protein, CD117, leucocyte common antigen (LCA) and Ki-67 were accomplished. RESULTS: Six females and five males with a mean age of 82 years were identified. Tumours were located on the face (n = 6), extremities (n = 3) and trunk (n = 1). At diagnosis, one patient was in stage Ia, six in stage Ib, three in stage II and one in stage III. All but one patient experienced wide surgical excision of the tumour. Additional treatment consisted of lymph node dissection in two patients, radiotherapy in four patients and systemic chemotherapy in one patient. Local recurrence developed in five patients. Three patients died because of MCC after 14 months of follow-up. Intermediate-size round cell proliferation was found in all cases. Additional small-size cell pattern and trabecular pattern were observed in seven and six cases, respectively. Eccrine and squamous cell differentiation were found in three cases. A dot-like paranuclear pattern was observed in all cases with CAM 5.2 and neurofilaments, and in 89% of cases with CK20. Seventy-five per cent of cases reacted with Ber EP4, chromogranin and synaptophysin, 70% with p53, 22% with S100 protein, 55% with CD117 and none with LCA. Ki-67 was found in 75% of tumoral cells on average. Fifty per cent of MCCs reacted with CK7 and showed eccrine differentiation areas. CONCLUSIONS: MCC is an aggressive neuroendocrine tumour of the elderly. Wide surgical excision is the recommended treatment. Lymph node dissection, adjuvant radiotherapy and chemotherapy decrease regional recurrences but have not been demonstrated to increase survival. Immunohistochemically, MCC is an epithelial tumour with neuroendocrine features.
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Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/terapia , Invasividad Neoplásica/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Carcinoma de Células de Merkel/mortalidad , Quimioterapia Adyuvante , Estudios de Cohortes , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , España , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Alopecia Areata/inducido químicamente , Interferón-alfa/efectos adversos , Ribavirina/efectos adversos , Alopecia Areata/inmunología , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Persona de Mediana Edad , Ribavirina/uso terapéuticoRESUMEN
Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in the culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells. Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, particularly in A375 and RMS cells, in which an inhibition of the proliferation rate was observed when IL-2 was blocked. Moreover, the combination of anti-IL-2R beta and anti-IL-2R gamma blocking antibodies induced a significant down-regulation of cell proliferation in the three melanoma cell lines, and the combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma blocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 endogenously produced by melanoma cells. These data show that IL-2 may modulate the growth of melanoma cells through autocrine or/and paracrine mechanisms.
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Interleucina-2/fisiología , Melanoma/inmunología , Melanoma/patología , Anticuerpos Monoclonales/inmunología , Comunicación Autocrina , División Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Humanos , Interleucina-2/biosíntesis , Interleucina-2/farmacología , Metástasis de la Neoplasia , Receptores de Interleucina-2/inmunología , Proteínas Recombinantes/farmacología , Células Tumorales CultivadasRESUMEN
In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.
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Antineoplásicos/uso terapéutico , Interferón-alfa/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/economía , Quimioterapia Adyuvante , Estudios de Cohortes , Análisis Costo-Beneficio , Supervivencia sin Enfermedad , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/economía , Masculino , Melanoma/economía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Proteínas Recombinantes , Factores de Riesgo , Neoplasias Cutáneas/economíaRESUMEN
Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma.