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RATIONAL: The absence of a specific tool to evaluate the impact of supportive care in general and socioesthetics (SE) in particular is undoubtedly at the origin of the lack of published research based on scientific standards. OBJECTIVE: We developed a supportive-care, patient-reported outcome questionnaire using the multistep methods, following COSMIN recommendations. METHODS: The Patient Centricity Questionnaire (PCQ) was developed using the standardized methodology for designing patient-reported outcome (PRO) questionnaires according to the following steps: elaboration of the questionnaire, measurement properties of the questionnaire, internal and external validation, test-retest validation and translation, cross-cultural adaptation, and cognitive debriefing. A multidisciplinary work group was designed including professionals, such as physicians, public health experts, sociologists, supportive-care experts, and socioestheticians. RESULTS: Our questionnaire includes 11 items. It is scored by adding each Visual Analogue Scale [VAS], making it range from 0 to 110, with a higher benefit when the score is higher. The Cronbach's α coefficient is 0.88 for the entire questionnaire. As the questionnaire is a reflection of the patient's feelings, it is quite natural that the name "Patient Centricity Questionnaire" (PCQ) was retained and validated by the Scientific Committee. The PCQ correlated negatively and moderately with the Perceived Stress Scale [PSS], positively and moderately with the mental dimension of the Short Form-12, and poorly with the Well Beng 12 [WB12], the physical dimension of the SF-12, and the satisfaction VAS. CONCLUSION: Constructed according to the recommendations, the PCQ meets the prerequisite for this type of questionnaire. Its short format and simplicity of use allow it to be used by a large number of people. The PCQ is a simple, reliable, easy-to-use, and validated tool for research teams, making it possible for randomized studies to prove the impact of supportive care in general and SE in particular, on the patient's quality of life.
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BACKGROUND: Immune checkpoint inhibitor (ICI)-mediated psoriasis poses significant diagnostic and therapeutic challenges. OBJECTIVE: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. METHODS: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. RESULTS: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P = .03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P < .001). Guttate psoriasis and grade 2 or 3 disease were significant positive predictors for antitumor response of ICI, whereas pruritus was a negative predictor. LIMITATIONS: Retrospective design. CONCLUSION: Acitretin, apremilast, and methotrexate are safe and effective modalities for ICI-mediated psoriasis. In most cases, ICI can be completed unhindered. A therapeutic algorithm is proposed.
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Fármacos Dermatológicos/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Acitretina/uso terapéutico , Anciano , Productos Biológicos/uso terapéutico , Quimioterapia Combinada/métodos , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Neoplasias/inmunología , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Resultado del TratamientoRESUMEN
Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.
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Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Mutación/genética , Medicina de Precisión/métodos , Transducción de Señal/efectos de los fármacos , Adolescente , Antineoplásicos/farmacología , Bencenosulfonatos/farmacología , Bencenosulfonatos/uso terapéutico , Butadienos/farmacología , Supervivencia Celular/efectos de los fármacos , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Quimioterapia Combinada/métodos , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Resultado Fatal , Femenino , Genes ras/genética , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Niacinamida/análogos & derivados , Nitrilos/farmacología , Compuestos de Nitrosourea/farmacología , Compuestos Organofosforados/farmacología , Compuestos de Fenilurea , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Piridinas/farmacología , Piridinas/uso terapéutico , Sorafenib , Resultado del TratamientoRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Hyperprogressive disease (HPD), an unexpected acceleration of tumor growth kinetics, is described in cancer patients treated with anti-PD-1/anti-PD-L1 agents. Here, our aim was to take into consideration the host and explore whether single nucleotide polymorphisms (SNPs) in key genes involved in immune response might predispose to HPD. DNA was extracted from blood-samples from 98 patients treated under CPI monotherapy. Four candidate genes (PD-1, PD-L1, IDO1 and VEGFR2) and 15 potential SNPs were selected. The TGKR (ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR≥2. TGKR calculation was feasible for 80 patients (82%). HPD was observed for 11 patients (14%) and was associated with shorter overall survival (P = 0.003). In univariate analysis, HPD was significantly associated with age ≥70 y (P = 0.025), immune-related toxicity (P = 0.016), VEGFR2 rs1870377 A/T or A/A (P = 0.005), PD-L1 rs2282055 G/T or G/G (P = 0.024) and PD-L1 rs2227981 G/A or A/A (P = 0.024). Multivariate analysis confirmed the correlation between HPD and age ≥70 y (P = 0.006), VEGFR2 rs1870377 A/T or A/A (P = 0.007) and PD-L1 rs2282055 G/T or G/G (P = 0.018). Immunogenetics could become integral predictive factors for CPI-based immunotherapy.
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Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Proliferación Celular , Progresión de la Enfermedad , Femenino , Humanos , Inmunogenética , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/mortalidad , Polimorfismo de Nucleótido Simple , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunologíaRESUMEN
Importance: Since 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies. Objectives: To evaluate the risk of a recurrence of immune toxic effects associated with anti-programmed cell death 1 antibody (anti-PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs. Design, Settings, and Participants: This cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti-PD-1 therapy between February 1, 2013, and December 31, 2016. The study cutoff was June 1, 2017. Statistical analysis was performed from June 1, 2016, to August 31, 2017. Exposures: Monotherapy with at least 1 cycle of ipilimumab that was associated with a grade 3 or 4 immune-related AE and subsequent treatment with at least 1 cycle of an anti-PD-1 (nivolumab or pembrolizumab) therapy. Main Outcomes and Measures: The primary outcome was the rate of immune-related AEs associated with anti-PD-1 therapy. Secondary outcomes were characteristics of ipilimumab-related and anti-PD-1 immune-related AEs and overall response rate and overall survival associated with anti-PD-1 therapy. Results: Of 56 patients with metastatic melanoma included in the study, all of whom experienced severe immune-related AEs after ipilimumab therapy (31 [55%] male; mean [SD] age, 64 [14.9] years), 20 (36%) experienced at least 1 immune-related AE associated with pembrolizumab (6 of 20 [30%]) or nivolumab (14 of 20 [70%]) therapy. A total of 12 patients (21%) experienced grade 3 or 4 immune-related AEs, and among these patients, 4 (33%) presented with the same immune-related AE as with ipilimumab therapy. Severe immune-related AEs were resolved with use of systemic corticosteroids (7 [58%]) and/or anti-tumor necrosis factor (1 [8%]), and no grade 5 toxic effects were reported. Five patients discontinued anti-PD-1 therapy because of immune-related AEs. The overall response rate was 43%, with a median overall survival of 21 months (interquartile range, 18 to ongoing). Conclusions and Relevance: The findings suggest that anti-PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects after ipilimumab therapy.
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Neoplasias Encefálicas/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Ipilimumab/administración & dosificación , Ipilimumab/efectos adversos , Estimación de Kaplan-Meier , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1/inmunología , Recurrencia , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
OBJECTIVE: Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune-related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. METHODS: A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. RESULTS: The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty-four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression-free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression-free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. CONCLUSION: Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
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Antineoplásicos Inmunológicos/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunosupresores/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/complicaciones , Femenino , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Supervivencia sin Progresión , Estudios Retrospectivos , Tasa de Supervivencia , Brote de los Síntomas , Resultado del TratamientoRESUMEN
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.
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Endotelio Vascular/metabolismo , Melanoma/metabolismo , Metástasis de la Neoplasia , Osteonectina/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Animales , Permeabilidad Capilar , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Pulmonares/secundario , Sistema de Señalización de MAP Quinasas , Melanoma/patología , Ratones Desnudos , Comunicación ParacrinaRESUMEN
BACKGROUND: Rarely, basal cell carcinomas (BCCs) have the potential to become extensively invasive and destructive, a phenomenon that has led to the term "locally advanced BCC" (laBCC). We identified and described the diverse settings that could be considered "locally advanced". METHODS: The panel of experts included oncodermatologists, dermatological and maxillofacial surgeons, pathologists, radiotherapists and geriatricians. During a 1-day workshop session, an interactive flow/sequence of questions and inputs was debated. RESULTS: Discussion of nine cases permitted us to approach consensus concerning what constitutes laBCC. The expert panel retained three major components for the complete assessment of laBCC cases: factors of complexity related to the tumour itself, factors related to the operability and the technical procedure, and factors related to the patient. Competing risks of death should be precisely identified. To ensure homogeneous multidisciplinary team (MDT) decisions in different clinical settings, the panel aimed to develop a practical tool based on the three components. CONCLUSION: The grid presented is not a definitive tool, but rather, it is a method for analysing the complexity of laBCC.
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Carcinoma Basocelular , Dermatología , Guías de Práctica Clínica como Asunto , Neoplasias Cutáneas , Sociedades Médicas , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/patología , Carcinoma Basocelular/terapia , Congresos como Asunto , Europa (Continente)/epidemiología , Humanos , Morbilidad/tendencias , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX(4) and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth. Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX(4) -associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis.
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Inhibidores Enzimáticos/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Luz , Melanoma/metabolismo , NADP/farmacología , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Aorta/citología , Aorta/efectos de los fármacos , Aorta/metabolismo , Apoptosis , Western Blotting , Ciclo Celular , Proliferación Celular , Espectroscopía de Resonancia por Spin del Electrón , Citometría de Flujo , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , NADP/análogos & derivados , NADPH Oxidasa 4 , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Neovascularización Patológica , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/metabolismo , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
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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Proteínas Quinasas Activadas por AMP/metabolismo , Melanoma/metabolismo , Melanoma/patología , Metformina/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Melanoma/genética , Metaloendopeptidasas/metabolismo , Ratones , Invasividad Neoplásica , Metástasis de la NeoplasiaRESUMEN
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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Melanoma/patología , Células Madre Neoplásicas/patología , Factor de Transcripción STAT3/antagonistas & inhibidores , Animales , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Senescencia Celular/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Melanoma/genética , Melanoma/metabolismo , Ratones , Ratones Desnudos , Fenotipo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Distribución Aleatoria , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Transfección , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Melanoma/tratamiento farmacológico , Metformina/administración & dosificación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/genética , Melanoma/metabolismo , Metformina/efectos adversos , Persona de Mediana Edad , Proyectos PilotoAsunto(s)
Benzamidas/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Anciano , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Humanos , Mesilato de Imatinib , Melanoma/metabolismo , Mutación Puntual , Proteínas Proto-Oncogénicas c-kit/metabolismo , Transducción de Señal/genética , Neoplasias Cutáneas/metabolismoAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanoma/tratamiento farmacológico , Mutación Puntual , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Antineoplásicos/farmacología , Arginina , Dorso , Supervivencia Celular/efectos de los fármacos , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Femenino , Humanos , Imidazoles/administración & dosificación , Imidazoles/farmacología , Indoles/administración & dosificación , Indoles/farmacología , Leucina , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Melanoma/genética , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Niacinamida/farmacología , Oximas/administración & dosificación , Oximas/farmacología , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/farmacología , Neoplasias Cutáneas/genética , Sorafenib , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , VemurafenibAsunto(s)
Inmunohistoquímica/métodos , Melanoma/patología , Mutación/genética , Células Neoplásicas Circulantes/patología , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Pruebas Genéticas/métodos , Humanos , Masculino , Melanoma/genética , Melanoma/metabolismo , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Células Neoplásicas Circulantes/metabolismo , Sensibilidad y Especificidad , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Adulto JovenRESUMEN
Reports of induction or exacerbation of psoriatic palmoplantaris pustulosis (PPPP) after anti-tumor necrosis factor-alpha (TNF-alpha) treatment are few. We describe 2 new cases of PPPP induced by infliximab. In 1999, a total of 442 patients in our department received anti-TNF-alpha treatment for a variety of chronic rheumatic conditions and were regularly followed. Medical records for 166 given infliximab were retrospectively reviewed for disease [rheumatoid arthritis (RA), spondylarthropathies (SpA) including psoriatic arthritis], disease duration, clinical characteristics, skin side-effects, and use of other potentially relevant medications. PPPP was observed in 2 patients treated with infliximab for symmetrical rheumatoid factor-positive RA; the patients had no personal or family history of psoriasis. In both cases, pustulosis appeared after several months of infliximab administration. There was no clinical, biological, or radiological evidence to support a diagnosis of psoriatic SpA. Both patients fulfilled ACR criteria for RA, and there was no reason to suspect previously unidentified psoriasis. Comorbid RA and psoriasis are unusual, and our patients exhibited a clear link between anti-TNF-alpha administration and cutaneous lesions, suggesting a direct effect in both cases. The 28 published cases of PPPP induced by anti-TNF-alpha treatment report lesions that tend towards pustulosis and palmoplantar localization. The mechanisms involved remain elusive. Disappearance of lesions in our second patient when switched to a soluble receptor suggests a molecule-specific side effect, while the literature describing variable reaction to switching anti-TNF agents, and/or their discontinuation and reintroduction, indicates otherwise. Given the rarity of this side effect, its elucidation will require systematic study.