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1.
Mol Cancer ; 23(1): 40, 2024 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-38383439

RESUMEN

Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.


Asunto(s)
Melanoma , ARN Largo no Codificante , Humanos , Ratones , Animales , Melanoma/patología , ARN Largo no Codificante/genética , Apoptosis/genética , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/uso terapéutico , Línea Celular Tumoral , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo
2.
J Eur Acad Dermatol Venereol ; 37(6): 1118-1134, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36965110

RESUMEN

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.


Asunto(s)
Síndromes Paraneoplásicos del Sistema Nervioso , Síndromes Paraneoplásicos , Animales , Ratas , Enfermedades Autoinmunes , Neoplasias/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/terapia , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Síndromes Paraneoplásicos del Sistema Nervioso/terapia , Sociedades Médicas
3.
J Dtsch Dermatol Ges ; 21(12): 1513-1523, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37907427

RESUMEN

BACKGROUND AND OBJECTIVES: This study analyzed the extent to which the recent introduction of more effective treatments has led to an improvement in real-world psoriasis patients. PATIENTS AND METHODS: Patient characteristics and the first-year treatment effectiveness in biologic-naive patients have been analyzed since 2004 until now, irrespective of treatment switches. RESULTS: Data from 2,729 patients were eligible for this analysis. The proportion of female patients increased significantly over the years from 29.9% to 36.2% (p < 0.028), while the number of patients with psoriatic arthritis declined from 36.6% to 30.0% (p < 0.001). Moreover, the duration of psoriatic disease and PASI at the start of the treatment significantly decreased. Last observation carrief forward (LOCF) analysis indicated that PASI 90 response increased from 18.9 to 44.6% at 3 months and from 32.9 to 66.8% at 12 months after treatment started. Similary, the PASI ≤ 3 rates increased from 33.2% to 66.0% at 3 months and from 41.9% to 78.9% at 12 months after the treatment started. CONCLUSIONS: The continuous introduction of more efficient biologics has led to significant improvements in patient care and clinical outcomes. Though one out of three to five patients, depending on the endpoint selected, nowadays still does not achieve an entirely satisfactory treatment response (i.e., PASI 90 or PASI ≤ 3).


Asunto(s)
Productos Biológicos , Psoriasis , Humanos , Femenino , Austria/epidemiología , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Resultado del Tratamiento , Productos Biológicos/uso terapéutico , Sistema de Registros , Índice de Severidad de la Enfermedad
4.
J Dtsch Dermatol Ges ; 19(8): 1170-1176, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34114338

RESUMEN

BACKGROUND AND OBJECTIVES: It has been postulated that psoriasis is associated with tongue lesions and geographic tongue might be "oral psoriasis". However, reports are inconclusive, prevalence rates vary and data for Europe are sparse. In this prospective case-control study we investigated the point-prevalence of tongue conditions in an Austrian cohort. PATIENTS AND METHODS: Psoriasis patients and healthy volunteers were assessed regarding tongue and skin lesions, age, sex, smoking habits, allergies, onset of psoriasis, PASI scores and anti-psoriatic treatment. RESULTS: We included 173 psoriasis patients, 58 women, 115 men (median age: 50 [37-60] years), and 173 volunteers, 79 women, 94 men (median age: 54 [43-64] years). Overall, 95 subjects had allergies, 64 psoriasis patients and 50 volunteers were smokers. Median age at onset of psoriasis was 26 (12-40) years, the median PASI score was 2 (0-4.1), most patients received ustekinumab (n = 47). Fissured tongue was significantly associated with psoriasis (25 [14.4 %] psoriasis patients, 13 [7.5 %] volunteers; P = 0.04). Geographic tongue was present in four individuals of each group (2.3%) and associated with smoking (P = 0.01) but not with psoriasis. CONCLUSIONS: Overall, we found a low point-prevalence of tongue lesions in this Austrian cohort. Psoriasis was associated with fissured tongue but not with geographic tongue. Thus, we cannot corroborate the hypothesis that geographic tongue is an oral manifestation of psoriasis.


Asunto(s)
Glositis Migratoria Benigna , Psoriasis , Lengua Fisurada , Estudios de Casos y Controles , Estudios Transversales , Femenino , Glositis Migratoria Benigna/diagnóstico , Glositis Migratoria Benigna/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/diagnóstico , Psoriasis/epidemiología , Lengua Fisurada/diagnóstico , Lengua Fisurada/epidemiología
5.
Wien Med Wochenschr ; 169(13-14): 314-322, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28091975

RESUMEN

Early stage melanomas can achieve remarkable outcomes with surgery alone, but stage IV metastatic melanoma requires significant intervention and has poor outcomes. Here we present evidence on the latest advances in melanoma treatment, discuss the scientific concepts behind new therapies, and analyze the potential of future treatment combinations.


Asunto(s)
Inmunoterapia , Melanoma , Terapia Molecular Dirigida , Terapia Combinada , Humanos , Melanoma/terapia
6.
Wien Med Wochenschr ; 169(13-14): 323-330, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30649651

RESUMEN

The aim of this study was to characterize clinical, histological, and outcome features of primary melanoma in 1329 patients managed at a single-center institution between 2000 and 2010. Parameters included age at diagnosis, sex, tumor location, histology, stage, Breslow thickness, and sentinel lymph node status among others. The mean age at diagnosis was 59.1 ± 16.7 years. Women were significantly younger than men when diagnosed (57.2 vs. 61.0 years; p < 0.001). Most melanomas (83%) were diagnosed on typically sun-exposed skin areas. Superficial spreading melanoma (39.5%) was the most frequent histological subtype. The median Breslow thickness was significantly higher for men compared to women (1.10 mm vs. 0.90 mm; p = 0.018). 38.3% of patients with positive and 12.9% of patients with negative sentinel biopsies progressed. Five-year survival analysis for a sub-cohort of 577 patients showed better 5­year overall survival for woman compared to men (75.8% vs. 63.6%; p = 0.025). Our findings indicate differences in patient characteristics between men and women, and underscore the importance of early melanoma detection to prevent disease progression.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Adulto , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología
9.
J Am Acad Dermatol ; 77(1): 123-129.e5, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28377030

RESUMEN

BACKGROUND: Effective medical treatment for patients with severe hidradenitis suppurativa (HS) is limited. OBJECTIVES: We sought to measure the impact of wide local excision on quality of life in HS Hurley grade III patients and to examine the rate of postoperative complications, disease recurrences, and satisfaction with the cosmetic results. METHODS: Seventy-four patients were enrolled. Outcome measures included Dermatology Life Quality Index responses, disease duration, recurrence, previous therapies, postoperative complications, and satisfaction with cosmetic results. RESULTS: Most patients had inguinogenital/gluteal disease (68.9%, P < .001). Involvement of both the axillary and the inguinogenital/gluteal areas were pronounced in male patients (P = .018). None of the patients was treated with tumor necrosis factor-α inhibitors. Most patients (71.6%) had a disease history of >5 years at the time of presentation and multiple unsuccessful attempts with systemic and local therapeutic interventions. Wide local excision improved Dermatology Life Quality Index scores from initially 27.89 to 5.31 after surgery (P < .001), independent of localization (P = .195). Forty-seven percent of patients had postoperative complications, most frequently pain and scarring. The vast majority of patients (70.3%) were satisfied with the cosmetic results. LIMITATIONS: The retrospective nature of the study was a limitation. CONCLUSIONS: Wide local excision significantly improves the quality of life of HS patients. Local recurrence rates are low, and satisfaction with the cosmetic results is high.


Asunto(s)
Hidradenitis Supurativa/cirugía , Adulto , Procedimientos Quirúrgicos Dermatologicos/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
10.
J Dtsch Dermatol Ges ; 15(3): 309-318, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28252852

RESUMEN

HINTERGRUND UND ZIELE: Biologika werden häufig zur Behandlung der Psoriasis eingesetzt und wurden in zahlreichen klinischen Studien getestet. Allerdings können sich Wirkungen und Nebenwirkungen (AEs) bei "real-world"-Patienten unterscheiden, da diese keiner solch strengen Auswahl und Überwachung unterzogen werden. Wir haben Therapieadhärenz ("Medikamenten-Überlebenszeit"), Wirksamkeit und AEs (Qualität, Zeitpunkt des Auftretens) bei "real-world"-Psoriasis-Patienten, die mit Etanercept, Adalimumab oder Ustekinumab behandelt wurden, untersucht. PATIENTEN UND METHODEN: Retrospektive Datenanalyse (1. Januar 2004 bis 30. Juni 2015) an Patienten, die an einer Psoriasis-Klinik in einem österreichischen Krankenhaus behandelt wurden. Alle Patienten, die mindestens eine Dosis von Etanercept, Adalimumab oder Ustekinumab erhalten hatten, wurden in die Analyse einbezogen. Wir analysierten Demographie, Therapieadhärenz, den Psoriasis Area and Severity Index (PASI) sowie Qualität und Zeitpunkt des Auftretens von AEs. ERGEBNISSE: In 209 Behandlungsreihen variierte die geschätzte mittlere Therapieadhärenz zwischen den verschiedenen Behandlungen: 21 Monate (SE: 6,9) für Etanercept, 61 Monate (SE: 9,4) für Adalimumab und 65 Monate (SE 1,4) für Ustekinumab. Männliches Geschlecht und Vorbehandlung mit einem Biologikum waren positive Prädiktoren für längere Therapie mit Adalimumab. Wir fanden keinen signifikanten Unterschied in der am PASI gemessenen Arzneimittelwirksamkeit. SCHLUSSFOLGERUNGEN: Die meisten AEs treten während des ersten Jahres der Behandlung auf. Adalimumab und Ustekinumab zeichnen sich im Vergleich zu Etanercept durch eine längere Therapieadhärenz aus.

11.
J Dtsch Dermatol Ges ; 15(3): 309-317, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28240404

RESUMEN

BACKGROUND AND OBJECTIVES: Widely used in the treatment of psoriasis, biologics have been tested in numerous clinical trials. However, drug efficacies and adverse events (AEs) may differ in 'real-world' patients as they do not undergo as rigorous selection and monitoring. Our objective was to examine drug survival, efficacy, and AEs (quality, time of onset) in 'real-world' psoriasis patients treated with etanercept, adalimumab, and ustekinumab. PATIENTS AND METHODS: Retrospective data analysis (Jan 1, 2004 to Jun 30, 2015) of patients treated at a psoriasis clinic in an Austrian hospital. All patients who had received at least one dose of etanercept, adalimumab, or ustekinumab were included in the analysis. We analyzed: demographics, drug survival, Psoriasis Area and Severity Index (PASI), as well as quality and time of onset of AEs. RESULTS: In 209 treatment series, the estimated median drug survival varied among the various treatments: 21 months (SE: 6.9) for etanercept, 61 months (SE: 9.4) for adalimumab, and 65 months (SE 1.4) for ustekinumab. Male gender and pretreatment with a biologic were positive predictors of longer drug survival in adalimumab. We found no significant difference in drug efficacy as determined by PASI. CONCLUSIONS: Most AEs occur during the first year of treatment. Adalimumab and ustekinumab are marked by longer drug survival compared to etanercept.


Asunto(s)
Adalimumab/administración & dosificación , Etanercept/administración & dosificación , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Ustekinumab/administración & dosificación , Adolescente , Adulto , Distribución por Edad , Anciano , Antiinflamatorios/administración & dosificación , Austria/epidemiología , Niño , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Resultado del Tratamiento , Adulto Joven
14.
J Am Acad Dermatol ; 75(4): 736-739, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27473452

RESUMEN

BACKGROUND: The infliximab originator's patent recently expired, leading to the production of biosimilar versions of the drug. The biosimilars' efficacy was not tested on patients with psoriasis but most regulatory authorities approved their use in psoriasis because of an extrapolation of data from studies conducted in other diseases. OBJECTIVE: We sought to describe the use of the infliximab biosimilar (Remsima; CT-P13) in patients with psoriasis. METHODS: Objective (Psoriasis Area and Severity Index) and subjective (visual analog pain scale) measurements of disease activity were collected in 2 cohorts of patients with moderate to severe plaque psoriasis: cohort 1 patients switched from the infliximab originator to the infliximab biosimilar; and cohort 2 patients were infliximab-naïve and started on the infliximab biosimilar. RESULTS: We observed no changes of Psoriasis Area and Severity Index and visual analog pain scale scores in 30 patients who switched from the infliximab originator to the biosimilar. Four of 5 infliximab-naïve patients who started infliximab biosimilar treatment achieved 75% improvement or better from baseline Psoriasis Area and Severity Index score at the end of the induction phase. LIMITATIONS: Number of patients and length of follow-up was limited. CONCLUSIONS: Patients with psoriasis taking infliximab originator treatment can switch to the infliximab biosimilar without experiencing a significant change in clinical response or additional adverse events. The use of the infliximab biosimilar could reduce the growing pressure on health care budgets.


Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Infliximab/uso terapéutico , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
18.
Biomed Microdevices ; 17(1): 15, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25653058

RESUMEN

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Early treatment may improve any chances of preventing metastatic disease, but diagnosis of small UM is challenging. Up to 95 % of all UMs carry somatic mutations in the G-coupled proteins GNAQ and GNA11 promoting anchorage-independent growth and proliferation. About 50 % of UMs are fatal. Once metastatic, patients have limited options for successful therapy. METHODS: We have developed functionalized gold nanoparticles (AuNPs) to visualize transcripts of mutant GNAQ mRNA in living cells. In addition to their suitability as a specific tool for GNAQ mutation detection, we have developed a novel linker that enables conjugation of siRNAs to AuNPs allowing for greater and more rapid intracellular release of siRNAs compared to previously described approaches. RESULTS: Binding of modified AuNPs to matching target mRNA leads to conformational changes, resulting in a detectable fluorescent signal that can be used for mutation detection in living cells. Knockdown of GNAQ with siRNA-AuNPs effectively reduced downstream signals and decreased cell viability in GNAQ mutant uveal melanoma cells. CONCLUSION: AuNPs may in future be developed to serve as sensors for mutations of vital importance. The new release system for siRNA-AuNP improves previous systems, which conceivably will be useful for future therapeutic gene regulatory approaches.


Asunto(s)
Técnicas Biosensibles/métodos , Subunidades alfa de la Proteína de Unión al GTP , Técnicas de Silenciamiento del Gen/métodos , Oro/química , Melanoma , Nanopartículas del Metal/química , Mutación , Proteínas de Neoplasias , ARN Mensajero , ARN Neoplásico , Neoplasias de la Úvea , Adulto , Línea Celular Tumoral , Supervivencia Celular/genética , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/patología
19.
J Am Acad Dermatol ; 71(4): 738-44, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25022849

RESUMEN

BACKGROUND: Evidence for the efficacy of various therapies of livedoid vasculopathy (LV) is limited. OBJECTIVE: We sought to determine efficacy and tolerability of 2 g/kg of intravenous immunoglobulins (IVIG) every 4 weeks in patients with LV. METHODS: This was a long-term follow-up study of 11 patients with LV treated with 2 g/kg of IVIG assessing the clinical characteristics, disease course, and quality of life. RESULTS: The treatment regimen led to complete remission of ulcerations and pain in 17 of 29 disease episodes (59%) after 3 cycles and in 25 of 29 episodes (86%) after 6 cycles. Two disease episodes showed remission after 7 and 8 cycles, resulting in a total number of remissions of 27 (93%). Subscore analysis showed resolution of pain in 80% after 2 IVIG cycles. Disease severity and quality of life were significantly improved after 6 cycles. Median duration of remissions was 26.7 months after initial and 7.5 months after subsequent disease episodes. LIMITATIONS: This was a retrospective study that did not include the comparison of IVIG efficacy and its impact on quality of life with treatment options. CONCLUSIONS: In our patients with LV, high-dose IVIG led to fast and complete resolution of pain and ulcerations and to substantial improvement in quality of life.


Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Livedo Reticularis/tratamiento farmacológico , Calidad de Vida , Enfermedades Cutáneas Vasculares/tratamiento farmacológico , Adulto , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Livedo Reticularis/diagnóstico , Livedo Reticularis/psicología , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Satisfacción del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/psicología , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
20.
J Am Acad Dermatol ; 71(6): 1102-1109.e1, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25440439

RESUMEN

BACKGROUND: BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) frequently cause cutaneous adverse events. OBJECTIVE: We sought to investigate the cutaneous safety profile of BRAFi versus BRAFi and MEKi combination regimens. METHODS: We performed a retrospective cohort study, collecting data from 44 patients with melanoma treated either with BRAFi (vemurafenib or dabrafenib) or BRAFi and MEKi combination regimens (vemurafenib + cobimetinib or dabrafenib + trametinib). Patient characteristics, and the occurrence and severity of cutaneous adverse events, are described. RESULTS: The development of cutaneous adverse events was significantly less frequent (P = .012) and occurred after longer treatment time (P = .025) in patients treated with BRAFi and MEKi combination regimen compared with patients treated with BRAFi monotherapy. Among patients who received both BRAFi and the combination of BRAFi and MEKi at different time points during their treatment course, the development of squamous cell carcinoma or keratoacanthoma was significantly less frequent when they received the combination regimen (P = .008). Patients receiving vemurafenib developed more cutaneous adverse events (P = .001) and in particular more photosensitivity (P = .010) than patients who did not. LIMITATIONS: There were a limited number of patients. CONCLUSION: Combination regimen with BRAFi and MEKi shows fewer cutaneous adverse events and longer cutaneous adverse event-free interval compared with BRAFi monotherapy.


Asunto(s)
Azetidinas/efectos adversos , Imidazoles/efectos adversos , Indoles/efectos adversos , Melanoma/tratamiento farmacológico , Oximas/efectos adversos , Piperidinas/efectos adversos , Piridonas/efectos adversos , Pirimidinonas/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azetidinas/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Imidazoles/administración & dosificación , Indoles/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Oximas/administración & dosificación , Piperidinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Sulfonamidas/administración & dosificación , Vemurafenib , Adulto Joven
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