RESUMO
The use of immunotherapies has shown promise against selective human cancers. Identifying novel combinations of innate and adaptive immune cell-activating agents that can work synergistically to suppress tumor growth and provide additional protection against resistance or recurrence is critical. The A20 murine lymphoma model was used to evaluate the effect of various combination immunotherapies administered intratumorally. We show that single-modality treatment with Poly(I:C) or GM-CSF-secreting allogeneic cells only modestly controls tumor growth, whereas when given together there is an improved benefit, with 50% of animals clearing tumors and surviving long-term. Neither heat nor irradiation of GM-CSF-secreting cells enhanced the response over use of live cells. The use of a TIM-3 inhibitory antibody and an OX40 agonist in combination with Poly(I:C) allowed for improved tumor control, with 90% of animals clearing tumors with or without a combination of GM-CSF-secreting cells. Across all treatment groups, mice rejecting their primary A20 tumors were immune to subsequent challenge with A20, and this longstanding immunity was T-cell dependent. The results herein support the use of combinations of innate and adaptive immune activating agents for immunotherapy against lymphoma and should be investigated in other cancer types.
Assuntos
Exantema , Anormalidades da Pele , Neoplasias Cutâneas , Humanos , Lactente , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: Neonatal lupus erythematosus (NLE) results from cross-placental transfer of maternal autoantibodies. Neonates can present with cardiac, cutaneous, hepatobiliary, hematologic, and neurologic complications from antibody-mediated organ toxicity. Scant evidence exists on long-term clinical characteristics and outcomes of patients with neonatal lupus. OBJECTIVES: To characterize the autoantibody profile, laboratory, and clinical features of patients with NLE. MATERIALS/METHODS: This was a single-site retrospective cohort study of patients at the Children's Hospital of Philadelphia with NLE. Data were collected on clinical, laboratory, and autoantibody profile at time of presentation, as well as long-term complications. RESULTS: Thirteen patients were included. Congenital cardiac findings were reported in 3 patients, with 1 having persistent cardiac sequelae. Cardiac manifestations were correlated with anti-Ro/SSA positivity in our cohort. Two patients had neurologic findings, with good long-term outcomes. Cutaneous findings were present in all patients, and many resolved without topical steroid treatment. Hematologic and hepatobiliary findings were common, but uncomplicated, with complete resolution by 6 months after initial presentation in all. Maternal rheumatologic disease, treatment, and race were not associated with systemic manifestations. CONCLUSIONS: Patients born to mothers with positive anti-Ro/SSA titers may benefit from routine cardiac monitoring in utero and at birth. Routine EEG or head ultrasound monitoring in patients who are autoantibody positive for NLE may be unnecessary. Information regarding long-term outcomes in NLE can be used to guide familial counseling and the use of serial laboratory testing.
Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Anticorpos Antinucleares , Criança , Feminino , Humanos , Recém-Nascido , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Philadelphia , Gravidez , Estudos RetrospectivosRESUMO
Plexiform fibrohistiocytic tumor (PFT) is a rare neoplasm of mesenchymal origin that can be identified by its propensity for children and adolescents combined with a characteristic histologic arrangement of histiocytes and osteoclast-like giant cells whorled within tumor islands. A 5-year-old female presented with a raised, intermittently tender, and slowly enlarging tumor on her chest, which was histologically confirmed to be a PFT. We present this case along with a comprehensive review of PFT cases reported in the literature to describe the demographic, histologic, and rarely metastatic behavior of this entity. It is important to include PFT on the differential diagnosis of an enlarging tumor in the pediatric population.
Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Histiocitoma Fibroso Maligno/patologia , Histiocitoma Fibroso Maligno/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Biópsia por Agulha , Pré-Escolar , Feminino , Histiocitoma Fibroso Maligno/diagnóstico , Humanos , Imuno-Histoquímica , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/diagnóstico , Parede Torácica/patologia , Resultado do TratamentoRESUMO
Basaloid follicular hamartoma is a relatively rare benign neoplasm of follicular origin that can be mistaken histologically for basal cell carcinoma, but hereditary forms of basaloid follicular hamartoma are associated with nevoid basal cell carcinoma syndrome, or Gorlin syndrome. The pathophysiology of basaloid follicular hamartoma development involves mutations in the patched gene, which is also causative in nevoid basal cell carcinoma syndrome. We present a mother and daughter with basaloid follicular hamartomas, with genetic testing confirming patched gene mutation in the daughter.
Assuntos
Síndrome do Nevo Basocelular/diagnóstico , Folículo Piloso/anormalidades , Hamartoma/diagnóstico , Dermatopatias Genéticas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto , Diagnóstico Diferencial , Feminino , Testes Genéticos , Hamartoma/patologia , Humanos , Lactente , Mutação , Receptor Patched-1/genética , Pele/patologiaRESUMO
We report a case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome in a girl with a novel VPS33B mutation. To our knowledge, this is the first reported case of ARC syndrome in the United States.
Assuntos
Artrogripose/genética , Colestase/genética , Insuficiência Renal/genética , Proteínas de Transporte Vesicular/genética , Artrogripose/complicações , Artrogripose/terapia , Colestase/complicações , Colestase/terapia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Mutação , Insuficiência Renal/complicações , Insuficiência Renal/terapiaRESUMO
We report on an 8-month-old girl with an ulcerated occipital infantile hemangioma resulting in significant hemorrhage. The hemangioma responded rapidly to systemic propranolol and prednisolone, and we believe that describing her atypical clinical course would be helpful for others managing complicated scalp hemangiomas.
Assuntos
Hemangioma/complicações , Hemorragia/etiologia , Neoplasias Cutâneas/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Hemangioma/tratamento farmacológico , Humanos , Lactente , Prednisolona/uso terapêutico , Propranolol/uso terapêutico , Couro Cabeludo , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND: There are few published data about pediatric dermatology (PD) consultations in the pediatric emergency department (PED). OBJECTIVE: We profiled PD consultations to determine patterns of dermatology utilization by the PED. METHODS: We reviewed electronic medical records of 347 PD consultations from the PED over a 36-month period from January 2011 to December 2013. We recorded patient age and gender; PED diagnosis; PD diagnosis; skin biopsy, if needed, with histopathology report; and outpatient PD follow-up. RESULTS: Patient age ranged from 3 days to 18 years with the majority (54.8%) of consultations for patients aged 0 days to 5 years. The most common diagnostic categories were infections and inflammatory skin disorders. Atopic dermatitis was the most common individual diagnosis. In all, 48.1% of patients had PD outpatient clinic follow-up. The rate of diagnostic agreement between the pediatric emergency medicine and PD provider was 58%. LIMITATIONS: Use of electronic medical records, retrospective study design, and population based at a tertiary-care children's hospital represent potential limitations. CONCLUSIONS: PD providers contribute to patient care in the PED. Dermatology education in the PED should include the more commonly encountered disorders identified in this study, including infectious diseases and atopic dermatitis.
Assuntos
Dermatite/diagnóstico , Dermatologia/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Dermatopatias Infecciosas/diagnóstico , Adolescente , Assistência ao Convalescente/estatística & dados numéricos , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Toxidermias/diagnóstico , Feminino , Hemangioma Capilar/diagnóstico , Humanos , Lactente , Recém-Nascido , Mordeduras e Picadas de Insetos/diagnóstico , Masculino , Síndromes Neoplásicas Hereditárias/diagnóstico , Estudos Retrospectivos , Escabiose/diagnóstico , Urticária/diagnósticoRESUMO
Linear morphea en coup de sabre (ECDS) is a form of localized scleroderma that predominantly affects the pediatric population, with a median age of 10 years at presentation. The existence of neurologic findings in association with ECDS has been well described in the literature. Here we describe 4 patients with ECDS who presented with headaches, which were typical migraines in 3 of the patients. The headaches preceded the onset of cutaneous findings by at least 6 months. Our patients' cases emphasize both the importance of recognizing headaches as a harbinger of ECDS and the necessity of performing thorough cutaneous examination in patients with unexplained headaches or other neurologic disease.
Assuntos
Cefaleia/etiologia , Transtornos de Enxaqueca/etiologia , Esclerodermia Localizada/diagnóstico , Adolescente , Biópsia , Encéfalo/patologia , Criança , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Cefaleia/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Metotrexato/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Prednisona/uso terapêutico , Couro Cabeludo/patologia , Esclerodermia Localizada/etiologia , Esclerodermia Localizada/patologiaRESUMO
PURPOSE: Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site. The present study addresses the utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer in vivo. EXPERIMENTAL DESIGN: HMSC were transduced with CRAds. We used a SCID mouse xenograft model to examine the effects of systemically injected CRAd loaded hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases (experimental metastases model) in vivo and on overall survival. RESULTS: Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231 pulmonary metastatic disease homed to the tumor site and led to extended mouse survival compared to mice treated with CRAd alone. CONCLUSION: Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.