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INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis. RESULTS: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.
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Antígeno CD47/metabolismo , Enfermedad de Hodgkin/patología , Células de Reed-Sternberg/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Niño , Femenino , Enfermedad de Hodgkin/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Matrices Tisulares , Adulto JovenRESUMEN
PURPOSE: The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment. METHODS: We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher's ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions. RESULTS AND CONCLUSIONS: We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Inflamación/epidemiología , Sobrecarga de Hierro/epidemiología , Hepatopatías/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Bleomicina/uso terapéutico , Dacarbazina/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Humanos , Incidencia , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Vinblastina/uso terapéuticoRESUMEN
Numerous study commissions have contended that departmental territoriality and lack of coordinated planning are stagnating contemporary medical education. As a cure, these commissions have recommended the creation of centralized academic management units empowered to oversee revitalization of the curriculum through a series of reforms, including better definition of graduation competencies, community-based training, interdisciplinary courses, problem-based learning, and modernization of evaluation strategies. To determine the extent to which these recommendations were being adopted, in 1990 the authors sent a questionnaire on curriculum committee functions, current innovation efforts, and future priorities to academic administrators and members of medical school curriculum committees at 143 North American medical schools. Responses were received from administrators (primarily associate deans for academic affairs) at 118 schools and committee members (primarily faculty) at 111 schools. Recommendations for enhancing curriculum committee effectiveness were also elicited. The authors conclude that centralization of curricular management has occurred at very few institutions, and that the commonly mentioned reforms are being adopted at a modest pace. The results are analyzed in light of theories of the institutional change process and strategies for introducing educational innovations into established institutions.
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Curriculum , Comité de Profesionales/normas , Facultades de Medicina/normas , Personal Administrativo , Canadá , Difusión de Innovaciones , Eficiencia , Humanos , Liderazgo , Innovación Organizacional , Objetivos Organizacionales , Filosofía Médica , Comité de Profesionales/organización & administración , Comité de Profesionales/tendencias , Puerto Rico , Facultades de Medicina/organización & administración , Facultades de Medicina/tendencias , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Two 46,XY phenotypic female siblings, aged 1 1/2 and 8 1/2 years, have peculiar facies, cardiac, renal, musculoskeletal, and ectodermal anomalies, short stature, streak gonads, and mild developmental delay. Previous reported cases of 46,XY gonadal dysgenesis have not had major associated malformations. These children present a new constellation of anomalies unlike those seen in other types of gonadal dysgenesis and represent a new familial syndrome of 46,XY gonadal dysgenesis.