Câncer e angiogênese: papel do fator de crescimento endotelial vascular (VEGF) e terapias alvo / Cancer and angiogenesis: the role of vascular endothelial growth factor (VEGF) and target therapy

- Introdução: As demandas tumorais são supridas pela angiogênese (surgimento de vasos sanguíneos). Em hipóxia, são secretadas moléculas pró-angiogênicas, como o fator de crescimento vascular endotelial (VEGF), ativando vias de progressão, invasão e metástase tumoral; portanto, tais substâncias tornaram-se alvo nas terapias anti-tumorais. Objetivo: Analisar produções científicas sobre câncer e angiogênese, focando em VEGF, seu mecanismo de ação e vias terapêuticas. Método: Revisão integrativa de literatura utilizando base de dados PubMed e Scielo, com os descritores angiogenesis, cancer, VEGF, anti-angiogenic e treatment. Resultados: O VEGF, especialmente VEGF-A, liga-se ao receptor tirosina-quinase VEGFR-2 para induzir a migração de células endoteliais e ativar vias intracelulares, promovendo a liberação de proteases destrutoras da matriz extracelular que permitem o brotamento de vasos sanguíneos. Drogas anti-angiogênicas inibem o mecanismo de VEGF/VEGFR-2. Conclusão: Inibidores de VEGF desaceleram o crescimento neoplásico e melhoram a distribuição sistêmica de fármacos associados, sendo ampla a recomendação da administração conjunta de fármacos anti-angiogênicos e quimioterápicos tradicionais

Introduction: Tumor demands are supplied by angiogenesis (arise of blood vessels). In hypoxia, pro-angiogenic molecules are secreted, as vascular endothelial growth factor (VEGF), which activate pathways of tumor progression, invasion and metastasis. Therefore, such substances have become a target in anti-tumor therapies. Objective: Analyse scientific productions on cancer and angiogenesis, focusing on VEGF, its mechanism and therapeutics pathways. Method: Integrative literature review using the online databases PubMed and Scielo and the terms angiogenesis, cancer, VEGF, anti-angiogenic and treatment. Results: VEGF, especially VEGF-2, binds at VEGFR-2 tyrosine kinase receptor to induce endothelial cells migration and activate intracellular pathways to promote the release of destructive proteases from the extracellular matrix,, which allow blood vessels to sprout. Anti-angiogenic drugs inhibit the mechanism of VEGF/ VEGFR-2. Conclusion: VEGF inhibitors slow neoplastic growth and improve systemic distribution of associated drugs, which are widely recommended in joint administration of traditional anti-angiogenic and chemotherapeutic drugs

Pseudoxantoma elástico / Pseudoxanthoma elastic

Resumo O pseudoxantoma elástico é uma doença generalizada do tecido conjuntivo envolvendo a pele, olhos e sistema cardiovascular desencadeando a fragmentação e calcificação das fibras elásticas. Geralmente ocorre após a puberdade, as manifestações características são manchas pequenas, circunscritas, amareladas, localizadas no pescoço, axila e pregas inguinais. Estrias angioides na retina, tendência à hemorragia e insuficiência arterial são as complicações mais comuns. Esta doença pode ser herdada como autossômica dominante ou recessiva. O tratamento das manifestações oculares convencional é através da fototerapia a laser impedindo a ocorrência de hemorragias locais. Entretanto, novas abordagens terapêuticas estão sendo desenvolvidas como a utilização em longo prazo de drogas antiangiogênicas, as quais atuam inibindo a neovascularização ocular. Apesar de não ter ainda efetivamente substituído o tratamento original, pesquisas recentes já evidenciam benefícios da nova técnica. O objetivo deste estudo é relatar sobre o caso de uma paciente de 37 anos, portadora do pseudoxantoma elástico, com estrias angioides e hemorragia ocular, e o tratamento eficaz com a terapia antiangiogênica no ambulatório de oftalmologia em Nova Iguaçu, Rio de Janeiro.

Abstract The pseudoxanthoma elasticum is a generalized disease of the connective tissue involving the skin, eyes and cardiovascular system triggering the fragmentation and calcification of elastic fibers. Usually occurs after puberty, the manifestations characteristics are small spots, circumscribed, yellowish, located on the neck, axilla and inguinal folds. Angioid streaks in the retina, tendency to hemorrhage and arterial insufficiency are the most common complications. This disease can be inherited as autosomal dominant or recessive. The treatment of ocular manifestations is through the conventional phototherapy laser preventing the occurrence of local hemorrhages. However, new therapeutic approaches are being developed as the long-term use of drugs antiangiogenic, which act by inhibiting the ocular neovascularization. Despite not having yet effectively replaced the original treatment, recent research already show benefits of new technique. The objective of this study is to report on a case of a patient of 37 years, the carrier of the Pseudoxanthoma Elasticum, with angioid streaks and ocular hemorrhage, and the effective treatment with antiangiogenic therapy at the clinic of Ophthalmology in Nova Iguaçu, Rio de Janeiro.

Caracterización de la Retinopatía de la prematuridad entre el período de 2008 y 2014 en Barranquilla - Colombia / Characterization of Retinopathy of prematurity between 2008 and 2014 in Barranquilla - Colombia

Objetivo: establecer la prevalencia, factores de riesgo y resultados anatómicos asociados a la Retinopatía de la Prematuridad en neonatos con edad gestacional menor o igual a 32 semanas y peso menor o igual de 1.750 g en 14 unidades de cuidados intensivos de la ciudad de Barranquilla ­ Colombia entre el periodo del 2008 al 2014. Diseño: estudio descriptivo transversal con análisis de casos y controles. Materiales y Métodos: datos recolectados de fuente secundaria. Criterios de inclusión: recién nacidos pretérmino de ≤32 semanas de Edad Gestacional y/o Peso al Nacer ≤ 1750 g y pacientes >32 semanas y peso al nacer >1750 g que por factores de riesgo sistémicos su neonatólogo solicitó el examen. Se excluyeron pacientes con historias clínicas incompletas. Las variables estudiadas fueron : edad gestacional, peso al nacer, sexo, edad cronológica, sepsis, oxigeno, enfermedad de membrana hialina, cirugías perinatales, hemorragias intraventriculares, transfusiones, embarazo gemelar, presencia de ROP, distribución de ROP por estadío, zonas y tipo, distribución según el tratamiento implementado y la relación de este con el peso y la edad gestacional. Se realizó tratamiento con Fotocoagulación Láser a pacientes con ROP Pre-umbral Tipo 1 y Tratamiento Combinado de Láser con Bevacizumab Intravítreo a los pacientes con enfermedad Umbral. Resultados: Se estudiaron 1038 ojos y de estos presentaron ROP Umbral 80 ojos con una prevalencia del 7.7% y ROP Preumbral Tipo 1 88 ojos con una prevalencia del 8.7% los cuales requirieron tratamiento. La mayor proporción de pacientes con ROP por edad gestacional estuvo en el rango de 27 a 28 semanas con el 37.8%, seguido del rango de 29 a 30 semanas con el 23.6% y luego el rango de 31-32 semanas con el 18.9%. De los pacientes con ROP, el 32.9% tenían entre 751 ­ 1000 g, seguidos del grupo de 1001 - 1250 g con el 30.7%. Se encontró una relación estadísticamente significativa con bajo peso al nacer, edad gestacional entre 26 y 28 semanas, oxigenoterapia y enfermedad de membrana hialina. El 96.6% de los pacientes con ROP Pre-Umbral Tipo 1 que fueron tratados con láser presentó involución de la ROP y sólo el 3.4% requirió Terapia de Rescate a los 15 días por actividad de su retinopatía. Ningún paciente en este grupo evolucionó a Estadío 4 y/o 5. El 93.7% de los pacientes con ROP Umbral que recibieron tratamiento combinado con Láser y Terapia Intravítrea con bevacizumab (0.65 mg/0.05 cc) presentó involución de la ROP; 73% requirieron una sola dosis de bevacizumab mientras que el 26.6% requirió 2 dosis. 4 ojos progresaron a estadío 4a. De los grupos tratados ningún caso evolucionó a Estadío 5. Conclusiones: la prevalencia de ROP Umbral fue de 7.7% y de ROP Pre-umbral Tipo 1 fue de 8.7% y el tratamiento oportuno fue eficaz en evitar la progresión de la retinopatía. Se resalta la necesidad de manejo multidisciplinario de la retinopatía del prematuro, el cual inicia con los programas de prevención primaria y prevención secundaria. Los factores de riesgo asociados a la ROP en nuestro medio son Edad gestacional < 28 semanas, peso al nacer < 1250g, oxigenoterapia y EMH.

Objective: to describe the prevalence, risk factors and anatomic results associated with retinopathy of prematurity (ROP) in infants with gestational age < 32 weeks and ≤1,750g in 14 NICUs in Barranquilla ­ Colombia between 2008 and 2014. Design: cross sectional study with casecontrol analysis. Materials and Methods: data collected from secondary sources. Inclusion criteria: infants ≤32 weeks and / or ≤ 1750 g and patients > 32 weeks and weight >1750 g if screening by risk factors was recommended by neonatologist. Patients with incomplete medical records were excluded. The variables studied were: gestational age, birth weight, gender, chronological age, twin pregnancy, sepsis, oxygen, respiratory distress, perinatal surgeries, intraventricular hemorrhage, blood transfusion, presence of ROP, distribution of ROP by stage, areas and type, distribution according to the treatment and the relationship with weight and gestational age. Laser photocoagulation treatment in patients with Pre-Threshold ROP Type 1 and a Combined Treatment of Laser and Intravitreal Bevacizumab in patients with Threshold Disease was performed. Results: we studied 1038 eyes. Threshold ROP was diagnosed in 80 eyes with a prevalence of 7.7% and Pre-Th reshold ROP Type 1 was diagnosed in 88 eyes with a prevalence of 8.7%. In both groups treatment were required. The largest proportion of patients with ROP by gestational age were ranged from 27 to 28 weeks group with 37. 8%, followed by the range of 29-30 weeks group in 23.6% and the 31-32 weeks group had 18.9%. 32.9% of patients with ROP were in 751 ­ 1000 g group, followed by 1001-1250 g group with 30.7%. A statistically significant diff erence was found between low birth weight, gestational age between 26 and 28 weeks, oxygen and respiratory distress. 96.6% of ROP Pre-Threshold Type 1 infants treated with Laser had a completed resolution of ROP. 3.4% required a Rescue Th erapy 15 days after initial treatment which consist of Intravitreal Inyection of Bevacizumab (0.65 mg/0.05 cc) and a second Laser treatment. Involution of ROP was achieved in all infants from this group. 93.7% of ROP Threshold infants treated with a combined treatment of Laser and Intravitreal Bevacizumab Inyection (0.65 mg / 0.05 cc). 73% of infants required a single dose of intravitreal bevacizumbab and 26.6% required 2 doses. 4 eyes progressed to Stage 4a. Conclusions: the prevalence of Threshold ROP was 7.7% and Pre-Threshold ROP Type 1 was 8.7%. A multidisciplinary management of ROP with programs of primary and secondary prevention is necessary to be implemented. Risk factors associated with ROP in our study are gestational age <28 weeks, birth weight <1250 g, oxygen and respiratory distress.

Terapia antiangiogénica ocular: experiencia clínica en México / Mexican clinical experience in ocular anti-angiogenic therapy

La angiogénesis patológica retiniana es la causa principal de pérdida visual en una gran cantidad de enfermedades: degeneración macular relacionada a la edad, retinopatía diabética y retinopatía del prematuro, en otras. Estas últimas dos son, además, problemas de salud pública en los países en desarrollo. Estudios recientes sobre la fisiopatología de estas enfermedades han demostrado el papel fundamental que los factores de crecimiento tienen sobre la angiogénesis. La terapia antiangiogénica ocular nació como un esfuerzo de inhibir la acción de estos factores sobre la angiogénesis patológica y preservar la visión. El objetivo de esta revisión es hacer un recuento de la experiencia en México en cuanto a esta modalidad terapéutica.

Retinal pathological angiogenesis is the leading cause of visual loss in a wide variety of ocular diseases. Some of the examples include: Age-related macular degeneration, diabetic retinopathy and retinopathy associated with prematurity. These last two entities are, in addition, public health problems in developing countries. Recent physiopathological studies, have demonstrated that growth factors play a key role on angiogenesis. Anti-angiogenic therapy came about as an attempt to inhibit the action of growth factors over the process of pathological angiogenesis in order to preserve vision. The objective of this review is to describe Mexico's experience using this therapeutic approach.