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Sample records for tratada con bevacizumab

  1. Bases tratadas con cemento, en California

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    Chinchilla, M.

    1962-05-01

    Full Text Available El uso de bases tratadas con cemento para autopistas se inició en el Estado de California en 1938, empleándose para carreteras con determinadas condiciones de tráfico. Inicialmente, se especificó el uso obligatorio de plantas mezcladoras para asegurar el debido control de las proporciones adecuadas.

  2. Riego subsuperficial con aguas residuales tratadas

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    Crespi, Raúl; Camacho, Emilio; Polo, María José

    2009-01-01

    La reutilización de aguas residuales tratadas para riego por goteo subsuperficial (RGS) de cultivos extensivos, es una práctica reconocida mundialmente, siendo la obturación de emisores un serio problema en la operación de estos sistemas. Durante el ciclo agrícola 2002/03, se realizó un ensayo experimental usando dos tipos de agua: limpia (AL) y residual tratada (AR) en un sistema mixto combinando un reactor biológico con laguna de maduración y tres tipos de protectores del emisor: micro dosi...

  3. VIDA COMERCIAL DE PITAHAYA AMARILLA TRATADA CON 1-MCP

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    LILIANA SERNA-COCK

    Full Text Available 1-metilciclopropeno (1-MCP, un inhibidor del etileno, ha sido utilizado para extender la vida comercial de diferentes frutas. El objetivo de este trabajo fue evaluar el efecto de la aplicación de soluciones acuosas de 10, 100 y 200 gL-1 de 1-MCP, con tiempos de exposición de 1, 5 y 10 minutos, sobre la vida comercial de pitahaya amarilla en estado de madurez 4. Durante 15 días de almacenamiento (25 ± 2°C y 75% de humedad relativa, se evaluaron cambios físicos como la pérdida de peso y la aparición de pardeamiento; y se midieron cambios químicos como sólidos solubles, pH, acidez e índice de madurez. Se presentaron diferencias significativas entre los tratamientos. Los resultados demostraron que aplicaciones de 200 gL-1 de 1-MCP durante 10 minutos prolongó por tres días, la vida comercial de la pitahaya amarilla, y redujo cambios en los sólidos solubles y la acidez

  4. PUDRICIÓN BASAL CAUSADA POR Phytophthora capsici EN PLANTAS DE CHILE TRATADAS CON VERMICOMPOST

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    Lidieth Uribe-Lor\\u00EDo

    2014-01-01

    Full Text Available Pudrición basal causada por Phytophthora capcisi en plantas de chile tratadas con vermicompost. El objetivo de este trabajo fue evaluar a nivel de invernadero el efecto de vermicompost sobre la incidencia y severidad de Phytophthora capcisi en plantas de chile (Capsicum annuum. Esta investigación se realizó entre febrero y marzo del 2012 en el Centro de Investigaciones Agronómicas, Sabanilla, San José, Costa Rica. Se utilizó un diseño completamente al azar con cuatro repeticiones y ocho plantas por unidad experimental en un arreglo factorial con los factores de dosis (0, 25% y 50% v/v vermicompost:suelo e inoculación (0 y 500 zoosporas por gramo de suelo. Se trasplantaron plántulas de 35 días, que fueron inoculadas dos semanas después del trasplante. La aplicación de vermicompost provocó un aumento significativo del peso fresco foliar y del peso seco foliar y radical; a mayor dosis, mayor fue el incremento. Las plantas de todos los tratamientos que incluyeron inoculación con P. capsici presentaron síntomas de la enfermedad en la raíz. Los valores de incidencia y severidad fueron mayores para el tratamiento con 50% de abono. En este tratamiento se presentaron síntomas de marchitez. La ausencia de diferencias en las variables de peso fresco y seco entre los tratamientos inoculados y sin inocular, a los que se adicionó abono al 25%, sugiere que esta dosis podría compensar el daño causado por el patógeno. Se observó una menor concentración de nutrimentos en los tejidos de las plantas inoculadas lo que indica que el daño causado a la raíz pudo haber afectado la adquisición de nutrimentos.

  5. Efectos del ibandronato sobre el metabolismo óseo y el perfil de riesgo cardiovascular en mujeres con osteoporosis postmenopáusica tratadas previamente con raloxifeno

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    Ferrer Piquer, Marta

    2015-01-01

    “Efectos del ibandronato sobre el metabolismo óseo y el perfil de riesgo cardiovascular en mujeres con osteoporosis postmenopáusica tratadas previamente con raloxifeno” La osteoporosis postmenopáusica es un problema sanitario mundial, dado que las fracturas por fragilidad suponen un aumento importante de morbimortalidad así como del coste económico. En los últimos años se han desarrollado nuevas terapias para el tratamiento de la osteoporosis, siendo por el momento los SERMs y los bi...

  6. Estudio comparativo de las maloclusiones de clase III tratadas con y sin cirugía

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    Martínez Asúnsolo, Pascual

    2014-01-01

    El objetivo de la presente tesis fue determinar si existen diferencias en la inclinación de los incisivos superiores e inferiores en pacientes de clase III tratados con cirugía o únicamente con “camuflaje ortodóncico”, así como su repercusión en la relación esquelética final. Para ello se realizó un estudio clínico comparativo y retrospectivo en la unidad docente de Ortodoncia del departamento de Estomatología de la Universidad de Valencia. La muestra consistió en 56 pacientes que cump...

  7. Consumo de alcohol en ratas adolescentes tratadas con reserpina y fluoxetina

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    Paul Ruiz

    2017-01-01

    Full Text Available Si bien se ha estudiado el vínculo entre los trastornos de estado de ánimo y el consumo de alcohol, tanto en humanos como en animales, todavía no es del todo claro cómo se da esta relación, y menos aún durante la adolescencia. La administración de reserpina, un depletor de monoaminas, es un modelo ampliamente utilizado en roedores adultos para inducir comportamientos asociados a depresión, pero se desconoce su utilidad en otras etapas del desarrollo. En este trabajo validamos este modelo en ratas adolescentes y posteriormente estudiamos el consumo de alcohol en estos animales, así como su modulación por antidepresivos. En el experimento 1 se administró reserpina (0.0 o 1.0 mg/kg, durante 4 días, IP a ratas Wistar machos de 30 días. El consumo de alcohol fue evaluado luego de observar comportamientos asociados a depresión e indagar indicadores neuroendocrinos de esta patología. En el experimento 2 los animales recibieron reserpina, seguida por el antidepresivo fluoxetina (0.0 o 10.0 mg/kg, durante 4 días, IG, y luego se evaluó el consumo de alcohol. Los resultados mostraron que la reserpina aumentó significativamente los comportamientos asociados a depresión y alteró los niveles de dopamina en la corteza insular y de hormonas tiroideas en sangre. En la prueba de consumo de alcohol los animales deprimidos, pero no los controles, mostraron un incremento en el consumo a través de los días. El segundo experimento replicó parcialmente este perfil, y no se observó un efecto significativo del antidepresivo en el consumo de alcohol. Los resultados indican que la reserpina es útil para modelar en ratas adolescentes comportamientos asociados a depresión. Se encontró una relación entre este estado y el consumo de alcohol, que no se pudo revertir con antidepresivos.

  8. Sorción de hidrolizados proteicos en lana tratada con bisulfito sódico: influencia en las propiedades químicas y físico-mecánicas.

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    Gómez de Paula, Ma Nieves; Naik Kardile, Arun; Juliá Ferrés, Ma. Rosa; Erra Serrabasa, Pilar

    1997-01-01

    La sorción de hidrolizados proteicos en fibras queratinicas provoca una mejora en las propiedades físicas y quimicas de fibras dañadas. En este trabajo se presentan los resultados de las modificaciones de estas propiedades en lana tratada con bisulfito sódico e hidrolizado proteico bien de colágeno o de queratina o de sus respectivos derivados anfifílicos cuaternizados y se comparan con las obtenidas para lana tratada sólo con bisulfito sódico. The sorption of protein hydrolisates in kerat...

  9. Inducción de la brotación in vitro de microplántulas de nogal (Juglans neotropica) tratadas con Thidiazuron (TDZ) y 6-Bencilaminnopurina (BAP)

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    Peña Tapia, Denisse Fabiola; Rocano Curillo, Melida Noemi; Salazar, Jazmin M.; Torres, Carlos S.; Universidad de Cuenca; Dirección de Investigación de la Universidad de Cuenca; DIUC

    2014-01-01

    El nogal (Juglans neotropica) es una especie de gran potencial para proyectos de conservación y agro-productivos en la eco-región Andina. No obstante, su baja capacidad germinativa limita su propagación para reforestación. El objetivo de este estudio fue determinar el efecto del tratamiento con Thidiazuron (TDZ) y 6-Bencilaminopurina (BAP) en la inducción in vitro de brotes de J. neotropica. Las microplántulas tratadas con BAP produjeron más brotes que aquellas tratadas con TDZ. Las microplán...

  10. Efecto inmunomodulador de la solución CM-95 tratada magnéticamente en ratones Balb/c inoculados con 5-fluorouracilo

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    Clara Martínez

    2011-04-01

    Full Text Available El 5-fluorouracilo es un antineoplásico usado en la terapia del cáncer y posee acción inmunosupresora al inhibir la proliferación de células del tejido hematopoyético. En este trabajo se evaluó el efecto inmunomodulador de la solución CM-95 tratada magnéticamente en ratones Balb/c inoculados con 5-fluorouracilo a través de su acción protectora rehabilitadora sobre parámetros celulares y tisulares del tejido hematopoyético. A los ratones, entre 20-22 g de peso y 6 semanas de nacidos, se les administró esta solución CM-95 tratada magnéticamente por vía intraperitoneal en un esquema de dos inoculaciones; luego se administró por la misma vía el 5_fluorouracilo a una dosis de 150 mg/m2 de superficie corporal de cada ratón. Se evaluó el conteo total y diferencial de leucocitos antes de inocular el 5-fluorouracilo, y a los tres y siete días de aplicado este. La celularidad de médula ósea y bazo y la observación microscópica del corte histológico de hígado y bazo por la técnica de inclusión en parafina y tinción con eosina hematoxilina al 10% se evaluaron a los siete días de haber aplicado el 5- fluorouracilo. La solución CM-95, tratada magnéticamente, logró modular los efectos del 5-fluorouracilo con una actividad protectora rehabiltadora, para los parámetros evaluados en médula ósea, sangre periférica, bazo e hígado. Estos resultados abren nuevas perspectivas para la aplicación del sistema acuoso tratado magnéticamente como inmunomodulador.

  11. MODELADO DE LA CINÉTICA DE SECADO DE MANGO PRE-TRATADAS CON DESHIDRATACIÓN OSMÓTICA Y MICROONDAS

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    MARIBEL GARCÍA-PATERNINA

    Full Text Available La aplicación de tecnologías complementarias como la deshidratación osmótica y microondas como pre-tratamientos al secado convencional contribuye al desarrollo de nuevos productos y favorece la disminución de los cambios físico-químicos y organolépticos en el mango. El objetivo del trabajo fue evaluar el efecto de la deshidratación osmótica con una solución a 65°Brix de 37 a 40°C por 60 min, tratamiento con microondas a 560 W por 7 min y combinado como pre-tratamientos al secado de hojuelas de mango a 70°C en una estufa tipo bandeja y al sol. Las muestras de mango con 11 a 14°Brix y humedad del 80% fueron dimensionadas a 1x1x0,4 cm. La pérdida de peso y el tiempo de secado en los pre-tratados presentaron diferencias significativas (p0,99 se ajustó para el secado sin pre-tratamiento y el modelo de Vermet et al. (R²>0,99 para los pre-tratados. La De ff para microondas y secado en estufa fue mayor. Las hojuelas de mango pre-tratadas con deshidratación osmótica fueron las que mejor conservaron la apariencia de las hojuelas de mango

  12. Effective treatment of common variable immunodeficiency associated diarrhea Diarrea asociada a inmunodeficiencia común variable tratada con budesonida

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    H. Córdova Guevara

    2009-03-01

    Full Text Available Common variable immunodeficiency disorder (CVID, the commonest symptomatic primary antibody deficiency syndrome, is characterised by recurrent bacterial infections, particularly of the upper and lower airways; it is also associated with an increased incidence of autoimmune and neoplastic disorders. CVID has a high prevalence of infectious, inflammatory and neoplastic gastrointestinal diseases. Up to 60% of the patients with non-treated CVID develop diarrhea and 10% associated idiopathic malabsorption with weight loss. The case of a 50-year-old woman with CVID-associated diarrhea, abdominal pain and bloating of one year's duration is reported. An exhaustive evaluation made for secondary causes of her symptoms was unrevealing; she was treated with loperamide and diet, without improvement. She later followed a course of oral budesonide for 3 months; her clinical symptoms disappeared and her quality of life improved. In conclusion, we report the case of a patient with CVID-related chronic diarrhea who responded well to oral budesonide treatment. This outcome provides the gastroenterologist with a new therapeutic option in this difficult group of patients.La inmunodeficiencia común variable (IDCV es la deficiencia primaria de anticuerpos sintomática más frecuente y está caracterizada por infecciones bacterianas recurrentes, especialmente de las vías aéreas superiores e inferiores, y también asociada a incremento de enfermedades autoinmunes y neoplasias. Presenta alta prevalencia de enfermedades gastrointestinales infecciosas, inflamatorias y neoplásicas. Hasta el 60% de los pacientes con IDCV no tratados desarrollan diarrea y el 10% desarrollan malabsorción idiopática asociado a pérdida de peso. Presentamos el caso de una mujer de 50 años con IDCV que presenta diarrea crónica, con dolor y distensión abdominal desde hace 1 año. Realizándose múltiples exploraciones y descartando causas secundarias de diarrea crónica, se inicia

  13. Maduración poscosecha de la feijoa (Acca sellowiana Berg tratada con CaCl2 en tres temperaturas de almacenamiento

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    Ramírez Juan Manuel

    2005-06-01

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    Con la finalidad de comprobar los efectos retardantes del calcio en la maduración de los frutos de feijoa (Acca sellowiana Berg, cultivar Quimba, se realizó un estudio sobre la aplicación poscosecha, mediante inmersiones de tres soluciones distintas de cloruro de calcio (5%, 10% y 15% y un testigo. La aplicación de CaCl2 prolongó la vida de almacenamiento de los fru­tos, ya que los tratamientos permitieron a los frutos so­portar las condiciones de almacenamiento. Se observó un efecto importante en la disminución de las pérdidas de peso; los frutos tratados con el porcentaje de calcio más alto (15% presentaron las menores pérdidas de peso en cada temperatura. En las fejioas almacenadas a temperatura ambiente (18° C, se observó que la in­cidencia de enfermedades fue más pequeña en los fru­tos tratados con CaCl2. La velocidad de pérdida de la firmeza de los frutos también se vio fortalecida por la adición de calcio. Con relación a las propiedades quí­micas de los frutos, no se presentaron diferencias sig­nificativas entre los tratamientos con cloruro de calcio para cada temperatura de almacenamiento; las feijoas tratadas con CaCl presentaron niveles superiores de sólidos solubles totales, a pesar de no ser significativos estadísticamente.

  14. Estudio de la sorción de hidrolizados proteicos en lana tratada con tioglicolato amónico. Parte 1: Influencia en las propiedades químicas.

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    Gómez de Paula, Ma Nieves; Naik, Arun; Juliá Ferrés, Ma. Rosa; Erra Serrabasa, Pilar

    1995-01-01

    La sorción de hidrolizados proteicos anfifílicos en fibras queratínicas produce mejoras en relación con las propiedades químicas y físicas de fibras dañadas aportando, además, nuevas cualidades. En este trabajo se presentan las modificaciones químicas, tales como solubilidad en álcali y en urea-bisulfito, causadas en lana tratada con tioglicolato amónico e hidrolizado proteico bien de colágeno, de queratina o de sus respectivos derivados anfifilicos cuaternizados y se comparan con las obtenid...

  15. Estabilidad de espumas formuladas con proteínas de soja tratadas a pH ácido

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    Cecilia Abirached

    2011-05-01

    Full Text Available Se estudió la influencia del tratamiento a pH ácido de aislados proteicos de soja sobre las propiedades espumantes mediante el análisis de las constantes cinéticas de desproporción y drenado y el relacionamiento de éstas con los parámetros de reología interfacial. Los aislados proteicos de soja fueron obtenidos a partir de harina desgrasada. Una porción se llevó a pH 8,0 y otra porción se trató a pH 2,0. De la porción a pH 2,0 una parte se dejó a este pH y otra parte se neutralizó a pH 8,0. Todas las porciones se liofilizaron. Para la identificación y caracterización estructural de las muestras se realizaron análisis de electroforesis desnaturalizante, calorimetría diferencial de barrido, solubilidad e hidrofobicidad superficial. Se obtuvieron espumas por el método de burbujeo de gas. Se determinó la velocidad inicial de pasaje de líquido a la espuma y el volumen máximo de líquido incorporado a la espuma. El proceso de desestabilización de las espumas formadas se analizó ajustando los datos obtenidos a una cinética de segundo orden bifásica. Se realizaron estudios de reología interfacial con un tensiómetro de gota. El tratamiento a pH ácido mejoró tanto la espumabilidad como la estabilidad de las espumas. La proporción de líquido drenado por escurrido gravitatorio fue significativamente superior al volumen drenado debido a la desproporción. El tratamiento a pH 2,0 redujo la desestabilización por desproporción de Ostwald, lo que sugiere la formación en la interfase de una película más cohesiva, que se confirma con los parámetros de reologíainterfacial.

  16. Estudios sobre la reactividad de harinas crudas de cemento tratadas con rápidos y diferentes calentamientos

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    Weisweiler, W.

    1988-09-01

    Full Text Available Not available.

    Estudios experimentales llevados a cabo a una temperatura dada de calcinación, sirvieron para observar el efecto de las altas velocidades de calentamiento sobre las reacciones del clinker. Mientras que un aumento de la reactividad de los materiales fue claramente detectada cuando la velocidad pasó de 20 K/min a tomar valores iguales y mayores a 100 K/min, un negativo efecto sobre el Tiempo de Reacción Completa o "Período de Calcinación a Punto" no pudo ser establecido. Considerando además que el tiempo necesario para llevar a la materia prima hasta la temperatura de reacción, es necesariamente un tiempo inefectivo, podrían las plantas productoras de cemento obtener mayores rendimientos en tiempo y espacio, utilizando altas cuotas de calentamiento. Estudios de microscopía probaron que con el aumento de las velocidades de calentamiento, hubo una mayor generación de microcristales incidiendo directamente sobre la molienda y calidad del clinker. [de] Untersuchungen zur Reaktivität van zementrohmehlen nach verschieden schneller Aufheizung. Modellversuche mit linearen Aufheizgeschwindigkeiten solten zeigen, ob bei einer vorgegebenen Brenntemperatur die Verklinkerungsreaktionen beeinfluβt werden können. Während eindeutige Steigerungen der Kalkbindungsraten lediglich zwischen 20 K/min und Aufheizgeschwindigkeiten >=100 K/min nachweisbar waren, konnten negative Auswirkungen auf die Garbranddauern bei keiner Versuchsserie festgestellt werden. Unter Berücksichtigung der zur Aufheizung der Rohstoffe notwendigen Totzeiten, können bei den technischen Zementproduktionsanlagen nach schneller Aufheizung höhere Raum-Zeit-Ausbeuten erreicht werden. Mikroskopische Untersuchungen ergaben, daβ durch Erhöhung der Aufheizraten der Anteil mikrokristalliner Klinkerphasen zunimmt, was sich direkt aut die Zementklinkermahibarkeit und die Klinkerqualität aswirkt.

  17. Adult height in Turner syndrome girls after long-term growth hormone treatment Talla adulta en pacientes con síndrome de Turner tratadas con hormona de crecimiento a largo plazo

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    Analía Morín

    2009-10-01

    Full Text Available We studied the adult height (AH outcome, and factors likely to influence it, in Turner Syndrome (TS girls treated with growth hormone (GH. A total of 25 TS girls treated with GH were compared with 10 TS girls not treated with GH. The percentage of girls who achieved normal third percentile was determined. Projected AH (PAH was calculated according to height standard deviation score (HSDS at the beginning of the treatment. Gain in height was determined as: AH - pretreatment PAH. The percentage of girls who achieved target range (midparental height±2 SD was determined. Multiple linear regression models were fitted on baseline variables- chronological age (CA, midparental height (MPH and HSDS; and treatment variablesduration of oestrogen-free GH therapy and duration of GH therapy+oestrogens. As for baseline data: median CA was 13.0 years (5.6-15.8. Mean HSDS was 0.25±1.1 SDS. PAH was 139.2±5.6 cm. MPH was 160.0±5.0 cm. As for follow up data: Median CA at onset oestrogens was 15.1 years (13.2-16.6. Median duration of GH therapy was 3.8 years (2.1-10.3. Median oestrogen-free GH period was 2.0 years (0.7-7.8, and median GH+oestrogens period, 1.8 years (1.0-3.2. Adult height: Mean AH was 150.4±7.0 cm in treated patients and 140.8±7.2 cm in the group not treated with GH (p=0.001. Fourteen (56% girls achieved normal third percentile compared with an initially predicted 1 (4%. Gain in height was 11.2±3.7 cm. Thirteen (59% girls reached an AH within target range. HSDS at the beginning of the treatment was the variable most strongly related to AH and duration of oestrogen-free GH period was the variable most strongly related to gain in height.Se estudió la talla adulta (TA y los factores que pudieran influenciarla en niñas con síndrome de Turner (ST tratadas con hormona de crecimiento (HC. Se compararon 25 pacientes con ST tratadas con HC y 10 niñas no tratadas. Se determinó: el porcentaje de niñas que alcanzó el tercer percentilo de la curva

  18. Atenuación del efecto hepatotóxico del tetracloruro de carbono en ratas tratadas con Polypodium polypodiodes

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    Isis B Bermúdez Camps

    1999-08-01

    Full Text Available Se comprobó experimentalmente en ratas la utilidad del Polypodium polypodiodes en la atenuación del efecto hepatotóxico provocado por el tetracloruro de carbono, que origina un incremento del nivel de los peróxidos lipídicos y las transaminasas sanguíneas. Se logró una disminución de la transaminasa glutamicopirúvica por debajo de los niveles normales con la administración del extracto de la planta a una dosis de 300 mg/kg de peso corporal. Los peróxidos lipídicos y la transaminasa glutamicooxalacética reducen su actividad, pero no notablemente, lo cual evidencia que el daño hepático persiste a pesar de la recuperación parcial. Los resultados fueron confirmados por un estudio anatomopatológico. Se determinó la toxicidad aguda por vía oral del extracto de la planta y se observó que la DL50 se encuentra por encima de 1 g/kg, por lo que puede considerarse esta preparación como relativamente inocua en los animales de experimentación.The benefits of Polypodium polypodiodes in reducing hepatotoxic effects caused by carbon tetrachloride which gives rise to increased level of lipid peroxides and blood transaminase were tested in rats under lab conditions. Glutamicpiruvic trnnsaminane level was lower tham the normal lavels due to the administration of a 300 mg/kg dosege of the plant extract. The activities of both lipid peroxides and glutamicoxalacetic transaminase were reduced but not in a remarkable way showing that the hepatic damage is still present despite the partial recovery. The results were confirmed using and anatomytological study. Lidewise, acute toxicity resulted from oral administration of plant extrac was determined. It was observed that DL50 level was over 1g/kg, so this preparation may be considered relatively harmless in lab animals.

  19. Síndrome serotoninérgico en anciano con falla renal crónica tratada con linezolid: reporte de caso

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    Mauricio Montoya Cañón

    2016-04-01

    Entre los factores de riesgo para desarrollo de síndrome serotoninérgico se encuentra el uso de linezolid, que en combinación de otros medicamentos con acción serotoninérgica —como los inhibidores selectivos de recaptación de serotonina, el litio, la trazodona, entre otros— se asocia con la presentación de este cuadro. El síndrome serotoninérgico puede ser evitado con una buena educación al personal médico y la modificación de las conductas de prescripción de medicamentos; el pilar del tratamiento se basa en la suspensión de los fármacos que están causando el cuadro y el planteamiento de medidas de soporte.

  20. Estudio de nuevos procedimientos de elaboración de aceitunas verdes tratadas con álcali, no fermentadas, conservadas mediante tratamientos térmicos

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    Montaño, Alfredo

    2007-09-01

    Full Text Available Two new procedures for the elaboration of alkali-treated green table olives, without fermentation, preserved by sterilization or pasteurization were studied. In each case, the aim was to obtain a product with good quality and guaranteed safety. In the sterilized product, it was demonstrated that by including a pitting step during elaboration, a product was obtained with both flavour and texture similar to those of «green ripe olives», but without the need to apply an excessive number of washes. Alkalizing agents added to the packing solution negatively affected the organoleptic olive properties. In case of the pasteurized product, a pitting step during elaboration was also demonstrated to be effective in improving olive flavour. Fruit texture was not significantly affected by this step. Both herbal extracts and monosodium glutamate added to the packing solution successfully masked the «cooked» flavour of olives associated with pasteurisation.En el presente trabajo se han estudiado dos nuevos procedimientos para la elaboración de aceitunas verdes tratadas con álcali no fermentadas, conservadas por esterilización o pasterización, con el objetivo de obtener, en cada caso, un producto de calidad adecuada y de total garantía en cuanto a seguridad. En el producto esterilizado, se demostró que la inclusión de una etapa de deshuesado durante la elaboración conseguía un sabor y textura similares a las aceitunas denominadas «green ripe olives», pero sin necesidad de aplicar un excesivo número de lavados. Sin embargo, la adición de agentes alcalinizantes afectó negativamente a las características organolépticas de este producto. En el caso del producto pasterizado, el deshuesado del fruto consiguió también una notable mejora del sabor sin afectar significativamente a la textura. La adición de extractos de hierbas aromáticas o de glutamato monosódico a la salmuera de envasado enmascaró el característico sabor a

  1. ESTUDIO DEL EFECTO COMPARATIVO SOBRE EL DOLOR Y LAS PARESTESIAS EN LA NEUROPATIA DIABETICA TRATADA CON ACUPUNTURA CON DOS FORMULAS DE PUNTOS

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    MUNOZ SAMAYOA, ENRIQUE

    2010-01-01

    LA NEUROPATIA DIABETICA ES UN DESORDEN CIRCULATORIO RELACIONADO CON LAS ALTERACIONES EN LA PERCEPCION SOMATOSENSITIVA, ES LA CAUSA DE DOLOR Y SENSACIONES PARESTESICAS. EL OBJETIVO DE ESTE TRABAJO ES DEMOSTRAR EL EFECTO ANALGESICO DE LA ACUPUNTURA EN EL MANEJO DE LA NEUROPATIA DIABETICA Y COMPARAR EL EFECTO EN LA REDUCCION DEL DOLOR Y DE LAS PARESTESIAS USANDO ZUSANLI E36, SANYINJIAO B6, XUEHAI B10, TAICHONG H3 COMO SELECCION ESTANDAR DE LOS ACUPUNTOS CONTRA LOS MISMOS PUNTOS MAS YUANYUE ...

  2. Dispensación en farmacia comunitaria a pacientes con osteoporosis postmenopáusica tratadas con bifosfonatos o ranelato de estroncio

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    Moranta Ribas F

    2011-09-01

    Full Text Available INTRODUCCIÓN La osteoporosis es una enfermedad que afecta sobre todo a las mujeres postmenopaúsicas. La estrategia terapéutica se basa en la administración de bifosfonatos o ranelato de estroncio con un aporte adecuado de calcio y vitamina D. En este estudio hemos evaluado el papel del farmacéutico comunitario en la mejora del conocimiento y proceso de uso de estos fármacos en relación al servicio de dispensación. MÉTODOS Estudio descriptivo transversal realizado en doce oficinas de farmacia de Mallorca, por dieciocho farmacéuticos comunitarios, entre el 17 de mayo y el 6 de junio de 2010. La población a estudio fueron mujeres en tratamiento para osteoporosis postmenopáusica con bifosfonatos o ranelato de estroncio. Los datos obtenidos se recogieron durante el proceso de dispensación de los medicamentos mencionados a las pacientes que aceptaron participar en el estudio, en un cuestionario diseñado a tal efecto. RESULTADOS/DISCUSIÓN De las 112 pacientes participantes en el estudio, sólo un 35,7% habían recibido información del farmacéutico comunitario durante la dispensación. De éstas, un 91,2% utilizaba correctamente el tratamiento para la osteoporosis, un 70% conocía la ingesta recomendada de calcio, un 65% no presentó ningún problema relacionado con el medicamento (PRM y, finalmente, ninguna de ellas presentó interacción alguna. Aunque el porcentaje de pacientes informadas durante la dispensación es bajo, la efectividad es más alta que la ofrecida por otros profesionales, como médicos especialistas o de familia, por lo que todas las pacientes deberían recibir el servicio de dispensación, independientemente de que ya hayan sido informadas por los médicos prescriptores.

  3. Displasia fibrosa maxilar poliostótica en paciente tratada con pamidronato: a propósito de un caso Maxilar polyostotic fibrous dysplasia treated with pamidronate: A case report

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    José María López-Arcas

    2011-06-01

    Full Text Available El término displasia fibrosa hace referencia a un conjunto de lesiones óseas benignas que se caracterizan por la sustitución del tejido óseo normal por tejido conectivo. Se presenta el caso de una paciente afectada de displasia fibrosa poliostótica de predominio maxilar tratada de forma conservadora con bisfosfonatos.The term fibrous dysplasia refers to a variety of bony diseases characterized by the substituion of the bone by abnormal connective tissue. A case report of patient affected by a polyostotic form of fibrous dysplasia with an uneven evolution of its disease after being treated with pamidronate is presented.

  4. Solución adyuvante CM-95 tratada magnéticamente en comparación con el adyuvante de Freund para la obtención del suero de Coombs en conejo

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    Clara Martínez

    2009-12-01

    Full Text Available En este trabajo se evaluó la aplicación de la solución CM-95 tratada magnéticamente como adyuvante inmunológico, en comparación con el adyuvante de Freund, para la obtención del suero de Coombs en conejos, de gran demanda en bancos de sangre y hospitales, para el diagnóstico clínico de conflictos Rh y la enfermedad hemolítica del recién nacido, entre otras. Conejos Nueva Zelanda Blancos se inocularon por la vía subcutánea con suero humano obtenido de 30 donantes O+, unido con la solución CM-95 tratada magnéticamente como adyuvante inmunológico. Se empleó un esquema de inmunización de 40 días, donde se evaluó la dinámica en el título de anticuerpos anti IgG humano por la técnica de hemoaglutinación en tubos. Al antisuero se le determinó la calidad inmunológica por el título de heteroaglutininas de los grupos sanguíneos A, B y O, de anticuerpos anticomplemento C3b, C3d y C4b y anti IgG, antes y después de su purificación. El suero de Coombs con la solución adyuvante CM-95 tratada magnéticamente mostró valores similares a los obtenidos con el adyuvante de Freund. En el mismo se cumplió con los requisitos establecidos por el Centro Estatal para el Control de la Calidad de los Medicamentos, según las normativas de la FDA para este diagnosticador. Estos resultados abren nuevas perspectivas para el uso de la solución adyuvante en la obtención del suero de Coombs.

  5. Fibrilação ventricular durante atividade esportiva tratada com sucesso Fibrilación ventricular durante actividad deportiva tratada con êxito Ventricular fibrillation during sport activity successfully treated

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    Maria Margarita Gonzalez

    2009-08-01

    Full Text Available A sobrevida após parada cardio-respiratória extra-hospitalar é estimada em menos de 5%. Apresentamos um caso de fibrilação ventricular, durante atividade esportiva. Ressuscitação cardio-pulmonar foi iniciada precocemente por pessoa leiga, e desfibrilação foi realizada em menos de três minutos, com desfibrilador externo automático, com sucesso. O programa de acesso público à desfibrilação tem aumentado a sobrevida após fibrilação ventricular extra-hospitalar. Devemos estimular o treinamento de pessoas leigas com relação ao uso de desfibriladores externos automáticos e o programa Suporte Básico de Vida, incentivando a implementação deste em locais com grande afluxo de pessoas e locais com risco elevado de ocorrer morte súbita, a exemplo de centros esportivos.La sobrevida tras una parada cardiorrespiratoria extrahospitalaria se estima en menos del 5%. Presentamos un caso de fibrilación ventricular durante actividad deportiva La resucitación cardiopulmonar fue iniciada precozmente por personal no técnico, y la desfibrilación se realizó en menos de tres minutos, con desfibrilador externo automático, con éxito. El programa de acceso público a la desfibrilación aumentó la sobrevida después de la fibrilación ventricular extrahospitalaria. Debemos estimular la capacitación de personas no técnicas con relación al uso de desfibriladores externos automáticos y el programa Soporte Básico de Vida, incentivando la implementación del mismo en locales con gran afluencia de personas y locales con riesgo elevado de ocurrencia de muerte súbita, como es el caso de los centros deportivos.Survival after out-of-hospital cardiopulmonary arrest is estimated at less than 5%. We report a case of ventricular fibrillation during sports activity. Cardiopulmonary resuscitation was initiated early by a layperson, and defibrillation was successfully performed within less than three minutes, with an automated external defibrillator. The

  6. Desensitization with ciprofloxacin in a patient with partially treated urinary tract infection Desensibilización con ciprofloxacina en una paciente con infección urinaria parcialmente tratada

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    Zulma Reina Cutta

    2010-02-01

    norfloxacina, la ciprofloxacina y la ofloxacina contra estreptococos y algunos anaerobios es limitada; tienen, además, buena biodisponibilidad oral y adecuada penetración en los tejidos. Se presentan reacciones características de hipersensibilidad aproximadamente en 1 por cada 50.000. tratamientos. Se describe un caso de desensibilización oral exitosa con ciprofloxacina en una paciente con infección urinaria crónica parcialmente tratada. Esta es la primera desensibilización con quinolonas reportada en Colombia.

  7. Litiasis única en vesícula doble tratada con ondas de choque extracorpórea Single lithiasis in double gallblader treated with extracorporeal shock waves

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    Domingo Pérez González

    2004-06-01

    Full Text Available La vesícula biliar doble es una anomalía congénita poco frecuente. Su diagnóstico puede realizarse con ultrasonido y colecistografía. Se presenta una paciente de 27 años de edad, con antecedentes de intolerancia a las grasas y cólicos biliares a repetición, con vesícula duplicada; exteriormente fundida y dos conductos císticos independientes que desembocan en el hepatocolécodo, con un cálculo único, de 12 mm de diámetro, retrotransparente y 0 unidades Houndfield, ubicado en el cuello de la vesícula más desarrollada. Se aplicaron 2 259 ondas de choque extracorpóreas de 20,4 kilovoltios, generadas por el principio electromagnético; en una sesión de litroticia. Se detuvo fragmentación completa del cálculo. El tratamiento fue ambulatorio. La paciente se reincorporó a su vida laboral a las 24 horas. Durante la expulsión de los fragmentos tuvo varias crisis de dolor que cedieron con analgésicos orales. A los 6 meses, la vesícula afectada se encontraba libre de fragmentos y funcional. No existió complicación y hasta el momento se mantiene asintomáticaDouble gall bladder is an uncommon congenital abnormality. It may be diagnosed by ultrasound and cholecystography. It is reported the case of a 27-year-old patient with history of intolerance to fats and repeated biliary cholics, with duplicated gallbladder externally fused, and two independent cystic ducts flowing to the hepatocholedoco with a single calculus of 12 mm of diameter, retrotransparent and 0 Houndfield units, located in the neck of the more developed gallbladder. 2 259 extracorporeal shock waves of 20.4 kilovolts generated by the electromagnetic principle were applied in a lithotripsy session. The complete fragmentation of the calculus was stopped. The treatment was ambulatory. The patient reincorporated to her working life at 24 hours. During the expulsion of the fragments, she had several pain crises that were resolved with oral analgesics. Six months later, the

  8. Relación de glutatión reducido/oxidado (GSH/GSSG en ratas diabéticas tratadas con maca (Lepidium meyenii walp

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    Ruth Cisneros

    2011-04-01

    Full Text Available Introducción: La diabetes mellitus y sus complicaciones representan un problema de salud pública. La hiperglucemia desencadena efectos bioquímicos dañinos para el organismo, como el estrés oxidativo y el proceso inflamatorio crónico, por lo que el uso de plantas medicinales con elevada capacidad antioxidante, como Lepidium meyenii Walp (maca, es una alternativa en el tratamiento de esta patología. Objetivo: Determinar si la ingestión de harina de maca mejora la relación glutatión reducido/oxidado (GSH/GSSG en ratas diabéticas. Diseño: Experimental. Institución: Centro de Investigación de Bioquímica y Nutrición, Facultad de Medicina, UNMSM, Lima, Perú. Material biológico: Harina de maca amarilla y ratas albinas Holtzman machos adultas. Intervenciones: Se utilizó 24 ratas, a los cuales se les indujo la diabetes con estreptozotocina (STZ 40 mg/kg de masa corporal y que fueron distribuidas aleatoriamente en cuatro grupos, de seis animales cada uno: control (CO, glibenclamida (GL 10 mg/kg de masa corporal, maca 4 g/día (M4 y maca 6 g/día (M6; el experimento duró 40 días. Se evaluó la glicemia, masa corporal y, al final del experimento, se determinó los niveles de GSH y GSSG en plasma y homogenizado de hígado. Principales medidas de resultados: Masa corporal, glicemia, GSH y GSSG en plasma y homogenizado de hígado. Resultados: A nivel plasmático, el glutatión circulante estuvo favorecido para la forma reducida. Los valores de la relación GSH/GSSG en los grupos tratados con maca estuvieron alrededor de 190, significativamente mayor al grupo CO. Conclusiones: La administración de harina de maca amarilla a ratas diabéticas incrementó la relación GSH/GSSG a nivel plasmático, contribuyendo a mejorar su estado redox.

  9. Evaluación citológica de la papilomatosis incipiente del paladar tratada con láser en portadores de prótesis

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    Milagros Calzado de Silva

    2002-04-01

    Full Text Available Se realizó un estudio prospectivo y longitudinal, consistente en la descripción citológica (tipo celular, porcentaje y variaciones del núcleo, citoplasma y fondo de lámina de las muestras obtenidas en 20 pacientes con papilomatosis incipiente del paladar duro, diagnosticados y atendidos en la consulta de Detección Precoz del Cáncer Bucal de la Clínica Estomatológica Provincial Docente de Santiago de Cuba, que reunieron criterios de inclusión para dicha entidad. Las muestras obtenidas por raspado a ambos lados de la mucosa fueron leídas al inicio del tratamiento a los 3, 6, 9, 12, 15 y 18 días para evaluar la recuperación epitelial bajo los efectos del láser infrarrojo de arsenurio de galio y aluminio, con dosis de 6 J/cm2 durante 12 a 15 sesiones. Las células intermedias de la mucosa mostraron el mayor nivel de multiplicación, la recuperación epitelial, según promedio de cambio celular, resultó más rápida en los casos de menos números de sesiones y el tiempo medio de recuperación fue indicado en esta muestra a partir del tercer día de evaluación citológica.A prospective longitudinal study consisiting in the cytological description (cellular type, percentage and variations of the nucleus, citoplasma and laminar fundus of the samples obtained from 20 patients with incipient papillomatosis of the hard palate that were diagnosed and treated at the Consulting Room of Early Detection of Oral Cancer of the Provincial Teaching Dental Clinic, in Santiago de Cuba, was conducted. Inclusion criteria were gathered for this entity. The samples obtained by curettage on both sides of the mucosa were read at the beginning of the treatment at 3,6, 9, 12, 15 and 18 days to evaluate the epithelial recovery under the effects of the infrared laser of gallium and alluminum arsenid at doses of 6 J/cm3 during 12 to 15 sessions. The intermediate cells of the mucosa showed the highest level of multiplication. The epithelial recovery according to

  10. Comportamiento de la poblacion de Avena fatua tratada con graminicidas postemergentes Effect of post-emergence graminicides on the control of Avena fatua

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    V.F. Juan

    1995-01-01

    Full Text Available En el sudoeste bonaerense de la República Argentina, avena fatua es una maleza que ocupa una significativa proporción del banco de semillas presentes en el suelo, causando severas pérdidas de rendimiento en los cultivos de trigo, lo cuál la caracteriza como una maleza invasora. A pesar de que en los cultivos, se utilizan normalmente prácticas de control com graminicidas selectivos, se observa una alta incidencia de la población de Avena fatua a través de la determinación del número de panojas y semillas por metro cuadrado remanentes de las plantas que escapan al control y que alcanzan el estado reproductivo antes de la cosecha del cereal. El objetivo de este estudio fue evaluar el efecto de varios graminicidas postemergentes selectivos para el cultivo de trigo sobre el crecimiento de la población de Avena fatua por metro cuadrado en un diseño estadístico de bloques al azar con cuatro repeticiones. Los tratamientos fueron los siguientes: testigo sin control, tralkoxydim (150 y 200 g/ha, fenoxaprop-p-etil (69 y 83 g/ha, pirifenop-n-butil (50 y 55 g/ha y diclofop metil (510 y 570 g/ha. En la primer campaña, con una baja infestación de la maleza (153 plantas/m2, todos los herbicidas y dosis probadas ejercieron una drástica reducción de los parámetros evaluados, no detectándose diferenciais significativas entre sí al evaluar el control por medio del número de panojas y semillas producidas por las plantas que escaparon al control. En cambio en la Segunda campaña com 285 plantas/m2 y habiéndoses realizado la aplicación delos avenicidas en un estado fenológico de la maleza más avanzado, el número de semilhas por metro quadradofue reducido a niveles que oscilaron entre un 60% y un 95% respecto del testigo sin control, detectándose diferencias entre los tratamientos. No obstante la reducción lograda, se comprobó en ciertos casos, un importante aporte de semillas que anualmente retornan al suelo, lo que podría significar sino

  11. Endocarditis due to vancomycin-resistant Enterococcus raffinosus successfully treated with linezolid: case report and review of literature Endocarditis por Enterococcus raffinosus resistente a vancomicina exitosamente tratada con linezolid: caso clínico y revisión de la literatura

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    A. Jasovich

    2008-12-01

    Full Text Available Enterococcus raffinosus is scarcely found in clinical samples and even less frequently as etiologic agent of endocarditis. We are herein presenting one case of mitral prosthetic-valve endocarditis in a 77-y-o male due to a vancomycinresistant Enterococcus raffinosus isolate, successfully treated with 6 weeks of linezolid, and a two-year follow up.Enterococcus raffinosus es una especie poco frecuente en materiales clínicos y menos aún como agente etiológico de endocarditis. En este trabajo se presenta un caso de endocarditis de válvula mitral protésica en un paciente de 77 años debida a Enterococcus raffinosus resistente a vancomicina y que fue exitosamente tratada con linezolid durante 6 semanas, con un seguimiento de 2 años.

  12. Descompensación distal postoperatoria (D.D.P. en curvas lenke 1a tratadas con tornillos pediculares: una revisión de 63 casos Descompensação distal pós-operatória (DDP em curvaturas lenke 1a tratadas com parafusos pediculares: análise de 63 casos Postoperative distal decompensation (PDD in lenke 1a curvatures treated with pedicular screws: analysis of 63 cases

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    Norberto Ventura

    2012-06-01

    Full Text Available OBJETIVO: Identificar los factores de riesgo de descompensación distal postoperatoria (D.D.P. y definir una estrategia quirúrgica segura en curvas tipo Lenke 1A tratadas con tornillos pediculares. MÉTODO: Estudio radiológico retrospectivo de 63 pacientes con escoliosis Lenke 1A, con un seguimiento mínimo de un año. Se evaluó, edad, sexo, grados Cobb, signo de Risser, relación de la vértebra distal instrumentada (V.D.I. con la vértebra distal de la curva (V.D., vértebra estable (V.E. y con la vértebra, cuya distancia a la línea central vertical al sacro (L.V.S. era superior a 10 mm "distancia vertebral" (D.V.. RESULTADOS: 8 casos (12,7% desarrollaron D.D.P. El signo de Risser fue 0 en 2 pacientes (25% y I en 2 pacientes (25%. Relación de V.D.I. con V.D.: 4 pacientes (50% mismo nivel (V.D. +0, 4 pacientes (50% un nivel caudal (V.D. (+1; relación V.D.I. con V.E.: 5 pacientes (62,5% 2 niveles cefálicos (V.E -2, 3 pacientes (37,5% 1 nivel cefálico (V. E.-1; relación V.D.I. con D.V.: 5 pacientes (62,5% un nivel cefálico D.V. (-1, 3 pacientes mismo nivel (D.V.+ 0. CONCLUSIONES: Riesgo de descompensación distal postoperatoria: V.D.I. mismo nivel V.D. (V.D. + 0, 2 niveles cefálicos V.E. (V.E.-2, 1 nivel cefálico D.V. (D.V. -1. Estrategia quirúrgica curvas Lenke 1A: V.D.I: 1/2 niveles caudales a V.D. (V.D. +1/+2, un nivel cefálico a V.E. (V.E -1, mismo nivel D.V. (D.V. +0.OBJETIVO: Identificar os fatores de risco de descompensação distal pós-operatória (DDP e definir estratégia cirúrgica de segurança em curvaturas de Lenke 1A, tratadas com parafusos pediculares. MÉTODO: Estudo radiológico retrospectivo de 63 pacientes com escoliose Lenke 1A, com acompanhamento mínimo de um ano. Os parâmetros avaliados foram idade, sexo, graus do ângulo de Cobb, sinal de Risser, relação da vértebra distal instrumentada (VDI com a vértebra distal da curvatura (VD, com a vértebra estável (VE e com a vértebra cuja distância da linha

  13. Efectos a corto plazo de la expansión ortopédica del maxilar tratada con un láser de baja intensidad en dentición mixta

    OpenAIRE

    García García, Valentín Javier

    2016-01-01

    OBJETIVOS: Establecer un patrón de tensión acumulada en diferentes partes de un disyuntor tras realizar una expansión rápida del maxilar (ERM) y relacionarlo con los diferentes patrones de crecimiento vertical. El estudio clínico fue realizado con 40 pacientes que presentabanmordida cruzada posterior y requerían una ERM. A continuación, se desarrolló un modelo de elementos finitos (MEF) de las fuerzas que se soportan tras una ERM, validando los datos con un test mecánico y posteriormente...

  14. Desenvolvimento puberal em meninas tratadas de LLA

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    Monteiro I.M.M.

    1998-01-01

    Full Text Available OBJETIVO: Com o objetivo de avaliar o desenvolvimento puberal após o tratamento de leucemia linfóide aguda (LLA na infância, foi realizado um estudo retrospectivo, em meninas tratadas de janeiro de 1980 a janeiro de 1991, no Centro de Investigações Hematológicas "Dr. Domingos A. Boldrini", em Campinas-SP. CASUÍSTICA E MÉTODO: Foram selecionadas 42 meninas, tratadas antes da puberdade com quimioterapia sistêmica e intratecal e radioterapia cranial, utilizando doses de 18 ou 24 Grays (Gy. RESULTADOS: As idades médias da telarca, pubarca e menarca foram inferiores às do grupo-controle, embora com significância estatística apenas para a idade da telarca. Não houve diferenças entre os grupos tratados com 18 ou 24Gy. As meninas tratadas antes dos cinco anos de idade apresentaram idade média da menarca estatisticamente inferior àquelas tratadas após cinco anos e em relação ao grupo-controle. CONCLUSÃO: Os resultados mostraram que o desenvolvimento puberal em meninas tratadas de LLA na infância foi mais precoce que o de meninas saudáveis.

  15. Resultado de las quemaduras tratadas mediante cultivo de células epidérmicas autólogas : reglamentos e implicaciones para ensayos clínicos internacionales con Productos de Terapia Avanzada

    NARCIS (Netherlands)

    Middelkoop, E.; Gardien, K.L.M.; Brouwer, K.M.; Waaijman, T.; Uhlrich, M.M.W.; Gibbs, S.; Ulrich, M.M.W.

    2016-01-01

    Introducción. Los Productos de Terapia Avanzada (ATMPs) son considerados el siguiente paso para mejorar la evolución de las quemaduras. Sin embargo, existen serios obstáculos para su aplicabilidad con respecto al reglamento internacional vigente. Aparte de las exigencias reglamentarias para los

  16. Fracturas perimplante de fémur tratadas con clavo retrógrado: reporte de un caso y descripción de la técnica quirúrgica.

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    Pablo Ariel Slullitel

    2016-02-01

    Full Text Available Existe un riesgo tácito de fractura peri-implante de fémur en pacientes con antecedente de fractura pertrocantérica de fémur tratados con tornillos deslizantes de cadera (TDC debido al aumento de la expectativa de vida y a las múltiples comorbilidades. Diversas opciones terapéuticas son posibles dependiendo de si se mantiene la osteosíntesis previa o no. Dada la baja prevalencia de estas fracturas, no existe consenso en la bibliografía actual sobre el tratamiento ideal. El objetivo de este trabajo es reportar un caso y describir la técnica quirúrgica de enclavado endomedular retrógrado para el tratamiento de fracturas peri-implante debajo de un TDC.

  17. Longitud del ciclo estral en ratas Sprague Dawley tratadas in útero con extracto de Roystonea regia Estrus cycle length in Sprague Dawley rats in uterus using Roystonea regia extract

    OpenAIRE

    Ariadne Gutiérrez Martínez; Rafael Gámez Menéndez; Balia Pardo Acosta; Gisela Marrero Cofiño

    2009-01-01

    El D-004 consiste en una mezcla de ácidos grasos que inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. El objetivo del presente estudio fue evidenciar los posibles efectos adversos sobre el ciclo estral de hembras F1 expuestas in útero al D-004. Se utilizaron ratas Sprague Dawley, distribuidas aleatoriamente en 4 grupos: un control y 3 tratados con D-004 a las dosis de 500, 750 y 1 000 mg/kg; las hembras recibieron la administración de la dosis por vía...

  18. Insuficiencia cardíaca congestiva por estenosis aórtica calcificada tratada con éxito en el hogar Congenital heart failure due to calcified aortic stenosis successfully treated at home

    Directory of Open Access Journals (Sweden)

    Roidel Pérez Pérez

    2003-12-01

    Full Text Available Se describe la historia de un paciente con una insuficiencia cardíaca congestiva debido a una estenosis aórtica calcificada, con un cuadro de arritmia cardíaca relativamente complejo, que fue ingresado en el hogar y tratado por el grupo básico de trabajo de su área de salud. Se le realizaron las investigaciones imprescindibles para un adecuado manejo médico, restableciéndosele la salud al paciente, e incorporándolo a su vida laboral, sin necesidad de ingreso hospitalario. Se demostró una vez más la ventaja de este estilo de trabajo en la atención médica de salud y el gran nivel de satisfacción de la población.The history of a patient suffering from congenital heart failure due to a calcified aortic stenosis, with a relatively complex picture of heart arrhytmia, that was admitted at home and treated by the basic working group in his health area, is described. All the investigations necessary for an adequate medical management were made. The patient's health was reestablished and he was able to work again without being hospitalized. It was proved once again the advantage of this working style in health care and the high level of the patient's satisfaction.

  19. EFICIENCIA DEL TRATAMIENTO QUÍMICO EN LA PREVENCIÓN DEL TAPONAMIENTO DE GOTEROS APLICANDO AGUA RESIDUAL SANITARIA TRATADA

    Directory of Open Access Journals (Sweden)

    RAFAEL OLIVEIRA BATISTA

    2009-01-01

    Full Text Available El objetivo de este trabajo fue el de verificar la eficiencia del tratamiento químico en la prevención del taponamiento de los sistemas de goteo, cuando se usa aguas residuales sanitarias tratadas. Para la realización del ensayo experimental fue construida una plataforma de ensayos con la finalidad de abastecer cuatro unidades de irrigación por goteo con aguas residuales sanitarias, tratada y filtradas mediante un filtro de disco de 120 mesh. Fueron ensayados tres modelos de goteros (M1, M2 y M3 durante un período de 560 horas. En el tratamiento químico fueron ensayadas las concentraciones de cloro residual libre de 0; 0,4; 1,0 y 1,9 mg L-1. A partir de los resultados obtenidos se tienen las siguientes conclusiones: el agua residual sanitaria, tratada por aplicación vía sistema de irrigación por goteo propicio la formación de un biofilme en los goteros, resultante de la interacción entre colonias de bacterias y algas. La aplicación de cloro en el agua residual sanitaria tratada, minimizó el desarrollo del biofilme en el interior de los goteros y de las líneas laterales de irrigación; además, se encontró que los goteros con mayor diámetro en el laberinto y con mas de un filtro secundario (M2 y M3, son mas susceptibles al taponamiento cuando trabajan con aguas residuales tratadas. La concentración de cloro residual libre de 0,4 mg L-1 fue mas sustentable en la prevención de taponamiento por biofilme en sistemas de riego por goteo que operan con agua residual domestica tratada.

  20. Cambios esqueléticos, dentales y faciales de la maloclusión clase III esquelética tratada con la filosofía de MEAW (Multiloop Edgewise Arch Wire: descriptivo restrospectivo

    Directory of Open Access Journals (Sweden)

    Ángela Anyur García Bernal

    2012-11-01

    Full Text Available Antecedentes: uno de los problemas más complejos del diagnósticoy tratamiento de las maloclusiones lo constituye la corrección de laclase III esquelética. Objetivo: determinar los cambios esqueléticos,dentales y faciales de la maloclusión clase III esquelética tratadacon la filosofía Edgewise Multiloop (MEAW, en pacientes queasistieron a una clínica odontológica privada entre marzo de 2009a septiembre de 2012. Métodos: se realizó un estudio descriptivoretrospectivo, donde se analizaron los registros clínicos de sietepacientes con diagnóstico de maloclusión clase III esquelética.Se evaluaron las variables edad, género, medidas cefalométricasiniciales y finales en radiografías y fotografías laterales. Resultados:los pacientes de ángulo alto fueron 60% mujeres, con edad mediade 21,8 años (DE± 7,25. El ángulo de la convejidad pasó de 10,58° a16,4°; el Indicador de Displasia Antero-Posterior (APDI disminuyóde 96,7° a 91,0°; el Plano Palatino (PP aumentó de 114,3°a 115,4° yel plano oclusal aumentó la inclinación de 17,8°a 24,7°. El promediode tiempo en el tratamiento fue de 19,4 meses. Conclusiones: lafilosofía MEAW es una alternativa terapéutica de camuflaje en eltratamiento de las maloclusiones clase III esquelética.

  1. Longitud del ciclo estral en ratas Sprague Dawley tratadas in útero con extracto de Roystonea regia Estrus cycle length in Sprague Dawley rats in uterus using Roystonea regia extract

    Directory of Open Access Journals (Sweden)

    Ariadne Gutiérrez Martínez

    2009-12-01

    Full Text Available El D-004 consiste en una mezcla de ácidos grasos que inhibe significativamente la hiperplasia prostática inducida por testosterona en roedores. El objetivo del presente estudio fue evidenciar los posibles efectos adversos sobre el ciclo estral de hembras F1 expuestas in útero al D-004. Se utilizaron ratas Sprague Dawley, distribuidas aleatoriamente en 4 grupos: un control y 3 tratados con D-004 a las dosis de 500, 750 y 1 000 mg/kg; las hembras recibieron la administración de la dosis por vía oral desde 15 días antes del apareo y hasta el fin de la lactancia. A una hembra por camada de la generación F1 se le estudió la citología vaginal y se calculó la longitud aproximada del ciclo, la cual no se vio afectada ya que no existieron diferencias significativas (p= 0,1537 entre los grupos tratados y el control. Estos resultados indican que el D-004 no reveló alteraciones del ciclo estral de las crías hembras expuestas in útero.D-004 is a mix of fatty acids inhibiting significantly Testosterone- induced prostatic hyperplasia in rodents. The aim of present paper was to demonstrate the potential side effects on estrus cycle of F1 female rats exposed in uterus to D-004. We used Sprague Dawley rats, distributed randomly in 4 groups: a control one and another three treated with D-004 at a dosage of 500, 750 and 1 000 mg/kg; in the female rats we administered the dose by mouth from the 15 days before mating, and up to breast feeding termination. In each female rat by litter of F1 generation, the vaginal cytology was studied, and we estimated the approximate length of cycle, remained un-affected since there were not significant differences (p= 0,1537 among treatment groups and the control one. These results show that D-004 fails to reveals alterations in the estrum cycle of female litters exposed in uterus.

  2. Contractura axilar por quemadura tratada con Integra®

    OpenAIRE

    Roa G,Ricardo; Las Heras F,Rocío; Piñeros B,José L; Correa S,Gerardo; Norambuena B,Hernán; Marré N,Diego

    2011-01-01

    Las quemaduras axilares severas son un accidente infrecuente que evolucionan a la retracción generando deficiencias cosméticas y funcionales. Estas cicatrices son difíciles de tratar por las características anatómicas del área, donde la corrección de un vector de movimiento puede alterar otro. Objetivo: Mostrar nuestros resultados utilizando el sustituto cutáneo Integra® en el tratamiento de cicatrices retráctiles axilares por quemadura. Pacientes y Métodos: Se recolectaron antecedentes médic...

  3. Serum insulin, glucose and non esterified fatty acids after administration of follicle-stimulating and luteinizing hormones in bitches Modificaciones de la glucemia, insulina y ácidos grasos no esterificados durante la sobrecarga de glucosa o insulina en perras tratadas con hormona folículo-estimulante y luteinizante

    Directory of Open Access Journals (Sweden)

    A. Renauld

    2003-01-01

    los tests de sobrecarga, los espacios de distribución de glucosa en sangre e insulina sérica o sus clearances plasmáticos no se vieron afectados por el tratamiento. Concluimos que la secreción de insulina como respuesta a una sobrecarga de glucosa aumenta significativamente en perras en anestro tratadas con FSH + LH. Al mismo tiempo se observa una moderada resistencia a la insulina, en los efectos hipoglucemiantes, lipogénicos y antilipolíticos de esta hormona durante esta prueba.

  4. Intravitreal Bevacizumab: Indications and Complications

    International Nuclear Information System (INIS)

    Jan, S.; Nazim, M.; Karim, S.; Hussain, Z.

    2016-01-01

    Background: Bevacizmab is still an unlicensed drug for intraocular use in spite of the fact that it has shown comparable efficacy to other anti-vascular endothelial growth factors (anti-VEGF) medications in some large sample randomized control trails. Although repackaged bevacizumab has got safety concerns but its use is growing because of easy availability and low cost. Our study focuses on the diverse and growing indications of intravitreal bevacizumab (IVB) and its ocular complications in our geographical setting. Method: This interventional case series was carried out at my private practice in Said Anwar Medical Complex, Dabgari, Peshawar, from January 2008 to July 2015. Total of 6107 injections were given to 4352 eyes. Intravitreal bevacizumab was injected in proper operating room setting. Bevacizumab injections were prepared from same vial by multiple withdrawals taking care of aseptic precautions. Follow up was done at 1 week and 20 days and adverse effects were noted. Results: Diabetic macular oedema (36 percent), central retinal vein occlusion (17.6 percent) and branched retinal vein occlusion (11 percent) were the top three indications of IVB. Other common indications were proliferative diabetic retinopathy (9.6 percent), neo-vascular glaucoma (5.9 percent), proliferative diabetic retinopathy with vitreous bleed (4.4 percent), proliferative diabetic retinopathy with tractional retinal detachment (3.7 percent), neo-vascular age related macular degeneration (2.9 percent), central serous retinopathy (1.48 percent) and Eale disease (1.48 percent). Endohthalmitis occurred in 3 eyes (0.069 percent) while retinal detachment was found in only 2 eyes (0.046 percent).Conclusion: Common indications of bevacizumab are diabetic macular oedema, central retinal vein occlusion and branched retinal vein occlusion. Complications like endophthalmitis and retinal detachment are rare. (author)

  5. Factores asociados con la hipertensión no tratada en los adultos mayores: resultados del estudio nacional sobre salud y envejecimiento en México, 2001 Factors associated with untreated hypertension among older adults: results of the Mexican health and aging study, 2001

    Directory of Open Access Journals (Sweden)

    Efrén Melano-Carranza

    2008-05-01

    Full Text Available OBJETIVO: Determinar los factores asociados con la falta de adhesión al tratamiento de la hipertensión arterial (HTA diagnosticada en una muestra representativa de adultos mayores mexicanos que viven en la comunidad. MÉTODOS: Estudio transversal con 2 029 personas de 65 años o más con diagnóstico de HTA, participantes en el Estudio Nacional sobre Salud y Envejecimiento en México realizado en el verano de 2001. La encuesta recabó información sobre algunas características sociodemográficas (edad, sexo, escolaridad, si vivía solo y si realizaba algún trabajo remunerado, entre otras, las enfermedades crónicas, los síntomas depresivos, el deterioro cognoscitivo, el índice de masa corporal, el tabaquismo, el consumo de bebidas alcohólicas y las dificultades para realizar actividades básicas (ABVD e instrumentales (AIVD de la vida diaria, entre otras. Se evaluó la asociación entre las variables estudiadas y el autoinforme de hipertensión arterial no tratada (HTNT mediante análisis de regresión logística simple y multifactorial. RESULTADOS: De los 2 029 participantes, 437 (21,5% declararon no seguir tratamiento alguno para controlar la HTA, 1 584 (78,1% afirmaron seguir un tratamiento y 8 (0,4% no respondieron a esa pregunta. El análisis multifactorial ajustado por posibles variables confusoras (edad, sexo, síntomas depresivos y deterioro cognoscitivo mostró que solo la baja escolaridad (razón de posibilidades [odds ratio, OR] ajustada = 1,70; intervalo de confianza de 95% [IC95%]: 1,10 a 2,64; P = 0,02 para la escolaridad de 1 a 6 años y OR ajustada = 3,32; IC95%: 2,10 a 5,24; P OBJECTIVE: To determine factors associated with failure to adhere to treatment for diagnosed hypertension among a representative sample of older Mexican adults living in the community. METHODS: A cross-sectional study of 2 029 individuals 65 years of age or older with diagnosed hypertension who participated in the Mexican Health and Aging Study

  6. Role of bevacizumab in uterine leiomyosarcoma.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

    2018-06-01

    In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Indications and Treatment Outcomes of Intravitreal Bevacizumab ...

    African Journals Online (AJOL)

    Bevacizumab and Ranibizumab for Retinal Diseases in Benin. City, Nigeria. Odarosa M. .... travel costs and risk of complications such as endophthalmitis and retinal detachment ... antiVEGF to be utilised considering reports of increased risk of.

  8. Safety of cupping during bevacizumab therapy.

    Science.gov (United States)

    Klempner, Samuel J; Costa, Daniel B; Wu, Peggy A; Ariyabuddhiphongs, Kim D

    2013-08-01

    This study reports on the safety of the complementary and alternative medicine (CAM) practice of cupping in a patient undergoing concomitant therapy with bevacizumab for advanced non-small-cell lung cancer (NSCLC), and raises awareness of the need for improved communication between CAM practitioners and oncologists during the care of patients with cancer. The practice of cupping generates local hyperemia, disrupts superficial vasculature in the dermis, and leads to cutaneous lesions including circular erythema, edema, and subsequently ecchymosis. There are no data on the safety of cupping in patients being treated with bevacizumab. This is a single-institution case report. The setting for this study was a tertiary-care academic medical center. A patient with advanced NSCLC received four cycles of carboplatin AUC 6, paclitaxel 200 mg/m(2), and bevacizumab 15 mg/kg, and was continued on every-3-week maintenance bevacizumab 15 mg/kg. The patient underwent glass dry cupping during cycle six of maintenance bevacizumab treatment without overt cutaneous adverse events or bleeding. The patient did not realize he should have communicated his cupping plans or recent bevacizumab treatment with his providers.

  9. Bevacizumab (Avastin® no tratamento da membrana neovascular coroidal secundária à degeneração macular relacionada à idade: relato de caso Bevacizumab (Avastin® in treatment of choroidal neovascularization secondary to age-related macular degeneration: a case report

    Directory of Open Access Journals (Sweden)

    Tiago Eugênio Faria e Arantes

    2007-12-01

    Full Text Available As drogas anti-angiogênicas foram introduzidas recentemente no arsenal terapêutico das membranas neovasculares coroidais. O objetivo deste relato é descrever um caso de membranas neovasculares coroidais oculta com extenso descolamento do epitélio pigmentado da retina, tratada com bevacizumab (Avastin® intravítrea. A eficácia da medicação foi avaliada por meio da acuidade visual e de exames complementares (angiografia fluoresceínica, videoangiografia com indocianina verde e tomografia de coerência óptica. Após três injeções intravítreas de bevacizumab, obteve-se uma resposta anatômica e visual satisfatória, denotando benefícios da droga, apesar do extenso descolamento do epitélio pigmentado da retina associada a membranas neovasculares coroidais oculta.The antiangiogenic drugs have been recently introduced in the therapeutic armamentarium of choroidal neovascularization. The purpose of this report is to describe a case of occult choroidal neovascularization with extensive retinal pigment epithelial detachment treated with intravitreal bevacizumab (Avastin®. The efficacy of the medication was evaluated by means of visual acuity and complementary exams (fluorescein angiography, indocyanine green video angiography and optical coherence tomography. After three intravitreal injections of bevacizumab a satisfactory anatomic and visual response was achieved, showing benefits of the drug, despite the extensive retinal pigment epithelial detachment associated with occult choroidal neovascularization.

  10. Fibrous membranes in diabetic retinopathy and bevacizumab.

    Science.gov (United States)

    Pattwell, David M; Stappler, Theodor; Sheridan, Carl; Heimann, Heinrich; Gibran, Syed K; Wong, David; Hiscott, Paul

    2010-01-01

    The purpose of this study was to determine the histopathologic characteristics of bevacizumab-treated human proliferative diabetic retinopathy (PDR) membranes with particular regard to membrane vasculature as a step toward addressing the effects of the drug on PDR membranes. Intravitreous injection of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, has recently been advocated as an adjunct in surgery for PDR. In this context, a clinically observed decrease in PDR epiretinal membrane vascularity (vascular regression) occurs from 24 hours to 48 hours after injection, but the exact mechanisms of drug action are unknown. A consecutive series of seven PDR membrane specimens that had been removed sequentially from seven bevacizumab-treated patients were studied retrospectively. The membrane specimens were examined using light microscopic methods, including immunohistochemistry. Five of the seven membranes were clinically avascular (one contained "ghost" vessels) and did not hemorrhage during excision. Of these 5 specimens, which included 1 removed 7 days after a total of 6 intravitreous injections of 1.25 mg bevacizumab, 4 contained histologically detectable capillaries (1 did not). These blood vessels were lined by endothelial cells as determined by immunohistochemistry for the endothelial markers CD31 and CD34. The two remaining membranes were clinically and histologically still vascularized despite bevacizumab treatment. All the specimens also contained smooth muscle actin-containing fibroblastic cells within the collagenous stroma. The findings do not support the concept that the clinical phenomenon of vascular regression in PDR membranes after bevacizumab injection in the vitreous is resulting from obliteration of the membrane blood vessels. Another mechanism appears to be involved in at least some patients, possibly a vasoconstrictive response. Such a mechanism might explain reversal of the effects of bevacizumab that has been reported

  11. Evaluación in vivo de la eficacia cosmética de dos procedimientos de bioestimulación con la aplicación de plasma rico en plaquetas en arrugas faciales, para mejorar la elasticidad y firmeza de la piel tratada

    OpenAIRE

    Cornejo Bravo, Juan Carlos

    2017-01-01

    Mi proyecto de titulación se orientó a buscar la eficacia cosmética de dos procedimientos de bioestimulación con Plasma Rico en Plaquetas en arrugas faciales, teniendo como resultado que la eficacia se encuentra en personas con mioenvejecimiento (30-40 años) con el procedimiento de Plasma Rico en Plaquetas Activado (PRPA). This project, prior to obtaining my Master’s degree was aimed towards seeking the cosmetic efficiency of two bio stimulation procedures using platelet-rich plasma applie...

  12. CARACTERÍSTICAS CRISTALOQUÍMICAS DE LA HIDROXIAPATITA SINTÉTICA TRATADA A DIFERENTES TEMPERATURAS

    Directory of Open Access Journals (Sweden)

    Marta Elena Londoño

    Full Text Available La hidroxiapatita sintética (HA es un fosfato de calcio con una composición química muy similar a la del hueso humano, lo cual la hace biocompatible con los tejidos vivos. La biocompatibilidad posibilita su uso en variadas aplicaciones médicas. En esta investigación se realizó un seguimiento a las propiedades cristaloquímicas de muestras de HA sintética tratadas a diferentes temperaturas, las que se sometieron a solución fisiológica de Ringer durante periodos de 5 y de 30 días. La medición de la conductividad y el análisis de las muestras, por medio de espectrofotometría UV-VIS, análisis por ion selectivo, DRX, FTIR y SEM, permitieron mostrar la gran dependencia de la cristalinidad con el tratamiento térmico. La muestra más cristalina se obtuvo a una temperatura de 1050 °C. La mayor solubilidad se presentó en las muestras más cristalinas; además, se evidenció la presencia de dos mecanismos que compiten cuando las muestras se someten a solución Ringer: la disolución y la precipitación.

  13. First-Line XELOX Plus Bevacizumab Followed by XELOX Plus Bevacizumab or Single-Agent Bevacizumab as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: The Phase III MACRO TTD Study

    Science.gov (United States)

    Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Abad, Albert; Valladares, Manuel; Rivera, Fernando; Safont, Maria J.; Martínez de Prado, Purificación; Gallén, Manuel; González, Encarnación; Marcuello, Eugenio; Benavides, Manuel; Fernández-Martos, Carlos; Losa, Ferrán; Escudero, Pilar; Arrivi, Antonio; Cervantes, Andrés; Dueñas, Rosario; López-Ladrón, Amelia; Lacasta, Adelaida; Llanos, Marta; Tabernero, Jose M.; Antón, Antonio; Aranda, Enrique

    2012-01-01

    Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. PMID:22234633

  14. Toxicidad por dosis repetidas de la solución CM-95 tratada magnéticamente en ratas Sprague Dawley

    Directory of Open Access Journals (Sweden)

    Clara E. Martínez

    2008-08-01

    Full Text Available En este trabajo se realizó la evaluación toxicológica a dosis repetidas por el método de test límite del candidato a inmunopotenciador, la solución CM-95 tratada magnéticamente, acorde con las regulaciones de la Organización para la Colaboración Económica y el Desarrollo, incluida en la Guía 407. El objetivo fue establecer las posibles lesiones orgánicas y funcionales ocasionadas por la solución CM-95, tratada magnéticamente con la máxima inducción magnética permisible (0,16 T, para la obtención del candidato a inmunopotenciador. Se emplearon tres grupos: Experimental, Control y Satélite. Como Biomodelo experimental se utilizaron ratas Sprague Dawley machos y hembras con pesos de 150 a 200 g. Durante el estudio no se registraron signos clínicos de toxicidad ni muertes en ninguno de los animales de los grupos tratados, ni en los controles. No hubo afectación del peso corporal durante el ensayo. Aunque hubo variaciones en los valores de algunos parámetros hematológicos y bioquímicos, estos no tuvieron significación biológica. No se encontraron lesiones macroscópicas, ni microscópicas; solo se observaron efectos proliferativos en el tejido linfoide de timo y bazo, relacionados con la respuesta del sistema inmune. La solución CM-95 tratada magnéticamente, no mostró toxicidad en el modelo animal y nivel de dosis utilizado, y bajo las condiciones experimentales ensayadas.

  15. Chemical composition and resistance to oxidation of high-oleic rapeseed oil pressed from microwave pre-treated intact and de-hulled seeds; Composición química y resistencia a la oxidación de aceite de colza alto oleico prensado de semillas intactas y descascarilladas pre-tratadas con microondas

    Energy Technology Data Exchange (ETDEWEB)

    Rękas, A.; Wroniak, M.; Siger, A.; Ścibisz, I.

    2017-07-01

    The influence of a microwave (MV) pre-treatment (3, 6, 9 min, 800W) on the physicochemical properties of high-oleic rapeseed oil prepared from intact (HORO) and de-hulled seeds (DHORO) was investigated in this study. A control DHORO contained higher levels of total tocopherols and carotenoids, while higher concentrations of total phenolic compounds and chlorophylls were detected in the HORO. The MV pre-treatment caused a decrease in the unsaturated fatty acids content that was more evident for the DHOROs. The microwaving time significantly affected phytochemical contents and the color of both types of oils. A vast increase in canolol concentration was noticeable following 9 min of microwaving, which increased 506- and 155-fold in the HORO and DHORO, respectively. At the same time, the antioxidant capacity of oil produced from MV pre-treated seeds for 9 min was nearly 4 times higher than that of the control oil for both types of oils. [Spanish] En este estudio se investigó la influencia del pretratamiento con microondas (MV) en las propiedades fisicoquímicas del aceite de colza alto oleico preparado a partir de semillas húmedas (HORO) y descascarilladas (DHORO) (3, 6, 9 min, 800W). El control DHORO contenía un nivel más alto de tocoferoles totales y carotenoides, mientras que se detectó una mayor concentración de compuestos fenólicos totales y clorofilas en el HORO. El pretratamiento de MV provocó una disminución en el contenido de ácidos grasos insaturados que fue más evidente para los DHOROs. El tiempo de microondas afectó significativamente al contenido fitoquímico y al color de ambos tipos de aceites. Se observó un gran aumento de la concentración de canolol después de 9 min de microondas, que aumentó 506 y 155 veces en el HORO y DHORO, respectivamente. Al mismo tiempo, la capacidad antioxidante del aceite producido a partir de semillas pretratadas de MV durante 9 min fue casi 4 veces mayor que la del aceite de control para ambos tipos de

  16. Acute anterior uveitis following intravitreal bevacizumab but not subsequent ranibizumab

    Directory of Open Access Journals (Sweden)

    Antonopoulos C

    2011-11-01

    Full Text Available Christina Antonopoulos1, Maxwell Stem2, Grant M Comer21Department of Ophthalmology, Boston University, Boston, MA, USA; 2WK Kellogg Eye Center, Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USAPurpose: Previous reports have identified noninfectious uveitis as a potential sequela following both intravitreal bevacizumab and ranibizumab injections. We present two unique cases of acute anterior uveitis following intravitreal bevacizumab that did not occur with subsequent ranibizumab injections.Methods: Case report.Conclusion: These cases may reflect differences in the etiology of anterior uveitis following intravitreal bevacizumab and ranibizumab. Given these differences, it may be reasonable to offer ranibizumab to patients who have experienced presumed bevacizumab-induced anterior uveitis.Keywords: adverse effect, age-related macular degeneration, anterior uveitis, bevacizumab, ranibizumab, uveitis

  17. Periodontal disease in a patient receiving Bevacizumab: a case report

    Directory of Open Access Journals (Sweden)

    Gujral Dorothy M

    2008-02-01

    Full Text Available Abstract Introduction Bevacizumab is a monoclonal antibody that inhibits the action of vascular endothelial growth factor (VEGF thereby acting as an angiogenesis inhibitor. As a result, supply of oxygen and nutrients to tissues is impaired and tumour cell growth is reduced. Reported side effects due to bevacizumab are hypertension and increased risk of bleeding. Bowel perforation has also been reported. Periodontal disease in patients on bevacizumab therapy has not been reported before. Case Presentation We report a case of a forty-three year old woman who developed periodontitis whilst receiving bevacizumab for lung cancer. The periodontal disease remained stable on discontinuation of the drug. Conclusion Further investigations are needed to determine the mechanism for bevacizumab-induced periodontal disease.

  18. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

    2009-01-01

    Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

  19. Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer

    NARCIS (Netherlands)

    Tol, Jolien; Koopman, Miriam; Cats, Annemieke; Rodenburg, Cees J.; Creemers, Geert J. M.; Schrama, Jolanda G.; Erdkamp, Frans L. G.; Vos, Allert H.; van Groeningen, Cees J.; Sinnige, Harm A. M.; Richel, Dirk J.; Voest, Emile E.; Dijkstra, Jeroen R.; Vink-Börger, Marianne E.; Antonini, Ninja F.; Mol, Linda; van Krieken, Johan H. J. M.; Dalesio, Otilia; Punt, Cornelis J. A.

    2009-01-01

    Background Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor ( VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor ( EGFR) antibody cetuximab

  20. Bevacizumab improves survival for patients with advanced cervical cancer

    Science.gov (United States)

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  1. Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

    Directory of Open Access Journals (Sweden)

    Thérèse H Franco

    2008-10-01

    Full Text Available Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF. It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007. Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab (Genetech, Inc. 2008. This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.Keywords: vascular endothelial growth factor, bevacizumab, metastatic cancer, chemotherapy, takotsubo, cardiomyopathy

  2. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

    OpenAIRE

    Moisseiev, Elad; Waisbourd, Michael; Ben-Artsi, Elad; Levinger, Eliya; Barak, Adiel; Daniels, Tad; Csaky, Karl; Loewenstein, Anat; Barequet, Irina S.

    2013-01-01

    Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. Methods Tw...

  3. Abdominal wall perforation in a patient with recurrent epithelial ovarian cancer after bevacizumab treatment

    Directory of Open Access Journals (Sweden)

    Efnan Algin

    2016-08-01

    Full Text Available Bowel perforation is a rare but well-described complication of bevacizumab, a VEGF monoclonal antibody. However, bevacizumab associated abdominal wall perforation is a more serious complication. In here, a patient with recurrent epithelial ovarian cancer developing both bowel and abdominal wall perforation after bevacizumab treatment is reported with review of the literature to point out the clinical significance of this rare complication. To our knowledge, this is the first case with bevacizumab associated abdominal wall perforation.

  4. Timing of Administration of Bevacizumab Chemotherapy Affects Wound Healing Following Chest Wall Port Placement

    OpenAIRE

    Erinjeri, Joseph P; Fong, Abigail J; Kemeny, Nancy E; Brown, Karen T; Getrajdman, George I; Solomon, Stephen B

    2010-01-01

    The risk of a wound dehiscence requiring chest wall port explant in patients treated with bevacizumab is inversely proportional to the interval between bevacizumab administration and port placement. There is significantly higher risk of wound dehiscence when the interval between bevacizumab administration and chest wall port placement is less than 14 days.

  5. 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

    Science.gov (United States)

    Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

    2017-01-01

    Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Effect of bevacizumab on radiation necrosis of the brain

    International Nuclear Information System (INIS)

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A.

    2007-01-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% (±22 SD), and the average change in the FLAIR images was 60% (±18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg (±3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment

  7. Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Fouad Mona N

    2011-08-01

    Full Text Available Abstract Background We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment. Methods We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US. Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression. Results Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026. Patients ≥ 75 years were less likely to receive bevacizumab than patients Conclusions One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.

  8. Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

    Science.gov (United States)

    Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

    ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

  9. Sigmoid-vaginal fistula during bevacizumab treatment diagnosed by fistulography.

    Science.gov (United States)

    Hayashi, C; Takada, S; Kasuga, A; Shinya, K; Watanabe, M; Kano, H; Takayama, T

    2016-12-01

    There have been several reports describing rectovaginal fistula development after bevacizumab treatment, and these fistulas were diagnosed by CT scan or colonoscopy. We report a case of sigmoid-vaginal fistula diagnosed by fistulography. The case is a 53-year-old woman who was treated for chronic myelogenous leukaemia and gynaecological cancers 8 years previously. At 52 years of age, she was diagnosed with colon cancer and had a partial colectomy performed. One year after surgery, colon cancer recurred, and she was treated with anticancer agents, including bevacizumab. During chemotherapy, she complained of a foul smelling discharge from the vagina. Fistulography revealed a sigmoid-vaginal fistula. This is the first report of vaginal fistulography performed on a patient who was treated with bevacizumab. Fistulography may be useful for detecting sigmoid-vaginal fistula. © 2016 John Wiley & Sons Ltd.

  10. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed [Brown University Oncology Group, Providence, RI (United States); Safran, Howard, E-mail: hsafran@lifespan.org [Brown University Oncology Group, Providence, RI (United States)

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  11. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

    Directory of Open Access Journals (Sweden)

    Deli Krizova

    2014-01-01

    Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

  12. A systematic review of bevacizumab efficacy in breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Christiansen, Ole Grummedal; Nielsen, Dorte Lisbet

    2014-01-01

    demonstrated an OS benefit. In the neoadjuvant setting 23 phase II and III trials were identified. All studies found increased pCR/tpCR but no benefit in terms of OS could be demonstrated. The only study conducted in the adjuvant setting failed to show any survival benefit of bevacizumab. CONCLUSION: Despite...

  13. Therapeutical evaluation of bevacizumab application in relapsed pterygium

    Directory of Open Access Journals (Sweden)

    Mayara Martins Abrahão

    Full Text Available Abstract Objective: Therapeutic evaluation of Bevacizumab application in relapsed pterygium concerning visual acuity, keratometry, refraction, symptomatology. Methods: Group 1 (4 patients received 0.1 ml of Bevacizumab (avastin, being evaluated posteriorly on the tenth and thirtieth days after the application, seeking to compare with the exam previously made, being it realized with the other two groups, in which Group 2 (4 patients received 0.2 ml of Bevacizumab and the Group 3 (3 patients received 1 ml of the placebo injection. Results: In this study, eleven eyes of eleven patients were evaluated. Among these patients, 7 were women (63.6% and 4 men (36.4%. There was a variation in the cylindrical diopter after the treatment with a dose of 0.1 ml of bevaciumab during the evaluation on the thirtieth day. Whereas the cylindrical shaft had a significantly larger modification after the application of 0.2 ml. Regarding the spherical diopter variation, there were modifications in the 3 groups. The keratometry varied in the 3 groups, mostly after the thirtieth day of evaluation. In relation to symptomatology, it was observed a reduction in the subjective evaluation of the eye burning sensation, the prurience mentioned by the patient and a reduction of the hyperemia biomicroscopy evaluation. Conclusion: In bevacizumab application in the recurrent pterygium treatment, there is modification of the spherical and cylindrical parameters of refraction, besides the changes in keratometry and the reduction of the symptomatology.

  14. Analysis on complications after intravitreal injection of bevacizumab

    Directory of Open Access Journals (Sweden)

    Cui-Wei Zhang

    2013-08-01

    Full Text Available AIM: To observe and analyze on the incidence rate and causes of complications after anintravitreal injection of bevacizumab. METHODS: Totally, 207 cases(207 eyeswith wet age-related macular degeneration were selected randomly. All cases were treated with intravitreal injections of bevacizumab(1.5mg/0.06mLand asked for chief complaints at 1 day, 1 week, 4, 12 weeks after operation, and also examined for routine visual acuity(best corrected visual acuity, BCVA, non-contact tonometer, slit lamp microscope and indirect ophthalmoscope etc.RESULTS: Among 207 cases(207 eyes, visual acuity improved efficiency was 90.8% 12 weeks after treatment, foreign body sensation was found in 7 cases(3.4%, eyelid skin pruritus in 1 case(0.5%, conjunctival congestion in 6 cases(2.9%, subconjunctival hemorrhage in 1 case(0.5%, post-operative intraocular pressure elevation in 2 cases(1.0%. CONCLUSION: The intravitreal injection of bevacizumab is effective with fewer complications. We propose to carry out a further randomized multicenter and larger-sample clinical research and further draw up the clinical application criterion of bevacizumab.

  15. Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis.

    Science.gov (United States)

    Cai, Jun; Ma, Hong; Huang, Fang; Zhu, Dichao; Bi, Jianping; Ke, Yang; Zhang, Tao

    2013-11-28

    With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients. We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR. The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46-0.72; P hypertension. Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer.

  16. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    Science.gov (United States)

    Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

    2014-01-01

    Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

  17. Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

    Science.gov (United States)

    Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

    2011-01-01

    BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

  18. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2016-01-01

    Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevac......Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...

  19. SECADO DE UCHUVA (Physalis peruviana L) POR AIRE CALIENTE CON PRETRATAMIENTO DE OSMODESHIDRATACIÓN

    OpenAIRE

    CASTRO, Adriana M; RODRÍGUEZ, Ligia; VARGAS, Edgar M

    2008-01-01

    En este trabajo se determinan las condiciones de temperatura más favorables para un proceso de secado de uchuva (Physalis peruviana L) con aire caliente, con deshidratación osmótica (DO) como pretratamiento, utilizando una solución de sacarosa de 70o Brix a 40oC durante 16 horas. Se realiza un seguimiento de la degradación de β-caroteno con el tiempo y la temperatura. En la fruta tratada con aire caliente a 60oC y pretratada con DO, se obtiene una pérdida total de β-caroteno del 98%. La fruta...

  20. A case report of long term bevacizumab treatment in multiresistant ovarian cancer

    DEFF Research Database (Denmark)

    Kargo, Anette Stolberg; Adimi, Parvin; Dahl-Steffensen, Karina

    2016-01-01

    Treatment of multiresistant ovarian cancer is palliative and patients have needs for less toxic treatment. Anti-angiogenic treatments have a less toxic profile, and bevacizumab has shown improvement of progression free survival (PFS) in front-line trials. Bevacizumab is generally introduced in co...... in combination with chemotherapy; however this case report will describe the use of single-agent bevacizumab for more than five years (102 cycles) in a patient with relapse of advanced ovarian cancer...

  1. Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma.

    Science.gov (United States)

    Wiestler, Benedikt; Radbruch, Alexander; Osswald, Matthias; Combs, Stephanie E; Jungk, Christine; Winkler, Frank; Bendszus, Martin; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Wick, Antje

    2014-03-01

    Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-naïve patients after progression occurs.

  2. Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study

    Energy Technology Data Exchange (ETDEWEB)

    Bostroem, J.P. [University of Bonn Medical Center, Department of Neurosurgery, Bonn (Germany); MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); Seifert, M.; Greschus, S. [University of Bonn Medical Center, Department of Radiology, Bonn (Germany); Schaefer, N.; Herrlinger, U. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); Glas, M. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); University of Bonn Medical Center, Stem Cell Pathologies, Institute of Reconstructive Neurobiology, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Lammering, G. [MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Heinrich-Heine-University of Duesseldorf, Department of Radiotherapy and Radiation Oncology, Duesseldorf (Germany)

    2014-04-15

    Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma. (orig.) [German] In zwei aktuellen retrospektiven Kohortenstudien konnte eine Wirksamkeit von Bevacizumab bei Patienten mit rezidivierenden atypischen und

  3. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    Directory of Open Access Journals (Sweden)

    Orozco-Hernández A

    2014-09-01

    Full Text Available Axel Orozco-Hernández,1 Ximena Ortega-Larrocea,1 Gustavo Sánchez-Bermúdez,1 Gerardo García-Aguirre,1 Virgilio Morales Cantón,1 Raul Velez-Montoya2 1Retina Department, Asociación para Evitar la Ceguera en México IAP, Mexico City, Mexico; 2Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, Aurora, CO, USA Background: Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods: This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results: Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were

  4. Alteraciones alimentarias en pacientes con diagnóstico de Trastorno Bipolar

    OpenAIRE

    Maldonado, Marianela

    2010-01-01

    Las Alteraciones Alimentarias constituyen un importante problema de la Salud Pública en la actualidad. Existen una serie de factores que han ido apareciendo en forma insidiosa como el aumento de su frecuencia y la dificultad en poder ser diagnosticadas y tratadas nutricionalmente en pacientes con Trastorno Bipolar. Los pacientes que presentan esta patología exhiben alteraciones alimentarias que por sus características o su gravedad, no solamente no alcanzan a cumplir con los cr...

  5. Growth of Scytalidium sp. in a counterfeit bevacizumab bottle

    Directory of Open Access Journals (Sweden)

    Gerardo Garcia-Aguirre

    2013-01-01

    Full Text Available After drawing a dose from an closed bevacizumab (Avastin bottle, a fungus-like foreign body was observed inside. Samples from the vial were cultured in Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment was observed after 10 days. The species was identified as Scytalidium sp.Vial, analysis reported that the seal was lacking proper identification measures and that the label, batch number and expiry date did not correspond to a genuine product. Chemical analysis showed no protein, but 3% of polyethylene glycol, citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a significant risk for ophthalmology and oncology patients. The medical community should be aware of this situation in order to enforce adequate preventive measures.

  6. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.

    Science.gov (United States)

    Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

    2014-09-18

    Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more

  7. CCR 20th Anniversary Commentary: Bevacizumab in the Treatment of Glioblastoma--The Progress and the Limitations.

    Science.gov (United States)

    Mar, Nataliya; Desjardins, Annick; Vredenburgh, James J

    2015-10-01

    Vredenburgh and colleagues conducted the first phase II study of bevacizumab plus irinotecan in recurrent malignant glioma, confirming the safety and efficacy of bevacizumab. This study, which was published in the February 15, 2007, issue of Clinical Cancer Research, was a stepping stone for subsequent research, leading to regulatory approval of bevacizumab for recurrent glioblastoma. ©2015 American Association for Cancer Research.

  8. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Science.gov (United States)

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  9. Intravitreal Bevacizumab (Avastin for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    Directory of Open Access Journals (Sweden)

    J. Fernando Arevalo

    2011-01-01

    Full Text Available This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB on diabetic retinopathy (DR including diabetic macular edema (DME and proliferative diabetic retinopathy (PDR at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD, and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

  10. Rediseño de una lavadora de bidones para envasado de agua tratada

    OpenAIRE

    Martinez Lozano, Ernesto Rolando

    2009-01-01

    El objetivo de esta tesis es aplicar los conocimientos adquiridos, para realizar el rediseño de una lavadora manual para bidones de una empresa de tratamiento de agua, se establecerán las condiciones de diseño optimo para disminuir el tiempo en el proceso de lavado de los bidones que son utilizados en el proceso de envasado del agua tratada el cual es realizado manualmente, en donde los tiempos de lavado varían entre 40 y 60 botellas por hora; queriendo llegar a obtener un tiempo estándar de ...

  11. Targeting Src family kinases inhibits bevacizumab-induced glioma cell invasion.

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    Deborah Huveldt

    Full Text Available Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM. Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab's influence on glioma biology and block it's actions towards cell invasion. To explore the mechanism(s of GBM cell invasion we have examined a panel of serially transplanted human GBM lines grown either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1 activation of Src family kinases (SFKs is common in GBM, 2 the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3 SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support testing the combination of dasatinib with bevacizumab in the clinic.

  12. Discontinuous Schedule of Bevacizumab in Colorectal Cancer Induces Accelerated Tumor Growth and Phenotypic Changes

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    Selma Becherirat

    2018-04-01

    Full Text Available Antiangiogenics administration in colorectal cancer patients seemed promising therapeutic approach. Inspite of early encouraging results, it however gave only modest clinical benefits. When AAG was administered with discontinuous schedule, the disease showed acceleration in certain cases. Though resistance to AAG has been extensively studied, it is not documented for discontinuous schedules. To simulate clinical situations, we subjected a patient-derived CRC subcutaneous xenograft in mice to three different protocols: 1 AAG (bevacizumab treatment for 30 days (group A (group B was the control, 2 bevacizumab treatment for 50 days (group C and bevacizumab for 30 days and 20 without treatment (group D, and 3 bevacizumab treatment for 70 days (group E and 70 days treatment with a drug-break period between day 30 and 50 (group F. The tumor growth was monitored, and at sacrifice, the vascularity of tumors was measured and the proangiogenic factors quantified. Tumor phenotype was studied by quantifying cancer stem cells. Interrupting bevacizumab during treatment accelerated tumor growth and revascularization. A significant increase of proangiogenic factors was observed when therapy was stopped. On withdrawal of bevacizumab, as also after the drug-break period, the plasmatic VEGF increased significantly. Similarly, a notable increase of CSCs after the withdrawal and drug-break period of bevacizumab was observed (P<.01. The present study indicates that bevacizumab treatment needs to be maintained because discontinuous schedules tend to trigger tumor regrowth, and increase tumor resistance and CSC heterogeneity.

  13. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

    Directory of Open Access Journals (Sweden)

    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  14. Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

    2014-01-01

    Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

  15. Cetuximab reduces the accumulation of radiolabeled bevacizumab in cancer xenografts without altering VEGF expression

    NARCIS (Netherlands)

    Heskamp, S.; Boerman, O.C.; Molkenboer-Kuenen, J.D.M.; Sweep, F.C.; Geurts-Moespot, A.; Engelhardt, M.S.; Graaf, W.T.A. van der; Oyen, W.J.G.; Laarhoven, H.W.M. van

    2014-01-01

    Introduction: Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the

  16. Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary to iris metastasis of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Stephanie Vale

    2018-03-01

    Conclusions & importance: A single intravitreal bevacizumab injection may be sufficient to achieve palliative control of neovascular glaucoma secondary to iris breast cancer metastasis. To our knowledge, this is the first case report in which a single intravitreal bevacizumab injection was used for the effective management of this condition.

  17. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  18. Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

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    Tugba Cakmak Argun

    2017-07-01

    Full Text Available AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.

  19. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

    2013-01-01

    standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

  20. Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

    Directory of Open Access Journals (Sweden)

    Eric K. Newcott

    2015-01-01

    Full Text Available Purpose. To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment. Methods. We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye. Results. Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision. Conclusion. Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

  1. Plexo nervioso subbasal y su relación con la magnitud de la ametropía en cirugía refractiva con láser excimer

    OpenAIRE

    Rojas Álvarez, Eduardo; González Sotero, Janet; Pérez Ruiz, Ariadna

    2013-01-01

    Objetivo: describir los cambios del plexo nervioso subbasal durante un año, posterior a tratamiento con láser excímer y relacionar estos cambios con la magnitud de la ametropía tratada. Métodos: estudio prospectivo y longitudinal en 78 pacientes (151 ojos) que cumplieron con los criterios de selección establecidos. La técnica quirúrgica empleada fue LASIK con microquerátomo pendular. Las imágenes se obtuvieron por microscopia confocal de la córnea con el microscopio ConfoScan 4. El análisis s...

  2. Exposição humana a trialometanos presentes em água tratada

    Directory of Open Access Journals (Sweden)

    Maria Y Tominaga

    1999-08-01

    Full Text Available Realizou-se uma revisão bibliográfica do período de 1974-1998, no MEDLINE, sobre compostos orgânicos halogenados derivados de hidrocarbonetos denominados de trialometanos. Muitos deles, reconhecidamente carcinogênicos para diferentes espécies animais, podem ser encontrados freqüentemente, inclusive entre nós, em águas tratadas e enviadas à população urbana. É o caso de compostos como o clorofórmio, bromodiclorometano, clorodibromometano e bromofórmio, resultantes da halogenação de precursores, principalmente substâncias húmicas e fúlvicas presentes na água que será tratada (clorada. Assim, descreve-se sua formação, fontes de exposição humana bem como os aspectos toxicológicos de maior importância: disposição cinética e espectro dos efeitos tóxicos (carcinogênicos, mutagênicos e teratogênicos decorrentes de exposições a longo prazo e baixas concentrações. Níveis seguros de exposição propostos são também fornecidos.

  3. Exposição humana a trialometanos presentes em água tratada

    Directory of Open Access Journals (Sweden)

    Tominaga Maria Y

    1999-01-01

    Full Text Available Realizou-se uma revisão bibliográfica do período de 1974-1998, no MEDLINE, sobre compostos orgânicos halogenados derivados de hidrocarbonetos denominados de trialometanos. Muitos deles, reconhecidamente carcinogênicos para diferentes espécies animais, podem ser encontrados freqüentemente, inclusive entre nós, em águas tratadas e enviadas à população urbana. É o caso de compostos como o clorofórmio, bromodiclorometano, clorodibromometano e bromofórmio, resultantes da halogenação de precursores, principalmente substâncias húmicas e fúlvicas presentes na água que será tratada (clorada. Assim, descreve-se sua formação, fontes de exposição humana bem como os aspectos toxicológicos de maior importância: disposição cinética e espectro dos efeitos tóxicos (carcinogênicos, mutagênicos e teratogênicos decorrentes de exposições a longo prazo e baixas concentrações. Níveis seguros de exposição propostos são também fornecidos.

  4. Evidencia neurofisiológica del estado neurocognitivo en pacientes con acromegalia tratada farmacológicamente

    OpenAIRE

    Caballero Martínez, Manuel

    2016-01-01

    Introducción: La acromegalia es un trastorno hormonal producido por la secreción aberrante de hormona del crecimiento (GH) y el consecuente incremento del factor de crecimiento similar a la insulina 1 (IGF-I) generalmente debido a la acción de un adenoma hipofisario, y que produce complicaciones sistémicas, incluyendo complicaciones neurocognitivas. Además, también se han descrito alteraciones neurofisiológicas en el análisis espectral...

  5. Identificación y caracterización de especies de Neosartorya aisladas de frutillas (Fragaria spp. frescas y tratadas térmicamente

    Directory of Open Access Journals (Sweden)

    Laura Frisón

    2012-12-01

    Full Text Available El género Aspergillus es uno de los géneros fúngicos más estudiados y de gran impacto a nivel industrial. La sección Fumigati incluye unas pocas especies anamorfas del género Aspergillus. Las especies que son teleomorfas se encuentran dentro del género Neosartorya. Este es un moho resistente al calor que causan problemas en las industrias alimentarias o enfermedades en los seres humanos. Sus ascosporas han sido aisladas a partir de frutas, pulpas y jugos, ya que pueden sobrevivir a los tratamientos de térmicos industriales pudiendo aparecer la contaminación post-pasteurización. El objetivo fue caracterizar aislados de Neosartorya de frutillas frescas recién cosechadas y tratadas térmicamente, analizando la ornamentación de las ascosporas, toxicidad y resistencia térmica. Se aislaron las colonias, y se identificaron macro y microscópicamente siguiendo la metodología de Pitt y Hocking (2009, de 60 muestras. Se caracterizaron las ascosporas por microscopía electrónica de barrido. Se determinó la capacidad toxicogénica de los extractos por cromatografía líquida de alta eficiencia. Se evaluó la resistencia térmica a diferentes temperaturas. Se aislaron 18 cepas de Neosartorya de frutillas recién cosechadas, y otros mohos termorresistentes como Arthrinium phaeospermum, Byssochlamys nivea y Talaromyces macrosporus. En las frutillas tratadas térmicamente no se aislaron mohos termorresistentes. Trece aislados mostraron ascosporascoincidentes con N. fischeri, el resto con N. spinosa. Los aislados de N. fischeri produjeron fumitremorgina A y B y verruculógeno en arroz, pero no lo hicieron en frutillas frescas. Los parámetros de resistencia térmica fueron: D80 ºC: 20 - 22 minutos, D85 ºC: 9 - 11 minutos, D90 ºC: 2 - 3 minutos y z: 10 - 11 ºC para N. fischeri y D80 ºC: > 120 minutos, D85 ºC: 11 - 94 minutos, D90 ºC: 3 - 15 minutos y z: 6 - 9 ºC para N. spinosa. Es indispensable aplicar buenas prácticas agrícolas y

  6. Identificación y caracterización de especies de Neosartorya aisladas de frutillas (Fragaria spp. frescas y tratadas térmicamente

    Directory of Open Access Journals (Sweden)

    Laura Frisón

    2012-01-01

    Full Text Available El género Aspergillus es uno de los géneros fúngicos más estudiados y de gran impacto a nivel industrial. La sección Fumigati incluye unas pocas especies anamorfas del género Aspergillus. Las especies que son teleomorfas se encuentran dentro del género Neosartorya. Este es un moho resistente al calor que causan problemas en las industrias alimentarias o enfermedades en los seres humanos. Sus ascosporas han sido aisladas a partir de frutas, pulpas y jugos, ya que pueden sobrevivir a los tratamientos de térmicos industriales pudiendo aparecer la contaminación post-pasteurización. El objetivo fue caracterizar aislados de Neosartorya de frutillas frescas recién cosechadas y tratadas térmicamente, analizando la ornamentación de las ascosporas, toxicidad y resistencia térmica. Se aislaron las colonias, y se identificaron macro y microscópicamente siguiendo la metodología de Pitt y Hocking (2009, de 60 muestras. Se caracterizaron las ascosporas por microscopía electrónica de barrido. Se determinó la capacidad toxicogénica de los extractos por cromatografía líquida de alta eficiencia. Se evaluó la resistencia térmica a diferentes temperaturas. Se aislaron 18 cepas de Neosartorya de frutillas recién cosechadas, y otros mohos termorresistentes como Arthrinium phaeospermum, Byssochlamys nivea y Talaromyces macrosporus. En las frutillas tratadas térmicamente no se aislaron mohos termorresistentes. Trece aislados mostraron ascosporas coincidentes con N. fischeri, el resto con N. spinosa. Los aislados de N. fischeri produjeron fumitremorgina A y B y verruculógeno en arroz, pero no lo hicieron en frutillas frescas. Los parámetros de resistencia térmica fueron: D80 ºC: 20 - 22 minutos, D85 ºC: 9 - 11 minutos, D90 ºC: 2 - 3 minutos y z: 10 - 11 ºC para N. fischeri y D80 ºC: > 120 minutos, D85 ºC: 11 - 94 minutos, D90 ºC: 3 - 15 minutos y z: 6 - 9 ºC para N. spinosa. Es indispensable aplicar buenas prácticas agrícolas y

  7. IS IT POSSIBLE TO USE BEVACIZUMAB BIOSIMILAR IN ALL INDICATIONS REGISTERED FOR ORIGINAL DRUG?

    Directory of Open Access Journals (Sweden)

    S. V. Orlov

    2016-01-01

    Full Text Available The possibility of extrapolation of indications for biosimilars is one of the issues widely discussed in modern literature. Currently, the European Medicines Agency (EMA and the Food and Drug Administration (FDA have identified specific conditions under which for biosimilars extrapolation of indications is possible. In2015, athe first bioanalogue bevacizumab, (produced by JSC "BIOCAD", has been registered. The article provides summary of the pivotal clinical study of Bevacizumab bioanalogue conducted in patients with non-small cell lung cancer. The article includes detailed scientific justification for the extrapolation of data on the efficacy, safety and immunogenicity obtained in the pivotal study to other indications, registered for the original bevacizumab drug.

  8. Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme

    DEFF Research Database (Denmark)

    Hofland, Kenneth F; Hansen, Steinbjørn; Sorensen, Morten

    2014-01-01

    BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated...... from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS....

  9. Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

    Directory of Open Access Journals (Sweden)

    Qingqing PAN

    2011-07-01

    Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

  10. Bevacizumab Improves Achilles Tendon Repair in a Rat Model

    Directory of Open Access Journals (Sweden)

    Herbert Tempfer

    2018-04-01

    Full Text Available Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days post-surgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young’s modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

  11. Bevacizumab: an option for refractory epistaxis in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Amann, Arno; Steiner, Normann; Gunsilius, Eberhard

    2015-08-01

    Recurrent epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients significantly decreases their quality of life. Treatment in therapy refractory patients is limited although various options have been tested so far. Herein, one patient is described that was treated for HHT for over 20 years with only intermediate benefits. As epistaxis duration and frequency increased continuously, bevacizumab 5 mg/kg was administered every 2 weeks. During the time of treatment (six doses) and up to 3 month afterwards clinical symptoms, blood pressure, cardiac output, pulmonary arterial hypertension (PAH), bleeding duration and frequency were assessed as criteria for treatment benefit. Duration and frequency of epistaxis decreased immediately after the first application resulting in reduced need of blood transfusions. After completion of six cycles, a further decrease in frequency and duration of bleeding was noted. Cardiac output and PAH decreased or remained stable, respectively, during time and after treatment. No increase in blood pressure could be found but a significant increase in heart rate was experienced after completion of all six applications. Unfortunately, the patient died due to a cerebral abscess. Bevacizumab led to an improvement of HHT related epistaxis, refractory to other treatments.

  12. An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

    Science.gov (United States)

    Wu, Lihteh; Evans, Teodoro

    2011-01-01

    The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

  13. Un caso de osteocondritis costal tífica tratado con vacunas y antivirus

    OpenAIRE

    Lleras Acosta, F.; Rueda H., Alfonso

    2011-01-01

    Por considerala de importancia práctica, presentamos la historiaclínica de una enferma afectada de osteocondritis costal de origen Eberthiano, tratada con éxito completo por las autovacunas y antivirus, Debemos esta interesante observación al Dr. Juan N. Carpas y al interno de su servicio de mujeres, Sr. Azuero, quienes galantemente nos suministraron los datos clínicos y las observaciones relativas a los efectos producidos por las vacunas.

  14. Un caso de Osteocondritis costal tífica tratado con vacunas y antivirus

    Directory of Open Access Journals (Sweden)

    F. Lleras Acosta

    1932-05-01

    Full Text Available Por considerala de importancia práctica, presentamos la historia clínica de una enferma afectada de osteocondritis costal de origen Eberthiano, tratada con éxito completo por las autovacunas y antivirus, Debemos esta interesante observación al Dr. Juan N. Carpas y al interno de su servicio de mujeres, Sr. Azuero, quienes galantemente nos suministraron los datos clínicos y las observaciones relativas a los efectos producidos por las vacunas.

  15. Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Jakobsen, J N; Urup, T; Grunnet, K

    2018-01-01

    The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination...... therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been......-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision...

  16. Fluorescently labeled bevacizumab in human breast cancer: defining the classification threshold

    Science.gov (United States)

    Koch, Maximilian; de Jong, Johannes S.; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E.; Adams, Arthur L. L.; Kranendonk, Mariëtte E. G.; Terwisscha van Scheltinga, Anton G. T.; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N.; Schröder, Carolien P.; Jorritsma-Smit, Annelies; Linssen, Matthijs D.; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B.; Elias, Sjoerd G.; Oliveira, Sabrina; Witkamp, Arjen J.; Mali, Willem P. Th. M.; Van der Wall, Elsken; Garcia-Allende, P. Beatriz; van Diest, Paul J.; de Vries, Elisabeth G. E.; Walch, Axel; van Dam, Gooitzen M.; Ntziachristos, Vasilis

    2017-07-01

    In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging.

  17. Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Kapelakis

    2017-05-01

    Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

  18. Bevacizumab compared with Diode Laser in stage 3 posterior retinopathy of prematurity: a 5 year follow-up

    LENUS (Irish Health Repository)

    O’Keeffe, N

    2016-02-01

    We conducted a prospective randomized study to compare outcomes of intravitreal Bevacizumab versus diode laser in thirty eyes of fifteen premature babies with zone 1 or posterior zone 2 retinopathy of prematurity (ROP). We recorded complications, regression\\/reactivation of ROP, visual outcome, refractive error and systemic complications. The Bevacizumab-treated eyes showed rapid regression of the ROP with resolution of plus disease and flattening of the ridge at 48 hours post injection. In 3 Bevacizumab-treated eyes, reactivation occurred and were treated with laser (3 eyes) or a further Bevacizumab injection (1 eye). Of the diode laser treated eyes, one showed progression and was treated with Bevacizumab. At 5-year follow-up, good outcomes were observed in both treatment groups. However, less myopia was found in the Bevacizumab compared with the diode laser treated eyes.

  19. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours

    DEFF Research Database (Denmark)

    Poulsen, H.S.; Grunnet, K.; Sorensen, M.

    2009-01-01

    MATERIAL AND METHODS: We retrospectively determined the efficacy and safety of a combination of bevacizumab and irinotecan in a consecutive series of 52 heavily pre-treated patients with recurrent high-grade brain tumours. Patients received bevacizumab (10 mg/kg) and irinotecan [340 mg/m(2...... acceptable safety and is a clinically relevant choice of therapy in heavily pre-treated patients with recurrent high-grade brain tumours Udgivelsesdato: 2009...

  20. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

    OpenAIRE

    Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

    2014-01-01

    Introduction Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. Methods First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligam...

  1. Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

    Science.gov (United States)

    Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

    2013-05-01

    Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

  2. Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Ivan Novitzky

    2016-01-01

    Full Text Available To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7 received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16, total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19 were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h bevacizumab injected mice (n=7 they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16 they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03 and sildenafil-treated (p=0.003 groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.

  3. Wound dehiscence and device migration after subconjunctival bevacizumab injection with Ahmed glaucoma valve implantation

    OpenAIRE

    Arezoo Miraftabi; Naveed Nilforushan

    2016-01-01

    Purpose: To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. Case Report: A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposur...

  4. Managed hypertensive crisis induced by bevacizumab in patient with metastatic lung adenocarcinoma

    International Nuclear Information System (INIS)

    Gracova, K.; Dolakova, L.

    2015-01-01

    Purpose and objective: The aim of the casuistry is to present a case report of a patient with metastatic lung adenocarcinoma and describe the successful management of hypertensive crisis, which is one of the most common cardiovascular complications of bevacizumab therapy. Casuistry: We describe 82-year old patient with lung adenocarcinoma verified by cytology of fluidothorax. Patient started chemotherapy in the scheme of carboplatin + paclitaxel with addition of bevacizumab since the third cycle. We provided a CT-scan which described partial tumour regression after six cycles of chemotherapy and four cycles of bevacizumab. Before the first cycle of maintenance therapy with bevacizumab patient overcame hypertensive crisis with neurological symptomatology which reacted positively to standard antihypertensives added to the therapy. After the stabilization we continued oncological treatment until disease progression and post chemotherapeutic ischemic colitis occurrence. Conclusion: Arterial hypertension is a common adverse effect of treatment with VEGF inhibitors. Considering the fact that the hypertension may occur at any time during the treatment with bevacizumab, blood pressure should be measured before, during and after the infusion. This side effect is reversible. On the basis of several case studies a positive association between arterial hypertension and prolonged survival in cancer patients has been found, as a difference from those without arterial hypertension during the treatment. Antihypertensive treatment does not reduce the antitumor effect of bevacizumab treatment. (author)

  5. Coriocarcinoma con metástasis pulmonar

    Directory of Open Access Journals (Sweden)

    Vicia Sánchez Abalos

    2014-05-01

    Full Text Available Se presenta el caso clínico de una fémina de 44 años de edad, con 32 semanas de embarazo, la cual fuera ingresada en la Unidad de Cuidados Intensivos del Hospital General Docente "Dr. Juan Bruno Zayas Alfonso" de Santiago de Cuba, por presentar insuficiencia respiratoria aguda como consecuencia de una sepsis. La paciente fue tratada con cefalosporina de tercera generación y ventilación mecánica no invasiva, pero se mantuvieron las características gasométricas de hipoxemia y una mala reacción terapéutica, por lo que se requirió instrumentación de las vías respiratorias y soporte hemodinámico, sin lograr regresión del cuadro clínico, lo cual condujo a un paro cardiorrespiratorio y, con ello, a la muerte. La necropsia mostró un coriocarcinoma del endometrio con metástasis pulmonar

  6. Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

    International Nuclear Information System (INIS)

    Britten, Carolyn D; Gomes, Antoinette S; Wainberg, Zev A; Elashoff, David; Amado, Rafael; Xin, Yan; Busuttil, Ronald W; Slamon, Dennis J; Finn, Richard S

    2012-01-01

    Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation

  7. Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

    Directory of Open Access Journals (Sweden)

    Jeevan Kumar

    2012-01-01

    Full Text Available We report a case of bevacizumab- (BEV- induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

  8. Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

    Directory of Open Access Journals (Sweden)

    Gelcimar Moresco

    2011-06-01

    Full Text Available O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA, que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA. Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

  9. Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

    Science.gov (United States)

    Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

    2018-06-09

    Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

  10. Reversal of cerebral radiation necrosis with bevacizumab treatment in 17 Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang Yang

    2012-08-01

    Full Text Available Abstract Background Bevacizumab has been suggested as a new treatment modality for cerebral radiation necrosis due to its ability to block the effects of vascular endothelial growth factor (VEGF in leakage-prone capillaries, though its use still remains controversial in clinical practice. Methods The use of bevacizumab in 17 patients with symptomatic cerebral radiation necrosis poorly controlled with dexamethasone steroid treatments was examined between March 2010 and January 2012. Bevacizumab therapy was administered for a minimum of two cycles (7.5 mg/kg, at two-week interval with a median of four bevacizumab injections. Changes in bi-dimensional measurements of the largest radiation necrosis lesions were observed by gadolinium-enhanced and T2-weighted magnetic resonance imaging (MRI. Additionally, dexamethasone dosage, Karnofsky performance status (KPS, adverse event occurrence and associated clinical outcomes were recorded for each patient. Results MRI analysis revealed that the average reduction was 54.9% and 48.4% in post-gadolinium and T2-weighted sequence analysis, respectively. Significant clinical neurological improvements were expressed in 10 patients according to KPS values. Dexamethasone reduction was achieved four weeks after initiation of bevacizumab in all patients, with four patients successfully discontinuing dexamethasone treatment. Mild to moderate bevacizumab-related adverse events, such as fatigue, proteinuria and hypertension were observed in three patients. Upon follow-up at 4 to 12 months, 10 patients showed clinical improvement, and 7 patient deaths occurred from tumor progression (5 patients, recurrent necrosis (1 patient, and uncontrolled necrosis-induced edema (1 patient. Conclusions These findings suggest bevacizumab as a promising treatment for cerebral radiation necrosis induced by common radiation therapies, including external beam radiotherapy (EBRT, stereotactic radiosurgery (SRS, and fractionated stereotactic

  11. Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

    Science.gov (United States)

    SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

    2016-01-01

    The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

  12. Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Tappenden, P; Jones, R; Paisley, S; Carroll, C

    2007-03-01

    To assess the clinical effectiveness and cost-effectiveness of bevacizumab and cetuximab in the treatment of individuals with metastatic colorectal cancer (CRC). Searches of main electronic databases were conducted in April and May 2005. For the assessment of bevacizumab, trials were included if they recruited participants with untreated metastatic CRC for first-line treatment. Only trials comparing bevacizumab in combination with irinotecan and/or established fluorouracil (5-FU)-containing or releasing regimens given as first-line therapy were included. For the assessment of cetuximab, trials were included if they recruited participants with epidermal growth-factor receptor-expressing metastatic CRC who had previously failed irinotecan-including therapy. Independent cost-effectiveness models of bevacizumab and cetuximab were developed using survival modelling methods. Adding bevacizumab to irinotecan in combination with 5-FU/folic acid (FA) plus irinotecan resulted in a statistically significant increase in median overall survival (OS) of 4.7 months. Adding bevacizumab to 5-FU/FA resulted in a non-significant increase in median OS of 3.7 months within one study and 7.7 months in another. Adding bevacizumab to irinotecan, fluorouracil and leucovorin (IFL) resulted in a statistically significant increase in median progression-free survival (PFS) of 4.4 months. Adding bevacizumab to 5-FU/FA resulted in a statistically significant increase in median PFS of 3.7 months, and a statistically significant increase in time to disease progression of 3.8 months compared to FU/FA alone. An overall tumour response rate of 44.8% was reported for bevacizumab plus IFL compared to 34.8% for IFL plus placebo. This addition was statistically significant. The addition of bevacizumab to 5-FU/FA resulted in a significant difference in tumour response rate within one study, but not another. Bevacizumab in combination with IFL or 5-FU/FA was observed to result in an increase of grade 3

  13. Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

    2011-01-01

    The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

  14. Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

    Science.gov (United States)

    Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

    2013-01-01

    The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

  15. Equinoterapia en niñas con síndrome de Rett

    OpenAIRE

    Ibáñez Ibáñez, Diana

    2013-01-01

    El presente estudio tiene como objetivo principal la valoración de los beneficios que la equinoterapia tiene en niñas afectadas con síndrome de Rett, y se llevará a cabo en un centro hípico que reúna las condiciones e instalaciones necesarias para poder realizar las sesiones de tratamiento. Será un estudio cualitativo y transversal, en el que participarán tanto fisioterapeutas expertos en el ámbito de la equinoterapia como niñas con síndrome de Rett que estén siendo tratadas co...

  16. Profilaxis de la hipertensión arterial tipo III con el uso de la aspirina

    OpenAIRE

    Rodríguez Santana, Maricela; García León, Lázaro; Valdés Suárez, Ernesto; Hernández Cabrera, Jesús

    1997-01-01

    Se realiza un estudio, en el período comprendido entre enero de 1994 hasta enero con 1995, de 104 gestantes diagnosticadas como hipertensas crónicas en la consulta externa del hospital docente ginecoobstétrico de Matanzas. Del total de la muestra, 54 fueron tratadas con dosis bajas en aspirina y en 50 no se aplicó este tratamiento. Las gestantes que utilizaron bajas dosis de aspirina, no desarrollaron hipertensión arterial tipo III (HTA III), ni se presentaron en las mismas complicaciones mat...

  17. Bevacizumab in Treatment of High-Risk Ovarian Cancer—A Cost-Effectiveness Analysis

    Science.gov (United States)

    Herzog, Thomas J.; Hu, Lilian; Monk, Bradley J.; Kiet, Tuyen; Blansit, Kevin; Kapp, Daniel S.; Yu, Xinhua

    2014-01-01

    Objective. The objective of this study was to evaluate a cost-effectiveness strategy of bevacizumab in a subset of high-risk advanced ovarian cancer patients with survival benefit. Methods. A subset analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high-risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost-effectiveness ratio per life-year saved was established. Results. The estimated cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high-risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of B was $167,771 per life-year saved. Conclusion. In this clinically relevant subset of women with high-risk advanced ovarian cancer with overall survival benefit after bevacizumab, our economic model suggests that the incremental cost of bevacizumab was approximately $170,000. PMID:24721817

  18. Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

    International Nuclear Information System (INIS)

    Finger, Paul T.

    2008-01-01

    Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

  19. Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

    Science.gov (United States)

    Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

    2018-04-18

    Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

  20. Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

    Science.gov (United States)

    Stokes, P; Rimmer, J

    2018-03-01

    Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT. A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life. A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis. Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments. The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

  1. Bevacizumab in the treatment of NSCLC: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Russo AE

    2017-12-01

    Full Text Available Alessia E Russo,1 Domenico Priolo,1 Giovanna Antonelli,1 Massimo Libra,2 James A McCubrey,3 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina (Messina, Italy; 2Laboratory of Translational Oncology & Functional Genomics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA Abstract: Non-small-cell lung cancer (NSCLC represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis. Bevacizumab (bev; Avastin® is a recombinant humanized monoclonal antibody that neutralizes VEGF’s biologic activity through a steric blocking of its binding with VEGF receptor. Currently, bev is the only antiangiogenic agent approved for the first-line treatment of advanced or recurrent nonsquamous NSCLC in “bev-eligible” patients. The ineligibility to receive bev is related to its toxicity. In the pivotal trials of bev in NSCLC, fatal bleeding events including pulmonary hemorrhage were observed with rates higher in the chemotherapy-plus-bev group. Therefore, in order to reduce the incidence of severe pulmonary hemorrhage, numerous exclusion criteria have been characteristically applied for bev such as central tumor localization or tumor cavitation, use of anticoagulant therapy, presence of brain metastases, age of patients (elderly. Subsequent studies designed to evaluate the safety of bev have demonstrated that this agent is safe and

  2. Desempenho inicial de plântulas de soja oriundas de sementes quimicamente tratadas

    Directory of Open Access Journals (Sweden)

    Rafael Oliveira Vergara

    2016-12-01

    Full Text Available A soja atualmente é um dos principais produtos do agronegócio brasileiro. Diversos fatores afetam a produtividade da cultura, entre eles o número de plantas estabelecidas merece devido destaque. Grande parte dos produtores brasileiros utiliza o tratamento químico de sementes com objetivo de melhorar o estande inicial de plantas. Neste trabalho se objetivou avaliar o desempenho inicial de sementes de soja tratadas quimicamente com os principais produtos disponíveis no mercado. Utilizou-se dois lotes da cultivar BMX Turbo RR, com distintos níveis de vigor, estes foram submetidos aos três principais tratamentos químicos do mercado. Foram avaliada emergência, índice de velocidade de emergência, comprimento e biomassa seca de raiz, área foliar. Ocorreu diferença entre os tratamentos, no lote de baixo vigor o tratamento quatro (fludioxonil, metalaxylm e tiametoxan melhorou o desempenho, em sementes de alto vigor o tratamento não favoreceu o desempenho das sementes.Initial performance of soybean seedlings derived from chemically treated seedAbstract: Soy is currently one of the main products of the Brazilian agribusiness. Several factors affect the productivity of the culture, including the number of established plants deserves due attention. Most Brazilian producers use chemical seed treatment in order to improve the plant stand. This work aimed to evaluate the initial performance of soybean seeds chemically treated with leading products on the market. We used two batches of growing BMX Turbo RR, with different levels of vigor, these were subjected to three main chemical treatments market. emergency were evaluated, emergency speed index, length and root dry biomass, leaf area. Was no difference between treatments in the lot of low force treatment four (fludioxonil, metalaxylm and Thiamethoxam improved performance in high vigor seed treatment did not improve the performance of seeds.

  3. Enraizamento de estacas lenhosas de ameixeiras tratadas com ácido indolbutírico

    Directory of Open Access Journals (Sweden)

    Mindêllo Neto Ubirajara Ribeiro

    2006-01-01

    Full Text Available Considerando o grande interesse pela ameixeira no mercado de frutas, existe a necessidade de buscar técnicas mais eficientes na produção de mudas de qualidade e com maior uniformidade. Buscou-se, neste trabalho, verificar o potencial de enraizamento de estacas lenhosas de 12 cultivares de ameixeira (América, Amarelinha, Letícia, Pluma 7, Reubennel, Rosa Mineira, Santa Rita, Santa Rosa, Simka, The First, Wade e XV de novembro tratadas com ácido indolbutírico (AIB, em concentrações de 0, 1000 e 3000mg L-1, em imersão rápida por 5 segundos na sua parte basal. O estudo foi desenvolvido de junho a setembro de 2004, na EMBRAPA Transferência de Tecnologia, localizada no município de Canoinhas, SC. Estacas lenhosas foram coletadas de plantas matrizes de dois anos, situadas em casa-de-vegetação e padronizadas com um comprimento médio de 12cm e diâmetro de 6mm, sendo acondicionadas em bandejas de poliestireno expandido com 72 células de 0,000015m3, contendo vermiculita como substrato e mantidas em casa de vegetação sem nebulização intermitente por 97 dias. O delineamento experimental foi o inteiramente casualizado com quatro repetições e 12 estacas por parcela. As maiores porcentagens de enraizamento (acima de 70% foram obtidas nas estacas das cultivares XV de Novembro, Rosa Mineira e Santa Rita. A aplicação de 1000mg L-1 AIB, foi melhor no enraizamento de estacas de ameixeira proporcionando maior número de raízes por estaca e maior comprimento das raízes.

  4. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Madsen, Christine Vestergaard; Andersen, Rikke Fredslund

    2014-01-01

    of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance......-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.......AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment...

  5. [A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].

    Science.gov (United States)

    Mori, Ayano; Kogawa, Takahiro; Arihara, Youhei; Abe, Masakazu; Tamura, Fumito; Abe, Seiichirou; Kukitsu, Takehiro; Ihara, Hideyuki; Sumiyoshi, Tetsuya; Yoshizaki, Naoto; Kondou, Hitoshi; Tsuji, Yasushi

    2013-05-01

    A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

  6. Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

    Science.gov (United States)

    Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

    2017-09-01

    Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

  7. An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

    Directory of Open Access Journals (Sweden)

    Giuseppe Lombardi

    2014-01-01

    Full Text Available Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

  8. [Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

    Science.gov (United States)

    Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

    2012-02-01

    Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

  9. An overview of fotemustine in high-grade gliomas: from single agent to association with bevacizumab.

    Science.gov (United States)

    Lombardi, Giuseppe; Farina, Patrizia; Della Puppa, Alessandro; Cecchin, Diego; Pambuku, Ardi; Bellu, Luisa; Zagonel, Vittorina

    2014-01-01

    Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

  10. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response...... and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

  11. Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation.

    Science.gov (United States)

    Miraftabi, Arezoo; Nilforushan, Naveed

    2016-01-01

    To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery.

  12. Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

    International Nuclear Information System (INIS)

    Gutin, Philip H.; Iwamoto, Fabio M.; Beal, Kathryn; Mohile, Nimish A.; Karimi, Sasan; Hou, Bob L.; Lymberis, Stella; Yamada, Yoshiya; Chang, Jenghwa

    2009-01-01

    Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.

  13. Effect of Intra Vitreal Injection of Bevacizumab on Intra-Occular Pressure

    International Nuclear Information System (INIS)

    Jaffar, S.; Tayyab, A.; Matin, Z. I.; Masrur, A.; Naqaish, R.

    2016-01-01

    Background: Bevacizumab has been in use as a therapeutic agent for macular oedema for several years. While its efficacy has been well documented, its use has been shown to cause a transient rise in the intra-ocular pressure. The aim of this study was to evaluate the long term effect of intra-vitreal injection of Bevacizumab on Intra-ocular pressure. Methods: One hundred eyes (n=100) of one hundred patients, requiring intra-vitreal injection of Bevacizumab for diabetic macular oedema were recruited from Shifa Foundation Community Health Centre (SFCHC) between January and December 2014. Patients of glaucoma, ocular hyper-tension, known allergy to Bevacizumab or had injections of Bevacizumab prior to the study were excluded. Intra-ocular pressure was measured using a Goldmann applanation tonometer, prior to, and at six and twelve months after the injection. The pre- and post- injection Intra-ocular pressure was entered into the database. Test of significance was applied to investigate whether there was a significant change in intra-ocular pressure after the injection. Results: The mean age of the patient was 56.97 years (±14.97). The mean intra-ocular pressure was 13.86 (±3.16) mmHg before injection, while post-injection mean Intra-Ocular pressure was 14.21 (±3.12) mmHg and 13.79 (±3.07) at six and twelve months respectively. Between baseline and six months there was a statistically significant difference in intra-ocular pressure (p=0.03), while no significant difference existed in the intra-ocular pressure between baseline and twelve months (p=0.92). Conclusion: Intra-vitreal injection of Bevacizumab is associated with a statically significant rise in intra-ocular pressure at six months, while no significant difference was seen at twelve months compared to baseline. (author)

  14. Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study.

    Science.gov (United States)

    Vandewalle, Evelien; Abegão Pinto, Luís; Van Bergen, Tine; Spielberg, Leigh; Fieuws, Steffen; Moons, Lieve; Spileers, Werner; Zeyen, Thierry; Stalmans, Ingeborg

    2014-01-01

    To investigate the efficacy and safety of a single intracameral bevacizumab injection to improve the outcome of trabeculectomy. A 12-month, prospective, randomised, double-masked, placebo-controlled trial. Patients with medically uncontrolled open-angle glaucoma scheduled for a primary trabeculectomy were recruited and randomised to receive 50 µL of either bevacizumab (1.25 mg) or placebo (balanced salt solution) peroperatively. Absolute success was defined as intraocular pressure (IOP) ≤18 mm Hg and >5 mm Hg with at least 30% reduction from baseline and no loss of light perception. Success through the use of additional medical and/or surgical IOP-lowering treatments was defined as qualified success. 138 patients completed a 12-month follow-up, 69 of whom were in the bevacizumab treated group. IOP at 1 year postoperatively was significantly lower than baseline (placebo: 25.6±9.9 mm Hg vs 11.5±3.9 mm Hg, p<0.01; bevacizumab: 24.8±8.1 mm Hg vs 11.9±3.8 mm Hg, p<0.01), with no difference between treatment groups (p=0.69). However, absolute success was higher in the bevacizumab group (71% vs 51%, p=0.02), with the need for IOP-lowering interventions (needlings) being lower in this group (12% vs 33%, p=0.003). Complication rates were low and comparable between groups. Peroperative administration of intracameral bevacizumab significantly reduces the need for additional interventions during the follow-up of patients undergoing trabeculectomy.

  15. Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

    Science.gov (United States)

    Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

    2015-01-01

    Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

  16. Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

    Science.gov (United States)

    Chapman, Suzannah J; McKavanagh, Daniel; Burge, Matthew E; McPherson, Ian; Walpole, Euan; Hollingworth, Samantha A

    2017-10-01

    Metastatic colorectal cancer has a large burden of disease in Australia. Medical therapy is fundamental to extending survival and improving quality of life. The benefits of two costly medicines, bevacizumab and cetuximab, used in Australia remain unclear. The aim of this study was to retrospectively examine the use of these two medicines in metastatic colorectal cancer across five public hospitals in south east Queensland and to compare clinical outcomes to those of published clinical trials. We extracted data from the chemotherapy prescribing database for patients planned for bevacizumab or cetuximab therapy between 2009 and 2013. Median overall survival was estimated using Kaplan-Meier methods. There were 490 bevacizumab-containing protocols planned and 292 patients received at least one dose of bevacizumab. Median overall survival was 17.2 months (95% confidence interval [CI], 15.4-19.3). Of 208 planned cetuximab-containing protocols, 134 patients received at least one dose of cetuximab. Median overall survival was 9.1 months (95% CI, 7.6-12.0). Thirty-day mortality rates from date of first dose were 0.7% for bevacizumab and 7.5% for cetuximab. Overall survival of patients receiving bevacizumab and cetuximab was consistent with clinical trials, providing some assurance that benefits seen in trials are observed in usual practice. This study provides a methodology of using routinely collected health data for clinical monitoring and research. Because of the high cost of these medicines and the lack of toxicity data in this study, further analysis in the postmarketing setting should be explored. © 2016 John Wiley & Sons Australia, Ltd.

  17. A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

    Science.gov (United States)

    Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

    2017-10-01

    This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

  18. Edema macular por tratamiento con rosiglitazona en diabetes mellitus

    OpenAIRE

    Asensio-Sánchez, V.M.; Asensio-Sánchez, M.J.; Gómez-Ramírez, V.

    2010-01-01

    Caso clínico: Mujer de 61 años diabética tipo 2 de 7 años de evolución en tratamiento con insulina. Se añade rosiglitazona (4mg al día) para conseguir un control glucémico adecuado. Un mes después, la paciente presenta edema generalizado y pérdida de visión. El estudio fundoscópico mostró edema macular bilateral. En la exploración sistémica destacaban edemas periféricos. La rosiglitazona fue suspendida y la paciente fue tratada de forma conservadora, con resolución rápida de los edemas perifé...

  19. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

    Directory of Open Access Journals (Sweden)

    Isis A. S. Brito

    2015-01-01

    Full Text Available Radiation retinopathy (RR is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab. One must be aware of distant side effects after intravitreal injections.

  20. Simultaneous application of bevacizumab and anti-CTGF antibody effectively suppresses proangiogenic and profibrotic factors in human RPE cells.

    Science.gov (United States)

    Bagheri, Abouzar; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Sheibani, Nader; Astaneh, Shamila Darvishalipour; Kanavi, Mozhgan Rezaei; Mohammadian, Azam

    2015-01-01

    Retinal pigment epithelial (RPE) cells play key roles in the development of choroidal neovascularization and subsequent fibrosis. We investigated the impact of bevacizumab, antihuman vascular endothelial growth factor (VEGF) antibody, and anticonnective tissue growth factor (anti-CTGF) neutralizing antibody, individually or in combination, on proangiogenic and profibrotic properties of RPE cells. Primary cultures of human RPE cells were incubated with different concentrations of bevacizumab (0.25, 0.5, and 0.8 mg/ml) and/or anti-CTGF (10 μg/ml), and cell proliferation and apoptosis were determined. Expression and activity of proangiogenic and profibrotic genes including matrix metalloproteinases (MMP)-2 and 9, VEGFA, CTGF, vascular endothelial growth factor receptor-1 (VEGFR-1), cathepsin D, tissue inhibitor of metalloproteinases (TIMP) -1 and -2, and alpha smooth muscle actin (α-SMA) were assessed with slot blot, real-time RT-PCR, and zymography. Bevacizumab alone inhibited proliferation of RPE cells while anti-CTGF or bevacizumab and anti-CTGF combined had no inhibitory effect in this regard. Bevacizumab increased MMP-2, MMP-9, and cathepsin D but decreased VEGFA and VEGFR-1 expression. The CTGF level was increased by using 0.25 mg/ml bevacizumab but decreased at the 0.8 mg/ml concentration of bevacizumab. Treatment with anti-CTGF antibody decreased MMP-2 expression whereas combined treatment with bevacizumab and anti-CTGF resulted in decreased expression of MMP-2, TIMP-1, cathepsin D, VEGFA, CTGF, and α-SMA in the treated cultures. Treatment of RPE cells with the combination of bevacizumab and anti-CTGF could effectively suppress the proangiogenic and profibrotic activity of RPE cells.

  1. A case of recipient bed melt and wound dehiscence after penetrating keratoplasty and subconjunctival injection of bevacizumab.

    Science.gov (United States)

    Bhasin, Purendra; Gujar, Prateek; Bhasin, Priyamvada

    2012-11-01

    We describe a case of recipient bed melt and wound dehiscence after uneventful penetrating keratoplasty and subconjunctival injection of bevacizumab. Three weeks postoperatively, the patient presented with limbal ischemia, recipient bed melt, and wound dehiscence corresponding to the area of bevacizumab injection. The melt was managed by application of cyanoacrylate glue along with bandage contact lens. Although the graft survived, there was a problem in re-epithelization. This case highlights the need for further studies to elucidate the therapeutic dose, side effects, and correct timing of using bevacizumab with respect to corneal transplant surgery.

  2. The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Klausen, Camilla; Caye-Thomasen, Per

    2015-01-01

    -34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported...... been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg...

  3. Optimizing bevacizumab dosing in glioblastoma: less is more.

    Science.gov (United States)

    Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

    2017-10-01

    Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

  4. Wound healing complications in brain tumor patients on Bevacizumab.

    Science.gov (United States)

    Ladha, Harshad; Pawar, Tushar; Gilbert, Mark R; Mandel, Jacob; O-Brien, Barbara; Conrad, Charles; Fields, Margaret; Hanna, Teresa; Loch, Carolyn; Armstrong, Terri S

    2015-09-01

    Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.

  5. Reinduction of Bevacizumab in Combination with Pegylated Liposomal Doxorubicin in a Patient with Recurrent Glioblastoma Multiforme Who Progressed on Bevacizumab/Irinotecan

    Directory of Open Access Journals (Sweden)

    Mohammed Almubarak

    2008-01-01

    Full Text Available Glioblastoma multiforme (GBM carries a dismal prognosis despite the current standard of multimodality treatments. Recent studies showed promising results to a regimen consisting of a VEGF inhibitor, (bevacizumab and a topoisomerase I inhibitor (irinotecan [BI] in recurrent GBM. However, those patients with GBM who progress on BI will succumb to their disease generally in a very short period of time. We report a case of a 56-year-old male patient with GBM who declined surgical resection and received chemoradiation with temozolomide. This treatment was withheld secondary to significant thrombocytopenia. Subsequently, he achieved stable disease for 10 months with a regimen consisting of thalidomide and tamoxifen before progressing. This was followed by bevacizumab with irinotecan [BI], for which he had a significant partial response for 8 months with subsequent progression. Reinducing the patient with bevacizumab in combination with a pegylated liposomal doxorubicin [PLD] (a topoisomerase II inhibitor demonstrated antitumor activity with significant shrinkage of contrast enhancing mass and peritumoral edema.

  6. Necrosis de la cabeza femoral tras fractura del cuello femoral tratada mediante osteosíntesis

    OpenAIRE

    Martínez Martín, Angel Antonio; Panisello Sebastiá, Juan José; Lallana Duplá, J.; Herrera Rodríguez, Antonio

    2000-01-01

    Se presenta un análisis retrospectivo de las necrosis aparecidas en 233 pacientes con fractura de cuello femoral fijada con tornillos de esponjosa. La edad media fue de 80,6 años. Setenta y un pacientes (26%) tuvieron una fractura no desplazada (Garden I o II) y 172 (74%) una fractura desplazada (Garden III o IV). Seis meses tras la cirugía 170 pacientes sobrevivían (72,9%). Treinta y cuatro de ellos (20%) habían desarrollado necrosis y 10 (5,9%) colapso. Tras un seguimiento de 12 meses 114 p...

  7. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer

    DEFF Research Database (Denmark)

    Bamias, A; Gibbs, E; Khoon Lee, C

    2017-01-01

    Background: In the open-label randomized phase III AURELIA trial, adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) significantly improved progression-free survival and response rate versus chemotherapy alone, but not overall survival (OS). We explored the effect of ...

  8. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  9. Vincristine, Irinotecan, and Bevacizumab in Relapsed Wilms Tumor With Diffuse Anaplasia.

    Science.gov (United States)

    Schiavetti, Amalia; Varrasso, Giulia; Collini, Paola; Clerico, Anna

    2018-05-01

    The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.

  10. When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

    Science.gov (United States)

    Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

  11. Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases

    Directory of Open Access Journals (Sweden)

    Rose Isono-Nakata

    2018-05-01

    Full Text Available Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV. One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

  12. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

    2010-01-01

    The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard tre...

  13. Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

    Science.gov (United States)

    Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

    2014-11-01

    To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

    Science.gov (United States)

    Lee, Koon-Ja; Lee, Ji-Young; Lee, Sung Ho; Choi, Tae Hoon

    2013-01-01

    To understand the corneal regeneration induced by bevacizumab, we investigated the structure changes of stroma and basement membrane regeneration. A Stick soaked in 0.5 N NaOH onto the mouse cornea and 2.5 mg/ml of bevacizumab was delivered into an alkali-burned cornea (2 μl) by subconjunctival injections at 1 hour and 4 days after injury. At 7 days after injury, basement membrane regeneration was observed by transmission electron microscope. Uneven and thin epithelial basement membrane, light density of hemidesmosomes, and edematous collagen fibril bundles are shown in the alkali-burned cornea. Injured epithelial basement membrane and hemidesmosomes and edematous collagen fibril bundles resulting from alkali-burned mouse cornea was repaired by bevacizumab treatment. This study demonstrates that bevacizumab can play an important role in wound healing in the cornea by accelerating the reestablishment of basement membrane integrity that leads to barriers for scar formation. [BMB Reports 2013; 46(4): 195-200] PMID:23615260

  15. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience

    International Nuclear Information System (INIS)

    Ocvirk, Janja; Moltara, Maja Ebert; Mesti, Tanja; Boc, Marko; Rebersek, Martina; Volk, Neva; Benedik, Jernej; Hlebanja, Zvezdana

    2016-01-01

    Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1 st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1 st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7–16.2) and 11.3 (95% CI, 10.2–12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4–28.9) and 27.4 (95% CI, 22.7–31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21

  16. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2014-02-01

    Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  17. Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

    Science.gov (United States)

    Cuppini, Lucia; Calleri, Angelica; Bruzzone, Maria Grazia; Prodi, Elena; Anghileri, Elena; Pellegatta, Serena; Mancuso, Patrizia; Porrati, Paola; Di Stefano, Anna Luisa; Ceroni, Mauro; Bertolini, Francesco; Finocchiaro, Gaetano; Eoli, Marica

    2013-01-01

    Background Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB). Methods rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. Results A baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001). Conclusions Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab. PMID:24069296

  18. The effect of intravitreal bevacizumab and transpupillary thermotherapy on choroidal metastases and literature review

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    Chun-Ju Lin

    2015-01-01

    Full Text Available Aims : To represent the effects of transpupillary thermotherapy (TTT and intravitreal bevacizumab on choroidal metastases and review the literature. Settings and Design : A retrospective, interventional, noncomparative case series. Materials and Methods : A retrospective, interventional, noncomparative case series of five eyes in three patients with choroidal metastases was conducted. Fundus findings of choroidal metastases were divided into two types: Solitary or diffuse type. The size of the tumor was termed small (15 mm diameter. All eyes received one session of TTT followed by 3 weekly intravitreal bevacizumab injections as an adjuvant therapy. The parameters of treatment for TTT were 1.2-3 mm spot size, 150-300 mW, 60 s with the whole lesion covered confluently. The changes in preoperative and postoperative best-corrected visual acuity (BCVA were recorded. Serial color fundus photography and optical coherent tomography were performed to measure the treatment efficacy. Results : All eight choroidal metastases were solitary type. The size of six tumors was small, the size of one tumor was medium, and the size of one tumor was large. All five eyes of the three patients had improvement of BCVA after treatment. Fundus photos revealed tumor shrinkage and the mean shrinkage percentage was 61.27 ± 21.71%. Optical coherence tomography revealed complete resolution of serous retinal detachment. There was no recurrence after 6 months follow-up. Conclusions : TTT combined with intravitreal bevacizumab injections brought about beneficial effects in reducing tumor size and improving vision in all five eyes of the three patients. Despite the retrospective nature of our study, the absence of control group and the size limitation that, of course, limit the statistical power, TTT combined with intravitreal bevacizumab seems to be efficient in providing another cost-reducing and time-saving treatment option for patients with choroidal metastases. The

  19. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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    Villegas VM

    2014-05-01

    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  20. Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

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    Ayse Oner

    2018-04-01

    Full Text Available AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

  1. Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

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    Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

    2015-01-01

    Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

  2. Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

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    Di Bartolomeo M

    2015-01-01

    Full Text Available Maria Di Bartolomeo,1 Claudia Maggi,1 Francesca Ricchini,1 Filippo Pietrantonio,1 Roberto Iacovelli,1 Filippo de Braud,1 Alessandro Inno2 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 2Department of Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy Abstract: Metastatic colorectal cancer (mCRC, like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a ­historical conservative approach. Keywords: bevacizumab, elderly, metastatic colorectal cancer, antivascular treatment, review

  3. Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

    Science.gov (United States)

    Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

    2018-05-01

    We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

  4. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

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    MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

    2014-01-01

    The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

  5. The Effect of Intravitreal Bevacizumab on Apoptosis of Rat Retina Cells

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    Özcan Kayıkçıoğlu

    2013-01-01

    Full Text Available Pur po se: To investigate the apoptotic effects of intravitreal bevacizumab on rat retinal cells. Ma te ri al and Met hod: Thirty-six male adult Swiss albino rats were randomly divided into two groups. The first group was applied 0.25 mg bevacizumab in 0.01 ml saline, and the second group received the same amount of saline intravitreally. Each group was divided into 3 subgroups. The animals were sacrificed and their globes were enucleated at the 3rd, 24th, and 72nd hours of the experiment. Enucleated eyes were preserved for histological analysis, immunohistochemical analysis of caspase-3, caspase-8, caspase-9, Fas/Fas L, VEGF and VEGF receptors (Flt-1, Flk-1, and TUNEL staining. Re sults: Histological evaluation showed no sign of retinal toxicity in both groups. In TUNEL staining, TUNEL(+ cells were detected in all subgroups, but the number of positive cells was relatively lower in bevacizumab treatment group that reached statistically significant level at 24 and 72 hours of treatment (p<0.001. Immunohistochemical analysis revealed that in saline-treated subgroups, immunoreactivity was more pronounced for all apoptosis-inducing proteins compared to bevacizumab-treated group. Also immunoreactivity of VEGF was prominent in saline treated group. For VEGF receptors, staining was only positive for Flt-1 at the 3rd hour in the control group. Dis cus si on: Bevacizumab did not have apoptosis-inducing potential compared to saline solution in short term, which was documented with TUNEL and immunohistochemical staining. (Turk J Ophthalmol 2013; 43: 39-44

  6. Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

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    Zhe-Li Liu

    2013-04-01

    Full Text Available AIM:To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD. METHODS: Among 60 Chinese patients with exudative AMD (60 eyes, 28 received intravitreal bevacizumab injections (1.25mg and 32 received intravitreal ranibizumab injections (0.5mg, once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA and central retinal thickness (CRT in both groups of patients. We also compared the occurrence of adverse events. RESULTS:At the 6-month follow-up, the mean BCVA (logMAR of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72μm and 352±36.9μm at baseline to 250.86±41.51μm and 243.22±41.38μm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

  7. Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

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    Zheng-Jun Hu

    2015-05-01

    Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3~5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34~38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

  8. Effects of topical bevacizumab application on early bleb failure after trabeculectomy: observational case series

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    Klos-Rola J

    2013-09-01

    Full Text Available Justyna Klos-Rola, Maria Tulidowicz-Bielak, Tomasz Zarnowski Department of Ophthalmology, Medical University of Lublin, Lublin, Poland Background: The aim of this study was to evaluate the influence of topical bevacizumab on the formation and function of filtering blebs in eyes with early bleb failure after antiglaucoma surgery. Methods: Of all patients who underwent mitomycin-augmented trabeculectomy for glaucoma in the Department of Ophthalmology at the Medical University in Lublin, Poland, between March 2009 and March 2010, a total of 21 eyes from 20 patients with injected filtration bleb 9.8 ± 4.7 days after surgery were included in this observational case series. All patients were treated with standard steroid therapy and topical bevacizumab 5 mg/mL five times a day for 20.9 ± 9.8 days. Patients were followed up every other day, and a full eye examination was performed 14, 30, 60, and 180 days after initiation of treatment. Blebs were evaluated for vascularity by slit-lamp examination with concomitant photographic documentation and intraocular pressure measurement. Results: Elevated functional bleb with significantly reduced vascularity was present in 16 eyes, and was flat and nonfunctional in five eyes. Intraocular pressure in all eyes decreased from a mean of 26.6 ± 9.6 mmHg before surgery to 14.6 ± 7.7 mmHg and 15.8 ± 8.3 mmHg at 2 and 6 months after surgery, respectively. Filtration bleb leak was noted in three eyes while on treatment with bevacizumab. Conclusion: Topical application of bevacizumab might favor functional bleb formation after trabeculectomy in eyes with a high risk of failure. Keywords: glaucoma, trabeculectomy, bleb failure, bevacizumab

  9. Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

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    Traina, Tiffany A; Rugo, Hope S; Caravelli, James F; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E; Park, John W; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D; Norton, Larry; Hudis, Clifford A; Dickler, Maura N

    2010-02-01

    Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months. Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

  10. Vida de vaso de inflorescências de Epidendrum ibaguense Kunth tratadas com inibidores de etileno

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    MARCELO AMARAL DE MOURA

    2010-12-01

    Full Text Available O objetivo deste trabalho foi avaliar a influência de inibidores da síntese e ação do etileno, incluindo ácido aminooxiacético (AOA, ácido aminoetoxivinilglicina (AVG, ácido acetilsalicílico (AAS e tiossulfato de prata (STS, aplicados na forma de pulverização ou solução de condicionamento sobre a qualidade de flores cortadas de Epidendrum ibaguense. As hastes foram colhidas e imediatamente submetidas aos seguintes tratamentos: (1 pulverização com 1,0 mM de AOA; (2 pulverização com 1,0 mM de AVG; (3 pulverização com 1,0 mM de AAS; (4 pulsing com 2,0 mM de STS, por 30 minutos; (5 pulverização com 1,0 mM de AOA + pulsing com 2,0 mM de STS, por 30 minutos; (6 pulverização com 1,0 mM de AVG + pulsing com 2,0 mM de STS; (7 pulverização com 1,0 mM de AAS + pulsing com 2,0 mM de STS; (8 pulverização + pulsing com água desionizada (controle. Após os tratamentos, as hastes foram mantidas em vasos com água desionizada, renovada a cada dois dias, para evitar o desenvolvimento de microrganismos. Ao final da longevidade, o qual variou de acordo com o tratamento, as inflorescências submetidas ao AVG e AVG + STS mostraram a maior porcentagem de abertura floral, visto que promoveram aumento de 49 e 88% em relação ao controle. A taxa de abscisão também foi influenciada pelos tratamentos, pois ao oitavo dia, as inflorescências controle apresentaram cerca de 51% de queda das flores, cujo início ocorreu, principalmente, a partir do quinto dia. As inflorescências tratadas ao AAS, AOA, STS, AVG, STS + AAS, STS + AOA e STS + AVG mostraram redução de 11, 39, 47, 71, 38, 61 e 86%, respectivamente. Além disso, houve atraso de 1, 2, 3, 4, 3, 3 e 8 dias para o início da abscisão, respectivamente. A longevidade de E. ibaguense foi afetada pelos inibidores do etileno, mas com exceção de AAS e AOA, os demais tratamentos foram significativamente maiores que o controle. O STS, AVG, AAS + STS, AOA + STS e AVG + STS tiveram longevidade

  11. Extracción y reología de Betaglucanos de cebada y elaboración de masas de pan sin gluten enriquecidas con los extractos

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    Rivero Hernández, Miguel

    2012-01-01

    La materia prima utilizada ha sido la cebada H13 tipo waxy, una cebada desnuda, es decir sin cáscara, con un contenido de beta-glucanos del 4,51%, de la que se obtuvieron tres extractos distintos: el primero procedente de la harina integral de la cebada (18,8 % de -glucanos), el segundo de esa misma harina integral tratada con etanol para inactivar las betaglucanasas (21,5 % de -glucanos), y el tercero procedente de la fracción gruesa de la molienda pretratada igualmente con ...

  12. Enfermidades tratadas e tratáveis pela acupuntura segundo percepção de enfermeiras Enfermedades tratadas y tratables por acupuntura, según la percepción de las enfermeras Nurses' perception about diseases that are treated by acupuncture

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    Leonice Fumiko Sato Kurebayashi

    2009-12-01

    Full Text Available Esse trabalho objetivou identificar e analisar as percepções dos enfermeiros acerca das enfermidades tratadas e tratáveis pela acupuntura. Foram consideradas: (1 as enfermidades das entrevistadas que já haviam se submetido ao tratamento com acupuntura; (2 as enfermidades que as enfermeiras têm e que poderiam ser tratáveis pela acupuntura; (3 sugestões de doenças tratáveis pela acupuntura para o paciente de Unidades de Saúde. Pesquisa de natureza exploratória foi realizada com 33 enfermeiras, em 11 Unidades de Saúde da Região Sudeste do Município de São Paulo, onde havia a terapia de acupuntura. Os resultados demonstraram que a acupuntura foi mais utilizada para o tratamento de estresse (3/21, equivalente a 10,7% e para ansiedade, enxaqueca, lombalgia, mioma e obesidade (2/21, correspondente a 7,1% cada uma. Foi mais sugerida para o tratamento de doenças músculo-esqueléticas (34/82, equivalente a 41,5%, e doenças crônico-degenerativas (8/82, equivalente a 10%.Este trabajo objetivó identificar y analizar las percepciones de las enfermeras acerca de las enfermedades tratadas y tratables por la acupuntura. Fueron consideradas: (1 las enfermedades de las entrevistadas que ya se habían sometido al tratamiento con acupuntura; (2 las enfermedades que las enfermeras tienen que podrían ser tratables por la acupuntura; (3 las sugestiones de enfermedades tratables por la acupuntura para el paciente de Unidades de Salud. Investigación de naturaleza exploratoria fue realizada con 33 enfermeras, en 11 Unidades de Salud de la Región Sureste del Municipio de São Paulo, donde había la terapia de acupuntura. Los resultados demostraron que la acupuntura fue más utilizada para el tratamiento de estrés (3/21, equivalente a 10,7% y para ansiedad, migraña, lumbalgia, mioma y obesidad (2/21, correspondiente a 7,1% cada una. Fue más sugerida para el tratamiento de enfermedades músculo-esqueléticas (34/82, equivalente a 41,5%, y

  13. Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography

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    Reza Golestani

    2013-06-01

    Full Text Available Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.

  14. Nanoparticles in Porous Microparticles Prepared by Supercritical Infusion and Pressure Quench Technology for Sustained Delivery of Bevacizumab

    Science.gov (United States)

    K.Yandrapu, Sarath; Upadhyay, Arun K.; Petrash, J. Mark; Kompella, Uday B.

    2014-01-01

    Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9 fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Flour 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. PMID:24131101

  15. Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

    International Nuclear Information System (INIS)

    Goyal, Sharad; Rao, Malay S.; Khan, Atif; Huzzy, Lien; Green, Camille; Haffty, Bruce G.

    2011-01-01

    Purpose: Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. Methods and Materials: After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Results: Fourteen patients were identified to have received bevacizumab plus RT. All patients receivedbevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced ≥Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Conclusion: Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

  16. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    International Nuclear Information System (INIS)

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-01-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis

  17. Efficient production of a bioactive Bevacizumab monoclonal antibody using the 2A self-cleavage peptide in transgenic rice callus

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2016-08-01

    Full Text Available Bevacizumab, a humanized monoclonal antibody (mAb targeting to the vascular endothelial growth factor (VEGF, has been widely used in clinical practice for the treatment of multiple cancers. Bevacizumab was mostly produced by the mammalian cell expression system. We here reported the first plant-derived Bevacizumab by using transgenic rice callus as an alternative gene expression system. Codon-optimized Bevacizumab light chain (BLC and heavy chain (BHC genes were designed, synthesized as a polyprotein with a 2A self-cleavage linker peptide from the Foot-and-mouth disease virus (FMDV, cloned into a plant binary vector under a constitutive maize ubiquitin promoter, and transformed into rice nuclear genome through Agrobacterium-mediated transformation. Southern blot and western blot analyses confirmed the integration and expression of BLC and BHC genes in transgenic rice callus. Enzyme linked immunosorbent assay (ELISA analysis indicated that the rice-derived Bevacizumab mAb was biologically active and the recombinant mAb was expressed at high levels (160.7-242.8 mg kg-1FW in transgenic rice callus. The mAb was purified by using protein A affinity chromatography and the purified antibody was tested for its binding affinity with its target hVEGF antigen by ELISA. Rice callus produced Bevacizumab and a commercial Bevacizumab (Avastin were shown to have similar binding affinity to hVEGF. These results indicated that rice callus produced Bevacizumab could have similar biological activity and might potentially be used as a cost-effective biosimilar molecule in future cancer treatment.

  18. Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab.

    Science.gov (United States)

    Yandrapu, Sarath K; Upadhyay, Arun K; Petrash, J Mark; Kompella, Uday B

    2013-12-02

    Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9-fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Fluor 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases.

  19. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes by...... these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection....

  20. Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ayumu Matsuoka

    Full Text Available Bevacizumab (BEV, a humanized anti-vascular endothelial growth factor (VEGF monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83 were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095; at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016. At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017. In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012.The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast

  1. Qualidade de vida de mulheres tratadas por câncer do colo de útero

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    Francieli Ana Dallabrida

    2014-01-01

    Full Text Available El objetivo fue evaluar la Calidad de Vida de mujeres con cáncer de cuello uterino. Investigación transversal, descriptiva, con 43 mujeres en tratamiento del cáncer en un Centro de Alta Complejidad de Oncología, en el Sur del Brasil. El instrumento utilizado fue el European Organization for Research and Treatment of Cancer – Quality of Life Questionnaire Core-30 , y los datos se analizaron mediante estadística descriptiva. La edad media fue de 54,6 años; prevalecieron casadas (53,4%, con educación primaria incompleta (72,1% y renta de uno a dos sueldos mínimos (62,8%. La Calidad de Vida fue considerada muy satisfactoria. En las escalas de desempeño del rol y del funcionamiento emocional, el resultado fue regular a satisfactorio. Los síntomas más comunes fueron fatiga, falta de apetito y dolor. Hay necesidad de estructuración de las políticas de salud pública para prevención del cáncer de cuello uterino a la población más vulnerable.

  2. Sinusoidal obstruction syndrome (veno-occlusive disease in a patient receiving bevacizumab for metastatic colorectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Agarwal Vijay

    2008-07-01

    Full Text Available Abstract Introduction We present the case of a patient with colon cancer who, while receiving bevacizumab, developed sinusoidal obstruction syndrome (veno-occlusive disease (SOSVOD. Certain antitumour agents such as 6-mercaptopurine and 6-thioguanine have also been reported to initiate hepatic SOSVOD in isolated cases. There have been no reports so far correlating bevacizumab with SOSVOD. Case presentation A 77-year-old man was being treated with oxaliplatin and a modified de Gramont regimen of 5-fluorouracil for metastatic colon cancer. Bevacizumab (7.5 mg/kg was added from the seventh cycle onwards. Protracted neutropenia and thrombocytopenia led to discontinuation of oxaliplatin after the ninth cycle. A computed tomography scan showed complete response and bevacizumab was continued for another 3 months, after which time the patient developed right hypochondrial pain, transudative ascites, splenomegaly and abnormal liver function tests. Upper gastrointestinal endoscopy showed oesophageal varices. Liver biopsy showed features considered to be consistent with SOSVOD. Bevacizumab was stopped and a policy of watchful waiting was adopted. He tolerated the acute damage to his liver and subsequently the ascites resolved and liver function tests normalised. Conclusion We need to be aware that bevacizumab can cause sinusoidal obstruction syndrome (veno-occlusive disease and that the occurrence of ascites should not be attributed to progressive disease without appropriate evaluation.

  3. INTEGRATION OF BEVACIZUMAB IN METASTATIC COLORECTAL CANCER CHEMOTHERAPY REGIMENS IN 2 CLINICAL CENTERS IN MOSCOW AND SAINT PETERSBURG

    Directory of Open Access Journals (Sweden)

    N. V. Dobrova

    2013-01-01

    Full Text Available The aim of this study was to estimate efficacy of first line chemotherapy with bevacizumab in metastatic colorectal cancer patients and investigate the impact of different prognostic factors on treatment outcome.Methods.During 2004–2008 48 colorectal cancer patients were included (29 in Russian N.N. Blokhin Cancer Research Center, 19 in St. Petersburg, who had unresectable distant metastases. Primary tumor was resected in 93.8 % patients. 52.1 % had rectal cancer. 87.5 % had liver metastases, 43.8 % had more than 1 organ affected. 66.7 % received chemotherapy with bevacizumab 5 mg/kg biweekly, 33.3 % received bevacizumab 7,5 mg/kg every 3 weeks. 62.5 % patients had oxaliplatin-based regimens, 35.4 % – only fluorpyrimidines, 2.1 % – chemotherapy with irinotecan.Results.Median time of bevacizumab use was 7.8 months. 60.3 % had objective response, 87.4 % had stable diseases during more than 6 months. Median progression-free survival (PFS was 11.5 months. Median overall survival (OS was 24.1 months.Conclusions.Survival and efficacy results are comparable to international experience. Combination of fluorpyrimidines with bevacizumab had comparable efficacy to combined chemotherapy regimens with no impact on quality of life. Integration of bevacizumab in combined treatment regimens reduced the impact of negative prognostic factors on PFS and OS. 

  4. Iodogen-mediated radiolabeling of Bevacizumab with I-123 for clinical applications

    International Nuclear Information System (INIS)

    Lemps, R. de; Desruet, M.; Bacot, S.; Ahmadi, M.; Ghezzi, C.; Desruet, M.; Fagret, D.; Berger, F.

    2014-01-01

    Bevacizumab is a monoclonal antibody, directed against vascular endothelial growth factor (VEGF), and is currently used in various types of cancers (breast, lung, colorectal). In order to administer to humans glioblastomas, we developed its iodine 123 radiolabeling for in vitro and in vivo studies subsequent. The aim of the study is to choose the best radioiodination conditions based on feasibility in a hospital radiopharmacy: Quick one step method under mild condition, reproducible, using materials for pharmaceutical use and in a closed-system. Method Bevacizumab was radiolabeled with "1"2"3I using Iodogen, the most widely used oxidants in direct labelling techniques for tyrosyl residues-containing compounds. We have been explored two crucial parameters for clinical transfer: the amount of oxidant required (50μg and 100μg) and the choice of the purification column (size exclusion column or anion exchange resin), respectively. Quality control was performed before and after purification of each condition in order to evaluate the radiochemical purity (RCP) and purification efficiency. The stability of the radiolabeled molecule is evaluated over time and also when the solution is diluted with unlabeled bevacizumab. Moreover, the in vitro stability of "1"2"3I-bevacizumab was determined in presence of human blood at 15, 30, 60 and 120 min. Labeling yield before purification was 96.5% for the first condition (50μg Iodogen) and 95.5% for the second one (100μg Iodogen). The radiochemical purity was 99.5% after purification on a size exclusion column and 99% after purification on anion exchange resin. The purification yield with size exclusion column is 75%, compared with 81% of the anionic exchange resin. The stability in the labeling medium of "1"2"3I-bevacizumab at 3, 6, 24 and 30 h after labeling showed a RCP at 100%, 93%, 99.8% and 99.8% for condition 1 so that it was found to be 99.2%, 100%, 99.3%, 99.5% for condition 2, respectively. In vitro incubation with

  5. Problemas médicos habituales relacionados con la paciente embarazada

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    V. Lorena Quiroz, DRA.

    2014-11-01

    Full Text Available Problemas médicos como enfermedades del tiroides, deficiencia de vitamina D, anemia, infecciones del tracto urinario e insulino resistencia entre otros, pueden complicar el embarazo. Dado las molestias propias de la gestación, muchas de estas patologías no son diagnosticadas ni tratadas, aumentando la morbilidad materna y fetal. Algunas de estas enfermedades tienen diferentes criterios diagnósticos comparados con la mujer no embarazada. Se revisan los criterios diagnósticos y tratamientos de los problemas médicos más frecuentes en el embarazo.

  6. Corrosão de parafusos fixados à madeira tratada com soluções de creosoto vegetal

    OpenAIRE

    Paes,Juarez Benigno; Benedito Rocha,Vital; Della Lucia,Ricardo Marius; Della Lucia,Terezinha Maria Castro

    2002-01-01

    O objetivo desta pesquisa foi avaliar a corrosão de parafusos auto-rosqueáveis fixados à madeira tratada com soluções preservativas preparadas com creosoto vegetal, em condições de campo. Obteve-se o creosoto vegetal bruto por meio da destilação à temperatura de 110 - 255masculineC do alcatrão vegetal. Uma fração dos destilados foi lavada com solução a 9% de bicarbonato de sódio, obtendo-se o creosoto vegetal purificado. Ambas as frações foram enriquecidas com 3% de naftenato de cobre; 3% de ...

  7. Effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells

    Directory of Open Access Journals (Sweden)

    Jun JH

    2016-06-01

    Full Text Available Jong Hwa Jun,1 Wern-Joo Sohn,2 Youngkyun Lee,2 Jae-Young Kim21Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung University, 2Department of Oral Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South KoreaAbstract: The molecular and cellular effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells (LECs were examined using both an immortalized human lens epithelial cell line and a porcine capsular bag model. After treatment with various concentrations of bevacizumab, cell viability and proliferation patterns were evaluated using the water-soluble tetrazolium salt assay and 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay, respectively. The scratch assay and Western blot analysis were employed to validate the cell migration pattern and altered expression levels of signaling molecules related to the epithelial–mesenchymal transition (EMT. Application of bevacizumab induced a range of altered cellular events in a concentration-dependent manner. A 0.1–2 mg/mL concentration demonstrated dose-dependent increase in proliferation and viability of LECs. However, 4 mg/mL decreased cell proliferation and viability. Cell migrations displayed dose-dependent retardation from 0.1 mg/mL bevacizumab treatment. Transforming growth factor-β2 expression was markedly increased in a dose-dependent manner, and α-smooth muscle actin, matrix metalloproteinase-9, and vimentin expression levels showed dose-dependent changes in a B3 cell line. Microscopic observation of porcine capsular bag revealed changes in cellular morphology and a decline in cell density compared to the control after 2 mg/mL treatment. The central aspect of posterior capsule showed delayed confluence, and the factors related to EMT revealed similar expression patterns to those identified in the cell line. Based on these results, bevacizumab modulates the proliferation

  8. Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

    Science.gov (United States)

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Chan, Kelvin K W; Virik, Kiran; Hammerman, Ariel; Brenner, Baruch; Flowers, Christopher R; Hall, Peter S

    2017-06-01

    In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel. © AlphaMed Press 2017.

  9. NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

    Science.gov (United States)

    Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

    2014-01-01

    BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM

  10. Efficiency and safety of subconjunctival injection of anti-VEGF agent - bevacizumab - in treating dry eye.

    Science.gov (United States)

    Jiang, Xiaodan; Lv, Huibin; Qiu, Weiqiang; Liu, Ziyuan; Li, Xuemin; Wang, Wei

    2015-01-01

    Dry eye is a chronic inflammatory ocular surface disease with high prevalence. The current therapies for dry eye remain to be unspecific and notcomprehensive. This study aims to explore safety and efficacy of a novel treatment - subconjunctival injection of bevacizumab - in dry eye patients. Sixty-four eyes of 32 dry eye patients received subconjunctival injection of 100 μL 25 mg/mL bevacizumab. Dry eye symptoms, signs (corrected visual acuity, intraocular pressure, conjunctival vascularity, corneal staining, tear break-up time, Marx line score, and blood pressure), and conjunctival impression cytology were evaluated 3 days before and 1 week, 1 month, and 3 months after injection. Significant improvements were observed in dry eye symptoms, tear break-up time, and conjunctival vascularization area at all the visits after injection compared to the baseline (Pdry eye disease.

  11. Macular Hole Progression after Intravitreal Bevacizumab for Hemicentral Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Manish Nagpal

    2011-01-01

    Full Text Available Macular edema secondary to retinal vein occlusion is commonly being treated with off-label intravitreal bevacizumab with good outcomes. A significant reduction in macular edema and improvement in visual acuity is seen following such a treatment with no serious adverse effects. In the reported case, a full-thickness macular hole was noticed one month after intravitreal bevacizumab for macular edema secondary to hemicentral retinal vein occlusion. On a detailed review of the pre- and postoptical coherence tomography scans, it was realized that there was a preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema at the fovea and the macular hole had progressed following the injection.

  12. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7)

    DEFF Research Database (Denmark)

    Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus

    2015-01-01

    BACKGROUND: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results...... of the trial. METHODS: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation....... This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. FINDINGS: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end...

  13. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

    International Nuclear Information System (INIS)

    Bukowski, Ronald M

    2010-01-01

    The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed

  14. A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

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    Erin D. Powell

    2009-07-01

    Full Text Available A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab.

  15. Combination of Laser Photocoagulation and Intravitreal Bevacizumab in Aggressive Posterior Retinopathy of Prematurity.

    Science.gov (United States)

    Altinsoy, Halil Ibrahim; Mutlu, Fatih Mehmet; Güngör, Riza; Sarici, S Ümit

    2010-03-09

    The response to combined laser photocoagulation and a single intravitreal injection of 0.75 mg bevacizumab to each eye on separate days in two patients with aggressive, posterior retinopathy of prematurity (ROP) is described. Combined treatment resulted in regression of zone-1 disease in Case 1, which had no retinal detachment. However, no significant regression or unfavorable anatomic response was observed in the second case with retinal detachment. Although the combination of laser photocoagulation and intravitreal bevacizumab injection seems to be well tolerated, inducing prompt regression of agressive zone-1 ROP without retinal detachment, further controlled studies with long-term follow-up are necessary for their use in the treatment of ROP with for potentially dangerous growth factor inhibitors in premature babies. Copyright 2010, SLACK Incorporated.

  16. Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial.

    Science.gov (United States)

    Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Fargeton, Anne-Emmanuelle; Roux, Adeline; Bréant, Valentine; Colombet, Bettina; Rivière, Sophie; Cartier, César; Lacombe, Pascal; Chinet, Thierry; Blivet, Sandra; Blondel, Jean-Hugues; Gilbert-Dussardier, Brigitte; Dufour, Xavier; Michel, Justin; Harle, Jean-Robert; Dessi, Patrick; Faure, Frédéric

    2016-09-06

    Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated. To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT. Randomized, multicenter, placebo-controlled, phase 2/3 clinical trial with dose selection at an intermediate analysis and prespecified stopping rules (nonbinding stopping for futility). Patients aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014 to January 2015 with a 6-month follow-up after the end of treatment. Participants had a history of self-reported nosebleeds with a monthly duration of more than 20 minutes in at least the 3 months prior to inclusion corroborated by epistaxis grids completed during the same preinclusion period. Eighty consecutive HHT patients were randomized and treated in the phase 2 study, with 4 parallel groups in a 1:1:1:1 ratio. One group received placebo (n = 21); the other 3 received bevacizumab nasal spray. Each bevacizumab group received a different dose of the drug (25 mg [n = 20], 50 mg [n = 20], or 75 mg [n = 19] per treatment) in 3 doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75 mg, 150 mg, and 225 mg in each treatment group. Mean monthly epistaxis duration for 3 consecutive months immediately after the end of the treatment. Of the 80 patients who were randomized (mean age, 60.47 [SD, 10.61] years; 37 women [46.25%]), 75 completed the study. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 59 patients receiving bevacizumab in comparison with the placebo group (P = .57) or between the bevacizumab groups

  17. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

    DEFF Research Database (Denmark)

    Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

    2014-01-01

    in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results...... treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor...... growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations...

  18. Perfil de proteases de lesões cutâneas experimentais em camundongos tratadas com a lectina isolada das sementes de Canavalia brasiliensis Proteases profile of skin wounds treated with lectin from Canavalia brasiliensis seeds

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    Flávio de Oliveira Silva

    2009-09-01

    Full Text Available O objetivo deste estudo foi determinar o perfil de proteases em lesões cutâneas experimentais tratadas com a lectina isolada das sementes da Canavalia brasiliensis (ConBr livre e conjugada com o seu açúcar específico. Lesões cirúrgicas foram produzidas assepticamente na região dorsal de camundongos (n=120, divididos de acordo com o tratamento empregado: Grupo NaCl (NaCl 150mM, Grupo manose (manose 100mM, Grupo ConBr (ConBr 100µg mL-1 e Grupo ConBr/manose (solução contendo ConBr 100µg mL-1 preparada em manose 100mM. Amostras da área lesada foram coletadas para determinação do perfil de proteases e atividade colagenolítica no 2°, no 7° e no 12° dia de pós-operatório. O perfil das proteínas realizado através de eletroforese SDS-PAGE demonstrou a presença de proteínas com massa molecular de 67kDa em todos os grupos. O Grupo ConBr/manose apresentou a maior atividade colagenolítica no 12° dia de pós-operatório. A lectina isolada das sementes da Canavalia brasiliensis influenciou a expressão de proteases com atividade colagenolítica podendo assim interferir no processo cicatricial das lesões cutâneas em camundongos.The objective of the present study was determining the proteases profile of cutaneous healings treated with free and conjugated lectin of Canavalia brasiliensis (ConBr and their specific sugar. An aseptic wound was produced in the thoracic area of the mice (n=120, divided according to the employed treatment: NaCl Group (150mM NaCl, manose Group (100mM manose, ConBr Group (100µg mL-1 ConBr and ConBr/manose Group (solution containing 100µg mL-1 ConBr prepared in 100mM manose. Samples of the injured area were collected for determination of proteases profile and collagenolytic activity on 2nd, 7th e 12th days after the surgery. Electrophoresis SDS-PAGE demonstrated proteins with molecular mass of 67kDa in all groups. Group IV presented the highest collagenolytic activity on the 12th day post surgery. Con

  19. In vitro induction of protein complexes between bevacizumab, VEGF-A¹⁶⁵ and heparin: explanation for deposits observed on endothelial veins in monkey eyes.

    Science.gov (United States)

    Julien, Sylvie; Biesemeier, Antje; Schraermeyer, Ulrich

    2013-04-01

    By investigating the effects of intravitreal bevacizumab on retinal vessels of monkeys, we found that bevacizumab accumulated locally at high concentration within individual blood vessels. It formed electron-dense fibrous deposits between endothelial cells and erythrocytes or granulocytes inducing retinal vein thrombosis. To better characterise the observed deposits, we investigated in vitro whether these deposits result from a complex between bevacizumab, vascular endothelial growth factor (VEGF)-A(165) and heparin. Cynomolgus monkeys were intravitreally injected with 1.25 mg bevacizumab. The eyes were enucleated between 1 and 14 days after injection and investigated by electron microscopy and immunohistochemistry. Human umbilical vein endothelial cells (HUVEC) were incubated with bevacizumab, VEGF-A(165) and heparin at different concentrations. Treatments with ranibizumab served as control. Bevacizumab and ranibizumab were detected immunohistochemically using Cy-3 or immunogold labelled antibodies. Treated animals showed bevacizumab locally at high concentration within retinal blood vessels. Electron-dense deposits inside retinal vessels and between erythrocytes were detected in three out of four treated monkeys. In vitro, many globular aggregates heavily stained with anti-human IgG were only observed with equimolar amounts (240 nM) of bevacizumab and VEGF-A(165) and 0.2 U/ml heparin and not after ranibizumab treatment. The immunogold labelling specifically localised ultrastructurally the complexes formed between bevacizumab, VEGF-A(165) and heparin at the surfaces of HUVEC cells. Heparin promotes bevacizumab immune complex deposition on to endothelial cells. Our in vitro results could explain the presence of deposits observed on endothelial veins in monkey eyes intravitreally injected with bevacizumab.

  20. Las células dendríticas generadas en presencia de vitamina D3 y activadas con lipopolisacáridos incrementan la producción de IL-1β, IL-8 e IL-10 y disminuyen su capacidad de inducir LT CD4+CD25hiFoxp3+

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    Sindy M. Muñoz

    2016-06-01

    Conclusión. Las células dendríticas generadas con vitamina D3 y tratadas con lipopolisacáridos presentaron un fenotipo ‘semimaduro’, así como la capacidad de secretar citocinas antiinflamatorias y citocinas promotoras de la reacción inflamatoria. Además, no se aumentó su capacidad de promover la polarización de LTCD4+ vírgenes alogénicos hacia LTreg.

  1. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eng, Cathy [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Maru, Dipen M. [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Clemons, Marilyn V. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

  2. Is more better than less? Caveats from bevacizumab and cetuximab combination in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2011-12-01

    Full Text Available In the past few years, impressing improvements have been made in the treatment of advanced colorectal cancer. Following decades of modest achievements, in which it was just a matter of dose and schedule for 5-FU and leucovorin—the only treatment then available—first, the development of irinotecan and oxaliplatin, and then the use of the two biologicals, bevacizumab and cetuximab, have dramatically improved the life expectancy of our colorectal cancer patients...

  3. Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

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    Reyin Lien

    Full Text Available The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB for the treatment of retinopathy of prematurity (ROP up to the age of 2 years.The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028 and psychomotor (p = 0.002 impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041. The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

  4. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

  5. Subconjunctival bevacizumab to augment trabeculectomy with mitomycin C in the management of failed glaucoma surgery

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    Saeed AM

    2014-09-01

    Full Text Available Ahmed M Saeed, Tarek Tawfeek AboulNasrOphthalmology Department, Benha University, Egypt Purpose: To provide a feasible solution to the problem of failed glaucoma surgery. The aim was to evaluate the efficacy and safety of the additional effects of a combined surgical approach. This approach augments the application of trabeculectomy with mitomycin C (MMC by adding subconjunctival bevacizumab injection. The results were compared with those of trabeculectomy with only adjunctive MMC. Methods: A randomized controlled prospective clinical trial included 28 eyes diagnosed with failed scarred bleb of a previous trabeculectomy. The eyes were divided into two equal groups: combined group A, “trabeculectomy with adjunctive MMC and subconjunctival bevacizumab,” and control group B, “trabeculectomy with adjunctive MMC only.” The main outcome results included the cumulative probability of surgical success, intraocular pressure (IOP values, and number of IOP-lowering medications needed to achieve the target IOP.Results: Group A achieved a cumulative probability of complete success of 0.769 and of qualified success of 0.231 at the end of the 24 month study period; group B achieved cumulative probabilities of 0.538 and 0.308, respectively. Group A achieved a lower mean IOP value than group B, with fewer antiglaucoma drugs at all postoperative visits, but this lower value did not reach a statistically significant level (P>0.05. There was no statistically significant difference between both groups regarding best corrected visual acuity, visual field parameters, operative and/or postoperative complications, and additional interventions. No significant adverse effects were caused by this combined approach.Conclusion: Bevacizumab was not found to add much to the favorable long-term outcome of conventional trabeculectomy with MMC as a solution to the problem of scarred failed bleb. Keywords: glaucoma, bevacizumab, mitomycin C, failed trabeculectomy

  6. The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer.

    Science.gov (United States)

    Silwal-Pandit, Laxmi; Nord, Silje; von der Lippe Gythfeldt, Hedda; Møller, Elen K; Fleischer, Thomas; Rødland, Einar; Krohn, Marit; Borgen, Elin; Garred, Øystein; Olsen, Tone; Vu, Phuong; Skjerven, Helle; Fangberget, Anne; Holmen, Marit M; Schlitchting, Ellen; Wille, Elisabeth; Nordberg Stokke, Mette; Moen Vollan, Hans Kristian; Kristensen, Vessela; Langerød, Anita; Lundgren, Steinar; Wist, Erik; Naume, Bjørn; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Engebraaten, Olav

    2017-08-15

    Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor-positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor-positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662-70. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled...... was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow-up examinations (P Macular thickness improved significantly at all time...

  8. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

    Science.gov (United States)

    Wells, John A; Glassman, Adam R; Ayala, Allison R; Jampol, Lee M; Bressler, Neil M; Bressler, Susan B; Brucker, Alexander J; Ferris, Frederick L; Hampton, G Robert; Jhaveri, Chirag; Melia, Michele; Beck, Roy W

    2016-06-01

    To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Randomized clinical trial. Six hundred sixty participants with visual acuity (VA) impairment from DME. Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Change in VA, adverse events, and retreatment frequency. Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials. Copyright © 2016 American Academy of Ophthalmology. All rights

  9. Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

    Science.gov (United States)

    Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

    2017-08-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up

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    Eleni Loukianou

    2010-05-01

    Full Text Available Eleni Loukianou, Dimitrios Brouzas, Eleni Georgopoulou, Chrysanthi Koutsandrea, Michael ApostolopoulosEye Department, University of Athens, Athens, GreecePurpose: To evaluate the safety and efficacy of intravitreal injections of bevacizumab (Avastin® as a treatment option for radiation maculopathy secondary to proton beam radiotherapy for choroidal melanoma.Case: A 61-year-old woman presented with a gradual decrease in left eye visual acuity (VA 29 months after proton beam radiotherapy for choroidal melanoma. On presentation, her best-corrected VA (BCVA was 2/10 in the left eye and the intraocular pressure was 15 mmHg. Fundoscopy revealed cystoid macular edema, intraretinal hemorrhages, epiretinal membrane in the posterior pole, and residual tumor scar with exudative retinal detachment and hard exudates in the periphery of the superotemporal quadrant. A treatment with intravitreal injections of bevacizumab (Avastin® was recommended. The injections were performed on a six-weekly basis.Results: The central retinal thickness prior to the treatment was 458 μm. After the first intravitreal injection of bevacizumab, the retinal thickness at the centre of the fovea was reduced to 322 μm. After the third injection, the central retinal thickness was 359 μm and 18 months after presentation, it reduced to 334 μm. The BCVA increased to 3/10 after the intravitreal injections of bevacizumab and remained stable during the follow-up period. The intraocular pressure was within normal range during the follow-up period.Conclusion: Bevacizumab should be regarded as a treatment option for macular edema due to proton beam radiotherapy for choroidal melanoma. By reducing the central retinal thickness, intravitreal bevacizumab can improve VA or ameliorate further decline caused by radiation maculopathy.Keywords: bevacizumab (Avastin®, choroidal melanoma, macular edema, radiation retinopathy

  11. Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

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    Portales Fabienne

    2009-09-01

    Full Text Available Abstract Background The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC. However, it was reported to have no efficacy in 3rd or later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin. Methods Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg in combination with FOLFIRI or simplified FOLFOX4 every 14 days. Results Ten patients (32.2% had an objective response (1 CR, 9 PR and 12 (38.8% were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2nd or 3rd line and 25% and 55% in 4th or later line respectively (p = 0.024 and p = 0.008. Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28 the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS and overall survival (OS were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients. Conclusion This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.

  12. Bevacizumab Injection in Patients with Age-Related Macular Degeneration Associated with Poor Initial Visual Acuity

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    Leila El Matri

    2012-01-01

    Full Text Available Purpose. To evaluate functional and anatomic effects of intravitreal bevacizumab in patients with neovascular AMD and initial low visual acuity. Methods. Retrospective case series of 38 eyes with neovascular AMD and initial visual acuity of 20/200 or less, treated with intravitreal bevacizumab injection. Results. Mean followup was 14.1 months ±7.1 (range: 5 to 24 months. Mean logMAR vision at baseline was 1.38 logMAR ±0.33, at 6 months was 1.14 logMAR ±0.37 (=0.001 and at 12 months was 1.22 logMar ±0.33 (=0.004. Mean baseline central retinal thickness was 431 μm ±159.7 at 6 months was 293.43 μm  ±122.79 (=10−4 and at 12 months was 293.1 μm  ±130 (=0.004. Visual acuity improved in both patients with or without prior PDT treatment. Conclusions. Intravitreal bevacizumab injection may increase the chance of visual acuity gain in neovascular AMD even in cases with initial low visual acuity.

  13. Restriction spectrum imaging of bevacizumab-related necrosis in a patient with GBM

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    Nikdokht eFarid

    2013-09-01

    Full Text Available Importance:With the increasing use of antiangiogenic agents in the treatment of high grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations:We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI, an advanced diffusion-weighted imaging (DWI technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.Conclusions and Relevance:Our report increases the number of pathologically-proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

  14. Cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single use vial

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    Perwez Khan

    2016-01-01

    Full Text Available The risk of endophthalmitis is always a concern when an intraocular procedure is performed. Intravitreal injection is a frequently used method for therapeutic management of many diseases, affecting the posterior segment of the eye. Hence, it is important to assess the risk of complications, especially endophthalmitis. Most studies conducted concentrate on risk assessment from single use from single drug vial. The present article reports the occurrence of cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single vial. Intravitreal injection of bevacizumab was administered to eight eyes of eight patients. Administered dose was prepared from single 4-ml vial of bevacizumab and was injected in the eye, after patient preparation and under aseptic conditions. The procedure was repeated for the remaining patients, thereby imparting multiple pricks in the same vial. Four of the eight patients reported to the hospital on the 3rd day after injection with complaints of pain, watering, and diminution of vision. Two patients reported the following day with similar complaints. Two patients who did not report by the 4th day were contacted and recalled for an examination. All the patients were thoroughly examined using slit lamp biomicroscopy and indirect ophthalmoscopy. Six out of eight were clinically diagnosed to have endophthalmitis and were administered intravitreal antibiotics. The present report highlights possibility of microbial contamination of the drug vial or during compounding process. However, from the present incident, we are encouraged to stay vigilant and wary of contamination

  15. Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma.

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    Hicks, Martin J; Funato, Kosuke; Wang, Lan; Aronowitz, Eric; Dyke, Jonathan P; Ballon, Douglas J; Havlicek, David F; Frenk, Esther Z; De, Bishnu P; Chiuchiolo, Maria J; Sondhi, Dolan; Hackett, Neil R; Kaminsky, Stephen M; Tabar, Viviane; Crystal, Ronald G

    2015-01-01

    The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.

  16. Long-Term Follow-Up of Intravitreal Bevacizumab in Retinal Arterial Macroaneurysm: A Case Report

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    Shani Golan

    2011-12-01

    Full Text Available Purpose: To present the long-term effect of intravitreal bevacizumab (Avastin® therapy in a patient suffering from retinal arterial macroaneurysm. Methods: Case report of a 72-year-old female diagnosed with retinal macroaneurysm in the superior temporal artery leading to macular edema. Functional and morphological data at baseline, 4 weeks, 2 months, and 13 months following treatment with two consecutive intravitreal bevacizumab injections are presented. Results: Best-corrected visual acuity improved from 20/160 at baseline to 20/20 at the3-months follow-up and remained stable through 13 months of follow-up. Central retinal thickness measured by optical coherence tomography decreased from 364 µm at baseline to 248 µm at the 13-months follow-up. No ocular or systemic side effects were detected. Conclusions: Intravitreal bevacizumab therapy may lead to resolution of macular edema associated with retinal macroaneurysm and consequently visual improvement. This treatment may promise a long-lasting effect but warrant further investigation in larger series.

  17. The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Simonds, Jana; Miller, Frank; Mandel, Jess; Davidson, Terence M

    2009-05-01

    Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. Retrospective pilot study. Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

  18. MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

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    Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

    2017-12-01

    To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

  19. Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

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    Kai Fang

    2013-01-01

    Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

  20. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

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    Ronald M Bukowski

    2010-03-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

  1. Physiological responses in the banana plantlets treateds with strobilurinsRespostas fisiológicas em mudas de banananeira tratadas com estrobilurinas

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    Sivia Helena Modenese-Gorla da Silva

    2012-04-01

    âmetro do pseudocaule e a massa da matéria seca da parte aérea de plantas tratadas com estrobilurinas foram superiores às de plantas não tratadas. O efeito do tratamento com fungicidas foi diferenciado, sendo mais pronunciado nas plantas tratadas com piraclostrobina do que nas plantas tratadas com azoxistrobina. Plantas tratadas com piraclostrobina apresentaram área foliar, atividade da redutase do nitrato e teor de clorofila a e de nitrogênio total foliar superiores às plantas tratadas com azoxistrobina e água, que não diferiram entre si. As estrobilurinas afetaram a fisiologia das mudas de bananeira, com destaque para a piraclostrobina.

  2. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

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    Ping Fang

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

  3. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer

    Science.gov (United States)

    Makondi, Precious Takondwa; Lee, Chia-Hwa; Huang, Chien-Yu; Chu, Chi-Ming; Chang, Yu-Jia

    2018-01-01

    Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID). Protein–protein interaction (PPI) networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING) and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs); the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1, early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4) revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS). The identified genes and pathways

  4. Short-term intraocular pressure changes after intravitreal injection of bevacizumab in diabetic retinopathy patients

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    Farhood QK

    2014-03-01

    Full Text Available Qasim Kadhim Farhood,1 Sinan Mohammad Twfeeq21College of Medicine, Babylon University, Babylon; 2Al-Jumhori teaching hospital, Mosul, IraqBackground: This study examined the changes in short-term intraocular pressure (IOP in a prospective series of patients undergoing intravitreal bevacizumab injection. The aim was to evaluate the frequency and predictive factors related to intraocular pressure (IOP elevation in patients receiving intravitreal bevacizumab.Patients and methods: This study included 52 patients with diabetic retinopathy between 28 to 75 years of age with a mean age of 51 years; 30 (58% were females, and 22 (42% were males. All patients received bevacizumab (1.25 mg/0.05 mL injected intravitreally in a standard fashion between May 2012 to February 2013 in the AL-Jumhoury teaching hospital. IOP was measured at baseline, 5, 10, and 30 minutes after injection using Goldman applanation tonometry.Statistics: Data were analyzed using the SPSS v.12.0 for windows. Basic, demographic, and clinical data were analyzed using means, proportions, and appropriate 95% confidence intervals (CIs.Results: Most patients (85% were diagnosed with proliferative diabetic retinopathy, while 15% presented with diabetic macular edema. The mean IOP values at baseline, 5, 10, and 30 minutes after injection were 14.0 mmHg (95% CI 13.4–14.7, 36.1 mmHg (95% CI 33.5–38.6, 25.7 mmHg (95% CI 23.8–27.5, and 15.5 mmHg (95% CI 12.4–16.51, respectively. Regression analysis showed a trend toward phakic patients having higher IOP at 30 minutes.Conclusion: Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all IOP returned to a safe range (<25 mmHg within 30 minutes. Elevated IOP 30 minutes after injection only occurs rarely, so routine prophylactic use of anti-glaucoma medication is not indicated.Keywords: intravitreal injection, bevacizumab, intraocular pressure, Goldmann applanation tonometry

  5. Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer.

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    Precious Takondwa Makondi

    Full Text Available Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO database (dataset, GSE86525 was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs. Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID. Protein-protein interaction (PPI networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs; the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A, toll-like receptor 4 (TLR4, CD19 molecule (CD19, breast cancer 1, early onset (BRCA1, platelet-derived growth factor subunit A (PDGFA, and matrix metallopeptidase 1 (MMP1 were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4 revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS. The identified genes and pathways

  6. Clinical study on Bevacizumab for macular edema induced by retinal vein occlusion

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    Zhi-Guang Duan

    2014-09-01

    Full Text Available AIM: To evaluate the safety and efficacy of intravitreal bevacizumab injection in patients with macular edema(MEinduced by retinal vein occlusion(RVO.METHODS: The records of patients treated with intravitreal injection of 1.75mg bevacizumab for ME induced by RVO were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography(OCTand fundus fluorescein angiography(FFA, etc. Best corrected visual acuity(BCVA, intraocular pressure, the change of lens and vitreous, central foveal thickness(CFTwere observed at 1, 2, 3, 6mo after treatment and compared with before treatment. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. All the cases were followed up at least 6mo. An intravitreal injection of bevacizumab(1.75mgwas given at 6wk intervals.RESULTS: Fifty patients(56 eyeswith the average of(57±18.56years old were included. The mean baseline of BCVA, CFT were(logMAR0.82±0.63,(626.5±178.0μm respectively. Although there was no significant decrease in mean CFT at 1wk after injection, the mean BCVA had significant improvement. Followed up at mean 10.26±5.87mo, BCVA, CFT showed significant improvements over baseline values. The statistics of CFT at 1, 2, 3mo after injection were significant differences compared with before injection in each of the three groups. CFT at 1, 3, 12mo after injection were(365.11±23.212μm,(333.42±35.526μm,(267.6±116.8μm, which had a significant difference(PP>0.05. OCT image showed that after injection macular retinal thickness was becoming thinner. FFA showed that after injection macular fluorescein leakage decreased. BCVA was improved by at least two lines in 48 eyes(86%,remained stable in 8 eyes(14%at the last visit. A total of 112 injections were performed and the average number of injections was 1.96 in the group. About 50% of reinjections gained at least two lines of vision improvement at 1

  7. Respuesta estral y tasa de preñez en cabras en anestro estacional tratadas con progestágenos y somatotropina bovina

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    Margarita Martínez Aguilar

    2011-01-01

    Full Text Available Se probó si la administración de la hormona del crecimiento bovino (bST durante el tratamiento para inducir la ovulación en cabras en anestro mejora la fertilidad. A 109 cabras adultas de 1 a 5 partos se les insertó una esponja intravaginal de acetato de fluorogestona (FGA durante 12 días. Al retirar la esponja todas las cabras recibieron 300 UI de gonadotropina coriónica equina (eCG. Cinco días antes de retirar el progestágeno, las cabras fueron asignadas al azar a dos grupos, 1 125 mg de bST vía subcutánea (n=53, 2 Testigo (n=56 sin bST. En siete cabras de cada grupo se determinaron las concentraciones de factor de crecimiento parecido a la insulina tipo I (IGF-I y de insulina diariamente a partir de la inyección de bST hasta el día 7 post estro. Una proporción mayor (P<0.05 de animales del grupo bST (73.5 % mostraron estro (testigo, 51.7 %. El porcentaje de concepción fue similar (P=0.12 entre grupos (bST, 82.0 % vs testigo, 65.5 %. La tasa de preñez fue mayor (P<0.01 en el grupo bST (60.3 % que en el testigo (33.9 %. La proporción de partos múltiples fue igual (P=0.9 entre los grupos (bST, 59 % vs testigo, 63 %. Las concentraciones de IGF-I e insulina fueron más altas (P<0.01 en el grupo bST. Se concluye que la administración de la hormona del crecimiento bovina durante el tratamiento para inducir la ovulación en cabras en anestro aumentó la proporción de animales en estro y la tasa de preñez.

  8. Supervivencia de pacientes con cáncer de cuello uterino tratadas en el Instituto Nacional de Cancerología

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    Constanza Pardo

    2009-09-01

    Conclusiones. Los resultados de supervivencia global son similares a los reportados en la literatura. Se recomienda desarrollar estudios en cohortes más grandes para aumentar la potencia del estudio e identificar otros factores de pronóstico.

  9. The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation.

    Science.gov (United States)

    Batman, Cosar; Ozdamar, Yasemin

    2010-01-01

    To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. Copyright 2010, SLACK Incorporated.

  10. Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

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    Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

    2018-01-01

    Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

  11. A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

    Science.gov (United States)

    Avallone, Antonio; Piccirillo, Maria Carmela; Aloj, Luigi; Nasti, Guglielmo; Delrio, Paolo; Izzo, Francesco; Di Gennaro, Elena; Tatangelo, Fabiana; Granata, Vincenza; Cavalcanti, Ernesta; Maiolino, Piera; Bianco, Francesco; Aprea, Pasquale; De Bellis, Mario; Pecori, Biagio; Rosati, Gerardo; Carlomagno, Chiara; Bertolini, Alessandro; Gallo, Ciro; Romano, Carmela; Leone, Alessandra; Caracò, Corradina; de Lutio di Castelguidone, Elisabetta; Daniele, Gennaro; Catalano, Orlando; Botti, Gerardo; Petrillo, Antonella; Romano, Giovanni M; Iaffaioli, Vincenzo R; Lastoria, Secondo; Perrone, Francesco; Budillon, Alfredo

    2016-02-08

    Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Overall this

  12. Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

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    Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

    2018-04-05

    Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

  13. Applying quantitative adiposity feature analysis models to predict benefit of bevacizumab-based chemotherapy in ovarian cancer patients

    Science.gov (United States)

    Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; More, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2016-03-01

    How to rationally identify epithelial ovarian cancer (EOC) patients who will benefit from bevacizumab or other antiangiogenic therapies is a critical issue in EOC treatments. The motivation of this study is to quantitatively measure adiposity features from CT images and investigate the feasibility of predicting potential benefit of EOC patients with or without receiving bevacizumab-based chemotherapy treatment using multivariate statistical models built based on quantitative adiposity image features. A dataset involving CT images from 59 advanced EOC patients were included. Among them, 32 patients received maintenance bevacizumab after primary chemotherapy and the remaining 27 patients did not. We developed a computer-aided detection (CAD) scheme to automatically segment subcutaneous fat areas (VFA) and visceral fat areas (SFA) and then extracted 7 adiposity-related quantitative features. Three multivariate data analysis models (linear regression, logistic regression and Cox proportional hazards regression) were performed respectively to investigate the potential association between the model-generated prediction results and the patients' progression-free survival (PFS) and overall survival (OS). The results show that using all 3 statistical models, a statistically significant association was detected between the model-generated results and both of the two clinical outcomes in the group of patients receiving maintenance bevacizumab (p<0.01), while there were no significant association for both PFS and OS in the group of patients without receiving maintenance bevacizumab. Therefore, this study demonstrated the feasibility of using quantitative adiposity-related CT image features based statistical prediction models to generate a new clinical marker and predict the clinical outcome of EOC patients receiving maintenance bevacizumab-based chemotherapy.

  14. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  15. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.

    Science.gov (United States)

    Shah, Manish A; Ramanathan, Ramesh K; Ilson, David H; Levnor, Alissa; D'Adamo, David; O'Reilly, Eileen; Tse, Archie; Trocola, Robin; Schwartz, Lawrence; Capanu, Marinela; Schwartz, Gary K; Kelsen, David P

    2006-11-20

    Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

  16. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

    2010-01-01

    , hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan....... Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating...

  17. Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study.

    Directory of Open Access Journals (Sweden)

    A M E Schauwvlieghe

    Full Text Available To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD.Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters.Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA score between 20 and 78 letters on an EDTRS like chart in the study eye.Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed.Primary outcome was the change in BCVA in the study eye from baseline to 12 months.The mean gain in BCVA was 5.1 (±14.1 letters in the bevacizumab group (n = 161 and 6.4 (±12.2 letters in the ranibizumab group (n = 166 (p = 0.37. The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038. No significant differences in absolute CRT and CRT change (p = 0.13 or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal differed significantly (p = 0.020, with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively.Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both

  18. Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept for treatment of corneal neovascularization

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    Tariq Al-Debasi

    2017-04-01

    Anti-VEGF agents (Bevacizumab, Ranibizumab and Aflibercept seem to have a higher efficiency and efficacy for corneal NV treatment. Both subconjunctival therapy and topical therapy of bevacizumab prohibit corneal NV, while early treatment with subconjunctival administration of ranibizumab may successfully reduce corneal NV. Therefore, establishment of safe doses is highly important before these drugs can be involved in the clinical setting. Further investigations and studies are highly warranted to adjust the dose and route of administration for the antibodies directed against VEGF to be the key therapeutic agents in the corneal NV treatment.

  19. A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

    Science.gov (United States)

    Wiley, Henry E; Thompson, Darby J S; Bailey, Clare; Chew, Emily Y; Cukras, Catherine A; Jaffe, Glenn J; Lee, Richard W J; Loken, Erin K; Meyerle, Catherine B; Wong, Wai; Ferris, Frederick L

    2016-04-01

    To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab

  20. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin

    2010-01-01

    PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow...

  1. The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

    Directory of Open Access Journals (Sweden)

    Christoforidis JB

    2013-01-01

    Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

  2. The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema.

    Science.gov (United States)

    Al-Dhibi, Hassan; Hamade, Issam H; Al-Halafi, Ali; Barry, Maan; Chacra, Charbel Bou; Gupta, Vishali; Tabbara, Khalid F

    2014-01-01

    Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41 ± 16 years with a mean followup of 4 ± 1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8 ± 0.8 at baseline to 0.4 ± 0.5 at 1 month and 0.3 ± 0.5 at 3 months (P < 0.002, at 3 months). The mean macular thickness was 430 ± 132 μm at baseline. Following IVBI macular thickness improved to 286 ± 93 μm at 1 month and to 265 ± 88 μm at 3 months of followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  3. The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

    Directory of Open Access Journals (Sweden)

    Hassan Al-Dhibi

    2014-01-01

    Full Text Available Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months. The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months. Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  4. Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

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    Rony Carlos Preti

    2012-02-01

    Full Text Available PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001 but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm reduced significantly one month (322 ± 127 µm, P=0.0001 and three months (439 ± 179 µm, P=0.01 after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

  5. Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

    Science.gov (United States)

    Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

    2009-01-01

    The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

  6. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    Science.gov (United States)

    Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

    2012-01-01

    Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

  7. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

    International Nuclear Information System (INIS)

    Finger, Paul T.; Chin, Kimberly J.

    2012-01-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6–8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  8. Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

    Science.gov (United States)

    Jeon, Sohee; Lee, Won Ki

    2014-01-01

    Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

  9. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

    2012-02-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  10. Results of the treatment with intravitreal bevacizumab injection in branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Osman Sayýn

    2017-06-01

    Material and Method: The files of patients who had macular edema caused by branch retinal vein occlusion and who were applied intravitreal bevacizumab injection were studied retrospectively. Visual acuity (logMAR in follow-ups of the patients before and after the injection and the macular thickness values of the quadrant of the occlusion were recorded and the effect of intravitreal bevacizumab on these parameters were analyzed. Results: 24 eyes of 24 patients, 17 of which are male and 7 of which are female, were included in the study. The mean age of the patients were 59.1±7.7. The mean visual acuity prior to the injection was determined to be 0.7±0.5 logMAR, and the mean macular thickness value 489.7±129.6 μm. The mean injection number applied was 1.5±0.7. The mean follow-up time after the injection was 3.5±2.7 months. The mean macular thickness was determined to be 393.1±5.7 μm and mean visual acuity was 0.5±0.1 logMAR in the 1st month. In the last follow-ups of the patients, the mean visual acuity was 0.26±0.28 logMAR and the mean macular thickness value was 317.4±71.5 μm. The increase in visual acuity and decrease in macular thickness between first and last control after the injection was found statistically significant. (p<0.001. Conclusion: The intravitreal bevacizumab injection used in macular edema secondary to BRVO increases visual acuity and decreases macular thickness. [J Contemp Med 2017; 7(2.000: 143-148

  11. Bandeo de cromosomas humanos con extracto crudo de frutas u hojas de papaya

    Directory of Open Access Journals (Sweden)

    María Virginia Solís

    2001-12-01

    Full Text Available Preparaciones de una semana de cromosomas humanos fueron tratadas con filtrados de una hoja de papaya (Carica papaya licuada (53 g en 100 ml de agua destilada, y tenidas con 1.5 % Giemsa (pH 6.8. Se obtuvo buen bandeo de cromosomas luego de 2 min de tratamiento. Soluciones que han sido congeladas por años son efectivas y el método es más barato y fácil que otrosOne week old human chromosome preparations were treated with filtrate from one liquefied leaf (53 g of papaya (Carica papaya in 100 ml of distilled water, and stained with 1.5 % Giemsa (pH 6.8. Good chromosome banding was obtained after 2 min of treatment. Solutions that have been frozen even for years are effective and the method is cheaper and easier than others

  12. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

    Science.gov (United States)

    Herbst, Roy S; Redman, Mary W; Kim, Edward S; Semrad, Thomas J; Bazhenova, Lyudmila; Masters, Gregory; Oettel, Kurt; Guaglianone, Perry; Reynolds, Christopher; Karnad, Anand; Arnold, Susanne M; Varella-Garcia, Marileila; Moon, James; Mack, Philip C; Blanke, Charles D; Hirsch, Fred R; Kelly, Karen; Gandara, David R

    2018-01-01

    EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive. We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2 ; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m 2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712). Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control

  13. An Association between Bevacizumab and Recurrent Posterior Reversible Encephalopathy Syndrome in a Patient Presenting with Deep Vein Thrombosis: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Mark Lazarus

    2012-01-01

    Full Text Available Background. The posterior reversible encephalopathy syndrome (PRES is a syndrome characterized by hypertension, headache, seizures, and visual disturbances. Causes of PRES include preeclampsia/eclampsia, hypertension, and recently bevacizumab, a monoclonal antibody vascular endothelial growth factor (VEGF inhibitor. There is no information to date about PRES recurrence in patients taking bevacizumab or descriptions of deep vein thrombosis (DVT in the setting of PRES. We reviewed data on a patient receiving bevacizumab who presented with a DVT and PRES and later developed recurrent PRES. Case. A 72-year-old man with metastatic pulmonary adenocarcinoma received maintenance bevacizumab following six cycles of carboplatin and paclitaxel. Following his eighth dose of bevacizumab, he developed a DVT as well as PRES. He made a rapid recovery and was discharged from the hospital but went on to develop PRES recurrence nine days following his original episode. Conclusion. Several mechanisms exist whereby exposure to bevacizumab could be related to the development of both DVT and PRES by inducing global endothelial dysfunction. Recurrent PRES may result from bevacizumab’s prolonged half-life (11–50 days and suboptimal blood pressure control. In the setting of bevacizumab, PRES surveillance may play a similar role in preeclampsia screening as both diseases share similar antiangiogenic signaling pathways.

  14. Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Urup, Thomas; Dahlrot, Rikke Hedegaard; Grunnet, Kirsten

    2016-01-01

    Background Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan....... Material and methods A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population. Prognostic models were generated by means of multivariate logistic and Cox regression analysis. Results In multivariate...

  15. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

    Science.gov (United States)

    Willett, Christopher G; Boucher, Yves; di Tomaso, Emmanuelle; Duda, Dan G; Munn, Lance L; Tong, Ricky T; Chung, Daniel C; Sahani, Dushyant V; Kalva, Sanjeeva P; Kozin, Sergey V; Mino, Mari; Cohen, Kenneth S; Scadden, David T; Hartford, Alan C; Fischman, Alan J; Clark, Jeffrey W; Ryan, David P; Zhu, Andrew X; Blaszkowsky, Lawrence S; Chen, Helen X; Shellito, Paul C; Lauwers, Gregory Y; Jain, Rakesh K

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. PMID:14745444

  16. THE ECSTACY OF GOLD Patent Expirations for Trastuzumab, Bevacizumab, Rituximab, and Cetuximab.

    Science.gov (United States)

    Serna-Gallegos, Tasha R; LaFargue, Christopher J; Tewari, Krishnansu S

    2017-11-22

    Fully humanized monoclonal antibodies have revolutionized the treatment of many solid tumors, including breast, lung, colorectal, and ovarian cancer. Among the most widely used monoclonal antibodies in clinical oncology are cetuximab, trastuzumab, rituximab, and bevacizumab. This article will review these four notable monoclonal antibodies, their role in clinical oncology, and the drug patents that are nearing expiration. They are used in both first and second line treatment regimens for multiple common malignancies. With recent patent expirations, pharmaceutical companies involved in biosimilar manufacture are looking to establish ownership over these financial monopolies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Intravitreal bevacizumab (Avastin for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Shah Parag

    2007-01-01

    Full Text Available Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type II/rush disease occurs in zone 1 or posterior zone 2. Treatment involves extensive near confluent laser ablation of a large area of avascular retina. Anterior segment ischemia is a rare complication that can occur due to injury to the long posterior ciliary arteries in the horizontal meridians during aggressive posterior laser treatment. The outcome of this rare complication is very poor. This case describes a favorable outcome of intravitreal injection of bevacizumab (Avastin in a case of anterior segment ischemia.

  18. Evaluación urodinámica con doxazocina en pacientes con hiperplasia prostática benigna (HPB. Hospital Pablo Tobón Uribe (HPTU de 1998-1999

    Directory of Open Access Journals (Sweden)

    Juan Aristizábal

    2001-04-01

    Full Text Available

    Tradicionalmente la HPB ha sido tratada quirúrgicamente, pero a
    partir de los años 80 ha aparecido una gran variedad de modalidades
    terapéuticas diferentes a la cirugía, basadas en medicamentos orales que disminuyen el tamaño de la próstata y/o los síntomas que esto genera.
    Se propone estudiar con todos los parámetros urodinámicos, la respuesta de los pacientes con HPB tratados con Doxazocina para evaluar su efecto en las curvas Flujo-Presión.

     

     

  19. Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models

    Science.gov (United States)

    Piao, Yuji; Park, Soon Young; Henry, Verlene; Smith, Bryan D.; Tiao, Ningyi; Flynn, Daniel L.

    2016-01-01

    Background Glioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy. Methods We investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone. Results In vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone. Conclusions Together, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma. PMID:26965451

  20. Tratamiento con estatinas en pacientes pediátricos con síndrome nefrótico resistente a esteroides. Reporte de dos casos

    Directory of Open Access Journals (Sweden)

    C Sánchez-García

    2017-01-01

    Full Text Available El síndrome nefrótico se define por la asociación de proteinuria, hipoalbuminemia, hiperlipidemia y edema. El 80% de los pacientes pediátricos con síndrome nefrótico primario responde a la terapia con esteroides; el 20% restante requiere asociar otros medicamentos para alcanzar la remisión (ciclofosfamida, ciclosporina. La hiperlipidemia en el síndrome nefrótico es debida tanto a un incremento en la síntesis acompañada de disminución en la eliminación de los lípidos de la sangre; siendo la causa directa de esto la proteinuria. La hiperlipidemia incrementa el riesgo cardiovascular, así como el daño glomerular. Con base en esto, la hiperlipidemia persistente en el síndrome nefrótico resistente a esteroides debe ser tratada. Los inhibidores de la 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA reductasa han demostrado efecto antiinflamatorio, inmunomodulador y antiproliferativo. Por ello el papel de las estatinas en el síndrome nefrótico va más allá de su efecto hipolipemiante. Presentamos dos casos de pacientes pediátricos con diagnóstico de síndrome nefrótico resistente a esteroides y su evolución durante el tratamiento con ciclosporina y estatinas.

  1. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab

    DEFF Research Database (Denmark)

    Eefsen, Rikke Løvendahl; Engelholm, Lars Henning; Willemoe, Gro L.

    2016-01-01

    with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy......The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing...... treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell...

  2. Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama

    Directory of Open Access Journals (Sweden)

    Delia B. Dalbert

    2013-04-01

    Full Text Available Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día, sintomáticas (con sangrado o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45% pacientes con factores de riesgo y en 1/65 (1.54% sin ellos (RA: 1.91, IC 95% 1.88 a 1.94. Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%,1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas. Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.

  3. Comparación analítica de los métodos ultravioleta selectivo y test spectroquant 1.14773.0001 en la determinación del ión nitrato en aguas tratadas

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Severiche Sierra

    2014-01-01

    Full Text Available La meta de un análisis químico de aguas es generar resultados correctos y confiables, siendo la comparación de métodos uno de los aspectos más importantes para conseguir este propósito; además, constituye un factor clave para la prestación de servicios analíticos. La determinación de ion nitrato en aguas es una de las metodologías analíticas más discutidas que se conoce en el ámbito científico técnico del análisis de aguas, dado los procedimientos complejos con los que se cuentan, la gran posibilidad de encontrar sustancias interferentes y los rangos de concentración limitados que presentan las diferentes técnicas. En la presente investigación, se hizo el cotejo de dos métodos analíticos, el UV selectivo y el test spectroquant 1.14773.0001, para la determinación del ión nitrato en aguas tratadas. El objetivo fue confirmar correctamente la aplicación de los métodos para el análisis de aguas; las muestras analizadas se tomaron de la red de agua potable de la ciudad de Cartagena de Indias, donde para ambos métodos se encontraron resultados satisfactorios en precisión y exactitud.

  4. Malformaciones congénitas en hijos de madres epilépticas con y sin tratamiento con anticonvulsivantes Congenital malformations in the offspring of epileptic mothers with and without anticonvulsant treatment

    Directory of Open Access Journals (Sweden)

    Jazmín Arteaga-Vázquez

    2012-12-01

    Full Text Available OBJETIVO: Determinar la frecuencia y tipo de malformaciones congénitas (MC en hijos de madres epilépticas (HME tratadas y no tratadas con anticonvulsivantes, la posible correlación anticonvulsivante/MC y la asociación con otras alteraciones del desarrollo. MATERIAL Y MÉTODOS: Estudio multicéntrico de casos y controles en 166 recién nacidos vivos HME identificados en 21 501 recién nacidos con MC y respectivos controles del Registro y Vigilancia Epidemiológica de Malformaciones Congénitas (RYVEMCE. RESULTADOS: La frecuencia de MC en HME tratadas fue mayor, (48.3% que en HME no tratadas (28.3%; (RM= 2.37 IC95% 1.08-5.40, p=0.03. Las MC más frecuentes fueron espina bífida, anomalías en reducción de miembros, labio/paladar hendido, microcefalia, anotia/microtia, hipospadias, paladar hendido, polidactilia, anoftalmia/microftalmia y onfalocele. No hubo diferencias entre uso de mono o politerapia. La difenilhidantoína, carbamazepina y ácido valproico fueron los anticonvulsivantes más utilizados. CONCLUSIONES: Los resultados confirman la teratogenicidad propia de la epilepsia y el efecto sinérgico de ciertos anticonvulsivantes, lo que evidencia la necesidad de un apropiado control periconcepcional de esta enfermedad y su tratamiento.OBJECTIVE: To determine the prevalence at birth and type of congenital malformations (CM in newborns of epileptic mothers (NEM treated and not treated with anticonvulsants, the correlation anticonvulsant/CM and other developmental disorders. MATERIALS AND METHODS: Multicenter case-control study, in 166 live births NEM diagnosed in 21 501 newborns with CM and respective controls from the Registro y Vigilancia Epidemiológica de Malformaciones Congénitas (RYVEMCE. RESULTS: The frequency of CM in NEM treated with anticonvulsants was higher (48.3% than in NEM of untreated mothers (28.3%, (OR= 2.37 IC95% 1.08-5.40, p=0.03. CMs most frequently found were: spina bifida, limb reduction defects, cleft lip palate

  5. Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

    Science.gov (United States)

    REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

    2012-01-01

    Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

  6. A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

    DEFF Research Database (Denmark)

    Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

    2012-01-01

    The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

  7. Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Diness, Laura V

    2018-01-01

    , there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced...

  8. The effect of bevacizumab for anterior segment neovascularization after silicone oil removal in eyes with previous vitreoretinal surgery.

    Science.gov (United States)

    Batman, C; Ozdamar, Y

    2010-07-01

    To report the outcomes of the use of intracameral bevacizumab for iris neovascularization occurring after silicone oil (SO) removal in eyes undergoing vitreoretinal surgery (VRS). This study included 12 eyes that had iris neovascularization after SO removal. The clinical outcomes of 12 eyes after intravitreal bevacizumab injection were reviewed. There were eight men and four women with an average age of 41.58+/-12.68 years. All eyes had VRS for various vitreoretinal diseases. After the mean follow-up period of 9.7+/-5.3 months, SO removal was performed. Then, the patients were followed for more than 2 months and detailed retinal examinations and intraocular pressure (IOP) were normal during this period, but rubeosis iridis (RI) developed. RI was treated with 1 dose of 1.25 mg bevacizumab into the anterior chamber. After a mean follow-up period of 4.8+/-2.2 months, the regression of iris neovacularization was detected and IOP was below 21 mmHg in all eyes. Anterior segment neovascularization (ASNV) may develop through various mechanisms in patients with VRS after SO removal, and anterior chamber injection of bevacizumab may lead to regression of ASNV.

  9. OUTCOMES AFTER LASER VERSUS COMBINED LASER AND BEVACIZUMAB TREATMENT FOR TYPE 1 RETINOPATHY OF PREMATURITY IN ZONE I.

    Science.gov (United States)

    Yoon, Je Moon; Shin, Dong Hoon; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Chang, Yun Sil; Park, Won Soon

    2017-01-01

    To investigate the anatomical and refractive outcomes in patients with Type 1 retinopathy of prematurity in Zone I. The medical records of 101 eyes of 51 consecutive infants with Type 1 retinopathy of prematurity in Zone I were analyzed. Infants were treated by conventional laser photocoagulation (Group I), combined intravitreal bevacizumab injection and Zone I sparing laser (Group II), or intravitreal bevacizumab with deferred laser treatment (Group III). The proportion of unfavorable anatomical outcomes including retinal fold, disc dragging, retrolental tissue obscuring the view of the posterior pole, retinal detachment, and early refractive errors were compared among the three groups. The mean gestational age at birth and the birth weight of all 51 infants were 24.3 ± 1.1 weeks and 646 ± 143 g, respectively. In Group I, an unfavorable anatomical outcome was observed in 10 of 44 eyes (22.7%). In contrast, in Groups II and III, all eyes showed favorable anatomical outcomes without reactivation or retreatment. The refractive error was less myopic in Group III than in Groups I and II (spherical equivalent of -4.62 ± 4.00 D in Group I, -5.53 ± 2.21 D in Group II, and -1.40 ± 2.19 D in Group III; P prematurity in Zone I, intravitreal bevacizumab with concomitant or deferred laser therapy yielded a better anatomical outcome than conventional laser therapy alone. Moreover, intravitreal bevacizumab with deferred laser treatment resulted in less myopic refractive error.

  10. Synthesis, radiolabeling and quality control of {sup 111}In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

    Energy Technology Data Exchange (ETDEWEB)

    Khorami-Moghadam, A.; Jalilian, A.R.; Yavari, K.; Alirezapour, B.; Mazidi, M.; Mirzaii, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

    2013-11-01

    In this study, bevacizumab was successively labeled with {sup 111}In-InCl{sub 3} after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of {sup 111}In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). {sup 111}In-DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology. (orig.)

  11. Bevacizumab as a treatment option for radiation-induced cerebral necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

    2011-02-15

    Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

  12. Umbilical cord blood-derived natural killer cells combined with Bevacizumab for colorectal cancer treatment.

    Science.gov (United States)

    Xu, Chen; Liu, Dongning; Chen, Zhixin; Zhuo, Fan; Sun, Huankui; Hu, Jiaping; Li, Taiyuan

    2018-06-19

    Colorectal cancer (CRC) is among cancers with highest incidence globally and currently ranks fourth as the leading cause of cancer-related deaths worldwide. It remains an urgent need for novel strategies in the management of patients with advanced CRC. Adoptive transfer of allogeneic natural killer (NK) cells represent an attractive option in the treatment of patients with CRC. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound IL-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of IFN-γ, TNF-α, GM-CSF and CCL3 compared with IL-2 stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. More NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Combination of bevacizumab can increase extravasation of adoptively transferred NK cells into the LoVo tumors and improve the therapeutic activity of eUCB-NK cells. These results justified clinical translation of this UCB-derived NK cell-based therapeutics, either used alone or combined with bevacizumab, as a novel treatment option for patients with CRC.

  13. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

    International Nuclear Information System (INIS)

    Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner; Staberg, Mikkel; Villingshøj, Mette; Lassen, Ulrik

    2014-01-01

    Glioblastoma multiforme (GBM) remains one of the most devastating tumors, and patients have a median survival of 15 months despite aggressive local and systemic therapy, including maximal surgical resection, radiation therapy, and concomitant and adjuvant temozolomide. The purpose of antineoplastic treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results of these studies along with relevant preclinical data will be described, and pitfalls in clinical and paraclinical endpoints will be discussed

  14. Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

    Science.gov (United States)

    Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

    2018-01-01

    Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

  15. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    Directory of Open Access Journals (Sweden)

    Grimelda Yuriana Sánchez-Castro

    2008-10-01

    Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

  16. Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

    Science.gov (United States)

    Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

    2013-01-01

    BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

  17. Bevacizumab as a treatment option for radiation-induced cerebral necrosis

    International Nuclear Information System (INIS)

    Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried; Nawatny, Jens; Hoffmann, Thomas K.; Peiper, Matthias; Orth, Klaus; Gerber, Peter Arne; Rusnak, Ethelyn; Lammering, Guido; MAASTRO Clinic, Maastricht

    2011-01-01

    Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

  18. Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

    Science.gov (United States)

    Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

    2009-06-01

    To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

  19. Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

    Science.gov (United States)

    Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

    2009-01-01

    Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10). Conclusion Tachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved. PMID:19516114

  20. Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2007-09-01

    Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

  1. Inseguridad de ebastina: ¿interacción con barnidipino

    Directory of Open Access Journals (Sweden)

    Cremades J

    2010-03-01

    Full Text Available Mujer de 46 años que, en julio de 2007, refiere haber observado desde hace 3 meses “una disminución en el número de veces que orina al día”. Se le ofrece el servicio de seguimiento farmacoterapéutico, que acepta. La paciente está siendo tratada por una hipertensión arterial (HTA con Fortzaar® (losartan/hidroclorotiazida desde hace años y con Libradin® (barnidipino desde mayo de ese mismo año. También utiliza desde hace años Ebastel Forte Flas® (ebastina durante la primavera para tratar su alergia y Ventolín® inhalador (salbutamol para los brotes asmáticos en esa época. Por otro lado, emplea desde hace años Daflon® (diosmina/hesperidina para tratar un problema de “circulación”, Condrosan ® (condroitin sulfato para la artrosis, Optovite B12® (cianocobalamina y Acfol® (ácido fólico por una anemia perniciosa y Gelocatil 1g® (paracetamol, Nolotil® cápsulas (metamizol y Neobrufen® 600 (ibuprofeno para el dolor.

  2. Fracturas de tibia, tratamiento con CIMB no fresados

    Directory of Open Access Journals (Sweden)

    Roberto Del Gordo D´Amato

    2013-10-01

    Full Text Available Se realizó un estudio descriptivo tipo serie de casos en el cual se analizan diversos aspectos inherentes al tratamiento quirúrgico de 92 fracturas de tibia diafisiarias cerradas y abiertas tipo I y II de Gustillo, tratadas con Clavos Intramedulares Bloqueados No Fresados (CIMBNF de las 125 atendidas servicio de ortopedia y traumatología de la Clínica El Prado de la Ciudad de Santa Marta D.T.C.H., entre diciembre del 2005 y diciembre del 2007. Se excluyeron de este estudio 33 casos en los cuales por diversas causas se realizó otro tipo de tratamiento fuera ortopédico o quirúrgico mediante colocación de fijadores externos. Utilizamos la clasificación del AO en la cual a este tipo de lesiones corresponde el número 42. Encontramos una alta incidencia en accidentes de transito como factor productor de este tipo de lesión y dentro de ellos la motocicleta como vehículo mas frecuente. Fueron evaluados 86 de los 92 pacientes que corresponde al 93.5% y dentro de ellos se presentaron complicaciones mayores en el 4.6%, cabe mencionar Infecciones post operatorias y deformidades a nivel proximal y distal por diversas causas, las cuales fueron corregidas con procedimientos ulteriores. (Duazary 2008; 1: 4 - 8

  3. Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

    International Nuclear Information System (INIS)

    Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

    2015-01-01

    The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

  4. Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

    Science.gov (United States)

    Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

    2011-01-01

    Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

  5. Varicocele e infertilidad con implantación de catgut

    Directory of Open Access Journals (Sweden)

    Kenia Ramos Padilla

    2013-10-01

    Full Text Available Introducción: la infertilidad es uno de los problemas médicos y psicosociales que en mayor cuantía está perjudicando a la población en edad reproductiva. De acuerdo con la Sociedad Americana de Medicina Reproductiva, afecta alrededor de 6,1 millones de personas en Estados Unidos, lo que equivale al 10 % de la población en edad reproductiva. Se ha estimado que la infertilidad está presente en el 15 % de las parejas. Aproximadamente el 35 %, la tercera parte de los casos, se deben a un factor masculino, siendo el varicocele la causa más frecuente. Presentación del caso: se trata de un paciente de 31 años de edad operado a los 12 años de atrofia testicular derecha no tratada por criptorquidea, que acude a la consulta de infertilidad del Hospital General Docente Abel Santamaría Cuadrado de Pinar del Río para estudio. Al examen físico se constata un testículo izquierdo compensador con varicocele grado III. Se realizan exámenes complementarios con valores dentro de límites normales, excepto el espermograma. Conclusiones: se procedió al tratamiento quirúrgico (sección y ligadura del cordón espermático y al uso de antioxidantes, sin lograr la fecundidad. Esta sucedió después de alcanzar valores normales en el espermograma con la implantación de catgut cromado en los puntos de acupuntura seleccionados.

  6. Evaluación de la toxicidad aguda oral e irritación sobre mucosa bucal de la solución CM-95 tratada magnéticamente Oral acute toxicity and irritation on buccal mucosa evaluation of the CM-95 solution magnetically treated

    Directory of Open Access Journals (Sweden)

    Jorge Díaz Bestard

    2008-12-01

    Full Text Available La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993

  7. Caracterização de Enterococcus spp. resistentes isolados de águas não tratadas destinadas ao consumo humano

    OpenAIRE

    Macedo, Ana Sofia

    2011-01-01

    Trabalho apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas. A água não tratada é constantemente desvalorizada como fonte de resistências a antibióticos em países desenvolvidos. Para averiguar este problema de saúde pública, neste trabalho isolaram-se Enterococcus spp. como bactérias indicadoras de contaminação fecal de poços, fontes e minas que fornecem água a diversas comunidades em Portugal e caracterizou-se o s...

  8. Evaluación de la recuperación del nitrógeno y fósforo de diferentes fuentes de fertilizantes por el cultivo de trigo irrigado con aguas residuales y de pozo

    OpenAIRE

    Sandra Grisell Mora Ravelo; Francisco Gavi Reyes; Leonardo Tijerina Chávez; Jesús Pérez Moreno; Juan José Peña Cabriales

    2014-01-01

    El empleo de fertilizantes nitrogenados y de aguas residuales no tratadas de origen urbano por los cultivos es una necesidad agronómica, económica y ambiental. El objetivo de este estudio fue evaluar la respuesta del cultivo de trigo a la aplicación de diferentes fertilizantes nitrogenados, irrigado con agua residual y de pozo. Se utilizó un suelo Vertisol Háplico. Se usó como cultivo indicador trigo variedad Tlaxcala F2000. Los fertilizantes aplicados fueron: Fertilizante comercial (FC) cons...

  9. Efecto del gas utilizado en el tratamiento térmico y la impurificación con Eu en las propiedades estructurales de nanofibras de TiO2 depositadas por electrohilado

    OpenAIRE

    Cruz-González, N.; Fernández Muñoz, J.L.; Zapata-Torres, M.; García-Hipólito, M.

    2013-01-01

    En este trabajo estudiamos la influencia de la atmósfera utilizada en el tratamiento térmico; así como la impurificación con Europio, en la transformación estructural de nanofibras de TiO2 crecidas por la técnica de electrohilado. Las muestras de TiO2 fueron tratadas térmicamente en atmósferas de Nitrógeno y Aire. Las muestras de TiO2:Eu fueron tratadas térmicamente en una atmosfera de aire. La morfología fue estudiada por Microscopia Electrónica de Barrido (SEM por sus siglas en ingles); y s...

  10. Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

    Science.gov (United States)

    Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

    2016-01-19

    Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

  11. Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer

    Science.gov (United States)

    Kuesters, Geoffrey M.

    Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo

  12. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

  13. Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

    International Nuclear Information System (INIS)

    Jan, S.; Khan, M.N.; Karim, S.; Khan, M.T.; Hussain, Z.; Khan, S.; Nazim, M.

    2010-01-01

    Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

  14. Bevacizumab treatment reduces retinal neovascularization in a mouse model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Fei; Feng; Yan; Cheng; Qing-Huai; Liu

    2014-01-01

    ·AIM: To evaluate the effect of different bevacizumab concentrations on retinal neovascularization in a retinopathy of prematurity(ROP) mouse model.·METHODS: A total of 60 of C57BL/6 J mice were exposed to 75% ±2% oxygen from postnatal d7 to postnatal d12. Fifteen nonexposed mice served as negative controls(group A). On d12, 30 mice(group C)were injected with 2.5 μg intravitreal bevacizumab(IVB),30 mice(group D) were injected with 1.25 μg IVB in one eye. The contralateral eyes were injected with balanced salt solution(BSS)(control group =group B). The adenosine diphosphatase(ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.Neovascularization was quantified by counting the endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina. Histological changes were examined by light microscopy. The mRNA levels of vascular endothelial growth factor(VEGF) were quantified by Real-time PCR. Western-blotting analysis was performed to examine the expression of P-VEGFR.· RESULTS: Comparing with the control group B,regular distributions and reduced tortuosity of vessels were observed in our retinal flat mounts in groups C and D. The endothelial cell count per histological section was lower in groups C(P <0.0001) and D(P <0.0001) compared with the control group B. Histological evaluation showed no retinal toxicity in any group. In all oxygen treated groups VEGF mRNA expression was significantly increased as compared to age-matched controls. No significant change in VEGF mRNA expression could be achieved in either of the treatments or the oxygen controls. The results of the Western blot were consistent with that of the Real-time PCR analysis.·CONCLUSION: An intravitreal injection of bevacizumab is able to reduce angioproliferative retinopathy in a mouse model for oxygen-induced retinopathy.

  15. Efficacy of Bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma

    Directory of Open Access Journals (Sweden)

    Qian Wang

    2018-03-01

    Full Text Available AIM:To investigate the efficacy of Bevacizumab intravitreal injection combined with EX-PRESS in the treatment of refractory glaucoma. METHODS: The research objects were 150 cases(150 eyesof patients with refractory glaucoma from June 2014 to December 2016 in our hospital. All patients were treated with EX-PRESS glaucoma drainage device implantation, and their medicine data were analyzed retrospectively. Totally 70 cases(70 eyeswere treated with EX-PRESS only were set as the control group; 80 cases(80 eyesreceived bevacizumab intravitreal injection on the basis of the treatment of the control group were set as the observation group. The successful rate of operation was evaluated, the intraocular pressure was measured before operation and at 7d, 1, 3, 6mo after treatment by non-contact conometer, followed by record of the visual acuity and complications before and after 6mo of treatment. RESULTS: The observation group's total surgical success rate was 72.5%, which was sharply higher than that of the control group(58.6%; while the partial success rate was 17.5%, which was significantly lower than that of the control group(30.0%, with statistical significance(χ2=5.453, P=0.028; χ2=4.213, P=0.047. Two groups' surgical failure rate had no distinct difference(χ2=0.000, P=1.000. There was no significant difference in visual acuity of the two groups before and after operation(P>0.05. There was no significant difference in intraocular pressure between the two groups(Fgroups=982.27, PFtime=941.88, PPP>0.05. The observation group's low intraocular pressure, anterior chamber bleeding and shallow anterior chamber incidence were significantly lower than those of the control group, there was statistical meaning(PCONCLUSION: Intravitreal injection of bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma can improve the complete success rate, as well as perform effective control on complications such as short-term intraocular pressure

  16. Evaluation of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy.

    Science.gov (United States)

    Ari, Seyhmus; Nergiz, Yusuf; Aksit, Ihsan; Sahin, Alparslan; Cingu, Kursat; Caca, Ihsan

    2015-03-01

    To evaluate the effects of intracameral injection of ranibizumab and bevacizumab on the corneal endothelium by scanning electron microscopy (SEM). Twenty-eight female rabbits were randomly divided into four equal groups. Rabbits in groups 1 and 2 underwent intracameral injection of 1 mg/0.1 mL and 0.5 mg/0.05 mL ranibizumab, respectively; group 3 was injected with 1.25 mg/0.05 mL bevacizumab. All three groups were injected with a balanced salt solution (BSS) into the anterior chamber of the left (fellow) eye. None of the rabbits in group 4 underwent an injection. Corneal thickness and intraocular pressure were measured before the injections, on the first day, and in the first month after injection. The rabbits were sacrificed and corneal tissues were excised in the first month after injection. Specular microscopy was used for the corneal endothelial cell count. Endothelial cell density was assessed and comparisons drawn between the groups and the control. Micrographs were recorded for SEM examination. The structure of the corneal endothelial cells, the junctional area of the cell membrane, the distribution of microvillus, and the cell morphology of the eyes that underwent intracameral injection of vascular endothelial growth factor (VEGF), BSS, and the control group were compared. Corneal thickness and intraocular pressure were not significantly different between the groups that underwent anti-VEGF or BSS injection and the control group on the first day and in the first month of injection. The corneal endothelial cell count was significantly diminished in all three groups; predominantly in group 1 and 2 (P<0.05). The SEM examination revealed normal corneal endothelial histology in group 3 and the control group. Eyes in group 1 exhibited indistinctness of corneal endothelial cell borders, microvillus loss in the luminal surface, excessive blebbing, and disintegration of intercellular junctions. In group 2, the cell structure of the corneal endothelium

  17. Paciente con esquizofrenia tratado con ziprasidona + clozapina

    Directory of Open Access Journals (Sweden)

    Pol Yanguas E.

    2013-05-01

    Full Text Available P es un paciente diagnosticado de esquizofrenia, sigue en un piso tutelado un programa de rehabilitación, está medicado con clozapina 500 mg/día y ziprasidona 280 mg/ día. Padece hipercolesterolemia, tabaquismo y sus hábitos alimenticios no son buenos. La medicación que utiliza desde 2007 hasta ahora se refleja en la tabla 1. El último tratamiento se le introdujo el 7 de agosto de 2012, habiendo presentado un electro cardiograma (ECG normal, pero con ligera taquicardia ventricular y prolactinemia de 44,8 ng/ml (valores normales: 2-18 ng/ml.

  18. Caracterização por FT-IR da superfície de borracha EPDM tratada via plasma por micro-ondas

    Directory of Open Access Journals (Sweden)

    Renata P. dos Santos

    2012-01-01

    Full Text Available A superfície de uma borracha de etileno-propileno-dieno (EPDM vulcanizada foi modificada via plasma por microondas, com gases Ar, Ar/O2, N2/O2 e N2/H2, tendo como objetivo melhorar as propriedades adesivas da superfície. A técnica FT-IR/UATR foi escolhida para caracterizar as superfícies após tratamento, pois apresentou menor interferência dos ingredientes da formulação da EPDM, dentre as técnicas analisadas (ATR/KRS-5 e Ge. Grupos oxigenados foram inseridos na superfície da amostra tratada, mesmo quando não foi utilizado o oxigênio, pois estes grupos foram formados quando a superfície ativada foi exposta à atmosfera. Já em tratamentos contendo N2, grupos oxigenados e possíveis grupos nitrogenados foram identificados por FT-IR. Redução nos valores do ângulo de contato, aumento no trabalho de adesão e aumento no ensaio de resistência ao descascamento (EPDM × Poliuretano foram observados após tratamento com Ar e N2/H2, resultando em melhora nas propriedades adesivas da superfície tratada.

  19. Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy

    Directory of Open Access Journals (Sweden)

    Freiberg FJ

    2013-06-01

    Full Text Available Florentina Joyce Freiberg,1 Juliane Matlach,1 Franz Grehn,1 Sabine Karl,2 Thomas Klink1 1Department of Ophthalmology, Julius Maximilian University, Wuerzburg, Germany; 2Institute of Mathematics, University of Wuerzburg, Wuerzburg, Germany Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61 who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months. Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0–15 (mean ± standard deviation and range, respectively 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12 (mean ± standard deviation and range, respectively 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005. There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU, yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008. No significant difference in best corrected visual acuity (P = 0.852 and visual field testing (P = 0.610 between preoperative to last follow

  20. Tendencia de la tensión arterial en mujeres con hipertensión arterial esencial-estadio II tratadas con un inhibidor de la enzima convertidora de angiotensina

    Directory of Open Access Journals (Sweden)

    Mario E. Garcés Ferrer

    1995-10-01

    Full Text Available Hypertension stage II women were treated with quinapril (10mg/day an inhibitor of the angiotensin converting enzyme in order to follow blood pressure behavotr. Blood pressure was measured four times at nine week intervals. The mean blood pressure responses with time we significanthy lowered after the second control step.

  1. Influence of zeolite treated with sulphuric acid and sodium hydroxide on the coagulation-flocculation process of drainage. Influencia de la zeolita tratada con acido sulfurico y con hidroxido de sodio en el proceso de coagulacion floculacion en aguas superficiales

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez Duque, M.; Herrera Vasconcelos, T.; Laria Piedra, N.

    1994-01-01

    The present paper has had as objective the treatment of natural zeolite from Tasajera with sulfuric acid and sodium hydroxide (residuals acid and basic from the regeneration of cationic and anionic resins of the ''Otto Parallada'' thermoelectric plant) at different times and concentrations, with a further comparison and testing of the effectiveness of the obtained zeolite in respect to the natural one as a coadyuvant of the coagulation-flocculation process in the treatment of superficial water. (Author)

  2. Influence of zeolite treated with sulphuric acid and sodium hydroxide on the coagulation-flocculation process of drainage. Influencia de la zeolita tratada con acido sulfurico y con hidroxido de sodio en el proceso de coagulacion floculacion en aguas superficiales

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez Duque, M; Herrera Vasconcelos, T; Laria Piedra, N

    1994-01-01

    The present paper has had as objective the treatment of natural zeolite from Tasajera with sulfuric acid and sodium hydroxide (residuals acid and basic from the regeneration of cationic and anionic resins of the ''Otto Parallada'' thermoelectric plant) at different times and concentrations, with a further comparison and testing of the effectiveness of the obtained zeolite in respect to the natural one as a coadyuvant of the coagulation-flocculation process in the treatment of superficial water. (Author)

  3. Hidro conversión de heptano sobre una bentonita colombiana y una saponita española pilarizadas con aluminio y activadas con ácido

    Directory of Open Access Journals (Sweden)

    Manuel Fredy Molina C.

    2011-03-01

    Full Text Available El presente trabajo estudia una arcilla tipo esmectita, una bentonita colombiana, la cual fue sometida a modificación por pilarización con especies de aluminio, y a modificación por tratamiento con ácido clorhídrico de diferentes concentraciones. Igualmente, se empleó una saponita española modificada por pilarización con Al y tratada con ácido clorhídrico de diferentes concentraciones, con el objetode establecer un paralelo entre los dos tipos de arcillas en su comportamiento frente a las modificaciones estudiadas.Los sólidos fueron caracterizados por técnicas convencionales, tales como análisis químico, capacidad de intercambio catiónico, difracción de rayos X, acidez total y análisis de textura. Los resultados indican que los dos tipos dearcilla fueron igualmente pilarizados con Al, independientemente del origen de la esmectita de partida.Los resultados catalíticos en la hidroconversión de heptano, obtenidos sobre catalizadores bifuncionales (arcilla modificada impregnada con Pt revelan que la AlP-saponita es más eficiente en la isomerización que la AIP-bentonita. Esta mayor eficiencia es atribuida a la presencia de sitios ácidos fuertes tipo Si-OH ... Al, los cuales están presentes únicamente en las esmectitas, donde las sustituciones isomórficas están localizadas en las láminas tetraédricas. En montmorillonitas (bentonita, estas sustituciones se encuentran presentes en las láminas octaédricas, de manera que este tipo de sitios ácidos son reducidos o simplemente están ausentes.

  4. Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

    Science.gov (United States)

    Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

    2018-01-01

    Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

  5. MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2015-01-01

    Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM). However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy. Recent findings from a randomized phase-3 study (AVAglio) indicate that patients...... with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study...... was to evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...

  6. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  7. Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

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    Koon-Ja Lee

    2013-04-01

    Full Text Available To understand the corneal regeneration induced by bevacizumab,we investigated the structure changes of stroma andbasement membrane regeneration. A Stick soaked in 0.5 NNaOH onto the mouse cornea and 2.5 mg/ml of bevacizumabwas delivered into an alkali-burned cornea (2 μl by subconjunctivalinjections at 1 hour and 4 days after injury. At 7 daysafter injury, basement membrane regeneration was observedby transmission electron microscope. Uneven and thin epithelialbasement membrane, light density of hemidesmosomes,and edematous collagen fibril bundles are shown in thealkali-burned cornea. Injured epithelial basement membraneand hemidesmosomes and edematous collagen fibril bundlesresulting from alkali-burned mouse cornea was repaired bybevacizumab treatment. This study demonstrates that bevacizumabcan play an important role in wound healing in thecornea by accelerating the reestablishment of basementmembrane integrity that leads to barriers for scar formation.[BMB Reports 2013; 46(4: 195-200

  8. Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 plus Bevacizumab

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    Satoshi Otsu

    2014-01-01

    Full Text Available This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE (version 3.0. The evaluation was especially focused on grade 2 oxaliplatin-induced neuropathy. The estimated median treatment time to occurrence of grade 2 sensory neuropathy was 7.3 months. The estimated median cumulative dose to occurrence of grade 2 sensory neuropathy was 931 mg/m 2 . This study clarified the treatment time from first dose as well as the cumulative dose of oxaliplatin leading to grade 2 neuropathy. It may be important to institute some clinical countermeasures when grade 2 neuropathy occurs so as to reduce the chance of progression to irreversible grade 3 neuropathy.

  9. Bioethics of intervention and the case of drugs Bevacizumab and Ranibizumab for retinal diseases

    Directory of Open Access Journals (Sweden)

    Flávio R. L. Paranhos

    2016-10-01

    Full Text Available From the year 2000, on a class of biological drugs, the anti-VEGF proved to be quite effective in the treatment of retinal diseases, which have in its pathophysiological mechanism an important vascular proliferation component that can lead to blindness. Two of these drugs, bevacizumab and ranibizumab, are quite similar and have the same efficacy and safety. They were developed by the same laboratory and are commercialized by two major pharmaceutical companies through an agreement made between them. However, there is a big difference in the price of the drugs. The aim of this article is to present the Bioethics of intervention as grounds for choosing the cheaper drug, even if forced to do so by regulatory entities.

  10. Bevacizumab in High Grade Gliomas: A Case Report and Review of the Literature

    International Nuclear Information System (INIS)

    Balana, Carme; Cardona, Andres Felipe

    2007-01-01

    Patients with anaplastic astrocytoma or glioblastoma generally have adverse prognosis. Currently, standard treatment for high grade glial cell tumors consists of the concomitant use of radiotherapy and Themozolamide, followed by six months with the alkilant. However, subjects diagnosed with novo or recurrent tumors have overall survival rates from 3 to 15 months. Multiple chemotherapeutic and biological agents have been used to control progression, with no improvement in survival rates. New medication is being developed aimed at molecular targets such as the endothelial growth factor which can be regulated by, among others, Bevacizumab (BEV). Recent results from phase 11 trials combining BEV and Irinotecan (CPT-11) in patients with high grade gliomas revealed improved response rates, as well as disease free and overall survival rates. The case of a female with recurrent glioblastoma who achieved complete response after initiating BEV/CPT- 11 is presented

  11. Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

    Science.gov (United States)

    Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

    2015-03-01

    Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

  12. Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

    Directory of Open Access Journals (Sweden)

    Ökkeş Baz

    2017-06-01

    Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

  13. Perfluorocarbon in vitreoretinal surgery and preoperative bevacizumab in diabetic tractional retinal detachment

    Institute of Scientific and Technical Information of China (English)

    J; Fernando; Arevalo; Martin; A; Serrano; Juan; D; Arias

    2014-01-01

    AIM: To describe the en bloc perfluorodissection(EBPD) technique and to demonstrate the applicabilityof using preoperative intravitreal bevacizumab duringsmall-gauge vitreoretinal surgery(23-gauge transconjunctival sutureless vitrectomy) in eyes with advancedproliferative diabetic retinopathy(PDR) with tractionalretinal detachment(TRD).METHODS: This is a prospective, interventional caseseries. Participants included 114(eyes) with advancedproliferative diabetic retinopathy and TRD. EBPD wasperformed in 114 eyes(consecutive patients) during23-gauge vitrectomy with the utilization of preoperativebevacizumab(1.25 mg/-0.05 mL). Patients mean age was 45 years(range, 21-85 years). Surgical time had a mean of 55 min(Range, 25-85 min). Mean follow up of this group of patients was 24 mo(range, 12-32 mo). Main outcome measures included best-corrected visual acuity(BCVA), retinal reattachment, and complications.RESULTS: Anatomic success occurred in 100%(114/-114) of eyes. Significant visual improvement [≥ 2 Early Treatment Diabetic Retinopathy Study(ETDRS) lines] was obtained in 69.2%(79/-114), in 26 eyes(22.8%) BCVA remained stable, and in 8 eyes(7%) BCVA decreased(≥ 2 ETDRS lines). Final BCVA was 20/-50 or better in 24% of eyes, between 20/-60 and 20/-400 in 46% of eyes, and worse than 20/-400 in 30% of eyes. Complications included cataract in 32(28%) eyes, iatrogenic retinal breaks in 9(7.8%) eyes, vitreous hemorrhage requiring another procedure in 7(6.1%) eyes, and phthisis bulbi in 1(0.9%) eye.CONCLUSION: This study demonstrates the usefulne-ss of using preoperative intravitreal bevacizumab and EBPD during smallgauge vitreoretinal surgery in eyes with TRD in PDR.

  14. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    International Nuclear Information System (INIS)

    Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert

    2015-01-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m 2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [ 18 F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [ 61 Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates

  15. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  16. Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yang Q

    2015-09-01

    Full Text Available Qiong Yang,1–4,* Chenxi Yin,1,3,4,* Fangxin Liao,1,3,4 Yuanyuan Huang,1,3,4 Wenzhuo He,1,3,4 Chang Jiang,1,3,4 Guifang Guo,1,3,4 Bei Zhang,1,3,4 Liangping Xia1,3,41VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workBackground: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%, 22 stable disease responses (62.9%, and six progressive disease responses (17.1% were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7–48.0 months, the median progression-free survival was 5.98 months (95% confidence interval: 4.76–7.2 months, and the median overall survival was 14.77 months (95% confidence interval: 11.45–18.1 months. In the univariate analysis

  17. Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Francesco Erovigni

    2016-10-01

    Full Text Available Medication-induced Osteonecrosis of the Jaw (MRONJ has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab, but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively. We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.

  18. Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

    Science.gov (United States)

    Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

    2017-12-01

    Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  19. Association of Primary Tumor Site With Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer.

    Science.gov (United States)

    Aljehani, Mayada A; Morgan, John W; Guthrie, Laurel A; Jabo, Brice; Ramadan, Majed; Bahjri, Khaled; Lum, Sharon S; Selleck, Matthew; Reeves, Mark E; Garberoglio, Carlos; Senthil, Maheswari

    2018-01-01

    Biologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT. To evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC. This population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides. Treatment with SC or SC plus bevacizumab or cetuximab. Mortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed. A total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared

  20. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

    2010-01-01

    complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23-37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity......, for which 1 patient needed plastic surgery. One patient was excluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except...... for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone....

  1. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

    Science.gov (United States)

    Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

    2015-04-01

    Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

  2. Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in Portugal: a retrospective, multicenter study

    International Nuclear Information System (INIS)

    Estevinho, Fernanda; Soares, Marta; Azevedo, Isabel; Queiroga, Henrique; Parente, Bárbara; Brito, Ulisses; Teixeira, Encarnação; Sotto-Mayor, Renato; Araújo, António

    2012-01-01

    Lung cancer is the leading cause of cancer-related mortality. In patients with nonsquamous non-small-cell lung cancer (NSCLC) stage IIIB/IV treatment with chemotherapy plus bevacizumab led to significant improvements in progression-free and median overall survival (OS). To report the experience of five Portuguese centers in treating patients with nonsquamous NSCLC in stage IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity outcomes. This was a retrospective, multicenter study on patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and chemotherapy from November 2007 to August 2010 through special use permits. We reviewed the medical records, registry of demographic characteristics, treatments provided, treatment responses, adverse events, and dates of death. Statistical analysis was performed with SPSS statistics software. Median OS and event-free survival (EFS) were calculated using the Kaplan–Meier method. From an eligible population of 41 patients, 37 participants were registered. Study participants were predominantly male (78.4%) with a median age of 53 years (29–75 years). In total, 83.8% patients had stage IV disease (TNM, 6th Ed.). The OS was 21.5 months (95% confidence interval [CI]: 12.6–30.5] and median EFS was 9.4 months (95% CI9: 7.1–11.7). Hematologic toxicity grade 3/4 occurred in 35.1% of patients, and nonhematologic toxicity in 24.3% patients. One fatal thromboembolic event was recorded (2.7%). The results of chemotherapy plus bevacizumab treatment for nonsquamous NSCLC obtained from the daily clinical practice of the centers involved in this study were similar to those of published clinical trials. Collaboration between the different Portuguese centers is crucial for this kind of study

  3. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

    2010-01-01

    , hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan...... of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy....

  4. Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    P William Conrad

    2008-06-01

    Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

  5. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.

    Science.gov (United States)

    Shah, Manish A; Jhawer, Minaxi; Ilson, David H; Lefkowitz, Robert A; Robinson, Edric; Capanu, Marinela; Kelsen, David P

    2011-03-01

    To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.

  6. Therapeutic significance of a D-dimer cut-off level of >3 μg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

    International Nuclear Information System (INIS)

    Mochizuki, Satoshi; Yoshino, Takayuki; Kojima, Takashi

    2010-01-01

    The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 μg/ml. The appropriate D-dimer cut-off level was 3 μg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 μg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 μg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 μg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy. (author)

  7. Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

    Directory of Open Access Journals (Sweden)

    Qi Quan

    2017-04-01

    Full Text Available PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS and progression-free survival (PFS were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001 and PFS (P < .001 than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001 and PFS (P = .001. PFS (P < .001 in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049. CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

  8. A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer.

    Science.gov (United States)

    Montero, Alberto J; Avancha, Kiran; Glück, Stefan; Lopes, Gilberto

    2012-04-01

    Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

  9. Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

    Science.gov (United States)

    Guthoff, Rainer; Guthoff, Tanja; Meigen, Thomas; Goebel, Winfried

    2011-01-01

    To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

  10. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    Science.gov (United States)

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  11. ELLIPSE Study: a Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Samson, Géraldine; Roux, Adeline; Fargeton, Anne-Emmanuelle; Rioufol, Catherine; Schwiertz, Verane; Disant, François; Chapuis, François; Donazzolo, Yves; Paintaud, Gilles; Edery, Patrick; Faure, Frederic

    2014-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. ClinicalTrials.gov Identifier #NCT01507480.

  12. Fracturas de clavícula. Tratamiento quirúrgico con clavos intramedulares flexibles

    Directory of Open Access Journals (Sweden)

    Roberto Joaquín Del Gordo D'amato

    2014-05-01

    Full Text Available Se realizó un estudio de tipo descriptivo en una serie de casos en el cual se presentan los resultados de 12 fracturas de clavícula tratadas en forma quirúrgica mediante clavos intramedulares flexibles. Todos los pacientes fueron tratados por los autores en la Clínica El Prado del D.T.C.H. de la Ciudad de Santa Marta mediante reducción cerrada bajo control radioscópico. Presentando resultados excelentes y buenos en todos los casos. Así mismo, se evidenció consolidación clínica a las cuatro semanas con reintegro a la vida laboral alrededor de las seis semanas. Todos los pacientes mostraron alto grado de satisfacción con el resultado obtenido. Se concluye que el tratamiento empleado es una alternativa terapéutica a tener en cuenta en aquellas fracturas desplazadas, sean estas del tercio externo, medio o interno que permite consolidación sin las complicaciones que con alguna frecuencia se presentan con el tratamiento conservador. (Duazary 2006; 2:115-120

  13. Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

    Science.gov (United States)

    Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

    2018-01-01

    Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

  14. Possibility of sandwiched liver surgery with molecular targeting drugs, cetuximab and bevacizumab on colon cancer liver metastases: a case report

    Directory of Open Access Journals (Sweden)

    Toyama Yoichi

    2012-06-01

    Full Text Available Abstract A 31-year-old man with sigmoid colon cancer with concomitant simultaneous multiple liver metastases had received FOLFIRI (leucovorin, fluorouracil and irinotecan and FOLFOX6 (leucovorin, fluorouracil and oxaliplatin after an ordinary sigmoidectomy. However, his serum carcinoembryonic antigen (CEA level increased rapidly during the fifteen months after the operation while he was on FOLFOX6. Abdominal computed tomography revealed expanding multiple liver tumors. As the third line chemotherapy, a combination therapy of cetuximab with irinotecan was given, which markedly reduced his levels of serum CEA, and the size and number of liver tumors. He underwent lateral segmentectomy of the liver and microwave coagulation of the liver metastases in the remnant liver. Thereafter, a good quality of life with tumor dormancy was obtained for 6 months. However, his serum CEA started to rise again in the absence of liver tumors. Therefore, FOLFOX6 with bevacizumab was chosen as the fourth line chemotherapy, and the serum CEA was reduced with tumor dormancy. A good quality of life was obtained again at 3 years after the first surgery. This report indicates the effectiveness of sandwiched liver surgery with the molecular targeting drugs cetuximab and bevacizumab on multiple liver metastases of colon cancer, and suggests the possibility of a regimen consisting of bevacizumab following cetuximab.

  15. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

    Science.gov (United States)

    Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

    2017-05-20

    Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

  16. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  17. Videojuego con Realidad Virtual

    OpenAIRE

    González Mora, César

    2017-01-01

    El objetivo del proyecto es el desarrollo de un videojuego deportivo que utilice realidad mixta. El videojuego se podrá utilizar con dispositivos de tipo cardboard, y utilizará realidad aumentada para la interacción del jugador con el videojuego. En el desarrollo se utilizará el motor Unity para conseguir una aplicación multiplataforma, y la librería Vuforia para implementar realidad mixta.

  18. Sistemas integrados con Arduino

    OpenAIRE

    EL YAKOUTI, MOHAMMED

    2017-01-01

    Design of a robot prototype remotely controllable from Bluetooth using Arduino. Control and testing of sensors and events interacting with Arduino and Bluetooth. Diseño de un prototipo de robot controlable remotamente con Bluetooth utilizando Arduino. Control y verificación de los sensores y eventos que interactúan mediante el Arduino y el Bluetooth. El Yakouti, M. (2017). Sistemas integrados con Arduino. http://hdl.handle.net/10251/89274. TFGM

  19. Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

    Directory of Open Access Journals (Sweden)

    Tobias Bäuerle

    2008-05-01

    Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

  20. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

    Directory of Open Access Journals (Sweden)

    Macedo Ligia

    2012-03-01

    Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

  1. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    Science.gov (United States)

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect. © 2015 UICC.

  2. Exposição humana a trialometanos presentes em água tratada Human exposure to trihalomethanes in drinking water

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    Maria Y Tominaga

    1999-08-01

    Full Text Available Realizou-se uma revisão bibliográfica do período de 1974-1998, no MEDLINE, sobre compostos orgânicos halogenados derivados de hidrocarbonetos denominados de trialometanos. Muitos deles, reconhecidamente carcinogênicos para diferentes espécies animais, podem ser encontrados freqüentemente, inclusive entre nós, em águas tratadas e enviadas à população urbana. É o caso de compostos como o clorofórmio, bromodiclorometano, clorodibromometano e bromofórmio, resultantes da halogenação de precursores, principalmente substâncias húmicas e fúlvicas presentes na água que será tratada (clorada. Assim, descreve-se sua formação, fontes de exposição humana bem como os aspectos toxicológicos de maior importância: disposição cinética e espectro dos efeitos tóxicos (carcinogênicos, mutagênicos e teratogênicos decorrentes de exposições a longo prazo e baixas concentrações. Níveis seguros de exposição propostos são também fornecidos.Halogenated hydrocarbon compounds, some of them recognized as carcinogenic to different animal species can be found in drinking water. Chloroform, bromodichloromethane, dibromochloromethane and bromoform are the most important trihalomethanes found in potable water. They are produced in natural waters during chlorinated desinfection by the halogenation of precursors, specially humic and fulvic compounds. The review, in the MEDLINE covers the period from 1974 to 1998, presents the general aspects of the formation of trihalomethanes, sources of human exposure and their toxicological meaning for exposed organisms: toxicokinetic disposition and spectrum of toxic effects (carcinogenic, mutagenic and teratogenic.

  3. Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas

    Directory of Open Access Journals (Sweden)

    Maria V. de Souza

    2014-06-01

    Full Text Available O plasma rico em plaquetas (PRP é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP. Foram utilizados sete equinos machos castrados, mestiços, hígidos, com idade entre 16 e 17 (16,14±0,63 anos. Três lesões em formato quadrangular (6,25cm² foram produzidas cirurgicamente nas regiões glúteas direita e esquerda de todos os animais. Doze horas após indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiões glúteas (Grupo tratado = GT, escolhida aleatoriamente. A região contralateral foi utilizada como controle (GC. As feridas foram submetidas à limpeza diária com água Milli Q, e amostras foram obtidas mediante biópsias realizadas com Punch de 6mm. Foram obtidas seis biópsias de pele, sendo a primeira realizada logo após a produção da ferida (T0, e as demais com 1 (T1 2 (T2 7 (T3 e 14 (T4 dias após a indução da lesão. A sexta biópsia (T5 foi obtida após completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT. Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5%. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correla

  4. Innovative methods for the identification of predictive biomarker signatures in oncology: Application to bevacizumab

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    Paul Delmar

    2017-03-01

    Full Text Available Current methods for subgroup analyses of data collected from randomized clinical trials (RCTs may lead to false-positives from multiple testing, lack power to detect moderate but clinically meaningful differences, or be too simplistic in characterizing patients who may benefit from treatment. Herein, we present a general procedure based on a set of newly developed statistical methods for the identification and evaluation of complex multivariate predictors of treatment effect. Furthermore, we implemented this procedure to identify a subgroup of patients who may receive the largest benefit from bevacizumab treatment using a panel of 10 biomarkers measured at baseline in patients enrolled on two RCTs investigating bevacizumab in metastatic breast cancer. Data were collected from patients with human epidermal growth factor receptor 2 (HER2-negative (AVADO and HER2-positive (AVEREL metastatic breast cancer. We first developed a classification rule based on an estimated individual scoring system, using data from the AVADO study only. The classification rule takes into consideration a panel of biomarkers, including vascular endothelial growth factor (VEGF-A. We then classified the patients in the independent AVEREL study into patient groups according to “promising” or “not-promising” treatment benefit based on this rule and conducted a statistical analysis within these subgroups to compute point estimates, confidence intervals, and p-values for treatment effect and its interaction. In the group with promising treatment benefit in the AVEREL study, the estimated hazard ratio of bevacizumab versus placebo for progression-free survival was 0.687 (95% confidence interval [CI]: 0.462–1.024, p = 0.065, while in the not-promising group the hazard ratio (HR was 1.152 (95% CI: 0.526–2.524, p = 0.723. Using the median level of VEGF-A from the AVEREL study to divide the study population, then the HR becomes 0.711 (95% CI: 0.435–1.163, p = 0

  5. Investigando con personas con dificultades de aprendizaje

    Directory of Open Access Journals (Sweden)

    Borja González Luna

    2013-12-01

    Full Text Available El artículo muestra los orígenes de lo que Walmsley (2008 denomina «investigación inclusiva». Para comprender qué se entiende por investigación inclusiva tenemos que remontarnos a los debates epistemológicos sobre las metodologías cuantitativas y cualitativas, acontecidos en la década de los 90, en torno a la revista Disability & Society. A partir de una síntesis de dichos debates, focalizados en el ámbito de la «discapacidad intelectual y del desarrollo», se exponen dos estrategias de colaboración con dicha población: a una aproximación etnográfica (de trabajo grupal, y b una aproximación biográfica (de trabajo individual. A continuación se esboza un posible diseño de trabajo de campo que intenta superar el paradigma cualitativo «clásico» con el objetivo de incluir a dicho colectivo más allá del rol de «sujetos de la investigación». Para finalizar se recoge el debate sobre la accesibilidad de los resultados de la investigación a los participantes en dichas investigaciones, y con ello la necesaria innovación en el ámbito de las «devoluciones» de los resultados, cuando se trata de incluir a personas que presentan limitaciones para la comprensión del lenguaje abstracto oral y/o escrito.

  6. A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

    Directory of Open Access Journals (Sweden)

    Satoshi Takeuchi

    2011-05-01

    Full Text Available High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.

  7. INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

    Science.gov (United States)

    Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

    2017-07-01

    To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

  8. Interacción de Tsukamurella paurometabola C-924 con Rhizobium leguminosarum biovar phaseoli CFH en el cultivo de frijol

    Directory of Open Access Journals (Sweden)

    Marieta Marín Bruzos

    2013-01-01

    Full Text Available En el estudio se evaluaron, mediante análisis de los parámetros fenológicos de las plantas, la interacción de Tsukamurella paurometabola C-924 con Rhizobium leguminosarum biovar phaseoli CFH en el cultivo de frijol. Se emplearon cuatro tratamientos: plantas sin inocular (control, inoculadas con T. paurometabola C-924, inoculadas con R. leguminosarum biovar phaseoli CFH e inoculadas con ambas cepas. Se observaron diferencias significativas (P < 0.01 en los porcentajes de germinación de las plantas tratadas con microorganismos de forma independiente o conjunta con respecto al control sin inocular. Se determinó que la inoculación de T. paurometabola C-924 afectó el proceso de nodulación de R. leguminosarum biovar phaseoli CFH. Sin embargo, esto no incidió de manera significativa en la altura de las plantas ni en el diámetro del tallo, ya que no se encontraron diferencias entre los tratamientos para estos parámetros. Para el número de hojas, los mejores resultados se obtuvieron con la aplicación de T. paurometabola C-924. Se concluyó que la interacción de T. paurometabola C-924 con R. leguminosarum biovar phaseoli CFH en el frijol estimuló significativamente la germinación de las semillas y el número de hojas de las plantas con respecto al control sin inocular. Aunque la aplicación de T. paurometabola C-924 no favoreció la nodulación de R. leguminosarum biovar phaseoli CFH, esto no afectó las características fenológicas del cultivo.

  9. Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

    Science.gov (United States)

    Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

    2018-04-24

    Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

  10. Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Hisanori Imai

    2011-09-01

    Full Text Available Purpose: To report a case of proliferative diabetic retinopathy (PDR showing transient macular edema (ME and deteriorated retinal function after intravitreal bevacizumab injection (IVB. Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+ in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

  11. Phase II trial of upfront bevacizumab and temozolomide for unresectable or multifocal glioblastoma

    International Nuclear Information System (INIS)

    Lou, Emil; Peters, Katherine B; Sumrall, Ashley L; Desjardins, Annick; Reardon, David A; Lipp, Eric S; Herndon, James E II; Coan, April; Bailey, Leighann; Turner, Scott; Friedman, Henry S; Vredenburgh, James J

    2013-01-01

    Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6–10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m 2 on days 1–5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 nonhematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials

  12. Posterior Pole Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab Injection in Posterior Retinopathy of Prematurity

    Directory of Open Access Journals (Sweden)

    Rebecca Kim

    2014-01-01

    Full Text Available Purpose. To report the results of the posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection (IVB in retinopathy of prematurity (ROP. Methods. A retrospective chart review of premature babies with ROP, all of whom received laser photocoagulation with IVB. Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation sparing posterior pole with concurrent IVB. The results were compared with those of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced ROP without involvement of the posterior pole. Results. The posterior pole sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly at postoperative day 1, the neovascular proliferation regressed by postoperative week 1, and the normal vascularization started at postoperative day 32 on the average. Two months after treatment, vascularization of the spared avascular area was completed. There was no macular dragging, tractional retinal detachment, foveal destruction by laser scars, or any other adverse event. No significant anatomical differences were identified from those of full-laser ablation combined with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable results without destruction of posterior pole retina.

  13. Bevacizumab loaded solid lipid nanoparticles prepared by the coacervation technique: preliminary in vitro studies

    Science.gov (United States)

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Solazzi, Ilaria; Giordano, Susanna Marzia Adele; Gigliotti, Casimiro Luca; Riganti, Chiara; Dianzani, Chiara

    2015-06-01

    Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer—an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.

  14. An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

    Science.gov (United States)

    DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

    2015-05-01

    Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

  15. Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

    Science.gov (United States)

    Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

    2013-12-01

    The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

  16. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    International Nuclear Information System (INIS)

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

  17. The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

    International Nuclear Information System (INIS)

    Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus; Peck-Radosavljevic, Markus; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus

    2017-01-01

    This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

  18. Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

    Science.gov (United States)

    Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

    2011-03-01

    The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

  19. Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

    Directory of Open Access Journals (Sweden)

    Lister J

    2012-10-01

    Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

  20. Giochiamo con i robot

    Directory of Open Access Journals (Sweden)

    Andrea Bonarini

    2009-01-01

    Full Text Available "Giochiamo con i robot" e' un laboratorio interattivo per grandi e piccini realizzato per l'edizione 2007 del Festival della Scienza di Genova. Lungo un percorso che va dalla telerobotica alla robotica evolutiva, il laboratorio sviluppa il tema di dare intelligenza ai robot. Questo percorso, le cui tappe sono le varie installazioni, si conclude nella "bottega" dove e' possibile costruire e programmare i propri robot o smontare e modificare quelli esposti durante il percorso didattico. I visitatori sono coinvolti in attivita' ludiche grazie alle quali possonoentrare in contatto con alcune delle idee potenti della robotica,

  1. disegnare con ... Alberto Pratelli

    Directory of Open Access Journals (Sweden)

    Roberto Mingucci

    2017-12-01

    Full Text Available Con questa breve intervista ad Alberto Pratelli, (non a caso scelto per aprire questa nuova rubrica intendia-mo inaugurare un dialogo con personalità significati-ve del Disegno di Architettura, che consenta riflessioni dedicate alle sue varie dimensioni, oggi più che mai da approfondire. La suggestione a farlo, viene da un’idea di Pablo Rodri-guez Navarro ed abbiamo quindi pensato di avviarla proprio in questo numero, che Pablo ha accettato di curare su un tema a lui particolarmente caro.

  2. Assessing Biological Response to Bevacizumab Using 18F-Fluoromisonidazole PET/MR Imaging in a Patient with Recurrent Anaplastic Astrocytoma

    Directory of Open Access Journals (Sweden)

    Ramon F. Barajas

    2015-01-01

    Full Text Available We present our initial experience in using single modality fluoromisonidazole (FMISO PET/MR imaging to noninvasively evaluate the biological effects induced by bevacizumab therapy in a patient treated for recurrent high grade glioma. In this index patient, bevacizumab therapy resulted in the development of nonenhancing tumor characterized by reduced diffusion and markedly decreased FMISO uptake in the setting of maintained CBF and CBV. These observations suggest that the dynamic biological interplay between tissue hypoxia and vascular normalization occurring within treated recurrent high grade glioma can be captured utilizing FMISO PET/MR imaging.

  3. A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

    Science.gov (United States)

    Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

    2017-02-28

    Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

  4. Clinical study on bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Li-Ping Yang1

    2017-06-01

    Full Text Available Objective: To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules. Methods: A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined. Results: 3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group. Conclusion: Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.

  5. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

    Directory of Open Access Journals (Sweden)

    Yamamoto D

    2012-09-01

    Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

  6. Primary Tumour Resection Could Improve the Survival of Unresectable Metastatic Colorectal Cancer Patients Receiving Bevacizumab-Containing Chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhiming Wang

    2016-09-01

    Full Text Available Background: The effect of primary tumour resection (PTR among metastatic colorectal cancer (mCRC patients remains controversial. Combination chemotherapy with bevacizumab could improve the clinical outcomes of these patients, which might change the importance of PTR in the multi-disciplinary treatment pattern. Methods: We performed a non-randomized prospective controlled study of mCRC pts whose performance status (PS scored ≤2 and who received bevacizumab combination chemotherapy (FOLFOX/XELOX/FOLFIRI as a first-line therapy. These patients were classified into the PTR group and the IPT (intact primary tumour group according to whether they underwent PTR before receiving the systemic therapy. The progression free survival (PFS time and overall survival (OS time, which were recorded from the start of the primary diagnosis until disease progression and death or last follow-up, were analysed. We also compared severe clinical events (such as emergency surgery, radiation therapy, and stent plantation between the two groups. Results: One hundred and nighty-one mCRC pts (108 male patients and 93 female patients were entered in this prospective observational study. The median age was 57.5 years old. The clinical characteristics (age, gender, performance status, primary tumour site, RAS status, and the number of metastatic organs did not significantly differ between the two groups. The median PFS and OS times of the PTR group were superior than those of the IPT group (10.0 vs 7.8 months, p Conclusions: The mCRC patients who received PTR and bevacizumab combination chemotherapy had better clinical outcomes than patients who did not receive PTR. PTR also decreased the incidence of severe clinical events and improved quality of life.

  7. Suggestion of added value by bevacizumab to chemotherapy in patients with unresectable or recurrent small bowel cancer.

    Science.gov (United States)

    Takayoshi, Kotoe; Kusaba, Hitoshi; Uenomachi, Masato; Mitsugi, Kenji; Makiyama, Chinatsu; Makiyama, Akitaka; Uchino, Keita; Shirakawa, Tsuyoshi; Shibata, Yoshihiro; Shinohara, Yudai; Inadomi, Kyoko; Tsuchihashi, Kenji; Arita, Shuji; Ariyama, Hiroshi; Esaki, Taito; Akashi, Koichi; Baba, Eishi

    2017-08-01

    Standard therapy for advanced small bowel adenocarcinoma (SBA) has not yet been established. The present study assessed the efficacy and safety of chemotherapy (CT) in association with molecular targeting approaches for SBA. The histories of 33 advanced SBA patients from six different institutions in Japan, who received CT from 2008 to 2016, were retrospectively examined for background, clinical course and outcome. Median patient age was 65 years (range 39-83). Primary tumor was located in the duodenum in 21 patients (67%), the ampulla of Vater in three patients (9%), the jejunum in seven patients (21%) and the ileum in one patient (3%). Histologically, well-to-moderately and poorly differentiated adenocarcinoma were identified in 20 (61%) and nine (27%) patients, respectively. Thirteen patients received a single CT regimen, seven patients received two types of CT regimen, and 13 patients received three or more CT regimens. As first-line CT, modified FOLFOX6, capecitabine plus oxaliplatin, and S-1 plus cisplatin were employed in 13, 1, and 4 patients, respectively. The response rate (RR) and median progression-free survival (PFS) were 25% and 6.0 months, respectively. Median overall survival (OS) was 13.0 months. Nine out of the 33 patients received bevacizumab-containing CT and three received cetuximab-containing CT. Median OS of bevacizumab-containing CT patients was 21.9 months. No unexpected serious adverse events were observed. The analysis indicates that combination CT for advanced SBA is associated with modest efficacy and safety, and bevacizumab-containing CT may contribute to favorable outcome in these patients.

  8. Conversando con Oriol Bohigas

    OpenAIRE

    Redondo Domínguez, Ernesto; Moya Sala, Joaquim

    2015-01-01

    [EN] Interview with Oriol Bohigas [ES] Entrevista con Oriol Bohigas Redondo Domínguez, E.; Moya Sala, J. (2015). Conversando con… Oriol Bohigas. EGA. Revista de Expresión Gráfica Arquitectónica. 20(26):22-35. doi:10.4995/ega.2015.4061 22 35 20 26

  9. DR Con o:

    African Journals Online (AJOL)

    which could fall under the Ugandan influence. The con-. flict in the ..... The Congolese people and international community within SADC, the AU ..... ments and make peace among themselves. However, one ... friends overnight.There is a great ...

  10. Armazenamento de sementes de braquiária peletizadas e tratadas com fungicida e inseticida Brachiaria coated seed storage treated with fungicide and insecticide

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Pereira

    2011-12-01

    Full Text Available A qualidade de sementes é fundamental para o sucesso da formação de pastagem, de forma que é importante viabilizar tecnologias para elas. Assim, objetivou-se com este trabalho avaliar o desempenho de sementes de Brachiaria decumbens peletizadas e tratadas com fungicida e inseticida, durante o armazenamento. As sementes foram tratadas com thiabendazol na dosagem de 200mL 100kg-1 de sementes, com fipronil na dosagem de 500mL 100kg-1 de sementes e com a mistura de ambos (nas mesmas dosagens e parte não foi submetida a esses tratamentos (testemunha. Posteriormente, as sementes foram peletizadas utilizando-se uma mistura de areia + microcelulose e cola Cascorex - PVA (20%, as quais em seguida foram armazenadas em condições ambientais em armazém convencional (temperatura e umidade relativa do ar média de 21,9°C e 68%, respectivamente, durante 12 meses. As sementes foram avaliadas inicialmente e a cada quatro meses com as seguintes avaliações: teor de água, teste de germinação, índice de velocidade de germinação, teste de emergência e índice de velocidade de emergência. A peletização das sementes de Brachiaria decumbens com areia e microcelulose prejudica a porcentagem e velocidade de germinação, bem como a emergência de plântulas durante o armazenamento. Sementes de Brachiaria decumbens cv. 'Basilisk' tratadas com fipronil, thiabendazol, ou com ambos, não devem ser armazenadas por mais de oito meses.The quality of seed is crucial to the success of pasture formation. Thus the aim of this research was to evaluate the performance of Brachiaria decumbens seeds pelleted and treated with fungicides and insecticides during storage. The seeds were treated with thiabendazole at a dosage of 200mL 100kg-1 of seeds, with fipronil at a dosage of 500mL 100kg-1 of seeds and a mixture of both (in the same dosages and some was not subjected to such treatment (control. Subsequently the seeds were coated using a mixture of sand

  11. Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

    Science.gov (United States)

    Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

    2014-05-01

    Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (SAiL study. No new safety signals were reported.

  12. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study

    International Nuclear Information System (INIS)

    Velenik, Vaneja; Omejc, Mirko; Ocvirk, Janja; Music, Maja; Bracko, Matej; Anderluh, Franc; Oblak, Irena; Edhemovic, Ibrahim; Brecelj, Erik; Kropivnik, Mateja

    2011-01-01

    Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m 2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower

  13. Is the routine use of bevacizumab in the treatment of women with advanced or recurrent cancer of the cervix sustainable?

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    Klag N

    2016-06-01

    Full Text Available Natalie Klag, Adam C Walter, Kristen M Sheely, Kelly J Manahan, John P Geisler Division of Gynecologic Oncology, Cancer Treatment Centers of America Newnan, Georgia, USA Background: New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. Patients and methods: A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP; regimen 2, CP with bevacizumab (CP+B; regimen 3, paclitaxel/topotecan (PT; and regimen 4, PT with bevacizumab (PT+B. Overall survival, cost, and complications were studied. Sensitivity analyses were performed. Results: Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER for CP+B was $133,559/quality adjusted life year (QALY. ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of <$50,000/QALY gained, the mean overall survival has to increase from 1.1 years with CP to 3.5 years with CP+B. An ICER <$50,000/QALY for the other regimens would take a survival of >10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel. Conclusion: CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs. Keywords: cervical cancer, chemotherapy, bevacizumab, cost-effectiveness

  14. fertilizada con diferentes abonos

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    Jorge Alberto Elizondo-Salazar

    2007-01-01

    Full Text Available Producción y calidad de la biomasa de morera (Morus alba fertilizada con diferentes abonos. Se llevó a cabo un experimento en la Estación Experimental “Alfredo Volio Mata” de la Universidad de Costa Rica con el fi n de evaluar la aplicación de 150 kg de N/ha/año proveniente de dos abonos orgánicos: lombriabono y compostaje; y de un fertilizante químico, sobre la producción y calidad de la biomasa de morera. El periodo experimental comprendió un ciclo de 12 meses, iniciando en julio del 2003 y fi nalizando en julio del 2004. Se utilizó una plantación de morera de 12 años de establecida con una densidad de siembra de 27.777 plantas/ ha. Se empleó un diseño de bloques completos al azar con cuatro tratamientos: dos abonos orgánicos, nitrato de amonio (33,5% N y un control. Las plantas se podaron a 0,6 m sobre el nivel del suelo al inicio del ensayo. Durante el periodo experimental, las plantas fueron podadas consecutivamente cada 90 días. Las hojas y los tallos fueron separados y analizados para determinar el contenido de materia seca y proteína cruda. La producción de materia seca fue 23% superior y el contenido de proteína cruda fue signifi cativamente mayor con el nitrógeno químico, mientras que el contenido de materia seca fue menor. No se encontraron diferencias signifi cativas entre el tratamiento control y los tratamientos orgánicos.

  15. Efecto del control de malezas con paraquat y glifosato sobre la erosión y pérdida de nutrimentos del suelo en cafeto

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    Robin G\\u00F3mez G\\u00F3mez

    2005-01-01

    Full Text Available Efecto del control de malezas con paraquat y glifosatosobre la erosión y pérdida de nutrimentos del suelo encafeto. En Alajuela, Costa Rica, se realizó un experimento enlos años 2002 y 2003 tendiente a determinar el control de malezas, la dinámica poblacional de las malezas y la erosión ypérdida de nutrimentos del suelo debido a aplicaciones sucesivas de paraquat y glifosato. Dos parcelas de 900 m2dentrode una plantación de café fueron aplicadas con paraquat y dosmás tratadas con glifosato. En el año 2003 una parcela de ca-da tratamiento fue disturbada aplicándole materia orgánica(broza de café y carbonato de calcio. El agua de escorrentía ylos sedimentos provenientes de parcelas de 2x7m fueron recogidos en colectores de 200 litros de capacidad y se midieronlas pérdidas de nutrientes. Al inicio de los tratamientos el control de malezas con ambos herbicidas fue de 90-100%, posteriormente con las continuas aplicaciones de herbicidas, sepresentaron malezas tolerantes, haciendo necesario el controlmecánico y aumentar la dosis del herbicida para controlarlas.Durante el 2002 las pérdidas de suelo de las parcelas tratadascon glifosato fueron el doble (3,956 t/ha comparadas con lasocurridas en las parcelas aplicadas con paraquat (1,936 t/ha.En el 2003, en las parcelas no disturbadas tratadas con paraquat se determinó menos erosión (0,231 t/ha en comparacióncon 0,329 t/ha en aquellas aplicadas con glifosato. Asimismo,en las parcelas disturbadas por enmiendas las pérdidas fueronmenores en las aplicadas con paraquat: 0,170 vs. 0,187 t/ha deglifosato. Los análisis de sedimentos y agua mostraron unapérdida importante de Ca, Mg y K, similar en ambos tratamientos. El rendimiento estimado en el año 2003 fue muy similar en ambos tratamientos

  16. ISOLAMENTO E IDENTIFICAÇÃO DE MICOBACTÉRIAS EM ÁGUAS TRATADAS PROVENIENTES DO SISTEMA DE ABASTECIMENTO DE ARARAQUARA-SP

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    Josiane Aparecida GASPAR-GRILLO

    2012-01-01

    Full Text Available A qualidade da água é muito importante para a saúde e bem-estar do ser humano e o sistema de abastecimento público deve fornecer água de qualidade e em quantidade suficiente para toda a população. As estações de tratamento de água constituem o principal caminho para obtenção de água de qualidade. Quando isso não ocorre vários problemas podem afetar a população que passa a consumir água com qualidade inadequada e com o risco constante de surgimento de várias doenças. A eliminação de micro-organismos em água tratada reduz a competição, favorecendo a multiplicação de bactérias resistentes ao cloro como as do gênero Mycobacterium frequentemente isoladas de águas tratadas e cloradas. Considerando a não indicação da pesquisa de micobactérias nos exames laboratoriais de rotina para controle de qualidade de água para consumo humano e outros usos, o objetivo deste trabalho foi verificar a presença, isolar e identificar as micobactérias ambientais no sistema de abastecimento de água de origem superficial da cidade de Araraquara – SP. Foram analisadas 40 amostras de águas, assim distribuídas: dez de água bruta colhidas na Estação de Tratamento de Água (ETA, dez colhidas após filtração, dez colhidas no reservatório após cloração e dez na rede de distribuição. Foram recuperados 43 isolados de micobactérias. Todos os isolados foram submetidos ao PCR-PRA. As espécies de micobactérias identificadas foram M. lentiflavum, M. parafortuitum, M. genavense, M. gordonae, M. fortuitum, M. confluentis, M. duvalii, M. avium subespécie paratuberculose e M. szulgai. Com esses resultados, concluiu-se que a água é importante fonte de micobactérias ambientais provavelmente relacionadas a várias doenças humanas, sugerindo-se a realização de acompanhamento contínuo desses micro-organismos no sistema de água potável.

  17. Eficacia del Fipronil en el control del ciclo peridomiciliario de Triatoma infestans en un área con resistencia a la Deltametrina

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    Alberto G. Gentile

    2004-10-01

    Full Text Available Se investigó la eficacia del Fipronil líquido al 1,0% contra T. infestans, administrado pour on en aves y mamíferos, tanto en condiciones de laboratorio como en el terreno. En laboratorio se trataron con Fipronil una gallina, un perro y un caprino y se alimentaron sobre ellos ninfas III resistentes a Deltametrina. Como grupo control se utilizaron ninfas del mismo estadio criadas en laboratorio. Durante la fase de terreno se impregnaron con Fipronil 4 perros, 1 gato y 2 gallinas cluecas. La infestación intradomiciliaria fue tratada mediante Aerotermia. En laboratorio la mortalidad ninfaria fue del 100,0% a los 7 días y del 88,8% a los 30 días. En terreno, la disminución del Índice de Densidad Triatomínea - medida a los 30 días - fue del 65,4%.

  18. Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Shields, Lisa BE; Kadner, Robert; Vitaz, Todd W; Spalding, Aaron C

    2013-01-01

    We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m 2 ) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m 2 × 5 days) and BEV were delivered monthly until progression or 12 months total. With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ

  19. Parametric Response Maps of Perfusion MRI May Identify Recurrent Glioblastomas Responsive to Bevacizumab and Irinotecan

    Science.gov (United States)

    Aquino, Domenico; Cuppini, Lucia; Anghileri, Elena; Finocchiaro, Gaetano; Bruzzone, Maria Grazia; Eoli, Marica

    2014-01-01

    Background Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome. Methods 42 rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged. Results An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8±0.9 versus 5.1±1.2, p = 0.38), whereas decreased in responsive patients (4.2±1.3 versus 3.8±1.6 p = 0.04), and re-increased progressively when patients approached tumor progression. Conclusions Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients. PMID:24675671

  20. Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Yoon, Sam S.; Duda, Dan G.; Karl, Daniel L.; Kim, Tae-Min; Kambadakone, Avinash R.; Chen, Yen-Lin; Rothrock, Courtney; Rosenberg, Andrew E.; Nielsen, G. Petur; Kirsch, David G.; Choy, Edwin; Harmon, David C.; Hornicek, Francis J.; Dreyfuss, Jonathan; Ancukiewicz, Marek

    2011-01-01

    Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62–72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants

  1. Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey.

    Science.gov (United States)

    Gunay, Murat; Sukgen, Emine Alyamac; Celik, Gokhan; Kocluk, Yusuf

    2017-03-01

    To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

  2. The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

    Science.gov (United States)

    Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

    2014-08-01

    To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

  3. Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

    International Nuclear Information System (INIS)

    Cabrera, Alvin R.; Cuneo, Kyle C.; Desjardins, Annick; Sampson, John H.; McSherry, Frances; Herndon, James E.; Peters, Katherine B.; Allen, Karen; Hoang, Jenny K.; Chang, Zheng; Craciunescu, Oana; Vredenburgh, James J.; Friedman, Henry S.; Kirkpatrick, John P.

    2013-01-01

    Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach

  4. Evaluation of 2-year outcomes following intravitreal bevacizumab (IVB for aggressive posterior retinopathy of prematurity

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    Murat Gunay

    2015-10-01

    Full Text Available ABSTRACTPurpose:To evaluate 2-year outcomes following intravitreal bevacizumab (IVB as monotherapy for aggressive posterior retinopathy of prematurity (APROP.Methods:Medical records of 40 infants were retrospectively reviewed. Group I included infants who had received IVB injections for APROP. Group II included infants who underwent laser treatment for APROP. Anatomic and refractive outcomes and the presence of anisometropia and strabismus were assessed at follow-up examinations.Results:Group I included 48 eyes of 25 infants (11 males with a mean gestational age (GA of 26.40 ± 1.82 weeks and a mean birth weight (BW of 901.40 ± 304.60 g. Group II included 30 eyes of 15 infants (6 males with a mean GA of 27.30 ± 1.82 weeks and a mean BW of 941.00 ± 282.48 g. GA, BW, and gender distributions were similar between groups (P=0.187, P=0.685, and P=1.000, respectively. Refractive errors were significantly less myopic in group I (0.42 ± 3.42 D than in group II (-6.66 ± 4.96 D at 2 years (P=0.001. Significantly higher rates of anisometropia and strabismus were observed in group II than in group I (P=0.009 and P=0.036, respectively.Conclusions:The study demonstrated that IVB monotherapy can be useful in the treatment of APROP. The decreased incidence of early unfavorable refractive and functional outcomes in the IVB group compared with the laser group showed a potential benefit for patients treated with IVB, and this needs to be better evaluated in future prospective studies.

  5. Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy

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    Paola Ulivi

    2017-06-01

    Full Text Available There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided in patients with metastatic colorectal cancer (mCRC. We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa”, randomized to receive first-line chemotherapy (CT or CT plus bevacizumab (CT + B. RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF, endothelial nitric oxide synthase (eNOS, cyclooxygenase-2 (COX2, ephrin type-B receptor 4 (EPHB4, hypoxia-inducible factor 1-alpha (HIF-1α, lactate dehydrogenase (LDH, and high-sensitivity C reactive protein (hs-CRP; and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017. Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

  6. Macular Structures, Optical Components, and Visual Acuity in Preschool Children after Intravitreal Bevacizumab or Laser Treatment.

    Science.gov (United States)

    Lee, Yung-Sung; See, Lai-Chu; Chang, Shu-Hao; Wang, Nan-Kai; Hwang, Yih-Shiou; Lai, Chi-Chun; Chen, Kuan-Jen; Wu, Wei-Chi

    2018-05-10

    To investigate the macular structures, optical components, and visual acuity in preschool-aged children with a history of type I retinopathy of prematurity who underwent either intravitreal bevacizumab (IVB), laser, or a combination of treatments. Comparative interventional case series. A referred medical center in Taiwan. 80 eyes from 42 patients (33 IVB-treated eyes from 17 children, 24 laser-treated eyes from 13 children, and 23 laser + IVB-treated eyes from 12 children). Spectral-domain optical coherence tomography. The retinal thickness in the foveal area and the associated morphologic changes in foveal depression. Compared with the laser-treated and laser + IVB-treated eyes, the IVB-treated eyes had less myopia and deeper anterior chamber depths but presented similar axial lengths and corneal curvatures (P = .001, .002, .95 and .16, respectively). The IVB-treated eyes had significantly thinner foveal, parafoveal, and perifoveal retinal thicknesses (P < .01 for all) and a higher incidence of foveal depression than the laser- or laser + IVB-treated eyes. The macular and subfoveal choroidal thicknesses did not differ among the groups (P = .21 and .63, respectively). Moreover, compared with the eyes treated with laser or laser + IVB, the IVB-treated eyes had better uncorrected visual acuity, although a significant difference was not observed in best-corrected visual acuity (P = .008 and .29, respectively). Compared with laser therapy, IVB-treated eyes were associated with deeper anterior chamber depths and thinner foveal, parafoveal and perifoveal thicknesses. Moreover, these IVB-treated eyes had less refractive errors and better uncorrected visual acuity. Copyright © 2018. Published by Elsevier Inc.

  7. Hepatocellular carcinoma: computed tomography assessment after invasive treatment;Hepatocarcinoma: Evaluacion con tomografia computada luego del tratamiento intervencionista

    Energy Technology Data Exchange (ETDEWEB)

    Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela [Servicio de Diagnostico por Imagenes Hospital General de Agudos ' Cosme Argerich' , CABA, Buenos Aires (Argentina); Departamento de Imagenes, CEMIC, Buenos Aires (Argentina); Eisele, Guillermo [Departamento de Imagenes, CEMIC, Buenos Aires (Argentina); Ridruejo, Ezequiel; Mando, Oscar [Seccion de Hepatologia. Departamento de Medicina, CEMIC, Buenos Aires (Argentina); Perazzo, Florencia [Seccion Oncologia. Departamento de Medicina, CEMIC, Buenos Aires (Argentina)

    2008-07-01

    diagnostico de hepatocarcinoma; todas fueron tratadas en forma minimamente invasiva. Para el tratamiento se dividio a los pacientes en dos grupos siguiendo el criterio de Milan. El primer grupo, constituido por 75 pacientes con 109 nodulos, fue tratado con quimioembolizacion. El segundo grupo, de 15 pacientes y 25 nodulos, fue tratado con ablacion por radiofrecuencia. Dentro de nuestra poblacion, hubo un subgrupo de 10 pacientes (14 nodulos) que se trato con ambos metodos. Resultados: De los 90 pacientes tratados, luego de los controles con TC realizados a un mes, 3 meses y cada 3 meses durante dos anios, en 63 casos (70%) se observo acumulacion homogenea del lipiodol, defecto parcial sin realce o ausencia de realce en la lesion tratada. A estos no se les realizo nuevo procedimiento luego del tratamiento inicial. En los 27 pacientes restantes (30%), se practico un nuevo tratamiento por visualizarse defecto parcial o ausencia del lipiodol con realce o realce periferico en la fase arterial de la lesion tratada. En este ultimo grupo, 16 pacientes tratados (17,7%) tuvieron nuevo realce nodular en el parenquima hepatico restante. Conclusion: La TC en las fases sin contraste y arterial, a un mes y cada 3 meses, permite evaluar la efectividad, enfermedad residual y/o la recaida del hepatocarcinoma luego del tratamiento minimamente invasivo. (autores)

  8. pacientes con falla cardiaca

    Directory of Open Access Journals (Sweden)

    Diana Marcela Achury Saldaña

    2007-01-01

    Full Text Available Objetivo: determinar la adherencia al tratamiento de pacientes con falla cardiaca hospitalizados, al aplicar un plan educativo quefomenta el autocuidado.Método: estudio cuasiexperimental (entrevistas enfermera-paciente realizado entre diciembre de 2004 y mayo de 2006, con unamuestra de 50 pacientes seleccionados por conveniencia. Se diseñó un instrumento para evaluar los comportamientos de los pacientes,con base en algunos resultados de la adherencia y sus respectivos indicadores de la taxonomía NOC (Nursing out comes classification. Laadherencia al tratamiento fue medida en dos momentos: el primero durante la hospitalización, seguido de la aplicación del plan educativoantes del alta, que proporcionaba información en el manejo de su enfermedad desde una dimensión física, psicológica y social quepromueve el autocuidado; y el segundo un mes después del alta en su domicilio.Resultados: diferencias estadísticamente significativas (P=0,0001 que demuestran cómo mediante la capacitación al paciente enel manejo de su tratamiento farmacológico y no farmacológico, el establecimiento de una sana relación entre el profesional de enfermeríay el paciente, y la participación de la familia, se logra una total adherencia al tratamiento.Conclusiones: para lograr una adherencia total del paciente con falla cardiaca al tratamiento es necesario un proceso educativo y unseguimiento continuo y personalizado que motive permanentemente al paciente y se le reconozca el papel protagónico en su cuidado y manejo de la enfermedad.

  9. Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy.

    Science.gov (United States)

    Goede, V; Coutelle, O; Neuneier, J; Reinacher-Schick, A; Schnell, R; Koslowsky, T C; Weihrauch, M R; Cremer, B; Kashkar, H; Odenthal, M; Augustin, H G; Schmiegel, W; Hallek, M; Hacker, U T

    2010-10-26

    The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; Panti-angiogenic treatment.

  10. Phase 1 dose-escalation study of the antiplacental growth factor monoclonal antibody RO5323441 combined with bevacizumab in patients with recurrent glioblastoma

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Chinot, Olivier L; McBain, Catherine

    2015-01-01

    BACKGROUND: We conducted a phase 1 dose-escalation study of RO5323441, a novel antiplacental growth factor (PlGF) monoclonal antibody, to establish the recommended dose for use with bevacizumab and to investigate the pharmacokinetics, pharmacodynamics, safety/tolerability, and preliminary clinica...

  11. Efficacy and safety assessment of the addition of bevacizumab to adjuvant therapy agents in cancer patients: A systematic review and meta-analysis of randomized controlled trials

    NARCIS (Netherlands)

    Ahmadizar, Fariba; Onland-Moret, N. Charlotte; De Boer, Anthonius; Liu, Geoffrey; Maitland-Van Der Zee, Anke H.

    2015-01-01

    Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

  12. Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T F; Carlsen, A L; Heegaard, N H H

    2015-01-01

    BACKGROUND: This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab.METHODS: The study included 68 patients. Blood samples (plasma) were collected b...

  13. Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiao ZHAO

    2012-01-01

    Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

  14. Redução de inóculo de Aphelenchoides besseyi em sementes de Brachiaria brizantha tratadas com óleos essenciais

    Directory of Open Access Journals (Sweden)

    Thalita Suelen Avelar Monteiro

    2014-07-01

    Full Text Available Óleos essenciais foram testados com o objetivo de controlar Aphelenchoides besseyi em sementes de Brachiaria brizantha cv. 'Marandu'. Sementes naturalmente infestadas por A. besseyi foram tratadas com óleos essenciais de mostarda (Brassica nigra, canela (Cinnamomum zeylanicum, verbena (Lippia citriodora e Bioprotector (r (produto comercial composto por extratos e óleos essenciais derivados de plantas, nas concentrações de 0,5% e 1,0%. Avaliou-se também o efeito dos tratamentos após aplicação direta nos juvenis (ensaio in vitro. Todos os óleos tiveram sua efetividade reduzida no ensaio em semente (in vivo em relação ao ensaio in vitro. Os tratamentos não erradicaram o nematoide das sementes, sendo que os óleos essenciais de canela e verbena, nas concentrações 0,5% e 1,0%, Bioprotector (r a 1,0% e óleo de mostarda a 1,0% reduziram o nível populacional do nematoide em sementes contaminadas. O óleo de mostarda a 1,0% destacou-se dos demais por ter apresentado ação nematicida sem alterar a germinação das sementes.

  15. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

    Science.gov (United States)

    Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

    2012-04-01

    We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

  16. EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Grunnet, Kirsten

    2015-01-01

    BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients...... response MRI (RANO criteria). Responders had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS (p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common...... in responders than nonresponders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reducedOS.CONCLUSIONS:Apoor baseline PS and the presence of necrosis were negatively associated...

  17. Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

    2016-01-01

    Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

  18. Comparison of structural outcome between intravitreal bevacizumab and laser treatment for type 1 retinopathy of prematurity after long-term follow-up

    Institute of Scientific and Technical Information of China (English)

    Yen-Yi Chen; Yun-Ju Chen; Yung-Ray Hsu; Fang-Ting Chen; Jia-Kang Wang

    2016-01-01

    Background:To compare the structural outcome of intravitreal bevacizumab (IVB) and laser treatment for type 1 retinopathy of prematurity (ROP). Methods: This is a retrospective comparative study. From December 2002 to April 2009, patients with type 1 ROP according to criteria of Early Treatment of Retinopathy of Prematurity (ETROP) study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern. From May 2009 to January 2015, we performed IVB for patients with type 1 ROP. The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group. The demographical data, postmenstrual age (PMA) for treatment, and fundus ifndings were recorded by chart review. The difference between laser and bevacizumab groups was compared by Studentt-test and Fisher exact test. Results: We collected 43 patients (86 eyes) with type 1 ROP, including 30 male and 13 female infants. Their mean gestation age and birth body weight (BBW) were 27.5 weeks and 1,034 gm. Zone I and zone II disease were found in 8 and 35 patients. The mean PMA for treatment was 37.3 weeks. The mean follow-up period was 54.4 months. Laser treatment was administered in 26 patients, and bevacizumab injection for 17 infants. Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization. Complete regression of ROP was found in 15 infants of bevacizumab group following the ifrst IVB. Four eyes in two patients (2/17, 11.7%) had recurrence of ROP and received additional injections and adjuvant laser treatment. There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management. Conclusions: Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes. Single session of laser ablation

  19. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells.

    Science.gov (United States)

    Dinc, Erdem; Ayaz, Lokman; Kurt, Akif Hakan

    2017-12-01

    This study aimed to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and combined CAPE-bevacizumab against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) in human retinal pigment epithelium. ARPE-19 cells were pretreated with 5, 10, and 30 μM CAPE alone and in combination with bevacizumab for 3 h, then exposed to H 2 O 2 for 16 h. Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vascular endothelial growth factor (VEGF) protein levels in the medium were measured using a human VEGF ELISA kit. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in ARPE-19 cells using the test kit from Rel Assay. Expression levels of VEGF, Bax, Bcl-2, cytochrome c, apoptotic protease activating factor-1 (apaf-1), and caspase-3 were determined using reverse transcription polymerase chain reaction. Pretreatment of ARPE-19 cells with 30 μM CAPE and combined CAPE-bevacizumab reduced H 2 O 2 mediated cell death. H 2 O 2 -induced oxidative stress increased TOS and VEGF production, which was significantly inhibited by CAPE and the CAPE-bevacizumab combination. VEGF, Bax, cytochrome c, apaf-1, and caspase-3 gene expressions were significantly decreased in cells pretreated with 5, 10, and 30 μM CAPE and combined CAPE-bevacizumab compared to the H 2 O 2 group. In addition, Bcl-2 expression was significantly increased in both the CAPE and CAPE-bevacizumab combination groups compared to the H 2 O 2 group. CAPE has a protective effect on ARPE-19 cells against oxidative stress, and VEGF protein level and expression can be decreased by incubation with different concentrations of CAPE. These results demonstrate that CAPE suppresses the mitochondria-mediated apoptosis in ARPE-19 cells under oxidative stress. In addition, the use of CAPE in combination with bevacizumab has an additive effect.

  20. A Feasibility Study of Bevacizumab Plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

    Science.gov (United States)

    McArthur, Heather L.; Rugo, Hope; Nulsen, Benjamin; Hawks, Laura; Grothusen, Jill; Melisko, Michelle; Moasser, Mark; Paulson, Matthew; Traina, Tiffany; Patil, Sujata; Zhou, Qin; Steingart, Richard; Dang, Chau; Morrow, Monica; Cordeiro, Peter; Fornier, Monica; Park, John; Seidman, Andrew; Lake, Diana; Gilewski, Theresa; Theodoulou, Maria; Modi, Shanu; D’Andrea, Gabriella; Sklarin, Nancy; Robson, Mark; Moynahan, Mary Ellen; Sugarman, Steven; Sealey, Jane E.; Laragh, John H.; Merali, Carmen; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

    2016-01-01

    Purpose Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin–cyclophosphamide (ddAC)→nanoparticle albumin−bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC→nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results The median age was 48 years (range, 27−75 years), and baseline LVEF was 68% (53%−82%). After 39 months’ median follow-up (5−45 months): median LVEF was 68% (53%−80%) at 2 months (n=78), 64% (51%−77%) at 6 months (n=66), 63% (48%−77%) at 9 months (n=61), and 66% (42%−76%) at 18 months (n=54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted CHF or HTN, respectively. Conclusions Bevacizumab with ddAC→nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials. PMID:21350003

  1. Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Lai XX

    2016-04-01

    Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

  2. Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

    Science.gov (United States)

    Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

    2012-10-01

    The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

    International Nuclear Information System (INIS)

    Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

    2012-01-01

    Background: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Materials and methods: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6–65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan–Meier survival curves (log-rank test). Results: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. Discussion and conclusion: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab

  4. MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

    Science.gov (United States)

    Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

    2012-06-01

    The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    Science.gov (United States)

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Background Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. Conclusion While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer. PMID:26109878

  6. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    International Nuclear Information System (INIS)

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer

  7. Cementos con cenizas volantes

    Directory of Open Access Journals (Sweden)

    Ossa M., Mauricio

    1984-03-01

    additions of 20 and 30% .

    Casi la generalidad de los estudios realizados sobre cementos con adición de cenizas volantes se refieren a sus características y comportamiento en pastas, morteros y hormigones, siempre en relación con aquéllos del cemento portland. Esta vez, se desarrolló un trabajo experimental orientado a relacionar entre sí los cementos con adiciones de cenizas volantes y de puzolana natural. Para ello se fabricaron a escala de laboratorio cementos de ambos tipos, empleando como materias primas comunes clinker y yeso y, como variables, diferentes porcentajes de las dos adiciones, que cumplieron previamente los requisitos normalizados en cuanto a sus actividades puzolánicas. La calidad de los cementos fabricados resultó adecuada y concordante con la del cemento portland-puzolánico obtenido a escala industrial con los mismos clinker, yeso y puzolana natural de este estudio. Posteriormente, se determinaron las características de los cementos experimentales y se confeccionaron morteros normales para la realización de ensayos físicos y mecánicos. Los resultados de ensayos indicaron que los cementos con adición de cenizas volantes (CCV requieren menos agua para consistencia normal, presentan tiempos de fraguado mayores y expansiones en autoclave menores que los cementos con adición de puzolana (CP. Los calores de hidratación a 7 y 28 días de edad fueron aproximadamente similares para ambos tipos de cemento. En morteros normales, los cementos CCV mostraron menor retracción de secado, mayor retentividad y mayor fluidez (para igual cantidad de agua que los cementos CP. En los ensayos de exudación se observó que ésta depende más de la finura que el tipo de adición. Finalmente, los ensayos mecánicos señalaron que las resistencias a compresión y flexotracción de los morteros con cementos CCV son menores a edades inferiores que 14 días (del orden de 5 a 10% a un día de edad, pero que a partir de entonces pasan a ser mayores que las de

  8. SER Y ESTAR CON ADJETIVOS – SIGNIFICACION DE LAS PROPOSICIONES SER Y ESTAR CON ADJETIVOS – SIGNIFICACION DE LAS PROPOSICIONES

    Directory of Open Access Journals (Sweden)

    Javier García de María

    2008-07-01

    Full Text Available Ser y estar: uno de los temas difíciles de la enseñanza/aprendizaje del español. Este trabajo expone un enfoque que recurre a la significación como hilo conductor. Por una parte, a la significación de ser y de estar como verbos, en sí mismos. Por otra, a la significación de los adjetivos. El planteamiento no es ya qué significa un determinado adjetivo con ser o con estar, sino cuál de estos verbos puede expresar su significado único o cada uno de sus significados. Sobre esta base el análisis considera, primero, los significados de ser/estar y los significados de un adjetivo dado y, segundo, los resultados significativos que arroja la relación entre verbos y adjetivo. Cuando el significado de un adjetivo se pueda expresar con los dos verbos, la elección vendrá determinada por la intencionalidad del hablante en el contexto comunicativo en que se encuentre. A partir de aquí las construcciones en las que aparecen ser y estar son tratadas como proposiciones retórico-argumentativas.Ser and estar: a difficult aspect of Spanish as a foreign language. This essay presents an approach that takes signification as guide line. On the one hand, the signification of ser and estar for their own cause; on the other hand the signification of the adjectives. The question is no longer what the meaning of a given adjective is with ser or with estar, but with which of the two verbs is it possible to express the unique meaning or each of the meanings of that adjective. Starting from this basis the approach considers first, the isolated meanings of the verbs and of the adjectives and, second, the resultant signification out of the relation between the two sides. If the meaning of a given adjective can be expressed by both verbs, the selection of the verb is determined by the intentionality of the speaker in the communicative context in which he negotiates. From this background on the syntactical constructions in which ser and estar appear are treated as

  9. Linfoma primario del sistema nervioso central en una paciente con lupus eritematoso sistémico

    Directory of Open Access Journals (Sweden)

    C. N. Pisoni

    2003-06-01

    Full Text Available Se presenta una paciente de 36 años con diagnóstico de lupus eritematoso sistémico tratada con prednisona y ciclofosfamida que se internó por cefalea, hemiparesia y hemianestesia braquiocrural derecha de dos semanas de evolución. Se realizó una tomografía computada y una resonancia magnética nuclear de cerebro que mostraron una lesión nodular frontal izquierda. Se efectuó una biopsia a cielo abierto de la lesión cerebral cuyo diagnóstico histopatológico fue linfoma B de celulas grandes, difuso. Se inició radioterapia, no completó el tratamiento por complicaciones y falleció. Son muy pocos los casos publicados de linfoma primario del sistema nervioso central asociado a lupus eritematoso sistémico.A 36 year-old woman with systemic lupus erythematosus was admitted to our hospital with headache, brachiocrural hemiparesis and hemianesthesia. She had been treated with prednisone and cyclophosphamide. CT scan and MRI revealed a 15 mm nodular mass enhanced with gadolinium in left frontal convexity. CNS biopsy was performed and a diffuse large B-cell lymphoma was diagnosed. She was treated with radiation therapy without response and died. There are few reports of erythematosus systemic lupus associated with primary central nervous system lymphoma.

  10. competencia con China

    Directory of Open Access Journals (Sweden)

    Elena de la Paz Hernández Águila

    2007-01-01

    Full Text Available El artículo ofrece un diagnóstico del desempeño de la industria mexicana del calzado desde la década de los ochenta hasta la actualidad. Analiza la problemática que ha enfrentado esta rama industrial a partir del proceso de apertura comercial y de la competencia en su mercado interno con productos provenientes de países asiáticos, particularmente China. Problematiza al respecto los retos y las perspectivas que a mediano plazo enfrentará este sector empresarial y sobre las posibilidades de competir en el mercado globalizado.

  11. Construir con Madera

    OpenAIRE

    Olabe-Velasco, F. (Fermín); Val-Hernández, Y. (Yolanda); Varela-de-la-Cruz, P. (Perla); Cabrero-Ballarín, J.M. (José Manuel)

    2010-01-01

    Guía divulgativa ‘Construir con madera’, elaborada por la Cátedra Madera de la Universidad de Navarra y el Gobierno de Navarra. La publicación pretende explicar de forma sencilla los beneficios y posibilidades de este material en la construcción, tanto en lo que respecta a su resistencia, comportamiento frente al fuego, durabilidad, capacidad de aislamiento, propiedades acústicas, estética, respeto al medio ambiente y sostenibilidad como fuente de energía. A modo de ejemplo, en la ...

  12. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor; Desenvolvimento de nanorradiofarmaco a base de Bevacizumabe marcado com tecnecio-99m para diagnostico precoce do tumor estromal gastrointestinal

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Thais Ligiero

    2015-06-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  13. Entrevista con Giovanni Levi

    Directory of Open Access Journals (Sweden)

    Monica Oliveira

    2017-06-01

    Full Text Available En esta entrevista, Giovanni Levi - como un conocedor del tema de Familia - realiza una importante evaluación sobre el actual estado de las investigaciones realizadas en el Brasil y em el exterior. Con estilo franco, agudo y lucido critica las visiones tradicionales y sus ilusiones ypropone nuevos conceptos y métodos. La historia de la familia debería ceder espacio para el estudio de las redes relacionales o de los mundos relacionales. De la misma forma, la historia cuantitativa debería abrir espacio para el estudio de las cualidades. Ya con relación a la historia de las elites, tan estudiada y reproducida en una diversidad de trabajos, que deberíase mirar en otra perspectiva. Es decir, no mirar a las reglas sociales predeterminadas, sino a los desvíos y a las variaciones. Levi defiende que los historiadores deben trascender a los documentos que se encuentran fácilmente y que pueden fortalecer perspectivas deformadas y esequilibradas de la sociedad. Para él, los historiadores deben esforzarse por estudiar a aquellos grupos que dejaron pocos rastros documentales. En ese esfuerzo existiría una nueva mirada sobre la historia de la familia.

  14. Entrevista con Patricia Ariza

    Directory of Open Access Journals (Sweden)

    Esperanza Londoño La Rotta

    2017-01-01

    Full Text Available Pensamiento, Palabra y Obra entrevista a una artista, feminista y activista política, quien como mujer y artista ha permitido pensar el arte más allá de un simple espectáculo. Toda una vida dedicada al teatro y a darle voz, a través de sus obras, a víctimas del conflicto colombiano, defensora de derechos humanos; además de hacer evidente en su vida y a través de la plataforma “Artistas por la paz”, las múltiples relaciones que se pueden establecer entre el arte, la construcción de paz y la resolución de conflictos. Hablamos en su casa, en medio del calor de la bienvenida con Patricia Ariza, directora del festival alternativo de teatro, de Mujeres en Escena y de la Corporación Colombiana de Teatro, entre otras muchas actividades que voluntariamente su espíritu libertario ha asumido. Esta entrevista se realizó antes del 2 de octubre, pero con la revisión de los acuerdos que propició el plebiscito ganado por una ínfima minoría por el no, sigue siendo vigente este planteamiento.

  15. Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

    Science.gov (United States)

    Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

    2014-01-01

    Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

  16. OLEORRESINA DE JÍCAMA Y CALIDAD DE SEMILLA DE FRIJOL INFESTADA CON Acanthoscelides obtectus Say

    Directory of Open Access Journals (Sweden)

    Jos\\u00E9 Antonio Rangel-Lucio

    2011-01-01

    Full Text Available El objetivo de este trabajo fue determinar el efecto de la oleorresina de jícama en la calidad de la semilla de frijol. En laboratorio se obtuvo el extracto de oleorresina media nte HPLC y se detectó la presencia de rotenona (15 mg/l. Se ensayaron tres concentraciones (Ci, g/ml del extracto: C1 (5x10-7, 5x10-6, ¿5x10-2; C2 (1x10-2, 2x10-2,¿6x10-2; C3 (5x10-1, 6x10-1,¿9x10-1 y testigo por concentración, en frascos de 300 ml con 50 g de semilla de frijol (varie dades Flor de Ma yo, Flor de Junio, Ma - yocoba y veinte gorgojos adultos. El ensayo sólo comprendió semillas de frijol tratadas con C2 por 48 horas para evaluar vigor y germinación estándar a los tres y sie te días después de la siembra, bajo normas de IS TA. El aumento de C2 fue gradual en el número de plántulas normales y germinación estándar en el primer recuento, en particular con las diluciones 3 x 10-2 a 6 x 10-2; en el segundo recuento se confirmó la germinación estándar total con estas mismas diluciones. El frijol Ma yocoba en presencia del extracto de semilla de jícama, mantuvo el vigor y valores porcentuales aceptables de germinación estándar de la semilla.

  17. Enraizamento de estacas de atemoieira ‘Gefner’ tratadas com auxinas Rooting of atemoya ‘Gefner’ cuttings treated with auxins

    Directory of Open Access Journals (Sweden)

    Gisela Ferreira

    2008-12-01

    Full Text Available A propagação da atemóia deve ser feita assexuadamente e, nesse contexto, a estaquia surge como alternativa. Dessa forma, objetivou-se determinar a parte do ramo de atemoieira (Annona cherimola Mill. x Annona squamosa L. cv. 'Gefner' mais apropriada para estaquia. O delineamento experimental foi o inteiramente casualizado, em esquema fatorial 3x3 (reguladores x tipos de estaca, com 5 repetições de 12 estacas. Os reguladores utilizados foram AIB 0,5% e ANA 0,5%, aplicados na forma de talco na base das estacas, além da testemunha. Os diferentes tipos de estacas foram retirados de 3 regiões do caule (apical, mediana e basal. As estacas tratadas foram colocadas para enraizar em bandejas de poliestireno contendo substrato comercial Plantmax® e levadas para câmara de nebulização intermitente, onde permaneceram durante 136 dias. As variáveis avaliadas foram: porcentagem de estacas vivas, porcentagem de estacas vivas com enraizamento, porcentagem de estacas enraizadas com folhas remanescentes, com brotações e com folhas remanescentes + brotações, porcentagem de estacas enraizadas sem folhas, número, comprimento médio e massa da matéria seca de raízes por estaca enraizada, área foliar e massa da matéria seca de folhas remanescentes e brotações. A atemoieira apresenta maior potencial para formação de mudas por estaquia empregando-se estacas apicais sem tratamento e medianas tratadas com ANA (0,5%.Atemoya propagation must be done asexually; in this context, cutting represents an alternative. This work aimed to verify the most appropriate branch part of atemoya (Annona cherimola Mill. x Annona squamosa L. cv. 'Gefner' for cutting. The experimental design was completely randomized, in a 3x3 factorial arrangement (plant growth regulators x cutting types, with 5 replicates of 12 cuttings. The plant growth regulators IBA 0.5% and NAA 0.5% were applied as talc in the base of cuttings, besides the control. The different cutting types were

  18. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

    Science.gov (United States)

    Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

    2016-11-01

    Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m 2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of

  19. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Dellas, Kathrin; Dunst, Jürgen; Höhler, Thomas; Reese, Thomas; Würschmidt, Florian; Engel, Erik; Rödel, Claus; Wagner, Wolfgang; Richter, Michael; Arnold, Dirk

    2013-01-01

    Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m 2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m 2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection

  20. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Braga, Thais Ligiero

    2015-01-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  1. Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

    Science.gov (United States)

    Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

    2015-07-01

    This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

  2. FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis.

    Science.gov (United States)

    Tomasello, Gianluca; Petrelli, Fausto; Ghidini, Michele; Russo, Alessandro; Passalacqua, Rodolfo; Barni, Sandro

    2017-07-13

    The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions. A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer). Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded. Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial. Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions. Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30

  3. Qualidade de uva 'Isabel' tratada com cloreto de cálcio em pós-colheita e armazenada sob atmosfera modificada

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    Rosana Sousa da Silva

    2012-03-01

    Full Text Available Uvas 'Isabel' foram tratadas após a colheita com cloreto de cálcio (CaCl2 e submetidas a atmosfera modificada para avaliação da manutenção de sua qualidade durante o armazenamento, a 12±1 ºC e 85±2% de UR. O experimento foi conduzido em delineamento inteiramente casualizado, em esquema fatorial 5 x 2 x 5, com 3 repetições, sendo cinco doses de CaCl2 (0,0; 0,5; 1,0; 2,0 e 4,0%, dois tipos de atmosfera [ambiente e modificada (AM] e cinco períodos, durante o armazenamento refrigerado. As avaliações foram acidez titulável (AT, sólidos solúveis (SS, relação SS/AT, pH, ácido ascórbico, incidência de podridão, perda de massa, aparência do engaço e índice de degrana. A AM reduziu a perda de massa, a incidência de podridão e manteve a aparência verde do engaço, ampliando a vida útil de uva 'Isabel' em seis dias. Doses de CaCl2 entre 0,5 e 2,0% reduziram a incidência de podridão. A aplicação de CaCl2 associado à AM reduziu a degrana em uva 'Isabel' durante o armazenamento refrigerado.

  4. Qualidade das águas cinza tratada com fitorremediação em unidades de produção agrícola

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    Verena S. Baracuhy

    2015-07-01

    Full Text Available A irrigação é uma atividade que necessita de grande quantidade de água, o tratamento de águas cinzas provenientes de uma lavanderia pública em regiões semiáridas para reuso passa a ser uma alternativa de sobrevivência neste ambiente e favorável no desenvolvimento econômico sustentável. Nesse contexto, a pesquisa foi realizada no distrito de Ribeira no município de Cabaceiras - PB objetivando-se avaliar a qualidade da água cinza tratada com fitorremediação nas unidades de produção agrícola. Foram realizados dois tratamentos com(Tanque 2 e sem fitorremediação(Tanque 1, a cultura utilizada foi o capim elefante roxo. Foram coletadas amostras mensais e analisadas os seguintes parâmetros fisicoquimicos: Turbidez, pH, Condutividade elétrica (Ce, Demanda Quimica de Oxigenio(DQO e Fostoro Total. Para a turbidez os valores dos tratamentos foram acima de 1.000 UNT. Na demanda química de oxigênio, o valor mínimo foi de 311mg/L (setembro e máximo de 438mg/L (outubro no tanque 2 em contrapartida no tanque 1 o valor mínimo foi de 354mg/L (setembro e máximo de 618mg/L (outubro. O tratamento com fitorremediação teve uma maior eficiência na redução de DQO.Palavras – chave: capim elefante roxo, reuso, irrigação

  5. Acanthamoeba sp.: un caso de queratitis no relacionada con el uso de lentes de contacto Acanthamoeba sp.: a case report in a non-contact lens wearer

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    Claudia Menghi

    2012-12-01

    Full Text Available La queratitis por Acanthamoeba sp. generalmente se relaciona con el uso de lentes de contacto y en menor proporción se vincula con el contacto con agua contaminada. Se caracteriza por una disminución de la capacidad visual y la presencia de un fuerte dolor ocular. al examen clínico, puede confundirse con una infección herpética. Si la infección no es diagnosticada y tratada a tiempo en forma adecuada, puede culminar en la perforación de la córnea y, eventualmente, en la pérdida del ojo. en este trabajo se informa uno de los pocos casos registrados de queratitis por Acanthamoeba sp. no relacionada con el uso de lentes de contacto.Acanthamoeba sp. keratitis is generally related to wearing contact lenses, and, to a lesser extent, to contaminated water. it is characterized by reduced visual capacity and the presence of severe ocular pain. Clinically, it can be mistaken for a herpes infection. if it is not diagnosed, and timely and adequately treated, it can result in corneal perforation and, eventually, in vision loss. One of the few registered cases of Acanthamoeba sp. keratitis not related to the use of contact lenses is herein reported.

  6. The value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Peck-Radosavljevic, Markus; Pinter, Matthias [Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna (Austria); Wang, Hao [Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing (China); Nanoff, Christian [Medical University of Vienna, Institute of Pharmacology, Vienna (Austria); Kaczirek, Klaus [Medical University of Vienna, Department of Surgery, Vienna (Austria)

    2017-09-15

    This prospective study was to investigate the value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [{sup 11}C]-acetate PET, [{sup 18}F]-FDG PET, and combined [{sup 11}C]-acetate and [{sup 18}F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [{sup 11}C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [{sup 18}F]-FDG with [{sup 11}C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

  7. The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ruan GY

    2018-01-01

    Full Text Available Guanyu Ruan,1,* Lixiang Ye,2,* Guifen Liu,3 Jian An,3 Jalid Sehouli,4 Pengming Sun1,3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, 2Fujian Center for Safety Evaluation of New Drugs, Fujian Medical University, 3Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Gynecologic Oncology and Gynecology, Charité Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer, University of Berlin, Berlin, Germany *These authors contributed equally to this work Abstract: The impact of bevacizumab (an anti-vascular endothelial growth factor therapy remains uncertain, which has been the focus of studies on the management of epithelial ovarian cancer (EOC. To investigate the efficacy of bevacizumab combinations with different regimens in the treatment of patients with EOC, a meta-analysis of Phase III randomized controlled trials was conducted. The databases searched included PubMed, Embase, ClinicalTrials.gov, Chinese Knowledge Infrastructure, as well as the Cochrane Central Register of Controlled Trials. After evaluation of quality, a meta-analysis of valid extracted data was performed using Review Manager (RevMan software. Five studies with 4,369 patients were included. Bevacizumab plus chemotherapy improved progression-free survival (hazard ratio [HR] =0.63; 95% confidence interval [CI], 0.51–0.77; P<0.01 and overall survival (HR =0.91; 95% CI, 0.84–0.99; P<0.05. Interestingly, in patients with a high risk of progression, the subgroups that received bevacizumab combined with different regimens of chemotherapy showed a significant improvement with paclitaxel plus carboplatin-based chemotherapy (HR =0.86; 95% CI, 0.77–0.95; P<0.01, but not with non-paclitaxel plus carboplatin-based chemotherapy (HR =0.91; 95% CI, 0

  8. Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2.

    Science.gov (United States)

    Narayanan, Raja; Panchal, Bhavik; Stewart, Michael W; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Hasnat Ali, Mohd

    2016-01-01

    The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion. Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months. The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval -221.50 to -135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval -246.49 to -140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06). Bimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it's required more often in patients treated with bevacizumab.

  9. Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2

    Science.gov (United States)

    Narayanan, Raja; Panchal, Bhavik; Stewart, Michael W; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Hasnat Ali, Mohd

    2016-01-01

    Purpose The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion. Patients and methods Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months. Results The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval −221.50 to −135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval −246.49 to −140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06). Conclusion Bimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it’s required more often in patients treated with bevacizumab. PMID:27330272

  10. The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

    Science.gov (United States)

    Li, Shuren; Peck-Radosavljevic, Markus; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus; Haug, Alexander; Hacker, Marcus

    2017-09-01

    This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

  11. Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials.

    Science.gov (United States)

    Cremolini, Chiara; Milione, Massimo; Marmorino, Federica; Morano, Federica; Zucchelli, Gemma; Mennitto, Alessia; Prisciandaro, Michele; Lonardi, Sara; Pellegrinelli, Alessio; Rossini, Daniele; Bergamo, Francesca; Aprile, Giuseppe; Urbani, Lucio; Morelli, Luca; Schirripa, Marta; Cardellino, Giovanni Gerardo; Fassan, Matteo; Fontanini, Gabriella; de Braud, Filippo; Mazzaferro, Vincenzo; Falcone, Alfredo; Pietrantonio, Filippo

    2018-04-01

    Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than

  12. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    Directory of Open Access Journals (Sweden)

    Hiroki Hashida

    2017-01-01

    Full Text Available It has been reported that many patients with lung metastasis of colorectal cancer (CRC underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI plus bevacizumab (BV therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped.

  13. Durable clinical activity of single-agent bevacizumab in a nonagenarian patient with metastatic alveolar soft part sarcoma.

    Science.gov (United States)

    Mir, Olivier; Boudou-Rouquette, Pascaline; Larousserie, Frédérique; Blanchet, Benoit; Babinet, Antoine; Anract, Philippe; Goldwasser, François

    2012-08-01

    Alveolar soft part sarcoma is a rare malignancy usually considered resistant to conventional chemotherapy, but recent data suggest that the multikinase inhibitors sunitinib and cediranib could be active in this setting. A 90-year-old lady with alveolar soft part sarcoma of the leg and lung metastases was started on sunitinib 37.5 mg daily. The treatment was poorly tolerated with grade 3 hypertension and grade 3 thrombocytopenia, which persisted after dose reduction to 25 mg daily. The patient was subsequently started on bevacizumab 10 mg/kg every 2 weeks, resulting in a marked improvement in pain and a partial response on lung metastases for 16 months and ongoing. Agents targeting the vascular endothelial growth factor-signalling pathway seem to exert clinically relevant and prolonged activity against alveolar soft part sarcoma and deserve further evaluation in the treatment of this rare soft tissue sarcoma.

  14. preescolares desnutridos con madres con obesidad y sin obesidad

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    Viridiana Vanessa Conzuelo-González

    2009-01-01

    Full Text Available El primer objetivo fue conocer cuántos menores de cinco años con diferentes grados de desnutrición tienen una madre con sobrepeso/obesidad/ en una comunidad indígena que vive en extrema pobreza y bajo condiciones de migración masculina internacional. El segundo fue comparar tres variables socionutricionales (ingreso familiar, educación de la madre y adecuación nutrimental de la dieta diaria entre estos hogares y los hogares con desnutrición infantil y madres sin obesidad. Se realizó un estudio transversal (2006-2007, en la comunidad mazahua de San Francisco Tepeolulco, Municipio de Temascalcingo; que incluyó a 85 hogares integrados por preescolares con desnutrición inscritos al programa Oportunidades. Se determinó el estado nutrición de los preescolares con indicadores antropométricos y se obtuvo el IMC de las madres de estos infantes. Se aplicó una encuesta socionutricional, incluida el recordatorio de 24 horas, y complementado con la observación participante (cualitativa. Se encontró que 83% de las madres mazahuas presentaron sobrepeso u obesidad. El estado de nutrición de los preescolares con madres con obesidad presentó un porcentaje mayor de desnutrición (76%. En la variable género, se encontró que 54% de los niños con madres con obesidad tenía baja talla. Al relacionar el nivel educativo de la madre, esta variable resultó ser estadísticamente significativa (p=0.015, donde el analfabetismo está más relacionado con la desnutrición infantil que tienen madres de bajo y/o peso normal. La elevada prevalencia de hogares conformados con preescolares con desnutrición y madres con obesidad, es un síntoma más de la pobreza en zonas indígenas en México, con bajo índice de desarrollo humano.

  15. Treatment of multifocal central nervous system AIDS-related Epstein Barr virus-associated malignant myopericytoma with bevacizumab

    Directory of Open Access Journals (Sweden)

    Linda Szymanski

    2017-09-01

    Full Text Available A 31 year-old man with HIV and pulmonary tuberculosis (TB status-post RIPE regimen presented with cough and throbbing headaches. Laboratory results were remarkable for a CD4 count of 2 kcells/L and a viral load of 2.7 million copies/mL. MRI of the brain reported multiple lobulated and cystic intracranial lesions associated with the dura that had thick rinds of enhancement. CT of the chest, abdomen and pelvis demonstrated axillary and inguinal lymphadenopathy, a mass within the right pelvis thought to represent necrotic lymph nodes, prominence of the right psoas muscle, a cystic nodule in the liver, and a right adrenal lesion. The patient was started on dexamethasone, RIPE therapy, and empiric antimicrobial therapy. He subsequently underwent stealth-guided brain biopsy and open craniotomy. Pathology returned a tissue diagnosis of an AIDS related EBV-associated smooth muscle tumor (EBV-SMT best categorized as a malignant myopericytoma. Following surgery, the patient began additional anti-retroviral therapy for HIV and was discharged. Despite treatment, three to four months following discharge the patient's symptoms progressed and he was found to have developed a severe bilateral homonymous hemianopsia. Repeat MRI demonstrated tumor growth and the patient subsequently received whole brain radiation along with sirolimus and pomalidomide. Approximately two months following radiation therapy the patient had increasing headaches along with nausea and vomiting. Repeat MRI was consistent with radiation arrested tumor growth but did not show any decrease in size of his intracranial lesions. Therapy with bevacizumab was initiated and he had marked improvement of his visual field deficits. The patient has since completed 20 cycles of treatment with bevacizumab and is currently 17 months post his initial diagnosis. Repeat imaging has demonstrated decreasing size of his lesions and no new lesions have developed.

  16. Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

    Science.gov (United States)

    Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

    2017-01-01

    The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

  17. Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

    International Nuclear Information System (INIS)

    Berruti, Alfredo; D’Avolio, Antonio; Priola, Adriano Massimiliano; Birocco, Nadia; Amoroso, Vito; Biasco, Guido; Papotti, Mauro; Dogliotti, Luigi; Fazio, Nicola; Ferrero, Anna; Brizzi, Maria Pia; Volante, Marco; Nobili, Elisabetta; Tozzi, Lucia; Bodei, Lisa; Torta, Mirella

    2014-01-01

    We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration number http://www.clinicaltrials.gov/ct2/show/NCT01203306?term

  18. <