Los médicos se reúnen en Copenhague para analizar los mejores enfoques para el futuro tratamiento con radioterapia para el cáncer cerebral, de próstata y pulmonar
Hoy, médicos de todo el mundo se reunirán en el 4th Brainlab European Radiotherapy User Meeting para compartir sus prácticas recomendadas y experiencias en el tratamiento de cánceres difíciles de tratar utilizando radioterapia avanzada.
La reunión de dos días celebrada en el Global Center of Stereotactic Radiotherapy en Rigs Hospitalet, Copenhagen University Hospital, Dinamarca, pretende analizar los mejores enfoques para el tratamiento de radiación futuro para lograr los mejores resultados para los pacientes. Más de 170 médicos de casi 90 centros de cáncer internacionales escucharán 33 enfoques avanzados diferentes para tratar el cáncer en el organismo utilizando técnicas de terapia de radiación modernas.
Los puntos destacados del encuentro serán las presentaciones de nuevos protocolos para el tratamiento del cáncer de pulmón, próstata y cerebro con radiocirugía. Estos protocolos mostrarán que la radiocirugía puede ofrecer tiempos de tratamiento más rápidos, periodos más cortos de tratamiento y a su vez permite tratar a mayor número de pacientes utilizando los mismos sistemas de radioterapia avanzados.
El especialista clínico en cáncer de próstata, el profesor Raymond Miralbell, responsable de Radiation Oncology en el University Hospital Geneva, Suiza, presentará sus experiencias tratando el cáncer de próstata utilizando un nuevo enfoque de radiocirugía:
"Utilizando un hipofraccionamiento extremo podremos mostrar cómo puede tratarse el cáncer de próstata con precisión y efectividad en un marco de tiempo muy corto, ofreciendo una opción de tratamiento no invasiva para los pacientes con resultados comparables a la cirugía abierta tradicional. En el encuentro podemos compartir los hallazgos y también lanzar una petición a los médicos para que utilicen este protocolo en sus propios centros y ayudar a reunir más resultados que permitirán mejoras en el tratamiento".
El encuentro de radioterapia bianual de Brainlab sigue inmediatamente el lanzamiento de la Global Center of Stereotactic Radiotherapy en Rigs Hospitalet, lanzado para los médicos locales el día anterior. La planta es uno de los centros de cáncer mejor equipados del mundo con tecnología avanzada que permite a los médicos tratar y buscar algunas de las técnicas más modernas disponibles para los pacientes.
El profesor Sven Aage Engelholm, responsable de Radiation Therapy, comentó: "Ahora tenemos algunas de las tecnologías más avanzadas en el mundo para tratar el cáncer. Esperamos que con la combinación de las últimas tecnologías y los mejorados protocolos de tratamiento podamos maximizar el número de pacientes que podemos tratar, y pretendemos tratar a 3.000 en los próximos cinco años".
Stefan Vilsmeier, fundador y consejero delegado de Brainlab, comentó: "Una iniciativa clave para Brainlab es promover las prácticas clínicas recomendadas y estamos encantados de estar implicados en asociaciones con centros claves que están impulsando la excelencia clínica en radiocirugía y cuidado del cáncer. Como compañía, tenemos una dedicación para apoyar a médicos para mejorar sus flujos de trabajo clínicos y a su vez mejorar el cuidado del cáncer para sus pacientes".
19 March 2012
Los "guerreros" de Bellvitge
Hace cinco meses que unos 200 vecinos de Bellvitge empezaron una ocupación pacífica del centro de asistencia primaria (CAP) La Marina para reclamar su reapertura. El centro, borrado del mapa sanitario de la Generalitat dentro de la política de recortes, absorbía la demanda médida de unos 15.000 vecinos de un barrio en el que viven más de 35.000.
Durante día y noche, los vecinos se turnan en grupos para mantener viva la protesta. "No nos vamos a ir de aquí hasta que nos devuelvan lo que es nuestro, hasta que traigan otra vez a los médicos y especialistas", advierten los ciudadanos, en su mayoría jubilados.
>> Si desea leer la noticia completa, abónese a e-Periodico
Durante día y noche, los vecinos se turnan en grupos para mantener viva la protesta. "No nos vamos a ir de aquí hasta que nos devuelvan lo que es nuestro, hasta que traigan otra vez a los médicos y especialistas", advierten los ciudadanos, en su mayoría jubilados.
>> Si desea leer la noticia completa, abónese a e-Periodico
Nanopills Release Drugs Directly from the Inside of Cells
Researchers at Universitat Autonoma de Barcelona (UAB) have created nanoparticles which could release drugs directly from the cells' interior. The technology, which has been named "nanopills," was licensed to the firm Janus Developments of the Barcelona Scientific Park, which verified its tolerance by administering it in vivo.
UAB researchers developed a new vehicle to release proteins with therapeutic effects. This is known as "bacteria-inclusion bodies," stable insoluble nanoparticles which normally are found in recombinant bacteria. Even though these inclusion bodies traditionally have been an obstacle in the industrial production of soluble enzymes and biodrugs, they were recently recognised as having large amounts of functional proteins with direct values in industrial and biomedical applications.
The research team led by Antoni Vallverde from the Institute of Biotechnology and Biomedicine (IBB) at UAB worked in collaboration with the Online Biomedical Research Centre for Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN) to verify the value of these nanoparticles as natural "nanopills" with a strong capacity to penetrate cells and carry out biological activities. The nanopill concept represents a new and promising platform for drug administration and illustrates the yet to be explored power of microbian materials in medicine.
The researchers, in a multidisciplinary study at UAB led by Dr Esther Vàzquez, packaged four proteins containing different therapeutic effects into experimental nanopills, the inclusion bodies of the bacteria Escherichia coli. They put the bacteria in contact with cell cultures of mammals under similar conditions to those found in real clinical pathologies, "sick" cells with low viability, and achieved to recover their activity.
Once the technology was licensed to Janus Developments, the tolerance of its administration in vivo were confirmed through experiments conducted by UAB researcher Ester Fernández. The results and detailed description of the "nanopill" were published this week in the journal Advanced Materials.
UAB researchers developed a new vehicle to release proteins with therapeutic effects. This is known as "bacteria-inclusion bodies," stable insoluble nanoparticles which normally are found in recombinant bacteria. Even though these inclusion bodies traditionally have been an obstacle in the industrial production of soluble enzymes and biodrugs, they were recently recognised as having large amounts of functional proteins with direct values in industrial and biomedical applications.
The research team led by Antoni Vallverde from the Institute of Biotechnology and Biomedicine (IBB) at UAB worked in collaboration with the Online Biomedical Research Centre for Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN) to verify the value of these nanoparticles as natural "nanopills" with a strong capacity to penetrate cells and carry out biological activities. The nanopill concept represents a new and promising platform for drug administration and illustrates the yet to be explored power of microbian materials in medicine.
The researchers, in a multidisciplinary study at UAB led by Dr Esther Vàzquez, packaged four proteins containing different therapeutic effects into experimental nanopills, the inclusion bodies of the bacteria Escherichia coli. They put the bacteria in contact with cell cultures of mammals under similar conditions to those found in real clinical pathologies, "sick" cells with low viability, and achieved to recover their activity.
Once the technology was licensed to Janus Developments, the tolerance of its administration in vivo were confirmed through experiments conducted by UAB researcher Ester Fernández. The results and detailed description of the "nanopill" were published this week in the journal Advanced Materials.
**Published in "SCIENCE DAILY"
Bone Marrow Transplant Arrests Symptoms in Model of Rett Syndrome
A paper published online March 18 in Nature describes the results of using bone marrow transplant (BMT) to replace faulty immune system cells in models of Rett Syndrome. The procedure arrested many severe symptoms of the childhood disorder, including abnormal breathing and movement, and significantly extended the lifespan of Rett mouse models. Exploring the function of microglia deficient in methyl-CpG binding protein 2 (Mecp2), the protein encoded by the "Rett gene," principal investigator Jonathan Kipnis, Ph.D. and his team at the University of Virginia School of Medicine uncovered a completely novel approach to this devastating neurological syndrome. The work was funded by the Rett Syndrome Research Trust and the Rett Syndrome Research Trust UK.
Rett Syndrome, the most physically disabling of the autism spectrum disorders, is caused by random mutations in the gene MECP2. Predominantly affecting girls, symptoms usually manifest between 6 and 18 months of age, when a frightening regression begins. Children lose acquired language skills and functional hand use; movement deteriorates as other Rett symptoms appear. These may include disordered breathing, Parkinsonian tremors, severe anxiety, seizures, digestive and circulatory problems and a range of autonomic nervous system and orthopedic abnormalities Although most children survive to adulthood, many are wheelchair-bound, rely on feeding tubes, are unable to communicate and require total, lifelong care.
Kipnis was drawn to Rett Syndrome from his perspective as a neuroimmunologist. "What began as intellectual curiosity," he explains, "has become an intense personal commitment to studying the correlation between neurological function and the immune system in Rett Syndrome. The impact of BMT on so many different symptoms has triggered a flood of experiments we are now pursuing at full speed."
The brain is largely composed of several types of glial cells, which have diverse and complex functions that include sustaining a healthy environment for neuronal growth and maintenance. Microglia are small glial cells that participate in the brain's immune response. One of their roles is to clean up normal cellular debris in the brain through the process of phagocytosis. Kipnis and his team discovered that when microglia lack properly functioning Mecp2, they are unable to perform this crucial duty efficiently. Because microglia are derived from immune progenitor cells, it is possible to replace them via a bone marrow transplant.
First author Noël Derecki and his colleagues began their work with male Rett mouse models, which lack any Mecp2. These Mecp2-null mice mimic the human disorder, with neurological symptoms beginning to appear at about 4 weeks of age and an approximate life expectancy of only 8 weeks. Radiation treatment was administered at 4 weeks, followed by a bone marrow transplant from normal (wild-type) mice. As engraftment -- the migration and repopulation of new microglia -- took place, the Rett mice began to grow instead of fail. Body and brain sizes approached those of wild-type mice, gait improved and mobility increased significantly. There were no signs of the severe tremors seen in untreated mice. Apneas and other breathing irregularities were markedly diminished. The oldest of these mice is now almost a year. Work with female Rett mouse models at more advanced stages of disease is currently underway.
Gail Mandel, Ph.D., whose Rett research focuses on astrocytes, another type of glial cell impaired by mutations in MECP2, comments, "A fascinating aspect of these findings is the data suggesting that deficits in the engulfing properties of microglia are a crucial aspect of Rett neuropathology. It will now be necessary to develop cellular assays to determine all the ways these immune cells are bolstering neuronal functions and whether they can be therapeutically harnessed." Dr. Mandel is a Senior Scientist at the Vollum Institute and a Professor in the Department of Biochemistry and Molecular Biology in the School of Medicine at Oregon Health & Science University and an Investigator of the Howard Hughes Medical Institute.
*Published in "SCIENCE DAILY"
Rett Syndrome, the most physically disabling of the autism spectrum disorders, is caused by random mutations in the gene MECP2. Predominantly affecting girls, symptoms usually manifest between 6 and 18 months of age, when a frightening regression begins. Children lose acquired language skills and functional hand use; movement deteriorates as other Rett symptoms appear. These may include disordered breathing, Parkinsonian tremors, severe anxiety, seizures, digestive and circulatory problems and a range of autonomic nervous system and orthopedic abnormalities Although most children survive to adulthood, many are wheelchair-bound, rely on feeding tubes, are unable to communicate and require total, lifelong care.
Kipnis was drawn to Rett Syndrome from his perspective as a neuroimmunologist. "What began as intellectual curiosity," he explains, "has become an intense personal commitment to studying the correlation between neurological function and the immune system in Rett Syndrome. The impact of BMT on so many different symptoms has triggered a flood of experiments we are now pursuing at full speed."
The brain is largely composed of several types of glial cells, which have diverse and complex functions that include sustaining a healthy environment for neuronal growth and maintenance. Microglia are small glial cells that participate in the brain's immune response. One of their roles is to clean up normal cellular debris in the brain through the process of phagocytosis. Kipnis and his team discovered that when microglia lack properly functioning Mecp2, they are unable to perform this crucial duty efficiently. Because microglia are derived from immune progenitor cells, it is possible to replace them via a bone marrow transplant.
First author Noël Derecki and his colleagues began their work with male Rett mouse models, which lack any Mecp2. These Mecp2-null mice mimic the human disorder, with neurological symptoms beginning to appear at about 4 weeks of age and an approximate life expectancy of only 8 weeks. Radiation treatment was administered at 4 weeks, followed by a bone marrow transplant from normal (wild-type) mice. As engraftment -- the migration and repopulation of new microglia -- took place, the Rett mice began to grow instead of fail. Body and brain sizes approached those of wild-type mice, gait improved and mobility increased significantly. There were no signs of the severe tremors seen in untreated mice. Apneas and other breathing irregularities were markedly diminished. The oldest of these mice is now almost a year. Work with female Rett mouse models at more advanced stages of disease is currently underway.
Gail Mandel, Ph.D., whose Rett research focuses on astrocytes, another type of glial cell impaired by mutations in MECP2, comments, "A fascinating aspect of these findings is the data suggesting that deficits in the engulfing properties of microglia are a crucial aspect of Rett neuropathology. It will now be necessary to develop cellular assays to determine all the ways these immune cells are bolstering neuronal functions and whether they can be therapeutically harnessed." Dr. Mandel is a Senior Scientist at the Vollum Institute and a Professor in the Department of Biochemistry and Molecular Biology in the School of Medicine at Oregon Health & Science University and an Investigator of the Howard Hughes Medical Institute.
*Published in "SCIENCE DAILY"
César Antón, director del Imserso, a EL PAIS: "“No se atiende igual a personas con la misma dependencia”
César Antón (Palencia, 1957) ha sido cocinero antes que fraile: de su etapa como consejero en Castilla y León conoce el proceder de las comunidades y ahora, como nuevo director del Instituto de Mayores y Servicios Sociales (Imserso), también el del Gobierno. Y en la implantación de la Ley de Dependencia la relación entre ambas Administraciones ha sido un constante tira y afloja. El objetivo del Gobierno, explica, es que, a igual grado de dependencia, dos personas reciban el mismo servicio en cualquier lugar de España. Quiere unificar los criterios para el copago del usuario, fijar indicadores comunes para determinar lo que cuesta la dependencia en cada comunidad y primar la prestación de servicios.
Pregunta. ¿Se prevén recortes en dependencia y servicios sociales?
Respuesta. Las prestaciones sociales seguirán siendo la prioridad del Gobierno.
P. ¿Por qué está paralizada la Ley de Dependencia?
R. Hay ritmos distintos por comunidades, cada una lo ha adaptado a sus circunstancias, pero, con respeto hacia ellas, han dado mejores resultados aquellas que han canalizado el desarrollo de la ley a través del sistema de servicios sociales. Sin embargo, hay diferencias en la aplicación.
P. Esas diferencias permiten que haya ciudadanos de primera y de segunda a la hora de percibir las ayudas. ¿Es tolerable?
R. Los ciudadanos tiene que ser iguales ante la ley. Hay que analizar cómo se ha puesto en marcha la norma y la evaluación de resultados y cómo se reconduce en el futuro. Agua pasada no mueve molinos. Es verdad que hay sitios donde los procedimientos se alargan por causas achacables a las Administraciones. Hay que dar un impulso, reordenar el procedimiento, entre todos.
P. ¿Y cómo se reconduce?
R. Nuestro objetivo es que ante situaciones iguales de dependencia se dé un tratamiento igual en todo el territorio, porque a igual grado no se está atendiendo de la misma forma. Tenemos, también, que acordar cómo se mide la capacidad económica del usuario y unificar su aportación económica, que tampoco es igual.
P. ¿Por qué las comunidades siguen sin dar datos reales de lo que les cuesta la dependencia?
R. No hay una valoración del coste porque no hemos fijado indicadores comunes para calcular esos costes. La ministra ha ofrecido la posibilidad de que se llegue a un acuerdo sobre la forma de medir la capacidad económica del usuario y su aportación al sistema para el conjunto del territorio. Y también para determinar el coste de los servicios. Luego sabremos quién aporta y cuánto. En los Presupuestos Generales del Estado se determina claramente la partida para la dependencia (nivel mínimo y nivel acordado, seguridad social, etcétera). ¿Acaso existe ese detalle en los presupuestos de las comunidades autónomas?
“Hay sitios donde los procedimientos se alargan por las Administraciones”
P. Trascendió la intención del Gobierno de financiar a las comunidades según el coste del servicio al ciudadano, y no de su grado de dependencia, como ahora.
R. El reparto de los créditos de los presupuestos del Estado debiera hacerse primando a las comunidades que prestan servicios frente a las que dan prestaciones económicas, porque es el espíritu de la ley. Hoy, para repartir los recursos se tienen en cuenta otras variables, como la extensión del territorio, pero lo más importante deben ser los servicios que se presten y las personas atendidas. No puede ser que la población pese más en este reparto; en todo caso debe pesar la población dependiente, la forma de atenderla y las personas atendidas.
P. ¿Van a simplificar el baremo, el examen que fija el grado de dependencia de los ciudadanos?
R. No hay nada predeterminado,pero hay que reflexionar sobre su eficacia.
P. ¿Ese baremo permite que entren en el sistema más grandes dependientes de media que los que tienen otros países?
R. En la única estimación que se hizo en España se calculó que habría 205.000 personas con el mayor grado de dependencia y estamos en más de 425.000, más del doble. Las estimaciones nunca aciertan del todo, pero parece que estamos por encima de la media de la UE.
P. En el otro extremo están los dependientes moderados, cuya atención ha sido aplazada un año por el Gobierno. ¿Cree que todos los dependientes moderados deben entrar bajo el paraguas de la dependencia?
Pregunta. ¿Se prevén recortes en dependencia y servicios sociales?
Respuesta. Las prestaciones sociales seguirán siendo la prioridad del Gobierno.
P. ¿Por qué está paralizada la Ley de Dependencia?
R. Hay ritmos distintos por comunidades, cada una lo ha adaptado a sus circunstancias, pero, con respeto hacia ellas, han dado mejores resultados aquellas que han canalizado el desarrollo de la ley a través del sistema de servicios sociales. Sin embargo, hay diferencias en la aplicación.
P. Esas diferencias permiten que haya ciudadanos de primera y de segunda a la hora de percibir las ayudas. ¿Es tolerable?
R. Los ciudadanos tiene que ser iguales ante la ley. Hay que analizar cómo se ha puesto en marcha la norma y la evaluación de resultados y cómo se reconduce en el futuro. Agua pasada no mueve molinos. Es verdad que hay sitios donde los procedimientos se alargan por causas achacables a las Administraciones. Hay que dar un impulso, reordenar el procedimiento, entre todos.
P. ¿Y cómo se reconduce?
R. Nuestro objetivo es que ante situaciones iguales de dependencia se dé un tratamiento igual en todo el territorio, porque a igual grado no se está atendiendo de la misma forma. Tenemos, también, que acordar cómo se mide la capacidad económica del usuario y unificar su aportación económica, que tampoco es igual.
P. ¿Por qué las comunidades siguen sin dar datos reales de lo que les cuesta la dependencia?
R. No hay una valoración del coste porque no hemos fijado indicadores comunes para calcular esos costes. La ministra ha ofrecido la posibilidad de que se llegue a un acuerdo sobre la forma de medir la capacidad económica del usuario y su aportación al sistema para el conjunto del territorio. Y también para determinar el coste de los servicios. Luego sabremos quién aporta y cuánto. En los Presupuestos Generales del Estado se determina claramente la partida para la dependencia (nivel mínimo y nivel acordado, seguridad social, etcétera). ¿Acaso existe ese detalle en los presupuestos de las comunidades autónomas?
“Hay sitios donde los procedimientos se alargan por las Administraciones”
P. Trascendió la intención del Gobierno de financiar a las comunidades según el coste del servicio al ciudadano, y no de su grado de dependencia, como ahora.
R. El reparto de los créditos de los presupuestos del Estado debiera hacerse primando a las comunidades que prestan servicios frente a las que dan prestaciones económicas, porque es el espíritu de la ley. Hoy, para repartir los recursos se tienen en cuenta otras variables, como la extensión del territorio, pero lo más importante deben ser los servicios que se presten y las personas atendidas. No puede ser que la población pese más en este reparto; en todo caso debe pesar la población dependiente, la forma de atenderla y las personas atendidas.
P. ¿Van a simplificar el baremo, el examen que fija el grado de dependencia de los ciudadanos?
R. No hay nada predeterminado,pero hay que reflexionar sobre su eficacia.
P. ¿Ese baremo permite que entren en el sistema más grandes dependientes de media que los que tienen otros países?
R. En la única estimación que se hizo en España se calculó que habría 205.000 personas con el mayor grado de dependencia y estamos en más de 425.000, más del doble. Las estimaciones nunca aciertan del todo, pero parece que estamos por encima de la media de la UE.
P. En el otro extremo están los dependientes moderados, cuya atención ha sido aplazada un año por el Gobierno. ¿Cree que todos los dependientes moderados deben entrar bajo el paraguas de la dependencia?
-“No hay valoración del coste porque faltan indicadores para calcularlo”
R. Debiéramos hacer un análisis entre todos para ver si muchas de esas personas no están siendo atendidas ya de forma muy similar por los servicios sociales, porque antes de la ley ya se atendían esas necesidades.
P. Si se les saca de la ley, su atención quedará al arbitrio de las comunidades autónomas, porque una ayuda de los servicios sociales no se adquiere por derecho, ya que están sujetas a la disponibilidad presupuestaria.
R. Yo no conozco que se haya dejado de atender a alguien que haya entrado a ser atendido en los servicios sociales. Las nuevas leyes de servicios sociales de las comunidades también garantizan esa atención por derecho.
P. Pero apenas hay tres comunidades con esas nuevas leyes.
R. Yo creo que cuatro o más.
P. Pero se trata del acceso a las ayudas. ¿Cómo se va a garantizar que tengan prestaciones en los servicios sociales cuando en algunos casos no se garantizan ni las ayudas que se conceden por la Ley de Dependencia?
R. No es solo el acceso, y siguen accediendo personas a los servicios sociales, sino también las que ya están atendidas. En España hay 451.366 usuarios de ayuda a domicilio, 165.294 plazas públicas de residencia de un total de 344.000. Aunque ha habido recortes presupuestarios, las comunidades y los Ayuntamientos han priorizado sus servicios sociales.
P. Un informe encargado por el Gobierno anterior determinó que el Imserso servía de poco tal cual estaba. ¿Para qué sirve?
R. Ha sido siempre un referente en política social y de mayores. Está totalmente justificado para dar cohesión, como ocurre en sanidad
P. Pero la cohesión sanitaria existe sin un Imserso.
R. Porque se hizo una ley para ello... Pero el Imserso, entre otras cosas, se hace cargo de las pensiones no contributivas, por ejemplo. Es el responsable de garantizar que todos los meses se cobren esas pensiones.
**Publicado en "EL PAIS"
R. Debiéramos hacer un análisis entre todos para ver si muchas de esas personas no están siendo atendidas ya de forma muy similar por los servicios sociales, porque antes de la ley ya se atendían esas necesidades.
P. Si se les saca de la ley, su atención quedará al arbitrio de las comunidades autónomas, porque una ayuda de los servicios sociales no se adquiere por derecho, ya que están sujetas a la disponibilidad presupuestaria.
R. Yo no conozco que se haya dejado de atender a alguien que haya entrado a ser atendido en los servicios sociales. Las nuevas leyes de servicios sociales de las comunidades también garantizan esa atención por derecho.
P. Pero apenas hay tres comunidades con esas nuevas leyes.
R. Yo creo que cuatro o más.
P. Pero se trata del acceso a las ayudas. ¿Cómo se va a garantizar que tengan prestaciones en los servicios sociales cuando en algunos casos no se garantizan ni las ayudas que se conceden por la Ley de Dependencia?
R. No es solo el acceso, y siguen accediendo personas a los servicios sociales, sino también las que ya están atendidas. En España hay 451.366 usuarios de ayuda a domicilio, 165.294 plazas públicas de residencia de un total de 344.000. Aunque ha habido recortes presupuestarios, las comunidades y los Ayuntamientos han priorizado sus servicios sociales.
P. Un informe encargado por el Gobierno anterior determinó que el Imserso servía de poco tal cual estaba. ¿Para qué sirve?
R. Ha sido siempre un referente en política social y de mayores. Está totalmente justificado para dar cohesión, como ocurre en sanidad
P. Pero la cohesión sanitaria existe sin un Imserso.
R. Porque se hizo una ley para ello... Pero el Imserso, entre otras cosas, se hace cargo de las pensiones no contributivas, por ejemplo. Es el responsable de garantizar que todos los meses se cobren esas pensiones.
**Publicado en "EL PAIS"
Genetic Variation in East Asians Found to Explain Resistance to Cancer Drugs
A multinational research team led by scientists at Duke-NUS Graduate Medical School has identified the reason why some patients fail to respond to some of the most successful cancer drugs.
Tyrosine kinase inhibitor drugs (TKI) work effectively in most patients to fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene.
These precisely targeted drugs shut down molecular pathways that keep these cancers flourishing and include TKIs for treating CML, and the form of NSCLC with EGFR genetic mutations.
Now the team at Duke-NUS Graduate Medical School in Singapore, working with the Genome Institute of Singapore (GIS), Singapore General Hospital, and the National Cancer Centre Singapore, has discovered that there is a common variation in the BIM gene in people of East Asian descent that contributes to some patients' failure to benefit from these tyrosine kinase inhibitor drugs.
"Because we could determine in cells how the BIM gene variant caused TKI resistance, we were able to devise a strategy to overcome it," said S. Tiong Ong, MBBCh, senior author of the study and associate professor in the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS and Division of Medical Oncology, Department of Medicine, at Duke University Medical Center.
"A novel class of drugs called the BH3-mimetics provided the answer," Ong said. "When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients."
Said Yijun Ruan, PhD, a co-senior author of this study and associate director for Genome Technology and Biology at GIS: "We used a genome-wide sequencing approach to specifically look for structural changes in the DNA of patient samples. This helped in the discovery of the East Asian BIM gene variant. What's more gratifying is that this collaboration validates the use of basic genomic technology to make clinically important discoveries."
The study was published online in Nature Medicine on March 18.
If the drug combination does override TKI resistance in people, this will be good news for those with the BIM gene variant, which occurs in about 15 percent of the typical East Asian population. By contrast, no people of European or African ancestry were found to have this gene variant.
"While it's interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations," said Patrick Casey, PhD, senior vice dean for research at Duke-NUS and James B. Duke Professor of Pharmacology and Cancer Biology.
"There may well be other, yet to be discovered gene variations that account for drug resistance in different world populations. These findings underscore the importance of learning all we can about cancer pathways, mutations, and treatments that work for different types of individuals. This is how we can personalize cancer treatment and, ultimately, control cancer."
"We estimate that about 14,000 newly diagnosed East Asian CML and EGFR non-small-cell lung cancer patients per year will carry the gene variant," Ong said. "Notably, EGFR NSCLC is much more common in East Asia, and accounts for about 50 percent of all non-small-cell lung cancers in East Asia, compared to only 10 percent in the West."
The researchers found that drug resistance occurred because of impaired production of BH3-containing forms of the BIM protein. They confirmed that restoring BIM gene function with the BH3 drugs worked to overcome TKI resistance in both types of cancer.
"BH3-mimetic drugs are already being studied in clinical trials in combination with chemotherapy, and we are hopeful that BH3 drugs in combination with TKIs can actually overcome this form of TKI resistance in patients with CML and EGFR non-small-cell lung cancer," Ong said. "We are working closely with GIS and the commercialization arm of the Agency for Science, Technology & Research (A*STAR), to develop a clinical test for the BIM gene variant, so that we can take our discovery quickly to the patient."
**Published in "SCIENCE DAILY"
Tyrosine kinase inhibitor drugs (TKI) work effectively in most patients to fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene.
These precisely targeted drugs shut down molecular pathways that keep these cancers flourishing and include TKIs for treating CML, and the form of NSCLC with EGFR genetic mutations.
Now the team at Duke-NUS Graduate Medical School in Singapore, working with the Genome Institute of Singapore (GIS), Singapore General Hospital, and the National Cancer Centre Singapore, has discovered that there is a common variation in the BIM gene in people of East Asian descent that contributes to some patients' failure to benefit from these tyrosine kinase inhibitor drugs.
"Because we could determine in cells how the BIM gene variant caused TKI resistance, we were able to devise a strategy to overcome it," said S. Tiong Ong, MBBCh, senior author of the study and associate professor in the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS and Division of Medical Oncology, Department of Medicine, at Duke University Medical Center.
"A novel class of drugs called the BH3-mimetics provided the answer," Ong said. "When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients."
Said Yijun Ruan, PhD, a co-senior author of this study and associate director for Genome Technology and Biology at GIS: "We used a genome-wide sequencing approach to specifically look for structural changes in the DNA of patient samples. This helped in the discovery of the East Asian BIM gene variant. What's more gratifying is that this collaboration validates the use of basic genomic technology to make clinically important discoveries."
The study was published online in Nature Medicine on March 18.
If the drug combination does override TKI resistance in people, this will be good news for those with the BIM gene variant, which occurs in about 15 percent of the typical East Asian population. By contrast, no people of European or African ancestry were found to have this gene variant.
"While it's interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations," said Patrick Casey, PhD, senior vice dean for research at Duke-NUS and James B. Duke Professor of Pharmacology and Cancer Biology.
"There may well be other, yet to be discovered gene variations that account for drug resistance in different world populations. These findings underscore the importance of learning all we can about cancer pathways, mutations, and treatments that work for different types of individuals. This is how we can personalize cancer treatment and, ultimately, control cancer."
"We estimate that about 14,000 newly diagnosed East Asian CML and EGFR non-small-cell lung cancer patients per year will carry the gene variant," Ong said. "Notably, EGFR NSCLC is much more common in East Asia, and accounts for about 50 percent of all non-small-cell lung cancers in East Asia, compared to only 10 percent in the West."
The researchers found that drug resistance occurred because of impaired production of BH3-containing forms of the BIM protein. They confirmed that restoring BIM gene function with the BH3 drugs worked to overcome TKI resistance in both types of cancer.
"BH3-mimetic drugs are already being studied in clinical trials in combination with chemotherapy, and we are hopeful that BH3 drugs in combination with TKIs can actually overcome this form of TKI resistance in patients with CML and EGFR non-small-cell lung cancer," Ong said. "We are working closely with GIS and the commercialization arm of the Agency for Science, Technology & Research (A*STAR), to develop a clinical test for the BIM gene variant, so that we can take our discovery quickly to the patient."
**Published in "SCIENCE DAILY"
First-ever integrative 'Omics' profile lets Stanford scientist discover, track his diabetes onset
Geneticist Michael Snyder, PhD, has almost no privacy. For more than two years, he and his lab members at the Stanford University School of Medicine pored over his body's most intimate secrets: the sequence of his DNA, the RNA and proteins produced by his cells, the metabolites and signaling molecules wafting through his blood. They spied on his immune system as it battled viral infections. Finally, to his shock, they discovered that he was predisposed to type-2 diabetes and then watched his blood sugar shoot upward as he developed the condition during the study. It's the first eyewitness account -- viewed on a molecular level -- of the birth of a disease that affects millions of Americans. It's also an important milestone in the realization of the promise of truly personalized medicine, or tailoring health care to each individual's unique circumstances.
The researchers call the unprecedented analysis, which relies on collecting and analyzing billions of individual bits of data, an integrative Personal "Omics" Profile, or iPOP. The word "omics" indicates the study of a body of information, such as the genome (which is all DNA in a cell), or the proteome (which is all the proteins). Snyder's iPOP also included his metabolome (metabolites), his transcriptome (RNA transcripts) and autoantibody profiles, among other things.
The researchers say that Snyder's diabetes is but one of myriad problems the iPOP can identify and predict, and that such dynamic monitoring will soon become commonplace. "This is the first time that anyone has used such detailed information to proactively manage their own health," said Snyder. "It's a level of understanding of health at the molecular level that has never before been achieved."
The research was published in the March 16 issue of Cell. Snyder, who chairs the Department of Genetics, is the senior author. Postdoctoral scholars Rui Chen, PhD, George Mias, PhD, Jennifer Li-Pook-Than, PhD, and research associate Lihua Jiang, PhD, are co-first authors of the study, which involved a large team of investigators.
The study provides a glimpse into the future of medicine -- peppered with untold data-management hurdles and fraught with a degree of self-examination and awareness few of us have ever imagined. And, despite the challenges, the potential payoff is great.
"I was not aware of any type-2 diabetes in my family and had no significant risk factors," said Snyder, "but we learned through genomic sequencing that I have a genetic predisposition to the condition. Therefore, we measured my blood glucose levels and were able to watch them shoot up after a nasty viral infection during the course of the study."
As a result, he was able to immediately modify his diet and exercise to gradually bring his levels back into the normal range and prevent the ongoing tissue damage that would have occurred had the disease gone undiagnosed.
Snyder provided about 20 blood samples (about once every two months while healthy, and more frequently during periods of illness) for analysis over the course of the study. Each was analyzed with a variety of assays for tens of thousands of biological variables, generating a staggering amount of information.
The exercise was in stark contrast to the cursory workup most of us receive when we go to the doctor for our regular physical exam. "Currently, we routinely measure fewer than 20 variables in a standard laboratory blood test," said Snyder, who is also the Stanford W. Ascherman, MD, FACS, Professor in Genetics. "We could, and should, be measuring many, many thousands."
For Snyder, one set of measurements was particularly telling. On day 301, about 12 days after a viral infection, his glucose regulation appeared to be abnormal. Shortly thereafter his glucose levels became elevated, prompting him to visit his primary care physician. On day 369, he was diagnosed with type-2 diabetes.
"We are all responsible for our own health," said Snyder, who is also the director of the Stanford Center for Genomics and Personalized Medicine. "Normally, I go for a physical exam about once every two or three years. So, under normal circumstances, my diabetes wouldn't have been diagnosed for one or two years. But with this real-time information, I was able to make diet and exercise changes that brought my blood sugar down and allowed me to avoid diabetes medication."
Snyder started his study in the months after arriving at Stanford in 2009, when whole-genome sequencing of individuals was just becoming a reality. Stephen Quake, PhD, who is Stanford's Lee Otterson Professor of Bioengineering, had recently completed the complete sequencing of his own genome and was working to use the information to predict his risk for dozens of diseases.
But while the predictive power in genomic information is due in part to its static nature -- because it doesn't change over time, a one-time analysis can hint at future events -- our bodies are dynamic. They use our DNA blueprints to churn out RNA and protein molecules in varying amounts and types precisely calibrated to respond to the changing conditions in which we live. The result is an exquisitely crafted machine that turns on a dime to metabolize food, flex our muscles, breathe air, fight off infections and make all the other little adjustments that keep us healthy. A misstep can lead to disease or illness.
To generate Snyder's iPOP, he first had his complete genome sequenced at a level of accuracy that has not been achieved previously. Then, with each sample, the researchers took dozens of molecular snapshots, using a variety of different techniques, of thousands of variables and then compared them over time. The composite result was a dynamic picture of how his body responded to illness and disease -- and it was a number of molecular cues that led to the discovery of his diabetes.
A number of molecular cues led to the discovery of Snyder's diabetes. His genomic sequence suggested he had an increased risk for high cholesterol, coronary artery disease (which he knew already), as well as basal cell carcinoma and type-2 diabetes, which was unexpected. Conversely, the sequence predicts his risk for hypertension, obesity and prostate cancer is lower than that of other men his age (54 when the study started). A check of his triglyceride levels at the start of the study confirmed that they were high: 321 mg/dL. Snyder took the cholesterol-lowering drug simvastatin, and his levels dropped dramatically to 81-116 mg/dL. Based on the type-2 diabetes prediction, the team decided to also monitor Snyder's blood sugar levels, which were normal when the study began.
Snyder, who has two small children, experienced two viral infections during the course of the study: one with rhinovirus (at day 0), and one with respiratory syncytial virus (beginning at day 289). Each time, his immune system reacted by increasing the blood levels of pro-inflammatory cytokines -- secreted proteins that cells use to communicate and coordinate their responses to external events such as an infection. Snyder also exhibited increased levels of auto-antibodies, or antibodies that reacted with his own proteins, after viral infection. Although auto-antibody production can be a normal, temporary reaction to illness, the researchers were interested to note that one in particular targeted an insulin receptor binding protein.
**Source: Stanford University Medical Center
The researchers call the unprecedented analysis, which relies on collecting and analyzing billions of individual bits of data, an integrative Personal "Omics" Profile, or iPOP. The word "omics" indicates the study of a body of information, such as the genome (which is all DNA in a cell), or the proteome (which is all the proteins). Snyder's iPOP also included his metabolome (metabolites), his transcriptome (RNA transcripts) and autoantibody profiles, among other things.
The researchers say that Snyder's diabetes is but one of myriad problems the iPOP can identify and predict, and that such dynamic monitoring will soon become commonplace. "This is the first time that anyone has used such detailed information to proactively manage their own health," said Snyder. "It's a level of understanding of health at the molecular level that has never before been achieved."
The research was published in the March 16 issue of Cell. Snyder, who chairs the Department of Genetics, is the senior author. Postdoctoral scholars Rui Chen, PhD, George Mias, PhD, Jennifer Li-Pook-Than, PhD, and research associate Lihua Jiang, PhD, are co-first authors of the study, which involved a large team of investigators.
The study provides a glimpse into the future of medicine -- peppered with untold data-management hurdles and fraught with a degree of self-examination and awareness few of us have ever imagined. And, despite the challenges, the potential payoff is great.
"I was not aware of any type-2 diabetes in my family and had no significant risk factors," said Snyder, "but we learned through genomic sequencing that I have a genetic predisposition to the condition. Therefore, we measured my blood glucose levels and were able to watch them shoot up after a nasty viral infection during the course of the study."
As a result, he was able to immediately modify his diet and exercise to gradually bring his levels back into the normal range and prevent the ongoing tissue damage that would have occurred had the disease gone undiagnosed.
Snyder provided about 20 blood samples (about once every two months while healthy, and more frequently during periods of illness) for analysis over the course of the study. Each was analyzed with a variety of assays for tens of thousands of biological variables, generating a staggering amount of information.
The exercise was in stark contrast to the cursory workup most of us receive when we go to the doctor for our regular physical exam. "Currently, we routinely measure fewer than 20 variables in a standard laboratory blood test," said Snyder, who is also the Stanford W. Ascherman, MD, FACS, Professor in Genetics. "We could, and should, be measuring many, many thousands."
For Snyder, one set of measurements was particularly telling. On day 301, about 12 days after a viral infection, his glucose regulation appeared to be abnormal. Shortly thereafter his glucose levels became elevated, prompting him to visit his primary care physician. On day 369, he was diagnosed with type-2 diabetes.
"We are all responsible for our own health," said Snyder, who is also the director of the Stanford Center for Genomics and Personalized Medicine. "Normally, I go for a physical exam about once every two or three years. So, under normal circumstances, my diabetes wouldn't have been diagnosed for one or two years. But with this real-time information, I was able to make diet and exercise changes that brought my blood sugar down and allowed me to avoid diabetes medication."
Snyder started his study in the months after arriving at Stanford in 2009, when whole-genome sequencing of individuals was just becoming a reality. Stephen Quake, PhD, who is Stanford's Lee Otterson Professor of Bioengineering, had recently completed the complete sequencing of his own genome and was working to use the information to predict his risk for dozens of diseases.
But while the predictive power in genomic information is due in part to its static nature -- because it doesn't change over time, a one-time analysis can hint at future events -- our bodies are dynamic. They use our DNA blueprints to churn out RNA and protein molecules in varying amounts and types precisely calibrated to respond to the changing conditions in which we live. The result is an exquisitely crafted machine that turns on a dime to metabolize food, flex our muscles, breathe air, fight off infections and make all the other little adjustments that keep us healthy. A misstep can lead to disease or illness.
To generate Snyder's iPOP, he first had his complete genome sequenced at a level of accuracy that has not been achieved previously. Then, with each sample, the researchers took dozens of molecular snapshots, using a variety of different techniques, of thousands of variables and then compared them over time. The composite result was a dynamic picture of how his body responded to illness and disease -- and it was a number of molecular cues that led to the discovery of his diabetes.
A number of molecular cues led to the discovery of Snyder's diabetes. His genomic sequence suggested he had an increased risk for high cholesterol, coronary artery disease (which he knew already), as well as basal cell carcinoma and type-2 diabetes, which was unexpected. Conversely, the sequence predicts his risk for hypertension, obesity and prostate cancer is lower than that of other men his age (54 when the study started). A check of his triglyceride levels at the start of the study confirmed that they were high: 321 mg/dL. Snyder took the cholesterol-lowering drug simvastatin, and his levels dropped dramatically to 81-116 mg/dL. Based on the type-2 diabetes prediction, the team decided to also monitor Snyder's blood sugar levels, which were normal when the study began.
Snyder, who has two small children, experienced two viral infections during the course of the study: one with rhinovirus (at day 0), and one with respiratory syncytial virus (beginning at day 289). Each time, his immune system reacted by increasing the blood levels of pro-inflammatory cytokines -- secreted proteins that cells use to communicate and coordinate their responses to external events such as an infection. Snyder also exhibited increased levels of auto-antibodies, or antibodies that reacted with his own proteins, after viral infection. Although auto-antibody production can be a normal, temporary reaction to illness, the researchers were interested to note that one in particular targeted an insulin receptor binding protein.
**Source: Stanford University Medical Center
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