An open-label study of rituximab, a monoclonal antibody for human CD20, was shown to be safe in patients with primary biliary cirrhosis (PBC) who had an incomplete response to the standard ursodeoxycholic acid (UDCA) therapy, also known as Ursodiol. Study details available in the February issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases, report that rituximab was successful in reducing the level of alkaline phosphatase (ALP) -- a protein used to measure liver injury. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), PBC -- an autoimmune liver disease characterized by inflammation of the bile ducts that ultimately causes bile to build up and damage the liver -- typically occurs between the ages of 40 and 60, primarily affecting women. Medical studies have identified the presence of anti-mitochondrial autoantibodies (AMA) to enzymes involved in the production of the body's energy (pyruvate dehydrogenase complex-PDC-E2) in up to 95% of PBC cases.
Currently, the standard therapy for PBC is UDCA or liver transplantation in patients who have progressed to end-stage liver disease. However, previous studies have shown that UDCA may be ineffective in up to 40% of PBC patients and 10% could require transplantation or die from the disease. "Small trials using immunosuppressants have failed to demonstrate significant clinical benefit or carry unacceptable safety profiles," said Dr. Christopher Bowlus with UC Davis Health System in California and lead author of the current study.
Dr. Bowlus added, "Given our previous work implicating B cells to the development of this disease, we hypothesized that a therapy such as rituximab, which depletes B cells, could offer a potentially effective treatment option with acceptable adverse effects." The team enrolled 6 patients between the ages of 18 and 65 years of age who were diagnosed with PBC and had an incomplete response to UDCA despite 6 months of therapy. Participants in this open-label study received an intravenous infusion of 1000 mg of rituximab on day 1 and day 15, with follow-up for 52 weeks. Two patients received one dose of rituximab due to latent varicella (chickenpox) activation in one and viral respiratory infection in the other.
The trial results found that rituximab was safe and well tolerated by PBC patients, with no serious adverse events reported. By 16 weeks post-treatment patients had significantly lower levels of immunoglobulins IgG, IgM, and IgA, which are the antibodies normally present in blood, but in the case of IgM are often elevated in PBC. In addition, the abnormal antibodies directed against mitochondria (AMA), were also reduced after treatment. However, levels returned to baseline by 36 weeks. Further, serum alkaline phosphatase decreased up to 36 weeks post-treatment.
The authors noted that rituximab therapy could clinically improve PBC through multiple pathways that include the reduction of anti-mitochondrial antibodies through depletion of memory B cells, increases in regulatory T cells associated with immune response, and modulation of cytokine production involved with inflammation. "Further investigation of B cell targeting strategies is necessary to develop potentially novel therapeutic options for patients with PBC," concludes Dr. Bowlus.
**Source: Wiley-Blackwell
06 February 2012
Understanding how bacteria come back from the dead
Salmonella remains a serious cause of food poisoning in the UK and throughout the EU, in part due to its ability to thrive and quickly adapt to the different environments in which it can grow. New research involving a team of IFR scientists, funded by BBSRC, has taken the first detailed look at what Salmonella does when it enters a new environment, which could provide clues to finding new ways of reducing transmission through the food chain and preventing human illness. Bacteria can multiply rapidly, potentially doubling every 20 minutes in ideal conditions. However, this exponential growth phase is preceded by a period known as lag phase, where no increase in cell number is seen. Lag phase was first described in the 19th Century, and was assumed to be needed by bacteria to prepare to exploit new environmental conditions. Beyond this, surprisingly little was known about lag phase, other than bacteria are metabolically active in this period. But exactly what are bacteria doing physiologically during this period?
To fill in this knowledge gap researchers at IFR, along with colleagues at Campden BRI, a membership-based organisation carrying out research and development for the food and drinks industry, have developed a simple and robust system for studying the biology of Salmonella during lag phase. In this system, lag phase lasts about two hours, but the cells sense their new environment remarkably quickly, and within four minutes switch on a specific set of genes, including some that control the uptake of specific nutrients.
For example, one nutrient accumulated is phosphate which is needed for many cellular processes, and a gene encoding a phosphate transporter was the most upregulated gene during the first four minutes of lag phase. The cellular uptake mechanisms for iron were also activated during lag phase, and are needed for key aspects of bacterial metabolism. This increase in iron leads to a short term sensitivity to oxidative damage. Manganese and calcium are also accumulated in lag phase, but are lost from the cell during exponential growth.
This new understanding of Salmonella metabolism during lag phase show how rapidly Salmonella senses favourable conditions and builds up the materials needed for growth. This study was carried out by two BBSRC-CASE studentships, which were partially funded by Campden BRI.
Future research to work out the regulatory mechanisms behind these processes and the switch from lag phase to exponential growth will tell us more about how Salmonella can flourish in different environments, and could point to new ways of controlling its transmission in the food chain.
**Source: Norwich BioScience Institutes
To fill in this knowledge gap researchers at IFR, along with colleagues at Campden BRI, a membership-based organisation carrying out research and development for the food and drinks industry, have developed a simple and robust system for studying the biology of Salmonella during lag phase. In this system, lag phase lasts about two hours, but the cells sense their new environment remarkably quickly, and within four minutes switch on a specific set of genes, including some that control the uptake of specific nutrients.
For example, one nutrient accumulated is phosphate which is needed for many cellular processes, and a gene encoding a phosphate transporter was the most upregulated gene during the first four minutes of lag phase. The cellular uptake mechanisms for iron were also activated during lag phase, and are needed for key aspects of bacterial metabolism. This increase in iron leads to a short term sensitivity to oxidative damage. Manganese and calcium are also accumulated in lag phase, but are lost from the cell during exponential growth.
This new understanding of Salmonella metabolism during lag phase show how rapidly Salmonella senses favourable conditions and builds up the materials needed for growth. This study was carried out by two BBSRC-CASE studentships, which were partially funded by Campden BRI.
Future research to work out the regulatory mechanisms behind these processes and the switch from lag phase to exponential growth will tell us more about how Salmonella can flourish in different environments, and could point to new ways of controlling its transmission in the food chain.
**Source: Norwich BioScience Institutes
A zap of cold plasma reduces harmful bacteria on raw chicken in Drexel study
A new study by food safety researchers at Drexel University demonstrates that plasma can be an effective method for killing pathogens on uncooked poultry. The proof-of-concept study was published in the January issue of the Journal of Food Protection. Although recent high-profile outbreaks of foodborne illness have involved contaminated fresh produce, the most common source of harmful bacteria in food is uncooked poultry and other meat products. The bacteria responsible for most foodborne illnesses, Campylobacter and Salmonella, are found on upwards of 70 percent of chicken meat tested.
Treating raw meat products to remove pathogens before they reach a consumer's home can reduce the risk of cross contamination during food preparation, according to senior author Dr. Jennifer Quinlan, an assistant professor in Drexel's College of Nursing and Health Professions. "If you could reduce contamination on the raw chicken, then you wouldn't have it in the kitchen," Quinlan said.
Past studies have shown that plasma could successfully reduce pathogens on the surface of fruits and vegetables without cooking them.
The value of using plasma "is that it is non-thermal, so there is no heat to cook or alter the way the food looks," said lead author Brian Dirks, a graduate student in the College of Arts and Sciences. Dirks and Quinlan worked with researchers from the University's Anthony J. Drexel Plasma Institute to test the use of plasma for poultry.
In the Drexel study, raw chicken samples contaminated with Salmonella enterica and Campylobacter jejuni bacteria were treated with plasma for varying periods of time. Plasma treatment eliminated or nearly eliminated bacteria in low levels from skinless chicken breast and chicken skin, and significantly reduced the level of bacteria when contamination levels were high.
The researchers also tested using plasma to treat samples of bacteria grown on agar, and demonstrated that antibiotic-resistant strains of bacteria were as susceptible to plasma as the wild-type strains.
Plasma, known as the "fourth state of matter" (after solid, liquid and gas), is a high-energy, charged mixture of gaseous atoms, ions and electrons. Plasma has a wide range of potential applications including energy production and control, biomedical treatments and environmental remediation.
Quinlan described the plasma treatment of poultry in this study as "proof of concept." Current plasma technology is expensive relative to the narrow cost margins involved in food production, and the technology is not currently being developed for processing poultry on a large scale.
If plasma technology becomes cost-effective for use in treating poultry, it may be used in conjunction with existing methods to reduce pathogens, Dirks said, and it may also help prolong the shelf-life of raw chicken if it can be honed to remove more microorganisms responsible for spoilage.
"Until these technologies are more fully developed, consumers should assume that raw poultry has pathogens on it and take care to prevent infection," Quinlan said. "That means cooking thoroughly and making sure not to cross contaminate when handling uncooked meat and poultry."
Quinlan holds a a Ph.D. in food microbiology from North Carolina State University and bachelor's and master's degrees in food science from Rutgers University. Her research focuses on the microbiological quality and safety of food. Her ongoing work focuses on safe consumer handling of food.
*Source: Drexel University
Treating raw meat products to remove pathogens before they reach a consumer's home can reduce the risk of cross contamination during food preparation, according to senior author Dr. Jennifer Quinlan, an assistant professor in Drexel's College of Nursing and Health Professions. "If you could reduce contamination on the raw chicken, then you wouldn't have it in the kitchen," Quinlan said.
Past studies have shown that plasma could successfully reduce pathogens on the surface of fruits and vegetables without cooking them.
The value of using plasma "is that it is non-thermal, so there is no heat to cook or alter the way the food looks," said lead author Brian Dirks, a graduate student in the College of Arts and Sciences. Dirks and Quinlan worked with researchers from the University's Anthony J. Drexel Plasma Institute to test the use of plasma for poultry.
In the Drexel study, raw chicken samples contaminated with Salmonella enterica and Campylobacter jejuni bacteria were treated with plasma for varying periods of time. Plasma treatment eliminated or nearly eliminated bacteria in low levels from skinless chicken breast and chicken skin, and significantly reduced the level of bacteria when contamination levels were high.
The researchers also tested using plasma to treat samples of bacteria grown on agar, and demonstrated that antibiotic-resistant strains of bacteria were as susceptible to plasma as the wild-type strains.
Plasma, known as the "fourth state of matter" (after solid, liquid and gas), is a high-energy, charged mixture of gaseous atoms, ions and electrons. Plasma has a wide range of potential applications including energy production and control, biomedical treatments and environmental remediation.
Quinlan described the plasma treatment of poultry in this study as "proof of concept." Current plasma technology is expensive relative to the narrow cost margins involved in food production, and the technology is not currently being developed for processing poultry on a large scale.
If plasma technology becomes cost-effective for use in treating poultry, it may be used in conjunction with existing methods to reduce pathogens, Dirks said, and it may also help prolong the shelf-life of raw chicken if it can be honed to remove more microorganisms responsible for spoilage.
"Until these technologies are more fully developed, consumers should assume that raw poultry has pathogens on it and take care to prevent infection," Quinlan said. "That means cooking thoroughly and making sure not to cross contaminate when handling uncooked meat and poultry."
Quinlan holds a a Ph.D. in food microbiology from North Carolina State University and bachelor's and master's degrees in food science from Rutgers University. Her research focuses on the microbiological quality and safety of food. Her ongoing work focuses on safe consumer handling of food.
*Source: Drexel University
Nuevo sistema de farmacovigilancia para Europa
La Agencia Europea del Medicamento (EMA) ha anunciado un cambio en el sistema de farmacovigilancia de los medicamentos registrados en la Unión Europea. La reforma, que incluye la creación del nuevo Comité de Farmacovigilancia y Evaluación del Riesgo (PRAC), permitirá a todos los ciudadados de la UE informar de los efectos adversos que experimenten con los fármacos e implicará una mayor transparencia de los procesos de la EMA.
"La introducción de la nueva legislación en julio de este año será el cambio más importante del marco legal desde la creción de la Agencia en 1995", informa la EMA en un comunicado. Durante los próximos cinco meses, la EMA ultimará los preparativos para la primera reunión del PRAC. Mientras, informará a las partes interesadas de los nuevos mecanismos para que puedan involucrarse en los nuevos procesos de vigilancia.
Por ejemplo, los médicos y pacientes. "Cualquier ciudadano de un Estado Miembro podrá informar a las autoridades nacionales correspondientes de la sospecha de un afecto adverso asociado a un fármaco", explica la agencia. Este sistema, que ya está disponible en algunos países de la Unión, se complementa con la obligación de las compañías farmacéuticas de remitir "la información clave de todos los productos autorizados y registrados" antes del próximo mes de julio.
Como ya se anunció el pasado mes de septiembre, esta información será almacenada en Eudravigilance una base de datos que podrán consultar los países de la UE, la EMA y la Comisión Europea, así como las empresas farmacéuticas, los profesionales de la salud y el público en general.
Además, el nuevo marco legal "aumentará significativamente la transparencia de las actividades de la EMA relacionadas con la vigilancia de los fármacos". Esto se logrará mediante "la publicación de las agendas, recomendaciones, opiniones y actas de sus comités científicos" del PRAC, del Comité de Productos Médicos de Uso Humano (CHMP) y del CMDh, un grupo de coordinación creado en 2005 cuyas competencias de han reforzado con la nueva ley.
"La introducción de la nueva legislación en julio de este año será el cambio más importante del marco legal desde la creción de la Agencia en 1995", informa la EMA en un comunicado. Durante los próximos cinco meses, la EMA ultimará los preparativos para la primera reunión del PRAC. Mientras, informará a las partes interesadas de los nuevos mecanismos para que puedan involucrarse en los nuevos procesos de vigilancia.
Por ejemplo, los médicos y pacientes. "Cualquier ciudadano de un Estado Miembro podrá informar a las autoridades nacionales correspondientes de la sospecha de un afecto adverso asociado a un fármaco", explica la agencia. Este sistema, que ya está disponible en algunos países de la Unión, se complementa con la obligación de las compañías farmacéuticas de remitir "la información clave de todos los productos autorizados y registrados" antes del próximo mes de julio.
Como ya se anunció el pasado mes de septiembre, esta información será almacenada en Eudravigilance una base de datos que podrán consultar los países de la UE, la EMA y la Comisión Europea, así como las empresas farmacéuticas, los profesionales de la salud y el público en general.
Además, el nuevo marco legal "aumentará significativamente la transparencia de las actividades de la EMA relacionadas con la vigilancia de los fármacos". Esto se logrará mediante "la publicación de las agendas, recomendaciones, opiniones y actas de sus comités científicos" del PRAC, del Comité de Productos Médicos de Uso Humano (CHMP) y del CMDh, un grupo de coordinación creado en 2005 cuyas competencias de han reforzado con la nueva ley.
Breastfeeding and lung function at school age: Does maternal asthma modify the effect?
Breastfeeding is associated with improved lung function at school age, particularly in children of asthmatic mothers, according to a new study from researchers in Switzerland and the UK. "In our cohort of school age children, breastfeeding was associated with modest improvement in forced mid-expiratory flow (FEF50) in our whole group and with improvements in forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) only in the children of asthmatic mothers," said Claudia E. Kuehni, MD, MSc, professor at the Institute of Social and Preventive Medicine at the University of Bern. "In contrast, some earlier studies have suggested that breastfeeding might be harmful in the offspring of mothers with asthma."
The findings were published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
The researchers analyzed data from a nested sample of 1458 children from the Leicestershire cohort studies, born between 1993 and 1997 in the UK. They assessed duration of breastfeeding, other exposures and respiratorysymptoms by repeated questionnaires. Post-bronchodilator FVC, FEV1, peak expiratory flow rates (PEF), FEF50 and skinprick tests were measured at age 12.
In the entire sample of children, FEF50was significantly higher in breastfed children compared with those who were not breastfed, increasing by 0.130 L/sec (P=.048) in those breastfed for 4-6 months and 0.164 L/sec (P=.041) in those breastfed for more than six months. These effects were larger among children of mothers with asthma, with increases of 0.375 L/sec (P=.015) in those breastfed for 4-6 months and 0.468 L/sec (P=.009) in those breastfed for more than six months. Significant improvements in FVC and FEV1with breastfeeding were seen only in the children of asthmatic mothers. Adjustments for respiratory infections in infancy and asthma and atopy in childhood did not change the results of these analyses.
The study had several limitations, including a modest response rate of the original cohort for laboratory examinations and the use of self-report for determining duration of breastfeeding, maternal asthma and infections during infancy.
"We observed modest improvements in lung function in breastfed children in our cohort, including the children of mothers with asthma. Furthermore, our data suggest that rather than acting by reducing respiratory infections, asthma or allergy, breastfeeding might have a direct effect on lung growth," said Dr. Kuehni. "This study supports a strong recommendation for breastfeeding in all children, including those with asthmatic mothers."
**Source: American Thoracic Society (ATS)
The findings were published online ahead of print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
The researchers analyzed data from a nested sample of 1458 children from the Leicestershire cohort studies, born between 1993 and 1997 in the UK. They assessed duration of breastfeeding, other exposures and respiratorysymptoms by repeated questionnaires. Post-bronchodilator FVC, FEV1, peak expiratory flow rates (PEF), FEF50 and skinprick tests were measured at age 12.
In the entire sample of children, FEF50was significantly higher in breastfed children compared with those who were not breastfed, increasing by 0.130 L/sec (P=.048) in those breastfed for 4-6 months and 0.164 L/sec (P=.041) in those breastfed for more than six months. These effects were larger among children of mothers with asthma, with increases of 0.375 L/sec (P=.015) in those breastfed for 4-6 months and 0.468 L/sec (P=.009) in those breastfed for more than six months. Significant improvements in FVC and FEV1with breastfeeding were seen only in the children of asthmatic mothers. Adjustments for respiratory infections in infancy and asthma and atopy in childhood did not change the results of these analyses.
The study had several limitations, including a modest response rate of the original cohort for laboratory examinations and the use of self-report for determining duration of breastfeeding, maternal asthma and infections during infancy.
"We observed modest improvements in lung function in breastfed children in our cohort, including the children of mothers with asthma. Furthermore, our data suggest that rather than acting by reducing respiratory infections, asthma or allergy, breastfeeding might have a direct effect on lung growth," said Dr. Kuehni. "This study supports a strong recommendation for breastfeeding in all children, including those with asthmatic mothers."
**Source: American Thoracic Society (ATS)
La Universidad de Granada utiliza una nueva técnica en 3D para identificar cadáveres
Científicos de la Universidad de Granada han 'remozado' la antigua técnica de identificación de cadáveres que consiste en comparar el cráneo que se encuentra con una fotografía hasta conseguir que sea tan fiable, y mucho más económica, que las pruebas de ADN.
El sistema, reconocen los investigadores, había caído en desuso porque se quedó obsoleto. Tras cinco años de trabajo, Fernando J. Navarro Merino, del Departamento de Medicina Legal de Granada, ha logrado localizar y digitalizar los puntos que sirven de referencia tanto en los cráneos como en las imágenes, desarrollando una metodología que permite realizar identificaciones en no más de una hora gracias a un escáner en tres dimensiones.
Hasta ahora, los puntos de referencia que se tienen en cuenta para analizar un cráneo no se corresponden totalmente con los de la piel o los ojos, lo que dificulta saber cómo eran los individuos cuando estaban vivos. Navarro Merino utilizó una muestra de 500 personas de origen mediterráneo, haciendo tomografías en 3D y comparando los puntos de los huesos craneales con los de los rostros.
El sistema, reconocen los investigadores, había caído en desuso porque se quedó obsoleto. Tras cinco años de trabajo, Fernando J. Navarro Merino, del Departamento de Medicina Legal de Granada, ha logrado localizar y digitalizar los puntos que sirven de referencia tanto en los cráneos como en las imágenes, desarrollando una metodología que permite realizar identificaciones en no más de una hora gracias a un escáner en tres dimensiones.
Hasta ahora, los puntos de referencia que se tienen en cuenta para analizar un cráneo no se corresponden totalmente con los de la piel o los ojos, lo que dificulta saber cómo eran los individuos cuando estaban vivos. Navarro Merino utilizó una muestra de 500 personas de origen mediterráneo, haciendo tomografías en 3D y comparando los puntos de los huesos craneales con los de los rostros.
-Análisis barato y fiable
Descubrió así que la relación entre ellos no era perpendicular, como se ha pensado hasta ahora, sino en ángulo. "Son esos vectores, su dirección, sentido y distancia, los que dan fiabilidad a las mediciones", explica a ELMUNDO.es.
"Se trata de un análisis mucho menos costoso que los estudios genéticos de ADN, y adémás es rápido y fiable. Y, en todo caso, sirve para hacer descartes previos a los genéticos, lo que supone un ahorro", argumenta.
Los 500 participantes se escogieron de una muestra de estudios tomográficos (TAC) de los hospitales de Castilla-La Mancha, con los que tiene un acuerdo la Universidad de Granada. Los científicos crearon una base de datos con las coordenadas en 3D tanto de los puntos craneales como los faciales y obtuvieron los vectores.
Para ver si la técnica funcionaba, hicieron un escáner en 3D del cráneo de un indiviudo fallecido y crearon un modelo virtual sobre el que localizaron y marcaron todos los puntos craneales (craneométricos), haciendo lo mismo en la fotografía de esta misma persona que facilitó la familia.
Los resultados fueron excepcionales. De hecho, ya se ha patentado el 'software' de la nueva técnica y países como México, donde hay un alto número de delitos en los que hay que identificar a las víctimas, ya han mostrado un gran interés. De hecho, el equipo ya está pensando en buscar los 'vectores' de otras poblaciones humanas, dado que varían según el grupo humano.
Navarro Merino señala que para que la técnica tenga éxito debe conservarse el cráneo entero, pero precisamente esta es una de las partes del cuerpo más duras, por lo que suelen estar en buen estado.
En España, también podría ser de utilidad para los que ahora están buscando a familiares que fueron asesinados durante la Guerra Civil, muchos de ellos enterrados en fosas comunes donde hay un revoltijo de huesos. El alto coste de los análisis de ADN ha sido, precisamente, uno de los problemas con los que se han encontrado los descendientes interesados en enterrar a sus muertos.
La investigación, presentada como tesis por Navarro Merino, ha sido dirigida por los profesores Miguel C. Botella López, Inmaculada Alemán Aguilera y Sergio Damas Arroyo.
Descubrió así que la relación entre ellos no era perpendicular, como se ha pensado hasta ahora, sino en ángulo. "Son esos vectores, su dirección, sentido y distancia, los que dan fiabilidad a las mediciones", explica a ELMUNDO.es.
"Se trata de un análisis mucho menos costoso que los estudios genéticos de ADN, y adémás es rápido y fiable. Y, en todo caso, sirve para hacer descartes previos a los genéticos, lo que supone un ahorro", argumenta.
Los 500 participantes se escogieron de una muestra de estudios tomográficos (TAC) de los hospitales de Castilla-La Mancha, con los que tiene un acuerdo la Universidad de Granada. Los científicos crearon una base de datos con las coordenadas en 3D tanto de los puntos craneales como los faciales y obtuvieron los vectores.
Para ver si la técnica funcionaba, hicieron un escáner en 3D del cráneo de un indiviudo fallecido y crearon un modelo virtual sobre el que localizaron y marcaron todos los puntos craneales (craneométricos), haciendo lo mismo en la fotografía de esta misma persona que facilitó la familia.
Los resultados fueron excepcionales. De hecho, ya se ha patentado el 'software' de la nueva técnica y países como México, donde hay un alto número de delitos en los que hay que identificar a las víctimas, ya han mostrado un gran interés. De hecho, el equipo ya está pensando en buscar los 'vectores' de otras poblaciones humanas, dado que varían según el grupo humano.
Navarro Merino señala que para que la técnica tenga éxito debe conservarse el cráneo entero, pero precisamente esta es una de las partes del cuerpo más duras, por lo que suelen estar en buen estado.
En España, también podría ser de utilidad para los que ahora están buscando a familiares que fueron asesinados durante la Guerra Civil, muchos de ellos enterrados en fosas comunes donde hay un revoltijo de huesos. El alto coste de los análisis de ADN ha sido, precisamente, uno de los problemas con los que se han encontrado los descendientes interesados en enterrar a sus muertos.
La investigación, presentada como tesis por Navarro Merino, ha sido dirigida por los profesores Miguel C. Botella López, Inmaculada Alemán Aguilera y Sergio Damas Arroyo.
**Publicado en "EL MUNDO"
New technology to tackle treatment-resistant cancers
Free-flowing cancer cells have been mapped with unprecedented accuracy in the bloodstream of patients with prostate, breast and pancreatic cancer, using a brand new approach, in an attempt to assess and control the disease as it spreads in real time through the body, and solve the problem of predicting response and resistance to therapies. In comparison to a previous generation of systems, the researchers state their test showed a significantly greater number of high-definition circulating tumour cells (HD-CTCs), in a higher proportion of patients, by using a computing-intensive method that enables them to look at millions of normal cells and find the rare cancer cells among them.
Their results, published February 3 2012, in IOP Publishing's journal Physical Biology, could help reveal the mechanisms behind the spread of solid tumours from one organ or tissue to another -- mechanisms that have, until now, remained a mystery.
Dr Jorge Nieva, an oncologist at Billings Clinic leading the study, said: "This technology will allow scientists to move away from mouse and cell culture systems and speed the delivery of cures for cancer in people. This is the technology we have been waiting for to solve the problem of resistance to chemotherapy drugs."
Senior technology author of the study, Professor Peter Kuhn, said: "In the future, our fluid biopsy can effectively become the companion to the patient for life. If we can assess the disease in real time, we can make quantitative treatment decisions in real time. These decisions include predictive decisions about therapeutic response, diagnostic decisions and prognostic decisions about outcome."
The researchers, based at the Scripps Physics Oncology Center in La Jolla, California, were able to find five or more CTCs in each milliliter of blood in 80% of the 20 patients they tested with prostate cancer; 70% in the 30 patients with breast cancer; and 50% in the 18 patients with pancreatic cancer.
The authors also report that their test showed significantly better results when compared with the commercial test, CellSearch®, which uses a slightly less accurate approach which effectively reduces the sample from approximately 50 million cells to just 5,000 before conducting fluorescent imaging, meaning important cells you wish to study could be lost.
In 7.5 mL of blood, the CellSearch® test found two or more CTCs in 5 out of the 15 patients tested whereas the new test found two or more CTCs in a single milliliter of blood in 14 out of the 15 patients tested.
The dyes used in this new approach contain antibodies that target, and then attach to, specific proteins that are expressed by the CTCs. Once attached, they fluoresce and allow the researchers to observe them. The result is a set of high resolution digital images that retain the intricate details of the cells and allow the researchers to effectively analyse them in the laboratory. Also striking is the quality of the images.
"The high definition method gives a detailed portrait of these elusive cells that are caught in the act of spreading around the body. It's unprecedented -- we've never been able to see them routinely and in high definition like this before," says diagnostic pathologist Kelly Bethel, MD, the senior clinical investigator on Kuhn's team.
"The science behind this approach, and the ability to obtain more detailed information about CTCs in a timely fashion, opens up opportunities to address some of the outstanding problems in cancer, such as drug-resistance. This is an example that bringing a physical sciences approach to a medical need has potential for profound consequences to greatly benefit cancer patients," said Dr Larry Nagahara of the National Cancer Institute.
**Source: Institute of Physics (IOP)
Their results, published February 3 2012, in IOP Publishing's journal Physical Biology, could help reveal the mechanisms behind the spread of solid tumours from one organ or tissue to another -- mechanisms that have, until now, remained a mystery.
Dr Jorge Nieva, an oncologist at Billings Clinic leading the study, said: "This technology will allow scientists to move away from mouse and cell culture systems and speed the delivery of cures for cancer in people. This is the technology we have been waiting for to solve the problem of resistance to chemotherapy drugs."
Senior technology author of the study, Professor Peter Kuhn, said: "In the future, our fluid biopsy can effectively become the companion to the patient for life. If we can assess the disease in real time, we can make quantitative treatment decisions in real time. These decisions include predictive decisions about therapeutic response, diagnostic decisions and prognostic decisions about outcome."
The researchers, based at the Scripps Physics Oncology Center in La Jolla, California, were able to find five or more CTCs in each milliliter of blood in 80% of the 20 patients they tested with prostate cancer; 70% in the 30 patients with breast cancer; and 50% in the 18 patients with pancreatic cancer.
The authors also report that their test showed significantly better results when compared with the commercial test, CellSearch®, which uses a slightly less accurate approach which effectively reduces the sample from approximately 50 million cells to just 5,000 before conducting fluorescent imaging, meaning important cells you wish to study could be lost.
In 7.5 mL of blood, the CellSearch® test found two or more CTCs in 5 out of the 15 patients tested whereas the new test found two or more CTCs in a single milliliter of blood in 14 out of the 15 patients tested.
The dyes used in this new approach contain antibodies that target, and then attach to, specific proteins that are expressed by the CTCs. Once attached, they fluoresce and allow the researchers to observe them. The result is a set of high resolution digital images that retain the intricate details of the cells and allow the researchers to effectively analyse them in the laboratory. Also striking is the quality of the images.
"The high definition method gives a detailed portrait of these elusive cells that are caught in the act of spreading around the body. It's unprecedented -- we've never been able to see them routinely and in high definition like this before," says diagnostic pathologist Kelly Bethel, MD, the senior clinical investigator on Kuhn's team.
"The science behind this approach, and the ability to obtain more detailed information about CTCs in a timely fashion, opens up opportunities to address some of the outstanding problems in cancer, such as drug-resistance. This is an example that bringing a physical sciences approach to a medical need has potential for profound consequences to greatly benefit cancer patients," said Dr Larry Nagahara of the National Cancer Institute.
**Source: Institute of Physics (IOP)
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