La OMC organiza, el próximo jueves 16 de junio, una jornada sobre el conflicto de intereses que giran en torno al medicamento para abordar con rigor esta problemática que puede poner en riesgo el contrato terapéutico entre médico y paciente. Es por ello que la profesión médica persigue dotarse de mecanismos para hacer frente a actuaciones que puedan poner en riesgo dicho contrato, y que ofrezcan una prescripción eficiente y de calidad, entendida ésta como la administración, por parte del médico, del medicamento adecuado, en el tiempo adecuado y al menor coste
En la actualidad, la prescripción de fármacos representa el 1,4 por ciento del Producto Interior Bruto (PIB). Sólo en Atención Primaria, el capítulo de farmacia supone entre el 65 y el 70 por ciento del presupuesto de los centros de salud.
En un momento de crisis como en el que está inmerso en estos momentos el sistema sanitario, los gobiernos, conscientes de la libertad de que goza el médico a la hora de prescribir y del impacto económico de sus decisiones, intentan poner límites, restricciones y orientaciones a su labor prescriptora, con el propósito de disminuir el gasto farmacéutico y el sanitario en su conjunto. A ello se suman actuaciones derivadas de la sociedad de mercado y de realidad económica, marcadas por el afán de ventas, promociones, beneficios,… que alientan conflictos de intereses entre todos los agentes del sector sanitario: Administración sanitaria, industria farmacéutica, médicos, pacientes y oficinas de farmacia.
Como señala, al respecto, el coordinador del Observatorio de la Prescripción de la Organización Médica Colegial, el doctor Pedro Hidalgo, “el liderazgo de la prescripción por parte del médico es esencial para que ésta esté avalada por criterios científicos de efectividad, seguridad y coste, y para reforzar el contrato terapéutico con el paciente, alejado de intereses ajenos a la salud del mismo”.
Es por ello que la profesión médica persigue dotarse de mecanismos para hacer frente a actuaciones que puedan poner en riesgo dicho contrato terapéutico entre el médico y el paciente, y que ofrezcan una prescripción eficiente y de calidad, entendida ésta como la administración, por parte del médico, del medicamento adecuado, en el tiempo adecuado y al menor coste.
La calidad de la prescripción se consigue: reduciendo la selección del número de fármacos, elegidos con evidencia científica y según criterios de selección de la OMS; incluyendo aquéllos que aporten un valor intrínseco elevado (VIE); y disminuyendo las unidades terapéuticas bajas (UTB). Como consecuencia de ello se obtendrán óptimos resultados económicos y de salud.
“Creemos fundamental identificar estos posibles conflictos que afectan tanto a la autorización y selección de fármacos, como a la evidencia científica en torno a la toma de decisiones sobre el medicamento, el papel de los agentes sobre la prescripción, y el seguimiento farmacoterapéutico, entre otros”, tal como explica el también presidente del Colegio de Médicos de Badajoz.
Todas estas cuestiones se pondrán sobre la mesa durante la celebración de la jornada “Médicos y Medicamentos: ¿Conflicto de Intereses?”, convocada por la Organización Médica Colegial, en su sede, el próximo 16 de junio.
La Jornada, dividida en dos mesas, una dedicada a la prescripción y seguimiento farmacoterapéutico: competencias y responsabilidades; y otra sobre autorización y selección de medicamentos, pretende ahondar sin complejos, de la mano de los máximos expertos en estos temas procedentes de todos los sectores sanitarios: organizaciones médicas, sociedades científicas, industria farmacéutica, esta problemática que frena la libertad y desprestigia a la profesión médica.
**Publicado en "MEDICOS Y PACIENTES"
Diario digital con noticias de actualidad relacionadas con el mundo de la salud. Novedades, encuestas, estudios, informes, entrevistas. Con un sencillo lenguaje dirigido a todo el mundo. Y algunos consejos turísticos para pasarlo bien
Traductor
10 June 2011
New European Survey of ITP: Insight into Treatment Experience for Patients with Rare Blood Disorder
Amgen announced today the results of a new European survey of people suffering from a rare blood disorder called immune thrombocytopenia (ITP) shows that one in four feels the impact of the condition on their daily lives is severe, causing them anxiety and concern. ITP is a rare, serious and often chronic immune disorder characterised by low platelet counts in the blood.
The survey also shows that two-thirds of people in the six countries surveyed would like to have more healthcare professional advice and expert information than they are currently receiving, to help them better manage their condition.
Adult chronic ITP affects an estimated 2.0 per 100,000 patients in the European Union (EU), (1,2) and is a rare and serious autoimmune disorder characterised by low platelet counts in the blood (thrombocytopenia), which can lead to severe bleeding events. ITP occurs when immune system cells (specialised lymphocytes) produce antibodies that cause the destruction of platelets in the spleen and other organs. The specific cause of ITP is unknown and in most adults it is a chronic condition.
The survey also shows that two-thirds of people in the six countries surveyed would like to have more healthcare professional advice and expert information than they are currently receiving, to help them better manage their condition.
Adult chronic ITP affects an estimated 2.0 per 100,000 patients in the European Union (EU), (1,2) and is a rare and serious autoimmune disorder characterised by low platelet counts in the blood (thrombocytopenia), which can lead to severe bleeding events. ITP occurs when immune system cells (specialised lymphocytes) produce antibodies that cause the destruction of platelets in the spleen and other organs. The specific cause of ITP is unknown and in most adults it is a chronic condition.
B vitamins in mother's diet reduce colorectal cancer risk in offspring
Mice born to mothers who are fed a diet supplemented with B vitamins are less likely to develop intestinal tumors, report scientists at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University. Previous research in humans and mice suggests that B vitamins, particularly folate, play a role in the prevention of colorectal cancer. Using a mouse model of naturally occurring colorectal cancer, the USDA HNRCA scientists examined whether a mothers' B vitamin intake impacts her offspring's cancer risk. Mothers were fed diets containing supplemental, adequate or mildly deficient quantities of vitamins B2, B6, B12 and folate prior to conception through weaning after which all of the offspring received the same adequate diet.
"We saw, by far, the fewest intestinal tumors in the offspring of mothers consuming the supplemented diet," says Jimmy Crott, PhD, senior author and a scientist in the Vitamins and Carcinogenesis Laboratory at the USDA HNRCA. "Although the tumor incidence was similar between offspring of deficient and adequate mothers, 54% of tumors in the deficient offspring were advanced and had invaded surrounding tissue while only 18% of tumors in the offspring of adequate mothers displayed these aggressive properties."
The results were published online June 9 in the journal Gut.
Crott and colleagues associated the tumor suppression seen in the offspring of supplemented mothers with a protection against disruptions to the Wnt signaling pathway, a network of genes commonly altered in colorectal cancer.
"The strongest expression of tumor-suppressing genes in the Wnt pathway was in the offspring of supplemented mothers and the weakest was in the offspring of the mildly deficient mothers," says first author Eric Ciappio, a PhD candidate at the Friedman School of Nutrition Science and Policy at Tufts.
"We attribute these differences in gene expression to epigenetics, modifications of DNA which are sensitive to environmental factors such as diet," Ciappio continues. "In this case, changing maternal B vitamin intake had lasting epigenetic effects in offspring and may explain the differences in tumor incidence and aggressiveness we observed".
It remains unclear whether maternal consumption of the four B vitamins could impact tumor development in humans. ""While evidence is beginning to accumulate to suggest that maternal consumption of supplements containing folate may afford some protection against childhood cancers in offspring, we don't yet have the ability to determine whether the same holds true for cancers that normally present in the mid to late decades of life," explains Crott, who is also an assistant professor at the Friedman School.
Crott adds, "Aside from the known protective effect of maternal folate against neural tube defects such as spina bifida, our results suggest that mothers consuming supplemental quantities of these B vitamins may also be protecting her children against colorectal cancer."
*Source: Tufts University, Health Sciences
"We saw, by far, the fewest intestinal tumors in the offspring of mothers consuming the supplemented diet," says Jimmy Crott, PhD, senior author and a scientist in the Vitamins and Carcinogenesis Laboratory at the USDA HNRCA. "Although the tumor incidence was similar between offspring of deficient and adequate mothers, 54% of tumors in the deficient offspring were advanced and had invaded surrounding tissue while only 18% of tumors in the offspring of adequate mothers displayed these aggressive properties."
The results were published online June 9 in the journal Gut.
Crott and colleagues associated the tumor suppression seen in the offspring of supplemented mothers with a protection against disruptions to the Wnt signaling pathway, a network of genes commonly altered in colorectal cancer.
"The strongest expression of tumor-suppressing genes in the Wnt pathway was in the offspring of supplemented mothers and the weakest was in the offspring of the mildly deficient mothers," says first author Eric Ciappio, a PhD candidate at the Friedman School of Nutrition Science and Policy at Tufts.
"We attribute these differences in gene expression to epigenetics, modifications of DNA which are sensitive to environmental factors such as diet," Ciappio continues. "In this case, changing maternal B vitamin intake had lasting epigenetic effects in offspring and may explain the differences in tumor incidence and aggressiveness we observed".
It remains unclear whether maternal consumption of the four B vitamins could impact tumor development in humans. ""While evidence is beginning to accumulate to suggest that maternal consumption of supplements containing folate may afford some protection against childhood cancers in offspring, we don't yet have the ability to determine whether the same holds true for cancers that normally present in the mid to late decades of life," explains Crott, who is also an assistant professor at the Friedman School.
Crott adds, "Aside from the known protective effect of maternal folate against neural tube defects such as spina bifida, our results suggest that mothers consuming supplemental quantities of these B vitamins may also be protecting her children against colorectal cancer."
*Source: Tufts University, Health Sciences
Mutations in essential genes often cause rare diseases
Mutations in genes essential to survival are behind so-called orphan diseases, explaining in part why these diseases are rare and often deadly, according to a study appearing in The American Journal of Human Genetics. The new finding contrasts sharply with what is known about mutations in non-essential genes being the drivers of common diseases having higher prevalence rates, according to scientists at Cincinnati Children's Hospital Medical Center who conducted the research.
The bioinformatics study – which used computer technology to link diseases with causative genes, interacting proteins, and shared molecular pathways – produced a global network map involving 1,772 orphan diseases caused by gene mutations. The map gives scientists a precise starting point to launch innovative research into developing new therapies or repositioning existing drugs for diseases that lack effective treatments, said Anil Jegga, Ph.D., a researcher in the Division of Biomedical Informatics and the study's senior investigator.
An orphan or rare disease is defined as one affecting less than 200,000 Americans. There are 8,000 orphan diseases that together impact more than 25 million people in the United States, Dr. Jegga explained. A number of orphan diseases start early in life, are influenced by genetics and the immune system, and include diseases like cystic fibrosis and various forms of childhood cancer.
"Only about 300 of these 8,000 diseases have effective drug therapy, so collectively orphan diseases pose a formidable challenge for public health authorities," Dr. Jegga said. "Previous studies on disease networks have not separated out these rare diseases, many of which are fatal while others induce chronic and debilitating illnesses."
By analyzing networks that offer a natural representation of orphan diseases – including the interactive links between causative genes, protein functions and pathways – researchers get a systems-level view of the complex associations that underlie these diseases, according to Minlu Zhang and Cheng Zhu, the study's co-first authors and members of the Department of Computer Science at the University of Cincinnati.
One of the study's key findings is that orphan disease genes encode hub proteins, which have multiple protein-to-protein interactions vital to cell function. Previous studies have shown that non-essential genes causing common diseases do not encode hub proteins. In fact, researchers report that deleting about 43 percent of orphan disease causing gene homologs in mice (which are similar to human genes) is lethal or cause premature death, indicating the essential survival role of the genes and related biological processes.
Researchers said the 1772 orphan diseases analyzed in their study are linked to a total of 2,124 mutant genes. Sixty-nine percent of the diseases have one implicated gene and the rest are caused by two or more genes. In fact, of the 2,124 orphan disease-causing genes, 1,393 are linked to only one disease, while the remaining 731 genes are causative for two or more diseases. An example noted in the study involves mutations of the gene LMNA, which are implicated in 17 orphan diseases. And the orphan disease, nonsyndromic genetic deafness, has the highest number of causative genes at 43.
Dr. Jegga and his colleagues say the study also shows that it is critical to go beyond taking a gene-based approach to diagramming interactive orphan disease maps.
"Our findings indicate that the wiring of the gene-based and function-based networks of orphan diseases is different," he said. "By considering the shared functions among causal genes, molecular targets for the treatment of orphan diseases can be revealed. These maps of molecular targets can then be used to create novel hypotheses and guide treatment strategies for orphan diseases."
In the 10 years prior to passage of the U.S. Orphan Drug Act in 1983, only 10 new drugs for rare diseases were approved by the Food and Drug Administration. In the 28 years since the act passed, more than 300 orphan disease drugs have been approved.
*Source: Cincinnati Children's Hospital Medical Center
The bioinformatics study – which used computer technology to link diseases with causative genes, interacting proteins, and shared molecular pathways – produced a global network map involving 1,772 orphan diseases caused by gene mutations. The map gives scientists a precise starting point to launch innovative research into developing new therapies or repositioning existing drugs for diseases that lack effective treatments, said Anil Jegga, Ph.D., a researcher in the Division of Biomedical Informatics and the study's senior investigator.
An orphan or rare disease is defined as one affecting less than 200,000 Americans. There are 8,000 orphan diseases that together impact more than 25 million people in the United States, Dr. Jegga explained. A number of orphan diseases start early in life, are influenced by genetics and the immune system, and include diseases like cystic fibrosis and various forms of childhood cancer.
"Only about 300 of these 8,000 diseases have effective drug therapy, so collectively orphan diseases pose a formidable challenge for public health authorities," Dr. Jegga said. "Previous studies on disease networks have not separated out these rare diseases, many of which are fatal while others induce chronic and debilitating illnesses."
By analyzing networks that offer a natural representation of orphan diseases – including the interactive links between causative genes, protein functions and pathways – researchers get a systems-level view of the complex associations that underlie these diseases, according to Minlu Zhang and Cheng Zhu, the study's co-first authors and members of the Department of Computer Science at the University of Cincinnati.
One of the study's key findings is that orphan disease genes encode hub proteins, which have multiple protein-to-protein interactions vital to cell function. Previous studies have shown that non-essential genes causing common diseases do not encode hub proteins. In fact, researchers report that deleting about 43 percent of orphan disease causing gene homologs in mice (which are similar to human genes) is lethal or cause premature death, indicating the essential survival role of the genes and related biological processes.
Researchers said the 1772 orphan diseases analyzed in their study are linked to a total of 2,124 mutant genes. Sixty-nine percent of the diseases have one implicated gene and the rest are caused by two or more genes. In fact, of the 2,124 orphan disease-causing genes, 1,393 are linked to only one disease, while the remaining 731 genes are causative for two or more diseases. An example noted in the study involves mutations of the gene LMNA, which are implicated in 17 orphan diseases. And the orphan disease, nonsyndromic genetic deafness, has the highest number of causative genes at 43.
Dr. Jegga and his colleagues say the study also shows that it is critical to go beyond taking a gene-based approach to diagramming interactive orphan disease maps.
"Our findings indicate that the wiring of the gene-based and function-based networks of orphan diseases is different," he said. "By considering the shared functions among causal genes, molecular targets for the treatment of orphan diseases can be revealed. These maps of molecular targets can then be used to create novel hypotheses and guide treatment strategies for orphan diseases."
In the 10 years prior to passage of the U.S. Orphan Drug Act in 1983, only 10 new drugs for rare diseases were approved by the Food and Drug Administration. In the 28 years since the act passed, more than 300 orphan disease drugs have been approved.
*Source: Cincinnati Children's Hospital Medical Center
Mayo Clinic-led research team tests alternative approach to treating diabetes
In a mouse study, scientists at Mayo Clinic Florida have demonstrated the feasibility of a promising new strategy for treating human type 2 diabetes, which affects more than 200 million people worldwide. In type 2 diabetes, the body stops responding efficiently to insulin, a hormone that controls blood sugar. To compensate for the insensitivity to insulin, many diabetes drugs work by boosting insulin levels; for example, by injecting more insulin or by increasing the amount of insulin secreted from the pancreas. The new study, published in the June 9 issue of PLoS ONE, showed that a different approach could also be effective for treating diabetes — namely, blocking the breakdown of insulin, after it is secreted from the pancreas.
"Insulin levels in the blood reflect the balance between how much is secreted and how fast it is broken down," says the study's lead researcher, Malcolm A. Leissring, Ph.D., from Mayo Clinic's Department of Neuroscience. "Blocking the breakdown of insulin is simply an alternative method for achieving the same goal as many existing diabetes therapies."
The researchers tested this idea by studying mice in which insulin-degrading enzyme (IDE) was "knocked out," or deleted genetically. IDE is a molecular "machine" that normally chews up the insulin hormone, breaking it down into smaller pieces. Levels of insulin in the blood are controlled, in part, by this process.
Compared to normal mice, IDE knockout mice had more insulin overall, weighed less, and were more efficient at controlling their blood sugar. They were, in effect, "super mice" with respect to their ability to lower their blood sugar after a meal, the process that is disrupted in diabetes, explains Dr. Leissring.
These findings suggest that drugs that inhibit IDE could be useful in treating diabetes. Dr. Leissring's team is actively working to develop such drugs. As reported in a separate study in PLoS ONE last year, Dr. Leissring and colleagues developed the first potent and selective inhibitors of IDE. The Mayo team has now developed more drug-like IDE inhibitors that they are preparing to test in animal models of diabetes.
"The reason we studied IDE knockout mice was to help us understand whether IDE inhibitors would be useful for treating diabetes," says Samer Abdul-Hay, Ph.D., first author on the study. But the IDE knockout mice are not a perfect model of how a drug will perform, he notes. "They are actually a better model of overdosing on an IDE inhibitor. We would never want a drug that inhibits IDE 100 percent in all tissues throughout life."
The effect of deleting all IDE in the mice was so strong, in fact, that the effect eventually backfired, the researchers say. Despite being "super mice" when young, as the IDE knockout mice aged, they slowly became resistant to the elevated insulin, gained weight, and lost control of their blood sugar. As a result, the older mice developed classic type 2 diabetes.
"The finding that older IDE knockout mice develop diabetes has confused a lot of people," says Dr. Leissring. "It's an example of too much of a good thing becoming bad for you." Drugs that inhibit IDE only partially or only transiently would not be expected to cause diabetes, he says. "Deleting all IDE is overkill."
The researchers say the Mayo study also has interesting implications for understanding how diabetes starts. "Deleting IDE produces elevated insulin levels — a condition known as hyperinsulinemia. Diabetes is usually believed to cause hyperinsulinemia, not the other way around," Dr. Leissring says. Nevertheless, in the IDE knockout mice, chronic hyperinsulinemia seemed to actually cause diabetes. As they aged, the mice appeared to adapt to the chronically high insulin levels, for example, by reducing the number of receptors for insulin in their tissues. "These adaptations make the mice less sensitive to insulin, which is the exact cause of type 2 diabetes."
Whether these findings apply to humans is unclear, Dr. Leissring cautions. He says these novel findings "represent early, but exciting days" in a new avenue of diabetes research. Dr. Leissring was recently awarded a five-year career development grant from the American Diabetes Association, which will help support this line of research.
**Source: Mayo Clinic
"Insulin levels in the blood reflect the balance between how much is secreted and how fast it is broken down," says the study's lead researcher, Malcolm A. Leissring, Ph.D., from Mayo Clinic's Department of Neuroscience. "Blocking the breakdown of insulin is simply an alternative method for achieving the same goal as many existing diabetes therapies."
The researchers tested this idea by studying mice in which insulin-degrading enzyme (IDE) was "knocked out," or deleted genetically. IDE is a molecular "machine" that normally chews up the insulin hormone, breaking it down into smaller pieces. Levels of insulin in the blood are controlled, in part, by this process.
Compared to normal mice, IDE knockout mice had more insulin overall, weighed less, and were more efficient at controlling their blood sugar. They were, in effect, "super mice" with respect to their ability to lower their blood sugar after a meal, the process that is disrupted in diabetes, explains Dr. Leissring.
These findings suggest that drugs that inhibit IDE could be useful in treating diabetes. Dr. Leissring's team is actively working to develop such drugs. As reported in a separate study in PLoS ONE last year, Dr. Leissring and colleagues developed the first potent and selective inhibitors of IDE. The Mayo team has now developed more drug-like IDE inhibitors that they are preparing to test in animal models of diabetes.
"The reason we studied IDE knockout mice was to help us understand whether IDE inhibitors would be useful for treating diabetes," says Samer Abdul-Hay, Ph.D., first author on the study. But the IDE knockout mice are not a perfect model of how a drug will perform, he notes. "They are actually a better model of overdosing on an IDE inhibitor. We would never want a drug that inhibits IDE 100 percent in all tissues throughout life."
The effect of deleting all IDE in the mice was so strong, in fact, that the effect eventually backfired, the researchers say. Despite being "super mice" when young, as the IDE knockout mice aged, they slowly became resistant to the elevated insulin, gained weight, and lost control of their blood sugar. As a result, the older mice developed classic type 2 diabetes.
"The finding that older IDE knockout mice develop diabetes has confused a lot of people," says Dr. Leissring. "It's an example of too much of a good thing becoming bad for you." Drugs that inhibit IDE only partially or only transiently would not be expected to cause diabetes, he says. "Deleting all IDE is overkill."
The researchers say the Mayo study also has interesting implications for understanding how diabetes starts. "Deleting IDE produces elevated insulin levels — a condition known as hyperinsulinemia. Diabetes is usually believed to cause hyperinsulinemia, not the other way around," Dr. Leissring says. Nevertheless, in the IDE knockout mice, chronic hyperinsulinemia seemed to actually cause diabetes. As they aged, the mice appeared to adapt to the chronically high insulin levels, for example, by reducing the number of receptors for insulin in their tissues. "These adaptations make the mice less sensitive to insulin, which is the exact cause of type 2 diabetes."
Whether these findings apply to humans is unclear, Dr. Leissring cautions. He says these novel findings "represent early, but exciting days" in a new avenue of diabetes research. Dr. Leissring was recently awarded a five-year career development grant from the American Diabetes Association, which will help support this line of research.
**Source: Mayo Clinic
Cancer protein discovery may aid radiation therapy
Farber Cancer Institute have uncovered a new role for a key cancer protein, a finding that could pave the way for more-effective radiation treatment of a variety of tumors. Many cancers are driven in part by elevated levels of cyclin D1, which allow the cells to escape growth controls and proliferate abnormally. In the new research, reported in the June 9 issue of Nature, researchers discovered that cyclin D1 also helps cancer cells to quickly repair DNA damage caused by radiation treatments, making the tumors resistant to the therapy.
Based on this finding, the researchers made cancer cells more sensitive to several cancer drugs and to radiation by using a molecular tool to lower the cancer cells' cyclin D1 levels, said Peter Sicinski, MD, PhD, senior author of the report and a professor of genetics at Dana-Farber.
"This is the first time a cell cycle protein has been shown to be directly involved in DNA repair," said Siwanon Jirawatnotai, PhD, the lead author of the paper. "If we could come up with a strategy to inhibit cyclin D1, it might be very useful in treating a variety of cancers."
The gene for cyclin D1 is the second most-overexpressed gene found in human cancers, including breast cancer, colon cancer, lymphoma, melanoma, and prostate cancer. Cyclin D1's normal function in cellular growth control is to temporarily remove a molecular brake, allowing the cell to manufacture more DNA in preparation for cell division. When cyclin D1 is mutated or is overactivated by external growth signals, the cell may run out of control and proliferate in a malignant fashion.
The findings came in a series of experiments by Jirawatnotai, a post-doctoral fellow in the Sicinski lab. With the goal of uncovering details of cyclin D1's function in human cancer cells, Jirawatnotai broke open four types of cancer cells, isolated the cyclin D1 protein, and searched for other proteins with which it interacted.
The experiment netted more than 132 partner proteins, most of them part of the cell cycle protein mechanism in which cyclin D1 is a major player. But unexpectedly, the scientists also observed that the cyclin D1 protein was binding to a cluster of DNA repair proteins, most importantly RAD51. The RAD51 protein is an enzyme that rushes to broken parts of the cancer cell's DNA instructions and repairs the damage, including damage caused by radiation therapy administered to stop cancer cells' division and growth. In another experiment, it was observed that cyclin D1 was recruited along with RAD51 to the DNA damage site.
"This was a surprise," said Jirawatnotai. "This finding showed that cyclin D1 has an unexpected function in repairing broken DNA." In additional experiments, he used a molecular tool, RNA interference (RNAi) to drastically reduce the level of cyclin D1 in the cancer cells. "When you lower D1 levels, you get poorer repair," he said.
When cancer cells with reduced cyclin D1 protein levels were administered to mice, the resulting tumor proved to be more sensitive to radiation than those grown from cells with overexpressed cyclin D1.
Currently, cyclin D1 is thought to be responsible for driving cancer cell proliferation. Agents that target cyclin D1 are currently in clinical trials, with the goal of reducing cancer cell growth. The new findings strongly suggest that targeting cyclin D1 may increase susceptibility of human cancers to radiation, said the scientists, and this discovery may encourage targeting cyclin D1 even in these cancers whose cells do not depend on cyclin D1 for proliferation.
"Our results potentially change the way we think about cyclin D1 and cancer and may encourage targeting cyclin D1 in a very large pool of human cancers which do not need cyclin D1 for proliferation, but may still depend on cyclin D1 for DNA repair," said Jirawatnotai, who also holds a faculty position at the Mahidol University in Bangkok, Thailand.
**Source: Dana-Farber Cancer Institute
Based on this finding, the researchers made cancer cells more sensitive to several cancer drugs and to radiation by using a molecular tool to lower the cancer cells' cyclin D1 levels, said Peter Sicinski, MD, PhD, senior author of the report and a professor of genetics at Dana-Farber.
"This is the first time a cell cycle protein has been shown to be directly involved in DNA repair," said Siwanon Jirawatnotai, PhD, the lead author of the paper. "If we could come up with a strategy to inhibit cyclin D1, it might be very useful in treating a variety of cancers."
The gene for cyclin D1 is the second most-overexpressed gene found in human cancers, including breast cancer, colon cancer, lymphoma, melanoma, and prostate cancer. Cyclin D1's normal function in cellular growth control is to temporarily remove a molecular brake, allowing the cell to manufacture more DNA in preparation for cell division. When cyclin D1 is mutated or is overactivated by external growth signals, the cell may run out of control and proliferate in a malignant fashion.
The findings came in a series of experiments by Jirawatnotai, a post-doctoral fellow in the Sicinski lab. With the goal of uncovering details of cyclin D1's function in human cancer cells, Jirawatnotai broke open four types of cancer cells, isolated the cyclin D1 protein, and searched for other proteins with which it interacted.
The experiment netted more than 132 partner proteins, most of them part of the cell cycle protein mechanism in which cyclin D1 is a major player. But unexpectedly, the scientists also observed that the cyclin D1 protein was binding to a cluster of DNA repair proteins, most importantly RAD51. The RAD51 protein is an enzyme that rushes to broken parts of the cancer cell's DNA instructions and repairs the damage, including damage caused by radiation therapy administered to stop cancer cells' division and growth. In another experiment, it was observed that cyclin D1 was recruited along with RAD51 to the DNA damage site.
"This was a surprise," said Jirawatnotai. "This finding showed that cyclin D1 has an unexpected function in repairing broken DNA." In additional experiments, he used a molecular tool, RNA interference (RNAi) to drastically reduce the level of cyclin D1 in the cancer cells. "When you lower D1 levels, you get poorer repair," he said.
When cancer cells with reduced cyclin D1 protein levels were administered to mice, the resulting tumor proved to be more sensitive to radiation than those grown from cells with overexpressed cyclin D1.
Currently, cyclin D1 is thought to be responsible for driving cancer cell proliferation. Agents that target cyclin D1 are currently in clinical trials, with the goal of reducing cancer cell growth. The new findings strongly suggest that targeting cyclin D1 may increase susceptibility of human cancers to radiation, said the scientists, and this discovery may encourage targeting cyclin D1 even in these cancers whose cells do not depend on cyclin D1 for proliferation.
"Our results potentially change the way we think about cyclin D1 and cancer and may encourage targeting cyclin D1 in a very large pool of human cancers which do not need cyclin D1 for proliferation, but may still depend on cyclin D1 for DNA repair," said Jirawatnotai, who also holds a faculty position at the Mahidol University in Bangkok, Thailand.
**Source: Dana-Farber Cancer Institute
Hormone test helps predict success in IVF
Given how much patients invest in in vitro fertilization (IVF), both financially and emotionally, tools to inform couples about what they might expect during their treatment can be welcome. A study by researchers at Brown University and Women & Infants Hospital shows that as the IVF cycle is beginning, a blood test for levels of a hormone called AMH, or antimullerian hormone, can help predict the number of eggs that will be harvested. "Clinicians can measure AMH before or during ovarian stimulation to counsel couples about their likelihood of success," said Geralyn Lambert-Messerlian, professor of pathology and laboratory medicine in the Warren Alpert Medical School of Brown University and a researcher in the Division of Medical Screening and Special Testing at Women & Infants Hospital. She co-authored a paper that will be published in an upcoming issue of the American Journal of Obstetrics and Gynecology. It appeared in advance online last month.
Lead author Andrew Blazar, a physician at Women & Infants' Division of Reproductive Endocrinology and Infertility, said the finding could be useful for adjusting IVF preparations on the fly, for instance by adjusting how much follicle stimulation hormone women are receiving in the week or so before eggs are extracted for fertilization.
"The main thrust of the paper is that you can do this test even after you have begun the preparations for initiating an IVF cycle, so it allows you to modify your treatment, at least in theory, so that your probability of success would be improved," said Blazar, who is also a clinical associate professor of obstetrics and gynecology at the Alpert Medical School. "Though not proven, this approach seems like a logical way to use this new information.
"What I'm hoping is that eventually it will turn out that you can now do this test in the same cycle and not wait until you have to do another cycle, which would be a considerable advantage to your patient," he said.
The research was partly supported by Beckman Coulter Inc., which makes the assay the team used for measuring AMH in blood samples.
AMH predicts eggs, pregnancy
AMH is made by small follicles in the ovary and helps regulate their growth. AMH levels in the blood are an indicator of how many follicles a woman has at the time of the hormone measurement.
In their research, Blazar and Lambert-Messerlian's team measured AMH levels in 190 IVF patients, ages 22 to 44, both at the beginning and end of their preparatory course of follicle stimulation hormone treatment. They counted the eggs that were eventually harvested and then performed blood tests and later an ultrasound to confirm pregnancy.
The researchers found that women with low AMH levels in the first test (less than one nanogram per milliliter) on average yielded only about six eggs, while women who had more than three times as much AMH provided about 20 eggs on average.
In this study, AMH similarly predicted whether pregnancy became established. Only about a quarter of women with less than one nanogram of AMH were pregnant five to six weeks after the IVF procedure. Among women with more than three nanograms, three in five were pregnant at that stage.
Lambert-Messerlian cautioned that most other studies have not found an association of AMH levels and pregnancy success though delivery.
Blazar noted that because some women with low AMH levels were still able to establish pregnancies, he wouldn't recommend that all such women necessarily forgo an upcoming IVF procedure.
**Source: Brown University
Lead author Andrew Blazar, a physician at Women & Infants' Division of Reproductive Endocrinology and Infertility, said the finding could be useful for adjusting IVF preparations on the fly, for instance by adjusting how much follicle stimulation hormone women are receiving in the week or so before eggs are extracted for fertilization.
"The main thrust of the paper is that you can do this test even after you have begun the preparations for initiating an IVF cycle, so it allows you to modify your treatment, at least in theory, so that your probability of success would be improved," said Blazar, who is also a clinical associate professor of obstetrics and gynecology at the Alpert Medical School. "Though not proven, this approach seems like a logical way to use this new information.
"What I'm hoping is that eventually it will turn out that you can now do this test in the same cycle and not wait until you have to do another cycle, which would be a considerable advantage to your patient," he said.
The research was partly supported by Beckman Coulter Inc., which makes the assay the team used for measuring AMH in blood samples.
AMH predicts eggs, pregnancy
AMH is made by small follicles in the ovary and helps regulate their growth. AMH levels in the blood are an indicator of how many follicles a woman has at the time of the hormone measurement.
In their research, Blazar and Lambert-Messerlian's team measured AMH levels in 190 IVF patients, ages 22 to 44, both at the beginning and end of their preparatory course of follicle stimulation hormone treatment. They counted the eggs that were eventually harvested and then performed blood tests and later an ultrasound to confirm pregnancy.
The researchers found that women with low AMH levels in the first test (less than one nanogram per milliliter) on average yielded only about six eggs, while women who had more than three times as much AMH provided about 20 eggs on average.
In this study, AMH similarly predicted whether pregnancy became established. Only about a quarter of women with less than one nanogram of AMH were pregnant five to six weeks after the IVF procedure. Among women with more than three nanograms, three in five were pregnant at that stage.
Lambert-Messerlian cautioned that most other studies have not found an association of AMH levels and pregnancy success though delivery.
Blazar noted that because some women with low AMH levels were still able to establish pregnancies, he wouldn't recommend that all such women necessarily forgo an upcoming IVF procedure.
**Source: Brown University
Subscribe to:
Comments (Atom)
CONTACTO · Aviso Legal · Política de Privacidad · Política de Cookies
Copyright © Noticia de Salud