A University of Colorado at Boulder research team has identified a type of skeletal muscle stem cell that contributes to the repair of damaged muscles in mice, which could have important implications in the treatment of injured, diseased or aging muscle tissue in humans, including the ravages of muscular dystrophy.
The newly identified stem cells are found within populations of satellite cells located between muscle fibers and the surrounding connective tissue that are responsible for the repair and maintenance of skeletal muscles, said Professor Bradley Olwin of CU-Boulder's molecular, cellular and developmental biology department.
When muscle fibers are stressed or traumatized, satellite cells divide to make more specialized muscle cells and repair the muscle, said Olwin. The stem cell population identified by the CU team within the satellite cells -- dubbed "satellite-SP" cells -- were shown to renew the satellite cell population after injection into injured muscle cells, contributing to recovery of muscle tissue in the laboratory mice.
"This research shows how satellite cells can maintain their populations within injured tissues," said Olwin. "The hope is this new method will allow us to repair damaged or diseased skeletal muscle tissue."
A paper on the subject was published in the March 5 issue of the journal Cell Stem Cell. Co-authors on the study included the MCD biology department's Kathleen Tanaka, John Hall and Andrew Troy, as well as Dawn Cornelison from the University of Missouri and Susan Majka from the University of Colorado Denver.
Stem cells are distinguished by their ability to renew themselves through cell division and differentiate into specialized cell types. In healthy skeletal muscle tissue, the population of satellite cells is constantly maintained, leading the CU-Boulder team to believe that at least some of the satellite cell population in the mouse study included stem cells.
For the study, the researchers injected 2,500 satellite-SP cells into a population of satellite cells within injured mouse muscle tissue. They found that 75 percent of the satellite cells that reproduced were derived from the previous satellite-SP cells injected into the tissue. The results demonstrated the injected satellite-SP cells were renewing the satellite cell pool, Olwin said.
"The key point here is we are not just repairing the tissue," said Olwin. "We injected a permanent, self-renewing population of stem cells. One advantage of using this technology is that we can use a relatively small number of stem cells and do the job with a small number of injections -- in this case, only one."
The research has implications for a number of human diseases, he said. In muscular dystrophy, the loss of a protein called dystrophin causes the muscle to literally tear itself apart, a process that cannot be repaired without cell-based intervention. Although injected cells will repair the muscle fibers, maintaining the muscle fibers requires additional cell injections.
The research was funded in part by the National Institutes of Health and the Muscular Dystrophy Association. Olwin is now collaborating with a group at the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle to extend the research.
Source: Bradley Olwin
University of Colorado at Boulder
среда, 12 октября 2011 г.
воскресенье, 9 октября 2011 г.
Deadly Fungus Decimating Bat Populations Cannot Be Controlled By Culling
Culling will not stop the spread of a deadly fungus that is threatening to wipe out hibernating bats in North America, according to a new mathematical model.
White-nose syndrome, which is estimated to have killed over a million bats in a three year period, is probably caused by a newly discovered cold-adapted fungus, Geomyces destructans. The new model examines how WNS is passed from bat to bat and concludes that culling would not work because of the complexity of bat life history and because the fungal pathogen occurs in the caves and mines where the bats live.
"Because the disease is highly virulent, our model results support the hypothesis that transmission occurs in all contact areas," write the paper's authors, Tom Hallam and Gary McCracken, both of the University of Tennessee. "Our simulations indicated culling will not control WNS in bats primarily because contact rates are high among colonial bats, contact occurs in multiple arenas, and periodic movement between arenas occurs."
Ground work on the model was initiated in a 2009 modeling workshop on white-nose syndrome held at the National Institute for Mathematical and Biological Synthesis (NIMBioS) in Knoxville, Tennessee. At the interdisciplinary workshop, experts in the fields of bat physiology, fungal ecology, ecotoxicology, and epidemiology discussed ways in which mathematical modeling could be applied to predict and control the spread of WNS.
"NIMBioS' support for the workshop that initiated this project was crucial in helping formulate models that could be useful in looking at white-nose syndrome," Hallam said.
Culling of bats in areas where the disease is present is one of several options that have been considered by state and federal agencies as a way to control the disease. However, a review of management options for controlling WNS in the paper indicates that culling is ineffective for disease control in wild animals and in some cases, can exacerbate the spread.
White-nose syndrome first appeared in a cave in upstate New York in 2006, and has since spread to 14 states and as far north as Canada. Regional extinctions of the most common bat species, the little brown bat, are predicted within two decades due to WNS.
Eating up to two-thirds of their body weight in insects every night, bats help suppress insect populations ultimately reducing crop damage and the quantities of insecticides used on crops. Bats also play an important ecological role in plant pollination and seed dissemination.
Citations: Hallam TG, McCracken GF. 2011. Management of the panzootic white-nose syndrome through culling of bats. Conservation Biology 25(1): 189-194.
Source:
Catherine Crawley
National Institute for Mathematical and Biological Synthesis (NIMBioS)
White-nose syndrome, which is estimated to have killed over a million bats in a three year period, is probably caused by a newly discovered cold-adapted fungus, Geomyces destructans. The new model examines how WNS is passed from bat to bat and concludes that culling would not work because of the complexity of bat life history and because the fungal pathogen occurs in the caves and mines where the bats live.
"Because the disease is highly virulent, our model results support the hypothesis that transmission occurs in all contact areas," write the paper's authors, Tom Hallam and Gary McCracken, both of the University of Tennessee. "Our simulations indicated culling will not control WNS in bats primarily because contact rates are high among colonial bats, contact occurs in multiple arenas, and periodic movement between arenas occurs."
Ground work on the model was initiated in a 2009 modeling workshop on white-nose syndrome held at the National Institute for Mathematical and Biological Synthesis (NIMBioS) in Knoxville, Tennessee. At the interdisciplinary workshop, experts in the fields of bat physiology, fungal ecology, ecotoxicology, and epidemiology discussed ways in which mathematical modeling could be applied to predict and control the spread of WNS.
"NIMBioS' support for the workshop that initiated this project was crucial in helping formulate models that could be useful in looking at white-nose syndrome," Hallam said.
Culling of bats in areas where the disease is present is one of several options that have been considered by state and federal agencies as a way to control the disease. However, a review of management options for controlling WNS in the paper indicates that culling is ineffective for disease control in wild animals and in some cases, can exacerbate the spread.
White-nose syndrome first appeared in a cave in upstate New York in 2006, and has since spread to 14 states and as far north as Canada. Regional extinctions of the most common bat species, the little brown bat, are predicted within two decades due to WNS.
Eating up to two-thirds of their body weight in insects every night, bats help suppress insect populations ultimately reducing crop damage and the quantities of insecticides used on crops. Bats also play an important ecological role in plant pollination and seed dissemination.
Citations: Hallam TG, McCracken GF. 2011. Management of the panzootic white-nose syndrome through culling of bats. Conservation Biology 25(1): 189-194.
Source:
Catherine Crawley
National Institute for Mathematical and Biological Synthesis (NIMBioS)
четверг, 6 октября 2011 г.
New $1.16 Million Study Investigates How Dietary Iron Is Used By Cells
A four-year study on iron metabolism within cells, an essential process that impacts both iron deficiency and iron toxicity, conditions responsible for a multitude of human diseases, is underway at the University at Buffalo funded by a $1.16 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Daniel Kosman, Ph.D., professor of biochemistry in the UB School of Medicine and Biomedical Sciences, is lead researcher on the study.
"The concern about how iron is managed in our cells has never been more acute," said Kosman. "The reasons for this are three-fold. First is the endemic problem of iron deficiency that the World Health Organization estimates afflicts 80 percent of the world's population, or more than 5 billion people.
"Iron deficiency is not confined to developing nations. In the U.S., 5 percent of newborns and 7 percent of new mothers have clinical symptoms of iron deficiency. Reducing the incidence of this nutritional deficit is one of the objectives of the U.S. Department of Health and Human Services' Healthy People 2010 program.
"Second is the broad recognition that the 'corrosive chemistry' associated with iron and oxygen interactions is a major factor in a multitude of human diseases."
Too much iron in tissues, called iron-loading, is thought to increase the risk of tumor development, infection, cardiomyopathy, joint disorders and several endocrine and neurodegenerative disorders.
"And third, we now have an increasingly sophisticated knowledge and understanding of iron metabolic pathways, the proteins involved in these pathways and how these pathways are regulated in all organisms, making this issue ripe for investigation," he said.
Kosman proposes that a general mechanism of cellular iron metabolism requires that iron-handling proteins involved in sequential steps in the pathway must be "architecturally arranged" contiguously in the cell's membranes, at the interfaces between membranes and soluble compartments or within soluble compartments.
The researchers will test this form-function model of ionic iron metabolism by focusing on three steps critical to maintaining the proper balance of iron in cells: 1) the reduction of ferric to ferrous iron and the subsequent transport of ferrous iron into a cell; 2) the "hand-off" of this ferrous iron from a membrane protein to iron chaperones in the cell's cytoplasm; and 3) the utilization of this ionic iron for the activation of essential iron-containing enzymes.
"These three components of cellular iron metabolism are relatively under-investigated," said Kosman, "yet they represent the essence of cell iron metabolism in all organisms."
Understanding the intermediary metabolism of iron is one of the primary objectives of a program announcement from NIH titled "Metals In Medicine," he noted. This announcement encourages studies that lead to the "identification and characterization of the macromolecular players and vesicular compartments involved in metal ion homeostasis and metal trafficking."
Arvinder Singh, Ph.D., a post-doctoral research associate in Kosman's lab; and William E. Wiltsie, a doctoral candidate in biochemistry, also will be involved in the research.
The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The School of Medicine and Biomedical Sciences is one of five schools that constitute UB's Academic Health Center. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs.
Contact: Lois Baker
University at Buffalo
Daniel Kosman, Ph.D., professor of biochemistry in the UB School of Medicine and Biomedical Sciences, is lead researcher on the study.
"The concern about how iron is managed in our cells has never been more acute," said Kosman. "The reasons for this are three-fold. First is the endemic problem of iron deficiency that the World Health Organization estimates afflicts 80 percent of the world's population, or more than 5 billion people.
"Iron deficiency is not confined to developing nations. In the U.S., 5 percent of newborns and 7 percent of new mothers have clinical symptoms of iron deficiency. Reducing the incidence of this nutritional deficit is one of the objectives of the U.S. Department of Health and Human Services' Healthy People 2010 program.
"Second is the broad recognition that the 'corrosive chemistry' associated with iron and oxygen interactions is a major factor in a multitude of human diseases."
Too much iron in tissues, called iron-loading, is thought to increase the risk of tumor development, infection, cardiomyopathy, joint disorders and several endocrine and neurodegenerative disorders.
"And third, we now have an increasingly sophisticated knowledge and understanding of iron metabolic pathways, the proteins involved in these pathways and how these pathways are regulated in all organisms, making this issue ripe for investigation," he said.
Kosman proposes that a general mechanism of cellular iron metabolism requires that iron-handling proteins involved in sequential steps in the pathway must be "architecturally arranged" contiguously in the cell's membranes, at the interfaces between membranes and soluble compartments or within soluble compartments.
The researchers will test this form-function model of ionic iron metabolism by focusing on three steps critical to maintaining the proper balance of iron in cells: 1) the reduction of ferric to ferrous iron and the subsequent transport of ferrous iron into a cell; 2) the "hand-off" of this ferrous iron from a membrane protein to iron chaperones in the cell's cytoplasm; and 3) the utilization of this ionic iron for the activation of essential iron-containing enzymes.
"These three components of cellular iron metabolism are relatively under-investigated," said Kosman, "yet they represent the essence of cell iron metabolism in all organisms."
Understanding the intermediary metabolism of iron is one of the primary objectives of a program announcement from NIH titled "Metals In Medicine," he noted. This announcement encourages studies that lead to the "identification and characterization of the macromolecular players and vesicular compartments involved in metal ion homeostasis and metal trafficking."
Arvinder Singh, Ph.D., a post-doctoral research associate in Kosman's lab; and William E. Wiltsie, a doctoral candidate in biochemistry, also will be involved in the research.
The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The School of Medicine and Biomedical Sciences is one of five schools that constitute UB's Academic Health Center. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs.
Contact: Lois Baker
University at Buffalo
понедельник, 3 октября 2011 г.
Minor Genetic Differences Between Individuals Change The Effect Of A Common Medication, Study Shows
Medicine has moved a little bit closer to the era of tailor-made treatments, based on the unique genetic profiles of individual patients, according to recent research conducted by Dr Rima Rozen of the Research Institute of the McGill University Health Centre (RI MUHC) at the Montreal Children's Hospital and McGill University. Her study, published June 18 in the journal Pharmacogenetics and Genomics, shows how minor genetic differences between individuals alter the way a common drug affects the body.
Rozen has measured the impact of Methotrexate -- a drug that inhibits the metabolism of folate -- on mice with an altered MTHFR gene, which is a gene crucial for folate metabolism. The results were striking: after treatment with Methotrexate, mice with the altered gene had approximately 20 per cent less hemoglobin and red blood cells than their counterparts with non-altered genes. The altered mice also showed increased susceptibility to liver and kidney damage following treatment.
"We know that these results are applicable to humans because a parallel mutation in the human MTHFR gene affects human folate metabolism similarly. The results demonstrate that medication affects subjects differently according to individual genetic traits," Dr. Rozen explained. "And tests exist to detect this mutation." Genetic testing would allow physicians the modify treatment based on each patient's personal genetic makeup, limiting potential side effects.
In earlier studies, Rozen's laboratory cloned the MTHFR gene and identified the common variant which interferes in folate metabolism in human populations. Between 10 and 15 per cent of the total caucasian population have two copies of the variant in MTHFR. Folate, a form of water-soluble Vitamin B2, is essential to the production of red blood cells and provides protection against spina bifida, other birth defects, and heart disease. Patients with cancer or auto-immune diseases are often treated with medications that affect folate metabolism, but physicians are not trained to verify how patients naturally metabolize folate, even though this could be an important factor in effective treatment.
"This is a first step towards personalized medicine that is based not only on symptoms but also on the patient's own genetic 'baggage,'" Rozen said. "This trend definitely represents the medicine of the future."
This release is available in French.
Dr. Rima Rozen is a Scientist in the Medical Genetics and Genomics Axis of the RI MUHC at the Montreal Children's Hospital. At McGill University, she holds the positions of Associate Vice-Principal (Research and International Relations) and Professor in the Human Genetics, Pediatrics and Biology Departments.
This study was funded by the Canadian Institutes of Health Research (CIHR) and the U.S. National Institutes of Health (NIH). Students working on Dr. Rozen's study also received scholarships, such as a Turkish Higher Education Council-Hacettepe University Hospital scholarship, a Cole Foundation Award, and a Studentship Award from the Montreal Children's Hospital Research Institute.
The Montreal Children's Hospital (MCH) is the pediatric teaching hospital of the McGill University Health Centre (MUHC) and is affiliated with McGill University. The MCH is a leader in providing a broad spectrum of highly specialized care to newborns, children, and adolescents from across Quebec. Our areas of medical expertise include programs in brain development/behaviour, cardiovascular sciences, critical care, medical genetics and oncology, tertiary medical and surgical services, and trauma care. Fully bilingual, the hospital also promotes multiculturalism and serves an increasingly diverse community in more than 50 languages. The Montreal Children's Hospital sets itself apart with its team approach to innovative patient care. Our health professionals and staff are dedicated to ensuring children and their families receive exceptional health care in a friendly and supportive environment.
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santГ© du QuГ©bec.
For further details visit: muhc.ca/research.
Source: Isabelle Kling
McGill University Health Centre
Rozen has measured the impact of Methotrexate -- a drug that inhibits the metabolism of folate -- on mice with an altered MTHFR gene, which is a gene crucial for folate metabolism. The results were striking: after treatment with Methotrexate, mice with the altered gene had approximately 20 per cent less hemoglobin and red blood cells than their counterparts with non-altered genes. The altered mice also showed increased susceptibility to liver and kidney damage following treatment.
"We know that these results are applicable to humans because a parallel mutation in the human MTHFR gene affects human folate metabolism similarly. The results demonstrate that medication affects subjects differently according to individual genetic traits," Dr. Rozen explained. "And tests exist to detect this mutation." Genetic testing would allow physicians the modify treatment based on each patient's personal genetic makeup, limiting potential side effects.
In earlier studies, Rozen's laboratory cloned the MTHFR gene and identified the common variant which interferes in folate metabolism in human populations. Between 10 and 15 per cent of the total caucasian population have two copies of the variant in MTHFR. Folate, a form of water-soluble Vitamin B2, is essential to the production of red blood cells and provides protection against spina bifida, other birth defects, and heart disease. Patients with cancer or auto-immune diseases are often treated with medications that affect folate metabolism, but physicians are not trained to verify how patients naturally metabolize folate, even though this could be an important factor in effective treatment.
"This is a first step towards personalized medicine that is based not only on symptoms but also on the patient's own genetic 'baggage,'" Rozen said. "This trend definitely represents the medicine of the future."
This release is available in French.
Dr. Rima Rozen is a Scientist in the Medical Genetics and Genomics Axis of the RI MUHC at the Montreal Children's Hospital. At McGill University, she holds the positions of Associate Vice-Principal (Research and International Relations) and Professor in the Human Genetics, Pediatrics and Biology Departments.
This study was funded by the Canadian Institutes of Health Research (CIHR) and the U.S. National Institutes of Health (NIH). Students working on Dr. Rozen's study also received scholarships, such as a Turkish Higher Education Council-Hacettepe University Hospital scholarship, a Cole Foundation Award, and a Studentship Award from the Montreal Children's Hospital Research Institute.
The Montreal Children's Hospital (MCH) is the pediatric teaching hospital of the McGill University Health Centre (MUHC) and is affiliated with McGill University. The MCH is a leader in providing a broad spectrum of highly specialized care to newborns, children, and adolescents from across Quebec. Our areas of medical expertise include programs in brain development/behaviour, cardiovascular sciences, critical care, medical genetics and oncology, tertiary medical and surgical services, and trauma care. Fully bilingual, the hospital also promotes multiculturalism and serves an increasingly diverse community in more than 50 languages. The Montreal Children's Hospital sets itself apart with its team approach to innovative patient care. Our health professionals and staff are dedicated to ensuring children and their families receive exceptional health care in a friendly and supportive environment.
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santГ© du QuГ©bec.
For further details visit: muhc.ca/research.
Source: Isabelle Kling
McGill University Health Centre
пятница, 30 сентября 2011 г.
First Compound That Specifically Kills Cancer Stem Cells Found
The cancer stem cells that drive tumor growth and resist chemotherapies and radiation treatments that kill other cancer cells aren't invincible after all. Researchers reporting online on August 13th in the journal Cell, a Cell Press publication, have discovered the first compound that targets those cancer stem cells directly.
"It wasn't clear it would be possible to find compounds that selectively kill cancer stem cells," said Piyush Gupta of the Massachusetts Institute of Technology (MIT) and the Broad Institute. "We've shown it can be done."
The team including MIT's Robert Weinberg and the Broad Institute's Eric Lander developed a new high-throughput screening method that makes it possible for the first time to systematically look for agents that kill cancer stem cells. That ability had previously eluded researchers due to the rarity of those cells within tumor cell populations and their relative instability in laboratory culture.
In the new study, the researchers manipulated cultured breast cancer cells to greatly enrich for those with the stem-like properties, including increased resistance to standard cancer drugs. They then screened a library of 16,000 natural and commercial chemical compounds for their ability to kill those stem-like cells and not other cancer cells. That screen turned up 32 contenders.
The researchers narrowed that list down to a handful of chemicals that they could readily get in sufficient quantities for further testing on normal cancer stem cells. Of those, one called salinomycin was the clear winner.
Salinomycin reduced the proportion of breast cancer stem cells by more than 100-fold compared to a commonly used chemotherapeutic drug for breast cancer called paclitaxel (aka Taxol™). Salinomycin-treated cells were less able than paclitaxel-treated ones to seed tumors when injected into mice, they report. Salinomycin treatment also slowed the growth of the animals' tumors.
Studies of salinomycin-treated human breast tumors also showed a loss in the activity of genes associated with cancer stem cells.
Exactly how salinomycin's works against cancer stem cells, the researchers don't yet know. As its name suggests, the chemical has antibiotic properties that likely aren't relevant to its newfound cancer stem cell-killing ability. It also disturbs cells' potassium balance.
It remains unclear whether salinomycin itself might find its way to the clinic, Gupta said, since many pharmaceutical steps are involved in the drug discovery process. Nevertheless, the chemical does serve as an immediate tool for manipulating cancer stem cell numbers and observing the effects on cancer's spread and progression.
The findings also highlight a new avenue for the development of cancer therapies, the researchers say.
" To date, rational cancer therapies have been designed to target specific genetic alterations present within tumors," they wrote. "The findings here indicate that a second approach may also prove useful - namely, searching for agents that target specific states of cancer cell differentiation. Accordingly, future therapies could offer greater possibilities for individualized treatment by considering both the genetic alterations and differentiation states present within the cancer cells of a tumor at the time of diagnosis."
They envision a future in which combination therapies might couple more traditional cancer drugs with those designed to hit the cancer stem cells that would otherwise get left behind.
The researchers include Piyush B. Gupta, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Tamer T. Onder, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA; Guozhi Jiang, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Kai Tao, Tufts Medical Center, Boston, MA; Charlotte Kuperwasser, Tufts Medical Center, Boston, MA; Robert A. Weinberg, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, MIT Ludwig Center for Molecular Oncology, Cambridge, MA; and Eric S. Lander, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA, Harvard Medical School, Boston, MA.
Source:
Cathleen Genova
Cell Press
View drug information on Taxol.
"It wasn't clear it would be possible to find compounds that selectively kill cancer stem cells," said Piyush Gupta of the Massachusetts Institute of Technology (MIT) and the Broad Institute. "We've shown it can be done."
The team including MIT's Robert Weinberg and the Broad Institute's Eric Lander developed a new high-throughput screening method that makes it possible for the first time to systematically look for agents that kill cancer stem cells. That ability had previously eluded researchers due to the rarity of those cells within tumor cell populations and their relative instability in laboratory culture.
In the new study, the researchers manipulated cultured breast cancer cells to greatly enrich for those with the stem-like properties, including increased resistance to standard cancer drugs. They then screened a library of 16,000 natural and commercial chemical compounds for their ability to kill those stem-like cells and not other cancer cells. That screen turned up 32 contenders.
The researchers narrowed that list down to a handful of chemicals that they could readily get in sufficient quantities for further testing on normal cancer stem cells. Of those, one called salinomycin was the clear winner.
Salinomycin reduced the proportion of breast cancer stem cells by more than 100-fold compared to a commonly used chemotherapeutic drug for breast cancer called paclitaxel (aka Taxol™). Salinomycin-treated cells were less able than paclitaxel-treated ones to seed tumors when injected into mice, they report. Salinomycin treatment also slowed the growth of the animals' tumors.
Studies of salinomycin-treated human breast tumors also showed a loss in the activity of genes associated with cancer stem cells.
Exactly how salinomycin's works against cancer stem cells, the researchers don't yet know. As its name suggests, the chemical has antibiotic properties that likely aren't relevant to its newfound cancer stem cell-killing ability. It also disturbs cells' potassium balance.
It remains unclear whether salinomycin itself might find its way to the clinic, Gupta said, since many pharmaceutical steps are involved in the drug discovery process. Nevertheless, the chemical does serve as an immediate tool for manipulating cancer stem cell numbers and observing the effects on cancer's spread and progression.
The findings also highlight a new avenue for the development of cancer therapies, the researchers say.
" To date, rational cancer therapies have been designed to target specific genetic alterations present within tumors," they wrote. "The findings here indicate that a second approach may also prove useful - namely, searching for agents that target specific states of cancer cell differentiation. Accordingly, future therapies could offer greater possibilities for individualized treatment by considering both the genetic alterations and differentiation states present within the cancer cells of a tumor at the time of diagnosis."
They envision a future in which combination therapies might couple more traditional cancer drugs with those designed to hit the cancer stem cells that would otherwise get left behind.
The researchers include Piyush B. Gupta, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Tamer T. Onder, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA; Guozhi Jiang, Massachusetts Institute of Technology, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA; Kai Tao, Tufts Medical Center, Boston, MA; Charlotte Kuperwasser, Tufts Medical Center, Boston, MA; Robert A. Weinberg, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, MIT Ludwig Center for Molecular Oncology, Cambridge, MA; and Eric S. Lander, Massachusetts Institute of Technology, Cambridge, MA, Whitehead Institute for Biomedical Research, Cambridge, MA, Broad Institute of MIT and Harvard, Cambridge, MA, Harvard Medical School, Boston, MA.
Source:
Cathleen Genova
Cell Press
View drug information on Taxol.
вторник, 27 сентября 2011 г.
Paradoxical Protein Might Prevent Cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
Molecular signal pathways that stimulate the division of stem cells are generally the same as those active in tumour growth. This limits the possibility of treating cancer as the drugs that kill cancer cells also often adversely affect the body's healthy cells, particularly stem cells. A new study from Karolinska Institutet, conducted in collaboration with an international team of scientists led by Professor Jonas FrisГ©n, is now focusing on an exception that can make it possible to treat a form of colon cancer.
The results concern a group of signal proteins called EphB receptors. These proteins stimulate the division of stem cells in the intestine and can contribute to the formation of adenoma (polyps), which are known to carry a risk of cancer. Paradoxically, these same proteins also prevent the adenoma from growing unchecked and becoming cancerous.
The new results show that EphB controls two separate signal pathways, one of which stimulates cell division and the other that curbs the cells' ability to become cancerous. Using this knowledge, the scientists have identified a drug substance called imatinib, which can inhibit the first signal pathway without affecting the other, protective, pathway.
"Imatinib or a similar substance could possibly be used for preventing the development of cancer in people who are in the risk zone for colon cancer instead of intestinal resection," says Maria Genander, one of the researchers involved in the study.
Imatinib has so far proved to inhibit cell division in intestinal tumour cells in vitro and in mice. The substance is a component of the drug Glivec, which is used, amongst other things, in the treatment of certain forms of leukaemia. Whether it can also be used against adenoma and colon cancer in humans remains to be seen. The company that manufactures the drug did not fund the study.
Publication:
Maria Genander, Michael M. Halford, Nan-Jie Xu, Malin Eriksson, Zuoren Yu, Zhaozhu Qiu, Anna Martling, Gedas Greicius, Sonal Thakar, Timothy Catchpole, Michael J. Chumley, Sofia Zdunek, Chenguang Wang, Torbjörn Holm, Stephen P. Goff, Sven Pettersson, Richard G. Pestell, Mark Henkemeyer & Jonas Frisén
Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression
Cell, print issue, 13 Nov 2009
Source: Press Officer Katarina Sternudd
Karolinska Institutet
Molecular signal pathways that stimulate the division of stem cells are generally the same as those active in tumour growth. This limits the possibility of treating cancer as the drugs that kill cancer cells also often adversely affect the body's healthy cells, particularly stem cells. A new study from Karolinska Institutet, conducted in collaboration with an international team of scientists led by Professor Jonas FrisГ©n, is now focusing on an exception that can make it possible to treat a form of colon cancer.
The results concern a group of signal proteins called EphB receptors. These proteins stimulate the division of stem cells in the intestine and can contribute to the formation of adenoma (polyps), which are known to carry a risk of cancer. Paradoxically, these same proteins also prevent the adenoma from growing unchecked and becoming cancerous.
The new results show that EphB controls two separate signal pathways, one of which stimulates cell division and the other that curbs the cells' ability to become cancerous. Using this knowledge, the scientists have identified a drug substance called imatinib, which can inhibit the first signal pathway without affecting the other, protective, pathway.
"Imatinib or a similar substance could possibly be used for preventing the development of cancer in people who are in the risk zone for colon cancer instead of intestinal resection," says Maria Genander, one of the researchers involved in the study.
Imatinib has so far proved to inhibit cell division in intestinal tumour cells in vitro and in mice. The substance is a component of the drug Glivec, which is used, amongst other things, in the treatment of certain forms of leukaemia. Whether it can also be used against adenoma and colon cancer in humans remains to be seen. The company that manufactures the drug did not fund the study.
Publication:
Maria Genander, Michael M. Halford, Nan-Jie Xu, Malin Eriksson, Zuoren Yu, Zhaozhu Qiu, Anna Martling, Gedas Greicius, Sonal Thakar, Timothy Catchpole, Michael J. Chumley, Sofia Zdunek, Chenguang Wang, Torbjörn Holm, Stephen P. Goff, Sven Pettersson, Richard G. Pestell, Mark Henkemeyer & Jonas Frisén
Dissociation of EphB2 Signaling Pathways Mediating Progenitor Cell Proliferation and Tumor Suppression
Cell, print issue, 13 Nov 2009
Source: Press Officer Katarina Sternudd
Karolinska Institutet
суббота, 24 сентября 2011 г.
Anti-inflammatory Effects Of Pomegranate In Rabbits: A Potential Treatment In Humans?
Oral ingestion of pomegranate extract reduces the production of chemicals that cause inflammation suggests a study published in BioMed Central's open access Journal of Inflammation. The findings indicate that pomegranate extract may provide humans with relief of chronic inflammatory conditions.
The group from the Department of Medicine of Case Western Reserve University, Cleveland Ohio, led by Tariq Haqqi, showed that blood samples collected from rabbits fed pomegranate extract inhibited inflammation.
Pomegranate extract is already used as a treatment in alternative medicine for inflammatory conditions, such as arthritis. Although pomegranate extract has antioxidant and anti-inflammatory actions in experiments on isolated tissues, it is not known whether ingestion of it can produce the same anti-inflammatory effects in living systems, either because the active compounds are not absorbed from the gut or because the levels of these compounds in the blood are not high enough.
Pomegranate extract, the equivalent of 175mls of pomegranate juice, was given to rabbits orally. The levels of antioxidants were measured in blood samples obtained after drinking the pomegranate extract and compared to blood samples collected before ingestion of pomegranate extract.
Plasma collected from rabbits following ingestion of pomegranate extract contained significantly higher levels of antioxidants than samples collected before ingestion of pomegranate extract; the extract also significantly reduced the activity of proteins that cause inflammation, specifically cyclooxygenase-2. It also reduced the production of pro-inflammatory compounds produced by cells isolated from cartilage.
The results of this study indicate the beneficial effects of pomegranate extract when ingested. According to Haqqi "the use of dietary nutrients or drugs based on them as an adjunct in the treatment of chronic inflammatory conditions may benefit patients". He adds that, "Current treatment with anti-inflammatory drugs can have serious side effects following long-term use. Further research is needed, however, especially on the absorption of orally ingested substances into the blood."
Notes:
1. Bioavailable Metabolites of Pomegranate (Punica granatum L) Fruit Extract Preferentially Inhibit COX2 Activity ex vivo and IL-1b-induced PGE2 Production in Articular Cartilage Chondrocytes in vitro.
Meenakshi Shukla, Kalpana Gupta, Zafar Rasheed, Khursheed A Khan and Tariq M Haqqi
Journal of Inflammation (in press)
Article available at the journal website: journal-inflammation/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Tariq Haqqi is now with the Department of Pathology, Microbiology & Immunology, School of Medicine, at the University of South Carolina, Columbia.
3. Journal of Inflammation is an Open Access, peer-reviewed online journal on all aspects of research into inflammation.
4. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
The group from the Department of Medicine of Case Western Reserve University, Cleveland Ohio, led by Tariq Haqqi, showed that blood samples collected from rabbits fed pomegranate extract inhibited inflammation.
Pomegranate extract is already used as a treatment in alternative medicine for inflammatory conditions, such as arthritis. Although pomegranate extract has antioxidant and anti-inflammatory actions in experiments on isolated tissues, it is not known whether ingestion of it can produce the same anti-inflammatory effects in living systems, either because the active compounds are not absorbed from the gut or because the levels of these compounds in the blood are not high enough.
Pomegranate extract, the equivalent of 175mls of pomegranate juice, was given to rabbits orally. The levels of antioxidants were measured in blood samples obtained after drinking the pomegranate extract and compared to blood samples collected before ingestion of pomegranate extract.
Plasma collected from rabbits following ingestion of pomegranate extract contained significantly higher levels of antioxidants than samples collected before ingestion of pomegranate extract; the extract also significantly reduced the activity of proteins that cause inflammation, specifically cyclooxygenase-2. It also reduced the production of pro-inflammatory compounds produced by cells isolated from cartilage.
The results of this study indicate the beneficial effects of pomegranate extract when ingested. According to Haqqi "the use of dietary nutrients or drugs based on them as an adjunct in the treatment of chronic inflammatory conditions may benefit patients". He adds that, "Current treatment with anti-inflammatory drugs can have serious side effects following long-term use. Further research is needed, however, especially on the absorption of orally ingested substances into the blood."
Notes:
1. Bioavailable Metabolites of Pomegranate (Punica granatum L) Fruit Extract Preferentially Inhibit COX2 Activity ex vivo and IL-1b-induced PGE2 Production in Articular Cartilage Chondrocytes in vitro.
Meenakshi Shukla, Kalpana Gupta, Zafar Rasheed, Khursheed A Khan and Tariq M Haqqi
Journal of Inflammation (in press)
Article available at the journal website: journal-inflammation/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Tariq Haqqi is now with the Department of Pathology, Microbiology & Immunology, School of Medicine, at the University of South Carolina, Columbia.
3. Journal of Inflammation is an Open Access, peer-reviewed online journal on all aspects of research into inflammation.
4. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
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