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
понедельник, 3 октября 2011 г.
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
среда, 21 сентября 2011 г.
Study Finds That Blood Test Can Gauge Prostate Cancer Risk
New genomics research has found that a simple blood test can determine which men are likely to develop prostate cancer. Researchers at Wake Forest University School of Medicine and colleagues found that five genetic variants previously associated with prostate cancer risk have a strong cumulative effect.
Reporting in New England Journal of Medicine, researchers found that a man with four of the five variants has an increased risk of 400 to 500 percent compared to men with none of the variants. The researchers then added a family history of prostate cancer to the equation for a total of six risk factors. A man with at least five of the six factors had increased risk of more than 900 percent.
The article was published "Online First" today and will be included in the Feb. 28 print issue.
The scientists say each variant was independently associated with prostate cancer risk and that the variants are fairly common in the population. Together, these five variants and a family history accounted for almost half (46 percent) of prostate cancer patients. The study involved analyzing DNA samples from 2,893 men with prostate cancer and 1,781 healthy individuals of similar ages all participants of a prostate cancer study in Sweden.
"This is significant and could affect clinical care," said senior researcher Jianfeng Xu, M.D., Dr. PH., professor of epidemiology and cancer biology. "The information could substantially improve physicians' ability to assess risk and determine the need for more aggressive screening or even a biopsy."
For example, the test may be especially useful in men with a family history of prostate cancer or those who have a marginally elevated PSA (prostate specific antigen), he said.
The study is also important because it is one of the first to illustrate how a combination of several genes can affect risk of disease. Genomics teams nationwide are currently searching for combinations of genes that may underlie common diseases such as cancer, diabetes and asthma.
Currently, age, race and family history are the three factors associated with increased risk of prostate cancer. Family history is believed to account for about 10 percent of prostate cancer cases. Strikingly, researchers estimated that the five variants combined could account for about 40 percent of cases.
"Our finding provides an opportunity to supplement the well-established risk factors by looking at how many of these variants a man has inherited," said Xu. "It may provide a much better weapon to guide clinicians."
Until last year, no specific genetic variants had been consistently identified as markers for prostate cancer risk. Then, advances in technology allowed researchers to take a more systematic approach to looking at the entire genome. Instead of solely studying genes that they suspected were related to disease susceptibility, they could study the entire genome and look for associations.
Through these searches, several research teams identified five genetic locations associated with risk of developing prostate cancer: three on chromosome 8q24, one on chromosome 17q12 and one on 17q24.3.
Each variant alone was associated with moderate risk, but the effect wasn't considered significant enough to justify testing individuals. The current study was the first to evaluate whether there is a cumulative effect from having multiple variants.
"When we considered the variants together we discovered their potential for predicting individual risk," said Xu. "Because of the cumulative effects of these risk variants and family history, for the first time associations found through genome-wide screening appear to be useful in clinical practice."
The researchers said further study is needed to determine how their findings of genetic testing may complement PSA (prostate-specific antigen) testing. The researchers found that the risk associated with the genetic variants is independent of PSA results.
"This suggests that a subset of men deemed to have a low risk of prostate cancer based on their PSA levels may in fact be at significantly elevated risk due to inheriting one or more of the genetic variants," said S. Lilly Zheng, M.D., associate professor of internal medicine and the first author of the paper.
Genetic testing of these five variants will soon be offered at a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory at Wake Forest University School of Medicine.
Co-researchers include senior author Henrik Gronberg, M.D., Ph.D. professor at the Karolinska Institutet in Stockholm, Sweden, and William B. Isaacs, Ph.D, professor at Johns Hopkins Medical Institutions in Baltimore, Md.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
www1.wfubmc
Reporting in New England Journal of Medicine, researchers found that a man with four of the five variants has an increased risk of 400 to 500 percent compared to men with none of the variants. The researchers then added a family history of prostate cancer to the equation for a total of six risk factors. A man with at least five of the six factors had increased risk of more than 900 percent.
The article was published "Online First" today and will be included in the Feb. 28 print issue.
The scientists say each variant was independently associated with prostate cancer risk and that the variants are fairly common in the population. Together, these five variants and a family history accounted for almost half (46 percent) of prostate cancer patients. The study involved analyzing DNA samples from 2,893 men with prostate cancer and 1,781 healthy individuals of similar ages all participants of a prostate cancer study in Sweden.
"This is significant and could affect clinical care," said senior researcher Jianfeng Xu, M.D., Dr. PH., professor of epidemiology and cancer biology. "The information could substantially improve physicians' ability to assess risk and determine the need for more aggressive screening or even a biopsy."
For example, the test may be especially useful in men with a family history of prostate cancer or those who have a marginally elevated PSA (prostate specific antigen), he said.
The study is also important because it is one of the first to illustrate how a combination of several genes can affect risk of disease. Genomics teams nationwide are currently searching for combinations of genes that may underlie common diseases such as cancer, diabetes and asthma.
Currently, age, race and family history are the three factors associated with increased risk of prostate cancer. Family history is believed to account for about 10 percent of prostate cancer cases. Strikingly, researchers estimated that the five variants combined could account for about 40 percent of cases.
"Our finding provides an opportunity to supplement the well-established risk factors by looking at how many of these variants a man has inherited," said Xu. "It may provide a much better weapon to guide clinicians."
Until last year, no specific genetic variants had been consistently identified as markers for prostate cancer risk. Then, advances in technology allowed researchers to take a more systematic approach to looking at the entire genome. Instead of solely studying genes that they suspected were related to disease susceptibility, they could study the entire genome and look for associations.
Through these searches, several research teams identified five genetic locations associated with risk of developing prostate cancer: three on chromosome 8q24, one on chromosome 17q12 and one on 17q24.3.
Each variant alone was associated with moderate risk, but the effect wasn't considered significant enough to justify testing individuals. The current study was the first to evaluate whether there is a cumulative effect from having multiple variants.
"When we considered the variants together we discovered their potential for predicting individual risk," said Xu. "Because of the cumulative effects of these risk variants and family history, for the first time associations found through genome-wide screening appear to be useful in clinical practice."
The researchers said further study is needed to determine how their findings of genetic testing may complement PSA (prostate-specific antigen) testing. The researchers found that the risk associated with the genetic variants is independent of PSA results.
"This suggests that a subset of men deemed to have a low risk of prostate cancer based on their PSA levels may in fact be at significantly elevated risk due to inheriting one or more of the genetic variants," said S. Lilly Zheng, M.D., associate professor of internal medicine and the first author of the paper.
Genetic testing of these five variants will soon be offered at a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory at Wake Forest University School of Medicine.
Co-researchers include senior author Henrik Gronberg, M.D., Ph.D. professor at the Karolinska Institutet in Stockholm, Sweden, and William B. Isaacs, Ph.D, professor at Johns Hopkins Medical Institutions in Baltimore, Md.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
www1.wfubmc
воскресенье, 18 сентября 2011 г.
Strategic Approach To Early-Detection Of Pancreatic Cancer Biomarkers
A cancer scientist from Johns Hopkins has convinced an international group of colleagues to delay their race to find new cancer biomarkers and instead begin a 7,000-hour slog through a compendium of 50,000 scientific articles already published to assemble, decode and analyze the molecules that might herald the furtive presence of pancreatic cancer.
With limited resources available for the exhaustive and expensive testing that needs to be done before any candidate can be considered a bona fide biomarker of clinical value, it's important to take stock of the big picture and strategize, says Akhilesh Pandey, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and founder and director of the Institute of Bioinformatics in Bangalore, India.
Having mined the literature to amass 2,516 potential biomarkers of pancreatic cancer, Pandey and his team published their compendium on April 6 in PLoS Medicine. They systematically cataloged the genes and proteins that are overexpressed in pancreatic cancer patients, then characterized and compared these biomarker candidates in terms of how worthy each is of further study.
More than 200 genes are shortlisted because they were reported in four or more published studies to be overexpressed - meaning that the proteins they make are in higher abundance in people with pancreatic cancer than in people without the disease. This qualifies them as "excellent candidates" for the further studies that are needed to validate them as sensitive and specific biomarkers, note the authors.
Pandey says he was motivated by the fact that even leading cancer investigators had no real idea about how many candidate biomarkers for pancreatic cancer had already been identified, much less how they stacked up against each other in terms of clinical value in detecting early stages of the disease. Such biomarkers are highly valued because they gallop Paul Revere-like through the bloodstream and can signal early warnings of clinically invisible cancers and other diseases.
"Curation and databases are not very sexy concepts," says Pandey. "But we can't keep doing the exciting new discovery stuff and never take the time to catalog our results and share them."
Taking pancreatic cancer biomarkers to prove the value of such a strategic "big picture" approach, Pandey says it could serve as a basis for other disease-marker research.
"For the first time with pancreatic cancer - and potentially with any cancer - we have a handle on the number of candidates already identified and a real sense of how big an army we should send on the mission of further testing them," says Pandey.
Pandey's ultimate goal is to ferret out the best protein biomarker for pancreatic cancer - a molecule that reveals itself in an accessible bodily fluid and therefore can be detected with ease and accuracy - just like the protein biomarker that's made early on by a developing fetus and is exploited by at-home pregnancy tests.
The "gold standard" pancreatic cancer biomarker would possess both high sensitivity and specificity for early diagnosis. Cancer, at its most basic, is an abnormal population of cells that produce specific molecules - biomarkers - which healthy, cancer-free bodies do not. Cancer also tends to be incipient, Pandey says.
The ideal biomarker would allow for easy diagnosis when a cancer is still young, before it spreads to other organs. It could also help clinicians make informed decisions about treatments and better predict of outcomes, Pandey says: "Biomarkers could tell us who should undergo surgery, who should get chemotherapy, and in which people a cancer is likely to recur."
Biomarker discovery is an exploding area of research, Pandey says, yielding ever-increasing amounts of data - more than any one person can hope to keep track of, unless it's all strategically collected for widespread study.
"We want to initiate a trend by proving the importance of collection and cataloging," Pandey says, "which are exercises that many might view as tedious."
The team's next step is to create a searchable Web database that is universally available and free.
Notes:
The research was supported in part by the Lustgarten Foundation for Pancreatic Cancer Research.
Authors of the paper, in addition to Pandey, are H.C. Harsha and Arivusudar Marimuthu of the Institute of Bioinformatics, Bangalore, India; Manipal University, Karnataka, India; and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University. Also, Kumaran Kandasamy, Suresh Mathivanan, and Manoj Kashyap of the Institute of Bioinformatics, Bangalore, India, and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University. Prathibha Ranganathan, Sandhya Rani, Subhashri Ramabadran, Sashikanth Gollapudi, Lavanya Balakrishman, Sutopa B. Dwivedi, Deepthi Telikicherla, Lakshmi Dhevi N. Selvan, and Renu Goel, of the Institute of Bioinformatics, Bangalore, India; Robert Vizza of The Lustgarten Foundation for Pancreatic Cancer Research, New York; Robert J. Mayer and James A. DeCaprio of the Dana-Farber Cancer Institute, Boston; Sudhir Srivastava of the Cancer Biomarkers Research Group, NIH; Samir M. Hanash of the Fred Hutchinson Cancer Research Center, Seattle; and Ralph H. Hruban of the Departments of Pathology and Oncology at the Sol Goldman Pancreatic Cancer Institute, Johns Hopkins.
Source:
Maryalice Yakutchik
Johns Hopkins Medical Institutions
With limited resources available for the exhaustive and expensive testing that needs to be done before any candidate can be considered a bona fide biomarker of clinical value, it's important to take stock of the big picture and strategize, says Akhilesh Pandey, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and founder and director of the Institute of Bioinformatics in Bangalore, India.
Having mined the literature to amass 2,516 potential biomarkers of pancreatic cancer, Pandey and his team published their compendium on April 6 in PLoS Medicine. They systematically cataloged the genes and proteins that are overexpressed in pancreatic cancer patients, then characterized and compared these biomarker candidates in terms of how worthy each is of further study.
More than 200 genes are shortlisted because they were reported in four or more published studies to be overexpressed - meaning that the proteins they make are in higher abundance in people with pancreatic cancer than in people without the disease. This qualifies them as "excellent candidates" for the further studies that are needed to validate them as sensitive and specific biomarkers, note the authors.
Pandey says he was motivated by the fact that even leading cancer investigators had no real idea about how many candidate biomarkers for pancreatic cancer had already been identified, much less how they stacked up against each other in terms of clinical value in detecting early stages of the disease. Such biomarkers are highly valued because they gallop Paul Revere-like through the bloodstream and can signal early warnings of clinically invisible cancers and other diseases.
"Curation and databases are not very sexy concepts," says Pandey. "But we can't keep doing the exciting new discovery stuff and never take the time to catalog our results and share them."
Taking pancreatic cancer biomarkers to prove the value of such a strategic "big picture" approach, Pandey says it could serve as a basis for other disease-marker research.
"For the first time with pancreatic cancer - and potentially with any cancer - we have a handle on the number of candidates already identified and a real sense of how big an army we should send on the mission of further testing them," says Pandey.
Pandey's ultimate goal is to ferret out the best protein biomarker for pancreatic cancer - a molecule that reveals itself in an accessible bodily fluid and therefore can be detected with ease and accuracy - just like the protein biomarker that's made early on by a developing fetus and is exploited by at-home pregnancy tests.
The "gold standard" pancreatic cancer biomarker would possess both high sensitivity and specificity for early diagnosis. Cancer, at its most basic, is an abnormal population of cells that produce specific molecules - biomarkers - which healthy, cancer-free bodies do not. Cancer also tends to be incipient, Pandey says.
The ideal biomarker would allow for easy diagnosis when a cancer is still young, before it spreads to other organs. It could also help clinicians make informed decisions about treatments and better predict of outcomes, Pandey says: "Biomarkers could tell us who should undergo surgery, who should get chemotherapy, and in which people a cancer is likely to recur."
Biomarker discovery is an exploding area of research, Pandey says, yielding ever-increasing amounts of data - more than any one person can hope to keep track of, unless it's all strategically collected for widespread study.
"We want to initiate a trend by proving the importance of collection and cataloging," Pandey says, "which are exercises that many might view as tedious."
The team's next step is to create a searchable Web database that is universally available and free.
Notes:
The research was supported in part by the Lustgarten Foundation for Pancreatic Cancer Research.
Authors of the paper, in addition to Pandey, are H.C. Harsha and Arivusudar Marimuthu of the Institute of Bioinformatics, Bangalore, India; Manipal University, Karnataka, India; and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University. Also, Kumaran Kandasamy, Suresh Mathivanan, and Manoj Kashyap of the Institute of Bioinformatics, Bangalore, India, and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University. Prathibha Ranganathan, Sandhya Rani, Subhashri Ramabadran, Sashikanth Gollapudi, Lavanya Balakrishman, Sutopa B. Dwivedi, Deepthi Telikicherla, Lakshmi Dhevi N. Selvan, and Renu Goel, of the Institute of Bioinformatics, Bangalore, India; Robert Vizza of The Lustgarten Foundation for Pancreatic Cancer Research, New York; Robert J. Mayer and James A. DeCaprio of the Dana-Farber Cancer Institute, Boston; Sudhir Srivastava of the Cancer Biomarkers Research Group, NIH; Samir M. Hanash of the Fred Hutchinson Cancer Research Center, Seattle; and Ralph H. Hruban of the Departments of Pathology and Oncology at the Sol Goldman Pancreatic Cancer Institute, Johns Hopkins.
Source:
Maryalice Yakutchik
Johns Hopkins Medical Institutions
четверг, 15 сентября 2011 г.
Canada's New Government Invests $583 Million In The Next Generation Of Canadian Researchers
Dr. Colin Carrie, Parliamentary Secretary to the Honourable Maxime Bernier, Minister of Industry and Minister responsible for the Natural Sciences and Engineering Research Council of Canada (NSERC), and Dr. Suzanne Fortier, President of NSERC, have announced the results of the 2007 Grants and Scholarships awards, which will see $583 million disbursed to 10,000 professors and students across Canada.
As a result of the current competition, some 3,300 professors from across Canada will receive $458.8 million in Discovery Grants to support their research in the natural sciences and engineering. (These awards are normally paid out over five years.)
In addition, 2,402 young university researchers - 2,148 at the graduate level and 254 at the postdoctoral level - will receive $99.2 million to pursue their studies in these fields, while 4,296 undergraduate students will receive Undergraduate Student Research Awards worth a total of $19.3 million to give them hands-on research experience in a laboratory.
"Our newly released science and technology strategy - Mobilizing Science and Technology to Canada's Advantage - recognizes the importance of doing more to turn ideas into innovations that provide solutions to our environmental, health and other important challenges, and to improve Canada's economic competitiveness," said Parliamentary Secretary Carrie. "These awards will help ensure that this country's best and brightest professors and students can continue their work and their contribution to the prosperity and well-being of all Canadians."
This year also sees the introduction of the Discovery Accelerator Supplements, a new NSERC initiative to foster research excellence. With a total of $6 million in new funding, this initiative will provide significant supplements to a select group of researchers in order to boost their productivity at a critical juncture in their careers.
"These new grants target 50 outstanding researchers. Based on their success and accomplishments so far, we believe they are poised to make real breakthroughs in their fields, and we believe it is critically important to support them financially at this time," observed Dr. Fortier.
NSERC is a federal agency whose role is to make investments in people, discovery and innovation for the benefit of all Canadians. The agency invests in people by supporting some 23,000 university students and postdoctoral fellows in their advanced studies. NSERC promotes discovery by funding more than 11,000 university professors every year and helps make innovation happen by encouraging about 1,300 Canadian companies to invest in university research and training. Over the past 10 years, NSERC has invested $6 billion in basic research, university-industry projects, and the training of Canada's next generation of scientists and engineers.
For more information, contact:
Isabelle Fontaine
Office of the Honourable Maxime Bernier
Minister of Industry
Background Information
The 15 universities receiving the largest allocation of NSERC grants and scholarships this year are:
University of Toronto: $65.8 million
University of British Columbia: $46.4 million
McGill University: $38.6 million
University of Alberta: $31.9 million
University of Waterloo: $29.9 million
The University of Western Ontario: $21.2 million
Universite de Montreal: $19.7 million
University of Calgary: $18.5 million
Dalhousie University: $18.0 million
Universite de Sherbrooke: $17.8 million
Universite Laval: $17.6 million
McMaster University: $17.3 million
Queen's University: $16.0 million
University of Ottawa: $15.7 million
University of Manitoba: $14.0 million
Contact: Michael Dwyer
Natural Sciences and Engineering Research Council
As a result of the current competition, some 3,300 professors from across Canada will receive $458.8 million in Discovery Grants to support their research in the natural sciences and engineering. (These awards are normally paid out over five years.)
In addition, 2,402 young university researchers - 2,148 at the graduate level and 254 at the postdoctoral level - will receive $99.2 million to pursue their studies in these fields, while 4,296 undergraduate students will receive Undergraduate Student Research Awards worth a total of $19.3 million to give them hands-on research experience in a laboratory.
"Our newly released science and technology strategy - Mobilizing Science and Technology to Canada's Advantage - recognizes the importance of doing more to turn ideas into innovations that provide solutions to our environmental, health and other important challenges, and to improve Canada's economic competitiveness," said Parliamentary Secretary Carrie. "These awards will help ensure that this country's best and brightest professors and students can continue their work and their contribution to the prosperity and well-being of all Canadians."
This year also sees the introduction of the Discovery Accelerator Supplements, a new NSERC initiative to foster research excellence. With a total of $6 million in new funding, this initiative will provide significant supplements to a select group of researchers in order to boost their productivity at a critical juncture in their careers.
"These new grants target 50 outstanding researchers. Based on their success and accomplishments so far, we believe they are poised to make real breakthroughs in their fields, and we believe it is critically important to support them financially at this time," observed Dr. Fortier.
NSERC is a federal agency whose role is to make investments in people, discovery and innovation for the benefit of all Canadians. The agency invests in people by supporting some 23,000 university students and postdoctoral fellows in their advanced studies. NSERC promotes discovery by funding more than 11,000 university professors every year and helps make innovation happen by encouraging about 1,300 Canadian companies to invest in university research and training. Over the past 10 years, NSERC has invested $6 billion in basic research, university-industry projects, and the training of Canada's next generation of scientists and engineers.
For more information, contact:
Isabelle Fontaine
Office of the Honourable Maxime Bernier
Minister of Industry
Background Information
The 15 universities receiving the largest allocation of NSERC grants and scholarships this year are:
University of Toronto: $65.8 million
University of British Columbia: $46.4 million
McGill University: $38.6 million
University of Alberta: $31.9 million
University of Waterloo: $29.9 million
The University of Western Ontario: $21.2 million
Universite de Montreal: $19.7 million
University of Calgary: $18.5 million
Dalhousie University: $18.0 million
Universite de Sherbrooke: $17.8 million
Universite Laval: $17.6 million
McMaster University: $17.3 million
Queen's University: $16.0 million
University of Ottawa: $15.7 million
University of Manitoba: $14.0 million
Contact: Michael Dwyer
Natural Sciences and Engineering Research Council
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