A protein that is crucial for regulating the self-renewal of normal prostate stem cells, needed to repair injured cells or restore normal cells killed by hormone withdrawal therapy for cancer, also aids the transformation of healthy cells into prostate cancer cells, researchers at UCLA have found.
The findings, by researchers with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, may have important implications for controlling cancer growth and progression.
Done in primary cells and in animal models, the findings from the three-year study appear Dec. 2, 2010 in the early online edition of the peer-reviewed journal Cell Stem Cell.
The protein, called Bmi-1, is often up-regulated in prostate cancer, has been associated with higher grade cancers and is predictive of poor prognosis, according to previous studies. However, its functional roles in prostate stem cell maintenance and prostate cancer have been unclear, said Dr. Owen Witte, who is director of the Broad Stem Cell Research Center, a Howard Hughes Medical Institute investigator and senior author of the study.
A study of loss and gain of function in prostate stem cells indicated that Bmi-1 expression was required for self-renewal activity and maintenance of prostate stem cells with highly proliferative abilities. Loss of Bmi-1 expression blocks the self-renewal activity, protecting prostate cells from developing abnormal growth changes which can lead to cancer.
More importantly, Bmi-1 inhibition slowed the growth of an aggressive form of prostate cancer in animal models, in which the PTEN tumor suppressor gene was removed allowing the cancer to run wild, Witte said.
"We conclude by these results that Bmi-1 is a crucial regulator of self-renewal in adult prostate cells and plays important roles in prostate cancer initiation and progression," Witte said. "It was encouraging to see that inhibiting this protein slows the growth of even a very aggressive prostate cancer, because that could give us new ways to attack this disease."
UCLA stem cell researchers have been studying the mechanisms of prostate stem cells for years on the theory that the mechanism that gives the cells their unique ability to self-renew somehow gets high jacked by cancer cells, allowing the malignant cells to grow and spread. If the mechanism for self-renewal could be understood, researchers could find a way to interrupt it once it is taken over by the cancer cells, Witte said.
Rita Lukacs, a doctoral student in Witte's laboratory and first author of the study, found that Bmi-1 inhibition also stops excessive self-renewal driven by other pathways. This suggests that the Bmi-1 pathway may be dominant to other genetic controls that affect the cancer phenotype.
"Prostate cancer can be initiated by so many different mutations, if we can find a key regulator of self-renewal, we can partially control the growth of the cancer no matter what the mutation is," Lukacs said. "We're attacking the process that allows the cancer cells to grow indefinitely. This provides us an alternate way of attacking the cancer by going to the core mechanism for cancer cell self-renewal and proliferation."
Witte said future work will be centered on searching for methods to control these pathways in human prostate cancer cells.
Prostate cancer is the most frequently diagnosed non-skin cancer and the second most common cause of cancer-related deaths in men. This year alone, more than 277,000 men in the United States will be diagnosed with prostate cancer. Of those, 32,000 men will die from the disease.
University of California - Los Angeles
Showing posts with label Prostate Cancer Research. Show all posts
Showing posts with label Prostate Cancer Research. Show all posts
Thursday, December 2, 2010
Wednesday, July 28, 2010
Dense bones linked to raised risk for prostate cancer
Men who develop prostate cancer, especially the more aggressive and dangerous forms that spread throughout the body, tend to retain denser bones as they age than men who stay free of the disease, suggests new research from Johns Hopkins and the National Institute on Aging (NIA), part of the National Institutes of Health.
The finding, published in the July British Journal of Urology International, could help scientists gain a better grasp on what causes prostate cancer and its spread.
Researchers have long known that prostate cancers that spread, or metastasize, often migrate to bone. That idea led Stacy Loeb, M.D., a resident in the Department of Urology at the Johns Hopkins University School of Medicine, and her colleagues to wonder whether there is a connection between bone characteristics and prostate cancer development and metastasis.
"We reasoned there may be some difference between men who develop prostate cancer, especially metastatic disease, and those who don't, and it was logical to see if there was something different about their bones," says Loeb.
To investigate, she and her colleagues used data from the NIA's Baltimore Longitudinal Study of Aging , a long-term study that has tracked various health-related information for hundreds of Baltimore-area participants since 1958. The researchers collected data on the bone mineral density of 519 men, measured from 1973 to 1984. They then used the same collection of data to see which men were eventually diagnosed with prostate cancer.
Typically, bone density declines with age in both men and women. However, Loeb and her colleagues found that the 76 men in their study who went on to develop prostate cancer had bone density that remained significantly higher as they aged, compared with those who remained cancer free. The findings held up even after the researchers accounted for lifestyle factors that might influence bone density, such as smoking, body mass index, and intake of dietary calcium and vitamin D.
Further examination showed that the 18 men who developed the high-risk form of the disease retained the highest bone density, but the researchers caution that the number of patients is too small to make any final conclusions about bone features and metastatic disease.
Loeb and her colleagues say that their findings don't mean that bone density scans should be used as a screening tool for prostate cancer. Rather, their goal was to better understand the link between prostate cancer and bone. They say their results suggest that the same factors that influence bone density, such as sex hormones or growth factors in bone, may also be spurring prostate cancer to develop and metastasize. She and her colleagues plan to continue searching for what common factors connect bone density and prostate cancer in future studies.
"If we can elucidate the underlying pathways, we could develop strategies for preventing prostate cancer from occurring or spreading," Loeb says.
Johns Hopkins Medical Institutions
The finding, published in the July British Journal of Urology International, could help scientists gain a better grasp on what causes prostate cancer and its spread.
Researchers have long known that prostate cancers that spread, or metastasize, often migrate to bone. That idea led Stacy Loeb, M.D., a resident in the Department of Urology at the Johns Hopkins University School of Medicine, and her colleagues to wonder whether there is a connection between bone characteristics and prostate cancer development and metastasis.
"We reasoned there may be some difference between men who develop prostate cancer, especially metastatic disease, and those who don't, and it was logical to see if there was something different about their bones," says Loeb.
To investigate, she and her colleagues used data from the NIA's Baltimore Longitudinal Study of Aging , a long-term study that has tracked various health-related information for hundreds of Baltimore-area participants since 1958. The researchers collected data on the bone mineral density of 519 men, measured from 1973 to 1984. They then used the same collection of data to see which men were eventually diagnosed with prostate cancer.
Typically, bone density declines with age in both men and women. However, Loeb and her colleagues found that the 76 men in their study who went on to develop prostate cancer had bone density that remained significantly higher as they aged, compared with those who remained cancer free. The findings held up even after the researchers accounted for lifestyle factors that might influence bone density, such as smoking, body mass index, and intake of dietary calcium and vitamin D.
Further examination showed that the 18 men who developed the high-risk form of the disease retained the highest bone density, but the researchers caution that the number of patients is too small to make any final conclusions about bone features and metastatic disease.
Loeb and her colleagues say that their findings don't mean that bone density scans should be used as a screening tool for prostate cancer. Rather, their goal was to better understand the link between prostate cancer and bone. They say their results suggest that the same factors that influence bone density, such as sex hormones or growth factors in bone, may also be spurring prostate cancer to develop and metastasize. She and her colleagues plan to continue searching for what common factors connect bone density and prostate cancer in future studies.
"If we can elucidate the underlying pathways, we could develop strategies for preventing prostate cancer from occurring or spreading," Loeb says.
Johns Hopkins Medical Institutions
Tuesday, July 13, 2010
High-risk prostate cancer associated with significantly lower bone mineral content loss
Men with prostate cancer lose significantly less bone mineral content (BMC) as they age than men who are free of the disease, according to research in the July issue of BJUI. The findings are important because loss of BMC can play a key role in the development of fragile bones, fractures and osteoporosis.
American researchers studied 519 participants who joined the Baltimore Longitudinal Study at an average age of 56 between 1973 and 1984. The maximum follow-up was 35 years and the median was 22 years. Seventy-six men who took part in the study were later diagnosed with prostate cancer, with just under a quarter (24 per cent) falling into the high-risk category.
When they charted the individual BMCs of the study subjects over an extended period, the researchers could clearly see that the decline was much larger in healthy men than in men later diagnosed with prostate cancer, especially those with high-risk prostate cancer. This occurred despite the fact that the initial baseline readings were very similar for all three groups.
The researchers also adjusted the figures to take account of other factors that affect BMC, such as smoking status, body mass index, dietary calcium and vitamin D. However, this did not change the significant differences between the healthy men and those with prostate cancer.
"There are numerous possible mechanisms to explain the relationship between prostate cancer and BMC" says lead author Dr Stacy Loeb, from Johns Hopkins University, Maryland, USA.
"It is well known that prostate cancer frequently metastasizes (spreads) to bone. Although the biology underlying the association between BMC and this form of cancer requires additional research, our findings suggest that common growth factors might be involved in both bone maintenance and the progression of prostate cancer.
"We believe that this may be why the patients with the highest risk prostate cancer also demonstrated the least loss of BMC as they got older, when compared with patients with non high-risk prostate cancer and no prostate cancer."
The baseline demographics between the three groups of men were similar when it came to their body mass index and smoking history.
The authors believe that this is the first study to explore the relationship between longitudinal BMC measurement and the long-term risk of prostate cancer and, more specifically, life-threatening disease. They point out that the study sample was primarily white (96 per cent) and, due to racial differences in bone density, may not be generally applicable to other ethnic groups.
"We would like to see our theories tested further in larger populations of men at risk of developing life-threatening prostate cancer" concludes Dr Loeb. "If we can better understand the link between prostate cancer and bone, it may help us to find ways of preventing the spread of this disease to bone in the future."
Wiley-Blackwell
American researchers studied 519 participants who joined the Baltimore Longitudinal Study at an average age of 56 between 1973 and 1984. The maximum follow-up was 35 years and the median was 22 years. Seventy-six men who took part in the study were later diagnosed with prostate cancer, with just under a quarter (24 per cent) falling into the high-risk category.
When they charted the individual BMCs of the study subjects over an extended period, the researchers could clearly see that the decline was much larger in healthy men than in men later diagnosed with prostate cancer, especially those with high-risk prostate cancer. This occurred despite the fact that the initial baseline readings were very similar for all three groups.
The researchers also adjusted the figures to take account of other factors that affect BMC, such as smoking status, body mass index, dietary calcium and vitamin D. However, this did not change the significant differences between the healthy men and those with prostate cancer.
"There are numerous possible mechanisms to explain the relationship between prostate cancer and BMC" says lead author Dr Stacy Loeb, from Johns Hopkins University, Maryland, USA.
"It is well known that prostate cancer frequently metastasizes (spreads) to bone. Although the biology underlying the association between BMC and this form of cancer requires additional research, our findings suggest that common growth factors might be involved in both bone maintenance and the progression of prostate cancer.
"We believe that this may be why the patients with the highest risk prostate cancer also demonstrated the least loss of BMC as they got older, when compared with patients with non high-risk prostate cancer and no prostate cancer."
The baseline demographics between the three groups of men were similar when it came to their body mass index and smoking history.
The authors believe that this is the first study to explore the relationship between longitudinal BMC measurement and the long-term risk of prostate cancer and, more specifically, life-threatening disease. They point out that the study sample was primarily white (96 per cent) and, due to racial differences in bone density, may not be generally applicable to other ethnic groups.
"We would like to see our theories tested further in larger populations of men at risk of developing life-threatening prostate cancer" concludes Dr Loeb. "If we can better understand the link between prostate cancer and bone, it may help us to find ways of preventing the spread of this disease to bone in the future."
Wiley-Blackwell
Thursday, May 6, 2010
FDA Conducting Safety Review of Commonly Used Prostate Cancer Drugs
Preliminary review suggests an increase in the risk of diabetes and certain cardiovascular diseases in men treated with GnRH agonists
Gonadotropin-Releasing Hormone (GnRH) agonists, a class of medications primarily used to treat men with prostate cancer, have been associated with a small increased risk for diabetes, heart attack, stroke, and sudden death in men treated with one of the medications, according to a preliminary and ongoing analysis of several studies by the U.S. Food and Drug Administration.
Based on initial findings, FDA advises:
Health care professionals should be aware of these potential risks and carefully weigh the benefits and risks of GnRH agonists when determining a treatment for patients with prostate cancer.
Patients receiving a GnRH agonist should be monitored for the development of diabetes and cardiovascular disease.
Cardiovascular risk factors such as smoking and increases in blood pressure, cholesterol, blood sugar and weight should be managed according to current clinical practice.
Patients should not stop treatment with a GnRH agonist unless instructed to do so by a health care professional.
At this time, FDA has not made any conclusions about whether GnRH agonists cause an increase in the risk of diabetes and heart disease in patients receiving one of these medications to treat prostate cancer.
“While our review of these prostate cancer treatments is ongoing and there are some limitations to the data, FDA believes it is important to tell patients and health care professionals that there may be an increased risk of serious side effects,” said Robert Justice, M.D., director of the Division of Drug Oncology Products in FDA’s Center for Drug Evaluation and Research.
Medications in the GnRH class are marketed under the brand names Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. There are also several generic products available.
The prostate gland is part of the male reproductive system. Prostate cancer is the second most common type of cancer among men in the United States, behind skin cancer, and usually occurs in older men. This year an estimated 203,415 new cases of prostate cancer will be diagnosed and about 28,372 men will die from the disease, according to the Centers for Disease Control and Prevention.
GnRH agonists are drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer. This type of treatment is called androgen deprivation therapy, or ADT. Suppressing testosterone has been shown to shrink or slow the growth of prostate cancer.
Some GnRH agonists are also used in women to help manage the pain caused by endometriosis, to improve anemia associated with uterine fibroids prior to hysterectomy and in some cases for palliative treatment of advanced breast cancer. Use of these products should not exceed one year for women except in treating breast cancer. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women taking GnRH agonists.
Some GnRH agonists are also used in children to treat central precocious puberty. There are no known studies that have evaluated the risk of diabetes and heart disease in children taking GnRH agonists.
Drug Safety Communication: Ongoing Safety Review of GnRH Agonists and Possible Increased Risk of Diabetes and Certain Cardiovascular Diseases
Gonadotropin-Releasing Hormone (GnRH) agonists, a class of medications primarily used to treat men with prostate cancer, have been associated with a small increased risk for diabetes, heart attack, stroke, and sudden death in men treated with one of the medications, according to a preliminary and ongoing analysis of several studies by the U.S. Food and Drug Administration.
Based on initial findings, FDA advises:
Health care professionals should be aware of these potential risks and carefully weigh the benefits and risks of GnRH agonists when determining a treatment for patients with prostate cancer.
Patients receiving a GnRH agonist should be monitored for the development of diabetes and cardiovascular disease.
Cardiovascular risk factors such as smoking and increases in blood pressure, cholesterol, blood sugar and weight should be managed according to current clinical practice.
Patients should not stop treatment with a GnRH agonist unless instructed to do so by a health care professional.
At this time, FDA has not made any conclusions about whether GnRH agonists cause an increase in the risk of diabetes and heart disease in patients receiving one of these medications to treat prostate cancer.
“While our review of these prostate cancer treatments is ongoing and there are some limitations to the data, FDA believes it is important to tell patients and health care professionals that there may be an increased risk of serious side effects,” said Robert Justice, M.D., director of the Division of Drug Oncology Products in FDA’s Center for Drug Evaluation and Research.
Medications in the GnRH class are marketed under the brand names Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. There are also several generic products available.
The prostate gland is part of the male reproductive system. Prostate cancer is the second most common type of cancer among men in the United States, behind skin cancer, and usually occurs in older men. This year an estimated 203,415 new cases of prostate cancer will be diagnosed and about 28,372 men will die from the disease, according to the Centers for Disease Control and Prevention.
GnRH agonists are drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer. This type of treatment is called androgen deprivation therapy, or ADT. Suppressing testosterone has been shown to shrink or slow the growth of prostate cancer.
Some GnRH agonists are also used in women to help manage the pain caused by endometriosis, to improve anemia associated with uterine fibroids prior to hysterectomy and in some cases for palliative treatment of advanced breast cancer. Use of these products should not exceed one year for women except in treating breast cancer. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women taking GnRH agonists.
Some GnRH agonists are also used in children to treat central precocious puberty. There are no known studies that have evaluated the risk of diabetes and heart disease in children taking GnRH agonists.
Drug Safety Communication: Ongoing Safety Review of GnRH Agonists and Possible Increased Risk of Diabetes and Certain Cardiovascular Diseases
Friday, April 16, 2010
UC to test targeted treatment for prostate cancer
The American Cancer Society estimates one man in six will get prostate cancer during his lifetime, making it the second-leading cause of cancer death in men. With a new partnership with Areva Med, UC researchers will investigate the use of a new drug in stopping the growth of prostate cancer tumors.
In the study, UC researchers in the lab of Zhongyun Dong, PhD, will test the efficacy of a new agent targeted against a specific protein on the surface of the tumor.
"It's been shown that human prostate cancer cells overexpress some proteins on their surface," says Dong, an associate professor of hematology oncology in the department of internal medicine. "This overexpression presents a novel target for management of advanced prostate cancer."
Dong says previous radiation therapy targeting these proteins has been shown to inhibit tumor growth in several animal models. UC's study will be the first to explore this approach for prostate tumors. In the work, researchers will bind the isotope 212-lead to an antibody targeting one of these proteins.
"When administered intravenously, the AREVA Med 2120lead-antibody is designed to bind to the tumor's surface, emit alpha particles in and selectively destroy the tumor cells," says Dong.
In the study, expected to run through the end of the year, researchers will measure the toxicity of the treatment and its efficacy in inhibiting cancer cell growth. Data will then be gathered to support phase-1 clinical trials in patients with advanced prostate cancer.
According to hematology oncology professor Olivier Rixe, MD, PhD, the agent represents a more targeted radiation therapy for cancer treatment. Rixe is the director of the UC's recently launched phase-1 clinical trials unit at the newly established Early Drug Development Program.
"Targeting a monoclonal antibody against this protein is not new," says Rixe. "What's new is that we will load the antibody with an isotope that can directly target the protein on the cancer cell and deliver very localized radiation to this specific target of the cancer.
"It's a very interesting concept for drug delivery and a novel strategy for cancer treatment."
University of Cincinnati Academic Health Center
In the study, UC researchers in the lab of Zhongyun Dong, PhD, will test the efficacy of a new agent targeted against a specific protein on the surface of the tumor.
"It's been shown that human prostate cancer cells overexpress some proteins on their surface," says Dong, an associate professor of hematology oncology in the department of internal medicine. "This overexpression presents a novel target for management of advanced prostate cancer."
Dong says previous radiation therapy targeting these proteins has been shown to inhibit tumor growth in several animal models. UC's study will be the first to explore this approach for prostate tumors. In the work, researchers will bind the isotope 212-lead to an antibody targeting one of these proteins.
"When administered intravenously, the AREVA Med 2120lead-antibody is designed to bind to the tumor's surface, emit alpha particles in and selectively destroy the tumor cells," says Dong.
In the study, expected to run through the end of the year, researchers will measure the toxicity of the treatment and its efficacy in inhibiting cancer cell growth. Data will then be gathered to support phase-1 clinical trials in patients with advanced prostate cancer.
According to hematology oncology professor Olivier Rixe, MD, PhD, the agent represents a more targeted radiation therapy for cancer treatment. Rixe is the director of the UC's recently launched phase-1 clinical trials unit at the newly established Early Drug Development Program.
"Targeting a monoclonal antibody against this protein is not new," says Rixe. "What's new is that we will load the antibody with an isotope that can directly target the protein on the cancer cell and deliver very localized radiation to this specific target of the cancer.
"It's a very interesting concept for drug delivery and a novel strategy for cancer treatment."
University of Cincinnati Academic Health Center
Thursday, March 11, 2010
VAI researchers develop tool to help study prostate cancer
Van Andel Research Institute (VARI) researchers have developed a new method to better study the cells that line and protect the prostate in relation to the development of cancer. Using the model, they found that normal cells and cancer cells depend on different factors to survive, which could aid in discovering how to target cancer cells without affecting normal cells when developing treatments.
Prostate cancer is the most common form of cancer in men, with more than 192,000 new cases and more than 27,000 deaths reported in the United States in 2009 (Source: National Cancer Institute).
"This new model will serve as a valuable tool for understanding secretory prostate epithelial cells, which until now have not been available for extensive analysis," said VARI Scientific Investigator Cindy Miranti, Ph.D., whose lab published its study in a recent issue of the Journal of Cell Science.
Epithelial cells line and protect the internal and external organs and structures of the body. The prostate contains two types of epithelial cells, basal and secretory, and prostate cancers arise from abnormal cells as they are converted from basal into secretory cells in the body.
Prior to this study, scientists were able to culture basal cells, but not secretory cells. Using the model, researchers found that, unlike cancer cells, normal secretory cells are not dependent on the male sex hormone androgen for survival, but are dependent for survival on binding to each other via the protein E-cadherin.
"Prostate cancers are dependent on androgen for survival, so we were interested in whether normal secretory prostate epithelial cells also depend on androgen," said Dr. Miranti. "However, the cell culture models available didn't allow us to study secretory cells, so we generated them by reconstructing the natural conversion process from basal into secretory cells in a petri dish."
The differences in how cancer cells and normal cells control their survival can be exploited to develop therapies that preferentially target the tumor cells, but not the normal cells.
"This cell model will be extremely useful to investigators who are interested in studying the cell biology of prostate cancer as well as benign prostate hyperplasia," said Donald J. Tindall, Ph.D., Professor, Director & Vice Chair of Urologic Research at the Mayo Clinic College of Medicine. "Such studies should facilitate our understanding of the cellular mechanisms involved in progression of these diseases and may lead to new prognostic capabilities and therapeutic interventions."
Van Andel Research Institute
Prostate cancer is the most common form of cancer in men, with more than 192,000 new cases and more than 27,000 deaths reported in the United States in 2009 (Source: National Cancer Institute).
"This new model will serve as a valuable tool for understanding secretory prostate epithelial cells, which until now have not been available for extensive analysis," said VARI Scientific Investigator Cindy Miranti, Ph.D., whose lab published its study in a recent issue of the Journal of Cell Science.
Epithelial cells line and protect the internal and external organs and structures of the body. The prostate contains two types of epithelial cells, basal and secretory, and prostate cancers arise from abnormal cells as they are converted from basal into secretory cells in the body.
Prior to this study, scientists were able to culture basal cells, but not secretory cells. Using the model, researchers found that, unlike cancer cells, normal secretory cells are not dependent on the male sex hormone androgen for survival, but are dependent for survival on binding to each other via the protein E-cadherin.
"Prostate cancers are dependent on androgen for survival, so we were interested in whether normal secretory prostate epithelial cells also depend on androgen," said Dr. Miranti. "However, the cell culture models available didn't allow us to study secretory cells, so we generated them by reconstructing the natural conversion process from basal into secretory cells in a petri dish."
The differences in how cancer cells and normal cells control their survival can be exploited to develop therapies that preferentially target the tumor cells, but not the normal cells.
"This cell model will be extremely useful to investigators who are interested in studying the cell biology of prostate cancer as well as benign prostate hyperplasia," said Donald J. Tindall, Ph.D., Professor, Director & Vice Chair of Urologic Research at the Mayo Clinic College of Medicine. "Such studies should facilitate our understanding of the cellular mechanisms involved in progression of these diseases and may lead to new prognostic capabilities and therapeutic interventions."
Van Andel Research Institute
Wednesday, March 10, 2010
First inherited prostate cancer genetic mutation found in African-American men
Shahriar Koochekpour, MD, PhD, Assistant Professor of Microbiology and Immunology, Biochemistry and Molecular Biology, and Genetics at LSU Health Sciences Center New Orleans, led research that has discovered, for the first time, a genetic mutation in African-American men with a family history of prostate cancer who are at increased risk for the disease. Dr. Koochekpour, who is also a member of the LSUHSC Stanley S. Scott Cancer Center, identified an inheritable genetic defect in the receptor for the male hormone, androgen (testosterone), that may contribute to the development of prostate cancer and its progression. Scientific reports linking inheritable androgen receptor mutations to prostate cancer in Caucasians are rare, and this is the first one that focuses on the African-American population. The study is available in the advance online publication of the Nature Publishing Group's Asian Journal of Andrology.
Dr. Koochekpour and his laboratory discovered this genetic change by testing DNA extracted from white blood cells of African-American and Caucasian men from Louisiana who had a proven medical history of prostate cancer in their families.
"We detected this mutation only in African-American men with prostate cancer," notes Dr. Koochekpour. "We found it in the cell's androgen receptor (AR), a protein which interacts and responds to male sex hormones. This protein is profoundly involved in prostate cancer formation and its progression to an advanced metastatic, incurable stage. We believe that this mutation increases the risk of the development and progression of prostate cancer, in part by altering the receptor's DNA-binding ability, and by regulating the activities of other genes and proteins involved in the growth and aggressive behavior of tumors."
African-American men have a higher incidence and death rate from prostate cancer, as well as clinically more aggressive disease than Caucasians. According to the American Cancer Society's most current data for 2009-2010, prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among American men. Between 2001 and 2005, the prostate cancer incidence rate was 59% higher in African-American men. African-American men also have the highest mortality rate for prostate cancer of any racial or ethnic group in the US. The death rate for prostate cancer is 2.4 times higher in African-American men than white men in the US.
"We are hopeful that this discovery will eventually lead to a simple genetic test for prostate cancer for African-American men who are at high risk for developing prostate cancer, allowing genetic counselling and earlier, potentially life-saving treatment" said Dr. Koochekpour.
Louisiana State University Health Sciences Center
Dr. Koochekpour and his laboratory discovered this genetic change by testing DNA extracted from white blood cells of African-American and Caucasian men from Louisiana who had a proven medical history of prostate cancer in their families.
"We detected this mutation only in African-American men with prostate cancer," notes Dr. Koochekpour. "We found it in the cell's androgen receptor (AR), a protein which interacts and responds to male sex hormones. This protein is profoundly involved in prostate cancer formation and its progression to an advanced metastatic, incurable stage. We believe that this mutation increases the risk of the development and progression of prostate cancer, in part by altering the receptor's DNA-binding ability, and by regulating the activities of other genes and proteins involved in the growth and aggressive behavior of tumors."
African-American men have a higher incidence and death rate from prostate cancer, as well as clinically more aggressive disease than Caucasians. According to the American Cancer Society's most current data for 2009-2010, prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among American men. Between 2001 and 2005, the prostate cancer incidence rate was 59% higher in African-American men. African-American men also have the highest mortality rate for prostate cancer of any racial or ethnic group in the US. The death rate for prostate cancer is 2.4 times higher in African-American men than white men in the US.
"We are hopeful that this discovery will eventually lead to a simple genetic test for prostate cancer for African-American men who are at high risk for developing prostate cancer, allowing genetic counselling and earlier, potentially life-saving treatment" said Dr. Koochekpour.
Louisiana State University Health Sciences Center
Thursday, February 25, 2010
Do men with early prostate cancer commit suicide more frequently?
The introduction of prostate-specific antigen (PSA) testing as a screening tool for early detection of prostate cancer (PCa) in the beginning of the 1990s drastically increased the detection of PCa. The risk of suicide is increased among cancer patients including men with PCa. To assess the risk of suicide among men diagnosed with PCa subsequent to PSA testing, a nation-wide study was carried out in Sweden. The results are published in the March issue of European Urology, the scientific journal of the European Association of Urology (EAU).
Anxiety related to a crisis reaction may develop into a depression, and several studies have shown that there is a high anxiety level among screeners in various screening programs. However, as in most countries, men who underwent PSA testing in Sweden at the time represent an opportunistic screening population and not a true population-based screening program by invitation. Therefore, they may have been more health conscious, less prone to develop depression, and more prepared to accept the potential side effects of curative treatment than the general population.
The number of suicides registered for cases in the Prostate Cancer Base Sweden (a database in which a number of different registers are merged) cohort was compared with the expected number of suicides in an age-matched general male Swedish population. The strengths of this study include the population-based design with inclusion of approximately 98% of all men in Sweden diagnosed with PCa between1997 and 2006.
There was no evidence for an increased risk of suicide among men diagnosed with early nonpalpable PCa detected by PSA testing. The suicide rate, however, was twice as high among men diagnosed with locally advanced or metastatic disease compared with the general male population. This is important to acknowledge in order to focus on the need to identify signs of depression and optimise treatment among this category of patients.
European Association of Urology
Anxiety related to a crisis reaction may develop into a depression, and several studies have shown that there is a high anxiety level among screeners in various screening programs. However, as in most countries, men who underwent PSA testing in Sweden at the time represent an opportunistic screening population and not a true population-based screening program by invitation. Therefore, they may have been more health conscious, less prone to develop depression, and more prepared to accept the potential side effects of curative treatment than the general population.
The number of suicides registered for cases in the Prostate Cancer Base Sweden (a database in which a number of different registers are merged) cohort was compared with the expected number of suicides in an age-matched general male Swedish population. The strengths of this study include the population-based design with inclusion of approximately 98% of all men in Sweden diagnosed with PCa between1997 and 2006.
There was no evidence for an increased risk of suicide among men diagnosed with early nonpalpable PCa detected by PSA testing. The suicide rate, however, was twice as high among men diagnosed with locally advanced or metastatic disease compared with the general male population. This is important to acknowledge in order to focus on the need to identify signs of depression and optimise treatment among this category of patients.
European Association of Urology
Tuesday, February 2, 2010
Loss of gene function makes some prostate cancer cells more aggressive, researchers find
Prostate cancer cells are more likely to spread to other parts of the body if a specific gene quits functioning normally, according to new data from researchers at UT Southwestern Medical Center.
Certain prostate cancer cells can be held in check by the DAB2IP gene. The gene’s product, the DABIP protein, acts as scaffolding that prevents many other proteins involved in the progression of prostate cancer cells from over-activation. When those cells lose the DAB2IP protein, however, they break free and are able to metastasize, or spread, drastically increasing the risk of cancer progression in other organs as the cells travel through the bloodstream or lymph system.
The study in mice, published in the Jan. 11 issue of the Proceedings of the National Academy of Sciences, found that eliminating the DAB2IP scaffolding in human carcinoma cells caused them to change from epithelial cells to mesenchymal cells – a hallmark of metastatic cancer.
Cells undergoing an epithelial to mesenchymal transition (EMT) experience biological changes that enable them to move freely and spontaneously throughout the body,” said Dr. Jer-Tsong Hsieh, director of the Jean H. & John T. Walker Jr. Center for Research in Urologic Oncology at UT Southwestern and the study’s senior author. “By restoring DAB2IP function in cancer cells in mice, we reversed their ability to change and metastasize.”
Dr. Hsieh said identifying the DAB2IP protein in human cells might serve as a biomarker, helping physicians identify patients who could have more aggressive, metastatic forms of prostate cancer.
EMT is known to play an important role in embryo implantation, embryogenesis and organ development, and tissue regeneration, as well as in cancer progression and metastasis. For cancer progression, EMT is believed to facilitate the migratory and invasive ability of cancer cells.
“Carcinoma cells undergo several changes that enable them to spread,” said Dr. Hsieh, also professor of urology. “The majority of human visceral tumors derived from carcinomas are primarily made up of epithelial cells. When they acquire mesenchymal phenotypes, they lose cell-to-cell adhesion and become more mobile throughout the body.”
In the current study, Dr. Hsieh and his team first shut down the DAB2IP gene expression in prostate epithelial cells in mice and found that the prostate cancers did indeed metastasize to lymph nodes and other organs in mice. When the researchers restored the DAB2IP genetic function to metastatic prostate cancer cells, the EMT process reversed, thereby inhibiting the cancer cells’ ability to spread.
“Based on the outcome of this paper, we believe the assessment of DAB2IP in these cancer cells can be a valuable prognostic biomarker for risk of the aggressiveness of certain prostate cancers,” said Dr. Daxing Xie, urology postdoctoral researcher and lead author of the study. “Further understanding of the DAB2IP function could also provide potential therapeutic strategies for treating prostate cancer.”
Other UT Southwestern researchers involved in this study were Crystal Gore and Michael Long, research technicians; Dr. Jun Liu, postdoctoral researcher; Rey-Chen Pong, senior research associate; Dr. Ralph Mason, professor of radiology; Dr. Guiyang Hao, postdoctoral researcher; Dr. Wareef Kabbani, assistant professor of pathology; Dr. Xiankai Sun, assistant professor of radiology in the Advanced Imaging Research Center; and Dr. David Boothman, professor of radiation oncology and pharmacology and associate director of translational research in the Harold C. Simmons Comprehensive Cancer Center.
The study was supported by the U.S. Army, the National Institutes of Health and the Department of Energy.
Visit www.utsouthwestern.org/cancercenter to learn more about UT Southwestern’s clinical services in cancer.
Southwestern Medical Center
Certain prostate cancer cells can be held in check by the DAB2IP gene. The gene’s product, the DABIP protein, acts as scaffolding that prevents many other proteins involved in the progression of prostate cancer cells from over-activation. When those cells lose the DAB2IP protein, however, they break free and are able to metastasize, or spread, drastically increasing the risk of cancer progression in other organs as the cells travel through the bloodstream or lymph system.
The study in mice, published in the Jan. 11 issue of the Proceedings of the National Academy of Sciences, found that eliminating the DAB2IP scaffolding in human carcinoma cells caused them to change from epithelial cells to mesenchymal cells – a hallmark of metastatic cancer.
Cells undergoing an epithelial to mesenchymal transition (EMT) experience biological changes that enable them to move freely and spontaneously throughout the body,” said Dr. Jer-Tsong Hsieh, director of the Jean H. & John T. Walker Jr. Center for Research in Urologic Oncology at UT Southwestern and the study’s senior author. “By restoring DAB2IP function in cancer cells in mice, we reversed their ability to change and metastasize.”
Dr. Hsieh said identifying the DAB2IP protein in human cells might serve as a biomarker, helping physicians identify patients who could have more aggressive, metastatic forms of prostate cancer.
EMT is known to play an important role in embryo implantation, embryogenesis and organ development, and tissue regeneration, as well as in cancer progression and metastasis. For cancer progression, EMT is believed to facilitate the migratory and invasive ability of cancer cells.
“Carcinoma cells undergo several changes that enable them to spread,” said Dr. Hsieh, also professor of urology. “The majority of human visceral tumors derived from carcinomas are primarily made up of epithelial cells. When they acquire mesenchymal phenotypes, they lose cell-to-cell adhesion and become more mobile throughout the body.”
In the current study, Dr. Hsieh and his team first shut down the DAB2IP gene expression in prostate epithelial cells in mice and found that the prostate cancers did indeed metastasize to lymph nodes and other organs in mice. When the researchers restored the DAB2IP genetic function to metastatic prostate cancer cells, the EMT process reversed, thereby inhibiting the cancer cells’ ability to spread.
“Based on the outcome of this paper, we believe the assessment of DAB2IP in these cancer cells can be a valuable prognostic biomarker for risk of the aggressiveness of certain prostate cancers,” said Dr. Daxing Xie, urology postdoctoral researcher and lead author of the study. “Further understanding of the DAB2IP function could also provide potential therapeutic strategies for treating prostate cancer.”
Other UT Southwestern researchers involved in this study were Crystal Gore and Michael Long, research technicians; Dr. Jun Liu, postdoctoral researcher; Rey-Chen Pong, senior research associate; Dr. Ralph Mason, professor of radiology; Dr. Guiyang Hao, postdoctoral researcher; Dr. Wareef Kabbani, assistant professor of pathology; Dr. Xiankai Sun, assistant professor of radiology in the Advanced Imaging Research Center; and Dr. David Boothman, professor of radiation oncology and pharmacology and associate director of translational research in the Harold C. Simmons Comprehensive Cancer Center.
The study was supported by the U.S. Army, the National Institutes of Health and the Department of Energy.
Visit www.utsouthwestern.org/cancercenter to learn more about UT Southwestern’s clinical services in cancer.
Southwestern Medical Center
Friday, June 26, 2009
Selenium Intake May Worsen Prostate Cancer In Some
Higher selenium levels in the blood may worsen prostate cancer in some men who already have the disease, according to a study by researchers at Dana-Farber Cancer Institute and the University of California, San Francisco.
A higher risk of more-aggressive prostate cancer was seen in men with a certain genetic variant found in about 75 percent of the prostate cancer patients in the study. In those subjects, having a high level of selenium in the blood was associated with a two-fold greater risk of poorer outcomes than men with the lowest amounts of selenium. By contrast, the 25 percent of men with a different variant of the same gene and who had high selenium levels were at 40 percent lower risk of aggressive disease. The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2), an enzyme that protects the body against harmful oxygen compounds.
The research findings suggest that "if you already have prostate cancer, it may be a bad thing to take selenium," says Philip Kantoff, MD, director of Dana-Farber's Lank Center for Genitourinary Oncology and senior author of the study that is published by the Journal of Clinical Oncology on its website now and later will be in a print journal. The lead author is June Chan, ScD, of the University of California, San Francisco.
The unexpected results are the first to raise concern about this potentially harmful consequence of taking supplemental selenium. Kantoff says, "These findings are interesting particularly in light of the recent negative results from the SELECT prevention study, which asked if selenium could protect against prostate cancer."
The new study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer, a finding that these investigators had shown in a previous study. The authors say the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.
Selenium is a mineral found widely in rocks and dirt. Small amounts of selenium are essential for health: 40 to 70 micrograms is the recommended daily intake. In recent years, supplemental selenium has been sold and promoted as a means of preventing prostate cancer, largely based on observational studies that found higher risk of prostate cancer incidence and mortality in areas of the country that are naturally low in selenium.
However, research aimed at confirming the benefits of selenium supplementation have been mixed. Recently, the SELECT study, which involved 35,000 men, was halted early when, after more than five years, it showed that the supplements didn't affect the incidence of prostate cancer.
Previous studies had found that the risk of developing prostate cancer was modified by a strong interaction between SOD2 and selenium. The new research was designed to look at the effect of this interaction on men already diagnosed with prostate cancer.
Scientists examined banked blood samples, DNA, and medical records of 489 male Dana-Farber patients diagnosed between 1994 and 2001 with localized or locally advanced prostate cancer. Their mean age was 62, and their mean PSA (prostate-specific antigen) measurement was 6.0 ng/mL. About half the men were assessed as having a good disease risk, one-third had an intermediate risk, and the remaining one-sixth were at poor risk. The researchers measured the level of selenium in the blood and, using the stored DNA, they determined the SOD2 genotype the specific form of the SOD2 gene carried by each patient.
Simply having a high level of selenium was associated with a slightly elevated risk of aggressive prostate cancer. But the risk was much more strongly affected by the interaction of selenium levels and whether the patient had a certain variant of the SOD2 gene. Men with the highest selenium levels and the "AA" form of the SOD2 gene were 40 percent less likely to have been diagnosed with aggressive prostate cancer than the men with same gene form but low levels of selenium.
But for men carrying the "V" form of the gene, selenium had the opposite effect. In these men, those with the highest levels of selenium in their blood were about twice as likely to have an aggressive type of prostate cancer as their counterparts with low selenium levels.
The study couldn't determine whether any of the men had been taking selenium supplements or not. But the researchers noted that men in the large SELECT prevention trial had a much higher average selenium level than those in the current study.
"Among the 25 percent of men with the AA genotype, having greater selenium levels may protect against aggressive disease," the authors concluded. "However, for the 75 percent of men who carry a V allele, higher selenium levels might increase the likelihood of having worse characteristics."
Therefore, they add, it is important to know which type of SOD2 gene a man has when considering the risks and potential benefits of taking selenium supplements. Additionally, the authors say the effects of the interaction between the SOD2 genotype and selenium may help explain apparently conflicting results of previous studies.
The results may seem counterintuitive to the public, who have been told for years that antioxidants can help people live longer, healthier lives with a lowered risk of cancer. However, Kantoff says, "There is some precedent to this research has suggested that antioxidants could be protective if you don't have cancer, but once you do, then antioxidants may be a bad thing."
In addition to Kantoff and Chan, other authors of the paper include William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe, PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women's Hospital and the Harvard School of Public Health, and Irena King, PhD, of the Fred Hutchinson Cancer Research Center, Seattle.
The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Dana-Farber Cancer Institute
A higher risk of more-aggressive prostate cancer was seen in men with a certain genetic variant found in about 75 percent of the prostate cancer patients in the study. In those subjects, having a high level of selenium in the blood was associated with a two-fold greater risk of poorer outcomes than men with the lowest amounts of selenium. By contrast, the 25 percent of men with a different variant of the same gene and who had high selenium levels were at 40 percent lower risk of aggressive disease. The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2), an enzyme that protects the body against harmful oxygen compounds.
The research findings suggest that "if you already have prostate cancer, it may be a bad thing to take selenium," says Philip Kantoff, MD, director of Dana-Farber's Lank Center for Genitourinary Oncology and senior author of the study that is published by the Journal of Clinical Oncology on its website now and later will be in a print journal. The lead author is June Chan, ScD, of the University of California, San Francisco.
The unexpected results are the first to raise concern about this potentially harmful consequence of taking supplemental selenium. Kantoff says, "These findings are interesting particularly in light of the recent negative results from the SELECT prevention study, which asked if selenium could protect against prostate cancer."
The new study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer, a finding that these investigators had shown in a previous study. The authors say the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.
Selenium is a mineral found widely in rocks and dirt. Small amounts of selenium are essential for health: 40 to 70 micrograms is the recommended daily intake. In recent years, supplemental selenium has been sold and promoted as a means of preventing prostate cancer, largely based on observational studies that found higher risk of prostate cancer incidence and mortality in areas of the country that are naturally low in selenium.
However, research aimed at confirming the benefits of selenium supplementation have been mixed. Recently, the SELECT study, which involved 35,000 men, was halted early when, after more than five years, it showed that the supplements didn't affect the incidence of prostate cancer.
Previous studies had found that the risk of developing prostate cancer was modified by a strong interaction between SOD2 and selenium. The new research was designed to look at the effect of this interaction on men already diagnosed with prostate cancer.
Scientists examined banked blood samples, DNA, and medical records of 489 male Dana-Farber patients diagnosed between 1994 and 2001 with localized or locally advanced prostate cancer. Their mean age was 62, and their mean PSA (prostate-specific antigen) measurement was 6.0 ng/mL. About half the men were assessed as having a good disease risk, one-third had an intermediate risk, and the remaining one-sixth were at poor risk. The researchers measured the level of selenium in the blood and, using the stored DNA, they determined the SOD2 genotype the specific form of the SOD2 gene carried by each patient.
Simply having a high level of selenium was associated with a slightly elevated risk of aggressive prostate cancer. But the risk was much more strongly affected by the interaction of selenium levels and whether the patient had a certain variant of the SOD2 gene. Men with the highest selenium levels and the "AA" form of the SOD2 gene were 40 percent less likely to have been diagnosed with aggressive prostate cancer than the men with same gene form but low levels of selenium.
But for men carrying the "V" form of the gene, selenium had the opposite effect. In these men, those with the highest levels of selenium in their blood were about twice as likely to have an aggressive type of prostate cancer as their counterparts with low selenium levels.
The study couldn't determine whether any of the men had been taking selenium supplements or not. But the researchers noted that men in the large SELECT prevention trial had a much higher average selenium level than those in the current study.
"Among the 25 percent of men with the AA genotype, having greater selenium levels may protect against aggressive disease," the authors concluded. "However, for the 75 percent of men who carry a V allele, higher selenium levels might increase the likelihood of having worse characteristics."
Therefore, they add, it is important to know which type of SOD2 gene a man has when considering the risks and potential benefits of taking selenium supplements. Additionally, the authors say the effects of the interaction between the SOD2 genotype and selenium may help explain apparently conflicting results of previous studies.
The results may seem counterintuitive to the public, who have been told for years that antioxidants can help people live longer, healthier lives with a lowered risk of cancer. However, Kantoff says, "There is some precedent to this research has suggested that antioxidants could be protective if you don't have cancer, but once you do, then antioxidants may be a bad thing."
In addition to Kantoff and Chan, other authors of the paper include William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe, PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women's Hospital and the Harvard School of Public Health, and Irena King, PhD, of the Fred Hutchinson Cancer Research Center, Seattle.
The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Dana-Farber Cancer Institute
Tuesday, June 9, 2009
Gene activity reveals dynamic stroma microenvironment in prostate cancer
As stroma – the supportive framework of the prostate gland – react to prostate cancer, changes in the expression of genes occur that induce the formation of new structures such as blood vessels, nerves and parts of nerves, said researchers at Baylor College of Medicine in a report that appears in the current issue of the journal Clinical Cancer Research.
In this study, using special techniques and gene chips that allowed them to sample the entire genome, the researchers found changes in 1,141 genes. They were either upregulated – meaning that there was more of the protein with which they were associated than expected – or downregulated, which meant the opposite, said Dr. Michael Ittmann, professor of pathology at BCM and a senior author of the report. These gene changes may explain why men with reactive stroma face a more aggressive disease, said Ittmann and Dr. Gustavo Ayala, professor in the departments of pathology and urology at BCM and another senior author.
"Often in prostate cancer, you don't see much change in the stromal cells," said Ittmann. "However, in this subgroup of patients (in which the stroma become visibly reactive), you see a histologically recognizable change in the appearance of the stroma. Dr. Ayala has shown previously that this correlates with a bad prognosis. We know the stroma are doing something to promote bad behavior in cancer cells."
"These findings are very important as this is the first step in discovering pathways and mechanisms in the tumor microenvironment that could be targeted as a novel therapeutic approach to treat prostate cancer by treating the cancer microenvironment niche", said Dr. David Rowley, professor of molecular and cellular biology and urology at BCM, and another author.
Dr. Chad Creighton, an assistant professor in the Dan L. Duncan Cancer Center at BCM, searched the scientific literature to determine the biological processes with which the genes with changes had been linked in prior studies.
"We found that the top terms linked to the genes were related to neurogenesis (the growth of neurons or nerve cells)," said Ittmann. "This independently supported Dr. Ayala's previous finding that prostate cancer prompts the growth of new nerve cells, which is linked to poor prognosis."
Other genes were linked to axongenesis, which refers to new axons, the slender projection that conducts nerve impulses away from the body of a nerve cell.
That finding was exciting because it confirmed the neurogenesis findings from a new direction, said Ittmann and Ayala.
"We also found many changes in the DNA damage pathway genes," Ittmann said. These genes reduce the negative effects of DNA changes on cells – either by correcting the DNA or prompting cell death. "This implies that there may be different kinds of DNA damaging stimuli going on in the stroma as well as cancer cells," said Ittmann. "DNA damage could be related to mutations in the stroma."
The researchers also found changes in growth factor pathways, including those for fibroblast growth factor and transforming growth factor beta as well as pathways linked to the growth and maintenance of stem cells, said Ittmann.
While many of the gene changes they found may have no role in prostate cancer, the report lays the groundwork for determining which players and processes may have a role, he said.
"One question is what are the pathways turning on some of these genes in response to signals from the cancer cells," he said. "This description is the start," said Ittmann. "Now we can work on the mechanisms."
"We know that of all men who get prostate cancer, only about 10 percent would die of it," he said. "Of those who have disease localized to the prostate gland, only 5 percent would die from the disease. How do we differentiate those who really need treatment from those who might not? Can we identify the biomarkers that differentiate those? There is probably more than one marker and some may be stromal-based."
Baylor College of Medicine
In this study, using special techniques and gene chips that allowed them to sample the entire genome, the researchers found changes in 1,141 genes. They were either upregulated – meaning that there was more of the protein with which they were associated than expected – or downregulated, which meant the opposite, said Dr. Michael Ittmann, professor of pathology at BCM and a senior author of the report. These gene changes may explain why men with reactive stroma face a more aggressive disease, said Ittmann and Dr. Gustavo Ayala, professor in the departments of pathology and urology at BCM and another senior author.
"Often in prostate cancer, you don't see much change in the stromal cells," said Ittmann. "However, in this subgroup of patients (in which the stroma become visibly reactive), you see a histologically recognizable change in the appearance of the stroma. Dr. Ayala has shown previously that this correlates with a bad prognosis. We know the stroma are doing something to promote bad behavior in cancer cells."
"These findings are very important as this is the first step in discovering pathways and mechanisms in the tumor microenvironment that could be targeted as a novel therapeutic approach to treat prostate cancer by treating the cancer microenvironment niche", said Dr. David Rowley, professor of molecular and cellular biology and urology at BCM, and another author.
Dr. Chad Creighton, an assistant professor in the Dan L. Duncan Cancer Center at BCM, searched the scientific literature to determine the biological processes with which the genes with changes had been linked in prior studies.
"We found that the top terms linked to the genes were related to neurogenesis (the growth of neurons or nerve cells)," said Ittmann. "This independently supported Dr. Ayala's previous finding that prostate cancer prompts the growth of new nerve cells, which is linked to poor prognosis."
Other genes were linked to axongenesis, which refers to new axons, the slender projection that conducts nerve impulses away from the body of a nerve cell.
That finding was exciting because it confirmed the neurogenesis findings from a new direction, said Ittmann and Ayala.
"We also found many changes in the DNA damage pathway genes," Ittmann said. These genes reduce the negative effects of DNA changes on cells – either by correcting the DNA or prompting cell death. "This implies that there may be different kinds of DNA damaging stimuli going on in the stroma as well as cancer cells," said Ittmann. "DNA damage could be related to mutations in the stroma."
The researchers also found changes in growth factor pathways, including those for fibroblast growth factor and transforming growth factor beta as well as pathways linked to the growth and maintenance of stem cells, said Ittmann.
While many of the gene changes they found may have no role in prostate cancer, the report lays the groundwork for determining which players and processes may have a role, he said.
"One question is what are the pathways turning on some of these genes in response to signals from the cancer cells," he said. "This description is the start," said Ittmann. "Now we can work on the mechanisms."
"We know that of all men who get prostate cancer, only about 10 percent would die of it," he said. "Of those who have disease localized to the prostate gland, only 5 percent would die from the disease. How do we differentiate those who really need treatment from those who might not? Can we identify the biomarkers that differentiate those? There is probably more than one marker and some may be stromal-based."
Baylor College of Medicine
Friday, April 24, 2009
Men With Prostate Cancer Worry Less About Recurrence Than Their Spouses Do
Researchers at The Mount Sinai Medical Center in New York have found that, when it comes to worrying about the recurrence of prostate cancer, male patients worry less than their female spouses or partners. The study was presented at the 30th annual meeting of the Society of Behavioral Medicine in Montreal.
In a study of 96 men and their spouses or partners, Michael Diefenbach, Ph.D., Associate Professor of Urology and Oncological Sciences at Mount Sinai School of Medicine, found that, at the time of prostate cancer diagnosis, the male patients described themselves as "moderately worried" about the chance of their disease recurring, while their female spouses and partners described themselves as "very much" worried.
Read more at Medical News Today.
In a study of 96 men and their spouses or partners, Michael Diefenbach, Ph.D., Associate Professor of Urology and Oncological Sciences at Mount Sinai School of Medicine, found that, at the time of prostate cancer diagnosis, the male patients described themselves as "moderately worried" about the chance of their disease recurring, while their female spouses and partners described themselves as "very much" worried.
Read more at Medical News Today.
Friday, April 17, 2009
Autopsy study links prostate cancer to single rogue cell
One cell…one initial set of genetic changes - that's all it takes to begin a series of events that lead to metastatic cancer. Now, Johns Hopkins experts have tracked how the cancer process began in 33 men with prostate cancer who died of the disease. Culling information from autopsies, their study points to a set of genetic defects in a single cell that are different for each person's cancer.
"These were not your average autopsies," says pathologist G. Steven Bova, M.D., assistant professor of pathology at Johns Hopkins. "We dissected every bit of tumor - in the primary and metastatic sites - and recorded exactly where each piece of tissue came from, analyzed it, and databased the findings." In total, Bova estimates that he and his colleagues examined 150,000 slides and 30,000 blocks of tissue.
The study took 14 years to complete, and part of the challenge was in finding men living with prostate cancer who would agree to have their body autopsied immediately after they died. "Many of the men were motivated to join the study in hopes of leaving some legacy that might lead to cures for this cancer," says Bova, who holds secondary appointments in the departments of pathology, genetic medicine, health sciences informatics, oncology, and urology at Johns Hopkins.
"Much is unclear and appears chaotic about how cancer spreads, but analyzing genetic markers allows us to trace its roots backward, somewhat like ancestry," says Bova. Findings from the study were published online April 12 in Nature Medicine.
Clues to finding the genetic culprit for cancer spread are hidden in the changes that occur in a cell's DNA, the alphabetical code made up of chemicals that guide the everyday life of a cell. Cancers are caused by alterations in DNA code that occur in a variety of ways: making errors in the nucleotide alphabet through mutations, changing the balance of chemicals attached to the on/off switches of genes, and altering the number of gene copies in a cell. When the number of gene copies is disrupted in a cell beyond the customary two copies inherited from each parent, a gene's function can be damaged. This process, called copy number variation, can set the stage for unchecked cell growth and spread, a hallmark of cancer.
For this study, the investigators scanned genes spanning the whole genome in the autopsy samples looking for areas of copy number variation. They did this by attaching the DNA to special silicon chips, and then photographed them with a computer program that produces a report with varying colors representing the amount of DNA in the sample.
The scientists compared the patterns of gains and losses in tissue samples from multiple metastatic sites in 29 of the men. Unique copy number changes were identified, as well as ones that were shared between multiple metastatic sites in each man and with other men in the study.
For example, in several men, the investigators found cells in different areas of metastasis that contained missing chunks of DNA in one common region of the genome. The exact location of the DNA loss was different for each man, but all occurred in the same DNA region. "Each person has a different set of defects that contributes to the cancer," explains Bova.
Metastatic sites develop from cancer cells that break off of the primary cancer. If cancer cells at more than one metastatic site carry a common set of nonrandom genetic defects, it is likely that these cells are derived from a single parent cell, says Bova. Tissue samples from 14 of the 33 men were studied at the highest available resolution, and all showed common genetic patterns across metastatic sites, suggesting a single cell source for their cancer.
Bova says that future studies will help determine whether the common set of changes shared by the various metastatic sites arose in a single "big bang" in the prostate or if the changes accumulated more slowly over time.
Bova says that such autopsy studies of metastatic cancer can provide a molecular catalogue of cellular defects specific to individuals and general groups. The findings, he says, could help narrow the focus of research and guide personalized cancer therapy.
Johns Hopkins Medical Institutions
"These were not your average autopsies," says pathologist G. Steven Bova, M.D., assistant professor of pathology at Johns Hopkins. "We dissected every bit of tumor - in the primary and metastatic sites - and recorded exactly where each piece of tissue came from, analyzed it, and databased the findings." In total, Bova estimates that he and his colleagues examined 150,000 slides and 30,000 blocks of tissue.
The study took 14 years to complete, and part of the challenge was in finding men living with prostate cancer who would agree to have their body autopsied immediately after they died. "Many of the men were motivated to join the study in hopes of leaving some legacy that might lead to cures for this cancer," says Bova, who holds secondary appointments in the departments of pathology, genetic medicine, health sciences informatics, oncology, and urology at Johns Hopkins.
"Much is unclear and appears chaotic about how cancer spreads, but analyzing genetic markers allows us to trace its roots backward, somewhat like ancestry," says Bova. Findings from the study were published online April 12 in Nature Medicine.
Clues to finding the genetic culprit for cancer spread are hidden in the changes that occur in a cell's DNA, the alphabetical code made up of chemicals that guide the everyday life of a cell. Cancers are caused by alterations in DNA code that occur in a variety of ways: making errors in the nucleotide alphabet through mutations, changing the balance of chemicals attached to the on/off switches of genes, and altering the number of gene copies in a cell. When the number of gene copies is disrupted in a cell beyond the customary two copies inherited from each parent, a gene's function can be damaged. This process, called copy number variation, can set the stage for unchecked cell growth and spread, a hallmark of cancer.
For this study, the investigators scanned genes spanning the whole genome in the autopsy samples looking for areas of copy number variation. They did this by attaching the DNA to special silicon chips, and then photographed them with a computer program that produces a report with varying colors representing the amount of DNA in the sample.
The scientists compared the patterns of gains and losses in tissue samples from multiple metastatic sites in 29 of the men. Unique copy number changes were identified, as well as ones that were shared between multiple metastatic sites in each man and with other men in the study.
For example, in several men, the investigators found cells in different areas of metastasis that contained missing chunks of DNA in one common region of the genome. The exact location of the DNA loss was different for each man, but all occurred in the same DNA region. "Each person has a different set of defects that contributes to the cancer," explains Bova.
Metastatic sites develop from cancer cells that break off of the primary cancer. If cancer cells at more than one metastatic site carry a common set of nonrandom genetic defects, it is likely that these cells are derived from a single parent cell, says Bova. Tissue samples from 14 of the 33 men were studied at the highest available resolution, and all showed common genetic patterns across metastatic sites, suggesting a single cell source for their cancer.
Bova says that future studies will help determine whether the common set of changes shared by the various metastatic sites arose in a single "big bang" in the prostate or if the changes accumulated more slowly over time.
Bova says that such autopsy studies of metastatic cancer can provide a molecular catalogue of cellular defects specific to individuals and general groups. The findings, he says, could help narrow the focus of research and guide personalized cancer therapy.
Johns Hopkins Medical Institutions
Monday, March 2, 2009
Study Of Prostate Cancer Risk Factors Funded At UIC By $3 Million Award
Researchers at the University of Illinois at Chicago's Institute for Health Research and Policy have been awarded a five-year, $3 million grant from the National Cancer Institute to study the link between body fat and prostate cancer progression.
Recent studies have found that obese men with prostate cancer have a higher likelihood of developing progressive or fatal disease regardless of their tumor grade and stage at diagnosis.
Read entire story at Medical News Today.
Recent studies have found that obese men with prostate cancer have a higher likelihood of developing progressive or fatal disease regardless of their tumor grade and stage at diagnosis.
Read entire story at Medical News Today.
Friday, February 20, 2009
Prostate Specific Antigen Testing May Be Unnecessary For Some Older Men
Certain men aged 75 to 80 are unlikely to benefit from routine prostate specific antigen (PSA) testing, according to a Johns Hopkins study published in the April 2009 issue of The Journal of Urology.
The researchers found that men in this age group with PSA levels less than 3 nanograms per milliliter are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that the use of PSA testing in many older men may no longer be needed.
Read entire story at Medical News Today.
The researchers found that men in this age group with PSA levels less than 3 nanograms per milliliter are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that the use of PSA testing in many older men may no longer be needed.
Read entire story at Medical News Today.
Thursday, January 29, 2009
Gene Mutations Increase Risk for Aggressive Prostate Cancer
Men who develop prostate cancer face an increased risk of having an aggressive tumor if they carry a so-called breast cancer gene mutation, scientists from the Albert Einstein College of Medicine of Yeshiva University report in today’s issue of Clinical Cancer Research. The findings could help to guide prostate-cancer patients and their physicians in choosing treatment options.
The study, involving 979 men with prostate cancer and 1251 men without the disease, looked at whether participants carried mutations for either of two genes, BRCA1 and BRCA2. Women carrying mutations in either gene face an increased risk of developing breast cancer, ovarian cancer, or both.
All the people enrolled in the Einstein study were of Ashkenazi Jewish descent. The study focused on them because they are five times likelier than people in the general population to carry a mutation of any kind in the BRCA1 or BRCA2 genes. The researchers looked for the presence of three particular mutations–two in BRCA1 and one in BRCA2. Scientists believe that genetic discoveries among the Ashkenazi can benefit society as a whole in terms of preventing and treating major diseases.
Having any of the three mutations did not increase a man’s risk of developing prostate cancer, the study found. But for those men who did develop prostate cancer, two of the mutations–BRCA1-185delAG and the mutated BRCA2 gene–increased the risk that tumors would be aggressive or high-grade, as defined by a Gleason score of 7 or above. The Gleason score, based on the microscopic appearance of prostate tissue removed during a biopsy or surgery, assesses the aggressiveness of a prostate tumor on a scale from 2 (least aggressive) to 10 (most aggressive).
Specifically, prostate cancer patients with high-grade, aggressive tumors (Gleason scores of 7 or above) were 3.2 times more likely to carry the BRCA2 gene mutation than were men in the control group. Carriers of the BRCA1-185delAG mutation were also at increased risk of having an aggressive prostate cancer.
Previous investigations into a possible link between prostate-cancer risk and the BRCA1 and BRCA2 genes have yielded conflicting results–perhaps because they involved small numbers of subjects and lacked well-matched control groups. “Our large study shows conclusively that prostate cancer patients with either the BRCA2 gene mutation or the BRCA1-185delAG mutation are more susceptible to aggressive cancers than people without that mutation,” says Robert Burk, M.D., professor of pediatrics (genetics) at Einstein and senior author of the study.
Routine genetic testing for BRCA mutations–done by analyzing blood samples or cells swabbed from the inside of one’s cheeks–wouldn’t be justified for most men, says Dr. Burk: the prevalence of the mutations in the general population is very low; and men with high Gleason scores already know that their prostate cancer is aggressive. But, notes Dr. Burk, “our findings might have practical implications for some men diagnosed with early-stage (low Gleason score) prostate cancers–particularly Ashkenazi Jewish men, who are much more likely to have these mutations.”
“One of the biggest problems with early-stage prostate cancer is being able to distinguish between tumors with the potential to become aggressive and those that may persist for many years without enlarging or spreading,” notes Dr. Burk. For that reason, he says, Ashkenazi men diagnosed with early-stage prostate cancer might want to consider getting tested for the BRCA2 and BRCA1-185delAG mutations.
Knowing they have the mutation—and that their tumor may become aggressive—may influence treatment options that patients pursue. For example, a prostate cancer patient who has the BRCA2 mutation might vote against ‘watchful waiting’—in which the growth of the cancer is monitored and treatment is held in abeyance—and instead opt for surgery or radiation treatments with or without hormone blockade therapy.
For early-stage prostate cancer patients in the general population, knowing they carry the BRCA1 or BRCA2 mutation would also be useful, says Dr. Burk. But these mutations are so rare in the general population—a prevalence of far less than one percent—that testing is unlikely to reveal their presence.
Albert Einstein College of Medicine of Yeshiva University
The study, involving 979 men with prostate cancer and 1251 men without the disease, looked at whether participants carried mutations for either of two genes, BRCA1 and BRCA2. Women carrying mutations in either gene face an increased risk of developing breast cancer, ovarian cancer, or both.
All the people enrolled in the Einstein study were of Ashkenazi Jewish descent. The study focused on them because they are five times likelier than people in the general population to carry a mutation of any kind in the BRCA1 or BRCA2 genes. The researchers looked for the presence of three particular mutations–two in BRCA1 and one in BRCA2. Scientists believe that genetic discoveries among the Ashkenazi can benefit society as a whole in terms of preventing and treating major diseases.
Having any of the three mutations did not increase a man’s risk of developing prostate cancer, the study found. But for those men who did develop prostate cancer, two of the mutations–BRCA1-185delAG and the mutated BRCA2 gene–increased the risk that tumors would be aggressive or high-grade, as defined by a Gleason score of 7 or above. The Gleason score, based on the microscopic appearance of prostate tissue removed during a biopsy or surgery, assesses the aggressiveness of a prostate tumor on a scale from 2 (least aggressive) to 10 (most aggressive).
Specifically, prostate cancer patients with high-grade, aggressive tumors (Gleason scores of 7 or above) were 3.2 times more likely to carry the BRCA2 gene mutation than were men in the control group. Carriers of the BRCA1-185delAG mutation were also at increased risk of having an aggressive prostate cancer.
Previous investigations into a possible link between prostate-cancer risk and the BRCA1 and BRCA2 genes have yielded conflicting results–perhaps because they involved small numbers of subjects and lacked well-matched control groups. “Our large study shows conclusively that prostate cancer patients with either the BRCA2 gene mutation or the BRCA1-185delAG mutation are more susceptible to aggressive cancers than people without that mutation,” says Robert Burk, M.D., professor of pediatrics (genetics) at Einstein and senior author of the study.
Routine genetic testing for BRCA mutations–done by analyzing blood samples or cells swabbed from the inside of one’s cheeks–wouldn’t be justified for most men, says Dr. Burk: the prevalence of the mutations in the general population is very low; and men with high Gleason scores already know that their prostate cancer is aggressive. But, notes Dr. Burk, “our findings might have practical implications for some men diagnosed with early-stage (low Gleason score) prostate cancers–particularly Ashkenazi Jewish men, who are much more likely to have these mutations.”
“One of the biggest problems with early-stage prostate cancer is being able to distinguish between tumors with the potential to become aggressive and those that may persist for many years without enlarging or spreading,” notes Dr. Burk. For that reason, he says, Ashkenazi men diagnosed with early-stage prostate cancer might want to consider getting tested for the BRCA2 and BRCA1-185delAG mutations.
Knowing they have the mutation—and that their tumor may become aggressive—may influence treatment options that patients pursue. For example, a prostate cancer patient who has the BRCA2 mutation might vote against ‘watchful waiting’—in which the growth of the cancer is monitored and treatment is held in abeyance—and instead opt for surgery or radiation treatments with or without hormone blockade therapy.
For early-stage prostate cancer patients in the general population, knowing they carry the BRCA1 or BRCA2 mutation would also be useful, says Dr. Burk. But these mutations are so rare in the general population—a prevalence of far less than one percent—that testing is unlikely to reveal their presence.
Albert Einstein College of Medicine of Yeshiva University
Friday, January 16, 2009
The Genetic Fingerprint of Prostate Cancer
One in six American men are diagnosed with prostate cancer within their lifetime and 186,000 will be diagnosed this year. For most men, their disease is confined to the prostate gland, making it easier to treat and less lethal. However, some unfortunate patients suffer from a more aggressive cancer that metastasizes, or spreads beyond the boundaries of the prostate gland. Physician-scientists are trying to uncover part of the disease's molecular fingerprint, with the hope of explaining why some forms metastasize. Their findings may help physicians provide tailored, and therefore, more effective treatments for patients.
Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College, and attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, believes that the common joining of two genes to form a new fusion gene influences a certain type of prostate cancer that is more aggressive and sensitive to hormones. In a recent article published in the Journal of the National Cancer Institute, Dr. Rubin describes how in addition to the male hormone testosterone, estrogen -- typically thought of as a female hormone -- can stimulate this fusion gene. Dr. Rubin's group is currently exploring how this mechanism may help us understand how aggressive prostate cancer progresses in the absence of male hormones.
Currently, Dr. Rubin and his colleague Dr. Francesca Demichelis, assistant professor in pathology and laboratory medicine and computational biomedicine at the Institute of Computational Biomedicine at Weill Cornell Medical College, are testing blood samples and comparing the DNA of over 2,500 men with and without prostate cancer. They hope to discover clear genetic indicators of prostate cancer, especially its aggressive forms. Their findings will potentially lead to the development of diagnostic tests and preventive drugs for prostate cancer.
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College, and attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, believes that the common joining of two genes to form a new fusion gene influences a certain type of prostate cancer that is more aggressive and sensitive to hormones. In a recent article published in the Journal of the National Cancer Institute, Dr. Rubin describes how in addition to the male hormone testosterone, estrogen -- typically thought of as a female hormone -- can stimulate this fusion gene. Dr. Rubin's group is currently exploring how this mechanism may help us understand how aggressive prostate cancer progresses in the absence of male hormones.
Currently, Dr. Rubin and his colleague Dr. Francesca Demichelis, assistant professor in pathology and laboratory medicine and computational biomedicine at the Institute of Computational Biomedicine at Weill Cornell Medical College, are testing blood samples and comparing the DNA of over 2,500 men with and without prostate cancer. They hope to discover clear genetic indicators of prostate cancer, especially its aggressive forms. Their findings will potentially lead to the development of diagnostic tests and preventive drugs for prostate cancer.
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Sunday, October 26, 2008
Prostates Grown from Stem Cells
New proof that the mouse prostate contains stem cells could aid cancer research.
A single adult stem cell from the prostate of a mouse can develop into an entire functional organ, scientists reported online yesterday in Nature. The finding proves that a population of stem cells exists in the adult prostate, as many have long suspected, and it could provide insight into how prostate cancer develops.
"It's extremely exciting, the concept that you can reconstitute an entire prostate from a single cell," says Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research, at MIT, who was not involved in the work. "That's impressive stuff."
Read full story at Technology Review.
A single adult stem cell from the prostate of a mouse can develop into an entire functional organ, scientists reported online yesterday in Nature. The finding proves that a population of stem cells exists in the adult prostate, as many have long suspected, and it could provide insight into how prostate cancer develops.
"It's extremely exciting, the concept that you can reconstitute an entire prostate from a single cell," says Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research, at MIT, who was not involved in the work. "That's impressive stuff."
Read full story at Technology Review.
Sunday, October 5, 2008
Weight linked to prostate cancer death
New research, funded in part by the Canadian Cancer Society, shows that men suffering from prostate cancer are up to 2 1/2 times more at risk of dying from the disease if they are overweight or obese. The men who participated in the study had been weighed prior to being diagnosed with prostate cancer.
Dr. Michael Pollak, senior author of the study, published online in The Lancet Oncology, says the research team was surprised by these strong findings. "Previous studies have suggested a relationship between prostate cancer progression and being overweight," he says. "This study strongly confirms those earlier findings and in fact points to a leading culprit which appears to be an excess secretion of insulin in these patients." Excess production of insulin - or hyperinsulinemia - is one of the many metabolic changes that occur in overweight and obese people.
Heather Chappell, Senior Manager of Cancer Control Policy with the Canadian Cancer Society says: "This study emphasizes the value of reaching out to the Canadian public about the importance of maintaining a healthy body weight. We need to work to identify barriers that keep Canadians from eating as well as possible, and being as physically active as possible. It appears that having a healthy body weight can help you survive a prostate cancer diagnosis in the future."
"Being healthy is not simply up to the individual," she says. "In addition, we need healthy public policies that will help Canadians to make easy, affordable and healthy choices."
"Men living in affluent societies are facing two epidemics - obesity and prostate cancer," says Dr. Pollak of McGill University. "This research provides further impetus for men to avoid becoming overweight by improved physical activity and diet."
"Up until now, oncologists and researchers felt that the only hormones relevant to prostate cancer were the male hormones known as androgens. These results suggest that the insulin family may also be involved in the disease," he says.
The study looked at 2,546 men diagnosed with prostate cancer during a long-term follow-up sub-study - part of the Physicians Health Study involving more than 22,000 doctors.
This research was co-funded by the Canadian Cancer Society and the U.S. National Institutes of Health.
Canadian Cancer Society
Dr. Michael Pollak, senior author of the study, published online in The Lancet Oncology, says the research team was surprised by these strong findings. "Previous studies have suggested a relationship between prostate cancer progression and being overweight," he says. "This study strongly confirms those earlier findings and in fact points to a leading culprit which appears to be an excess secretion of insulin in these patients." Excess production of insulin - or hyperinsulinemia - is one of the many metabolic changes that occur in overweight and obese people.
Heather Chappell, Senior Manager of Cancer Control Policy with the Canadian Cancer Society says: "This study emphasizes the value of reaching out to the Canadian public about the importance of maintaining a healthy body weight. We need to work to identify barriers that keep Canadians from eating as well as possible, and being as physically active as possible. It appears that having a healthy body weight can help you survive a prostate cancer diagnosis in the future."
"Being healthy is not simply up to the individual," she says. "In addition, we need healthy public policies that will help Canadians to make easy, affordable and healthy choices."
"Men living in affluent societies are facing two epidemics - obesity and prostate cancer," says Dr. Pollak of McGill University. "This research provides further impetus for men to avoid becoming overweight by improved physical activity and diet."
"Up until now, oncologists and researchers felt that the only hormones relevant to prostate cancer were the male hormones known as androgens. These results suggest that the insulin family may also be involved in the disease," he says.
The study looked at 2,546 men diagnosed with prostate cancer during a long-term follow-up sub-study - part of the Physicians Health Study involving more than 22,000 doctors.
This research was co-funded by the Canadian Cancer Society and the U.S. National Institutes of Health.
Canadian Cancer Society
Tuesday, September 16, 2008
Prostate cancer genes behave like those in embryo
Gene activity in prostate cancer is reminiscent of that in the developing fetal prostate, providing further evidence that all cancers are not equal, Johns Hopkins researchers report. The finding could help scientists investigate how to manipulate the genetic program to fight a disease whose biology remains poorly understood despite more than half a century of investigation.
Read full story at Machines Like Us.
Read full story at Machines Like Us.
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