 |
|
Scientists find one reason why bladder cancer hits more men
April 23, 2007Scientists have discovered one of the reasons why bladder cancer is so much more prevalent in men than women: A molecular receptor or protein that is much more active in men than women plays a role in the development of the disease. The finding could open the door to new types of treatment with the disease.
In an article in the April 4 issue of the Journal of the National Cancer Institute, Chawnshang Chang, Ph.D., of the University of Rochester Medical Center and colleagues show that the androgen receptor, which is central to the action of testosterone and other hormones that are much more plentiful in men than women, appears to play a key role in the disease.
In experiments reported in the journal, mice without the receptor had dramatically lower rates of bladder cancer compared to normal mice with the receptor, and human cancer cells with the receptor were much more aggressive than those without it. Mice develop bladder cancer for many of the same reasons people do, and the molecular signals that control cancer development in mice mirror those in humans.
The disease hits about three times as many men as women, including estimates of 50,000 men and 17,000 women in the United States in 2007, according to the American Cancer Society. Some scientists have suspected that male hormones working in concert with the androgen receptor might play a role, but hard evidence has been minimal until now, said Edward Messing, M.D., a bladder cancer expert and chair of Urology. Instead, scientists have suspected that factors like greater exposure of men to cigarettes and industrial chemicals has been responsible.
"For many years, people have recognized that men are more likely than women to get bladder cancer," said Messing, one of the authors of the paper. "More and more women are smoking and working with chemicals in the workplace, yet their bladder cancer rates have not really changed much. There is no longer any question that the androgen receptor is playing a role in bladder cancer."
The work by a team of collaborators from Rochester and from Yokohama City University Graduate School of Medicine in Japan was led by Chang, director of the George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center and a faculty member in the departments of Urology and Pathology and the James P. Wilmot Cancer Center.
Chang is an expert on the androgen receptor, which is central to many diseases and conditions, most notably prostate cancer. For that disease, hormone therapy to block the supply of hormones that turn on the receptor is a staple of treatment for men with advanced disease. The new findings open the possibility that perhaps someday, drugs that target male hormones, like those used against prostate cancer, might help men with bladder cancer.
The strongest evidence for the involvement of male hormones in bladder cancer was what happened when Chang's team disabled the androgen receptor in mice. While their normal counterparts with the androgen receptor got significant levels of bladder cancer when exposed to a carcinogen - 92 percent of the males and 42 percent of the females - not a single mouse whose androgen receptor was knocked out developed bladder cancer. The mice without the receptor also had significantly fewer premalignant changes in their bladder.
Besides opening the door to possible new treatments, Chang says the findings could help doctors decide which cases of bladder cancer are most likely to re-occur. His team found a correlation between the frequency of the androgen receptor in tumor cells and the recurrence of the tumor - tumors more likely to re-appear had more of the protein. If the finding holds up in wider testing in human tumors, it would help doctors know which patients to treat aggressively right from the start.
The JNCI paper is the latest installment in a body of research Chang has compiled that shows that the story of the androgen receptor and male hormones like testosterone is much more complex than was once thought. For years it's been widely thought by doctors and scientists that all male hormones, and only male hormones, work through the androgen receptor.
But he felt there was more to the story. If anyone would know, it would be Chang, who in 1988 was the first person to clone the androgen receptor, and was the first to discover that the protein needs molecular allies called co-factors to accomplish many of its tasks. Now more than 80 co-factors are known, offering many new targets to stop conditions like male-pattern baldness and diseases like prostate cancer.
Nearly a decade ago, Chang showed that molecules other than male hormones like testosterone are able to activate the androgen receptor. That finding isn't simply gathering dust in textbooks; it likely explains why hormone therapy for men in the advanced stages of prostate cancer ultimately fails. His work explained a long-baffling phenomenon in these patients, where drugs that work well for a few years suddenly make the cancer grow again late in the course of the disease.
In the recent paper, Chang continued this line of work, only in bladder cancer instead of prostate cancer. He took a closer look at the nearly disease-free male mice that didn't get bladder cancer despite exposure to a carcinogen. Some of those mice then received a drug known as DHT, a male hormone. In theory, such a drug only works if the androgen receptor is present, so the drug should not have had an effect. But 25 percent of these mice then got bladder cancer, clear evidence that the hormone is able to somehow side-step the traditional, receptor-mediated, pathway and still have an effect.
The work shows starkly that simply cutting off the supply of hormones like testosterone will have only a limited effect. The androgen receptor can still play a crucial role in the development of cancer, even without the hormones. The team has shown in other studies that even female hormones such as estrogen can turn on the androgen receptor.
"The activity of the androgen receptor is different from the activity of hormones that target the receptor," said Chang. "We've shown very clearly that even without these hormones, the receptor is still active in the development of cancer. This is crucial information as doctors seek to develop treatments for diseases like prostate or bladder cancer in men."
To knock out the androgen receptor, the team used a compound known as ASC-J9, a synthetic chemical compound that is loosely based on a compound found in curcumin. Chang's laboratory, in collaboration with San Diego-based AndroScience Corp., has screened hundreds of compounds for their activity involving the androgen receptor. Just last month, the team showed that ASC-J9 offers promise against a rare neuromuscular disease known as Kennedy's disease.
The compound is now being tested as a cream to treat acne in a clinical trial run by AndroScience, a biotech company founded by Chang, Charles C-Y Shih, and Por-Hsiung Lai in 2000. The University owns a stake in the company, which has licensed several of Chang's research findings.
University of Rochester Medical Center
The disease hits about three times as many men as women, including estimates of 50,000 men and 17,000 women in the United States in 2007, according to the American Cancer Society. Some scientists have suspected that male hormones working in concert with the androgen receptor might play a role, but hard evidence has been minimal until now, said Edward Messing, M.D., a bladder cancer expert and chair of Urology. Instead, scientists have suspected that factors like greater exposure of men to cigarettes and industrial chemicals has been responsible.
"For many years, people have recognized that men are more likely than women to get bladder cancer," said Messing, one of the authors of the paper. "More and more women are smoking and working with chemicals in the workplace, yet their bladder cancer rates have not really changed much. There is no longer any question that the androgen receptor is playing a role in bladder cancer."
The work by a team of collaborators from Rochester and from Yokohama City University Graduate School of Medicine in Japan was led by Chang, director of the George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center and a faculty member in the departments of Urology and Pathology and the James P. Wilmot Cancer Center.
Chang is an expert on the androgen receptor, which is central to many diseases and conditions, most notably prostate cancer. For that disease, hormone therapy to block the supply of hormones that turn on the receptor is a staple of treatment for men with advanced disease. The new findings open the possibility that perhaps someday, drugs that target male hormones, like those used against prostate cancer, might help men with bladder cancer.
The strongest evidence for the involvement of male hormones in bladder cancer was what happened when Chang's team disabled the androgen receptor in mice. While their normal counterparts with the androgen receptor got significant levels of bladder cancer when exposed to a carcinogen - 92 percent of the males and 42 percent of the females - not a single mouse whose androgen receptor was knocked out developed bladder cancer. The mice without the receptor also had significantly fewer premalignant changes in their bladder.
Besides opening the door to possible new treatments, Chang says the findings could help doctors decide which cases of bladder cancer are most likely to re-occur. His team found a correlation between the frequency of the androgen receptor in tumor cells and the recurrence of the tumor - tumors more likely to re-appear had more of the protein. If the finding holds up in wider testing in human tumors, it would help doctors know which patients to treat aggressively right from the start.
The JNCI paper is the latest installment in a body of research Chang has compiled that shows that the story of the androgen receptor and male hormones like testosterone is much more complex than was once thought. For years it's been widely thought by doctors and scientists that all male hormones, and only male hormones, work through the androgen receptor.
But he felt there was more to the story. If anyone would know, it would be Chang, who in 1988 was the first person to clone the androgen receptor, and was the first to discover that the protein needs molecular allies called co-factors to accomplish many of its tasks. Now more than 80 co-factors are known, offering many new targets to stop conditions like male-pattern baldness and diseases like prostate cancer.
Nearly a decade ago, Chang showed that molecules other than male hormones like testosterone are able to activate the androgen receptor. That finding isn't simply gathering dust in textbooks; it likely explains why hormone therapy for men in the advanced stages of prostate cancer ultimately fails. His work explained a long-baffling phenomenon in these patients, where drugs that work well for a few years suddenly make the cancer grow again late in the course of the disease.
In the recent paper, Chang continued this line of work, only in bladder cancer instead of prostate cancer. He took a closer look at the nearly disease-free male mice that didn't get bladder cancer despite exposure to a carcinogen. Some of those mice then received a drug known as DHT, a male hormone. In theory, such a drug only works if the androgen receptor is present, so the drug should not have had an effect. But 25 percent of these mice then got bladder cancer, clear evidence that the hormone is able to somehow side-step the traditional, receptor-mediated, pathway and still have an effect.
The work shows starkly that simply cutting off the supply of hormones like testosterone will have only a limited effect. The androgen receptor can still play a crucial role in the development of cancer, even without the hormones. The team has shown in other studies that even female hormones such as estrogen can turn on the androgen receptor.
"The activity of the androgen receptor is different from the activity of hormones that target the receptor," said Chang. "We've shown very clearly that even without these hormones, the receptor is still active in the development of cancer. This is crucial information as doctors seek to develop treatments for diseases like prostate or bladder cancer in men."
To knock out the androgen receptor, the team used a compound known as ASC-J9, a synthetic chemical compound that is loosely based on a compound found in curcumin. Chang's laboratory, in collaboration with San Diego-based AndroScience Corp., has screened hundreds of compounds for their activity involving the androgen receptor. Just last month, the team showed that ASC-J9 offers promise against a rare neuromuscular disease known as Kennedy's disease.
The compound is now being tested as a cream to treat acne in a clinical trial run by AndroScience, a biotech company founded by Chang, Charles C-Y Shih, and Por-Hsiung Lai in 2000. The University owns a stake in the company, which has licensed several of Chang's research findings.
University of Rochester Medical Center
Bladder Cancer Current Events and Bladder Cancer News RSSSelenium may prevent high risk-bladder cancer
A study published in the December issue of Cancer Prevention Research, a journal of the American Association for Cancer Research, suggests that selenium, a trace mineral found in grains, nuts and meats, may aid in the prevention of high-risk bladder cancer.
Bladder cancer detected via amplified gene in cells found in urine
Counting the copies of a specific gene in cells gathered from a urine sample may provide a simple, noninvasive way to detect bladder cancer, a team led by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.
NewYork-Presbyterian/Columbia leads research into robotic surgery for kidney cancer
Clinical research at NewYork-Presbyterian Hospital/Columbia University Medical Center is helping bring the advantages of robotic surgery, including reduced pain and quicker recovery, to kidney cancer patients.
Patients unaware of link between smoking and bladder cancer
Even though cigarette smoking accounts for up to half of all bladder cancer cases, few people are aware of the connection - including more than three-quarters of patients who have bladder cancer.
Pregnancy may help protect against bladder cancer
Pregnancy seems to confer some protection against bladder cancer in mice, scientists have found.
Biomarker predicts malignancy potential of HG-PIN lesions in the prostate
Men whose prostate cancer screenings show high grade prostatic intraepithelial neoplasia (HG-PIN) may find themselves in limbo, "stuck" between diagnoses - they are told prostate cancer has not yet developed, but it might, and they are advised to undergo repeated needle biopsies as a precaution.
New type of drug shrinks primary breast cancer tumors significantly in just 6 weeks
A drug that targets the cell surface receptors that play an important role in many types of cancer can bring about significant tumour regression in breast cancer after only six weeks of use.
UAB Study Shows Drug May Fight Biliary Cancers
Laboratory studies by University of Alabama at Birmingham (UAB) researchers have shown that the drug triphendiol (NV-196) causes cell death in pancreatic and bile duct cancer cell lines, slows tumor growth and sensitizes tumors to chemotherapy treatments.
Extract of broccoli sprouts may protect against bladder cancer
A concentrated extract of freeze dried broccoli sprouts cut development of bladder tumors in an animal model by more than half, according to a report in the March 1 issue of Cancer Research, a journal of the American Association for Cancer Research.
Study looks at new bladder cancer therapy for patients unresponsive to standard treatment
As many as half of patients with superficial bladder cancer do not respond to the standard first-line chemotherapy placed into the bladder, according to current multi-center outcomes data. When this happens, typically, their only option is surgical removal of the bladder.
More Bladder Cancer Current Events and Bladder Cancer News Articles
 | The Guide to Living with Bladder Cancer by Mark P. Schoenberg Bladder cancer is one of the most common cancers--and one of the least discussed. But bladder cancer, like other kinds of cancer, will greatly change the life of anyone who has the disease. Learning to live with the challenge of bladder cancer means getting good medical care, building a support group, and gathering as much information as you can. In The Guide to Living with Bladder Cancer, Dr.... |
 | Bladder Cancer (Cleveland Clinic Guide) by M D Raghavan, Kathleen Tuthill Cancer that arises in the bladder is one of the most common malignancies in industrialized societies and yet is not well understood in the community at large. Bladder Cancer: A Cleveland Clinic Guide provides simple, non-medical explanations of this disease for people who have to deal with this illness, either as patients or as those who care for these... |
 | Bladder Cancer: A Resource Guide for Patients and Their Families by Gary Dunetz If you, a loved one or friend has been diagnosed with bladder cancer, learning the basics is of utmost importance. It is essential to understand the nature of the disease, the work up and variety of treatments which are available. This book is comprehensive yet user friendly. It is written in a question and answer format in conversational tone. The physician author is a clinical urologist who has... |
 | 100 Questions & Answers About Bladder Cancer by Pamela Ellsworth, Brett Carswell Approximately 62,000 people are diagnosed with bladder cancer each year, making bladder cancer the fourth most common type of cancer in men and the eighth most common type in women. Whether you're a newly diagnosed bladder cancer patient, a survivor, or a friend or relative of either, this book offers help. The only book to provide both the doctor's and patient's views, 100 Questions & Answers... |
 | Textbook of Bladder Cancer A comprehensive reference, drawing on the expertise of international leaders in the field, this text covers everything from epidemiology, pathology, and diagnosis to the treatment of both superficial and invasive bladder cancers . The book contains over 300 to quality... |
 | Treatment and Management of Bladder Cancer This second edition is expertly updated and follows the same easy to read format as the previous edition. Topics covered... |
 | Carcinoma of the Bladder (Contemporary Issues in Cancer Imaging) This volume of the successful Contemporary Issues in Cancer Imaging brings in contributions from the entire multidisciplinary team for a full picture of the role of imaging in bladder cancer. Imaging techniques continue to evolve and this volume explores the relevance of CT with multidetector array, MRI, and computer-based reconstructions such as 'virtual cystoscopy' to treatment choices in... |
 | Bladder Cancer (Cancer Surveys, Vol 31) (Cancer Surveys, Vol 31) by R. T. D. Oliver, M. J. Coptcoat Published for the Imperial Cancer Research Fund. For clinicians, researchers, and... |
| Bladder Cancer (Butterworth International Medical Reviews. Urology, Vol 1) (v. 1) | |
| Understanding Cancer of the Bladder by CancerBACUP |
| © 2009 BrightSurf.com |