In the online edition of the British Journal of Urology International, Dr. David Webb and associates from Melbourne, Australia report the bladder neck contracture rates in men undergoing open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RALP).
A single-surgeon series of 200 consecutive men undergoing RP at two medical centers in Melbourne between March 2003 and September 2007 were analyzed. The 100 ORP patients had a conventional approach with bladder neck mucosa eversion and longitudinal racquet handle repair posteriorly. The urethra and bladder were anastomosed over a 20 F silicone catheter using four interrupted full thickness 2-0 absorbable sutures. In addition, a posterior suture at the 6 o'clock position held the bladder to the urethra in apposition. The catheter was removed at 5-6 days after RP. RALP was performed in 100 men with a nerve-sparing technique and none had bladder neck racquet handle reconstruction. The urethra-vesical anastomosis was made using continuous 3-0 absorbable sutures. Between 12 and 14 passages of the suture were made. The Foley catheter was removed 6-7 days after surgery. Worsening urinary stream or urinary retention resulted in endoscopic visualization to diagnose bladder neck contracture (BNC). Any BNC was endoscopically incised at the 6 o'clock position. Patients were then either discharged with a catheter, or on self-intermittent catheterization for 4-6 weeks. No patient had worsening continence due to BNC incision.
The rate of BNC was 0% in the RALP group compared to 9% in the ORP group. In addition, the ORP group had a higher prostate weight (54 vs. 46.5 gms) and preoperative PSA (7.3ng/ml vs. 5.0ng/ml). None of the 7 men with a prior history of TURP experienced a BNC. The time to BNC was 5 months and most occurred within 8 weeks.
Webb DR, Sethi K, Gee K
BJU Int. 2008 Dec 5. Epub ahead of print.
doi:10.1111/j.1464-410X.2008.08278.x
Monday, March 16, 2009
Top Belgian Cancer Center Becomes First In Country To Introduce RapidArc Radiotherapy Treatments From Varian Medical Systems
A 74-year-old prostate cancer patient has become the first person in Belgium to be treated using a new, faster form of radiotherapy that extends more advanced care to more patients. The University Hospital of Leuven delivered the faster treatment using RapidArc radiotherapy technology from Varian Medical Systems (NYSE: VAR).
The patient, a retired military aircraft engineer from Kortenberg near Leuven, said he was pleased to be the country's first to receive this advanced form of image-guided intensity modulated radiotherapy (IMRT). By coincidence, his older brother was also treated for prostate cancer at the hospital two years ago, receiving a successful course of conventional IMRT.
"This patient is now feeling very well and he is very proud of being number one in Belgium," says Dr. Karin Haustermans, head of the Department of Oncology. "We are identifying patients for whom RapidArc is a beneficial treatment and we have been very pleased with the early results. Not everyone will be treated in this way but it appears to have major advantages in speed and precision for many of our prostate cancer patients."
Frank Van den Heuvel, director of physics, believes RapidArc will enable the hospital to bring down standard treatment slots from 12 minutes to ten minutes, enabling six patients to be treated per hour rather than five. "This is an entirely new technique for us so early treatments will inevitably take a little longer but once it becomes a part of our routine I believe we can achieve these targets," he said.
Prior to starting RapidArc treatments, research physicist Wouter Crijns carried out a series of tests revealing that RapidArc treatments could offer five significant benefits over and above conventional IMRT treatments. Along with time-savings he identified an improvement in sparing nearby organs at risk from being affected by the radiation, an ability to boost the dose from 74 to 78 Gy while achieving a 30% reduction in 'monitor units' used during treatment, and an ability to tighten margins from 1cm to 0.7cm because of less prostate motion during the shorter treatment. In addition, patient comfort is improved because the time they need to lie on the treatment table is shortened considerably.
"The team at Leuven has done a great job in introducing RapidArc treatments so quickly and becoming among the first in Europe to begin treatments using this technique," said Vincent Ronfle, Varian's regional sales manager. "This hospital is well-known for its innovative approach and technical choices and it has been quick to implement an advanced treatment technique which improves quality while saving time."
The University Hospital of Leuven treats up to 200 patients per day on five Varian Clinac(R) linear accelerators. The hospital was one of the earliest in Europe to introduce IMRT treatments and the technique is now used routinely for prostate, head & neck, oesophagus and rectal cancer treatments. As the hospital becomes more familiar with the technique, RapidArc image-guided IMRT treatments will gradually be introduced for indications other than prostate cancer.
About Varian Medical Systems
Varian Medical Systems, Inc., of Palo Alto, California, is the world's leading manufacturer of medical devices and software for treating cancer and other medical conditions with radiotherapy, radiosurgery, proton therapy, and brachytherapy. The company supplies informatics software for managing comprehensive cancer clinics, radiotherapy centers and medical oncology practices. Varian is a premier supplier of tubes and digital detectors for X-ray imaging in medical, scientific, and industrial applications and also supplies X-ray imaging products for cargo screening and industrial inspection. Varian Medical Systems employs approximately 5,100 people who are located at manufacturing sites in North America and Europe and in its 60 sales and support offices around the world. For more information, visit http://www.varian.com.
The patient, a retired military aircraft engineer from Kortenberg near Leuven, said he was pleased to be the country's first to receive this advanced form of image-guided intensity modulated radiotherapy (IMRT). By coincidence, his older brother was also treated for prostate cancer at the hospital two years ago, receiving a successful course of conventional IMRT.
"This patient is now feeling very well and he is very proud of being number one in Belgium," says Dr. Karin Haustermans, head of the Department of Oncology. "We are identifying patients for whom RapidArc is a beneficial treatment and we have been very pleased with the early results. Not everyone will be treated in this way but it appears to have major advantages in speed and precision for many of our prostate cancer patients."
Frank Van den Heuvel, director of physics, believes RapidArc will enable the hospital to bring down standard treatment slots from 12 minutes to ten minutes, enabling six patients to be treated per hour rather than five. "This is an entirely new technique for us so early treatments will inevitably take a little longer but once it becomes a part of our routine I believe we can achieve these targets," he said.
Prior to starting RapidArc treatments, research physicist Wouter Crijns carried out a series of tests revealing that RapidArc treatments could offer five significant benefits over and above conventional IMRT treatments. Along with time-savings he identified an improvement in sparing nearby organs at risk from being affected by the radiation, an ability to boost the dose from 74 to 78 Gy while achieving a 30% reduction in 'monitor units' used during treatment, and an ability to tighten margins from 1cm to 0.7cm because of less prostate motion during the shorter treatment. In addition, patient comfort is improved because the time they need to lie on the treatment table is shortened considerably.
"The team at Leuven has done a great job in introducing RapidArc treatments so quickly and becoming among the first in Europe to begin treatments using this technique," said Vincent Ronfle, Varian's regional sales manager. "This hospital is well-known for its innovative approach and technical choices and it has been quick to implement an advanced treatment technique which improves quality while saving time."
The University Hospital of Leuven treats up to 200 patients per day on five Varian Clinac(R) linear accelerators. The hospital was one of the earliest in Europe to introduce IMRT treatments and the technique is now used routinely for prostate, head & neck, oesophagus and rectal cancer treatments. As the hospital becomes more familiar with the technique, RapidArc image-guided IMRT treatments will gradually be introduced for indications other than prostate cancer.
About Varian Medical Systems
Varian Medical Systems, Inc., of Palo Alto, California, is the world's leading manufacturer of medical devices and software for treating cancer and other medical conditions with radiotherapy, radiosurgery, proton therapy, and brachytherapy. The company supplies informatics software for managing comprehensive cancer clinics, radiotherapy centers and medical oncology practices. Varian is a premier supplier of tubes and digital detectors for X-ray imaging in medical, scientific, and industrial applications and also supplies X-ray imaging products for cargo screening and industrial inspection. Varian Medical Systems employs approximately 5,100 people who are located at manufacturing sites in North America and Europe and in its 60 sales and support offices around the world. For more information, visit http://www.varian.com.
Male Sexual Function Comes Back Faster With New Surgical Procedure Developed At CINJ
A new robotic surgical technique developed at The Cancer Institute of New Jersey (CINJ) for the removal of all or part of the prostate gland is showing what investigators call a "dramatic improvement" in a male's sexual potency rate. The results were recently presented at the 26th World Congress Endourology meeting in Shanghai, China. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School and has also developed a Center of Excellence for robotic surgery.
Robotic prostatectomy allows a surgeon to control a set of robotic arms that holds the surgical instruments in order to remove prostate cancer through several incisions that are smaller than a quarter. It allows for additional precision, reduced blood loss, shorter hospital stays and faster recovery for the patient. Isaac Kim, MD, PhD, who is the director of CINJ's Urologic Oncology Program and assistant professor of surgery at UMDNJ-Robert Wood Johnson Medical School, found a way to enhance the procedure, by developing a new technique known as Athermal Intrafascial Robotic (AIR) prostatectomy.
In AIR prostatectomy, the nerve that controls a man's ability to have an erection is better preserved by sparing over 90 percent of the tissues that surrounds the prostate. In the conventional open or robotic radical prostatectomy, typically only 40 to 50 percent of the tissue around the prostate is spared. Additional tissues that are located at the top of the prostate are nearly impossible to spare during an open prostatectomy due to the presence of a major vein called the dorsal venous complex.
Typically with the conventional method, the sexual potency rate is between 65 and 75 percent at one year following the surgery. With the AIR procedure, investigators at CINJ found the potency level was at 91 percent nine months post surgery. At the nine-month mark for the conventional robotic method, the potency rate was only 67 percent.
Dr. Kim, who has performed more than 450 robotic prostatectomies over the past four years at CINJ's Flagship hospital, Robert Wood Johnson University Hospital in New Brunswick, notes the results are significant, "Not only does the AIR procedure help men regain sexual function in a quicker fashion, but it also helps them to regain control over their bladder faster as well as reducing incontinence."
At six months, the continence rate (defined as requiring no protective pads) following the AIR procedure was 93 percent.
About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey is the state's first and only National Cancer Institute-designated Comprehensive Cancer Center, and is dedicated to improving the prevention, detection, treatment and care of patients with cancer. CINJ's physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice quite literally bringing research to life. The Cancer Institute of New Jersey is a center of excellence of UMDNJ-Robert Wood Johnson Medical School. To support CINJ, please call the Cancer Institute of New Jersey Foundation at 1-888-333-CINJ.
The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides a mechanism to rapidly disseminate important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. Affiliate Hospitals: Bayshore Community Hospital, Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, CentraState Healthcare System, Cooper University Hospital*, Jersey Shore University Medical Center, JFK Medical Center, Raritan Bay Medical Center, Robert Wood Johnson University Hospital at Hamilton (CINJ at Hamilton), Saint Peter's University Hospital, Somerset Medical Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate
Michele Fisher
Media Relations Specialist
Office of Communications
The Cancer Institute of New Jersey
195 Little Albany Street
New Brunswick, NJ 08903
http://www.cinj.org
Robotic prostatectomy allows a surgeon to control a set of robotic arms that holds the surgical instruments in order to remove prostate cancer through several incisions that are smaller than a quarter. It allows for additional precision, reduced blood loss, shorter hospital stays and faster recovery for the patient. Isaac Kim, MD, PhD, who is the director of CINJ's Urologic Oncology Program and assistant professor of surgery at UMDNJ-Robert Wood Johnson Medical School, found a way to enhance the procedure, by developing a new technique known as Athermal Intrafascial Robotic (AIR) prostatectomy.
In AIR prostatectomy, the nerve that controls a man's ability to have an erection is better preserved by sparing over 90 percent of the tissues that surrounds the prostate. In the conventional open or robotic radical prostatectomy, typically only 40 to 50 percent of the tissue around the prostate is spared. Additional tissues that are located at the top of the prostate are nearly impossible to spare during an open prostatectomy due to the presence of a major vein called the dorsal venous complex.
Typically with the conventional method, the sexual potency rate is between 65 and 75 percent at one year following the surgery. With the AIR procedure, investigators at CINJ found the potency level was at 91 percent nine months post surgery. At the nine-month mark for the conventional robotic method, the potency rate was only 67 percent.
Dr. Kim, who has performed more than 450 robotic prostatectomies over the past four years at CINJ's Flagship hospital, Robert Wood Johnson University Hospital in New Brunswick, notes the results are significant, "Not only does the AIR procedure help men regain sexual function in a quicker fashion, but it also helps them to regain control over their bladder faster as well as reducing incontinence."
At six months, the continence rate (defined as requiring no protective pads) following the AIR procedure was 93 percent.
About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey is the state's first and only National Cancer Institute-designated Comprehensive Cancer Center, and is dedicated to improving the prevention, detection, treatment and care of patients with cancer. CINJ's physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice quite literally bringing research to life. The Cancer Institute of New Jersey is a center of excellence of UMDNJ-Robert Wood Johnson Medical School. To support CINJ, please call the Cancer Institute of New Jersey Foundation at 1-888-333-CINJ.
The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides a mechanism to rapidly disseminate important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. Affiliate Hospitals: Bayshore Community Hospital, Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, CentraState Healthcare System, Cooper University Hospital*, Jersey Shore University Medical Center, JFK Medical Center, Raritan Bay Medical Center, Robert Wood Johnson University Hospital at Hamilton (CINJ at Hamilton), Saint Peter's University Hospital, Somerset Medical Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate
Michele Fisher
Media Relations Specialist
Office of Communications
The Cancer Institute of New Jersey
195 Little Albany Street
New Brunswick, NJ 08903
http://www.cinj.org
Removable Stent Provides Viable Solution To Patients Recovering From Complications Of Bladder And Prostate Cancer Operations
Allium Group, the developer and manufacturer of innovative stents for the urinary, gastro-intestinal, pulmonary and peripheral vascular tracts, announced that it has been awarded a CE mark for its large caliber, removable posterior urethral stent. This is a novel solution for patients who developed a stenosis at the bladder neck after radical removal of the prostate or the bladder for cancer.
"As the fourth stent to receive a CE Mark, Allium's technology is rapidly gaining an established presence throughout Europe as more hospitals and physicians discover the significant advantages of using removable stents as an effective solution," said Limor Domnitz Gishri, CEO of Allium Medical. "Allium is at the forefront of the expanding stent industry, developing the only next generation stents designed to fit site specific areas in the urinary and gastro-intestinal tracts. Allium's goal is to provide the global medical market with the tools to enhance patient treatment, comfort and quality of life with a minimally invasive approach."
The Allium Bladder-neck Stent is a removable device comprised of a super-elastic structure inserted into the posterior urethra of patients who have undergone radical prostatectomy (for prostate cancer) and radical cystoprostatectomy (for bladder cancer). In up to 18% of these patients a stenosis may develop at the anastomosis site, necessitating repeated dilatations to allow for a reasonable voiding. Currently, the conventional management of these stenoses is frequently performed mechanical dilations, endoscopic incisions or laser vaporization. The success rate of these procedures is low and patients have to undergo repeated treatments. The bladder-neck stent was developed based on the experience of Prof. Daniel Yachia, who successfully used removable stents in this difficult to treat area.
"We are glad that with the CE Mark, more European hospitals and physicians can offer their patients with Allium's new stents as a viable option that does not require a highly specialized reconstructive bladder neck repair procedure," commented Professor Daniel Yachia, founder and CSO of Allium Medical, an urologist and acknowledged international authority on urinary system stenting. "More urologists will also be able to perform this simple once a year treatment under regional anesthesia proven to be more effective than conventional treatments which have to be repeated frequently."
Allium's biliary and ureteral stents are currently being distributed through numerous partners in various European markets including Italy, United Kingdom, Germany and Austria, Benelux, Spain, Greece, Scandinavia and South Africa.
About Allium Medical
Founded in 2001, Allium Medical is a privately owned medical device company offering next-generation stents based on a proprietary technological platform that enables physicians to offer more effective stent solutions for enhancing patients' quality of life. Allium Medical has developed site-specific, anatomically and functionally compatible stents with applications in the urinary and gastro-intestinal tracts. Allium was awarded CE marks for its biliary and ureteral stents, commencing sales in Europe in June 2007 and receiving follow-up orders from its distributors thereafter. Distribution of Allium's new prostatic stent which also recently received a CE Certification, and the posterior urethral /bladder-neck stents will begin during the first months of 2009. Allium's headquarters, R&D and manufacturing facilities are located in Caesarea, Israel.
"As the fourth stent to receive a CE Mark, Allium's technology is rapidly gaining an established presence throughout Europe as more hospitals and physicians discover the significant advantages of using removable stents as an effective solution," said Limor Domnitz Gishri, CEO of Allium Medical. "Allium is at the forefront of the expanding stent industry, developing the only next generation stents designed to fit site specific areas in the urinary and gastro-intestinal tracts. Allium's goal is to provide the global medical market with the tools to enhance patient treatment, comfort and quality of life with a minimally invasive approach."
The Allium Bladder-neck Stent is a removable device comprised of a super-elastic structure inserted into the posterior urethra of patients who have undergone radical prostatectomy (for prostate cancer) and radical cystoprostatectomy (for bladder cancer). In up to 18% of these patients a stenosis may develop at the anastomosis site, necessitating repeated dilatations to allow for a reasonable voiding. Currently, the conventional management of these stenoses is frequently performed mechanical dilations, endoscopic incisions or laser vaporization. The success rate of these procedures is low and patients have to undergo repeated treatments. The bladder-neck stent was developed based on the experience of Prof. Daniel Yachia, who successfully used removable stents in this difficult to treat area.
"We are glad that with the CE Mark, more European hospitals and physicians can offer their patients with Allium's new stents as a viable option that does not require a highly specialized reconstructive bladder neck repair procedure," commented Professor Daniel Yachia, founder and CSO of Allium Medical, an urologist and acknowledged international authority on urinary system stenting. "More urologists will also be able to perform this simple once a year treatment under regional anesthesia proven to be more effective than conventional treatments which have to be repeated frequently."
Allium's biliary and ureteral stents are currently being distributed through numerous partners in various European markets including Italy, United Kingdom, Germany and Austria, Benelux, Spain, Greece, Scandinavia and South Africa.
About Allium Medical
Founded in 2001, Allium Medical is a privately owned medical device company offering next-generation stents based on a proprietary technological platform that enables physicians to offer more effective stent solutions for enhancing patients' quality of life. Allium Medical has developed site-specific, anatomically and functionally compatible stents with applications in the urinary and gastro-intestinal tracts. Allium was awarded CE marks for its biliary and ureteral stents, commencing sales in Europe in June 2007 and receiving follow-up orders from its distributors thereafter. Distribution of Allium's new prostatic stent which also recently received a CE Certification, and the posterior urethral /bladder-neck stents will begin during the first months of 2009. Allium's headquarters, R&D and manufacturing facilities are located in Caesarea, Israel.
Algeta To Enroll US Patients Into Global Phase III ALSYMPCA Trial Following Successful End Of Phase II Meeting With FDA
Algeta ASA (OSE: ALGETA), the cancer therapeutics company, announces that it is to enroll US patients into its ALSYMPCA phase III trial evaluating Alpharadin as a new treatment for bone metastases in patients with hormone-refractory prostate cancer (HRPC). This decision follows a successful end-of-phase II meeting* with the US Food and Drug Administration (FDA), held on 30 January 2009.
Algeta began enrolling patients for its global phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) study in June 2008 and aims to enroll approximately 750 HRPC patients with bone metastases. Recruitment of US patients into the study is now planned to commence this year.
Alpharadin (radium-223) is Algeta's lead clinical candidate and has demonstrated in phase II studies strong evidence that it can prolong patient survival times, improves quality of life and offers a placebo-like safety profile.
These exciting clinical results combined with Alpharadin's unique bone-targeting properties highlight the potential of this novel cancer therapeutic to be an important new treatment for bone metastases that frequently arise from a number of high incidence cancers as well as HRPC (e.g. breast, lung and kidney). Bone metastases are a serious consequence of certain advanced cancers causing intractable and debilitating pain as well as further reducing life expectancy.
Andrew Kay, Algeta's President and CEO, said: "Our recent and previous discussions with FDA have been productive and we believe they have contributed positively to the overall clinical development plan for Alpharadin. We are therefore extremely pleased to enroll US patients into our pivotal ALSYMPCA study following the successful end-of-phase II meeting with the FDA. We will be focusing on initiating the study at key clinical centers in the US over the coming months."
ALSYMPCA phase III clinical study
The ALSYMPCA study is a double-blind, randomized, controlled trial that enrolls symptomatic HRPC patients who will be randomized to receive Alpharadin plus best standard of care or placebo plus best standard of care.
The primary efficacy endpoint of the trial is overall survival. Patients are being randomized 2-to-1 in favor of Alpharadin, which will be given as six injections of 50 kBq/kg body weight, four weeks apart. Secondary endpoints include time to occurrence of specified disease-related events, and time to progression of certain key biomarkers indicative of disease status, including blood levels of serum prostate-specific antigen (PSA) and total alkaline phosphatase (ALP). In addition, the trial will monitor and evaluate both the acute and long-term safety profiles of Alpharadin treatment as well as its impact on quality of life.
For more information on the ALSYMPCA trial, please go to http://www.algeta.com and click on the ALSYPMCA link in the menu bar.
About Algeta
Algeta ASA is a cancer therapeutics company built on world-leading, proprietary technology. Algeta is developing new, targeted cancer therapeutics that harness the unique characteristics of alpha particle emitters and are potent, well-tolerated and convenient to use.
Algeta's lead product candidate, Alpharadin (based on radium-223), has blockbuster potential for treating bone metastases arising from multiple major cancer types, owing to its bone-targeting nature, potent efficacy (therapeutic and palliative) and benign, placebo-like safety profile. Development of Alpharadin is most advanced targeting bone metastases resulting from hormone-refractory prostate cancer (HRPC), and it entered an international phase III clinical trial (ALSYMPCA) in mid-2008 based on compelling clinical results from a comprehensive phase II program.
Algeta's strategy is to launch Alpharadin as a first or second line treatment for cancer patients with bone metastases either alone or in combination with current standard of care therapies, thereby maximizing its commercial potential.
Algeta is also developing other technologies for delivering alpha emitters. These include microparticles, liposomes, and methods to enhance the potency of therapeutic antibodies and other tumor-targeting molecules by linking them to the alpha particle emitter thorium-227. The Company is headquartered in Oslo, Norway, and was founded in 1997. Algeta listed on the Oslo Stock Exchange in March 2007 (Ticker: ALGETA).
Alpharadin and Algeta are trademarks of Algeta ASA.
About Bone Metastases
Bone is the most common organ to be affected by metastatic cancer (Ref. 1). Approximately 1.5 million cancer patients suffer from bone metastases worldwide and there are some 300,000 new cases each year. Importantly, metastases may stay confined to the skeleton with subsequent morbidity and eventual death almost entirely due to skeletal complications and their treatment.
Some 80% of bone metastases are due to prostate and breast carcinomas. For these high incidence cancers, 65-75% patients with advanced disease will have bone metastases (Ref. 2). They may suffer multiple skeletal complications over several years because the clinical course of metastatic bone disease is relatively long. The effects are often debilitating (intractable bone pain, fractures, hypercalcaemia, and spinal cord compression) and profoundly impair a patient's quality of life.
Bone metastases also occur frequently in patients with lung, kidney and thyroid cancers - respectively in 30-40%, 20-25% and 60% of patients with advanced disease.
Current treatments for skeletal metastases are largely palliative. They include opioid analgesics, external beam radiotherapy, beta-emitting radionuclides and bisphosphonates.
References
1. Coleman, R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s-6249s. Review
2. Rubens, R.D, and Coleman, R.E. Bone Metastases. In: Abaloff, M.D., Armitage, J.O., Lichter, A.S. and Niederhuber, J.E. Clinical Oncology 1995: 643-665
Forward Looking Statement
This news release contains forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on results of operations and the financial condition of Algeta. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements. Theses factors include, among other things, risks associated with technological development, the risk that research & development will not yield new products that achieve commercial success, the impact of competition, the ability to close viable and profitable business deals, the risk of non-approval of patents not yet granted and difficulties of obtaining relevant governmental approvals for new products
Algeta began enrolling patients for its global phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) study in June 2008 and aims to enroll approximately 750 HRPC patients with bone metastases. Recruitment of US patients into the study is now planned to commence this year.
Alpharadin (radium-223) is Algeta's lead clinical candidate and has demonstrated in phase II studies strong evidence that it can prolong patient survival times, improves quality of life and offers a placebo-like safety profile.
These exciting clinical results combined with Alpharadin's unique bone-targeting properties highlight the potential of this novel cancer therapeutic to be an important new treatment for bone metastases that frequently arise from a number of high incidence cancers as well as HRPC (e.g. breast, lung and kidney). Bone metastases are a serious consequence of certain advanced cancers causing intractable and debilitating pain as well as further reducing life expectancy.
Andrew Kay, Algeta's President and CEO, said: "Our recent and previous discussions with FDA have been productive and we believe they have contributed positively to the overall clinical development plan for Alpharadin. We are therefore extremely pleased to enroll US patients into our pivotal ALSYMPCA study following the successful end-of-phase II meeting with the FDA. We will be focusing on initiating the study at key clinical centers in the US over the coming months."
ALSYMPCA phase III clinical study
The ALSYMPCA study is a double-blind, randomized, controlled trial that enrolls symptomatic HRPC patients who will be randomized to receive Alpharadin plus best standard of care or placebo plus best standard of care.
The primary efficacy endpoint of the trial is overall survival. Patients are being randomized 2-to-1 in favor of Alpharadin, which will be given as six injections of 50 kBq/kg body weight, four weeks apart. Secondary endpoints include time to occurrence of specified disease-related events, and time to progression of certain key biomarkers indicative of disease status, including blood levels of serum prostate-specific antigen (PSA) and total alkaline phosphatase (ALP). In addition, the trial will monitor and evaluate both the acute and long-term safety profiles of Alpharadin treatment as well as its impact on quality of life.
For more information on the ALSYMPCA trial, please go to http://www.algeta.com and click on the ALSYPMCA link in the menu bar.
About Algeta
Algeta ASA is a cancer therapeutics company built on world-leading, proprietary technology. Algeta is developing new, targeted cancer therapeutics that harness the unique characteristics of alpha particle emitters and are potent, well-tolerated and convenient to use.
Algeta's lead product candidate, Alpharadin (based on radium-223), has blockbuster potential for treating bone metastases arising from multiple major cancer types, owing to its bone-targeting nature, potent efficacy (therapeutic and palliative) and benign, placebo-like safety profile. Development of Alpharadin is most advanced targeting bone metastases resulting from hormone-refractory prostate cancer (HRPC), and it entered an international phase III clinical trial (ALSYMPCA) in mid-2008 based on compelling clinical results from a comprehensive phase II program.
Algeta's strategy is to launch Alpharadin as a first or second line treatment for cancer patients with bone metastases either alone or in combination with current standard of care therapies, thereby maximizing its commercial potential.
Algeta is also developing other technologies for delivering alpha emitters. These include microparticles, liposomes, and methods to enhance the potency of therapeutic antibodies and other tumor-targeting molecules by linking them to the alpha particle emitter thorium-227. The Company is headquartered in Oslo, Norway, and was founded in 1997. Algeta listed on the Oslo Stock Exchange in March 2007 (Ticker: ALGETA).
Alpharadin and Algeta are trademarks of Algeta ASA.
About Bone Metastases
Bone is the most common organ to be affected by metastatic cancer (Ref. 1). Approximately 1.5 million cancer patients suffer from bone metastases worldwide and there are some 300,000 new cases each year. Importantly, metastases may stay confined to the skeleton with subsequent morbidity and eventual death almost entirely due to skeletal complications and their treatment.
Some 80% of bone metastases are due to prostate and breast carcinomas. For these high incidence cancers, 65-75% patients with advanced disease will have bone metastases (Ref. 2). They may suffer multiple skeletal complications over several years because the clinical course of metastatic bone disease is relatively long. The effects are often debilitating (intractable bone pain, fractures, hypercalcaemia, and spinal cord compression) and profoundly impair a patient's quality of life.
Bone metastases also occur frequently in patients with lung, kidney and thyroid cancers - respectively in 30-40%, 20-25% and 60% of patients with advanced disease.
Current treatments for skeletal metastases are largely palliative. They include opioid analgesics, external beam radiotherapy, beta-emitting radionuclides and bisphosphonates.
References
1. Coleman, R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s-6249s. Review
2. Rubens, R.D, and Coleman, R.E. Bone Metastases. In: Abaloff, M.D., Armitage, J.O., Lichter, A.S. and Niederhuber, J.E. Clinical Oncology 1995: 643-665
Forward Looking Statement
This news release contains forward-looking statements and forecasts based on uncertainty, since they relate to events and depend on circumstances that will occur in the future and which, by their nature, will have an impact on results of operations and the financial condition of Algeta. There are a number of factors that could cause actual results and developments to differ materially from those expressed or implied by these forward-looking statements. Theses factors include, among other things, risks associated with technological development, the risk that research & development will not yield new products that achieve commercial success, the impact of competition, the ability to close viable and profitable business deals, the risk of non-approval of patents not yet granted and difficulties of obtaining relevant governmental approvals for new products
R&B Artist Charlie Wilson Announces Prostate Cancer Diagnosis
Charlie Wilson, the famed R&B artist widely known as the lead vocalist for the GAP Band in the 1980s and his gold-certified album, Charlie Last Name Wilson, announced that he is undergoing treatment for prostate cancer. He also announced that he is teaming with the Prostate Cancer Foundation (PCF) to raise awareness and research funds for prostate cancer. His second solo album on Jive Records, Uncle Charlie, featuring the top-ten single There Goes My Baby, is scheduled for release on February 17.
"When I was diagnosed with prostate cancer in September, I thought to myself 'I'm too young… this isn't a cancer I should be getting,'" says Wilson. "While I was surprised to discover that this disease strikes one out of every six American men, I was astounded to learn that African American men are 1.6 times more likely than others to be diagnosed with prostate cancer. My wife, Mahin, and I are very fortunate. I was lucky to be diagnosed and begin treatment early. My prognosis is excellent."
Wilson is buoyed by the fact that his cancer was detected early. Following his diagnosis in September, he consulted with his doctor to select a treatment option that was right for him. He started on a course of therapy on November 21.
Scientists do not yet understand why prostate cancer odds-both incidence and death rates-are higher among African American men. Genetic differences, lifestyle and nutrition habits, and access to healthcare may all play a role in the statistics.
In dealing with his situation, Wilson understood two things: he had to decide on a treatment that was right for him and he had to do something about getting the word out about prostate cancer to African American and all men. "For years I've spent my life performing," explains Wilson. "Now I need to spend time informing.
"Although men are 35 percent more likely to develop prostate cancer than women are to be diagnosed with breast cancer, no one seems to talk about the disease," says Wilson. "We men don't want to consider or vocalize our vulnerabilities. It was my wife who kept after me to see my doctor for a screening. I thank God she did. Now I feel compelled to spread the word about prostate cancer."
Wilson will be taking the message of early detection and treatment on the road with him as he starts his media and concert tours for his new album this spring. He plans to deliver his message overseas to U.S. troops serving in Iraq and Kuwait when he performs for them in late February.
Wilson will also be helping the Prostate Cancer Foundation raise funds to support prostate cancer research, specifically by supporting a PCF Creativity Research Grant. These grants support creative research ideas with high potential and no current funding. They encourage the development of high-risk/high-reward concepts that, if successful, could provide the basis for dramatically reducing death and suffering from prostate cancer. They are intended to bridge the gap between an idea and the results necessary to justify increased funding. Those wanting to make a donation to the Charlie Wilson-PCF Creativity Research Grant can go to http://www.unclecharliewilson.com. There they will find more information on Wilson's support of PCF research and a direct link for making donations online or by mail.
"I am excited to be working with the PCF. They are the driving force behind many of the advances that have been made in prostate cancer treatment to date," says Wilson. "Their work has helped reduce the death rate by nearly 40 percent in the past few years. Together, I believe we can make an important impact."
About the Prostate Cancer Foundation
The Prostate Cancer Foundation is the world's largest philanthropic source of support for prostate cancer research focused on discovering better treatments and a cure for recurrent prostate cancer. Founded in 1993, the PCF has raised more than $370 million and provided funding to more than 1,500 research projects nearly 200 institutions worldwide. The PCF also advocates for greater awareness of prostate cancer and more governmental research funds. PCF advocacy has helped produce a 20-fold increase in government funding for prostate cancer since 1994. More information about prostate cancer and the PCF can be found at http://www.pcf.org.
"When I was diagnosed with prostate cancer in September, I thought to myself 'I'm too young… this isn't a cancer I should be getting,'" says Wilson. "While I was surprised to discover that this disease strikes one out of every six American men, I was astounded to learn that African American men are 1.6 times more likely than others to be diagnosed with prostate cancer. My wife, Mahin, and I are very fortunate. I was lucky to be diagnosed and begin treatment early. My prognosis is excellent."
Wilson is buoyed by the fact that his cancer was detected early. Following his diagnosis in September, he consulted with his doctor to select a treatment option that was right for him. He started on a course of therapy on November 21.
Scientists do not yet understand why prostate cancer odds-both incidence and death rates-are higher among African American men. Genetic differences, lifestyle and nutrition habits, and access to healthcare may all play a role in the statistics.
In dealing with his situation, Wilson understood two things: he had to decide on a treatment that was right for him and he had to do something about getting the word out about prostate cancer to African American and all men. "For years I've spent my life performing," explains Wilson. "Now I need to spend time informing.
"Although men are 35 percent more likely to develop prostate cancer than women are to be diagnosed with breast cancer, no one seems to talk about the disease," says Wilson. "We men don't want to consider or vocalize our vulnerabilities. It was my wife who kept after me to see my doctor for a screening. I thank God she did. Now I feel compelled to spread the word about prostate cancer."
Wilson will be taking the message of early detection and treatment on the road with him as he starts his media and concert tours for his new album this spring. He plans to deliver his message overseas to U.S. troops serving in Iraq and Kuwait when he performs for them in late February.
Wilson will also be helping the Prostate Cancer Foundation raise funds to support prostate cancer research, specifically by supporting a PCF Creativity Research Grant. These grants support creative research ideas with high potential and no current funding. They encourage the development of high-risk/high-reward concepts that, if successful, could provide the basis for dramatically reducing death and suffering from prostate cancer. They are intended to bridge the gap between an idea and the results necessary to justify increased funding. Those wanting to make a donation to the Charlie Wilson-PCF Creativity Research Grant can go to http://www.unclecharliewilson.com. There they will find more information on Wilson's support of PCF research and a direct link for making donations online or by mail.
"I am excited to be working with the PCF. They are the driving force behind many of the advances that have been made in prostate cancer treatment to date," says Wilson. "Their work has helped reduce the death rate by nearly 40 percent in the past few years. Together, I believe we can make an important impact."
About the Prostate Cancer Foundation
The Prostate Cancer Foundation is the world's largest philanthropic source of support for prostate cancer research focused on discovering better treatments and a cure for recurrent prostate cancer. Founded in 1993, the PCF has raised more than $370 million and provided funding to more than 1,500 research projects nearly 200 institutions worldwide. The PCF also advocates for greater awareness of prostate cancer and more governmental research funds. PCF advocacy has helped produce a 20-fold increase in government funding for prostate cancer since 1994. More information about prostate cancer and the PCF can be found at http://www.pcf.org.
New Treatment Hope For Prostate Cancer
Scientists at Melbourne's Burnet Institute have developed a potential new treatment for patients with prostate cancer. An article, which described the invention, has recently been published in the prestigious international journal The Journal of Clinical Investigation.
Head of the Burnet Institute's Cancer Immunotherapy Laboratory, Associate Professor Pei Xiang Xing said his group has produced a monoclonal antibody to a unique tumour marker for the treatment of prostate cancer. The monoclonal antibody is directed at cancer-producing cells carrying the specific molecule known as PIM-1, which is responsible for cell survival, proliferation and differentiation. Over-expression of PIM-1 plays a critical role in the development, progression and metastasis of prostate cancer and other cancers such as leukaemia. The monoclonal antibody significantly inhibited cancer cell growth when used in laboratory models of prostate cancer.
Professor Xing's group demonstrated that the monoclonal antibody binds to PIM-1 present in cancer cells and creates a chain of events leading to the death of the cells. In particular, the therapeutic effect was improved by combination of the antibody with other drugs currently used to treat prostate cancer.
Prostate cancer is one of the most frequently diagnosed invasive cancers and the third leading cause of death in men worldwide. More than 3,000 men die each year from prostate cancer, equal to the number of women who die from breast cancer; and more than 18,000 new cases are diagnosed in Australia each year. A new strategy to treat prostate cancer is urgently needed as there is no efficient method to treat advanced prostate cancer.
Director of the Burnet Institute, Professor Brendan Crabb said that while the therapy was still in its early days this was the first time that researchers had found a treatment that targeted prostate cancer cells with a specific antibody to PIM-1 and which resulted in the death of the malignant cells and a reduction in tumour size.
"This is an exciting step in the development of new treatments for patients with prostate cancer with very promising laboratory-test results," Professor Crabb said.
While further laboratory research is still required to refine the treatment, it is expected that clinical trials of the new therapy will commence in the near future.
----------------------------
Article adapted by Medical News Today from original press release.
Head of the Burnet Institute's Cancer Immunotherapy Laboratory, Associate Professor Pei Xiang Xing said his group has produced a monoclonal antibody to a unique tumour marker for the treatment of prostate cancer. The monoclonal antibody is directed at cancer-producing cells carrying the specific molecule known as PIM-1, which is responsible for cell survival, proliferation and differentiation. Over-expression of PIM-1 plays a critical role in the development, progression and metastasis of prostate cancer and other cancers such as leukaemia. The monoclonal antibody significantly inhibited cancer cell growth when used in laboratory models of prostate cancer.
Professor Xing's group demonstrated that the monoclonal antibody binds to PIM-1 present in cancer cells and creates a chain of events leading to the death of the cells. In particular, the therapeutic effect was improved by combination of the antibody with other drugs currently used to treat prostate cancer.
Prostate cancer is one of the most frequently diagnosed invasive cancers and the third leading cause of death in men worldwide. More than 3,000 men die each year from prostate cancer, equal to the number of women who die from breast cancer; and more than 18,000 new cases are diagnosed in Australia each year. A new strategy to treat prostate cancer is urgently needed as there is no efficient method to treat advanced prostate cancer.
Director of the Burnet Institute, Professor Brendan Crabb said that while the therapy was still in its early days this was the first time that researchers had found a treatment that targeted prostate cancer cells with a specific antibody to PIM-1 and which resulted in the death of the malignant cells and a reduction in tumour size.
"This is an exciting step in the development of new treatments for patients with prostate cancer with very promising laboratory-test results," Professor Crabb said.
While further laboratory research is still required to refine the treatment, it is expected that clinical trials of the new therapy will commence in the near future.
----------------------------
Article adapted by Medical News Today from original press release.
Low Dose Combinations Of 2-Methoxyestradiol And Docetaxel Block Prostate Cancer Cells In Mitosis And Increase Apoptosis
Docetaxel (Doc) is the gold standard chemotherapy drug used clinically against androgen-independent prostate cancer (AI-PC) and when combined with prednisone results in a small but significant increase in survival. It is likely other drugs combined with Doc will further increase survival, which is the ultimate goal for treating patients with AI-PC. We chose to study the combination of 2-methoxyestradiol (2ME2) with Doc using preclinical models of human prostate cancer cell lines and the FG/Tag transgenic mouse model of AI-PC. Doc and 2ME2 target microtubules, block mitosis, and eventually increase apoptotic cell death. Although the combination of Doc + 2ME2 at first appears counterintuitive, i.e., they both have similar mechanisms targeting microtubules, our results provide interesting insights in preclinical models.
An attractive feature of 2ME2 is its non-toxic effect on normal cells and tissues. Since Doc has been shown to have neuropathy side effects in patients, our interest was to determine if lower, less toxic doses of Doc can be used in combination with 2ME2. Our results in prostate cancer cell lines and in the FG/Tag mice showed that lower doses of Doc combined with 2ME2 blocked mitosis and increased cell death via apoptosis or non-apoptotic mechanisms. Unfortunately, combining higher doses of Doc and 2ME2 provided no additional benefits compared to the single high doses. Clinically, perhaps it will be better to use the low dose combination for less toxicity to normal cells and tissues but still obtain a strong anti-prostate cancer effect.
In our study, the most important prognostic marker for measuring drug response or prostate cancer cell death is the ability of Doc, 2ME2, or their combinations to block mitosis. In FG/Tag mice, the Doc + 2ME2 combination blocked mitosis after one day of treatment. Only the doses of Doc and 2ME2 that resulted in mitotic block had an increase in apoptosis and reduced the weights of the primary prostate tumors. Strikingly, all or most treatments reduced angiogenesis and proliferation but only the doses of 2ME2 and Doc that blocked mitosis increased cell death and reduced tumor weights. Clinically, perhaps a measure of biological response to antimitotic drugs could be measuring cell cycle from biopsies after treatment for a short time.
An aspect of our study that surprised us was that the 2ME2 + Doc combination did not increase apoptosis in PC-3 AI-PC cells, yet there was an effect as measured by the clonogenic assay, which can measure all forms of cell death. We term this death by a non-apoptotic mechanism. It may be that prostate cancer cells like PC-3, which are defective in apoptosis (mutant p53), can still be killed by drugs using a mechanism termed necroptosis or necrosis. Investigating the mechanisms of how antimitotic drugs can increase non-apoptotic cell death in prostate cancer cells like PC-3 is a current interest in the Perez-Stable laboratory. Whereas we were previously frustrated that many drugs had little effect on increasing apoptosis in cells like PC-3, we are now encouraged that they can be killed by non-apoptotic mechanisms that are still intact in the most aggressive advanced prostate cancer cells. Our hope is that a better understanding of these non-apoptotic cell death mechanisms will lead to chemotherapy combinations that will increase survival to a greater extent than the Doc + prednisone combination.
An attractive feature of 2ME2 is its non-toxic effect on normal cells and tissues. Since Doc has been shown to have neuropathy side effects in patients, our interest was to determine if lower, less toxic doses of Doc can be used in combination with 2ME2. Our results in prostate cancer cell lines and in the FG/Tag mice showed that lower doses of Doc combined with 2ME2 blocked mitosis and increased cell death via apoptosis or non-apoptotic mechanisms. Unfortunately, combining higher doses of Doc and 2ME2 provided no additional benefits compared to the single high doses. Clinically, perhaps it will be better to use the low dose combination for less toxicity to normal cells and tissues but still obtain a strong anti-prostate cancer effect.
In our study, the most important prognostic marker for measuring drug response or prostate cancer cell death is the ability of Doc, 2ME2, or their combinations to block mitosis. In FG/Tag mice, the Doc + 2ME2 combination blocked mitosis after one day of treatment. Only the doses of Doc and 2ME2 that resulted in mitotic block had an increase in apoptosis and reduced the weights of the primary prostate tumors. Strikingly, all or most treatments reduced angiogenesis and proliferation but only the doses of 2ME2 and Doc that blocked mitosis increased cell death and reduced tumor weights. Clinically, perhaps a measure of biological response to antimitotic drugs could be measuring cell cycle from biopsies after treatment for a short time.
An aspect of our study that surprised us was that the 2ME2 + Doc combination did not increase apoptosis in PC-3 AI-PC cells, yet there was an effect as measured by the clonogenic assay, which can measure all forms of cell death. We term this death by a non-apoptotic mechanism. It may be that prostate cancer cells like PC-3, which are defective in apoptosis (mutant p53), can still be killed by drugs using a mechanism termed necroptosis or necrosis. Investigating the mechanisms of how antimitotic drugs can increase non-apoptotic cell death in prostate cancer cells like PC-3 is a current interest in the Perez-Stable laboratory. Whereas we were previously frustrated that many drugs had little effect on increasing apoptosis in cells like PC-3, we are now encouraged that they can be killed by non-apoptotic mechanisms that are still intact in the most aggressive advanced prostate cancer cells. Our hope is that a better understanding of these non-apoptotic cell death mechanisms will lead to chemotherapy combinations that will increase survival to a greater extent than the Doc + prednisone combination.
Usefulness Of The 2005 International Society Of Urologic Pathology Gleason Grading System In Prostate Biopsy And Radical Prostatectomy Specimens
Historically, the Gleason grading system was most commonly used for prostate cancer (CaP) pathologic analysis. In 2005, the International Society of Urologic Pathology (ISUP) Gleason Grading Consensus was proposed. The ISUP differs in that:
a) a Gleason score (GS) of <4 in biopsy tissue is rarely made
b) most cribriform patterns would be diagnosed as Gleason pattern 4 while rare cribriform patterns would be Gleason pattern 3
c) different GS used for biopsy and RP specimens, high-grade tumor of any quantity on biopsy should be included within the GS
d) for tertiary pattern on biopsy the primary pattern and highest grade should be recorded and in RP specimens when a different GS occurs in separate tumor nodule then a separate GS should be recorded.
This Japanese report evaluates the ISUP system for biochemical recurrence, and compares conventional GS (CGS)to ISUP GS (IGS) in biopsy and RP specimens.
The cohort consisted of 250 men with clinical stage T1-2 N0M0 CaP diagnosed between 1996 and 2006. All patients had TRUS with biopsy and RP. Of these men, 103 did not have neoadjuvant or adjuvant therapies and were eligible for this analysis. One uropathologist determined the IGS scoring. D'Amico risk stratification classified 34 men as low risk, 37 men as intermediate risk and 32 men as high risk.
The conventional CGS for the biopsy specimen was concordant with the RP in 64% of cases with undergrading in 28% and overgrading in 8%. The IGS was undergraded in 27% with slightly higher concordance (70%) than for CSG while overgrading was significantly lower (3%). There were no significant differences between CSG and IGS for RP specimens. By D'Amico categories, 10 of 34 (29%) classified as low risk on IGS were intermediate risk according to CGS. Five (14%) and four (11%) of the 37 intermediate risk based on CGS were low and high risk respectively, by IGS. However, there were no statistically significant differences between CGS and IGS for D'Amico stratification. Also, no differences in pathological staging between CGS and IGS were statistically significant. Biochemical recurrence-free survival (BRFS) in men with biopsy specimens classified by CGS did not differ among GS groups (<6, 7 and >8), however when IGS was applied to the biopsy specimens there was a significant difference in BRFS among the 3 groups. Also, the BRFS in RP specimens classified by GS groups (<6, 7 and >8) by CGS were not different. However, application of IGS to the biopsy demonstrated BRFS differed significantly among the 3 groups. This suggests that application of the IGS to the prostate biopsy specimen more closely correlates with BRFS.
Uemura H, Hoshino K, Sasaki T, Miyoshi Y, Ishiguro H, Inayama Y, Kubota Y
BJU Int. 2008 Dec 5. Epub ahead of print.
doi:10.1111/j.1464-410X.2008.08197.x
a) a Gleason score (GS) of <4 in biopsy tissue is rarely made
b) most cribriform patterns would be diagnosed as Gleason pattern 4 while rare cribriform patterns would be Gleason pattern 3
c) different GS used for biopsy and RP specimens, high-grade tumor of any quantity on biopsy should be included within the GS
d) for tertiary pattern on biopsy the primary pattern and highest grade should be recorded and in RP specimens when a different GS occurs in separate tumor nodule then a separate GS should be recorded.
This Japanese report evaluates the ISUP system for biochemical recurrence, and compares conventional GS (CGS)to ISUP GS (IGS) in biopsy and RP specimens.
The cohort consisted of 250 men with clinical stage T1-2 N0M0 CaP diagnosed between 1996 and 2006. All patients had TRUS with biopsy and RP. Of these men, 103 did not have neoadjuvant or adjuvant therapies and were eligible for this analysis. One uropathologist determined the IGS scoring. D'Amico risk stratification classified 34 men as low risk, 37 men as intermediate risk and 32 men as high risk.
The conventional CGS for the biopsy specimen was concordant with the RP in 64% of cases with undergrading in 28% and overgrading in 8%. The IGS was undergraded in 27% with slightly higher concordance (70%) than for CSG while overgrading was significantly lower (3%). There were no significant differences between CSG and IGS for RP specimens. By D'Amico categories, 10 of 34 (29%) classified as low risk on IGS were intermediate risk according to CGS. Five (14%) and four (11%) of the 37 intermediate risk based on CGS were low and high risk respectively, by IGS. However, there were no statistically significant differences between CGS and IGS for D'Amico stratification. Also, no differences in pathological staging between CGS and IGS were statistically significant. Biochemical recurrence-free survival (BRFS) in men with biopsy specimens classified by CGS did not differ among GS groups (<6, 7 and >8), however when IGS was applied to the biopsy specimens there was a significant difference in BRFS among the 3 groups. Also, the BRFS in RP specimens classified by GS groups (<6, 7 and >8) by CGS were not different. However, application of IGS to the biopsy demonstrated BRFS differed significantly among the 3 groups. This suggests that application of the IGS to the prostate biopsy specimen more closely correlates with BRFS.
Uemura H, Hoshino K, Sasaki T, Miyoshi Y, Ishiguro H, Inayama Y, Kubota Y
BJU Int. 2008 Dec 5. Epub ahead of print.
doi:10.1111/j.1464-410X.2008.08197.x
Health-Related Quality Of Life After Permanent I-125 Brachytherapy And Conformal External Beam Radiotherapy For Prostate Cancer
Currently, the most common curative treatment options for men with localized (stage T1-2) prostate cancer are external beam radiotherapy (EBRT), interstitial permanent brachytherapy (BT) and radical prostatectomy. A number of series published equivalent outcomes concerning biochemical recurrence rates. Therefore, treatment decisions should particularly consider the specific risk and toxicity profile of a treatment method.
Several reports have already compared toxicities after EBRT and BT. However, methodical problems remain with often retrospective data, missing health-related quality of life (HRQOL) results and consistent differences concerning baseline patient characteristics. Generally, patients receiving BT are of younger ages. The patient age has a large impact both on the pre-treatment sexual function and a treatment-associated erectile dysfunction - well explaining better results after BT in comparison to EBRT. Furthermore, in accordance with treatment recommendations, patients receiving BT have smaller prostate volumes. A neoadjuvant hormonal therapy can additionally change the toxicity results in different HRQOL domains.
To further improve the knowledge in this field, thus the treatment decision for the involved physicians and patients, a matched pair analysis was performed. A group of 104 patients (52 in each group) has been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). The multi-item scale scores were transformed linearly to a 0-100 scale, with higher scores representing better HRQOL. All patients in the EBRT-group were treated with 1.8-2.0Gy fractions up to a total dose of 70.2-72.0Gy. BT was performed as monotherapy with a prescription dose of 145Gy. Only patients who answered all questionnaires have been included. Pairs were matched according to following criteria: age+5years, prostate volume+10cc, use of anti-androgens, and erectile function.
Patients scheduled for BT presented with significantly better urinary bother and urinary obstructive/irritative scores before treatment. Other scores did not differ >5 points. However, compared to baseline levels, both urinary function and urinary bother scores (obstructive/irritative scores in particular) decreased more after BT both at time B and time C. Comparing patients with baseline urinary bother scores <90 vs. >90, significantly lower scores - with a similar decrease - were found in both groups after BT. After EBRT, urinary bother scores improved significantly (+11 points) in the patient group with initial scores <90. Bowel function and bowel bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C, respectively; p<0.05 for differences at times B and C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). Sexual function and bother scores decreased significantly in both treatment groups, without any remarkable differences (81% vs. 84% with preserved ability to have an erection; 67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT).
Patients opting for a permanent I-125 brachytherapy need to consider a higher risk of urinary obstructive/irritative problems, but a lower risk of proctitis-associated problems compared to external beam radiotherapy. In view of a further deterioration of long-term mean urinary scores after permanent brachytherapy - in contrast to an improvement after external beam radiotherapy - patients with greater urinary problems before treatment should preferably be selected for external beam radiotherapy.
Several reports have already compared toxicities after EBRT and BT. However, methodical problems remain with often retrospective data, missing health-related quality of life (HRQOL) results and consistent differences concerning baseline patient characteristics. Generally, patients receiving BT are of younger ages. The patient age has a large impact both on the pre-treatment sexual function and a treatment-associated erectile dysfunction - well explaining better results after BT in comparison to EBRT. Furthermore, in accordance with treatment recommendations, patients receiving BT have smaller prostate volumes. A neoadjuvant hormonal therapy can additionally change the toxicity results in different HRQOL domains.
To further improve the knowledge in this field, thus the treatment decision for the involved physicians and patients, a matched pair analysis was performed. A group of 104 patients (52 in each group) has been surveyed prospectively before EBRT/BT (time A), at the last day of EBRT or one month after BT (time B), and a median time of 16 months after EBRT/BT (time C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). The multi-item scale scores were transformed linearly to a 0-100 scale, with higher scores representing better HRQOL. All patients in the EBRT-group were treated with 1.8-2.0Gy fractions up to a total dose of 70.2-72.0Gy. BT was performed as monotherapy with a prescription dose of 145Gy. Only patients who answered all questionnaires have been included. Pairs were matched according to following criteria: age+5years, prostate volume+10cc, use of anti-androgens, and erectile function.
Patients scheduled for BT presented with significantly better urinary bother and urinary obstructive/irritative scores before treatment. Other scores did not differ >5 points. However, compared to baseline levels, both urinary function and urinary bother scores (obstructive/irritative scores in particular) decreased more after BT both at time B and time C. Comparing patients with baseline urinary bother scores <90 vs. >90, significantly lower scores - with a similar decrease - were found in both groups after BT. After EBRT, urinary bother scores improved significantly (+11 points) in the patient group with initial scores <90. Bowel function and bowel bother scores tended to be higher after BT, with a lower percentage of patients with painful bowel movements (BT: 12%/27%/15%; EBRT: 19%/52%/35% at time A/B/C, respectively; p<0.05 for differences at times B and C) and rectal bleeding (BT: 12%/12%/12%; EBRT: 8%/14%/17%). Sexual function and bother scores decreased significantly in both treatment groups, without any remarkable differences (81% vs. 84% with preserved ability to have an erection; 67% vs. 61% with preserved erections firm enough for intercourse after BT vs. EBRT).
Patients opting for a permanent I-125 brachytherapy need to consider a higher risk of urinary obstructive/irritative problems, but a lower risk of proctitis-associated problems compared to external beam radiotherapy. In view of a further deterioration of long-term mean urinary scores after permanent brachytherapy - in contrast to an improvement after external beam radiotherapy - patients with greater urinary problems before treatment should preferably be selected for external beam radiotherapy.
Appropriate Candidates For Hemiablative Focal Therapy Are Rarely Found Among Men Selected For Radical Prostatectomy In Contemporary Cohort
We found that while 20% of men undergoing radical prostatectomy have unilateral disease, only about 1 in 10 have unilateral disease with low risk features (defined as a PSA level <10 ng/mL, Gleason score <7, and PTI <10%). With limitations on prostate imaging, currently hemiablative therapy (HAT) for unilateral disease is the most logical approach to focal therapy. We believe that at this time ideal candidates would be those with small volume, low risk, unilateral disease.
We recently undertook a study to examine if men with unilateral disease had better pathologic and oncologic outcomes than those with bilateral disease. Interestingly we found that while men with unilateral disease had lower rates of biochemical recurrence and favorable pathologic features, this was a result of risk stratification. Ultimately, we found that men with low risk disease (Gleason <7, <10) had similar pathologic and oncologic outcomes regardless of whether they had unilateral or bilateral prostate cancer. This suggests that even men with bilateral disease and low risk disease may one day be candidates for subtotal gland ablative therapy (STAT) with sparing of at least one neurovascular bundle.
The greatest challenge facing focal therapy at this time is appropriate selection of candidates based on biopsy, clinical and imaging data. We have shown that biopsy alone is a poor predictor of laterality. Advances in MRI and other imaging technologies will ultimately be needed in order to accurately map clinically significant lesions. Ideally, with advances in mapping and focal ablative technologies such as high intensity focused ultrasound (HIFU) and photovaporization, the treatment of prostate cancer may very well shift to a precise lesion ablative therapy (LAT) in the near future. Our challenge as a urology community will be to ensure oncologic efficacy by appropriately selecting candidates who are best suited for these types of ablative therapies.
Written by Basir Tareen, MD and Samir S. Taneja, MD as part of Beyond the Abstract on UroToday.com.
1 Tareen, B. Godoy G, Sankin A, Temkin S, Lepor H, Taneja SS. Latterality alone should not drive selection of candidates for hemiablative focal therapy of prostate cancer. Journal of Urology. 2008. In press.
2 Taneja SS, Tareen B. Targeting prostate cancer for focal destruction: can we find it? Cancer. 2008. Oct 1;113(7):1500-1.
3 Tareen B, Godoy G, Sankin A, Temkin S, Lepor H, Taneja SS. Can Contemporary Transrectal Prostate Biopsy Accurately Select Candidates for Prostate Cancer Hemiablative Focal Therapy? BJUI. 2009. In Press.
We recently undertook a study to examine if men with unilateral disease had better pathologic and oncologic outcomes than those with bilateral disease. Interestingly we found that while men with unilateral disease had lower rates of biochemical recurrence and favorable pathologic features, this was a result of risk stratification. Ultimately, we found that men with low risk disease (Gleason <7, <10) had similar pathologic and oncologic outcomes regardless of whether they had unilateral or bilateral prostate cancer. This suggests that even men with bilateral disease and low risk disease may one day be candidates for subtotal gland ablative therapy (STAT) with sparing of at least one neurovascular bundle.
The greatest challenge facing focal therapy at this time is appropriate selection of candidates based on biopsy, clinical and imaging data. We have shown that biopsy alone is a poor predictor of laterality. Advances in MRI and other imaging technologies will ultimately be needed in order to accurately map clinically significant lesions. Ideally, with advances in mapping and focal ablative technologies such as high intensity focused ultrasound (HIFU) and photovaporization, the treatment of prostate cancer may very well shift to a precise lesion ablative therapy (LAT) in the near future. Our challenge as a urology community will be to ensure oncologic efficacy by appropriately selecting candidates who are best suited for these types of ablative therapies.
Written by Basir Tareen, MD and Samir S. Taneja, MD as part of Beyond the Abstract on UroToday.com.
1 Tareen, B. Godoy G, Sankin A, Temkin S, Lepor H, Taneja SS. Latterality alone should not drive selection of candidates for hemiablative focal therapy of prostate cancer. Journal of Urology. 2008. In press.
2 Taneja SS, Tareen B. Targeting prostate cancer for focal destruction: can we find it? Cancer. 2008. Oct 1;113(7):1500-1.
3 Tareen B, Godoy G, Sankin A, Temkin S, Lepor H, Taneja SS. Can Contemporary Transrectal Prostate Biopsy Accurately Select Candidates for Prostate Cancer Hemiablative Focal Therapy? BJUI. 2009. In Press.
Role Of Prostate Specific Membrane Antigen And Pepsinogen C Tissue Expression As An Adjunctive Method To Prostate Cancer Diagnosis
In the February 2009 issue of the Journal of Urology, Dr. Alberto Antunes and colleagues from Sao Paulo, Brazil reported on the use of a gene microarray to identify an expression profile that may improve the ability to diagnose prostate cancer (CaP).
The study included tissue from 50 patients who underwent surgery between 1997 and 2000. Two study groups were established; group 1 was comprised of CaP tissue from 33 patients and a control group of 9 patients treated surgically for BPH and group 2 consisted of BPH tissue from 17 men who had CaP and a control of 9 patients with BPH. RNA was extracted from frozen tissue and synthesis of cDNA was performed by reverse transcription. Six previously identified genes were chosen for study; PSMA, TMEFF2, GREB1, TH1L, IGH3 and PGC. These genes were selected from 4,147 genes with different expressions related to the presence of CAP and/or the presence of androgen receptor pathways. RT-PCR was used to analyze the cDNA relative expression. PSMA is a type II membrane protein with high expression in CaP. PGC is an aspartic acid proteinase expressed by gastric tissue, but also expressed in cancers. It is associated with favorable clinical outcomes.
PSMA was always overexpressed (a mean of 9 fold) and PGC was always underexpressed (a mean of 1.3 x 10-4 fold) in CaP compared to BPH cases. The other 4 genes did not express a pattern that differentiated between CaP and BPH tissue. PSMA expression was statistically similar among men with stage T2 and T3 tumors, while PGC was underexpressed in stage T3 compared to T2 tumors. Expression stratified by high and low Gleason score was statistically similar for both genes. In the second group, similar results to the first group were validated.
The potential for clinical utility is to use a gene expression profile such as this to help stratify patients for the likelihood of having prostate cancer. This approach may be especially useful for patients with an elevated PSA and a negative initial biopsy.
Antunes AA, Leite KR, Sousa-Canavez JM, Camara-Lopes LH, Srougi M
J Urol. 2009 Feb;181(2):594-600
doi:10.1016/j.juro.2008.10.007
Written by disease4info.blogspot.com Contributing Editor Christopher P. Evans, MD, FACS
The study included tissue from 50 patients who underwent surgery between 1997 and 2000. Two study groups were established; group 1 was comprised of CaP tissue from 33 patients and a control group of 9 patients treated surgically for BPH and group 2 consisted of BPH tissue from 17 men who had CaP and a control of 9 patients with BPH. RNA was extracted from frozen tissue and synthesis of cDNA was performed by reverse transcription. Six previously identified genes were chosen for study; PSMA, TMEFF2, GREB1, TH1L, IGH3 and PGC. These genes were selected from 4,147 genes with different expressions related to the presence of CAP and/or the presence of androgen receptor pathways. RT-PCR was used to analyze the cDNA relative expression. PSMA is a type II membrane protein with high expression in CaP. PGC is an aspartic acid proteinase expressed by gastric tissue, but also expressed in cancers. It is associated with favorable clinical outcomes.
PSMA was always overexpressed (a mean of 9 fold) and PGC was always underexpressed (a mean of 1.3 x 10-4 fold) in CaP compared to BPH cases. The other 4 genes did not express a pattern that differentiated between CaP and BPH tissue. PSMA expression was statistically similar among men with stage T2 and T3 tumors, while PGC was underexpressed in stage T3 compared to T2 tumors. Expression stratified by high and low Gleason score was statistically similar for both genes. In the second group, similar results to the first group were validated.
The potential for clinical utility is to use a gene expression profile such as this to help stratify patients for the likelihood of having prostate cancer. This approach may be especially useful for patients with an elevated PSA and a negative initial biopsy.
Antunes AA, Leite KR, Sousa-Canavez JM, Camara-Lopes LH, Srougi M
J Urol. 2009 Feb;181(2):594-600
doi:10.1016/j.juro.2008.10.007
Written by disease4info.blogspot.com Contributing Editor Christopher P. Evans, MD, FACS
Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates In Men Presurgery
A multi-site randomized controlled trial to test the effects of low fat and /or flaxseed-supplemented diets is reported in the December 2008 issue of Cancer Epidemiology, Biomarkers and Prevention. Flaxseed is an oilseed commonly consumed in the Middle Ages, and is not common in the modern era due to its short shelf life. Flaxseed is rich in dietary lignan, which has anti-mitotic, anti-angiogenesis, anti-oxidant and phytoestrogenic effects. It also reduces testosterone and 5-reductase.
A total of 161 men diagnosed with prostate cancer (CaP) and scheduled for radical prostatectomy at least 21 days after accrual were enrolled in the study. They were randomized into 4 groups - control (usual diet), flaxseed-supplemented (30gm/day), low-fat diet (<20% of energy from dietary fat), or flaxseed-supplemented plus low fat. Dietary questionnaires, serum and urine levels of relevant compounds and prostatectomy tissue were assessed. The primary study endpoint was proliferation index (by Ki-67 staining using the antibody MIB-1) in the prostatectomy tissue.
The dropout rate was 7.5%. Most participants had early stage CaP, and dietary logs revealed good to excellent adherence. Both erythrocytes and prostatic tissue had significantly higher levels of longer chained fatty acids. Tumor proliferation was significantly lower in the flaxseed-supplemented arm (proliferation index = 1.66), compared to 3.23 for controls, 2.56 for low-fat diet, and 1.50 for the combined flaxseed with low-fat diet. No differences were noted between groups for apoptosis, Gleason sum, or serum markers although serum PSA, testosterone, IFG-1, and IFGBP-3 decreased in all groups. Men in the low-fat diet group had significant reductions in body mass index and total and low-density lipoprotein cholesterol.
Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th, Snyder DC, Owzar K, Hars V, Albala DM, Walther PJ, Robertson CN, Moul JW, Dunn BK, Brenner D, Minasian L, Stella P, Vollmer RT.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3577-87.
doi:10.1158/1055-9965.EPI-08-0008 Prev. 2008;17:3577-87
A total of 161 men diagnosed with prostate cancer (CaP) and scheduled for radical prostatectomy at least 21 days after accrual were enrolled in the study. They were randomized into 4 groups - control (usual diet), flaxseed-supplemented (30gm/day), low-fat diet (<20% of energy from dietary fat), or flaxseed-supplemented plus low fat. Dietary questionnaires, serum and urine levels of relevant compounds and prostatectomy tissue were assessed. The primary study endpoint was proliferation index (by Ki-67 staining using the antibody MIB-1) in the prostatectomy tissue.
The dropout rate was 7.5%. Most participants had early stage CaP, and dietary logs revealed good to excellent adherence. Both erythrocytes and prostatic tissue had significantly higher levels of longer chained fatty acids. Tumor proliferation was significantly lower in the flaxseed-supplemented arm (proliferation index = 1.66), compared to 3.23 for controls, 2.56 for low-fat diet, and 1.50 for the combined flaxseed with low-fat diet. No differences were noted between groups for apoptosis, Gleason sum, or serum markers although serum PSA, testosterone, IFG-1, and IFGBP-3 decreased in all groups. Men in the low-fat diet group had significant reductions in body mass index and total and low-density lipoprotein cholesterol.
Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th, Snyder DC, Owzar K, Hars V, Albala DM, Walther PJ, Robertson CN, Moul JW, Dunn BK, Brenner D, Minasian L, Stella P, Vollmer RT.
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3577-87.
doi:10.1158/1055-9965.EPI-08-0008 Prev. 2008;17:3577-87
News From The Journal Of The National Cancer Institute, Feb. 10, 2009
Identification of Potential Surrogate Endpoints of Long-Term Survival in Prostate Cancer
Lack of general treatment failure or distant metastases 3 years after the start of treatment may be surrogate endpoints for long-term survival in patients with early prostate cancer.
Prostate cancer is a slowly progressing malignancy in many patients. The long natural history of the disease makes evaluation of new therapies difficult because patients must be followed for many years. If researchers could identify a surrogate clinical endpoint that accurately reflects long-term clinical outcomes for prostate cancer, clinical trials would be easier and faster.
To look for possible surrogate endpoints, Michael E. Ray, M.D., Ph.D., of ThedaCare and Bellin Health Systems in Appleton and Green Bay, Wisconsin, and colleagues evaluated the ability of general treatment failure and metastasis-free survival at 3 and 5 years to predict long-term survival in patients who had taken part in a clinical trial. A total of 1,521 patients who participated in the Radiation Therapy and Oncology Group 92-02 randomized controlled trial were included in the current analysis.
The authors found that both distant metastasis and general clinical treatment failure at 3 years were consistent with the four statistical criteria developed by Prentice for surrogate endpoints. At 5 years, only three of the four criteria were potentially fulfilled because prostate-cancer specific survival was not statistically significantly different between the two trial arms.
"The potential surrogate endpoints, distant metastasis and general clinical treatment failure, should be further and prospectively evaluated in future clinical trials along with overall and prostate cancer-specific survival endpoints," the authors conclude.
In an accompanying editorial, Ross L. Prentice, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, who developed Prentice's criteria, discusses the difficulty of establishing surrogate endpoints and the importance of doing so. "The issue of full mediation by a potential surrogate is of more than academic interest, in view of multiple examples in which a clear treatment effect on a presumed surrogate did not translate to a corresponding effect on the clinical outcome of interest," the editorialist writes.
Netrin-1 and Its Dependence Receptor Implicated in Non-Small Cell Lung Cancer
Netrin-1 is overexpressed in a substantial fraction of human non-small cell lung cancer (NSCLC) tumors and interferes with apoptosis in NSCLC cells grown in culture.
Netrin-1 may promote colorectal and breast cancer. Previous studies suggest that the tumors may become dependent on its binding to particular receptors, referred to as dependence receptors. In the absence of netrin-1 binding these receptors trigger cell death. However netrin-1's potential role in NSCLC was unknown.
In the current study, Patrick Mehlen, Ph.D., of the Université de Lyon in France, and colleagues tested 92 human tumor samples for netrin-1 expression and examined the impact of inhibiting its expression in NSCLC cells grown in vitro and in xenograft animal models.
Netrin-1 was overexpressed in 43 (47%) of the human samples tested. Inhibition of netrin-1 expression induced apoptosis in NSCLC cell lines and reduced tumor growth in animal models.
"In conclusion, our findings raise the possibility that a targeted treatment that is based on inhibition of the interaction between netrin-1 and its dependence receptors might be of benefit to patients suffering from lung cancer whose primary tumors show high netrin-1 expression," the authors write.
In an accompanying editorial, Michael P. Schön, M.D., and Margarete Schön, Ph.D., of Georg August University in Göttingen, Germany, review the phenomenon of dependence receptors in cancer and the role of netrin-1 in normal biology and tumor progression, including the newly reported data by Mehlen and colleagues. "Additional studies will be needed to determine whether selectively targeting netrin-1 will become a useful addition to the therapeutic armamentarium in NSCLCs," the editorialists conclude.
Meta-Analysis Shows Aspirin Can Reduce Recurrence of Colon Polyps
Regular aspirin use is associated with a statistically significant reduction in the development of colorectal adenomas, which are precursor lesions to colorectal cancer, in individuals at high risk of developing colorectal cancer.
Multiple lines of evidence, including data from randomized clinical trials, suggest that aspirin may reduce the risk of colon adenomas and perhaps cancer. A quantitative summary of the clinical data - and a more precise estimate of the magnitude of the benefit associated with aspirin use -has been missing.
In the current study, Bernard F. Cole, Ph.D., of the University of Vermont in Burlington, and colleagues performed a meta-analysis of all available randomized clinical trials that examined adenoma formation in participants assigned to regular aspirin use or placebo.
Among 2,698 participants who underwent colonoscopic follow-up after randomization, 37% of the participants assigned to placebo developed adenomas compared with 33% of those assigned to aspirin. Moreover 12% of the participants assigned to placebo developed advanced adenomas compared with 9% of the participants assigned to aspirin. The pooled analysis indicated that regular aspirin use resulted in an absolute risk reduction of 6.7% for developing adenomas relative to placebo.
"The substantial size of the relative reduction in risk seen in our analysis (28% for advanced adenomas) and seen in clinical trials that evaluated the effect of aspirin on colorectal cancer risk (26% reduction) indicates the potentially important health benefits of aspirin use," the authors write. "Of course, these benefits need to be considered in the context of all of the health effects of aspirin, positive and negative."
Nonsteroidal Anti-inflammatory Drug Use After 3 Years of Aspirin Associated with Reduction in Colorectal Adenoma Risk
Data from an observational study conducted at the end of a randomized placebo-controlled trial indicate that continued use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the risk of developing colorectal adenomas, which are precursor lesions to colorectal cancer.
The randomized placebo-controlled Aspirin/Folate Polyp Prevention Study showed that regular use of low dose aspirin (81 mg) reduced the risk of colorectal polyp formation in individuals at high risk compared with placebo. To determine whether continued NSAID use might be beneficial, researchers invited the study participants to enroll in an follow-up study. This observational study examined their NSAID use and the risk of a diagnosis of colorectal adenoma at their next colonoscopy, on average 4 years after the end of randomized aspirin treatment.
In the current analysis, John Baron, M.D., of Dartmouth Medical School in Lebanon, N.H., and colleagues found that individuals who were initially assigned to low-dose aspirin in the randomized trial and continued to take NSAIDs four or more days per week during the follow-up period had a statistically significantly lower risk of adenomas than those who were assigned to placebo during the randomized trial and used NSAIDs less than two days per week during the observational study. The risk of adenomas among frequent NSAID users was 26.8 percent versus 39.9 percent among placebo subjects who later used NSAIDs sporadically.
"These findings imply that aspirin does not lose its antine¬oplastic properties over time and that these effects persist and may even be accentuated with prolonged NSAID use," the authors write.
Lack of general treatment failure or distant metastases 3 years after the start of treatment may be surrogate endpoints for long-term survival in patients with early prostate cancer.
Prostate cancer is a slowly progressing malignancy in many patients. The long natural history of the disease makes evaluation of new therapies difficult because patients must be followed for many years. If researchers could identify a surrogate clinical endpoint that accurately reflects long-term clinical outcomes for prostate cancer, clinical trials would be easier and faster.
To look for possible surrogate endpoints, Michael E. Ray, M.D., Ph.D., of ThedaCare and Bellin Health Systems in Appleton and Green Bay, Wisconsin, and colleagues evaluated the ability of general treatment failure and metastasis-free survival at 3 and 5 years to predict long-term survival in patients who had taken part in a clinical trial. A total of 1,521 patients who participated in the Radiation Therapy and Oncology Group 92-02 randomized controlled trial were included in the current analysis.
The authors found that both distant metastasis and general clinical treatment failure at 3 years were consistent with the four statistical criteria developed by Prentice for surrogate endpoints. At 5 years, only three of the four criteria were potentially fulfilled because prostate-cancer specific survival was not statistically significantly different between the two trial arms.
"The potential surrogate endpoints, distant metastasis and general clinical treatment failure, should be further and prospectively evaluated in future clinical trials along with overall and prostate cancer-specific survival endpoints," the authors conclude.
In an accompanying editorial, Ross L. Prentice, Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, who developed Prentice's criteria, discusses the difficulty of establishing surrogate endpoints and the importance of doing so. "The issue of full mediation by a potential surrogate is of more than academic interest, in view of multiple examples in which a clear treatment effect on a presumed surrogate did not translate to a corresponding effect on the clinical outcome of interest," the editorialist writes.
Netrin-1 and Its Dependence Receptor Implicated in Non-Small Cell Lung Cancer
Netrin-1 is overexpressed in a substantial fraction of human non-small cell lung cancer (NSCLC) tumors and interferes with apoptosis in NSCLC cells grown in culture.
Netrin-1 may promote colorectal and breast cancer. Previous studies suggest that the tumors may become dependent on its binding to particular receptors, referred to as dependence receptors. In the absence of netrin-1 binding these receptors trigger cell death. However netrin-1's potential role in NSCLC was unknown.
In the current study, Patrick Mehlen, Ph.D., of the Université de Lyon in France, and colleagues tested 92 human tumor samples for netrin-1 expression and examined the impact of inhibiting its expression in NSCLC cells grown in vitro and in xenograft animal models.
Netrin-1 was overexpressed in 43 (47%) of the human samples tested. Inhibition of netrin-1 expression induced apoptosis in NSCLC cell lines and reduced tumor growth in animal models.
"In conclusion, our findings raise the possibility that a targeted treatment that is based on inhibition of the interaction between netrin-1 and its dependence receptors might be of benefit to patients suffering from lung cancer whose primary tumors show high netrin-1 expression," the authors write.
In an accompanying editorial, Michael P. Schön, M.D., and Margarete Schön, Ph.D., of Georg August University in Göttingen, Germany, review the phenomenon of dependence receptors in cancer and the role of netrin-1 in normal biology and tumor progression, including the newly reported data by Mehlen and colleagues. "Additional studies will be needed to determine whether selectively targeting netrin-1 will become a useful addition to the therapeutic armamentarium in NSCLCs," the editorialists conclude.
Meta-Analysis Shows Aspirin Can Reduce Recurrence of Colon Polyps
Regular aspirin use is associated with a statistically significant reduction in the development of colorectal adenomas, which are precursor lesions to colorectal cancer, in individuals at high risk of developing colorectal cancer.
Multiple lines of evidence, including data from randomized clinical trials, suggest that aspirin may reduce the risk of colon adenomas and perhaps cancer. A quantitative summary of the clinical data - and a more precise estimate of the magnitude of the benefit associated with aspirin use -has been missing.
In the current study, Bernard F. Cole, Ph.D., of the University of Vermont in Burlington, and colleagues performed a meta-analysis of all available randomized clinical trials that examined adenoma formation in participants assigned to regular aspirin use or placebo.
Among 2,698 participants who underwent colonoscopic follow-up after randomization, 37% of the participants assigned to placebo developed adenomas compared with 33% of those assigned to aspirin. Moreover 12% of the participants assigned to placebo developed advanced adenomas compared with 9% of the participants assigned to aspirin. The pooled analysis indicated that regular aspirin use resulted in an absolute risk reduction of 6.7% for developing adenomas relative to placebo.
"The substantial size of the relative reduction in risk seen in our analysis (28% for advanced adenomas) and seen in clinical trials that evaluated the effect of aspirin on colorectal cancer risk (26% reduction) indicates the potentially important health benefits of aspirin use," the authors write. "Of course, these benefits need to be considered in the context of all of the health effects of aspirin, positive and negative."
Nonsteroidal Anti-inflammatory Drug Use After 3 Years of Aspirin Associated with Reduction in Colorectal Adenoma Risk
Data from an observational study conducted at the end of a randomized placebo-controlled trial indicate that continued use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the risk of developing colorectal adenomas, which are precursor lesions to colorectal cancer.
The randomized placebo-controlled Aspirin/Folate Polyp Prevention Study showed that regular use of low dose aspirin (81 mg) reduced the risk of colorectal polyp formation in individuals at high risk compared with placebo. To determine whether continued NSAID use might be beneficial, researchers invited the study participants to enroll in an follow-up study. This observational study examined their NSAID use and the risk of a diagnosis of colorectal adenoma at their next colonoscopy, on average 4 years after the end of randomized aspirin treatment.
In the current analysis, John Baron, M.D., of Dartmouth Medical School in Lebanon, N.H., and colleagues found that individuals who were initially assigned to low-dose aspirin in the randomized trial and continued to take NSAIDs four or more days per week during the follow-up period had a statistically significantly lower risk of adenomas than those who were assigned to placebo during the randomized trial and used NSAIDs less than two days per week during the observational study. The risk of adenomas among frequent NSAID users was 26.8 percent versus 39.9 percent among placebo subjects who later used NSAIDs sporadically.
"These findings imply that aspirin does not lose its antine¬oplastic properties over time and that these effects persist and may even be accentuated with prolonged NSAID use," the authors write.
Miraculins Announces Improved Detection Of Aggressive Prostate Cancer With Combination Of PSP94 And Free Over Total PSA Ratio
Miraculins Inc. (TSX VENTURE:MOM), a medical diagnostic company focused on developing and commercializing diagnostic tests for unmet clinical needs, is pleased to announce results which demonstrate that PSP94 in urine can be used to improve the performance of free over total (F/T) PSA ratio in detecting aggressive prostate cancer. The improvement offered by PSP94 is believed to be a novel discovery.
"The free PSA test is marketed by a number of large diagnostic companies and this discovery of the improvement offered by PSP94 is a tremendous addition to our prostate cancer package. We believe that this discovery could help significantly improve and differentiate the standard free PSA test," said Christopher Moreau, President and Chief Executive Officer of Miraculins Inc.
In Miraculins' recent immunoassay testing, the Company successfully demonstrated that standardized PSP94 combined with F/T PSA ratio was able to differentiate men with aggressive prostate cancer (Gleason Score of 7-10, n equals 18) from men with favorable pathologies (Gleason Score of 6 or less, BPH or healthy men, n equals 70) with a sensitivity of 94% and specificity of 49% (AUC equals 0.80). This result was much stronger than the individual performance of F/T PSA in the same samples, which had a sensitivity of 94% and specificity of 16%. When men with the confounding condition of hypertension were removed from testing, the combination yielded even better results and successfully separated the same populations with a sensitivity of 100% and a specificity of 84% (AUC equals 0.87, n equals 7 aggressive cancer and n equals 37 favorable pathologies).
"These results are important because they support the use of PSP94 in combination with F/T PSA ratio as a tool to help patients avoid unnecessary suffering from prostate cancer," stated Dr. Stephen Frost, Director of Research and Development for Miraculins. "As prostate cancer is often slow-growing, a number of men are currently engaged in watchful waiting programs as opposed to more aggressive treatment regimens. With a reliable tool for determining prostate cancer aggressiveness, only the highest risk patients would require repeat biopsy and therefore the physical and psychological cost of biopsies for men with non-aggressive forms of the disease could be avoided. A tool of this type may also enable more men to pursue watchful waiting as a treatment option."
"Additionally, a number of patients who have aggressive prostate cancer may not normally be referred to biopsy, such as men in the lower PSA range or those considered too old for PSA screening. These men could also benefit from a test which would allow those with aggressive forms of the disease to seek appropriate medical treatment," added Dr. Frost.
"The need for improved, non-invasive diagnostic tools for determining the aggressiveness of prostate cancer is well known and interest in this research area is growing within the scientific and medical fields. We believe that our discovery can make a contribution to this effort," concluded Moreau.
About Miraculins Inc.
Miraculins is a medical diagnostic development company focused on non-invasive tests for unmet clinical needs. Miraculins is bridging the gap between commercially available diagnostic tests and research conducted at leading research institutions around the world.
About F/T PSA Testing
PSA exists in several forms in the blood including bound to proteins and free (unbound). Free PSA is known to contribute to the diagnosis of prostate cancer when total PSA is modestly elevated, in addition to having been associated with prostate cancer aggressiveness in the literature. F/T PSA is based on a measurement of conventional (total) PSA and free PSA.
Caution Regarding Forward-Looking Information
Certain statements contained in this press release constitute forward-looking information within the meaning of applicable Canadian provincial securities legislation (collectively, "forward-looking statements"). These forward-looking statements relate to, among other things, our objectives, goals, targets, strategies, intentions, plans, beliefs, estimates and outlook, including, without limitation, our anticipated future operating results, and can, in some cases, be identified by the use of words such as "believe," "anticipate," "expect," "intend," "plan," "will," "may" and other similar expressions. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements.
These statements reflect management's current beliefs and are based on information currently available to management. Certain material factors or assumptions are applied in making forward-looking statements, and actual results may differ materially from those expressed or implied in such statements. Important factors that could cause actual results to differ materially from these expectations include, among other things: Miraculins' early stage of development, lack of product revenues and history of operating losses, uncertainties related to clinical trials and product development, rapid technological change, uncertainties related to forecasts, competition, potential product liability, additional financing requirements and access to capital, unproven markets, supply of raw materials, income tax matters, management of growth, partnerships for development and commercialization of technology, effects of insurers' willingness to pay for products, system failures, dependence on key personnel, foreign currency risk, risks related to regulatory matters and risks related to intellectual property and other risks detailed from time to time in Miraculins' filings with Canadian securities regulatory authorities, as well as Miraculins' ability to anticipate and manage the risks associated with the foregoing. Additional information about these factors and about the material factors or assumptions underlying such forward-looking statements may be found in the body of this news release. Miraculins cautions that the foregoing list of important factors that may affect future results is not exhaustive. When relying on Miraculins' forward-looking statements to make decisions with respect to Miraculins investors and others should carefully consider the foregoing factors and other uncertainties and potential events.
These risks and uncertainties should be considered carefully and prospective investors should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, Miraculins cannot provide assurance that actual results will be consistent with these forward-looking statements. Miraculins undertakes no obligation to update or revise any forward-looking statement.
The TSX Venture Exchange does not accept responsibility for the adequacy or accuracy of this release.
"The free PSA test is marketed by a number of large diagnostic companies and this discovery of the improvement offered by PSP94 is a tremendous addition to our prostate cancer package. We believe that this discovery could help significantly improve and differentiate the standard free PSA test," said Christopher Moreau, President and Chief Executive Officer of Miraculins Inc.
In Miraculins' recent immunoassay testing, the Company successfully demonstrated that standardized PSP94 combined with F/T PSA ratio was able to differentiate men with aggressive prostate cancer (Gleason Score of 7-10, n equals 18) from men with favorable pathologies (Gleason Score of 6 or less, BPH or healthy men, n equals 70) with a sensitivity of 94% and specificity of 49% (AUC equals 0.80). This result was much stronger than the individual performance of F/T PSA in the same samples, which had a sensitivity of 94% and specificity of 16%. When men with the confounding condition of hypertension were removed from testing, the combination yielded even better results and successfully separated the same populations with a sensitivity of 100% and a specificity of 84% (AUC equals 0.87, n equals 7 aggressive cancer and n equals 37 favorable pathologies).
"These results are important because they support the use of PSP94 in combination with F/T PSA ratio as a tool to help patients avoid unnecessary suffering from prostate cancer," stated Dr. Stephen Frost, Director of Research and Development for Miraculins. "As prostate cancer is often slow-growing, a number of men are currently engaged in watchful waiting programs as opposed to more aggressive treatment regimens. With a reliable tool for determining prostate cancer aggressiveness, only the highest risk patients would require repeat biopsy and therefore the physical and psychological cost of biopsies for men with non-aggressive forms of the disease could be avoided. A tool of this type may also enable more men to pursue watchful waiting as a treatment option."
"Additionally, a number of patients who have aggressive prostate cancer may not normally be referred to biopsy, such as men in the lower PSA range or those considered too old for PSA screening. These men could also benefit from a test which would allow those with aggressive forms of the disease to seek appropriate medical treatment," added Dr. Frost.
"The need for improved, non-invasive diagnostic tools for determining the aggressiveness of prostate cancer is well known and interest in this research area is growing within the scientific and medical fields. We believe that our discovery can make a contribution to this effort," concluded Moreau.
About Miraculins Inc.
Miraculins is a medical diagnostic development company focused on non-invasive tests for unmet clinical needs. Miraculins is bridging the gap between commercially available diagnostic tests and research conducted at leading research institutions around the world.
About F/T PSA Testing
PSA exists in several forms in the blood including bound to proteins and free (unbound). Free PSA is known to contribute to the diagnosis of prostate cancer when total PSA is modestly elevated, in addition to having been associated with prostate cancer aggressiveness in the literature. F/T PSA is based on a measurement of conventional (total) PSA and free PSA.
Caution Regarding Forward-Looking Information
Certain statements contained in this press release constitute forward-looking information within the meaning of applicable Canadian provincial securities legislation (collectively, "forward-looking statements"). These forward-looking statements relate to, among other things, our objectives, goals, targets, strategies, intentions, plans, beliefs, estimates and outlook, including, without limitation, our anticipated future operating results, and can, in some cases, be identified by the use of words such as "believe," "anticipate," "expect," "intend," "plan," "will," "may" and other similar expressions. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements.
These statements reflect management's current beliefs and are based on information currently available to management. Certain material factors or assumptions are applied in making forward-looking statements, and actual results may differ materially from those expressed or implied in such statements. Important factors that could cause actual results to differ materially from these expectations include, among other things: Miraculins' early stage of development, lack of product revenues and history of operating losses, uncertainties related to clinical trials and product development, rapid technological change, uncertainties related to forecasts, competition, potential product liability, additional financing requirements and access to capital, unproven markets, supply of raw materials, income tax matters, management of growth, partnerships for development and commercialization of technology, effects of insurers' willingness to pay for products, system failures, dependence on key personnel, foreign currency risk, risks related to regulatory matters and risks related to intellectual property and other risks detailed from time to time in Miraculins' filings with Canadian securities regulatory authorities, as well as Miraculins' ability to anticipate and manage the risks associated with the foregoing. Additional information about these factors and about the material factors or assumptions underlying such forward-looking statements may be found in the body of this news release. Miraculins cautions that the foregoing list of important factors that may affect future results is not exhaustive. When relying on Miraculins' forward-looking statements to make decisions with respect to Miraculins investors and others should carefully consider the foregoing factors and other uncertainties and potential events.
These risks and uncertainties should be considered carefully and prospective investors should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, Miraculins cannot provide assurance that actual results will be consistent with these forward-looking statements. Miraculins undertakes no obligation to update or revise any forward-looking statement.
The TSX Venture Exchange does not accept responsibility for the adequacy or accuracy of this release.
Researchers Discover Metabolite Linked To Aggressive Prostate Cancer
Researchers from the University of Michigan Comprehensive Cancer Center have identified a panel of small molecules, or metabolites, that appear to indicate aggressive prostate cancer.
The finding could lead to a simple test that would help doctors determine which prostate cancers are slow-growing and which require immediate, aggressive treatment.
Results of the study appear in the Feb. 12 issue of Nature.
"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.
The researchers looked at 1,126 metabolites across 262 samples of tissue, blood or urine associated with benign prostate tissue, early stage prostate cancer and advanced, or metastatic, prostate cancer. They mapped the alterations in metabolites and identified about 10 that were present more often in prostate cancer than in the benign cells and were present most often in the advanced cancer samples.
"When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development," says Chinnaiyan, a Howard Hughes Medical Institute investigator.
One metabolite in particular, sarcosine, appeared to be one of the strongest indicators of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79 percent of the metastatic prostate cancer samples and in 42 percent of the early stage cancer samples. None of the cancer-free samples had detectable levels of sarcosine.
In the study, sarcosine was a better indicator of advancing disease than the traditional prostate specific antigen, or PSA, test that is currently used to monitor or screen for prostate cancer. Sarcosine was detected in the urine, which has researchers hopeful that a simple urine test could be used.
In addition, the researchers found that sarcosine is involved in the same pathways that are linked to cancer invasiveness. This suggests sarcosine as a potential target for future drug development.
"This research gets at characterizing the chemical complexity of a sample of cancer progression. In the future, this science will drive how doctors make treatment recommendations for their patients," says study author Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School.
Results are preliminary at this point and will need years of further testing and development before this technology would be available for patients.
Prostate cancer statistics: 186,320 Americans will be diagnosed with prostate cancer this year and 28,660 will die from the disease, according to the American Cancer Society.
Additional authors: From the University of Michigan: Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaemun Byun, Gilbert S. Omenn, Subramaniam Pennathur, John T. Wei and Sooryanarayana Varambally. From Metabolon Inc.: Danny C. Alexander, Alvin Berger and Jeffrey R. Shuster. From Penn State University: Debashis Ghosh.
Funding: National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Wellcome Foundation, and the Doris Duke Charitable Foundation
Disclosure: The University of Michigan has exclusively licensed all pending patents covering this technology to Metabolon, a company with expertise in discovering biomarkers using metabolomics. Beecher, Alexander, Shuster and Chinnaiyan own equity in Metabolon and Chinnaiyan serves on its Scientific Advisory Board. Beecher is a previous employee of Metabolon.
Reference: Nature, Vol. 457, No. 7231, pp. 910-915, Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
The finding could lead to a simple test that would help doctors determine which prostate cancers are slow-growing and which require immediate, aggressive treatment.
Results of the study appear in the Feb. 12 issue of Nature.
"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.
The researchers looked at 1,126 metabolites across 262 samples of tissue, blood or urine associated with benign prostate tissue, early stage prostate cancer and advanced, or metastatic, prostate cancer. They mapped the alterations in metabolites and identified about 10 that were present more often in prostate cancer than in the benign cells and were present most often in the advanced cancer samples.
"When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development," says Chinnaiyan, a Howard Hughes Medical Institute investigator.
One metabolite in particular, sarcosine, appeared to be one of the strongest indicators of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79 percent of the metastatic prostate cancer samples and in 42 percent of the early stage cancer samples. None of the cancer-free samples had detectable levels of sarcosine.
In the study, sarcosine was a better indicator of advancing disease than the traditional prostate specific antigen, or PSA, test that is currently used to monitor or screen for prostate cancer. Sarcosine was detected in the urine, which has researchers hopeful that a simple urine test could be used.
In addition, the researchers found that sarcosine is involved in the same pathways that are linked to cancer invasiveness. This suggests sarcosine as a potential target for future drug development.
"This research gets at characterizing the chemical complexity of a sample of cancer progression. In the future, this science will drive how doctors make treatment recommendations for their patients," says study author Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School.
Results are preliminary at this point and will need years of further testing and development before this technology would be available for patients.
Prostate cancer statistics: 186,320 Americans will be diagnosed with prostate cancer this year and 28,660 will die from the disease, according to the American Cancer Society.
Additional authors: From the University of Michigan: Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaemun Byun, Gilbert S. Omenn, Subramaniam Pennathur, John T. Wei and Sooryanarayana Varambally. From Metabolon Inc.: Danny C. Alexander, Alvin Berger and Jeffrey R. Shuster. From Penn State University: Debashis Ghosh.
Funding: National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Wellcome Foundation, and the Doris Duke Charitable Foundation
Disclosure: The University of Michigan has exclusively licensed all pending patents covering this technology to Metabolon, a company with expertise in discovering biomarkers using metabolomics. Beecher, Alexander, Shuster and Chinnaiyan own equity in Metabolon and Chinnaiyan serves on its Scientific Advisory Board. Beecher is a previous employee of Metabolon.
Reference: Nature, Vol. 457, No. 7231, pp. 910-915, Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Metabolite Linked To Aggressive Prostate Cancer Discovered By Researchers
Researchers from the University of Michigan Comprehensive Cancer Center have identified a panel of small molecules, or metabolites, that appear to indicate aggressive prostate cancer.
The finding could lead to a simple test that would help doctors determine which prostate cancers are slow-growing and which require immediate, aggressive treatment.
Results of the study appear in the Feb. 12 issue of Nature.
"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.
The researchers looked at 1,126 metabolites across 262 samples of tissue, blood or urine associated with benign prostate tissue, early stage prostate cancer and advanced, or metastatic, prostate cancer. They mapped the alterations in metabolites and identified about 10 that were present more often in prostate cancer than in the benign cells and were present most often in the advanced cancer samples.
"When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development," says Chinnaiyan, a Howard Hughes Medical Institute investigator.
One metabolite in particular, sarcosine, appeared to be one of the strongest indicators of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79 percent of the metastatic prostate cancer samples and in 42 percent of the early stage cancer samples. Sarcosine was not found at all in the cancer-free samples.
In the study, sarcosine was a better indicator of advancing disease than the traditional prostate specific antigen, or PSA, test that is currently used to monitor or screen for prostate cancer. Sarcosine was detected in the urine, which has researchers hopeful that a simple urine test could be used.
In addition, the researchers found that sarcosine is involved in the same pathways that are linked to cancer invasiveness. This suggests sarcosine as a potential target for future drug development.
"This research gets at characterizing the chemical complexity of a sample of blood. In the future, this science will drive how doctors make treatment recommendations for their patients," says study author Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School.
Results are preliminary at this point and will need years of further testing and development before this technology would be available for patients.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Prostate cancer statistics: 186,320 Americans will be diagnosed with prostate cancer this year and 28,660 will die from the disease, according to the American Cancer Society
Additional authors: From the University of Michigan: Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaemun Byun, Gilbert S. Omenn, Subramaniam Pennathur, John T. Wei and Sooryanarayana Varambally. From Metabolon Inc.: Danny C. Alexander, Alvin Berger and Jeffrey R. Shuster. From Penn State University: Debashis Ghosh.
Funding: National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Wellcome Foundation, and the Doris Duke Charitable Foundation
Disclosure: The University of Michigan has exclusively licensed all pending patents covering this technology to Metabolon, a company with expertise in discovering biomarkers using metabolomics. Beecher, Alexander, Shuster and Chinnaiyan own equity in Metabolon and Chinnaiyan serves on its Scientific Advisory Board. Beecher is a previous employee of Metabolon.
Reference: Nature, Vol. 457, No. 7231, pp. 910-915, Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
The finding could lead to a simple test that would help doctors determine which prostate cancers are slow-growing and which require immediate, aggressive treatment.
Results of the study appear in the Feb. 12 issue of Nature.
"One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up overtreating our patients because physicians don't know which tumors will be slow-growing. With this research, we have identified a potential marker for the aggressive tumors," says senior study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.
The researchers looked at 1,126 metabolites across 262 samples of tissue, blood or urine associated with benign prostate tissue, early stage prostate cancer and advanced, or metastatic, prostate cancer. They mapped the alterations in metabolites and identified about 10 that were present more often in prostate cancer than in the benign cells and were present most often in the advanced cancer samples.
"When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development," says Chinnaiyan, a Howard Hughes Medical Institute investigator.
One metabolite in particular, sarcosine, appeared to be one of the strongest indicators of advanced disease. Levels of sarcosine, an amino acid, were elevated in 79 percent of the metastatic prostate cancer samples and in 42 percent of the early stage cancer samples. Sarcosine was not found at all in the cancer-free samples.
In the study, sarcosine was a better indicator of advancing disease than the traditional prostate specific antigen, or PSA, test that is currently used to monitor or screen for prostate cancer. Sarcosine was detected in the urine, which has researchers hopeful that a simple urine test could be used.
In addition, the researchers found that sarcosine is involved in the same pathways that are linked to cancer invasiveness. This suggests sarcosine as a potential target for future drug development.
"This research gets at characterizing the chemical complexity of a sample of blood. In the future, this science will drive how doctors make treatment recommendations for their patients," says study author Christopher Beecher, Ph.D., professor of pathology at the U-M Medical School.
Results are preliminary at this point and will need years of further testing and development before this technology would be available for patients.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Prostate cancer statistics: 186,320 Americans will be diagnosed with prostate cancer this year and 28,660 will die from the disease, according to the American Cancer Society
Additional authors: From the University of Michigan: Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaemun Byun, Gilbert S. Omenn, Subramaniam Pennathur, John T. Wei and Sooryanarayana Varambally. From Metabolon Inc.: Danny C. Alexander, Alvin Berger and Jeffrey R. Shuster. From Penn State University: Debashis Ghosh.
Funding: National Cancer Institute Early Detection Research Network, National Institutes of Health, an MTTC grant, the Burroughs Wellcome Foundation, and the Doris Duke Charitable Foundation
Disclosure: The University of Michigan has exclusively licensed all pending patents covering this technology to Metabolon, a company with expertise in discovering biomarkers using metabolomics. Beecher, Alexander, Shuster and Chinnaiyan own equity in Metabolon and Chinnaiyan serves on its Scientific Advisory Board. Beecher is a previous employee of Metabolon.
Reference: Nature, Vol. 457, No. 7231, pp. 910-915, Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression
Circulating Tumor Cells As Indicators Of Prostate Cancer Status
A new study suggests that monitoring circulating tumor cells (CTCs), the cells that have broken free from the tumor, may be a useful way to assess the status of prostate cancer that is more reliable than the PSA (prostate specific antigen) test, although the findings would need to be confirmed in clinical trials, said the authors.
The study was the work of researchers at the Memorial Sloan-Kettering Cancer Center in New York, other research centers in the US and the Royal Marsden Hospital in London, UK, and is published in the early online issue of the The Lancet Oncology on 11 February.
The main purpose of the study was to find another way to monitor progress in drug trials that gives reliable intermediate results so that approval timescales can be shortened. The authors decided to investigate whether measuring CTCs might be a useful way to predict survival in patients who are undergoing chemotherapy to treat progressive prostate cancer that has started to spread.
For the study, the researchers identified 164 men with progressive metastatic castration-resistant prostate cancer who were undergoing first line chemotherapy in the IMMC38 trial. In this trial, the CTCs were isolated from blood samples using a method called immunomagnetic capture; this was done at the start and end of the trial.
The researchers analysed the association between survival and the before and after values of a number of variables, including CTC count, levels of PSA, lactate dehydrogenase (LDH) and others, and assessed how well they identified patients at high and low risk of survival.
The results showed that:
* Variables linked to a high risk of death included: high LDH, high CTC, and high PSA, low albumin and low haemoglobin at baseline (start of study).
* After 4 weeks, 8 weeks and 12 weeks, changes in CTC counts were strongly linked to risk, whereas PSA was not.
* The strongest predictors for survival were LDH concentration and CTC counts.
The authors concluded that:
"CTC number, analysed as a continuous variable, can be used to monitor disease status [of prostate cancer] and might be useful as an intermediate endpoint of survival in clinical trials. "
They suggested the results were strong enough to warrant "prospective recording of CTC number as an intermediate endpoint of survival in randomised clinical trials".
Commenting on the findings, John Neate, Chief Executive of The Prostate Cancer Charity in the UK told the press that:
"Once prostate cancer has advanced to the stage where chemotherapy is an option -- which is at a late stage of the disease, unlike in many other cancers -- one of the problems that doctors face is uncertainty about the effectiveness of the treatment. "
He said that current tests aren't very effective at tracking progress of the disease in chemotherapy, they work reasonably well, but something better is needed, he said.
"Whilst further trials are necessary, this new research shows that measuring the number of circulating tumour cells seems to improve prediction of how men will respond to chemotherapy," said Neate, adding that measuring CTCs seems to be:
"More finely attuned to the effects of the chemotherapy than previously thought. There are, therefore, circumstances where some men will benefit from further courses of chemotherapy treatment when at present they may not be offered it," explained Neate.
He also said that a more accurate measure may help to reduce the anxiety that comes when there is insufficient clarity about the progress of the disease adding to the difficulty of deciding if the treatment is working or not.
"Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data."
Howard I Scher, Xiaoyu Jia, Johann S de Bono, Martin Fleisher, Kenneth J Pienta, Derek Raghavan, Glenn Heller.
The Lancet Oncology, Early Online Publication, 11 February 2009.
doi:10.1016/S1470-2045(08)70340-1
The study was the work of researchers at the Memorial Sloan-Kettering Cancer Center in New York, other research centers in the US and the Royal Marsden Hospital in London, UK, and is published in the early online issue of the The Lancet Oncology on 11 February.
The main purpose of the study was to find another way to monitor progress in drug trials that gives reliable intermediate results so that approval timescales can be shortened. The authors decided to investigate whether measuring CTCs might be a useful way to predict survival in patients who are undergoing chemotherapy to treat progressive prostate cancer that has started to spread.
For the study, the researchers identified 164 men with progressive metastatic castration-resistant prostate cancer who were undergoing first line chemotherapy in the IMMC38 trial. In this trial, the CTCs were isolated from blood samples using a method called immunomagnetic capture; this was done at the start and end of the trial.
The researchers analysed the association between survival and the before and after values of a number of variables, including CTC count, levels of PSA, lactate dehydrogenase (LDH) and others, and assessed how well they identified patients at high and low risk of survival.
The results showed that:
* Variables linked to a high risk of death included: high LDH, high CTC, and high PSA, low albumin and low haemoglobin at baseline (start of study).
* After 4 weeks, 8 weeks and 12 weeks, changes in CTC counts were strongly linked to risk, whereas PSA was not.
* The strongest predictors for survival were LDH concentration and CTC counts.
The authors concluded that:
"CTC number, analysed as a continuous variable, can be used to monitor disease status [of prostate cancer] and might be useful as an intermediate endpoint of survival in clinical trials. "
They suggested the results were strong enough to warrant "prospective recording of CTC number as an intermediate endpoint of survival in randomised clinical trials".
Commenting on the findings, John Neate, Chief Executive of The Prostate Cancer Charity in the UK told the press that:
"Once prostate cancer has advanced to the stage where chemotherapy is an option -- which is at a late stage of the disease, unlike in many other cancers -- one of the problems that doctors face is uncertainty about the effectiveness of the treatment. "
He said that current tests aren't very effective at tracking progress of the disease in chemotherapy, they work reasonably well, but something better is needed, he said.
"Whilst further trials are necessary, this new research shows that measuring the number of circulating tumour cells seems to improve prediction of how men will respond to chemotherapy," said Neate, adding that measuring CTCs seems to be:
"More finely attuned to the effects of the chemotherapy than previously thought. There are, therefore, circumstances where some men will benefit from further courses of chemotherapy treatment when at present they may not be offered it," explained Neate.
He also said that a more accurate measure may help to reduce the anxiety that comes when there is insufficient clarity about the progress of the disease adding to the difficulty of deciding if the treatment is working or not.
"Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data."
Howard I Scher, Xiaoyu Jia, Johann S de Bono, Martin Fleisher, Kenneth J Pienta, Derek Raghavan, Glenn Heller.
The Lancet Oncology, Early Online Publication, 11 February 2009.
doi:10.1016/S1470-2045(08)70340-1
Can The Mediterranean Diet Prevent Prostate Cancer?
We recently reviewed evidence relating diet and prostate cancer, suggesting that a traditional Cretan Mediterranean style diet based on a variety of plant foods (fruits, vegetables, wholegrain cereals, nuts and legumes), olive oil as the main source of fat, low intake of red meat, moderate to low intake of dairy foods, moderate to high intake of fish and moderate intake of wine, mostly consumed with meals, may be helpful in reducing prostate cancer risk.
Importantly, the Mediterranean diet has other health benefits that further support its widespread adoption. A recent meta-analysis of prospective cohort studies using an a priori score to assess adherence to a Mediterranean diet found that stronger adherence was associated with reduced all cause, cardiovascular and cancer mortality, as well as decreased incidence of Parkinson's and Alzheimer's diseases (1).
Two intervention studies have supported the benefits of a Mediterranean style diet on metabolic risk factors (2) (3). In a Spanish study, men and women with elevated levels of cardiovascular risk factors were randomized to either of two "Mediterranean" diets and provided with either olive oil or nuts, or to a control low fat diet. After 3 months the Mediterranean diet groups had lower mean plasma glucose, systolic blood pressure and total/HDL cholesterol ratio than the control group (2). Italian adults with the Metabolic Syndrome were randomized to a "Mediterranean" diet or a "prudent" diet, both with similar macronutrient composition. The "Mediterranean" diet was associated with greater improvements in markers of vascular risk and endothelial function than the control group (3). It should be noted however that in both studies the "Mediterranean" diet groups received more nutrition education than the control groups.
The Lyon Heart Study demonstrated that a modified Cretan diet low in butter and meats, and high in fish, fruits and enriched with α-linolenic acid from canola oil was more effective than a 'prudent' diet in the secondary prevention of coronary events and overall mortality (4). We have also shown that a Cretan style diet reduced HbA1c from a mean of 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012), in people with type 2 diabetes (unpublished data).
Simopoulos (5) notes that the traditional Greek diet resembles the Paleolithic diet in terms of fibre, antioxidants, saturated and monounsaturated fat, thus is consistent with human evolution. While traditional diets must reflect the regionally available foods, the characteristics of the traditional Greek diet can be applied in many countries, notwithstanding the likely effect of environment and growing methods on the nutrient composition of plant and animal foods. The evidence suggests that a traditional Greek or Cretan style diet is consistent with what humans have evolved to consume and may protect against common chronic diseases, including prostate cancer.
Written by Allison Hodge, MD, and Catherine Itsiopoulos, MD as part of Beyond the Abstract on UroToday.com.
References:
1. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008;337:a1344.
2. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
3. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc 2004;292:1440-6.
4. de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. In: Simopoulos AP, Visioli F, eds. Mediterranean Diets. World Review Nutr Diet. Basel: Karger, 2000:1-23.
5. Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev 2004;13:219-30.
Importantly, the Mediterranean diet has other health benefits that further support its widespread adoption. A recent meta-analysis of prospective cohort studies using an a priori score to assess adherence to a Mediterranean diet found that stronger adherence was associated with reduced all cause, cardiovascular and cancer mortality, as well as decreased incidence of Parkinson's and Alzheimer's diseases (1).
Two intervention studies have supported the benefits of a Mediterranean style diet on metabolic risk factors (2) (3). In a Spanish study, men and women with elevated levels of cardiovascular risk factors were randomized to either of two "Mediterranean" diets and provided with either olive oil or nuts, or to a control low fat diet. After 3 months the Mediterranean diet groups had lower mean plasma glucose, systolic blood pressure and total/HDL cholesterol ratio than the control group (2). Italian adults with the Metabolic Syndrome were randomized to a "Mediterranean" diet or a "prudent" diet, both with similar macronutrient composition. The "Mediterranean" diet was associated with greater improvements in markers of vascular risk and endothelial function than the control group (3). It should be noted however that in both studies the "Mediterranean" diet groups received more nutrition education than the control groups.
The Lyon Heart Study demonstrated that a modified Cretan diet low in butter and meats, and high in fish, fruits and enriched with α-linolenic acid from canola oil was more effective than a 'prudent' diet in the secondary prevention of coronary events and overall mortality (4). We have also shown that a Cretan style diet reduced HbA1c from a mean of 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012), in people with type 2 diabetes (unpublished data).
Simopoulos (5) notes that the traditional Greek diet resembles the Paleolithic diet in terms of fibre, antioxidants, saturated and monounsaturated fat, thus is consistent with human evolution. While traditional diets must reflect the regionally available foods, the characteristics of the traditional Greek diet can be applied in many countries, notwithstanding the likely effect of environment and growing methods on the nutrient composition of plant and animal foods. The evidence suggests that a traditional Greek or Cretan style diet is consistent with what humans have evolved to consume and may protect against common chronic diseases, including prostate cancer.
Written by Allison Hodge, MD, and Catherine Itsiopoulos, MD as part of Beyond the Abstract on UroToday.com.
References:
1. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008;337:a1344.
2. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
3. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc 2004;292:1440-6.
4. de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. In: Simopoulos AP, Visioli F, eds. Mediterranean Diets. World Review Nutr Diet. Basel: Karger, 2000:1-23.
5. Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev 2004;13:219-30.
Discovery Of New Prostate Cancer Marker In Urine
Howard Hughes Medical Institute researchers have identified a new biological marker present in the urine of patients with prostate cancer that indicates whether the cancer is progressing and spreading.
In experiments reported in the February 12, 2009, issue of the journal Nature, the scientists identified 10 metabolites that become more abundant in prostate cells as cancer progresses. Their studies showed that one of these chemicals, sarcosine, helps prostate cancer cells invade surrounding tissue.
HHMI investigator Arul Chinnaiyan and colleagues at the University of Michigan showed that as prostate cancer develops and progresses, sarcosine levels increase in both tumor cells and urine samples, suggesting that measurements of the metabolite could aid in non-invasively diagnosing the disease. Researchers might also be able to inhibit prostate cancer's spread by designing drugs that manipulate the sarcosine pathway.
The study is the first to analyze the levels of more than 1,000 different metabolites in human tumors. Scientists know that cells undergo complex changes as cancer develops and progresses to metastatic disease. Chinnaiyan's lab, which has extensively analyzed how genes and proteins in prostate cancer cells reflect these changes, thought that profiling cells' metabolites would offer an even more "holistic picture of the molecular alterations that occur," he said.
"This allows us to have more of a systems perspective of cancer development," he noted. "We are also looking at gene and protein markers, for therapeutic consideration, biomarker consideration, and just understanding the biology. We are not sure yet how it's going to sort out, so we're being non-discriminatory with what types of technologies we use."
In the experiments reported in Nature, the scientists used mass spectrometry, a technique that identifies chemicals based on the size and electrical charge of their components, to compare the levels of 1,126 metabolites in healthy prostate tissue, clinically localized prostate cancer, and metastatic prostate cancer. Sixty metabolites were present in tumor cells, but not in benign tissue. Of these, there were about 10 molecules whose levels increased dramatically during cancer progression. "This is proof-of-principle that we can identify metabolites, or panels of metabolites, that might be correlated with aggressive prostate cancer versus slower-growing prostate cancer," Chinnaiyan said.
Having demonstrated that "metabolomic" profiles change in predictable ways as cancer progresses, the group began more focused analyses. "We began to mine the data to look for metabolites that might serve as biomarkers or as therapeutic targets," Chinnaiyan explained. They chose to focus on sarcosine because it was elevated in clinically localized disease and very highly elevated in metastatic cancer.
They confirmed these dramatic increases in a new set of tissue samples, and also found that there was more sarcosine in the urine of patients with prostate cancer than in healthy individuals.
The team went on to test how sarcosine affected the behavior of cancer cells grown in the laboratory. Adding the chemical to prostate cells or manipulating cells' biochemical pathways so they produced more sarcosine on their own caused benign prostate cells to become cancerous and invasive. Conversely, shutting down sarcosine production in cancer cells blocked invasion.
"This really told us that sarcosine is involved biologically in some of the processes of a cancer cell," Chinnaiyan said. The results suggest that drugs that alter sarcosine metabolism might be useful in treating prostate cancer, but Chinnaiyan cautions that these Petri-dish findings still need further validation in animal models.
An important next step, he says, will be to do similar experiments on the other nine potential biomarkers they identified in this study. For reliable diagnosis of aggressive disease, he said, "we need to have panels, not just rely on a single metabolite."
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Source: Jennifer Michalowski
Howard Hughes Medical Institute
In experiments reported in the February 12, 2009, issue of the journal Nature, the scientists identified 10 metabolites that become more abundant in prostate cells as cancer progresses. Their studies showed that one of these chemicals, sarcosine, helps prostate cancer cells invade surrounding tissue.
HHMI investigator Arul Chinnaiyan and colleagues at the University of Michigan showed that as prostate cancer develops and progresses, sarcosine levels increase in both tumor cells and urine samples, suggesting that measurements of the metabolite could aid in non-invasively diagnosing the disease. Researchers might also be able to inhibit prostate cancer's spread by designing drugs that manipulate the sarcosine pathway.
The study is the first to analyze the levels of more than 1,000 different metabolites in human tumors. Scientists know that cells undergo complex changes as cancer develops and progresses to metastatic disease. Chinnaiyan's lab, which has extensively analyzed how genes and proteins in prostate cancer cells reflect these changes, thought that profiling cells' metabolites would offer an even more "holistic picture of the molecular alterations that occur," he said.
"This allows us to have more of a systems perspective of cancer development," he noted. "We are also looking at gene and protein markers, for therapeutic consideration, biomarker consideration, and just understanding the biology. We are not sure yet how it's going to sort out, so we're being non-discriminatory with what types of technologies we use."
In the experiments reported in Nature, the scientists used mass spectrometry, a technique that identifies chemicals based on the size and electrical charge of their components, to compare the levels of 1,126 metabolites in healthy prostate tissue, clinically localized prostate cancer, and metastatic prostate cancer. Sixty metabolites were present in tumor cells, but not in benign tissue. Of these, there were about 10 molecules whose levels increased dramatically during cancer progression. "This is proof-of-principle that we can identify metabolites, or panels of metabolites, that might be correlated with aggressive prostate cancer versus slower-growing prostate cancer," Chinnaiyan said.
Having demonstrated that "metabolomic" profiles change in predictable ways as cancer progresses, the group began more focused analyses. "We began to mine the data to look for metabolites that might serve as biomarkers or as therapeutic targets," Chinnaiyan explained. They chose to focus on sarcosine because it was elevated in clinically localized disease and very highly elevated in metastatic cancer.
They confirmed these dramatic increases in a new set of tissue samples, and also found that there was more sarcosine in the urine of patients with prostate cancer than in healthy individuals.
The team went on to test how sarcosine affected the behavior of cancer cells grown in the laboratory. Adding the chemical to prostate cells or manipulating cells' biochemical pathways so they produced more sarcosine on their own caused benign prostate cells to become cancerous and invasive. Conversely, shutting down sarcosine production in cancer cells blocked invasion.
"This really told us that sarcosine is involved biologically in some of the processes of a cancer cell," Chinnaiyan said. The results suggest that drugs that alter sarcosine metabolism might be useful in treating prostate cancer, but Chinnaiyan cautions that these Petri-dish findings still need further validation in animal models.
An important next step, he says, will be to do similar experiments on the other nine potential biomarkers they identified in this study. For reliable diagnosis of aggressive disease, he said, "we need to have panels, not just rely on a single metabolite."
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
Source: Jennifer Michalowski
Howard Hughes Medical Institute
NeoPharm Submits Application For A Multicenter, Open-Label, Phase II Study Of LE-DT For Castrate Resistant Prostate Cancer
NeoPharm, Inc. (NASDAQ: NEOL) announced that it has submitted a Phase II protocol to the FDA for the study of liposome entrapped docetaxel (LE-DT), a novel, proprietary liposomal delivery system of docetaxel, the active ingredient of Taxotere®, in hormone refractory metastatic prostate cancer patients.
"The preliminary results from our Phase I trial, which has not yet concluded, have been encouraging. As a result, we plan to evaluate the efficacy of LE-DT in prostate cancer patients who have failed radiation and hormonal treatment and we have submitted a Phase II protocol for such a study to the FDA," commented Mr. Laurence Birch, President and Chief Executive Officer of NeoPharm Inc. "While FDA approval is needed before commencing patient enrollment, we believe this submission is yet another example of our commitment to progressing our drug product candidates through development."
Dr. Aquilur Rahman, Chief Scientific Adviser of NeoPharm commented, "We are pleased with the ongoing results from our Phase I trial of LE-DT. To that end, this open-label, Phase II study is designed to determine the antitumor effect on serum Prostate Specific Antigen (PSA) levels, disease response, progression free survival, and quality of life in patients with metastatic prostate cancer. We anticipate enrolling 40 patients in this Phase II trial at three locations".
About NeoPharm, Inc.
NeoPharm, Inc., based in Lake Bluff, Illinois, is a publicly traded biopharmaceutical company dedicated to the research, development and commercialization of new and innovative cancer and other drugs for therapeutic applications. Additional information, including ongoing clinical trials, can be obtained by visiting NeoPharm's Web site at http://www.NeoPharm.com.
Forward Looking Statements
This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as "expects," "intends," "projects," "hopes," "anticipates," "believes," "could," "may," "evidences" and "estimates," and other similar expressions, but these words are not the exclusive means of identifying such statements. Such statements include, but are not limited to, any statements relating to the Company's drug development programs, the initiation, progress, and outcomes of clinical trials of the Company's drug product candidates including, but not limited to LE-DT, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, risks and uncertainties relating to difficulties or delays that may arise in the development, testing, regulatory approval, production, and marketing of the Company's drug and non-drug compounds, including, but not limited to, LE-DT, the Company's possible need to reduce its funding of certain of its development projects in order to conserve its cash resources, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug product candidates, including, but not limited to, LE-DT, that could slow or prevent products coming to market, uncertainty regarding the Company's ability to commercialize any of its drug product candidates, including, but not limited to, LE-DT, and other risks detailed from time to time in filings the Company makes with the Securities and Exchange Commission including its annual report on Form 10-K for the calendar year ended December 31, 2007, as subsequently updated by the Company in its quarterly reports on Form 10-Q. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release. Accordingly, you should not rely on these forward-looking statements as a prediction of actual future results.
"The preliminary results from our Phase I trial, which has not yet concluded, have been encouraging. As a result, we plan to evaluate the efficacy of LE-DT in prostate cancer patients who have failed radiation and hormonal treatment and we have submitted a Phase II protocol for such a study to the FDA," commented Mr. Laurence Birch, President and Chief Executive Officer of NeoPharm Inc. "While FDA approval is needed before commencing patient enrollment, we believe this submission is yet another example of our commitment to progressing our drug product candidates through development."
Dr. Aquilur Rahman, Chief Scientific Adviser of NeoPharm commented, "We are pleased with the ongoing results from our Phase I trial of LE-DT. To that end, this open-label, Phase II study is designed to determine the antitumor effect on serum Prostate Specific Antigen (PSA) levels, disease response, progression free survival, and quality of life in patients with metastatic prostate cancer. We anticipate enrolling 40 patients in this Phase II trial at three locations".
About NeoPharm, Inc.
NeoPharm, Inc., based in Lake Bluff, Illinois, is a publicly traded biopharmaceutical company dedicated to the research, development and commercialization of new and innovative cancer and other drugs for therapeutic applications. Additional information, including ongoing clinical trials, can be obtained by visiting NeoPharm's Web site at http://www.NeoPharm.com.
Forward Looking Statements
This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. The Company has tried to identify such forward-looking statements by use of such words as "expects," "intends," "projects," "hopes," "anticipates," "believes," "could," "may," "evidences" and "estimates," and other similar expressions, but these words are not the exclusive means of identifying such statements. Such statements include, but are not limited to, any statements relating to the Company's drug development programs, the initiation, progress, and outcomes of clinical trials of the Company's drug product candidates including, but not limited to LE-DT, and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, risks and uncertainties relating to difficulties or delays that may arise in the development, testing, regulatory approval, production, and marketing of the Company's drug and non-drug compounds, including, but not limited to, LE-DT, the Company's possible need to reduce its funding of certain of its development projects in order to conserve its cash resources, the ability of the Company to procure additional future sources of financing, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug product candidates, including, but not limited to, LE-DT, that could slow or prevent products coming to market, uncertainty regarding the Company's ability to commercialize any of its drug product candidates, including, but not limited to, LE-DT, and other risks detailed from time to time in filings the Company makes with the Securities and Exchange Commission including its annual report on Form 10-K for the calendar year ended December 31, 2007, as subsequently updated by the Company in its quarterly reports on Form 10-Q. Such statements are based on management's current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release. Accordingly, you should not rely on these forward-looking statements as a prediction of actual future results.
Scientists Hopeful Of Simple Urine Test For Prostate Cancer
US scientists have found that a molecule called sarcosine, a byproduct of metabolism that is eliminated via urine, could be an effective marker for prostate cancer and that simple urine tests that measure concentrations of this marker might one day reduce the need for invasive biopsies.
The research behind the discovery is written up as an article in the 12 February issue of Nature, and was the work of Dr Christopher Beecher at the University of Michigan in Ann Arbor, and a large team of colleagues, including researchers from other centers in the US.
For this study, the researchers inspected metabolites (byproducts of natural chemical reactions in the body) in 262 samples from prostate cancer patients who were at various stages of the disease, so that samples ranged from containing benign cells to aggressive metastized tumors that had already spread to other organs. As cancers progress from early to late stages, the concentration of metabolites associated with these changes vary.
Scientists already have a list of "likely suspects" for metabolic byproducts that could indicate changes in prostate cancer progression, but what is special about this study is that Beecher and colleagues decided to widen their search to include all the metabolites present in the samples they had, including some that were not considered "likely suspects". They were able to do this because they used mass spectrometry, which picks up all the molecules in a sample and presents a unique signature for each one.
And, as often happens in science, the result was a complete surprise, because the best contender was not among the "likely suspects".
As Beecher explained to Nature News:
"We would never have expected to see sarcosine, nor would we have expected to look for it."
Sarcosine is a byproduct of the amino acid glycine. Beecher and colleagues actually found at least 6 metabolites that were present in higher concentrations in the more advanced metastatic cancer samples compared to samples of earlier stages of the disease, but sarcosine was by far the highest.
The researchers went on to identify the enzymes that make and break down sarcosine and altered the genes that control these processes in lab cultured cells.
As Beecher explained, any time the researchers did anything that increased the production of sarcosine, the cells "started to move so much they could get themselves into a sample of gelatine under their own force", a characteristic behaviour of cancerous cells. The researchers found that just adding sarcosine to benign prostate cells made them act like cancerous cells.
This suggests that sarcosine is not only a marker of how aggressive a cancer is, but it is also active in making cells cancerous.
The researchers said their findings could offer targets for new treatments, as Malcolm Mason, a prostate cancer expert from Cardiff University in Wales, UK, who also works for Cancer Research UK, explained, there is enough evidence here to warrant looking at using sarcosine as a new drug target:
"Not only have they got a marker that has a fundamental role in invasion and metastasis, the molecule itself is regulated by systems that have been directly implicated in prostate cancer."
However, Mason emphasized that the findings need to be confirmed by other studies, and he also cautioned that sarcosine is unlikely to be used widely in screening programs; there are several studies under way in Europe looking at possible new markers already. Mason said urine tests for sarcosine would not be like tests you can do in the pharmacy: they will most likely be used to help specialists decide if and when to do biopsies.
However, Beecher is hopeful that sarcosine will play a bigger role and tests based on it will one day replace current tests.
"This may actually be superior to PSA," he said. The researchers suggested that there could one day be a test for a "panel of metabolites".
Beecher and colleagues are planning to use their research method to look at metabolites of other diseases.
Present ways of screening for prostate cancer rely primarily on testing concentrations of prostate specific antigen (PSA) in the blood. PSA is a protein that binds to prostate cancer cells. The free PSA test is another guide: it checks how much of the PSA has not bound to cancer cells, and the theory is that the more free PSA there is the less cancer there is, but as many specialists know, it is not an exact science, and biopsy is still the definitive way of checking whether the cancer is there and if so how aggressive it is.
There is also another test called the PCA3 test that looks for a particular protein in the urine; PCA3 is a protein that is only released by prostate cancer cells. However, according to Cancer Research UK, the test is still new and there is not enough information about how reliable it is, although the company that markets the test says it is. So in reality, the prostate cancer specialist does not rely solely on markers for a firm diagnosis, but may well use them to decide whether to proceed with a biopsy now or later.
Having another marker, as suggested by this study, is likely to help them make that decision with more confidence, but as Mason suggests, perhaps delaying biopsy rather than avoiding it altogether. Either way it gives them another view on how to assess the status of any potential prostate cancer.
Figures from Cancer Research UK suggest that more than 670,000 men worldwide discover they have prostate cancer every year. Survival varies depending on screening and treatment methods, but in the UK it is estimated that about 30 per cent of men die within 5 years of being diagnosed with the disease.
"Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression."
. Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaeman Byun, Gilbert S. Omenn, Debashis Ghosh, Subramaniam Pennathur, Danny C. Alexander, Alvin Berger, Jeffrey R. Shuster, John T. Wei, Sooryanarayana Varambally, Christopher Beecher, Arul M. Chinnaiyan.
Nature 457, pp 910 - 914 (12 Feb 2009).
doi: 10.1038/nature07762
The research behind the discovery is written up as an article in the 12 February issue of Nature, and was the work of Dr Christopher Beecher at the University of Michigan in Ann Arbor, and a large team of colleagues, including researchers from other centers in the US.
For this study, the researchers inspected metabolites (byproducts of natural chemical reactions in the body) in 262 samples from prostate cancer patients who were at various stages of the disease, so that samples ranged from containing benign cells to aggressive metastized tumors that had already spread to other organs. As cancers progress from early to late stages, the concentration of metabolites associated with these changes vary.
Scientists already have a list of "likely suspects" for metabolic byproducts that could indicate changes in prostate cancer progression, but what is special about this study is that Beecher and colleagues decided to widen their search to include all the metabolites present in the samples they had, including some that were not considered "likely suspects". They were able to do this because they used mass spectrometry, which picks up all the molecules in a sample and presents a unique signature for each one.
And, as often happens in science, the result was a complete surprise, because the best contender was not among the "likely suspects".
As Beecher explained to Nature News:
"We would never have expected to see sarcosine, nor would we have expected to look for it."
Sarcosine is a byproduct of the amino acid glycine. Beecher and colleagues actually found at least 6 metabolites that were present in higher concentrations in the more advanced metastatic cancer samples compared to samples of earlier stages of the disease, but sarcosine was by far the highest.
The researchers went on to identify the enzymes that make and break down sarcosine and altered the genes that control these processes in lab cultured cells.
As Beecher explained, any time the researchers did anything that increased the production of sarcosine, the cells "started to move so much they could get themselves into a sample of gelatine under their own force", a characteristic behaviour of cancerous cells. The researchers found that just adding sarcosine to benign prostate cells made them act like cancerous cells.
This suggests that sarcosine is not only a marker of how aggressive a cancer is, but it is also active in making cells cancerous.
The researchers said their findings could offer targets for new treatments, as Malcolm Mason, a prostate cancer expert from Cardiff University in Wales, UK, who also works for Cancer Research UK, explained, there is enough evidence here to warrant looking at using sarcosine as a new drug target:
"Not only have they got a marker that has a fundamental role in invasion and metastasis, the molecule itself is regulated by systems that have been directly implicated in prostate cancer."
However, Mason emphasized that the findings need to be confirmed by other studies, and he also cautioned that sarcosine is unlikely to be used widely in screening programs; there are several studies under way in Europe looking at possible new markers already. Mason said urine tests for sarcosine would not be like tests you can do in the pharmacy: they will most likely be used to help specialists decide if and when to do biopsies.
However, Beecher is hopeful that sarcosine will play a bigger role and tests based on it will one day replace current tests.
"This may actually be superior to PSA," he said. The researchers suggested that there could one day be a test for a "panel of metabolites".
Beecher and colleagues are planning to use their research method to look at metabolites of other diseases.
Present ways of screening for prostate cancer rely primarily on testing concentrations of prostate specific antigen (PSA) in the blood. PSA is a protein that binds to prostate cancer cells. The free PSA test is another guide: it checks how much of the PSA has not bound to cancer cells, and the theory is that the more free PSA there is the less cancer there is, but as many specialists know, it is not an exact science, and biopsy is still the definitive way of checking whether the cancer is there and if so how aggressive it is.
There is also another test called the PCA3 test that looks for a particular protein in the urine; PCA3 is a protein that is only released by prostate cancer cells. However, according to Cancer Research UK, the test is still new and there is not enough information about how reliable it is, although the company that markets the test says it is. So in reality, the prostate cancer specialist does not rely solely on markers for a firm diagnosis, but may well use them to decide whether to proceed with a biopsy now or later.
Having another marker, as suggested by this study, is likely to help them make that decision with more confidence, but as Mason suggests, perhaps delaying biopsy rather than avoiding it altogether. Either way it gives them another view on how to assess the status of any potential prostate cancer.
Figures from Cancer Research UK suggest that more than 670,000 men worldwide discover they have prostate cancer every year. Survival varies depending on screening and treatment methods, but in the UK it is estimated that about 30 per cent of men die within 5 years of being diagnosed with the disease.
"Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression."
. Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaeman Byun, Gilbert S. Omenn, Debashis Ghosh, Subramaniam Pennathur, Danny C. Alexander, Alvin Berger, Jeffrey R. Shuster, John T. Wei, Sooryanarayana Varambally, Christopher Beecher, Arul M. Chinnaiyan.
Nature 457, pp 910 - 914 (12 Feb 2009).
doi: 10.1038/nature07762
Pelvic Lymph Node Dissection (Extended Vs Standard) And Prostate Cancer
The purpose of this article was to review the recent medical papers about the role and potential benefits of extended lymphadenectomy in prostate cancer.
We analyzed clinical prognostic factors on lymphatic disease, imaging techniques used in clinical staging, and reasons for performing an ileo-obturator lymphadenectomy versus an extended lymphadenectomy.
The therapeutic role of the lymphadenectomy in prostate cancer is controversial. However, it is generally accepted that the role of the lymphadenectomy at the time of surgery is the best method of diagnosing lymphatic involvement. Clinical and imaging staging cannot detect lymphatic disease in many instances.
Nevertheless, a number of patients with prostate cancer do not need a pelvic lymphadenectomy. Clinical staging methods allow the selection of patients for lymphadenectomy. The question is, do patients with unfavorable prognostic factors for lymphatic disease require extended lymphadenectomy? Recent reports show that lymphatic prostate drainage occurs at three lymphatic levels and not exclusively at the ileo-obturator level. This scenario justifies an extended lymphadenectomy.
Although an extended lymphadenectomy may accurately pinpoint the lymphatic staging with a low morbidity, there are no papers demonstrating that extended lymphadenectomy improves biochemical progression-free survival.
We analyzed clinical prognostic factors on lymphatic disease, imaging techniques used in clinical staging, and reasons for performing an ileo-obturator lymphadenectomy versus an extended lymphadenectomy.
The therapeutic role of the lymphadenectomy in prostate cancer is controversial. However, it is generally accepted that the role of the lymphadenectomy at the time of surgery is the best method of diagnosing lymphatic involvement. Clinical and imaging staging cannot detect lymphatic disease in many instances.
Nevertheless, a number of patients with prostate cancer do not need a pelvic lymphadenectomy. Clinical staging methods allow the selection of patients for lymphadenectomy. The question is, do patients with unfavorable prognostic factors for lymphatic disease require extended lymphadenectomy? Recent reports show that lymphatic prostate drainage occurs at three lymphatic levels and not exclusively at the ileo-obturator level. This scenario justifies an extended lymphadenectomy.
Although an extended lymphadenectomy may accurately pinpoint the lymphatic staging with a low morbidity, there are no papers demonstrating that extended lymphadenectomy improves biochemical progression-free survival.
Discovery Of New Biomarker For Fatal Prostate Cancer
New research findings out of Wake Forest University School of Medicine and the University of Wisconsin may help provide some direction for men diagnosed with prostate cancer about whether their cancer is likely to be life-threatening.
In a study that appears in the February issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, researchers confirmed their earlier findings that men who have too much calcium in their bloodstreams subsequently have an increased risk of fatal prostate cancer. Now researchers have also identified an even more accurate biomarker of the fatal cancer: high levels of ionized serum calcium.
"Scientists have known for many years that most prostate cancers are slow-growing and that many men will die with, rather than of, their prostate cancer," said Gary G. Schwartz, Ph.D., senior author of the study and an associate professor of cancer biology at the School of Medicine, a part of Wake Forest University Baptist Medical Center. "The problem is, how can we determine which cancers pose a significant threat to life and need aggressive treatment versus those that, if left alone, are unlikely to threaten the patient's life? These findings may shed light on that problem."
This was the first study to examine fatal prostate cancer risk in relation to prediagnostic levels of ionized serum calcium, and researchers found that men in the highest third of ionized serum calcium levels are three times more likely to die of prostate cancer than those with the least amount of ionized serum calcium. Researchers also confirmed a previous finding of a doubling of risk for fatal prostate cancer among men whose level of total serum calcium falls in the highest third of the total serum calcium distribution.
Ionized serum calcium is the biologically active part of total serum calcium. About 50 percent of total serum calcium is inactive, leaving only the ionized serum calcium to directly interact with cells.
The findings have both scientific and practical implications, said Halcyon G. Skinner, Ph.D., of the University of Wisconsin, the study's lead author. From a scientific standpoint, it helps focus research on what it is about calcium that may promote prostate cancer. On a practical level, the finding may offer some guidance to men trying to decide whether or not to seek treatment for a recent prostate cancer diagnosis. If confirmed, the findings could also lead to the general reduction of over-treatment of prostate cancer.
"Many men with this diagnosis are treated unnecessarily," Schwartz said. "Within months of initial diagnosis of prostate cancer, many men opt to undergo either radiation or radical surgery. The problem is, we don't know who needs to be treated and who doesn't, so we treat most men, over-treating the majority. These new findings, if confirmed, suggest that men in the lower end of the normal distribution of ionized serum calcium are three times less likely than men in the upper distribution to develop fatal disease.
"These men may choose to delay treatment or perhaps defer it altogether," Schwartz added. "It also suggests that medicine may be able to help in lowering the risk of fatal prostate cancer by reducing serum calcium levels."
Schwartz added that much of the ongoing research into the development of prostate cancer is focused on identifying characteristics of aggressive tumors, whereas this research is focused on identifying characteristics of the men who will develop the tumors before they actually develop.
He cautioned that calcium in serum is little influenced by calcium in the diet. Serum calcium levels are controlled genetically and are stable over much of an individual's life, he said.
"These results do not imply that men need to quit drinking milk or avoid calcium in their diets," Schwartz added.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
The study was funded by grants from the National Institutes of Health and the American Cancer Society.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Jessica Guenzel
In a study that appears in the February issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, researchers confirmed their earlier findings that men who have too much calcium in their bloodstreams subsequently have an increased risk of fatal prostate cancer. Now researchers have also identified an even more accurate biomarker of the fatal cancer: high levels of ionized serum calcium.
"Scientists have known for many years that most prostate cancers are slow-growing and that many men will die with, rather than of, their prostate cancer," said Gary G. Schwartz, Ph.D., senior author of the study and an associate professor of cancer biology at the School of Medicine, a part of Wake Forest University Baptist Medical Center. "The problem is, how can we determine which cancers pose a significant threat to life and need aggressive treatment versus those that, if left alone, are unlikely to threaten the patient's life? These findings may shed light on that problem."
This was the first study to examine fatal prostate cancer risk in relation to prediagnostic levels of ionized serum calcium, and researchers found that men in the highest third of ionized serum calcium levels are three times more likely to die of prostate cancer than those with the least amount of ionized serum calcium. Researchers also confirmed a previous finding of a doubling of risk for fatal prostate cancer among men whose level of total serum calcium falls in the highest third of the total serum calcium distribution.
Ionized serum calcium is the biologically active part of total serum calcium. About 50 percent of total serum calcium is inactive, leaving only the ionized serum calcium to directly interact with cells.
The findings have both scientific and practical implications, said Halcyon G. Skinner, Ph.D., of the University of Wisconsin, the study's lead author. From a scientific standpoint, it helps focus research on what it is about calcium that may promote prostate cancer. On a practical level, the finding may offer some guidance to men trying to decide whether or not to seek treatment for a recent prostate cancer diagnosis. If confirmed, the findings could also lead to the general reduction of over-treatment of prostate cancer.
"Many men with this diagnosis are treated unnecessarily," Schwartz said. "Within months of initial diagnosis of prostate cancer, many men opt to undergo either radiation or radical surgery. The problem is, we don't know who needs to be treated and who doesn't, so we treat most men, over-treating the majority. These new findings, if confirmed, suggest that men in the lower end of the normal distribution of ionized serum calcium are three times less likely than men in the upper distribution to develop fatal disease.
"These men may choose to delay treatment or perhaps defer it altogether," Schwartz added. "It also suggests that medicine may be able to help in lowering the risk of fatal prostate cancer by reducing serum calcium levels."
Schwartz added that much of the ongoing research into the development of prostate cancer is focused on identifying characteristics of aggressive tumors, whereas this research is focused on identifying characteristics of the men who will develop the tumors before they actually develop.
He cautioned that calcium in serum is little influenced by calcium in the diet. Serum calcium levels are controlled genetically and are stable over much of an individual's life, he said.
"These results do not imply that men need to quit drinking milk or avoid calcium in their diets," Schwartz added.
----------------------------
Article adapted by Medical News Today from original press release.
----------------------------
The study was funded by grants from the National Institutes of Health and the American Cancer Society.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Jessica Guenzel
Mediterranean Diet May Help Prevent Prostate Cancer
We recently reviewed evidence relating diet and prostate cancer, suggesting that a traditional Cretan Mediterranean style diet based on a variety of plant foods (fruits, vegetables, wholegrain cereals, nuts and legumes), olive oil as the main source of fat, low intake of red meat, moderate to low intake of dairy foods, moderate to high intake of fish and moderate intake of wine, mostly consumed with meals, may be helpful in reducing prostate cancer risk.
Importantly, the Mediterranean diet has other health benefits that further support its widespread adoption. A recent meta-analysis of prospective cohort studies using an a priori score to assess adherence to a Mediterranean diet found that stronger adherence was associated with reduced all cause, cardiovascular and cancer mortality, as well as decreased incidence of Parkinson's and Alzheimer's diseases (1).
Two intervention studies have supported the benefits of a Mediterranean style diet on metabolic risk factors (2) (3). In a Spanish study, men and women with elevated levels of cardiovascular risk factors were randomized to either of two "Mediterranean" diets and provided with either olive oil or nuts, or to a control low fat diet. After 3 months the Mediterranean diet groups had lower mean plasma glucose, systolic blood pressure and total/HDL cholesterol ratio than the control group (2). Italian adults with the Metabolic Syndrome were randomized to a "Mediterranean" diet or a "prudent" diet, both with similar macronutrient composition. The "Mediterranean" diet was associated with greater improvements in markers of vascular risk and endothelial function than the control group (3). It should be noted however that in both studies the "Mediterranean" diet groups received more nutrition education than the control groups.
The Lyon Heart Study demonstrated that a modified Cretan diet low in butter and meats, and high in fish, fruits and enriched with α-linolenic acid from canola oil was more effective than a 'prudent' diet in the secondary prevention of coronary events and overall mortality (4). We have also shown that a Cretan style diet reduced HbA1c from a mean of 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012), in people with type 2 diabetes (unpublished data).
Simopoulos (5) notes that the traditional Greek diet resembles the Paleolithic diet in terms of fibre, antioxidants, saturated and monounsaturated fat, thus is consistent with human evolution. While traditional diets must reflect the regionally available foods, the characteristics of the traditional Greek diet can be applied in many countries, notwithstanding the likely effect of environment and growing methods on the nutrient composition of plant and animal foods. The evidence suggests that a traditional Greek or Cretan style diet is consistent with what humans have evolved to consume and may protect against common chronic diseases, including prostate cancer.
References:
1. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008;337:a1344.
2. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
3. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc 2004;292:1440-6.
4. de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. In: Simopoulos AP, Visioli F, eds. Mediterranean Diets. World Review Nutr Diet. Basel: Karger, 2000:1-23.
5. Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev 2004;13:219-30.
Importantly, the Mediterranean diet has other health benefits that further support its widespread adoption. A recent meta-analysis of prospective cohort studies using an a priori score to assess adherence to a Mediterranean diet found that stronger adherence was associated with reduced all cause, cardiovascular and cancer mortality, as well as decreased incidence of Parkinson's and Alzheimer's diseases (1).
Two intervention studies have supported the benefits of a Mediterranean style diet on metabolic risk factors (2) (3). In a Spanish study, men and women with elevated levels of cardiovascular risk factors were randomized to either of two "Mediterranean" diets and provided with either olive oil or nuts, or to a control low fat diet. After 3 months the Mediterranean diet groups had lower mean plasma glucose, systolic blood pressure and total/HDL cholesterol ratio than the control group (2). Italian adults with the Metabolic Syndrome were randomized to a "Mediterranean" diet or a "prudent" diet, both with similar macronutrient composition. The "Mediterranean" diet was associated with greater improvements in markers of vascular risk and endothelial function than the control group (3). It should be noted however that in both studies the "Mediterranean" diet groups received more nutrition education than the control groups.
The Lyon Heart Study demonstrated that a modified Cretan diet low in butter and meats, and high in fish, fruits and enriched with α-linolenic acid from canola oil was more effective than a 'prudent' diet in the secondary prevention of coronary events and overall mortality (4). We have also shown that a Cretan style diet reduced HbA1c from a mean of 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012), in people with type 2 diabetes (unpublished data).
Simopoulos (5) notes that the traditional Greek diet resembles the Paleolithic diet in terms of fibre, antioxidants, saturated and monounsaturated fat, thus is consistent with human evolution. While traditional diets must reflect the regionally available foods, the characteristics of the traditional Greek diet can be applied in many countries, notwithstanding the likely effect of environment and growing methods on the nutrient composition of plant and animal foods. The evidence suggests that a traditional Greek or Cretan style diet is consistent with what humans have evolved to consume and may protect against common chronic diseases, including prostate cancer.
References:
1. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. Bmj 2008;337:a1344.
2. Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
3. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. J Am Med Assoc 2004;292:1440-6.
4. de Lorgeril M, Salen P. Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer. In: Simopoulos AP, Visioli F, eds. Mediterranean Diets. World Review Nutr Diet. Basel: Karger, 2000:1-23.
5. Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev 2004;13:219-30.
Subscribe to:
Posts (Atom)
Posts
