Articles about new Prostate Cancer drugs, treatment methods, research etc.

May 2006 - April 2007

*Combination Of Genetic Mutation And Viral Infection May Cause Prostate Cancer
*Young Men With Prostate Cancer Benefit From Radiation Therapy
*Obesity In Prostate Cancer Patients Predicts Cancer Recurrence And Progression
*Genetic Fingerprint Strongly Linked To Prostate Cancer Risk
*Does Light-activated Drug Fulfill Early Promise In Prostate Cancer Treatment? Major MUHC Study
*A New Diagnostic Tool For Prostate Cancer And How A ?bigger? Chromosome 8 Can Predict Poorer Outcomes In Prostate Cancer Patients
*Pomegranate Juice Helps Keep PSA Levels Stable In Men With Prostate Cancer
*Prostatic Irradiation Doesn't Lead To Any Appreciable Increase In Rectal Cancer Risk
*Researchers Uncover How Prostate Cancer Cells Defy Death
*Altering Fatty Acid Levels In Diet May Reduce Prostate Cancer Growth Rate, UCLA Study Shows
*Some Low-risk Prostate Cancer Patients Overtreated
*PSA Test Has Higher Accuracy For Patients Taking Finasteride
*Diet Changes And Stress Management Training Effective In Slowing Or Halting The Spread Of Prostate Cancer
*Sunshine Vitamin For Prostate Cancer
*Early Prostate Cancers: Study Drug Holds Promise As Alternative To Castration
*Prostate Cancer: Major Genetic Risk Factor Found
*Gene Therapy Study Takes Aim At Prostate Cancer
*The Relationship Of Ultrasensitive Measurements Of Prostate-specific Antigen Levels To Prostate Cancer Recurrence After Radical Prostatectomy
*U.S. Genomics And Lahey Clinic Announce Collaboration To Study The Role Of MicroRNAs In The Prognosis Of Urologic Cancers
*Lower cholesterol may cut risk of aggressive prostate cancer
*A 23-Year Survival Analysis of Prediagnostic BMI and Risk of Lethal Prostate Cancer
*Adding Radiation Therapy For Treatment Of Advanced Prostate Cancer May Be Beneficial
*Obesity, Diabetes, And Risk Of Prostate Cancer: Results From The Prostate Cancer Prevention Trial
*PSA Velocity Over 2 NG/ML Year Pre Diagnosis Independently Predicts Prostate Cancer Mortality In Men Treated With Radical Prostatectomy/Radiotherapy
*Peregrine Pharmaceuticals Reports Preclinical Data That Shows Bavituximab Equivalent Plus Docetaxel Reduces Growth Of Human Prostate Tumors
*Treating Your Prostate Cancer Sooner Rather Than Later Could Be Better Than Wait And See
*Mucinous Adenocarcinoma Of The Prostate Does Not Confer Poor Prognosis
*Statin Use Associated With Decreased Risk Of Advanced Prostate Cancer
*Study Suggests Role For Y Chromosome In Prostate Cancer
*The Prognostic Significance Of Perineural Invasion In Prostatic Cancer Biopsies
*International Multi-centre Research Group Finds Genetic Defect Contributing To Cancer Susceptibility
*Green Tea And COX-2 Inhibitors Combine To Slow Growth Of Prostate Cancer
*Obesity At The Time Of Prostate-Cancer Diagnosis Dramatically Increases The Risk Of Dying From The Disease
*New Blood Test Uses DNA To Diagnose Prostate Cancer
*Inflammation May Play Role In Metastasis Of Prostate Cancer
*Curecumin(TM) May Be An Effective Treatment For Prostate Cancer
*Soy Found Protective Against Localized Prostate Cancer Only
*Relationship Between Body Mass Index And Prostate Cancer Screening In The United States
*New Data For Prolonging Hormonal Response In Locally Advanced And Metastatic Prostate Cancer
*Pomegranate Juice May Be Good For The Prostate And Heart, Reports The Harvard Men's Health Watch
*Prostate Specific Antigen Velocity Threshold For Predicting Prostate Cancer In Young Men
*Age Adjusted Prostate Specific Antigen And Prostate Specific Antigen Velocity Cut Points In Prostate Cancer Screening
*The Effect Of Androgen Deprivation Therapy On Periodontal Disease In Men With Prostate Cancer
*Long-Term Prostate Cancer Control Using Palladium-103 Brachytherapy And External Beam Radiotherapy In Patients With A High Likelihood Of Cancer
*More Reliable Blood Test For Prostate Cancer Shows Promise
*Biopsy May Underestimate Prostate Cancer In Obese And Overweight Men
*Fungal Compound To Combat Prostate Cancer?

Combination Of Genetic Mutation And Viral Infection May Cause Prostate Cancer

04 May 2006 - Significant recent interest in the literature (JAMA 2006;295:1503, Lancet, epub) and by patients has arisen in response to a presentation given by Dr. Eric Klein of the Cleveland Clinic at the 2006 Prostate Cancer Symposium in San Francisco, February 24, 2006. Dr. Klein presented their work on a potential viral etiology for Prostate Cancer (CaP).

The ideas originated from thinking that CaP might be linked to an infectious etiology in some patients. The Human Prostate Cancer 1 gene (HPC1) encodes an antiviral protein called RNaseL that is activated by viral infection. Alterations or mutations in RNaseL may increase the susceptibility for CaP. In particular, men homozygous for the SNP R462Q were hypothesized to more likely be associated with a viral cause for CaP.

CaP tissue was isolated from 86 radical prostatectomy specimens and mRNA extracted. Corresponding cDNA was examined for the presence of viral sequences. This was performed using a DNA microarray representing more that 5,000 conserved viral sequences. Localization of viruses in tissue was performed with immunohistochemistry and fluorescence in situ hybridization.

In 20 men who were homozygous for RNaseL, 45% had viral sequences found, compared to 1.5% of 66 controls with one or no RNaseL mutations. Especially fascinating was that viral cloning demonstrated that in all cases, the same 1 virus was identified. This virus, named XMRV is related to the xenotropic murine leukemia viruses, which are know to cause cancer in mice.

The localization studies found the virus in the stromal cells adjacent to tumor tissue, suggesting a paracrine effect. The researchers found the virus in the LNCaP cell line and it was replication competent. These exciting data provide new insight into etiologies for CaP in genetically predisposed men.

By Christopher P. Evans, MD

Young Men With Prostate Cancer Benefit From Radiation Therapy

12 May 2006

For men under the age 55 with localized prostate cancer, external beam radiation may be an effective alternative to both conservative and more invasive treatments, according to a new study. Published in the June 15, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study reveals that external beam radiation therapy is as effective in younger prostate cancer patients as it is in older patients with same stage, localized disease. The study is the first to investigate the outcome of radiation in men under 55 years of age.

Age remains a controversial factor in prostate cancer, with younger age at diagnosis perceived to be associated with more aggressive disease and poorer prognosis. Consequently, physicians tend to recommend more aggressive treatments, such as radical prostatectomy, to younger patients, even those with local, non-metastatic disease. Older patients diagnosed with similar organ-limited disease, however, are offered more choices, including external beam radiation therapy. Recently studies have shown that radiation therapy is effective in treating localized prostate cancer in elderly patients and in men under 65 years of age.

Andre Konski, M.D., M.B.A., M.A, Clinical Research Director, Radiation Oncology Department at the Fox Chase Cancer Center in Philadelphia, and colleagues compared how men 55 and under fared five years after diagnosis compared to men between 60 and 69 and men 70 and over, looking at survival, disease progression, and whether blood tests (PSA) showed signs of disease recurrence. All the men had localized prostate cancer and were treated with external beam radiation.

They found no statistically significant differences in the outcomes of these three age groups after five years: 94 percent, 95 percent and 87 percent of patients in each respective age category were alive five years after diagnosis; 96 percent, 97 percent and 98 percent of patients in each respective age category were without metastatic disease; and 82 percent, 76 percent, and 70 percent of patients in each respective age category had no evidence of disease recurrence according to blood.

While this study did not compare radiation to other therapies, "external beam radiation at appropriate dose levels has been shown to be equivalent to permanent prostate seed implant and radical prostatectomy in the treatment of patients with stage T1-2 prostate cancer," say the authors. Because younger men with localized disease respond as well as older men to radiation, the authors suggest that this less invasive treatment option should be considered for this patient population.

Obesity In Prostate Cancer Patients Predicts Cancer Recurrence And Progression

28 Jun 2006

Obesity in a patient is an independent predictor of whether localized prostate cancer will progress following radiotherapy treatment, say researchers at M. D. Anderson Cancer Center.

In a study reported in the Aug. 1 issue of the journal Cancer, researchers found that moderately and severely obese patients had a 99 percent greater risk of developing biochemical failure (an early marker of cancer progression) than other patients. The study also reports that obese patients had a 66 percent increased risk of having a tumor that recurs or becomes metastatic than did non-obese patients.

This finding mirrors results from a parallel study by M. D. Anderson researchers, reported last year in Clinical Cancer Research, that found that a history of weight gain or obesity at the time of diagnosis also played a role in how aggressive prostate cancer may become after surgery.

"Together, these studies confirm that a man's body mass index (BMI = weight/height2) can be a significant factor in how well he fares after standard treatments for prostate cancer," says the lead researcher of both studies, Sara Strom, Ph.D., an associate professor in the Department of Epidemiology.

"The fact that the same association was found among patients with different risk profiles, and who were treated with different therapies, would suggest that poorer outcomes in obese men are not related to differences in treatment as much as to differences in tumor behavior between obese and non-obese men," she says.

Strom adds that these findings suggest that obese prostate cancer patients should be followed more closely after treatment. "When patients and their physicians are uncertain about the need for further therapy, our research indicates that a man's weight should be factored into that decision," she says.

According to Strom, the study is the first to examine the relationship between obesity and prostate cancer progression after primary therapy with external beam radiotherapy, a common treatment option. The researchers sought to determine whether obesity is an independent predictor of biochemical failure - a rising prostate specific antigen (PSA) level that can indicate advancing cancer - and they also wanted to know if the cancer actually progressed among those patients.

To conduct the study, the scientists examined the records of 873 patients whose prostate cancer was locally confined, and who were treated with radiotherapy at M. D. Anderson between 1988 and 2001. Of these patients, 18 percent were mildly obese and 5 percent were moderately to severely obese.

They found that patients who were obese tended to be diagnosed with prostate cancer at an earlier age than patients who were not obese, and also that African-American men had the highest obesity rates.

After an average follow-up period of 96 months, 295 patients experienced biochemical failure, and cancer recurred in 127 of these patients.

After adjusting for clinical and treatment variables among patients, the researchers found that BMI significantly predicted whether a patient would experience both rising PSA and a return of prostate cancer. For example, biochemical failure occured more quickly with increased BMI: an average of 30 months for patients with normal weight, and 26 months for patients deemed moderately to severely obese. Researchers also found that when comparing obese patients with non-obese patients, obese men had a significantly higher rate of cancer recurrence.

Strom and her colleagues cannot yet say why excess BMI contributed to cancer progression, or whether losing weight after a prostate cancer diagnosis will make any difference in outcome. "But by knowing this association, we may be able to design rational preventive strategies," she says.

Genetic Fingerprint Strongly Linked To Prostate Cancer Risk

08 May 2006

According to new research carried out in Iceland, men who carry a genetic marker are more susceptible to developing prostate cancer. This new discovery could help doctors decide which men need to be monitored more closely, following genetic testing.

Men who carry this market have a 60% higher risk of developing prostate cancer.

The study was carried out by Kari Stefansson and team at deCode Genetics, Reykjavik, Iceland. The scientists say the marker is located somewhere within Chromosome 8.

You can read about this study online in the journal Nature Genetics, last Sunday's issue. The full report will come out in the journal's June issue.

Scientists say the reason black men are more predisposed to prostate cancer may have something to do with a higher incidence of this genetic marker. They found that twice as many black men carry the genetic marker as white men.

According to the researchers, this marker could account for one twelfth of all prostate cancers among men of European descent, and perhaps one sixth of prostate cancers among men of African men.

The researchers believe those who carry the marker are also more likely to suffer from the more aggressive forms of prostate cancer.

The study looked at 3,430 patients with prostate cancer and 2,675 men who did not have prostate cancer. They found a significantly higher presence of the DNA variant (genetic marker) among prostate cancer patients when compared to the healthy group.

The average man has a 15% chance of developing prostate cancer during his lifetime. Men of African descent have a higher risk. If a man has a brother or close relative who has had prostate cancer, his risk is also higher. The older a man is the greater is his risk.

Does Light-activated Drug Fulfill Early Promise In Prostate Cancer Treatment? Major MUHC Study

07 May 2006

Early trials of an experimental photosensitizer cancer drug called Tookad have yielded dramatic results, according to Dr. Mostafa Elhilali, Chief Surgeon at the McGill University Health Centre (MUHC) and study principal investigator. In a recently-completed trial, 46 percent of patients showed no evidence of prostate cancer after treatment with optimum doses of Tookad and the correct light intensity. A larger study to determine the drug's efficacy is now underway at the MUHC.

"This new trial is designed to treat patients whose prostate cancers have recurred despite radiation therapy," explains Dr. Elhilali. "From previous studies, we have learned optimum light intensity and drug dosages. Now, we plan to treat patients, using this information to deliver optimum therapy to all participants. If the trial also shows beneficial effects, we will go to the next phase - registering the drug to make it generally available for therapy."

"Results so far are unprecedented," adds Dr. Armen Aprikian, Chief of Urology at MUHC and study co-investigator. "However, they are not conclusive. The upcoming trial is so important because it will give us definitive evidence of how effective Tookad therapy is. Good results will lead to wider use."

Tookad (from a Hebrew word meaning the warmth of light) is a non-toxic, light-activated drug derived from chlorophyll. Injected into the patient, it remains inactive until exposed to laser light, which is shone into the target tumour using fibre optics. Once activated, Tookad produces a chemical that blocks blood vessels in the immediate area and chokes off the tumour's blood supply.

"The mechanism is local, not systemic," explains Dr. Elhilali. "The drug is activated only where light is shining, so nearby healthy tissue is spared. Tookad has another advantage: it is eliminated in two hours. Previously, we had to keep people in the dark for weeks after treatment with these types of agents."

MUHC researchers are now recruiting patients with recurring prostate cancer to participate in phase two trials with Tookad. Candidates should contact Dr. Elhilali or Dr. Aprikian at the MUHC to learn more, or call Joanne Savard at 934-1934, extension 34037.

Current Canadian studies of Tookad in recurrent prostate cancer patients are the first of their kind anywhere. "This is totally new," says Dr. Aprikian. "It's appropriate that the MUHC, as an internationally recognized institution, is leading the way in this area."

A New Diagnostic Tool For Prostate Cancer And How A ?bigger? Chromosome 8 Can Predict Poorer Outcomes In Prostate Cancer Patients

16 Jul 2006

According to the World Health Organization there are about 250,000 new cases of prostate cancer every year but, when caught in time, the disease has a cure rate of over 90%. The problem is that the current methods of disease testing are still associated with too many misdiagnoses. Now however, research by Portuguese and Norwegian scientists, just published on the journal Clinical Cancer Research describes, not only how whole genome analysis can help to increase the accuracy of patient testing, but also identifies a new molecular marker that ?tags? prostate cancers with worse prognoses These results have important implications for the clinical management of patients as they will allow, together with standard methods of cancer analysis, better informed therapeutic measures.

Prostate cancer results from abnormal uncontrolled growth of cells in the prostate, which is a doughnut-shaped gland in the male reproductive system responsible for the fluid that carries the sperm during ejaculation. The disease is strongly related to the Western lifestyle and affects mostly males over the age of 65, while rarely occurring before 40 years of age.

Initial diagnosis is done by measuring prostate-specific antigen (PSA), a protein produced by the healthy male prostate, but also by cancer cells. When high levels of PSA are detected, indicating an increased likelihood of cancer, a prostate biopsy is done. The sample collected in this way is analysed by microscope, and, if a carcinoma is detected, radical prostatectomy (removal of the prostate) and radiotherapy follows. The problem is that biopsy samples are very small and, in consequence, it is difficult not only to know how representative of the tumour are the cells tested, but also to determine accurately the tumour's stage (degree of advancement of the disease) and grade (tumour's malignancy and aggressiveness)

And in fact, studies looking at diagnoses obtained from biopsies samples, and comparing these with those obtained later from the same prostates after surgery, concluded that biopsies analyses tended to downgrade about 57% of tumours, while overgrading a significant 20% of them. This, together with the fact that PSA testing can give a positive result to slow-growing tumours that probably will never create problems, further raises the problem of misdiagnoses in prostate cancer and the need to improve testing methods.

Franclim R. Ribeiro, Manuel R.Teixeira and colleagues from Portugal and Norway, have previously found that it was possible, from biopsies samples, to do a full genome analysis which, in combination with the microscopic analyses, should allow a much more accurate tumour classification

In the research now published, the group of scientists show the possibilities of this new method by studying 61 patients with high levels of PSA and microscopic evidence of prostate cancer, to find that the total number of genomic aberrations found in these patient's prostate cells is directly associated with cancer severity (higher number of aberrations - increased disease severity). A number of healthy individuals were also analysed and shown to have no genomic changes in their prostate cells, confirming the specificity of the patients' findings.

Furthermore, Ribeiro, Teixeira and colleagues found that the gain of chromosomal material within the long arm of chromosome 8 (all human chromosomes have 2 arms, one shorter and one longer) was an accurate predictor of poor survival in prostate cancer patients. This was true even when patients were aggregated according to the tumour grade and disease stage, as in the case of patients with tumours with Gleason score 7 (Gleason grading system goes from 2 to 10, with 10 being tumours with the worst prognosis). This is especially interesting as grade 7 tumours are known, not only by being very aggressive but also by being difficult to evaluate in terms of prognostic. Teixeira and colleagues believe that the use of genomic analysis, together with the more standard methods now employed, can help to achieve better diagnoses by detecting more effectively both aggressive and less aggressive carcinomas. In the later case, correct diagnosis would allow doctors to chose to close monitoring the tumours, instead of rush into radical prostatectomy with its inherent psychological and health problems.

Pomegranate Juice Helps Keep PSA Levels Stable In Men With Prostate Cancer

05 Jul 2006

Drinking an eight ounce glass of pomegranate juice daily increased by nearly four times the period during which PSA levels in men treated for prostate cancer remained stable, a three-year UCLA study has found.

The study involved 50 men who had undergone surgery or radiation but quickly experienced increases in prostate-specific antigen or PSA, a biomarker that indicates the presence of cancer. UCLA researchers measured "doubling time," how long it takes for PSA levels to double, a signal that the cancer is progressing, said Dr. Allan Pantuck, an associate professor of urology, a Jonsson Cancer Center researcher and lead author of the study.

Doubling time is crucial in prostate cancer, Pantuck said, because patients who have short doubling times are more likely to die from their cancer. The average doubling time is about 15 months. In the UCLA study, Pantuck and his team observed increases in doubling times from 15 months to 54 months, an almost four-fold increase.

"That's a big increase. I was surprised when I saw such an improvement in PSA numbers," Pantuck said. "In older men 65 to 70 who have been treated for prostate cancer, we can give them pomegranate juice and it may be possible for them to outlive their risk of dying from their cancer. We're hoping we may be able to prevent or delay the need for other therapies usually used in this population such as hormone treatment or chemotherapy, both of which bring with them harmful side effects."

The study appears in the July 1 issue of Clinical Cancer Research, the peer-reviewed journal of the American Association of Cancer Research.

"This is not a cure, but we may be able to change the way prostate cancer grows," Pantuck said. "We don't know yet the specific factors behind this response - that's our next step in this research. We want to find out what cell signaling pathways might be affected, what is happening to keep PSA levels stable."

Pomegranate juice is known to have anti-inflammatory effects and high levels of anti-oxidants, which are believed to protect the body from free-radical damage. It also contains poly-phenols, natural antioxidant compounds found in green tea, as well as isoflavones commonly found in soy, and ellagic acid, which is believed to play a role in cancer cell death.

"There are many substances in pomegranate juice that may be prompting this response," Pantuck said. "We don't know if it's one magic bullet or the combination of everything we know is in this juice. My guess is that it's probably a combination of elements, rather than a single component."

The levels of PSA in men immediately following treatement should be undetectable, Pantuck said. If PSA can be detected, it's an indication of an aggressive cancer that is likely to progress. The men in Pantuck's study all had detectable PSA following treatment. Of the 50 men enrolled, more than 80 percent experienced improvement in doubling times.

Conventional treatment for men with recurrent prostate cancer includes hormonal therapy, a chemical castration which removes testosterone from the system. Men treated with hormonal therapy can experience hot flashes, osteoporosis, fatigue, depression, muscle wasting, loss of libido and erectile dysfunction. If drinking pomegranate juice can delay or prevent the need for hormonal therapy, patients would experience a better quality of life for a longer time, Pantuck said.

The patients in Pantuck's study experienced no side effects and none of the participants had cancers that metastasized during the study.

Pantuck, along with UCLA colleagues including Dr. Arie Belldegrun, professor and chief of urologic oncology, and Dr. David Heber, professor and director of the Center for Human Nutrition, first began research on pomegranate juice in prostate cancer about six years ago, conducting preclinical research in cell cultures and in animals. Those studies showed pomegranate juice slowed the growth of prostate cancer, Pantuck said.

The data was impressive enough to test pomegranate juice in clinical trials, Pantuck said. To confirm their findings, a larger Phase III study, headed up by UCLA, will be conducted at ten centers across the county. UCLA is the only Southern California center involved in the study.

Pantuck said he has men on the study more than three years out who are not being treated for prostate cancer other than drinking pomegranate juice and their PSA levels continue to be suppressed.

"The juice seems to be working," he said.

Prostatic Irradiation Doesn't Lead To Any Appreciable Increase In Rectal Cancer Risk

05 Jul 2006

Men who receive radiation therapy for prostate cancer are not at any appreciable increased risk of developing rectal cancer compared to those not given radiation therapy, according to a new study published in the July 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

This year, 235,000 American men will be diagnosed with prostate cancer. The main ways of dealing with the disease are radiation therapy, surgery and watchful waiting ? each of which has its benefits and disadvantages. Researchers have hypothesized that one disadvantage of using radiation to kill the cancer cells in the prostate is that it might also make men more likely to develop cancer in the nearby rectum.

In this study, doctors in Canada evaluated the records of 237,773 men who had prostate cancer. Of them, 33,841 received radiation therapy, 167,607 had their prostate removed surgically and 36,335 received neither treatment. On an initial simple evaluation, doctors found that rectal cancer developed in 243 men who received radiation (0.7 percent), 578 men treated with surgery (0.3 percent), and 227 of the men given neither treatment (0.8 percent). Once doctors had adjusted for the age differences between all the men in the irradiated and non-irradiated groups, they could not find any significant increased risk of rectal cancer in the irradiated men compared to those not given radiation therapy.

"Rectal cancer from other causes is frequent enough in our population to obscure any small incidence of radiation-induced cancer. I hope that the results of this study will help men with prostate cancer and their families put these risks in their proper perspective, and not let their concerns about rectal cancer dissuade them from choosing radiation therapy as a treatment for this disease," said Wayne S. Kendal, M.D., Ph.D., an Associate Professor in Radiation Oncology at the Ottawa Hospital Regional Cancer Centre in Ontario, Canada.

For more information on radiation therapy for prostate cancer, please visit

Researchers Uncover How Prostate Cancer Cells Defy Death

31 Jul 2006

New findings about how prostate cancer cells are able to resist hormone treatment and defy death may lead to more effective drug treatments, according to researchers from Wake Forest University School of Medicine and colleagues.

"We hope this will lead to new treatments or ways to monitor treatment to make sure it's having its intended effect," said George Kulik, Ph.D., D.V.M., assistant professor of cancer biology and senior researcher.

The goal of the research was to uncover how prostate cancer cells become resistant to treatment that lowers levels of male hormones such as testosterone, which the cells normally need to survive. They found that a protein known as BAD is involved in three different survival strategies used by the cancer cells. Their results are published in the July 28th issue of the Journal of Biological Chemistry.

"The normal response of prostate cells when male hormones are blocked is cell death," said Kulik. "The cancer cells find a way to resist the treatment and we wanted to discover the mechanism."

Treatments for prostate cancer include surgery, radiation therapy and hormone therapy, also known as androgen ablation therapy because it reduces levels of the male hormones that can stimulate the growth certain types of prostate cancer. Lowering hormone levels makes prostate cancer shrink or grow more slowly. It is considered the most efficient systemic therapy for prostate cancer. However, nearly all prostate cancers become resistant to this treatment over time.

The researchers evaluated three different pathways involved in cell signaling, the complex system of communication that governs cell actions. It had previously been shown that three pathways (activated by vasoactive intestinal peptide, epidermal growth factor or phosphoinositide 3-kinase) are known to be involved in cell survival. The goal of the researchers was to learn how these pathways are involved in the cancer cells resisting death. They found that all three signaling pathways work by inactivating a protein known as BAD that causes cell death.

Kulik said it appears that each of the three molecules is separately capable of inactivating BAD, which means that prostate cancer cells have three redundant survival mechanisms.

"Our findings suggest that BAD is an important switch in the development and growth of prostate cancer," said Kulik.

Next, the researchers hope to conduct animal studies to test their findings.

"If our finding is confirmed in animals and in human tumors, there are important implications for therapy," said Kulik.

For example, scientists could develop a drug to prevent BAD from being inhibited. Or, they could use the findings to test current drugs designed to block the effects of PI3K, one of the molecules. This would involve monitoring the status of BAD to see if the drugs were having their intended effects.

According to the American Cancer Society, prostate cancer is the most common type of cancer found in American men, other than skin cancer. The society estimates that there will be about 234,460 new cases of prostate cancer in the United States in 2006. About 27,350 men will die of this disease. Prostate cancer is the third leading cause of cancer death in men, after lung cancer and colorectal cancer.

Altering Fatty Acid Levels In Diet May Reduce Prostate Cancer Growth Rate, UCLA Study Shows

05 Aug 2006

UCLA researchers found that altering the fatty acid ratio found in the typical Western diet to include more omega-3 fatty acids and decrease the amount of omega-6 fatty acids may reduce prostate cancer tumor growth rates and PSA levels.

Published in the August issue of the journal Clinical Cancer Research, this initial animal-model study is one of the first to show the impact of diet on lowering an inflammatory response known to promote prostate cancer tumor progression and could lead to new treatment approaches.

The omega-6 fatty acids contained in corn, safflower oils and red meats are the predominant polyunsaturated fatty acids in the Western diet. The healthier marine omega-3 fatty acids are found in cold-water fish like salmon, tuna and sardines.

"Corn oil is the backbone of the American diet. We consume up to 20 times more omega-6 fatty acids in our diet compared to omega-3 acids," said principal investigator Dr. William Aronson, a professor in the department of urology at the David Geffen School of Medicine at UCLA and a researcher with UCLA's Jonsson Cancer Center. "This study strongly suggests that eating a healthier ratio of these two types of fatty acids may make a difference in reducing prostate cancer growth, but studies need to be conducted in humans before any clinical recommendations can be made."

Scientists used a special mouse model for hormone-sensitive prostate cancer that closely mirrors the disease in humans. Researchers fed one group of mice a diet comprised of 20 percent fat with a healthy one-to-one ratio of omega-6 to omega-3 fatty acids. A second group of mice were fed the same diet but with the fat derived from mostly omega-6 fatty acids.

The study showed that tumor cell growth rates decreased by 22 percent and PSA levels were 77 percent lower in the group receiving a healthier balance of fatty acids compared with the group that received predominantly omega-6 fatty acids.

The most likely mechanism for the tumor reductions, according to researchers, was due to an increase of the prostate tumor omega-3 fatty acids DHA and EPA and a lowering of the omega-6 acid known as arachidonic acid. These three fatty acids compete to be converted by cyclooxgenase enzymes (COX-1 and COX-2) into prostaglandins, which can become either pro-inflammatory and increase tumor growth, or anti-inflammatory and reduce growth.

Researchers found that pro-inflammatory prostaglandin (PGE-2) levels were 83 percent lower in tumors in the omega-3 group than in mice on the predominantly omega-6 fatty acid diet, demonstrating that higher levels of DHA and EPA may lead to development of more anti-inflammatory prostaglandins.

"This is one of the first studies showing changes in diet can impact the inflammatory response that may play a role in prostate cancer tumor growth," Aronson said. "We may be able to use EPA and DHA supplements while also reducing omega-6 fatty acids in the diet as a cancer prevention tool or possibly to reduce progression in men with prostate cancer."

Currently, the research team is conducting a clinical trial with men who are undergoing prostate removal due to cancer to compare the effects of a low-fat diet using omega-3 supplements and a balanced Western diet. Aronson said that positive findings from this study may lead to larger clinical trials.

In addition, Aronson said that further study might show that COX-2 inhibitors or non-steroidal anti-inflammatories (NSAIDS) combined with omega-3 supplements also may lower the inflammatory response in prostate cancer development.

Some Low-risk Prostate Cancer Patients Overtreated

Article Date: 15 Aug 2006 - 15:00pm (PDT)

Rather than receiving radiotherapy or having their prostate removed, as is sometimes currently the case, many low-risk prostate cancer patients would be better off if their doctors kept an eye on their cancer until treatment became necessary, say researchers from the University of Michigan in Ann Arbor, USA. You can read about this in the Journal of the National Cancer Institute, August 16 issue.

Past guidelines for early-stage prostate cancer was to remove the prostate. However, as cancers are easier to detect these days, prostate cancers are being detected at ever earlier stages. The researchers suggest that treating the prostate cancer today at a very early stage may not be in the best interests of the patient. In fact, studies have found that early aggressive treatment does nothing to improve patient survival, and could even harm his health.

The researchers looked at data on 71,602 men, all aged over 70, who were diagnosed with prostate cancer in the period 2000-2002. They then broke them down into those who received various therapies and those who were not treated (a ?wait and see' approach).

24,825 of them had lower-risk prostate cancers. Assuming waiting for treatment would have been the best approach for these cancers, the team found that 10% of these patients were overtreated with prostate removal and 44% with radiation therapy.

The researchers wrote "Efforts to reduce overtreatment should be a clinical and public health priority."

PSA Test Has Higher Accuracy For Patients Taking Finasteride

17 Aug 2006

Finasteride increases prostate-specific antigen (PSA) testing's ability to detect prostate cancer, a study in the August 16 Journal of the National Cancer Institute reports.

Finasteride is a drug prescribed for men whose prostates have become enlarged. The drug decreases prostate swelling and helps men with urinary problems. However, an increased number of high-grade tumors in men taking finasteride in the Prostate Cancer Prevention Trial (PCPT) has some physicians worried about the effect of the drug.

Ian M. Thompson, M.D., of the University of Texas Health Science Center in San Antonio, and colleagues examined the PSA test's ability to detect prostate cancer in the PCPT in men taking finasteride or a placebo. The group studied the PSA test's sensitivity and diagnostic accuracy for both groups.

The authors found that finasteride changed the diagnostic characteristics of the PSA test so that it detected prostate cancer with higher sensitivity and accuracy in men in the finasteride group than men in the placebo group. They suggest that the increased detection of high-grade prostate cancers in the finasteride arm of the PCPT may be related to the drug's ability to improve the PSA test's performance and not to it's induction of high-grade disease.

The authors write, "This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride." #


# Will Sansom, 210-567-2579, [email protected]

Diet Changes And Stress Management Training Effective In Slowing Or Halting The Spread Of Prostate Cancer

18 Aug 2006

Statistics say that one out of six American men will develop prostate cancer and more than a third of them will experience a recurrence after undergoing treatment, putting them at high risk to die of the disease. In a recent study published in SAGE publication's Integrative Cancer Therapies, Dr. Gordon A. Saxe and colleagues at the Moores Cancer Center and School of Medicine at the University of California, San Diego found that diet changes, reinforced by stress management training, appeared to be effective in slowing or halting the spread of this deadly cancer.

The study, published in the September issue of Integrative Cancer Therapies, focused on the change in the levels of prostate-specific antigen (PSA), an indicator of the cancer, in response to a plant-based diet and stress reduction. Patients were taught to increase consumption of plant-based foods such as whole grains, cruciferous and leafy green vegetables, beans and legumes, and fruit, and to decrease the intake of meat, dairy products, and refined carbohydrates. They were also provided with stress management training, which incorporated meditation, yoga and Tai Chi exercises. The plant-based diet and stress reduction were effective in significantly reducing the PSA rate, indicating a reduction in the rate of progression of the prostate cancer.

"The magnitude of effect of these findings is the strongest observed to date among dietary and nutritional interventions in this patient population," states Dr. Saxe, assistant professor of Family and Preventive Medicine. "These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for management of recurrent prostate cancer."

The article "Potential Attenuation of Disease Progression in Recurrent Prostate Cancer Progression With Plant-based Diet and Stress Reduction" can be accessed at no-charge for a limited time on the SAGE Publications' Integrative Cancer Therapies web site at

Sunshine Vitamin For Prostate Cancer

23 Aug 2006

Relaxing in the bright sunshine on a warm autumn day does more than lift your spirits; it also stimulates your body to produce huge amounts of vitamin D. Often called the ?sunshine vitamin,? vitamin D is not really a vitamin at all, but rather a versatile hormone produced by the body in response to sunlight.

When a person is exposed to the sun, a cascade of chemical reactions begins in the skin and converts vitamin D produced in the skin into the active form of vitamin D through further modification in the liver and kidneys. Researchers have known for a long time that vitamin D helps the body absorb calcium to build strong bones and teeth. Vitamin D also helps to strengthen the immune system and seems to protect against some types of cancers and as well as other diseases. Scientists and researchers worldwide are working to understand and capitalize on the process to prevent and/or treat as many as 17 types of cancer.

Evidence of vitamin D's protective effect against cancer is compelling. Regular sun exposure is associated with lower mortality rates from certain kinds of cancers. Some studies indicate that vitamin D may help prevent cancer of the breast, colon, ovaries and prostate. A recent report indicated those individuals with higher levels of vitamin D in the blood had as much as a 50% lower cancer risk of many types for cancer.

Currently scientists at Roswell Park Cancer Institute, under the direction of Donald Trump, MD, Associate Director, and Candace Johnson, PhD, Senior Vice President for Translational Research are analyzing vitamin D in cancer prevention and treatment. Their focus is on the most potent form of vitamin D - calcitriol - which has many roles in how the body's immune system reacts to challenges and how cancer cells grow.

In the laboratory, scientists are examining the molecular and vascular mechanisms of vitamin D to help define how to make the vitamin more effective in fighting disease. In the clinics, studies are trying to determine if linking calcitriol with chemotherapy will be a new treatment option for patients diagnosed with advanced prostate cancer. Dr. Trump has significant experience with the clinical aspects of vitamin D in the treatment of solid tumors and has performed more clinical trials in cancer with vitamin D than anyone else in the world.

Early Prostate Cancers: Study Drug Holds Promise As Alternative To Castration

25 Aug 2006

For those unwilling to undergo chemical castration however, results of an international study led by a Medical College of Wisconsin researcher show promise for an oral drug as an alternative. The study appears in the August issue of the Journal of Cancer Research and Clinical Oncology.

"In patients with locally-advanced disease, a daily 150 mg dose of bicalutamide, (Casodex TM) following initial radiotherapy, has shown significant clinical benefits in terms of overall survival and progression-free survival, compared with radiotherapy alone," says study author William A See, M.D., chairman and professor of urology at the Medical College in Milwaukee, and chief of urologic surgery at Froedtert Hospital.

The double-blind, randomized study followed 1,370 early prostate cancer patients in the U.S., Sweden and Europe who received radiotherapy with curative intent. After a median follow-up of 7.2 years, the researchers found that those receiving a daily, 150 mg oral dose of Casodex TM reduced their risk of disease progression by 44 percent, and their overall risk of death by 35 percent, compared to those receiving a placebo. "Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life," says Dr. See "Here we have evaluated the efficacy and tolerability of a non-castration-based therapy, and found the survival rates to be similar."

Prostate Cancer: Major Genetic Risk Factor Found

24 Aug 2006

Harvard Medical School researchers have identified a DNA segment on chromosome 8 that is a major risk factor for prostate cancer, especially in African American men. The paper appears in the August electronic edition of the Proceedings of the National Academy of Sciences (also see PNAS's news tip below).

"This paper identifies a genetic risk factor that about doubles the likelihood of prostate cancer in younger African American men," says principal investigator David Reich, PhD, Harvard Medical School assistant professor of genetics with the HMS Department of Genetics and the Broad Institute. "This finding may explain why younger African Americans have an increased risk for prostate cancer than do other populations--and may also explain why this increased risk in African Americans attenuates with older age."

"This is one of the first genetic risk factors found that is responsible for an appreciable fraction of sporadic prostate cancer cases, particularly for the African American population," says lead author Matthew Freedman, Harvard Medical School instructor of medicine at the Dana-Farber Cancer Institute and the Broad Institute "Interestingly, we found that this region also confers risk for prostate cancer for diverse ethnic groups. The actual gene, however, remains to be identified."

The researchers used their newly developed method of "admixture mapping" to screen through the genome in African Americans (who have both African and European ancestry), searching for the segments where individuals with disease have more of one ancestry than the average. The key epidemiological fact is that prostate cancer occurs approximately 1.6-fold times more often in African Americans than in other populations. This prompted the hypothesis that there is a genetic risk factor for prostate cancer that occurs at higher frequency in African than in other populations, and that can be found by searching for a region where the proportion of African ancestry is higher than the genome average.

Reich, Freedman and their colleagues studied 1,597 African Americans with prostate cancer. They found a section of the genome in the patients that had much more than the average proportion of African ancestry, rising from 78 percent to about 85 percent. The risk factor is localized to a tiny fraction (about a thousandth) of the genome, a section on chromosome 8 containing just 9 genes.

A particularly exciting aspect of this work is that in May a separate research team also identified a genetic variant occurring within the same region, which increases risk for prostate cancer. The study by Reich and colleagues makes two additional advances. One important result is that the genetic risk factor is more important for individuals with younger age. Second, they show that the specific genetic variant reported in the earlier paper can explain only at most a small fraction of the increased risk to African Americans. Thus, major unidentified risk factors remain to be found.

Press Tip from the Proceedings of the National Academy of Sciences

Press Summary: Chromosome Region for African-American Prostate Cancer Risk

A whole genome analysis has revealed a section on chromosome 8 as significantly associated with African-American's increased risk to prostate cancer. African Americans have about a 1.6 higher risk of developing prostate cancer than European Americans; at least part of this difference is likely a result of genetic factors. Taking advantage of recent advances, David Reich and colleagues used admixture mapping to try and find these factors. The concept of admixture mapping is to scan the genes of mixed ancestry populations (such as African Americans, descended from Africans and Europeans over the last 15 generations), searching for regions where the proportion of DNA inherited from one side is unusual. The authors found that a 3.8 million base region of chromosome 8, termed 8q24, substantially increased prostate cancer risk in men who inherited the African ancestry. Interestingly, this increase was greater in men diagnosed before the age of 72, correlating with observations that prostate cancer risk in African Americans attenuates with age. This same region, which contains 9 known genes, was recently identified by linkage analysis. However, the authors found their results cannot be explained by the two genes proposed in the other analysis; therefore, the major risk gene(s) for prostate cancer remain unidentified.

Scientific Summary:
Admixture mapping reveals locus for prostate cancer risk

Admixture mapping entails scanning the genes of mixed ancestry populations to find regions where the proportion of DNA inherited from either ancestral side is unusual compared to the genome-wide average. This technique could be useful in uncovering risk variants, although it has only recently become practical. Matthew Freedman et al. have now applied admixture mapping to find genes for prostate cancer, taking advantage of its markedly increased incidence rates in African American men. Their analysis of 1,597 cancer cases and 873 controls revealed a 3.8 Mb section of chromosome 8, termed 8q24, that contributes to an increased cancer risk in African Americans with African (as opposed to European) ancestry at this region. There is also a highly significant association between risk and age at 8q24, which correlates with epidemiology studies that show that the elevated incidence of prostate cancer in African Americans compared with other populations attenuates with age. A recent linkage analysis also highlighted a risk association in this region, but Freedman et al. report that the previously described alleles only explain a fraction of the admixture signal; therefore 8q24 still contains a major unidentified risk gene for prostate cancer.

Gene Therapy Study Takes Aim At Prostate Cancer

27 Sep 2006

Researchers at Baylor College of Medicine (BCM) are hoping a new gene therapy that takes a gene called RTVP-1 directly into the prostate tumor will prove effective in preventing recurrence of the disease.

The first phase of the study is designed to test the safety of the treatment and determine the proper dosage of gene, said Dr. Dov Kadmon, professor of urology at BCM. It will be carried out in the department of urology at BCM as well as at Ben Taub General Hospital, The Methodist Hospital and Michael E. DeBakey Veterans Affairs Medical Center.

"We are treating patients who are scheduled for a prostatectomy (prostate removal) but who also have a high risk that their disease will recur (or come back)," said Kadmon. "The operation itself is highly successful in eradicating local tumors (in the prostate)."

The design of the study is simple, said Kadmon.

"One injection into the prostate that should take no more than 10 minutes, although patients will be monitored in a special unit of the hospital for 23 hours to make sure there are no side effects. After that, they come to the unit for a check-up once a week."

After about 30 days, the subjects undergo their surgery, which has already been scheduled, he said. He said the hope is that the gene therapy will reduce the risk that cancer will recur at or near the site of the tumor as well as in distant points in the body.

"We hope that by generating a systemic immune response, we are enabling the body to destroy prostate cancer cells that have moved elsewhere," he said. Kadmon and his colleagues plan to test six different doses of the gene.

The gene therapy involves attaching an inactivated adenovirus (related to viruses that cause respiratory infections) to the RTVP-1 gene. As the virus infects the tumor cells, it will introduce the gene into the cells as well. (RTVP stands for related to testes-specific, vespid and pathogenesis proteins.) The RTVP-1 gene was isolated in the laboratory of Dr. Timothy Thompson, also a professor of urology at BCM.

As Thompson began to study the gene, he found that it was a target for a tumor suppressor gene called p53, which is a major controller of cell activity in prostate and other cancers. He found that the human form of the gene is normally present in benign prostate or low grade tumor but is lost as the tumors become more malignant. "This characterized it as a tumor suppressor gene that is active in the prostate," said Kadmon.

When the gene is introduced into the tumors of animals lacking RTVP-1, it suppresses the formation of new blood vessels. It causes what is known as "apoptosis" or programmed cell death in prostate cancer cells and also activates the immune system to fight cancer cells.

"We are proceeding carefully, step-by-step," said Kadmon. He said they do not think the study presents a significant risk.

They will inject the virus-gene compound directly into the prostate. While there is a risk of infection with the injection, he said patients will receive antibiotics. Most patients will have some fever after the injection, but it can probably be handled with Tylenol.

Doctors will monitor patients after their surgery to determine the effect of the gene therapy on their disease.

Funding for the study, which will include as many as 36 subjects, comes from the National Cancer Institute and the Baylor Special Program for Research Excellence in Prostate Cancer that is NCI-funded.

Others involved in the study include Thompson, Dr. Brian J. Miles, BCM professor of urology; Dr. Adrian Gee, BCM professor of medicine and pediatrics in the section of hematology oncology; Dr. Thomas M. Wheeler, BCM professor of pathology and urology; Dr. Gustavo E. Ayala, BCM professor of pathology and urology; Dr. Martha P. Mims, BCM assistant professor of medicine in the section of hematology-oncology; and Dr. Teresa G. Hayes, BCM assistant professor of medicine, section of hematology-oncology.

Patients qualified to participate in this study are individuals diagnosed with high grade prostate cancer (Gleason grade 7 or higher), or who have a blood PSA level of 10ng/ml or higher and are contemplating surgery (radical prostatectomy).

The Relationship Of Ultrasensitive Measurements Of Prostate-specific Antigen Levels To Prostate Cancer Recurrence After Radical Prostatectomy

28 Sep 2006

A rising PSA following radical prostatectomy (RP) for prostate cancer (CaP) suggests disease recurrence. Ultrasensitive PSA (USPSA) tests can detect PSA at values as low as 0.001ng/ml. Dr. Taylor and colleagues publish a report in the September 2006 issue of the BJU International that evaluates USPSA values in the context of clinical outcomes.

A cohort of 225 patients who underwent RP between 1997 and 2001 had up to 65 months of follow-up. PSA was measured by the Elecsys (Roche) USPSA assay, with a sensitivity of 0.002ng/ml. Clinical and demographic data was collected and correlated.

Patients were separated into those with disease recurrence and those without. USPSA levels for each group were put into pre-set periods that were established to approximate follow-up times of 6, 12, 18, 24, 36 and 60 months.

Follow-up was similar for the 2 groups, with a median of 31 months. In patients with disease recurrence, the pretreatment PSA levels and age were slightly higher. A USPSA level of >0.002ng/ml was found in 21 men; 11 then received salvage radiotherapy and/or androgen deprivation therapy. Ten patients went on observation and all had USPSA levels that continued to rise. A significant difference was found in the recurrence and no recurrence groups for every time point except 60 months. USPSA levels remained constant in those without recurrence. Of those with no recurrence, 89 patients (44%) had an undetectable PSA level outside the range of the USPSA assay during the follow-up; only 3 of 21 (14%) with a recurrence attained this level (P=0.009).

Fluctuations in the USPSA levels precluded calculating useful PSA kinetics. Although there were statistically significant differences in USPSA levels between groups, the clinical translation was meaningless due to the significant overlap of the two groups. This possibly reflects ?assay noise'. However, an undetectable USPSA level was associated with a favorable outcome. Presently, USPSA assays do not have adequate data to substantiate their use in initiating salvage therapy in CaP patients with detectable levels after RP.

By Christopher P. Evans, M.D.

U.S. Genomics And Lahey Clinic Announce Collaboration To Study The Role Of MicroRNAs In The Prognosis Of Urologic Cancers

20 Oct 2006

U.S. Genomics Inc. and Lahey Clinic announce the signing of a discovery agreement to study the role microRNAs play in the development of urologic cancers. The objective of the collaboration is to develop more accurate prognoses for bladder and prostate cancer patients. The collaboration combines U.S. Genomics' patented Trilogy(R) 2020 platform and Direct(TM) miRNA assay with Lahey Clinic's expertise in the analysis of tumor progression and experience in disease management.

"This collaboration is intended to expedite the development of next-generation molecular diagnostic tests to determine the prognosis of several major urologic cancers," said John Libertino M.D., Chairman of the Department of Urology, Lahey Clinic.

"MicroRNAs hold great promise as biomarkers for several disease states, and we are very pleased to be working with U.S. Genomics to explore these new diagnostic markers for urologic oncology patients," said Ian Summerhayes, Ph.D., Executive Director of Research, Lahey Clinic Medical Center.

"U.S. Genomics is excited about working with Lahey Clinic to study the potential for microRNA-based tests for the prognosis of bladder and prostate cancer," said John Canepa, CEO and President of U.S. Genomics. "Use of our Trilogy(R) 2020 single molecule detection platform and assays partnered with Lahey Clinic's unique expertise and the guidance of Drs. Libertino and Summerhayes has the potential to result in significantly more accurate prognostic tests for these diseases," added Duncan Whitney, VP, Research & Development (U.S. Genomics).

Lower cholesterol may cut risk of aggressive prostate cancer

Men with lower cholesterol are less likely to experience high-grade prostate cancer - an aggressive form of the disease with poor prognosis. Johns Hopkins epidemiologists, in a prospective study of U.S. men, say lower blood levels of the heart-clogging fat may reduce a man's risk of this form of cancer by one-third.

Cholesterol, often stored in tumors, may change the structure of fatty cell membranes to produce signals that influence cancer cell growth and survival.

In the study, Elizabeth Platz, Sc.D., M.P.H., epidemiologist at the Johns Hopkins Bloomberg School of Public Health and Kimmel Cancer Center and her colleagues compared a group of 698 men with prostate cancer to an equal number with no evidence of the disease. All participants were part of Harvard's Health Professionals Follow-up Study. There were no differences in blood cholesterol levels in either group when matched up to the incidence of low-grade disease. But men with higher levels of blood cholesterol were one-third less likely to get high-grade cancers that tend to spread and grow faster.

Platz and her colleagues previously linked lower risk of advanced prostate cancer to men taking cholesterol-lowering statin-drugs. "These two studies suggest that we may be able to prevent dangerous prostate cancers by tampering with cholesterol metabolism," she added.

This study was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute.

Co-authors include Steven K. Clinton from Ohio State University and Edward Giovannucci from Harvard University.

A 23-Year Survival Analysis of Prediagnostic BMI and Risk of Lethal Prostate Cancer

A team of Harvard scientists has peered into 23 years of health data on more than 22,000 physicians and concluded that men who are overweight or obese years before being diagnosed with prostate cancer are more likely to die of the disease than those who are of normal weight.

While no studies have definitively shown that obesity and/or higher Body Mass Index, or BMI, which measures body fat, increases the risk of developing prostate cancer, these studies showed that obese men at the time of diagnosis were more likely to have a cancer recurrence.

But according to Jing Ma, M.D., Ph.D., a researcher at the Brigham and Women's Hospital-based Channing Laboratory and associate professor of medicine at Harvard Medical School, few studies have focused on obesity and the risk of dying from prostate cancer.

In fact, she said, there is "considerable debate in the urology and cancer fields regarding whether rising PSA (Prostate Specific Antigen) is a good indicator for whether people will eventually die from prostate cancer or not."

Ma and her co-workers at Brigham and Women's Hospital and at the Harvard School of Public Health examined 23 years of data from the Physician's Health Study, which began in 1982 as a randomized, double-blind trial of aspirin and beta-carotene. More than 22,000 U.S. male physicians were recruited for the trial to study the role of aspirin and beta-carotene in preventing heart disease and cancer.

About 15,000 men provided blood samples at enrollment, along with information on their body weight and height, and their BMI was calculated. Approximately 99 percent of the original participants were tracked through questionnaires for 23 years, including cause of death.

By the end of 2005, 2,367 men had developed prostate cancer, while 265 died of the disease. They found that 39 percent of the participants were overweight and 3.4 percent were obese at the beginning of the study, and that higher BMI was positively associated with the risk of dying from prostate cancer. They also showed that the risk of dying from prostate cancer increased 8 percent for each point increase in BMI.

A person with a BMI of between 25 and 29.9 is considered overweight, whereas someone with a BMI of 30-plus is called obese. The physicians were in relatively good shape compared to the U.S. population in general. U.S. males between 50 and 69 are approximately 40 percent overweight and more than 30 percent are obese.

"It was surprising since it is a moderate association and the BMI was measured in 1982 and was on average eight to 10 years before developing prostate cancer," Ma said. "The beauty of the study is that we could factor out smoking at baseline, and tumor grade and stage didn't affect the trend."

"Some people might think that what they do today has little to do with cancer risk, especially for prostate cancer," Ma said, "and some individuals probably wouldn't believe that obesity has anything to do with prostate cancer. But we have found that if a man develops prostate cancer, being obese could put him at a higher risk of dying from the cancer. There is something many men can do about that."

She and her co-workers are exploring the underlying mechanisms that link being overweight and/or obese to prostate cancer progression. A better understanding of the risk factors that influence the disease's progression, said Ma, is imperative.

Prostate cancer is the most common type of cancer found in American men, other than skin cancer, and the third leading cause of cancer death in men. The American Cancer Society estimates that there will be about 234,460 new cases of prostate cancer in the United States in 2006, with approximately 27,350 deaths from the disease.

Complete article:

Adding Radiation Therapy For Treatment Of Advanced Prostate Cancer May Be Beneficial

18 Nov 2006

Treating advanced prostate cancer with radiation therapy after removal of the prostate gland reduces the risk of disease recurrence, but does not appear to significantly improve the length of survival, according to a study in the November 15 issue of JAMA, a theme issue on men's health.

Gregory Swanson, M.D., of the University of Texas Health Science Center, San Antonio, presented the findings of the study on 14-Nov-2006 at a JAMA media briefing on men's health in New York.

Radical prostatectomy (removal of the prostate gland) is selected for treatment of localized prostate cancer by approximately one-third of the 230,000 patients newly diagnosed each year in the United States. It is commonly accepted that this treatment has optimal results in patients with cancer confined to the prostate. But cancer outside of the prostate is detected at radical prostatectomy in 38 percent to 52 percent of patients, and this is associated with a risk of disease recurrence, progression, and death, according to background information in the article. Adding (adjuvant) radiation therapy to treatment has been used for more than 4 decades to reduce the risk of disease recurrence, but it is unknown if this reduces the risk of the cancer spreading or improves survival.

Dr. Swanson and colleagues conducted a study comparing usual care with adjuvant radiation therapy for 425 men with cancer outside of the prostate after radical prostatectomy to determine the effect on metastasis-free survival and overall survival. The patients were enrolled between August 1988 and January 1997, with median (midpoint) follow-up of 10.6 years. Men were randomly assigned to receive external beam radiotherapy (n = 214) or usual care plus observation (n = 211).

A total of 43.1 percent of the patients in the observation group were diagnosed with metastatic disease or died (median metastasis-free estimate, 13.2 years) vs. 35.5 percent of the patients in the adjuvant radiotherapy group (median metastasis-free estimate, 14.7 years), a difference that was not statistically significant. There were no significant between-group differences for overall survival (71 deaths in the radiotherapy group vs. 83 deaths in the observation group).

The researchers did find that patients in the adjuvant radiotherapy group had a 57 percent lower risk of PSA relapse, and a 38 percent reduced risk of disease recurrence, compared to patients in the observation group.

Adverse effects were more common with radiotherapy vs. observation (23.8 percent vs. 11.9 percent), including rectal complications and urinary incontinence.

"The results of this study provide guidance for clinicians and patients in weighing options for adjuvant radiotherapy for pathologically advanced disease. Arguments in favor of radiation include the approximately 50 percent reduction in risk of PSA relapse or disease recurrence, and perhaps the nonsignificant reduction in risk of metastasis-free survival, the primary study end point," the authors write. "Arguments against adjuvant radiotherapy must include that the study had negative findings, ie., a significant reduction in metastatic disease was not demonstrated. Despite prolonged follow-up of these patients, the rate of metastatic disease was significantly less than anticipated."

Obesity, Diabetes, And Risk Of Prostate Cancer: Results From The Prostate Cancer Prevention Trial

21 Nov 2006 - The association between obesity and prostate cancer risk remains controversial. In the October issue of Cancer Epidemiology Biomarkers and Prevention, Gong and colleagues present data obtained from the PCPT which addresses this very issue.

Of 10,258 patients enrolled in the study who had a prostate biopsies performed, cancer was diagnosed in 1,936 patients (18.8%). The relationship between body-mass index and diabetes mellitus to prostate cancer aggressiveness was ascertained.

Compared to patients with a normal BMI < 25, obese patients (BMI ≥ 30) exhibited a 29% increased risk of high-grade prostate cancer (Gleason ≥ 7), with an odds ratio of 1.78 (95% CI, 1.0 to 1.67). The risk was highest for developing prostate cancers of Gleason score 8-10 (OR 1.78; 78% increased risk). Interestingly, obese patients were found to have an 18% decreased risk of low-risk prostate cancer (OR = 0.82, 95% CI 0.69 to 0.98). The presence of abdominal obesity only increase prostate cancer risk independent of BMI in men with a family history of prostate cancer. These differences were seen in both the placebo and finasteride arms.

Furthermore, the presence of diabetes mellitus independently decreased the risk of low-grade prostate cancer by 47% and of high grade disease by 28%. This statistical significance persisted on multivariate analysis after adjusting for BMI.

These unique data obtained from a prospective randomized trial suggest that obesity may preferentially increase the risk of high-grade prostate cancer, while decreasing the risk of developing low-grade tumors. The authors suggest that this may explain why no association between BMI and prostate cancer has been found in studies that have not subdivided patients based on Gleason score.

PSA Velocity Over 2 NG/ML Year Pre Diagnosis Independently Predicts Prostate Cancer Mortality In Men Treated With Radical Prostatectomy/Radiotherapy

21 Nov 2006 - In the past, prostate cancer risk stratification before definitive treatment had been largely based on preoperative serum PSA, Gleason score, clinical stage, and the percent of positive biopsies on biopsy. Recently, PSA velocity before diagnosis has been increasingly implicated in prostate cancer prognosis.

In the December supplement of the Journal of Urology, D'Amico, Catalona and colleagues present data from 1453 men with clinical stage T1-T2 cancer treated either with radical prostatectomy (1095) or external beam radiotherapy (358) over a 12 year period at Barnes Jewish Hospital or Harvard Medical School, respectively. Prostate cancer-related mortality was assessed and compared with preoperative variables. Median follow-up was 5 years for the surgical group and 4 years for the radiotherapy group.

A pre-treatment PSA velocity greater than 2 ng/ml/year was independently associated with an increased risk of dying of prostate cancer in men treated with radical prostatectomy (Hazard ratio 12, 95% CI 3 to 51) and radiotherapy (HR: 12, 95% CI 3 to 54). Interestingly, in the cohort of 947 patients with low-risk prostate cancer (77% clinical stage T1 disease, 100% Gleason score 6 or less) those patients with a PSA velocity > 2 ng/ml per year exhibited a 7-year actuarial risk of prostate cancer death of 5% after surgery and 19% after RT, compared with 0.5% and 0% in those with a PSAv < 2 ng/ml/year, respectively.

These data adds to the growing body of evidence suggesting that patients with what had been traditionally considered "low risk" prostate cancer should be treated as high risk patients if their PSA velocity before diagnosis is greater than 2 ng/ml/year.

Peregrine Pharmaceuticals Reports Preclinical Data That Shows Bavituximab Equivalent Plus Docetaxel Reduces Growth Of Human Prostate Tumors

13 Dec 2006

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus (HCV) infection, announced that preclinical studies being presented today demonstrate that a mouse equivalent to its first-in-class anti-phospholipid agent bavituximab significantly decreased growth in human prostate tumors in mice when given in combination with docetaxel, a chemotherapy drug widely used to treat prostate, breast and lung cancers. Tumor growth was reduced by as much as 94%, with no toxicity observed from the addition of the bavituximab equivalent to the docetaxel regimen. The study findings will be presented today by Dr. Philip Thorpe, professor of pharmacology at UT Southwestern Medical Center and a member of the Peregrine Scientific Resource Board, at the "Antibody Therapeutics -- Advancing Clinical Development of Therapeutic Antibodies" meeting in San Diego, California.

In the study, Dr. Thorpe and colleagues at UT Southwestern studied a bavituximab equivalent antibody, 2aG4, in combination with the standard-of-care chemotherapy drug docetaxel in a mouse model of human prostate cancer. Tumor suppression in the group treated with the combination of the bavituximab equivalent and docetaxel was significantly better (p<0.01) than for either agent alone. In mice treated with the combination of docetaxel and the bavituximab equivalent, the growth of well-established tumors was inhibited by up to 94%. Similar to other preclinical bavituximab studies, this new study confirmed that the bavituximab equivalent appears safe -- therapy with the bavituximab equivalent and docetaxel was no more toxic than docetaxel alone.

"These new findings further strengthen the rationale for clinical trials assessing the utility of bavituximab and docetaxel used in combination to treat human prostate cancer," said Dr. Thorpe. "These encouraging results are consistent with the positive findings in our previous preclinical cancer studies combining a bavituximab equivalent and chemotherapy or radiation. We look forward to the results of the first tests in human cancer patients of bavituximab combined with docetaxel, which are currently on-going."

Bavituximab is a monoclonal antibody that binds to a phospholipid called phosphatidylserine, normally located inside normal cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors, thus creating a specific target for anti-cancer treatments. Bavituximab is currently in Phase Ia safety trials as monotherapy and in Phase Ib trials in combination with common cancer chemotherapy agents, including docetaxel, in patients with advanced solid cancers, including prostate, breast and lung cancers.

"Preclinically, we have now shown that bavituximab antibodies significantly enhance the anti-tumor activity of cancer chemotherapy and radiation in prostate, breast, lung, brain and pancreatic cancers," said Steven W. King, president and CEO of Peregrine. "This new study is especially timely since it further demonstrates the rationale for including docetaxel in our bavituximab Phase Ib combination therapy cancer trial in India, which is currently enrolling patients receiving one of three major chemotherapy agents for prostate, breast and other solid cancers."

Prostate cancer is the most commonly diagnosed cancer in men, accounting for 30% of all male cancers, and prostate cancer is second only to lung cancer as a leading cause of cancer deaths in men. Currently, there is no cure for locally advanced or metastatic prostate cancer.

This study, entitled "Antibodies to Phosphatidylserine for Targeting Tumor Blood Vessels and Viruses," will be presented by Dr. Thorpe at "Antibody Therapeutics -- Advancing Clinical Development of Therapeutic Antibodies" at the San Diego Convention Center on December 12, 2006 at 2:20 pm PST/ 5:20 pm EST. Conference presentations are not available via webcast.

Treating Your Prostate Cancer Sooner Rather Than Later Could Be Better Than Wait And See

13 Dec 2006

A new study cautiously suggests that elderly men with low and medium risk, localized prostate cancer may be better off having treatment than waiting to see how the cancer develops.

The study was published today in The Journal of the American Medical Association.

The study looked at 44,630 men aged from 65-80 years who had been diagnosed between 1991 and 1999 and lived more than 12 months afterwards. All the men had localized prostate cancer, that is it had not spread to other parts of the body. The researchers compared men who received treatment, such as surgery or radiation therapy (32,022 patients), with those who were under observation only ("wait and see", 608 patients).

The scientists found that over a 12-year period, a higher percentage of men in the observation group had died than in the treatment group. And the treatment group had a higher 5- and 10-year survival. The survival advantage of being in the treatment group was statistically significant, including in subgroups such as men with low-risk disease, black men, and men aged 75-80 years at diagnosis.

The study excluded patients who received hormonal therapy only and the researchers suggest more research is needed to confirm the results.

Treatment of low and medium risk prostate cancer in elderly men is a controversial issue. There are two options: to treat or to "wait and see".

In older men with prostate cancer, the likelihood that death will occur from other causes is greater (compared to younger men), making decisions about treatment very difficult. The most common treatments are surgical removal of the prostate (prostatectomy), radiation or hormone therapy, and less commonly, chemotherapy. Prostate-specific antigen (PSA) screening, where a blood test shows if cancer traces are present, has led to more men being diagnosed at an early stage, before the cancer has spread to other organs.

The prostate is a gland that sits in a man's pelvic area, just below the bladder and above the testicles. Prostate cancer usually develops in men over 50 and often causes pain, difficulty urinating, and erectile dysfunction. It is the most common form of cancer for men in the US, and takes second place to lung cancer as the biggest killer of US males.

"Survival Associated With Treatment vs Observation of Localized Prostate Cancer in Elderly Men"
Yu-Ning Wong, MD; Nandita Mitra, PhD; Gary Hudes, MD; Russell Localio, PhD; J. Sanford Schwartz, MD; Fei Wan, MS; Chantal Montagnet, MA, MPhil; Katrina Armstrong, MD, MSCE
JAMA. 2006;296:2683-2693

Mucinous Adenocarcinoma Of The Prostate Does Not Confer Poor Prognosis

02 Jan 2007 - While mucinous adenocarcinoma of the colon and breast demonstrate poor and favorable prognoses, respectively, the clinical behavior of mucinous adenocarcinoma of the prostate (MC) is unknown. A report by Dr. Lane and associates at the Cleveland Clinic suggest that the clinical course of MC is similar to conventional prostate adenocarcinoma (AC). This paper appears in the October 2006 issue of Urology.

Between 1987 and 2005, complete data on 2,572 radical prostatectomy (RP) patients who did not receive adjuvant therapy was available for analysis. A total of 32 cases were identified: 14 with MC and 18 with AC with focal mucin (AFM). Pathological and clinical variables were correlated with outcomes. All pathology was re-reviewed by a single pathologist.

In the MC cohort, pathologic Gleason score was 6 in one, 7 in 4, and 8 in three patients. In 6 patients it was not evaluable due to neoadjuvant hormonal therapy. Non-organ confined disease was present in 12 (37.5%) with MC or AFM including 12 with extraprostatic extension, 6 with positive surgical margins, and 4 with seminal vesicle invasion. One-half of patients had a pelvic lymphadenectomy and none had metastatic disease. There was no statistically significant difference between the patients with MC, AFM or AC with regard to PSA levels, clinical T stage, biopsy or pathologic Gleason score, or non-organ confined disease.

In follow-up, 26 patients had at least 2 follow-up PSA tests. Of these 26 men, biochemical failure occurred in 1 patient with MC and 5 patients with AFM (23%) at a median of 4.2 years. Overall survival showed no statistical difference among those with MC, AFM or AC. The 5-year overall survival rate was 100%, 100%, and 96.6%, for those with MC, AFM or AC, respectively. The overall 5-year biochemical recurrence-free survival rate was 100%, 69.2%, and 77.8%, for those with MC, AFM or AC, respectively.

This data is the largest known series of MC patients and suggests that MC can be treated in a fashion similar to AC.

Statin Use Associated With Decreased Risk Of Advanced Prostate Cancer

31 Dec 2006

Use of cholesterol-lowering medications called statins is not associated with a lower risk of prostate cancer overall, but it is associated with a decreased risk of advanced disease, a large prospective study finds.

Two recently reported studies found an association between statin use and a reduced risk of prostate cancer. However, other observational studies and clinical trials have not confirmed those findings.

To investigate a possible association between statin use and the risk of prostate cancer and advanced prostate cancer, Elizabeth A. Platz, Sc.D., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md., and colleagues analyzed data from the Health Professionals Follow-up Study, a cohort of 34,989 U.S. men ages 40 to 75. From 1990 to 2002, the men were asked every other year about several factors, including use of cholesterol-lowering drugs.

In 1990, 4.4% of the men reported taking statins. By 2000, that number increased to 23.8%. Current statin use was not associated with risk of prostate cancer overall or of localized disease. However, current use of statins was associated with a reduced risk of advanced prostate cancer. Compared with men who had never taken statins, men currently taking statins had half the risk of advanced disease and less than half the risk of metastatic or fatal disease. The authors calculated that the incidence of advanced prostate cancer among current statin users was 38 cases per 100,000 men per year, and 89 cases per 100,000 men per year among nonusers. The inverse association was even stronger for metastatic and fatal prostate cancers combined, and the reduced risk of advanced disease was even lower with longer use of statins.

A possible confounding factor of the study is that more statin users than nonusers reported undergoing prostate-specific antigen (PSA) screening, a test often used as an early indicator of prostate cancer. Men who underwent multiple PSA tests were more likely to be diagnosed with localized prostate cancer and less likely to be diagnosed with advanced disease. The authors calculated that PSA screening did not account for their results, but they caution that it may have been a source of bias in the analysis.

"- It is premature to recommend the use of statins for the prevention of advanced prostate cancer," the authors write. "Further work is needed to address the role of PSA screening as a possible explanation for these findings and to identify the biologic mechanisms that may underlie the inverse association, if this association is indeed causal."

Study Suggests Role For Y Chromosome In Prostate Cancer

05 Jan 2007

A new study finds that, among a group of men in Israel, men with only daughters had a 40 percent higher risk of prostate cancer than men with at least one son. The study raises the possibility that some mutation or variant on the Y chromosome may be involved in prostate cancer.

Although several studies have identified risk factors for prostate cancer and found some gene mutations that are associated with the disease, none of these can account for large numbers of prostate cancer cases. Some studies have suggested that prostate cancer risk may be associated with alterations on the X or Y chromosomes.

Because alterations on the sex chromosomes might affect the probability of having sons or daughters, Susan Harlap, M.D., of Columbia University in New York, decided to study cancer incidence and offspring among men participating in the Jerusalem Perinatal Study. During the study period, 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had a 40 percent increased risk of prostate cancer. Men with no daughters had no increase or decrease in prostate cancer risk compared with men with offspring of both sexes.

"Overall, our findings are consistent with hypotheses that tie Y chromosome loci to prostate cancer, although other explanations cannot be excluded," they write.

Contact: Stephanie Berger; Columbia University Office of Public Affairs

The Prognostic Significance Of Perineural Invasion In Prostatic Cancer Biopsies

11 Jan 2007 Whether perineural invasion (PNI) identified in prostate cancer (CaP) biopsies is associated with disease recurrence is unclear from the literature. In an attempt to resolve this uncertainty, a systematic review was performed by Dr. Patricia Hamden and colleagues in the UK and published in the online edition of Cancer. What they found was that variable study design, execution and reporting excluded a definitive meta-analysis, but evidence suggests that PNI in biopsies was a significant prognostic indicator.

The authors' strategy used 128 search terms to identify articles published between 1990 and 2005. A total of 41,295 titles were reviewed by at least 2 reviewers and 128 articles identified for close evaluation. Ultimately, 10 surgical and 11 radiotherapy articles on PNI in biopsies as it related to patient outcomes were used in the report. Data items specific to biopsy PNI in CaP included biopsy procedure (amount of cores, number of nerves present and identification of PNI), histological slide preparation and pathological interpretation (consistency of identification, inclusion of information if no nerves were present).

No study reported on all data items and incomplete items ranged from 18% to 61% with a median of 39%. Exclusion criteria were variable, but included a history of prior treatment, unavailability of biopsies for review or the failure to obtain at least 4 biopsies. Only 1 surgical and 1 radiotherapy article was prospective. In surgical patients details on nerve sparing was generally lacking. In 12 studies, biopsies were reviewed for the presence of PNI and in 1 study 60% of biopsies were reviewed for this. In 5 studies the slides were not reviewed but the diagnosis was taken from the original report and in 3 articles the information was not provided. Only 2 articles reported blinded pathologic review. Individual patient data was sufficient in 5 articles to permit reanalysis.

The proportion of patients with PNI varied between 7% and 12% (median 9%) when the diagnosis was obtained form the original report and between 7% and 43% (median 23%) when slides were reviewed to identify PNI. Most studies had short (<6 months) of clinical follow-up. Overall, 6 of 10 surgical and 5 of 11 radiotherapy studies identified PNI as a prognostic factor in univariate analysis. Surgical articles that included a larger number of patients with less patient exclusion reported that PNI was independently prognostic in multivariate analysis with PSA and biopsy Gleason score. More than two-thirds of external radiotherapy studies but no brachytherapy study showed prognostic significance for perineural invasion. The highest incidence of PNI was found in locally-advanced disease.

Surprising to the authors were that none of the articles considered that the presence of nerves in the biopsies was a prerequisite for patient inclusion and no article provided data on the reproducibility of the PNI diagnosis. The authors conclude that the importance of PNI was likely to have been underestimated by the inclusion of uninformative test results (biopsies with no nerves in the specimens) and that despite this, the majority of studies including those performing multivariate analysis found prognostic significance to PNI. The weight of evidence supports PNI as of prognostic significance.

International Multi-centre Research Group Finds Genetic Defect Contributing To Cancer Susceptibility

11 Feb 2007

An international multi-centre research effort has identified a new genetic defect as a potential heritable breast cancer susceptibility candidate. The same PALB2 mutation also seems to in some measure cause prostate cancer.

Cancer is a complex and common disease caused by a combination of both genetic and environmental factors. An inherited predisposition seems to be involved in at least 5�"10 per cent of all cases of breast cancer. The two major familial breast cancer susceptibility genes BRCA1 and BRCA2 only explain 20-30 per cent of families with site-specific female breast cancer, which suggests the contribution of additional susceptibility genes. According to Dr Robert Winqvist, who coordinates the research effort, the identification of these genes may help to clarify the genetic background contributing to breast cancer and suggest novel pharmaceutical targets. It could also lead to genetic screening that identifies individuals at increased breast cancer risk and result in improved prevention efforts and treatment.

About a year ago, Dr Bing Xia and Professor David Livingston at the Dana-Farber Cancer Institute in Boston identified a novel BRCA2 binding factor, PALB2 that regulates certain key functions of normal BRCA2 activity. The next step was to set out to evaluate the newly detected PALB2 gene as a potential heritable breast cancer susceptibility candidate by screening for disease-related alterations. The results of this international research effort were recently published in Nature.

The research first involved comprehensive screening for genetic aberrations in 113 Finnish breast cancer families. The same constitutional mutation in PALB2 was observed in three families. It was later showed that the relevant mutant protein is deficient in its ability to support the kinds of DNA damage responses in which PALB2 normally participates. The mutation was further also investigated in 1,918 specimens from an unselected series of Finnish breast cancer individuals. This study revealed 18 mutation-positive individuals, about one per cent of the studied patients, most of whom turned out to have a familial pattern of disease development. The study also involved 141 unselected male breast cancer patients, 188 familial and 288 unselected colorectal cancers, as well as 164 familial and 475 unselected prostate cancer patients. In prostate cancer, one multigenerational cancer family was found where cancer occurred in several generations and all patients showed the single mutation in PALB2 that was studied. According to Winqvist, this suggests that this Finnish founder mutation may be important in heritable prostate cancer as well. Male breast cancer and colorectal cancer cases did not display the mutation.

The constitutional mutation elevates the risk of breast cancer four-fold

"Present results show that the discovered PALB2 mutation elevates the risk of breast cancer four-fold. However, we still need more research to better assess the effect on cancer development. As the comprehensive mutation analysis was originally conducted on only 113 cancer families, it may be that there still are other PALB2 genetic defects accounting for heritable breast and prostate cancer susceptibility. Recent results also imply that PALB2 might be a cancer susceptibility gene in other populations as well. It's been shown that two of the mutations identified in Fanconi anemia patients in non-Finnish populations seem to be associated with familial breast cancer," says Winqvist.

Winqvist points out that, in spite of recent advances, known factors can only explain a fraction of heritable susceptibility to breast cancer. He is nonetheless disposed to believe that the evaluation of yet other biologically significant factors will in time improve the situation. "Hopefully, increased knowledge of underlying mechanisms will provide better conditions for cancer prevention, diagnostics and treatment," Winqvist says.

The multi-centre research involved researchers from Oulu, Tampere, Kuopio and Helsinki Universities or university hospitals in Finland as well as from the US National Cancer Institute. The other research coordinator was Professor David Livingston from Boston. The discovery of the PALB2 genetic mutation was made by HanneleErkko, a PhD student in the Winqvist laboratory, who also carried out a number of the genetic analyses that followed. Dr Xia from the Livingston team was in charge of key analyses to prove the biological significance of the mutation.

The funding bodies behind the research include the Academy of Finland, the Foundation for the Finnish Cancer Institute, the Northern-Ostrobothnia Health Care District and the University of Oulu as well as by the US National Cancer Institute NCI.

New Study Shows Cough Medicine Effective Against Prostate Cancer

17 Feb 2007

A presentation made at the 17th International Prostate Cancer Update Conference in Vail, Colorado, has shown noscapine to be effective against prostate cancer.

Noscapine, a non-addictive derivative of opium, has been used worldwide since the 1950's as an anti-cough medication. Noscapine was originally proposed as an anti-cancer agent in the early 1960's. However major studies of its broad anti-cancer effects were only done in recent years.

The study in prostate cancer is the result of ongoing collaboration between the Prostate Cancer Research and Educational Foundation (PC-REF) and MedInsight Research Institute.

Dr. Israel Barken, Founder and Medical Director of the Prostate Cancer Research and Educational Foundation (PC-REF) in San Diego, California, has used noscapine for treating prostate cancer for over a decade. Encouraged by successful results, Dr. Barken's foundation funded a laboratory study to confirm noscapine's effectiveness and mode of action in treating prostate cancer.

"In our study noscapine administered orally to animals had a tumor inhibition rate of 60%, and reduced metastasis by just over 65%. Incredibly, this was achieved with no toxicity thus demonstrating noscapine's potential not only as an effective anti-cancer agent, but a very safe one too," says Dr. Barken.

Dr. Barken is now planning on facilitating clinical trials with noscapine in patients suffering from prostate cancer. He has also pioneered a web-based patient tracking system, which allows for trials to be carried out with ease, and at substantially reduced costs. This will allow global participation of patients, which will drastically cut the time necessary to complete the study.

Moshe Rogosnitzky, Director of Research at MedInsight Research Institute, is very encouraged by the findings. "Noscapine has been used for cough- suppression for close to half a century. Recent discoveries are pointing to its effectiveness in treating a broad variety of cancers."

"Additionally, Iranian scientists have shown it very effective in treating strokes. It is a drug that is readily available, and in many countries can be bought without a prescription. Noscapine is a safe low-cost option that has the potential to successfully fight several life-threatening diseases."

Green Tea And COX-2 Inhibitors Combine To Slow Growth Of Prostate Cancer

01 Mar 2007

Drinking a nice warm cup of green tea has long been touted for its healthful benefits, both real and anecdotal. But now researchers have found that a component of green tea, combined with low doses of a COX-2 inhibitor, could slow the spread of human prostate cancer.

In the March 1 issue of Clinical Cancer Research, researchers from University of Wisconsin-Madison demonstrate that low doses of the COX-2 inhibitor celecoxib, administered with a green tea polyphenol called pigallocatechin-3-gallate (EGCG), can slow the growth of human prostate cancer. Their experiments were performed in cell cultures and in a mouse model for the disease.

"Celecoxib and green tea have a synergistic effect -- each triggering cellular pathways that, combined, are more powerful than either agent alone," said Hasan Mukhtar, Ph.D., professor of dermatology at the University of Wisconsin and member of Wisconsin's Paul Carbone Comprehensive Cancer Center. "We hope that a clinical trial could lead to a preventative treatment as simple as tea time."

Previous research has linked the cyclooxygenase-2 enzyme, commonly known as COX-2, to many cancer types, including prostate cancer, said Mukhtar. Mukhtar and his colleagues have previously shown COX-2 inhibitors like celecoxib (known under the brand name Celebrex?) suppress prostate cancer in animal models. COX-2 inhibitors also have been shown to cause adverse cardiovascular effects when administered at high doses over long durations.

In 2004, Mukhtar and his colleagues demonstrated that green tea polyphenol EGCG has cancer-fighting abilities of its own. Their study, published in Cancer Research, showed that EGCG can modulate the insulin-like growth factor-1 (IGF-1)-driven molecular pathway in a mouse model for human prostate cancer, pushing the cells toward programmed cell death (apoptosis).

"We believed that COX-2 inhibitors may still prove beneficial if used in combination with complementary agents," Mukhtar said. "Our studies showed that the additive effect of green tea enables us to utilize the cancer-fighting abilities of COX-2 inhibitors, but at lower, safer doses."

In this latest research, Mukhtar and his colleagues looked at the effects of the two substances on cultured human prostate cancer cells. Alone, both EGCG and NS-398, a COX-2 inhibitor similar to celecoxib, demonstrated the ability to slow cancer cell growth and limit the presence of known cancer-promoting proteins within the cell samples. Together, EGCG and NS-398 suppressed cell growth by an additional 15 to 28 percent.

The researchers repeated the experiment in mouse models of prostate cancer, using celecoxib and an oral suspension of the decaffeinated green tea polyphenol. By using pharmacy-grade celecoxib and actual tea, they had hoped to replicate real-life conditions.

"The idea is that it would be easier to get people to drink green tea than it would be to take an additional dietary supplement," Mukhtar said.

In mice that were not treated with either substance, the tumor volume averaged 1,300 cubic millimeters, whereas mice given either the tea or celecoxib had tumors averaging 835 cubic millimeters and 650 cubic millimeters, respectively. Tumors taken from mice given both agents, however, measured on average a volume of 350 cubic millimeters.

In parallel to tumor growth inhibition, mice that received a combination of green tea and celecoxib registered a greater decrease in prostate specific antigen (PSA) levels compared to that in celecoxib alone or green tea alone treated animals. PSA is a protein produced by the cells of the prostate and is used as a marker for detection and progression of prostate cancer. These results, combined with a marked decrease in the presence of cancer-promoting proteins, offered clear indications that green tea and celecoxib, combined, could be useful in slowing prostate cancer growth, Mukhtar said.

"Prostate cancer typically arises from more than one defect in the cellular mechanics, which means that a single therapeutic might not work fighting a particular cancer long-term," Mukhtar said. "If tests in human trials replicate these results, we could see a powerful combined therapy that is both simple to administer and relatively cost effective."

The study was funded by the National Cancer Institute.

Obesity At The Time Of Prostate-Cancer Diagnosis Dramatically Increases The Risk Of Dying From The Disease

15 Mar 2007

Obese men who are diagnosed with prostate cancer have more than two-and-a-half times the risk of dying from the disease as compared to men of normal weight at the time of diagnosis, according to a study by researchers at Fred Hutchinson Cancer Research Center. The findings by senior author Alan Kristal, Dr.P.H., and colleagues appear online and will be published in the March 15 print edition of the journal Cancer.

"I was very surprised by the findings," said Kristal, member and associate head of the Cancer Prevention Program in the Hutchinson Center's Public Health Sciences Division. "We found the prostate-cancer-specific mortality risk associated with obesity was similar regardless of treatment, disease grade or disease stage at the time of diagnosis," he said.

"If a man is obese at the time of diagnosis, he faces a 2.6-fold greater risk of dying as compared to a normal-weight man with the same diagnostic profile, regardless of whether he has a radical prostatectomy or radiation therapy, whether or not he gets androgen-deprivation therapy, whether he has low- or high-grade disease and whether he has localized, regional or distant disease," Kristal said, referring to the degree of cancer spread.

The researchers also found that obese men diagnosed with local or regional disease -- that is, disease that is confined to the prostate or has spread to into surrounding tissue -- face a 3.6-fold increased risk of cancer spreading into distant organs, or metastasis, as compared to prostate-cancer patients of normal weight. The association of obesity with disease progression was strongest among men with regional stage at diagnosis, whose cancer had already spread beyond the prostate, as compared to men with early, localized disease.

The mechanisms behind the link between obesity and prostate cancer metastasis and death are believed to involve both steroid hormones and inflammation. "We are now beginning to appreciate that obesity is a massive inflammatory condition," Kristal said, "and obesity also increases levels of serum estrogens and growth factors that can promote cancer growth."

For the study, Kristal, first author Zhihong Gong, Ph.D., a postdoctoral research fellow in the Hutchinson Center's Cancer Prevention Program, and colleagues at the Hutchinson Center and the University of Washington followed 752 recently diagnosed middle-aged, Seattle-area prostate-cancer patients for about 10 years. Body-mass index, or BMI, in the year before diagnosis was determined in an initial interview; 17 percent of the participants were classified as obese, with a BMI of 30 or more. Of the men studied, 50 died of prostate cancer and 64 died of other causes.

Only one other study has examined obesity and prostate-cancer outcome; this study reported no association between the two, but the study was limited to men at one hospital, all of whom received radical prostatectomy.

Kristal's study is the first long-term, population-based study of prostate-cancer patients who have undergone a variety of treatments. A strength of the study is that it used metastasis and mortality as an endpoint versus biochemical recurrence (the presence of circulating prostate-specific antigen, or PSA, in the blood after treatment, a biomarker of limited value in predicting death from prostate cancer).

"I think this study represents the first good piece of evidence that losing weight may in fact reduce the risk of dying of prostate cancer," Kristal said. "Although one would need a randomized clinical trial to definitively determine whether weight loss could be an effective complimentary treatment for obese men diagnosed with prostate cancer, these results offer yet another good reason for men to achieve and maintain a healthy weight," he said.

The National Institutes of Health, the National Cancer Institute and Fred Hutchinson Cancer Research Center funded this study.

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New Blood Test Uses DNA To Diagnose Prostate Cancer

17 Mar 2007

Scientists at St George's, University of London, are working on a blood test that uses DNA markers to identify prostate cancer cells that are shed into the bloodstream.

The researchers have demonstrated that by measuring the levels of these markers, not only can an accurate diagnosis of cancer be made, but the stage the cancer has reached whether it is still localized or already has spread and become metastatic can be identified.

In addition, certain markers, if switched on, will hopefully give information on how quickly the cancer will develop, and, therefore, when treatment must be introduced.

The current, most widely used method of detecting prostate cancer is the serum Prostate Specific Antigen (PSA) test, which is only 50 per cent accurate. Increased levels of PSA are elevated in non-malignant conditions, such as benign prostatic hyperplasia, prostatitis and even urinary tract infections. This new test, which is able to detect one prostate cancer cell among a sample of 100 million blood cells, is 95 per cent accurate.

Because of its inaccuracy, most elevated serum PSA results are followed up. This is done using a core needle biopsy. Samples of tissue are removed by inserting a needle through the wall of the rectum into the prostate gland. When pulled out, the needles remove a cylinder of tissue, usually about 1/2-inch long and 1/16-inch across. Up to 12 needles are normally used to ensure the prostate is thoroughly sampled.

After this invasive procedure, tissue samples are sent to a laboratory for analysis, often taking a week or so for results to be confirmed.

Owing to a high serum PSA, some men will invariably have a biopsy in which the result will been negative for prostate cancer. It is hoped that the new test, with its increased accuracy, will encourage men who suspect they have prostate problems to seek medical attention early on, enabling early treatment and leading, hopefully, to less men having prostate biopsies.

The research has been partly funded by Prostate Research Campaign UK. Brigadier John Anderson, Chief Executive of the charity says: "Many men fear seeking medical help, even when they suspect they have prostate problems, for fear that the diagnosis will involve painful and undignified tests. This simple, speedy, non-invasive test means patients need not fear traumatic tests to diagnose prostate cancer. And receiving an accurate diagnosis within days rather than weeks could mean they are treated more quickly and stand a greater chance of total recovery."

The research has also been funded by the Everard and Mina Goodman Charitable Foundation.

The test is currently at the stage of validation, with further development regarding standardisation and formatting, and could be introduced on to the market next year.

Inflammation May Play Role In Metastasis Of Prostate Cancer

19 Mar 2007

Many would assume that "mounting an immune response" or "having your body fight the cancer" is a good thing. Now, research at the University of California, San Diego (UCSD) School of Medicine strongly suggests that inflammation associated with the progression of tumors actually plays a key role in the metastasis of prostate cancer.

The research, appearing online March 19 in advance of publication in the journal Nature, identifies a mechanism which triggers metastasis, which is the spread of cancer in late stages of prostate cancer development. The findings by Michael Karin, Ph.D., professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, and colleagues may help solve the puzzle of why it takes so long for cancer to metastasize, as well as what causes it to do so. Furthermore, this new work may lead to development of anti-metastatic therapies.

A major hypothesis in cancer research has been that whether the cancer metastisizes or not is determined by genetic changes within the cancer cell itself. But this hypothesis didn't explain why metastases appear many years after the initial tumor.

"Our findings suggest that promoting inflammation of the cancerous tissue, for instance, by performing prostate biopsies, may, ironically, hasten progression of metastasis," said Karin. "We have shown that proteins produced by inflammatory cells are the 'smoking gun' behind prostate cancer metastasis. The next step is to completely indict one of them."

One in six men will be diagnosed with prostate cancer, and one in 33 will die of metastatic disease. Early tumors confined to the prostate can be treated, but no effective treatments are available for metastatic disease, according to Steven L. Gonias, M.D., Ph.D., professor and chair of the UCSD Department of Pathology, a study investigator.

"This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive," said Gonias.

In research using mouse models and confirmed in human tissue, the scientists observed that a protein kinase called IĸB kinase α (IKKα) turns down the expression of a single gene called Maspin, which has well-established anti-metastatic activity in breast and prostate cancers. They found that the production of Maspin is repressed by a series of events triggered by tumor inflammatory cells, with the result that prostate cancer cells spread.

"An excellent inverse correlation between IKKα activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKα in their nuclei and express little or no Maspin," said Karin. He noted that a perfect correlation between nuclear accumulation of activated IKKα and reduced maspin expression was also seen in human prostate cancer, and both correlated with the clinical stage of the disease.

Karin and his colleagues discovered a signaling pathway that increased metastases in a mouse model of prostate cancer. The pathway is activated by a ligand that binds to a Receptor that Activates Nuclear factor Kappa-B (RANK). RANK ligand has been shown in previous studies to be an important inflammatory protein (cytokine) that can lead to bone loss through activation of bone resorbing cells.

RANK ligand, produced by inflammatory cells that invade advanced prostate tumors, triggers a chain reaction in which IKKα is activated, allowing it to enter the nucleus of the cancer cell, repressing Maspin. IKKα is a key linchpin in the pathway that turns off the Maspin gene and activates the metastatic program. The new results also support the view that RANK ligand is a general promoter of prostate, and possibly breast, cancer metastasis.

"Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKα," said Karin.

Malignancies progress through stages. In early, non-metastatic tumors, a high level of Maspin is present, but it is turned off in late stages. Early tumors contain low amounts of active nuclear IKKα, whereas late-stage tumors contain the highest levels of active nuclear IKKα. The researchers also found a striking elevation in expression of RANK ligand in late tumors, but it was not expressed by the cancer cells. Instead, it is expressed by invading inflammatory cells. Interference with RANK ligand production or activation, as well as interference with IKKα activation, may offer new therapeutic strategies for prevention of metastatic disease.

The study was funded by the National Institutes of Health, the U.S. Army Medical Research and Material Command, the Prostate Cancer Foundation, the Aventis-UICC Translational Cancer Research Fellowship, the Lopiccola Fellowship of the UCSD Moores Cancer Center, and the Life Science Research Fellowship.

Additional contributors include first author Jun-Li Luo,Wei Tan and Olexandr Korchynskyi, UCSD Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Moores Cancer Center; David A. Cheresh and Jill M. Ricono, UCSD Department of Pathology and the Moores Cancer Center; and Ming Zhang, Baylor College of Medicine, Department of Molecular and Cellular Biology.

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Soy Found Protective Against Localized Prostate Cancer Only

20 Mar 2007

The largest study examining the relationship between the traditional soy-rich Japanese diet and development of prostate cancer in Japanese men has come to a seemingly contradictory conclusion: intake of isoflavone chemicals, derived largely from soy foods, decreased the risk of localized prostate cancer but increased the risk of advanced prostate cancer.

The prospective study of 43,509 men, published in the March issue of Cancer Epidemiology, Biomarkers & Prevention, suggests that the effects of isoflavones on prostate cancer development may differ according to disease stage, say researchers at the National Cancer Center in Japan.

One possible explanation is that isoflavones may delay the progression of latent prostate cancer only; once tumors lose estrogen-receptor beta expression and become aggressive, isoflavones may fail to protect against the development of advanced cancer, and might even increase the risk of progression, possibly by reducing serum testosterone, researchers say. It is also possible that advanced and localized prostate cancer may be different tumor subtypes, which may react differently to isoflavones.

"The present findings provide no clear understanding of when or how localized cancer will develop to aggressive cancer, and of the related effect of isoflavones," said the study's first author, Norie Kurahashi, M.D., of the Epidemiology and Prevention Division of the National Cancer Center.

"Given that Japanese consume isoflavones regularly throughout life, we do not know the period during which the effects of isoflavones on prostate cancer are preventive, and further research is required to find that out, including well-designed clinical trials," she said.

Until those studies are done, the researchers recommend that Japanese men continue to consume isoflavones through their food and not through supplements.

"Consumption of isoflavones from traditional Japanese food throughout life may protect against the incidence of prostate cancer, but we cannot recommend the use of isoflavones from supplements for people who do not regularly consume these chemicals, because the relationship between isoflavones and the risk of advanced prostate cancer is not yet clear," Kurahashi said.

Isoflavones act as both strong antioxidants and plant-based estrogens. Soybeans are the most common source of isoflavones, especially genistein and daidzein, which have been shown in some animal studies to exert a protective effect against prostate cancer.

Japanese men eat significantly more soy-based foods than do Western men, and the incidence of prostate cancer is much lower in Asian countries than in Western countries. Still, reviews of latent, or clinically insignificant, prostate cancer findings in autopsy reports have revealed no difference between the populations so scientists have theorized that isoflavones stop latent cancers from developing further.

But because smaller epidemiological studies in Japan have reached differing conclusions about the protective effects of soy on prostate cancer development, this research team conducted the most comprehensive analysis to date. They polled thousands of men age 40-69 about their consumption of 147 foods, the most popular of which were miso soup (primarily made from fermented soybeans), natto (also a product of fermented soybeans) and tofu, made from soy milk. Japanese consume miso soup more frequently, usually daily, than other soy foods, and miso, natto, and tofu account for about 90 percent of the population's consumption of daidzein and genistein, according to Kurahashi.

The researchers then followed participants from 1995 through 2004 and found that 307 men were diagnosed with prostate cancer. In this group, 74 cases were advanced, 218 were confined to the prostate organ, and 15 were of undetermined stage.

They concluded that intake of genistein, daidzein, miso soup and soy food had no overall link to diagnosis of prostate cancer. However, they calculated that the risk of developing localized prostate cancer was 50 percent lower in men who ate the most isoflavones compared to men who ate the least - meaning that men in the top category ate between two and three times as much isoflavone-rich food.

However, in a discovery they cannot explain, they also calculated that the risk of developing advanced prostate cancer was twice as high in men who consumed two or more bowls of miso soup a day than in men who ate less than one bowl of soup.

They also found that the protective effect of isoflavone-rich food was strongest in men who were older than 60: the more isoflavones they ate, the more they reduced their risk of developing localized prostate cancer. "Isoflavone may be protective for localized prostate cancer only in men aged more than 60 years, and may not have a protective effect in the early stage of prostate cancer in younger men," the researchers conclude in their study.

The inconsistencies in the finding - that isoflavones decreased the risk of localized prostate cancer, but not the risk of advanced prostate cancer - could be errors in food measurement, or could be due to the fact that the number of participants who developed advanced prostate cancer was small, said Kurahashi. Or, as researchers speculate, isoflavones could interact with the estrogen receptor on prostate tissue enough to inhibit production of testosterone, which can fuel prostate cancer. When tumors lose all of their estrogen receptors and stop responding to isoflavone-induced hormonal interference, they grow aggressively.

"A broad body of research is required to clarify the timing and period of isoflavones' preventive effect on prostate cancer development," Kurahashi said.

Curecumin(TM) May Be An Effective Treatment For Prostate Cancer

20 Mar 2007

Bioponic Phytoceuticals, Inc. ("Bioponic" or "the Company") (OTC PK: BPYT) today announced that its Curecumin(TM) (a Bioresonant Phytotherapeutic(R) form of Turmeric containing curcumin), may be an important treatment for prostate cancer.

"Curcumin, a turmeric root extract, has been shown to possess activity in the treatment and prevention of cancer, multiple sclerosis, and Alzheimer's disease," according to a 3/7/2007 article posted on "The molecular mechanism for its anticancer effect is largely unknown, although it is thought to inhibit the synthesis of MDM2, an oncoprotein known to bind p53 and modulate p21 expression. In the March 1 issue of Cancer Research, Li and colleagues from the Comprehensive Cancer Center of the University of Alabama report on a study designed to elucidate the molecular anticancer effect of curcumin in a preclinical prostate cancer model." "Curcumin was found to decrease the mRNA and protein expression of the oncoprotein MDM2 and to enhance the expression of tumor modulator p21." "This well-performed study provides an elegant mechanistic explanation for the anticancer effect of curcumin."

It is estimated by the Prostate Cancer Foundation that "prostate cancer currently strikes an estimated one in six Americans. More than 218,000 men in the United States will be diagnosed with prostate cancer this year."

"We are particularly interested in the potential of our Curecumin(TM) product to provide a viable treatment strategy for those with prostate cancer. If proven effective, we may have an efficacious, cost effective, natural treatment for prostate cancer sufferers," said Steven M. Schorr, Chairman & CEO -Bioponic Phytoceuticals, Inc.

Bioponic Phytoceuticals is engaged in the development, production and distribution of Bioresonant Phytotherapeutic(TM) products for sale in the Complementary Alternative Medicine ("CAM") and natural products markets. The Company has developed several branded product lines in distribution (including the nationally recognized natural nasal spray: Flight Spray). Bioponic is focused on the production of natural products that are used to promote health and well-being.

All statements other than statements of historical fact included in this press release are "forward-looking statements" within the meaning of federal securities laws. Such forward-looking statements are subject to a number of risks and uncertainties, some of which are beyond the Company's control that could cause actual results or events to differ materially from current expectations.

Bioponic Phytoceuticals, Inc.

Relationship Between Body Mass Index And Prostate Cancer Screening In The United States

20 Mar 2007 In the last several years, the urological community a significant amount of interest has developed in the study of the association between body mass index and prostate cancer risk. Some studies have suggested that BMI holds no relationship with prostate cancer risk, while other more recent studies segregating patients based on Gleason score suggest otherwise. Patients with an elevated BMI seem to have a decreased risk of lower grade disease while exhibiting an increased risk for high grade disease. While some investigators have suggested that obese patients present with more advanced prostate cancer due to differences in screening behavior, this hypothesis has not been extensively studied.

In the February issue of the Journal of Urology, Scales, Moul and colleagues from Duke report the results of an epidemiological study of 57,827 men age 40 years or older who underwent prostate cancer screening. All patients formed part of the 2002 Behavioral Risk Factor Surveillance System, a telephone-based survey conducted by the Centers for Disease Control and Prevention. Respondent characteristics recorded included age, BMI, race, household income, marital status, overall health, number of physician visits, census region, and history of diabetes mellitus.

The mean age of the cohort was 55 years with 61% of patients being age 50 or older. Forty-eight percent of patients reported being overweight and 25% obese. Obese men were more likely than men with a normal BMI to ever have had a serum PSA test (62% vs. 56%, p < 0.001) or a test within the last year (44% vs. 38%, p < 0.001). Obese men also visited their physician more frequently than non-obese men (OR 2.88, 95% CI 2.57 to 3.22).

These data from a large epidemiological study showed that obese men undergo prostate cancer screening at a higher rate than non-obese men. This study suggests that the observed higher incidence of high grade disease in obese men may not be explained by different screening behavior alone and may be due to underlying differences in tumor biology.

New Data For Prolonging Hormonal Response In Locally Advanced And Metastatic Prostate Cancer

23 Mar 2007

Treating locally advanced or metastatic prostate cancer patients - who experience disease progression after first-line, castration-based therapy - with 'step-up' to Combined Androgen Blockade (CAB) therapy can substantially prolong the 'hormonal response'1. This is the key finding of new research presented recently at the European Association of Urology (EAU) meeting in Berlin, Germany.

Male hormones (also known as 'androgens', such as testosterone and its metabolite dihydrotestosterone) stimulate prostate cancer growth, so one of the most important goals in treating the disease is to reduce the amount of circulating hormone. There is currently no standard treatment for patients who experience disease progression after first-line hormonal therapy.

All patients in this new study were treated with first-line goserelin (ZOLADEX) monotherapy, administered using the ZOLADEX SafeSystem. Goserelin - a luteinising hormone-releasing hormone agonist (LHRHa) - works by reducing the level of the hormone testosterone in the body. After disease progression, patients received CAB 'step-up' treatment whereby they continued goserelin treatment but then boosted their androgen blockade by the addition of bicalutamide 50mg (CASODEX). Bicalutamide binds to receptors on tumour tissue and so prevents testosterone from binding and stimulating tumour growth.

Dr Heather Payne, Consultant in Clinical Oncology, University College Hospital, London, UK, who presented the study at EAU said: "These data tell us that CAB step-up therapy can reduce a patient's PSA* count and keep it down, even after first-line, standard, hormonal therapy starts to fail.

"This is important because it gives physicians another chance to prolong a patient's response to hormonal treatment and extend the time the treatment keeps working, which means we can stave off hormone-refractory disease for longer, a disease setting that is much harder to treat."

Dr Payne presented an on-going analysis from 122 patients with locally advanced or metastatic prostate cancer who were treated with first-line goserelin (ZOLADEX) monotherapy. Goserelin has proven survival benefits across a broad range of prostate cancer settings, including adjuvant neoadjuvant5 and monotherapy in locally advanced disease. After disease progression, all 122 patients received CAB 'step-up' treatment, by the addition of bicalutamide 50mg (CASODEX) to their existing goserelin treatment in order to boost their androgen blockade.

The retrospective analysis shows:

* One in three (30.3%) patients experienced a PSA response (defined as a PSA decrease >50% at first assessment, followed by a subsequent PSA decrease at the second assessment point); in the overall study population of 122 patients, three out of four (74.6%) experienced at least a partial PSA response.

* For the 30.3% of patients who had a PSA response, the median time to treatment failure in this group was 291 days; in the overall study population, the median time to treatment failure following CAB was 193 days.

CAB should be used more often & have clearer guidelines - international survey reveals At the same meeting, Dr Payne also co-authored new research8 that showed physicians are supportive of CAB treatment. Seventy-one percent of physicians who took part in an international survey felt that CAB should be used more often for treating patients with advanced prostate cancer8. The survey comprised the views and perceptions of 339 oncologists and urologists from 92 countries. While almost all survey respondents (95%) treating patients with advanced prostate cancer said they used CAB, less than half of them (47%) did so in more than 50% of their patients.

When exploring factors that could encourage increased CAB usage, 66% of physicians cited the need for clinical evidence. The survey explored physicians' views on current clinical guidelines for the management of advanced prostate cancer with CAB and showed that more than half of the respondents (52%) believe that the guidelines are too numerous, lack clarity or are outdated.

Dr Heather Payne commented: "While these survey findings show there is a good overall level of support for CAB, it seems very clear that the clinical community would welcome improved guidelines and greater clarity on the benefits of CAB, to ensure that patients with advanced prostate cancer have access to this treatment and the greatest chance for extending survival."

Pomegranate Juice May Be Good For The Prostate And Heart, Reports The Harvard Men's Health Watch

27 Mar 2007

Few American men have heard of the pomegranate, and fewer still have eaten this curious-looking fruit loaded with red seeds. But new scientific findings suggest that pomegranates may one day find a place in healthful diets, reports the April 2007 issue of Harvard Men's Health Watch.

Two recent studies suggest that pomegranate juice may help fight prostate cancer. In one study, scientists grew cells from highly aggressive cases of human prostate cancer in tissue cultures. Pomegranate fruit extracts slowed the growth of the cultured cancer cells and promoted cell death. The researchers then implanted the cancer cells in mice. A group of mice that received water laced with pomegranate juice developed significantly smaller tumors than the untreated animals. In a preliminary study of men with prostate cancer, pomegranate juice lengthened patients' PSA doubling time (the longer the doubling time, the slower the tumor is growing) from 15 months before treatment to 54 months on the juice.

Preliminary results in test tubes, animals, and humans suggest that pomegranates may also have beneficial effects on cardiovascular disease. Studies show that pomegranate juice can protect LDL (bad) cholesterol from oxidative damage. The juice has also been shown to slow the progression of plaques in mice with atherosclerosis. Results from two small clinical studies are even more intriguing, showing that carotid artery thickness decreased and cardiac blood flow improved in pomegranate juice drinkers. However, preliminary research also suggests that pomegranate juice may interact with certain medications, much like grapefruit juice does.

The bottom line: Early studies raise hopes that pomegranates may have potential benefits for prostate cancer and heart disease, but more research is needed to determine whether these hopes are justified.

Harvard Health Publications

Prostate Specific Antigen Velocity Threshold For Predicting Prostate Cancer In Young Men

26 Mar 2007 Traditionally, a prostate biopsy has been recommended for patients with a PSA velocity of 0.75 ng/ml per year due to its increased association with prostate cancer. The relationship between PSA velocity and prostate cancer in young men has not been extensively studied.

In the March issue of the Journal of Urology, Loeb and colleagues from Georgetown, Northwestern, and Washington University report the results of a cohort of 6,844 men age 60 years or younger who enrolled in a prospective prostate cancer screening study. The overall prostate cancer detection rate for the cohort was 5%. Various thresholds of PSA velocity were evaluated to determine the highest predictive value for prostate cancer.

A PSA velocity threshold of 0.4 ng/ml per year or greater was independently predictive of cancer irrespective of age, total PSA, family history of prostate cancer, or race. What was most dramatic was that this criterion had the strongest association to cancer in multivariate analysis, even in patients with a total PSA less than 2.5 ng/ml. Using a PSA velocity threshold of 0.4 ng/ml/year was found to have a sensitivity of 67%, specificity of 81%, positive predictive value of 16%, and negative predictive value of 98%.

This study suggests that using a PSA velocity biopsy threshold of 0.75 ng/ml/year for men younger than 60 years may be inappropriate. Using a PSA velocity of 0.4 ng/ml/year or greater may enhance prostate cancer early detection especially in men with a total PSA lower than 2.5 ng/ml.

Age Adjusted Prostate Specific Antigen And Prostate Specific Antigen Velocity Cut Points In Prostate Cancer Screening

26 Mar 2007 Traditional recommendations for prostate biopsy have included a total serum PSA of 4.0 ng/ml or greater and a PSA velocity of 0.75 ng/ml per year or greater. While recent trends have moved towards a PSA threshold of 2.5 ng/ml or greater in men younger than 65 years, specific recommendations for PSA velocity thresholds in younger men have not been agreed upon.

In the February issue of the Journal of Urology, Moul, Albala, and colleagues from Duke University report the results of a cohort of 33,643 men who formed part of a prostate serum PSA values over a 2 year period. Total PSA and PSA velocity threshold values with the highest sensitivity and specificity for prostate cancer detection were identified for men 50 to 59 years old.

In men cancer early detection study. Of these men, 11,861 patients were identified with 2 or more age 50 to 59 years, a serum PSA threshold for biopsy of 2.0 ng/ml or greater achieved the highest sensitivity (84%) when compared to thresholds of 2.5 ng/ml, 3.0 ng/ml, and 3.5 ng/ml with sensitivities of 82%, 79%, and 77%, respectively. The specificity of a PSA threshold of 2.0 ng/ml in these men was acceptable at 74.4%, which was not significantly different from the specificity of using a threshold of 2.5 ng/ml (80%).

Using a PSAv of 0.4 ng/ml/year in men age 50 to 59 years achieved a specificity of 84% and sensitivity of 72%, compared with a PSA threshold of 0.75 ng/ml with sensitivity and specificity of 70% and 84%, respectively.

These data from a large cohort of patients suggests that lowering the PSA threshold for biopsy in younger men is associated with an increase in sensitivity without compromising specificity significantly.

In the accompanying editorial, Ankerst and Thompson note that these data are not consistent with the results of the PCPT, which found a significantly lower rate of prostate cancer detection in this age group of patients. They explain these differences invoking verification bias, since a disproportionate number of men in the Moul study who underwent biopsy were included in the study and were referred with a serum PSA of 4.0 ng/ml or greater. In the PCPT, all men were biopsied regardless of their serum PSA. While the editorial comment is statistically correct, the Moul study is clinically relevant because its cohort was constituted by the "typical patient" who visits an early detection clinic.

The Effect Of Androgen Deprivation Therapy On Periodontal Disease In Men With Prostate Cancer

26 Mar 2007 Well recognized potential side effects of androgen deprivation therapy include anemia, decreased libido, the metabolic syndrome, memory loss, weight gain, hot flashes, and osteoporosis. Since periodontal disease results in absorption of alveolar bone, some have suggested that generalized bone mineral loss may exacerbate periodontal disease. The relationship between androgen deprivation therapy and periodontal disease has not been studied.

In the March issue of the Journal of Urology, Famili and colleagues from the University of Pittsburg compared the incidence of periodontal disease in men with prostate cancer treated with or without androgen deprivation therapy.

A total of 81 men with prostate cancer and a mean age of 68.5 years enrolled in the study. Sixty-eight men with prostate cancer underwent periodontal examinations, including 27 men not receiving androgen deprivation (non-ADT) and 41 men on androgen deprivation therapy (ADT). There was no difference between groups with regards to race, history of smoking, previous dental visits, missing teeth, denture use, dental hygiene, or previous periodontal disease. Of these 68 men, 81% of men receiving androgen deprivation therapy were found to have periodontal disease, compared with 3.8% in the non-ADT group (Hazard ratio = 3.33, 95% CI 1.07 to 10.3, p < 0.038). This three-fold increase in periodontal disease was significant even after adjusting for race, history of smoking, or previous periodontal treatment. Interestingly, bone mineral density was not statistically significantly different between the ADT and non-ADT groups.

This study with a small sample size is the first to suggest that men with prostate cancer receiving androgen deprivation therapy exhibit a three-fold higher risk of periodontal disease compared with controls. While the authors suggest that alveolar bone osteoporosis may account for this effect, no differences were found in bone mineral density between groups. These data should be confirmed in a larger cohort of patients to further clarify its etiology and potentially identify measures of prevention for patients embarking on androgen deprivation therapy.

Long-Term Prostate Cancer Control Using Palladium-103 Brachytherapy And External Beam Radiotherapy In Patients With A High Likelihood Of Cancer

26 Mar 2007 Brachytherapy is recommended for low risk prostate cancer (CaP). For intermediate and high risk patients, some have advocated combining brachytherapy with external beam radiotherapy (EBRT). In Urology, Dr. Dattoli and colleagues report their long term CaP outcomes using brachytherapy and EBRT in 243 patients.

The patients were staged with clinical T2 and T3 CaP and received palladium-103 plus supplemental EBRT from 1992 to 1996. Of the patient cohort, 243 had at least one higher risk feature; Gleason >7 in 192, PSA >10ng/ml in 166 and PAP level greater than 2.5U in 66 patients. Of the 243 participants, 135 had all three high-risk features. Staging pelvic lymphadenectomy and post-procedure biopsies were not performed. ERBT consisted of 41Gy to a limited pelvic field followed one month later by a Pd-103 boost. The minimal Pd-103 dose was 80-90 Gy. A median Pd-103 dose of 102mCi was implanted. Neoadjuvant or adjunctive androgen deprivation was given to 103 men, but not for longer than 6 months. Freedom from biochemical failure was defined as a serum PSA <0.2ng/ml. The median follow up period for all patients was 9 years.

A total of 41 men developed biochemical recurrence, and the overall actuarial freedom from biochemical progression rate at 13 years was 81%, with 198 men followed longer than 5 years. For the 93 patients with a Gleason score of 7 or greater or a PSA level of 10ng/ml or more, the overall freedom from biochemical failure was 72% at 10 years. Of those 41 patients experiencing biochemical failure, 27 (66%) developed failure within the first 3 years of treatment. Those patients with biochemical failure had follow-up prostate biopsies performed and no local failures were documented. Neoadjuvant and adjunctive androgen deprivation did not affect the failure rate in the 103 men who received it. The overall 5- and 10-year survival rate was 93% and 70%, respectively. Cancer-specific survival rates at 5- and 10-years were 97% and 84%, respectively. These data suggest good long-term local control in a cohort of men at risk for locally advanced disease.

More Reliable Blood Test For Prostate Cancer Shows Promise

27 Apr 2007

US scientists are hopeful that a blood test for a newly discovered protein will vastly increase the reliability of screening for prostate cancer. The protein is called early prostate cancer antigen-2 (EPCA-2).

The study is published in Urology and was led by Robert H Getzenberg, professor of urology and director of research at the James Buchanan Brady Urological Institute at The Johns Hopkins University School of Medicine in Baltimore, Maryland.

Prostate cancer is the most common cancer in American men. According to the American Cancer Society, over 200,00 new cases of the disease will be found in the US in 2007, and over 27,000 men will die from it.

The current blood test for prostate cancer looks for another blood protein called prostate-specific antigen (PSA). If PSA is above a certain level (2.5 nanograms per milliliter), men are referred for biopsy to verify presence of cancerous cells.

However, there are three problems with the PSA based test:

(1) It has a high level of false positives: most of the biopsies come back normal. According to Prof Getzenberg, 80 per cent of the 1.6 million men referred for prostate biopsy in the US every year return negative results.
(2) It has a high level of false negatives as well: it fails to find prostate cancers that have a low level of PSA. Prof Getzenberg suggests that 15 per cent of men with prostate cancer go undetected because their PSA level is below the cutoff.
(3) It can't tell if the cancer has spread to other parts of the body.

The researchers reckon their new test will improve prostate cancer screening and testing on all three counts.

Prof Getzenberg said in a prepared statement:

"A blood test based on EPCA-2 may greatly improve our ability to accurately detect prostate cancer early and minimize the number of false positives, therefore lowering the number of unnecessary biopsies."

"This is the first time we have a test that effectively distinguishes between men with cancer confined to the prostate and those whose disease has spread outside of the gland," he added.

The researchers tested the blood of 330 Hopkins patients for EPCA-2 levels. The patients were grouped as:

-- Men with normal PSA who had prostate cancer.
-- Men with normal PSA who did not have prostate cancer.
-- Men with elevated PSA but negative biopsies.
-- Men with a noncancerous prostate condition called benign prostatic hypertrophy (BPH) who did not have biopsies.
-- Men with prostate cancer that had not spread.
-- Men with prostate cancer that had spread elsewhere.
-- Patients with benign conditions of other organs.
-- Patients with other types of cancer.

They used a cut off level of 30 nanograms of EPCA-2 per milliliter. They settled on this level after doing a pilot study of 30 blood samples.

The results showed that:

-- The EPCA-2 test detected 97 per cent of the patients who did not have prostate cancer.
-- Men with no evidence of the disease (regardless of their PSA level) had EPCA-2 levels below the cutoff.
-- Patients with other types of cancer and benign conditions also had EPCA-2 levels below the cutoff.
-- The EPCA-2 test detected 94 per cent of the men with prostate cancer.
-- 90 percent of the men with organ-confined prostate cancer had EPCA-2 levels at or above the cutoff.
-- 98 percent of the men with disease outside the prostate also had EPCA-2 levels at or above the cutoff.

The results also showed that 77 per cent of the patients with BPH had EPCA-2 levels below the cutoff, which the researchers say is within the likely percentage rage of BPH patients who do not have prostate cancer. This is a particularly encouraging result, they said, because patients with BPH often have elevated PSA which results in misdiagnosis and unnecessary biopsies.

Also, the EPCA-2 levels for prostate cancers that had spread were significantly higher than for those that had not. The test was dramatically better at separating these groups, the researchers found.

Prof Getzenberg said:

"This is important, since cancer that has spread outside the prostate is more deadly, which makes it even more crucial to have a tool that detects it early."

The researchers concluded that:

"The results of our study have shown that EPCA-2 is a novel biomarker associated with prostate cancer that has high sensitivity and specificity and accurately differentiates between men with organ-confined and non-organ-confined disease."

Larger clinical trials for EPCA-2 are currently being planned, and the scientists hope this could make the test available to the public in approximately 18 months.

The study was funded by the National Cancer Institute of the National Institutes of Health, and Onconome Inc, a company that employs Prof Getzenberg as a consultant. Prof Getzenberg will also receive royalties from the product.

Biopsy May Underestimate Prostate Cancer In Obese And Overweight Men

31 Mar 2007

Obese and overweight men who are diagnosed with prostate cancer by biopsy are more likely than healthy weight men to actually have a more aggressive case of the disease than the biopsy results would indicate, according to a study led by a Duke University Medical Center researcher.

The finding suggests that misleading biopsy results may be causing many obese and overweight men to receive inadequate or inappropriate treatment that is not aggressive enough to combat the true nature of their disease, said study leader Stephen Freedland, M.D., an assistant professor in the Division of Urology and the Duke Prostate Center.

"We already know that it's more difficult to diagnose prostate cancer in obese men because they have lower levels of prostate-specific antigen, or PSA, a common blood marker for prostate cancer, and because their larger-sized prostates make it more likely for a biopsy to miss the cancer," he said. "These findings further suggest that we could be missing even more high-grade disease among obese men."

Gaining a better understanding of links between biopsies and prostate cancer also may help physicians improve patient treatment, said Freedland, who also holds an appointment in surgery at the Durham Veterans Affairs Medical Center.

"If we can determine through additional biopsies that an obese or overweight man has more aggressive prostate cancer, we can discuss whether the cancer should be treated with more than one approach, such as combining hormonal therapy with radiation, to reduce the risk of the cancer spreading and improve the chances of cure," Freedland said. "We must also keep in mind that even if a well-done biopsy shows low-grade cancer in an obese patient, there is still a reasonable likelihood that the patient may have high-grade disease."

The researchers, from six universities, published the findings in the March 2007 issue of the journal Urology.

The study was funded by the Department of Veterans Affairs, the National Institutes of Health, the Georgia Cancer Coalition and the American Urological Association Foundation.

Prostate cancer is the second most common cancer, following skin cancer, in men in the United States, and a man has a one-in-six chance of being diagnosed with prostate cancer at some point during his life, according to the Prostate Cancer Foundation. Obese men diagnosed with the disease are 20 percent more likely to die from it than men of healthy weight.

Doctors typically conduct a biopsy when cancer is indicated by screening tests, such as a blood test for PSA, or by an irregular finding on a digital rectal exam. To perform a biopsy, a physician inserts a needle into the prostate and removes tissue for analysis.

In the study, the researchers analyzed data on more than 1,100 men who underwent surgery between 1996 and 2005 to remove the prostate gland, a common treatment for prostate cancer. They compared the aggressiveness of each patient's cancer as suggested by examination of samples obtained during diagnostic biopsy with the actual aggressiveness of disease found by microscopic examination of the diseased prostate tissue removed at the time of surgery.

Obese men were 89 percent more likely than healthy weight men to have a more aggressive form of prostate cancer than was indicated by biopsy, Freedland said. Men with a body mass index (BMI) greater than 30 are considered obese. BMI is a measurement of weight adjusted for height. On this scale, a five-foot, 11-inch man weighing more than 215 pounds would be obese.

The researchers also found that men who were overweight but not obese were 44 percent more likely to have aggressive cancers than suggested by biopsy. Men with a body mass index between 25 and 29.9 are considered overweight; a five-foot, 11-inch man weighting more than 180 pounds would be overweight.

Freedland said the reasons for the discrepancies are unclear, but could be related to the fact that obese and overweight men have larger-sized prostates, which could mean that the usual number of samples taken during a biopsy is insufficient to reveal the gland's actual status.

To help reduce the number of obese men whose prostate cancers are incorrectly classified, doctors should conduct biopsies on more areas of the prostate gland, Freedland said.

"Performing more biopsy samples will help determine the true aggressiveness of the prostate cancer and will allow treatment to be better tailored to the patients' needs," he said

Fungal Compound To Combat Prostate Cancer?

09 Apr 2007

Can a substance from a fungus that grows on decaying trees provide a cure for aggressive prostate cancer? This is the hope of researchers at Lund University in Sweden. In an interdisciplinary collaborative effort involving urologists, molecular biologists and chemists in Malm? and Lund, scientists are trying to develop this compound into a means for combating certain forms of prostate cancer.

In 2006 in Europe, an estimated 345,900 prostate cancer cases were diagnosed. In Sweden with nearly 10,000 new cases of prostate cancer per year, this is the most common form of cancer among men in Sweden. The disease often develops slowly, but the proportion of more aggressive forms of prostate cancer is growing. The fungal compound galiellalactone could be used against tumors that cannot be treated with surgery or radiation and does not respond to hormone treatment.

"In our trials this compound has curbed the growth of prostate cancer cells both in animal experiments and in laboratory experiments," says the researcher Rebecka Hellsten. The research team she belongs to was recently granted SEK 1.3 million from the Holger K. Christiansen Foundation in Denmark. The team consists of Dr. Rebecka Hellsten and Professor Anders Bjartell from the Section for Urological Cancer Research at the University Hospital in Malm? and Professor Olov Sterner and Dr. Martin Johansson from the Section for Organic Chemistry at Lund University.

Olov Sterner and his associates do research on organic molecules from plants, fungi, and marine organisms, and how they can be used in the development of drugs or industrially useful substances. They have developed a synthetic method for producing the fungal compound and will now attempt to tweak the substance to make it even more effective against tumor cells.

The mushroom the substance originates from is called Galiella rufa, which grows in clusters on old wood in eastern North America. The fungi are bowl-shaped, dark on the outside, reddish yellow on the inside, and a few centimeters across. It was discovered that this particular mushroom can be used to fight prostate cancer in connection with a study run by a German research team, when they were testing extracts from various species of fungi to find substances that could disrupt a certain signaling pathway in human cells.

"The German scientists were not thinking about prostate cancer, but the signaling pathway the study targeted is also relevant to these particular tumor cells. If we can alter the fungal substance synthetically so it impacts the signaling in tumor cells even more effectively, we could have a drug for tumors that we can't deal with today," says Rebecka Hellsten.

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