Key Event In Prostate Cancer Progression Discovered

ScienceDaily (July 28, 2009) — A study led by researchers at the Ohio State University Comprehensive Cancer Center and Dana-Farber Cancer Institute reveals how late-stage, hormone-independent prostate tumors gain the ability to grow without need of hormones.

The onset of hormone-independent growth marks an advanced and currently incurable stage of prostate cancer.

The study, published in the July 24, 2009, issue of the journal Cell, focuses on androgen receptors, molecules located in the nucleus of cells of the prostate gland and other tissues. Male sex hormones – androgens – bind with these receptors to activate genes that control cell growth.

The researchers show that in androgen-independent prostate cancer, androgen receptors are reprogrammed to regulate a group of genes involved in a different, later, phase of cell division, triggering rapid cell growth. They further show that a modification of a chief component of the chromosome is responsible for this reprogramming.

"Some late-phase prostate cancer does not require androgen hormones for tumor growth, but it does require androgen receptors," says first author and co-corresponding author Qianben Wang, assistant professor of molecular and cellular biochemistry and a researcher with the Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute.

"Our study reveals the role of androgen receptors in hormone independent prostate cancer, how they become active in that disease and what genes they regulate to promote tumor growth."

The findings provide a better understanding of prostate cancer and could identify new therapeutic targets and lead to new treatments for this lethal stage of the disease, he says.

Prostate cancer is the most frequently diagnosed cancer in men. An estimated 192,280 new cases are expected in the United States in 2009, along with 27,360 deaths from the disease.

To conduct the study, Wang working with corresponding author Dr. Myles Brown, professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, and a group of colleagues used hormone-dependent and hormone independent prostate cancer cell lines, gene expression data and tissue from human tumors.

They showed that in hormone-dependent disease, androgen receptors regulate an early phase of cell cycle. In hormone-independent prostate cancer, however, the receptors are reprogrammed to selectively regulate genes involved in actual cell division, that is, the mitotic phase of the cycle.

A gene called UBE2C was a standout among these genes, and increased expression of that gene correlated with progression to the hormone-independent phase.

Furthermore, a chemical change – an epigenetic change – in a histone protein associated with that gene enabled androgen receptors to bind with and activate the gene in hormone-independent prostate cancer.

Finally, they show that over-expression of this gene is necessary for the growth of the hormone-independent prostate cancer cells.

"Interestingly," Wang says, "the UBE2C gene is also over-expressed in breast, lung, ovary, bladder, thyroid and esophageal cancers, suggesting that our findings could have wide application."

Funding from the National Cancer Institute and Department of Defense supported this research.

Adapted from materials provided by Ohio State University Medical Center, via EurekAlert!, a service of AAAS.

Longer Hormone Treatment May Improve Prostate Cancer Outlook

European and U.S. studies find similar results


WEDNESDAY, June 10 (HealthDay News) -- Men with moderately advanced prostate cancer who get hormone-blocking drugs after radiation therapy do better when the drug treatment is continued for two or more years after an initial six-month regimen, a European study has found.

The results pretty much mirror those of a similar American trial reported in May, said Dr. Eric M. Horwitz, acting chairman of radiation oncology at Fox Chase Cancer Center in Philadelphia, who led the group that did the U.S. study.

"We have long believed that longer-term hormone therapy is the standard of care," Horwitz said. "These studies support that belief."

The results apply to men whose cancer shows signs of growth but has not spread beyond the prostate gland -- perhaps a quarter of all cases of prostate cancer, Horwitz said.

Earlier studies in the United States and Europe established the value of radiation therapy followed by six months of hormone-blocking treatment in such cases, he said. The new studies were designed to determine whether continuation of drug therapy that blocks the cancer-promoting activity of the male hormone testosterone could improve those results.

Though the studies differed in size and length, their results were similar in most respects.

The European trial, reported in the New England Journal of Medicine, included 970 men who were assigned to radiation therapy followed by either six months or three years of hormone-suppressing treatment. The five-year death rate of men in the longer-treatment group was 15.2 percent, compared with 19 percent for those in the shorter-term treatment group.

The U.S. study, published in the Journal of Clinical Oncology, included 1,554 men who were followed for 10 years. The study found no significant difference in overall survival -- 51.6 percent for the short-term group, given four months of treatment, and 53.9 percent for the long-term group, treated for two years.

But it did find a difference among men who were alive and cancer-free after 10 years. The disease-free survival rate for the short-term group was 13.2 percent, compared with 22.5 percent for those treated longer.

Other measures, such as the spread of cancer to other parts of the body and greater growth of the malignancy within the prostate gland, were consistently better for men in the U.S. study who'd had the longer-term therapy.

Horwitz said that differences between the American and European results were not unexpected. Similar differences had been found in the studies that established the value of the radiation-plus-hormone therapy, he said. One possible explanation, he said, is that prostate cancers tend to be diagnosed at an earlier stage in the United States because of extensive screening programs.

Both studies reported the expected side effects of hormone-blocking therapy, including hot flashes, weight gain, osteoporosis and loss of sexual function.

"Some men get them and some do not," Horwitz said. "Over the last few years, there has been a lot of attention paid to these side effects, in the medical literature and in public awareness, and there has been more reluctance to use this therapy. These studies clearly identify a group of men who benefit from this therapy."

But Dr. Peter C. Albertsen, chairman of urology at the University of Connecticut Health Center, said that it's those side effects that should limit the use of longer hormone-blocking therapy to a specific group of men with prostate cancer -- those with "disease that is clinically evident on palpation [by touching] but with no evidence that it has spread outside the prostate," Albertsen wrote in an accompanying editorial in the journal.

He agreed that earlier forms of the cancer are more often detected in the United States than in Europe because of extensive screening programs. The side effects that balance the benefits of hormone-blocking therapy rule against extended therapy for those men, Albertsen said.

"For men with localized disease that is screening-detected, the equation is quite different," he said.

More information:

The U.S. National Cancer Institute has more on prostate cancer.

New Approach For Treating Recurrent Prostate Cancer On The Horizon

ScienceDaily (June 15, 2009) — A new study shows that an alpha-particle emitting radiopeptide—radioactive material bound to a synthetic peptide, a component of protein—is effective for treating prostate cancer in mice, according to researchers at SNM's 56th Annual Meeting in Toronto. The results could eventually result in a significant breakthrough in prostate cancer treatment, especially for patients whose cancer recurs after the prostate is removed.

"Our study shows that this novel form of treatment has the potential to target and destroy cancer cells with minimal damage to surrounding healthy tissue," said Damian Wild, University Hospital Basel, Basel, Switzerland, lead author of the study. "Eventually, this therapy could give hope to some of the hardest-to-treat prostate cancer patients and also could be applied to other types of cancer."

Every year, more than 186,000 men in the United States are newly diagnosed with prostate cancer. The most common types of treatment include surgical removal of some, or all, of the prostate, followed by radiation therapy. More than 30,000 men each year who have had their prostates removed experience recurrence of the cancer. In most of these cases, the disease cannot be localized and treated adequately with conventional treatments; therefore, a systemic treatment that efficiently kills small tumors is needed.

Because tumor cells readily bind with certain peptides, researchers have been able to develop highly specific radiopeptides that bind with tumor cells and treat them using specific therapeutic radioactive substances attached to the radiopeptide. Prostate cancer cells—and many other types of cancer cells—have an overabundance of gastrin-releasing peptide receptors, making the cancer a strong candidate for treatment with radiopeptides.

The study compared two different types of radiopeptides. One group of mice was injected with 213 Bi-DOTA-PESIN, which emits alpha particles that are effective at killing cancer cells. The other group was injected with beta-emitting 177 Lu-DOTA-PESIN, which are also effective in tumor cell-killing, but can also cause damage to nearby healthy cells. Alpha particles are able to kill cancer cells without damaging surrounding healthy tissue. A third group of mice received no treatment.

However, at the maximum tolerated dose, the alpha-emitting 213 Bi-DOTA PESIN was significantly more effective, tripling the survival rate of the mice that received the therapy. The results indicate that the alpha-emitting radiopeptide could provide a new approach for treating prostate cancer and eventually other types of cancer.


Adapted from materials provided by Society of Nuclear Medicine.

Dramatic Outcomes In Prostate Cancer Study

ScienceDaily (June 19, 2009) — Two Mayo Clinic patients whose prostate cancer had been considered inoperable are now cancer free thanks in part to an experimental drug therapy that was used in combination with standardized hormone treatment and radiation therapy. The men were participating in a clinical trial of an immunotherapeutic agent called MDX-010 or ipilimumab.

In these two cases, physicians say the approach initiated the death of a majority of cancer cells and caused the tumors to shrink dramatically, allowing surgery. In both cases, the aggressive tumors had grown well beyond the prostate into the abdominal areas.

"The goal of the study was to see if we could modestly improve upon current treatments for advanced prostate cancer," says Eugene Kwon, M.D., Mayo Clinic urologist and leader of the clinical trial. "The candidates for this study were people who didn't have a lot of other options. However, we were startled to see responses that far exceeded any of our expectations."

The patients first received a type of hormone therapy called androgen ablation, which removes testosterone and usually causes some initial reduction in tumor size. Researchers then introduced a single dose of ipilimumab, an antibody, which builds on the anti-tumor action of the hormone and causes a much larger immune response, resulting in massive death of the tumor cells.

Both men experienced consistent drops in their prostate specific antigen (PSA) counts over the following weeks until both were deemed eligible for surgery. Then, during surgery, came a greater surprise.

"The tumors had shrunk dramatically," says Michael Blute, M.D., Mayo urologist, co-investigator and surgeon, who operated on both men. "I had never seen anything like this before. I had a hard time finding the cancer. At one point the pathologist (who was working during surgery) asked if we were sending him samples from the same patient."

One patient underwent radiation therapy after surgery; both have resumed their regular lives. Further research is being planned to understand more about the mechanisms of the antibody and how best to use the approach in practice. The researchers, however, note the significance of their findings.

"This is one of the holy grails of prostate cancer research," says Dr. Kwon. "We've been looking for this for years."

The research was supported by the Department of Defense, The Richard M. Schulze Family Foundation, the Mayo Clinic Cancer Center and the Mayo Clinic Center for Translational Science Activities. Medarex, Inc. provided the study drug free of charge and supported safety monitoring during the protocol.

Source: Mayo Clinic (2009, June 19). Dramatic Outcomes In Prostate Cancer Study.

Hormone Therapy May Confer More Aggressive Properties To Prostate Tumors

ScienceDaily (June 10, 2009) — Hormone therapy is often given to patients with advanced prostate cancer. While it is true that the treatment prevents growth of the tumour, it also changes its properties. Some of these changes may result in the tumour becoming more aggressive and more liable to form metastases.

This is one of the conclusion of a thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden.

Hormone therapy has serious side effects and is therefore used only when the tumour has grown too large to be treated in any other way, or when the tumour has spread and formed metastases. The hormone that is given causes the natural production of male sex hormone to fall, and the tumour stops growing. Pain also usually decreases.

"Our results suggest that the tumour properties change following hormone therapy such that the tumours at a later stage can continue to grow and spread in the body. For this reason, it is probably necessary to supplement the hormone therapy in order to compensate for these changes", says pharmacist Karin Jennbacken, author of the thesis.

The results show that patients who have been given hormone therapy have higher levels of the proteins that enable the cancer cells to move through the body and attach to other organs. One of these proteins is known as "N-cadherin", and this protein is present in higher levels in patients who have been given hormone therapy.

"We don't have any good treatment alternatives in cases where the tumour returns after hormone therapy, and this means that it is particularly important to study how such tumours are controlled and how they behave. The properties that we have identified may become targets for new anti-metastatic drugs in advanced prostate cancer", says Karin Jennbacken.


Prostate Cancer

Approximately 9,000 new cases of prostate cancer are diagnosed each year in Sweden, making it the most common of all cancer forms. Many of the tumours grow very slowly and give no symptoms, but prostate cancer can also display a more aggressive course, spreading metastases to lymph nodes, the skeleton and other locations. The complete prostate is often surgically removed if the cancer is diagnosed early. Other treatments available are radiation therapy and hormone therapy.

Title of the thesis: Invasive and metastatic properties of advanced prostate cancer.

Adapted from materials provided by University of Gothenburg.

From Prostate Imaging to Prostate Cancer Imaging

DENVER—Magnetic resonance imaging (MRI) is customarily used for prostate imaging. However, by modifying a chemotherapy drug with a radioactive component, scientists should be able to image prostate cancer specifically while simultaneously providing therapy for the disease.

John P. Michael Sedelaar, PhD, MD, a postdoctoral research fellow at Johns Hopkins University, presented these findings at the American Association for Cancer Research 100th Annual Meeting 2009, noting that “By adding a radioactive imaging probe in these compounds, we can combine therapeutics with diagnostic imaging.”

The study, conducted in mice, employed the drug thapsigargin, a nonspecific, highly cytotoxic agent. The researchers added a tyrosine ring to this agent for the coupling of imaging probes. Once in the body, this prodrug is made active by proteins—either prostate-specific membrane antigen (PSMA) or prostate-specific antigen (PSA)—which are more prominently present in prostate cancer, and even more prevalent in highgrade prostate cancer and metastasis.

“This inactivated compound has an amino acid tail specifically chosen so that it can only be ‘clipped' by PSA or PSMA,” Dr Sedelaar explained in an interview with Oncology Nursing News. “When this tail is clipped off, the chemical compound is released and activated and can be taken up into the cell and be therapeutically active.”

“It's like a smart bomb, to use a military analogy,” he continued. “By retooling chemotherapy agents, we may be able to get more accurate treatment monitoring and follow-up.”

Unlike other targeted therapies, this treatment is based upon the general principles of prostate cancer, not the individual patient's genetic makeup. “These smart bombs we're developing are not `tailor-made,'” noted Dr Sedelaar; rather, they are based on “the fact that prostate cancers have elevated amounts of PSA and PSMA.”

The need for targeted approaches to prostate cancer is essential, according to Dr Sedelaar. “An increasing number of patients have minimal prostate cancer, and opt for either very focused treatment or the watchful waiting approach,” he noted. “In this environment, the need for an accurate imaging tool is paramount.”

In terms of the study results, singlephoton emission computed tomography imaging of the tumor-bearing mice showed uptake by tumors together with uptake by thyroid, liver, and spleen. The PSMA imaging drug was also detectable in the kidneys and bladder. No toxicity was noted; and even more importantly, there was a measurable reduction in prostate cancer cells.

When asked whether this approach might be transferable to other cancers and other drugs, Dr Sedelaar would say only that “there could be possibilities to retool the compounds for other chemotherapeutic agents, but we haven't reached that stage yet.”

Dr Sedelaar told Oncology Nursing News that a small multicenter trial of these PSMA therapies will start this year, but in terms of the imaging compounds, “We're still in the animal experiments. The compounds are not yet as specific as we want them to be.” He could provide no details about future human trials.

ASCO: Gene Test Predicts Prostate Cancer

ORLANDO, June 2 -- A set of six genes, measured in a blood test, can be used to tell whether a man has prostate cancer, a researcher said here.

In a case-control study, the six-gene panel outperformed a standard test -- age-adjusted prostate specific antigen -- in distinguishing between men with cancer and those without, according to Robert Ross, M.D., of Dana-Farber Cancer Institute in Boston.

When prostate specific antigen (PSA) levels were added to the group of genes, the performance of the test improved even more, Dr. Ross told attendees at the annual meeting of the American Society of Clinical Oncology.

The gold standard for diagnosing prostate cancer is a biopsy, he said, but 60% of biopsies in men thought to be at risk for the disease turn out to be negative.

The goal of this test is to avoid the "pain, discomfort, and anxiety" associated with biopsies, Dr. Ross said, by winnowing out the 60% of men who don't need the procedure.

Dr. Ross and his colleagues started with a set of 392 genes associated with inflammation, cancer, and the epidermal growth factor receptor, as well as some identified in other genetic studies of cancer.

In a training set of 76 healthy men and 76 with prostate cancer, six genes were significantly associated with disease. Of the six, five are less active in those with the disease and one has greater activity, the researchers found.

The finding was validated in a second cohort of 128 men with cancer and 94 without, he said.

In the second group, the six-gene test correctly detected 85.9% of the men with disease, compared with 69.5% detected by age-adjusted PSA, Dr. Ross said.

The six-gene test had a specificity of 83%, compared with 93.6% for PSA, he said.

When the researchers did both the six-gene test and measured PSA levels, the sensitivity and specificity improved -- to 87.5% and 92.6%, respectively.

The results are a "significant improvement" over the predictive value of PSA alone, Dr. Ross said.

"From a clinical hypothesis standpoint, this is great data," Dr. Ross said. But, he cautioned, "this is a case-control study (and) you'd like to see it validated prospectively."

He said his institution and several others are collaborating on a 1,000-patient prospective study -- dubbed PRECISE -- among men who meet the criteria for a biopsy, but have not yet had the test.

The goal will be to see if the test can predict the results of biopsy, he said.

Although the test is still in development, it will not be expensive, especially compared with the $2,000 it costs for a biopsy, said Karl Wassman, of Source MDx, the Boulder, Colo. company that has developed the test.

He said the blood test can be read by standard equipment, using a kit of primers and probes developed by Source MDx, so that the cost will be in the range of "a couple of hundred" dollars.

The various forms of PSA testing are "extremely valuable" in screening for prostate cancer, said Howard Sandler, M.D., of Cedars-Sinai Medical Center in Los Angeles, who was not involved in the study.
But the jury is out on whether screening and early detection have any benefit for patients, he said.

"If screening is beneficial, then better screening is important," he said, but there's no high-quality evidence that early detection is useful.

Dr. Sandler said the "weakness of this test" is that it doesn't answer the most important question about prostate cancer.

"The question is do you have clinically relevant prostate cancer or not?" he said. "Do you have potentially lethal cancer or do you have the cancer that will never kill you?"

Dr. Ross agreed that that question is important and said he and his colleagues have preliminary data that suggests it may be possible to use such a test to distinguish between types of cancer.

The study was supported by Source MDx, Dana Farber and the Harvard Cancer Center, the Gelb Center, and the Bing Sound Wong Fund.
Several researchers reported financial links with Source MDx.

Dr. Sandler reported financial links with sanofi-aventis, Genentech, Amgen, and AstraZeneca.

Primary source: Journal of Clinical Oncology
Source reference:
Ross RW, et al "Sensitivity and specificity of a whole-blood RNA transcript-based diagnostic test for the diagnosis of prostate cancer (CaP) compared with prostate-specific antigen (PSA) alone" J Clin Oncol 2009; 27(15S): Abstract 5052.

New Blood Test Greatly Reduces False-positives In Prostate Cancer Screening

ScienceDaily (May 28, 2009) — A new blood test used in combination with a conventional prostate-specific antigen (PSA) screening sharply increases the accuracy of prostate cancer diagnosis, and could eliminate tens of thousands of unneeded, painful, and costly prostate biopsies annually, according to a study led by researchers at Dana-Farber Cancer Institute.

At the annual meeting of the American Society of Clinical Oncology in Orlando, Fla., William K. Oh, M.D., and Robert W. Ross, M.D., will report that the six-gene molecular diagnostic test, when combined with a PSA test, accurately detected prostate cancer more than 90 percent of the time. Earlier studies suggest that the conventional PSA test is 60-70 percent accurate in detecting cancer. The findings will be discussed at a poster session on May 31.

Men who are found to have elevated levels of PSA in routine screening tests are often referred for a biopsy of the gland to check for tumors. Nearly two-thirds of biopsies performed -- a painful procedure with some risk of complications -- do not find any cancerous cells. This high rate of "false positive" PSA test results underscores the need for a more accurate method for detecting prostate cancer, said Oh, who is the clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber.

The two-year study involved 484 participants. The group comprised 204 men with known prostate cancer, 110 men with benign prostatic hypertrophy (BPH), and 170 healthy men in a control group. (BPH can elevate PSA levels in the blood, which often leads to a biopsy to rule out prostate cancer.) These groups were split into age-matched training and validation sets.

The researchers sought to measure the accuracy of a six-gene whole blood RNA transcript-based diagnostic test developed by Source MDx in Boulder, Colo., both in terms of its sensitivity (the ability to detect prostate cancer) and specificity (the ability to identify people who don't have prostate cancer).

Source MDx researchers developed the test after initially working with a set of 174 candidate genes whose activity was compared in the different study groups. They narrowed the pool down to just six genes that, as a group, were highly sensitive in predicting which patients had prostate cancer and which were normal.

The study found that "the six-gene model was more accurate than PSA alone at predicting cancer if you had it and no cancer if you didn't," said Oh. The test's accuracy improved even more when PSA measurements were added. Combined, the two tests achieved a diagnostic accuracy of more than 90 percent in specificity and sensitivity and eliminated most of the false-positives yielded by the PSA test.

Based on these findings, the researchers are planning to conduct a larger, multicenter clinical trial involving approximately 1,000 men to determine if the findings remain valid.

"These findings are very encouraging and suggest that this new test could spare tens of thousands of men from undergoing an unnecessary biopsy," Oh said. "However, until we can verify our findings, it is important to recognize that the PSA test, despite its limitations, is still the best test available for diagnosing prostate cancer at this time."

The study was funded in part by Source MDx and a Prostate Cancer SPORE grant at Dana-Farber/Harvard Cancer Center.

Carbohydrate Restriction May Slow Prostate Tumor Growth

ScienceDaily (May 26, 2009) — Restricting carbohydrates, regardless of weight loss, appears to slow the growth of prostate tumors, according to an animal study being published this week by researchers in the Duke Prostate Center.

"Previous work here and elsewhere has shown that a diet light in carbohydrates could slow tumor growth, but the animals in those studies also lost weight, and because we know that weight loss can restrict the amount of energy feeding tumors, we weren't able to tell just how big an impact the pure carbohydrate restriction was having, until now," said Stephen Freedland, M.D., a urologist in the Duke Prostate Center and lead investigator on this study.

The researchers believe that insulin and insulin-like growth factor contribute to the growth and proliferation of prostate cancer, and that a diet devoid of carbohydrates lowers serum insulin levels in the bodies of the mice, thereby slowing tumor growth, Freedland said.

Animals in the study were fed one of three diets: a very high fat/ no carbohydrate diet; a low-fat/ high carbohydrate diet; and a high fat/ moderate-carbohydrate diet, which is most similar to the "Western" diet most Americans eat, Freedland said. They were then injected with prostate tumors at the same time.

"The mice that were fed a no-carbohydrate diet experienced a 40 to 50 percent prolonged survival over the other mice," Freedland said.

Mice on the no-carbohydrate diet consumed more calories in order to keep body weights consistent with mice on the other study arms.

"We found that carbohydrate restriction without energy restriction – or weight loss – does indeed result in tumor growth delay," he said.

The researchers plan to begin recruiting patients at two sites – Duke and the University of California – Los Angeles – for a clinical trial to determine if restricting carbohydrate intake in patients with prostate cancer can similarly slow tumor growth. The trial should begin within a few weeks.

"It's very exciting – this is a potential new mechanism to fight prostate cancer growth and help patients live longer with their disease," Freedland said.

The findings appear in the May 26, 2009 online edition of the journal Cancer Prevention Research. Funding was provided by the United States Department of Veterans Affairs, the Department of Defense Prostate Cancer Research Program; the American Urological Association/ Foundation Astellas Rising Star in Urology Award, and the Robert C. Atkins Foundation. The Atkins Foundation supported this study but had no additional input or influence on the results.

Other researchers involved in this study include John Mavropoulos, William Buschmeyer, Alok Tewari, Dmitriy Rohkfeld, Phillip Febbo, Gayathri Devi, Eric Westman, Bercedis Peterson and Salvatore Pizzo of Duke; Michael Pollak and Yunhua Zhao of McGill University; Pinchas Cohen and David Hwang of UCLA and Wendy Demark-Wahnefried of the University of Texas – M.D. Anderson Cancer Center.

Protein That Suppresses Androgen Receptors Could Improve Prostate Cancer Diagnosis, Treatment

ScienceDaily (May 20, 2009) — A protein that helps regulate expression of androgen receptors could prove a new focal point for staging and treating testosterone-fueled prostate cancer, Medical College of Georgia researchers say.

Levels of the protein, βarrestin2, are lower in some prostate cancer cells than in normal prostate cells while expression of testosterone-fed androgen receptors is higher, they recently reported in Proceedings of the National Academy of Sciences Online Early Edition.

"An increase in the number of androgen receptors is believed responsible for prostate cancer progression in men with advanced disease," says the study's corresponding author, Dr. Yehia Daaka, Distinguished Chair in Oncologic Pathology in the MCG School of Medicine.

With increased numbers of androgen receptors, prostate cancer can make use of the limited testosterone available after a diseased prostate gland is removed or after testosterone production is blocked by drug therapy. In fact, the increased number of androgen receptors may mutate so they can start feeding off other steroids or even growth factors, Dr. Daaka says.

These wily skills help explain why cancer returns despite initially promising treatment results.

"It is clear that signaling by the androgen receptor is paramount for not only the initiation but also the progression of the disease, including escape to a hormone-refractory disease," he says. Moves androgen receptors make to support cancer growth make it "unbeatable at this point," for some patients.

However increased levels of βarrestin2 appear to halt the potentially deadly increase in androgen receptor expression, the MCG research team has found.

Androgen receptors have co-factors that can activate or repress their activity. "You could make the leap and say perhaps prostate cancer initiation and progression may be regulated by expression or non-expression of these co-factors," says Dr. Daaka, a Georgia Cancer Coalition Distinguished Cancer Scholar.

Their studies in human tissue – both in culture and transplanted into mice – show this appears the case for βarrestin2. First the team identified βarrestin2 as cofactor for androgen receptors. Next they found a reciprocal relationship: androgen receptor expression is low when βarrestin2 expression increases. That's the scenario in healthy prostate cells while the exact opposite is true in some prostate cancer. When they forced increased expression of βarrestin2, androgen receptor expression and activity went down.

βarrestin2 locks up an androgen receptor by binding to it, then the pair bind to yet another protein, ubiquitin ligase, which tags the receptor as waste and the trio make their way to the cell's garbage dump. "The neat thing about it is βarrestin2 inhibits or blunts the androgen receptor by promoting its degradation. So it disappears," Dr. Daaka says.

His future studies include determining what happens when βarrestin2 expression is further decreased in the face of prostate cancer. These studies will also help determine how big a player βarrestin2 is in prostate cancer progression, says Dr. Daaka, noting that numerous other corepressors and activators of androgen receptors are known.

Since all the happenings occur inside prostate cells, the findings don't point toward a new blood or urine test for prostate cancer but could lead to new ways to stage prostate cancer from the first biopsy. In fact, Dr. Daaka and his team already are collecting samples from patients whose cancer has been staged to see if specific levels of βarrestin2 expression correlate with different stages of disease.

Another goal is to develop a small molecule that can get inside a patient's cell and mimic βarrestin2's ability to suppress androgen receptor expression and so restore healthy levels found in prostate cells.

Prostate cancer falls behind skin cancer as the second most common cancer in men and more than 192,000 new cases will be diagnosed this year in the United States, according to the American Cancer Society.

Collaborators include Dr. Vijayabaskar Lakshmikanthan, postdoctoral fellow; Dr. Lin Zou, former postdoctoral fellow; Jae Kim, graduate student; Dr. Nidia C. Messias, assistant professor; and Dr. Zhongzhen Nie, assistant professor; from the MCG Department of Pathology; and Drs. Allison Michal and Jeffrey L. Benovic from Thomas Jefferson University.

Quick Test For Prostate Cancer

ScienceDaily (May 18, 2009) — A new 3-minute test could help in diagnosing prostate cancer, the most common cancer in men in the UK, according to scientists.

Researchers have developed the test by using light energy to measure the level of citrate in fluid samples from the prostate gland. The technique could provide the basis of a rapid means of detecting prostate cancer in the future. Almost a quarter of male cancers in the UK are diagnosed as prostate cancer and more than 10,000 men die from the disease each year.

Scientists, led by Prof David Parker from Durham University's Chemistry Department, have worked with experts from the University of Maryland, USA to develop the technique that measures the wavelength of light as it is shone through diluted samples of body fluids.

The research team, funded by the North East Proof of Concept Fund and the EPSRC, believe that the technique which can measure, with speed and accuracy, how citrate levels fall in the prostate gland as cancer develops, could also find use for the diagnosis of other medical conditions, associated with poor kidney function.

Prof Parker said: "Citrate provides a significant biomarker for disease that may provide a reliable method for screening and detecting prostate cancer, and for the monitoring of people with the disease. This technique could form the basis of a simple screening procedure for prostate cancer that could be used in outpatient departments at local hospitals."

His team have shone light into over 100 different chemical structures to see how they function and respond to the presence of certain important bioactive species. They have looked particularly closely at how citrate and lactate bind to luminescent structures within fluids.

Citrate and lactate are vital for our bodies' metabolism for normal function. Citrate provides energy for cells and the amount found in the prostate varies considerably due to an enzyme called m-aconitase which transforms it. This enzyme is very sensitive to zinc and, in prostate cancer sufferers, zinc levels are depressed and the enzyme switches on again.

Prof Leslie Costello from the University of Maryland said: "Citrate is formed in cell metabolism processes which alter as cancers grow. The analysis of the citrate concentration of prostatic fluid can provide an accurate way to screen and diagnose prostate cancer.

Since citrate concentrations decrease markedly early in malignancy, this technique makes it possible to analyse what's happening quickly in the early and treatable stage of prostate cancer. It shows much promise as a clinical tool."

The new test requires only a microlitre of fluid and the sample can be easily measured in an optical instrument. Using samples from male volunteers, the researchers have developed a portable instrument that can give results in 3 minutes.

The team's challenge has been how to accurately measure changes in the amount of citrate or lactate in fluid samples using the technique. The early results are promising and the team intends to look at the analysis of other body fluids. A possible way forward is to examine the citrate levels in seminal fluid samples, which are made up of 50% prostate fluid.

The University has launched a spin-out company called FScan Ltd to develop the technique and to seek commercial backing. The team has looked at 20 samples so far and verified the analysis in every case. The next stage is to work with a local hospital and examine samples from 200 volunteers to see whether the first Durham results correlate.

Prof Parker says: "It's been a complex process to develop the technique but we're very optimistic about it. Ultimately, this could provide an accurate method of screening for prostate cancer in men that could be carried out in 3-minutes once a biopsy has been obtained from the patient at a hospital outpatient department."

The discovery follows the invention in 2006 by Durham University Professor Douglas Newton of a Urine Flow Meter. The UFlow Meter helps men to assess if they have a restricted rate of urine flow - one of the warning signs of prostate problems.

The establishment of FScan Ltd is part of the University's aim to enhance the exploitation of the Intellectual Property generated by high quality research activities.

Tim Hammond, Head of Technology Transfer at Durham University, said: '"We quickly realised the potential of this research and have worked closely with Professor Parker and his team to secure initial proof of concept funding through NorthStar Equity Investors and the North East Proof of Concept Fund and to establish FScan Limited as the vehicle to validate and commercialise the technology."


Process for testing:

• Sample of prostatic fluid taken from patient in hospital using local anaesthetic 200 fold dilution of 1 microlitre of sample with a buffer solution into pre-coated disposable cuvettes.
• Optical spectroscopy on the sample, using a versatile bench top instrument with easy to use software.
• Reading of results after 3 min measurement cycle directly reading out actual citrate concentration.
• The sample is taken from the prostate gland – this is part of the biopsy procedure during clinical analysis in urology.

Molecular Pathway Behind Invasive Prostate Cancers

ScienceDaily (May 18, 2009) — University of Cincinnati (UC) cancer and cell biologists have identified a new molecular pathway key to the development of invasive prostate cancers.

In a preclinical study led by Maria Diaz-Meco, PhD, the UC team found that simultaneous inactivation of two particular genes—known as PTEN and Par-4—caused the rapid development of invasive prostate cancer tumors in mice.

"We knew that independent mutations in either of these genes could result in benign tumors, but when those changes occur simultaneously it appears to have a synergistic effect that causes prostate cancer," explains Diaz-Meco, an associate professor of cancer and cell biology at UC and corresponding author of the paper. "This switch affects the cell's ability to both grow and survive, leading to more aggressive and invasive tumors."

"This is an important discovery because—until now—those signaling pathways were not clearly defined. Without a clear molecular target, it's impossible to develop effective drugs to treat this disease without causing harm to the patient," she adds.

Diaz-Meco and her team report their findings online ahead of print in Proceedings of National Academy of Sciences (PNAS) the week of May 18.

PTEN is a well-defined gene shown to be suppressed in prostate cancer tumors, as well as in other types of cancer. Its mutation has been shown to result in the formation of benign tumors. Par-4 gene is also mutated in prostate cancer, but this study is the first to report its relationship with PTEN mutations and aggressive prostate cancer tumor development.

The UC study was done in a laboratory mouse model over the course of two years. Data from the mouse model was correlated and compared to human prostate cancer tissue samples to determine if their findings were applicable in humans as well.

"Theoretically, this new knowledge could be used to better categorize a tumor's aggressiveness by measuring the levels of PTEN and Par-4 expressed in a tissue biopsy," adds Diaz-Meco. "That would help clinicians make tough decisions about how aggressively to treat a patient's prostate cancer and minimize unnecessary treatment."

Cancer and cell biologists are working on identifying the molecular targets involved in cancer progression to develop a better understand the mechanisms of action that lead to prostate cancer so that pharmaceutical companies and clinicians can develop better methods of diagnosing and treating the disease.

Funding for this study comes from the National Cancer Institute and National Institutes of Health. Coauthors of the study include UC's Shadi Abu-Baker, Jayashree Joshi, Anita Galvez, Elias Castilla, and Jorge Moscat, PhD. Spanish National Cancer Research Center's scientists Pablo Fernandez-Marcos, Marta Canamero, Manuel Collado, Gema Moreno-Bueno and Manuel Serrano and Carmen Saez of the Biotechnology Centre of Oslo in Norway also contributed to the study.

Men With Prostate Cancer Worry Less About Recurrence Than Their Spouses Do

Researchers at The Mount Sinai Medical Center in New York have found that, when it comes to worrying about the recurrence of prostate cancer, male patients worry less than their female spouses or partners. The study was presented at the 30th annual meeting of the Society of Behavioral Medicine in Montreal.

In a study of 96 men and their spouses or partners, Michael Diefenbach, Ph.D., Associate Professor of Urology and Oncological Sciences at Mount Sinai School of Medicine, found that, at the time of prostate cancer diagnosis, the male patients described themselves as "moderately worried" about the chance of their disease recurring, while their female spouses and partners described themselves as "very much" worried.

"We know that illness perception and worries about cancer recurrence influence the emotional well-being of patients. But our studies show that this worry is actually a greater stress on spouses and partners. This research can help us develop programs to address the emotional health of the entire family unit," said Dr. Diefenbach.

For both groups, the concern about recurrence decreased over the next 12 months, though it decreased more for the male patients than it did for their spouses and partners.

This led to an even greater disparity after one year than what was observed at the time of diagnosis, with the men describing themselves as "a little bit" worried and their spouses and partners saying they were "moderately worried."

The study also showed that men were less likely to worry about their cancer recurring if they believed that treatment options for their cancer would be effective, while their spouses' and partners' worries were generally unaffected by outside factors.

"For the male patients, the main driver of worry about cancer recurrence was whether they believed that effective treatment was available for their disease," said Dr. Diefenbach.

"But for their spouses and partners it was not possible to determine the main driver of worry, as their response was mainly an emotional one. The one factor we could really measure that affects the level of spouse and partner worry is age in general, the older the spouse or partner, the more concerned they were about cancer recurrence."

Dr. Diefenbach leads a federally funded research program that aims to improve treatment decision making, patient-physician communication and quality of life through innovative patient and family focused programs. He is also the developer of the Prostate Interactive Education System (PIES), a Web tool that helps prostate cancer patients weigh their treatment options.

Source: Mount Sinai Medical Center

Video: Da Vinci Prostatectomy

The following video provides an overview of the radical prostatectomy with the daVinci System from www.intuitivesurgical.com. Dr. J.H. Witt www.pznw.de St. Antonius Hospital Gronau, Germany.

Scientists Find New Way to Identify Deadly Forms of Prostate Cancer

Researchers have discovered a new method to help doctors identify the most aggressive forms of prostate cancer.

A struggle for medical professionals in identifying prostate cancer is determining which forms are very aggressive and will require surgery and which forms are dormant and can be left untreated without risk.

Reporting in the British Journal of Cancer Research, scientists noted that bubbles of fat passed through the urine could provide new clues to deciding how to treat individuals with prostate cancer.

With about 34,000 new cases being found each year, prostate cancer is the most common form of cancer among men in the UK.

Doctors have previously used prostate specific antigen testing to screen patients for prostate cancer.

PSA testing can produce faulty results. Researchers have discovered that fatty capsules, called exosomes, come directly from the tumor and contain genetic information about they cancer.

“We hope that this innovative approach to studying prostate cancer will reveal new biomarkers for aggressive tumors,” said Dr Jonas Nilsson, at the VU University Medical Centre in Amsterdam.

“Tumor-derived RNA is preserved in these capsules and gives us an insight into the genetics of an individual’s tumor.”

But Matthew Shuford, urologist at Baylor University Medical Center at Dallas, said that PSA testing is still effective, and it saves lives.

“Keep in mind that it is only curable when caught early; it can only be caught early by screening; and the screening is a simple blood test that is cheap and easy.”

Approximately 90 percent of all prostate cancers are currently diagnosed at an early stage, according to the National Cancer Institute.

“Early diagnosis greatly increases a man’s chances of successful treatment,” said Dr. Shuford.

AUA: Statin Benefits Linked to Prostate Cancer, BPH, ED

By Charles Bankhead, Staff Writer, MedPage Today
Published: April 28, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

CHICAGO, April 28 -- Men who were taking statins at the time of radical prostatectomy had a 30% reduction in prostate cancer recurrence, data reported here showed.

Statin users also had lower PSA values and were more likely to have T1 disease than nonusers, Robert J. Hamilton, M.D., of the University of Toronto, said at the American Urological Association meeting.

"Our findings suggest that statins may slow prostate cancer progression after radical prostatectomy," said Dr. Hamilton. However, he emphasized, "at this point we cannot say with confidence that statins reduce the risk of prostate cancer recurrence after radical prostatectomy."

He said the findings require confirmation in other studies, such as a randomized controlled trial placing men on statins who are about to undergo surgery.

Dr. Hamilton's study was one of a half-dozen statin-related abstracts featured at an AUA press briefing. Collectively, the studies suggested that statins have favorable effects on prostate cancer risk, lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), and erectile dysfunction.

Dr. Hamilton reported findings from a study of 1,325 men who underwent radical prostatectomy for prostate cancer. Information collected before surgery included current statin use -- 237 (18%) men were taking one of the drugs at the time of surgery. The principal outcomes were pathologic features of the cancer and biochemical recurrence.

There were no differences between those taking statins and those not taking the drugs with respect to the frequency of positive surgical margins, seminal vesicle invasion, extracapsular extension, or lymph node metastases. However, significantly more statin users had a Gleason score of 7 (60% versus 49%, P=0.003).

Statin users presented a mixed bag of risk characteristics. They had a lower mean PSA value (6.2 ng/mL versus 6.9 ng/mL, P=0.04), and 67% of statin users had stage T1c disease compared with 58% of nonusers (P=0.009).

On the negative side, statin users were 2 years older and had a higher rate of obesity, as well as the higher proportion of Gleason 7 disease.

In a multivariate analysis, statin users had an odds ratio for recurrence of 0.70 compared with nonusers (95% CI 0.50 to 0.97, P=0.03).

Adding to statins' association with prostate cancer, Lionel Banez, M.D., of Duke University in Durham, N.C., reported findings from an analysis of obesity, statin use, and tumor inflammation.

Mounting evidence suggests inflammation may play a role in prostate cancer evolution and progression. Obesity has been associated with inflammation and more aggressive cancer, Dr. Banez said. Statins, on the other hand, have well-documented anti-inflammatory activity and have been associated with reduced cancer risk.

Dr. Banez and colleagues reviewed data on 254 men who underwent radical prostatectomy. About half of the patients reported statin use.

One pathologist graded all of the surgical specimens with respect to inflammatory infiltrates.

Significantly more statin users were overweight (48%) and obese (31%, P<0.001). p="0.07)." p="0.01).">

Dr. Banez disclosed relationships with AstraZeneca and Veridex.
Dr. Nehra disclosed relationships with GlaxoSmithKline, Pfizer, and sanofi-aventis.
Dr. Thrasher disclosed a relationship with sanofi-aventis.

Primary source: American Urological Association
Source reference:Hamilton RJ et al "Statin medication use and the risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database" AUA 2009; Abstract 1598.

Additional source: American Urological Association
Source reference:Banez LL et al. "Association between statins, obesity, and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy" AUA 2009; Abstract 575.

Additional source: American Urological Association
Source reference:Loeb S et al. "Is statin use associated with prostate cancer aggressiveness?" AUA 2009; Abstract 576.

American Urological Association Counters Mainstream Recommendations With New Best Practice Statement On PSA Testing

ScienceDaily (Apr. 27, 2009) — The American Urological Association (AUA) has issued new clinical guidance – which directly contrasts recent recommendations issued by other major groups – about prostate cancer screening, asserting that the prostate-specific antigen (PSA) test should be offered to well-informed, men aged 40 years or older who have a life expectancy of at least 10 years.

The PSA test, as well as how it is used to guide patient care (e.g., at what age men should begin regular testing, intervals at which the test should be repeated, at what point a biopsy is necessary) is highly controversial; however, the AUA believes that, when offered and interpreted appropriately the PSA test may provide essential information for the diagnosis, pre-treatment staging or risk assessment and post-treatment monitoring of prostate cancer.

The new Best Practice Statement updates the AUA's previous guidance, which was issued in 2000. Major changes to the AUA statement include new recommendations about who should be considered for PSA testing, as well as when a biopsy is indicated following an abnormal PSA reading.

According to the AUA, early detection and risk assessment of prostate cancer should be offered to well-informed men 40 years of age or older who have a life expectancy of at least 10 years. The future risk of prostate cancer is closely related to a man's PSA score; a baseline PSA level above the median for age 40 is a strong predictor of prostate cancer.

Such testing may not only allow for earlier detection of more curable cancers, but may also allow for more efficient, less frequent testing. Men who wish to be screened for prostate cancer should have both a PSA test and a digital rectal exam (DRE).

The Statement also notes that other factors such as family history, age, overall health and ethnicity should be combined with the results of PSA testing and physical examination in order to better determine the risk of prostate cancer. The Statement recommends that the benefits and risks of screening of prostate cancer should be discussed including the risk of over-detection, detecting some cancers which may not need immediate treatment

"The single most important message of this statement is that prostate cancer testing is an individual decision that patients of any age should make in conjunction with their physicians and urologists. There is no single standard that applies to all men, nor should there be at this time," Dr. Carroll said. He also notes that the "panel carefully reviewed the most recently reported trials of PSA testing in both the United States and Europe before finalizing their guidelines. The strengths and limitations of these trials are reviewed in the guideline."

In regard to biopsy, a continuum of risk exists at all values, and major studies have demonstrated that there is no safe PSA value below which a man may be reassured that he does not have biopsy-detectable prostate cancer.

Therefore, the AUA does not recommend a single PSA threshold at which a biopsy should be obtained. Rather, the decision to biopsy should take into account additional factors, including free and total PSA, PSA velocity and density, patient age, family history, race/ethnicity, previous biopsy history and co-morbidities.

Additionally, the AUA statement emphasizes that not all prostate cancers require active treatment and that not all prostate cancers are life-threatening. The decision to proceed to active treatments is one that men should discuss in detail with their urologists to determine whether active treatment is necessary, or whether surveillance may be an option for their prostate cancer.

"Prostate cancer comes in many forms, some aggressive and some not," said Peter Carroll, MD, chair of the panel that developed the Statement. "But the bottom line about prostate cancer testing is that we cannot counsel patients about next steps for cancer that we do not know exist." He also notes that "the AUA is committed to the timely, expert and appropriate care for men either with or at risk of getting prostate cancer and is prepared to revise these guidelines continuously as new information becomes available."

Additionally, the Best Practice Statement clarifies a number of key points about the use of PSA in treatment selection and post-treatment follow up of prostate cancer patients:

• Serum PSA predicts the response of prostate cancer to local therapy.
• Routine use of a bone scan is not required for staging asymptomatic men with clinically localized prostate cancer when their PSA level is equal to or less than 20.0 ng/mL.
• Computed tomography or magnetic resonance imaging scans may be considered for the staging of men with high-risk clinically localized prostate cancer when the PSA is greater than 20.0 ng/mL or when locally advanced or when the Gleason score is greater than or equal to 8.
• Pelvic lymph node dissection for clinically localized prostate cancer may not be necessary if the PSA is less than 10.0 ng/mL and the Gleason score is less than or equal to 6.
• Periodic PSA determinations should be offered to detect disease recurrence.
• Serum PSA should decrease and remain at undetectable levels after radical prostatectomy.
• Serum PSA should fall to a low level following radiation therapy, high intensity focused ultrasound and cryotherapy and should not rise on successive occasions.
• PSA nadir (low point) after androgen suppression therapy predicts mortality.
• Bone scans are indicated for the detection of metastases following initial treatment for localized disease, but the PSA level that should prompt a bone scan is uncertain. Additional important prognostic information can be obtained by evaluation of PSA kinetics (velocity).
• The kinetics of PSA rise after local therapy for prostate cancer can help distinguish between local and distant recurrence.

The new AUA statement is based on panel review of all available professional literature, members' clinical experience and expert opinion.

Adapted from materials provided by American Urological Association, via EurekAlert!, a service of AAAS.

3-D Research Model Tackles Prostate Cancer Spread

ScienceDaily (Apr. 24, 2009) — One of the few research projects to study the spread of prostate cancer to the bones using three-dimensional models of tissue-engineered bone is underway at QUT's Institute of Health and Biomedical Innovation (IHBI).

Shirly Sieh, a PhD student at IHBI, is studying the way cancer cells escape from the prostate through the bloodstream to form tumour colonies, most often in the spine and long bones.

"It is an innovative study which uses a tissue engineering platform technology developed by IHBI's Professor Dietmar W. Hutmacher in order to investigate the interaction between bones and cancer cells," Ms Sieh said.

"Tissue-engineered bone provides the 3D architecture for the cancer cells which more closely resemble bone metastasis instead of growing the cancer cells and bone cells on a flat Petrie dish.

"I am growing prostate cancer cells on the tissue-engineered bone to observe the interactions between the cells and the surrounding tissue so it is a way of mimicking the cancer cells invading the bone environment."

Ms Sieh said it was still not clear to researchers how bones and cancer cells interacted.

"With this 3D method we can see if and how the cancer cells 'set up home' in the bone cells," she said.

"We want to study how the cancer cells degrade the matrix, or the mix of proteins and growth factors produced by these cells, and remodel the environment to suit the cancer cells to grow a tumour."

Ms Sieh said scientists also wanted to understand why prostate cancer cells were attracted to the bone sites. She and Amy Lubik, a PhD student supervised by Professor Colleen Nelson, are studying the effect the cancer cells in the bone have on male hormone production, particularly on the hormone, androgen.

"People with advanced cancer who have had prostate removal surgery should have low levels of androgen and the cancer cells should be suppressed. However, sometimes the cancer cells do recur," she said.

"We think it might have something to do with the fact that the cancer cells are very sensitive to androgen and even low levels of androgen in the body could promote the growth of these cancer cells."

Ms Sieh said previous research had found that when the prostate cancer cells changed the bone environment they eventually induced more bone formation.

"But it is very abnormal growth which can cause bone fractures and painful spinal compression for the person," she said.


Adapted from materials provided by Queensland University of Technology.

Colonoscopy—What to Expect

In a previous post I outlined the reasons why I have been scheduled for a colonoscopy see: Managing Chronic Radiation Proctitis .

Below, I offer some facts about the procedure for those who may find themselves in a similar situation.

A colonoscopy is a diagnostic examination that allows a doctor to look inside the entire colon and rectum. The examination is used to determine the cause of colorectal problems and is also used as a screening test for colorectal cancer in people who have no symptoms.


About the procedure

During a colonoscopy, the doctor inserts a colonoscope (a long, thin, flexible tube) into the anus. Pain medication and a sedative (medication that causes drowsiness) are given to help reduce discomfort. The tube is slowly advanced through the rectum and the full length of the colon. The doctor views the image from the colonoscope on a video monitor. If the doctor finds an abnormal growth, or polyp, in your colon, a biopsy (removal of a small amount of tissue for examination under a microscope) of a part or the entire polyp can be taken using a tool at the end of the colonoscope. When the examination is complete, the colonoscope is slowly removed from the body.


The medical team

Most colonoscopies are performed by a gastroenterologist with the help of a nurse.

A gastroenterologist is a medical doctor who has completed five to six years of specialized training in gastroenterology, the study of the function and diseases of the esophagus, stomach, small intestine, colon and rectum, pancreas, gallbladder, bile ducts, and liver.

A gastroenterologist receives specific training in endoscopy (the use of a thin, flexible tube with an attached light and view lens to look inside the body) and how to interpret the results of endoscopic studies to make treatment recommendations.


Questions to ask your doctor

Before your colonoscopy, consider asking your doctor the following questions:

• Why do you recommend that I have a colonoscopy?
• Who will perform the colonoscopy, and who else will be in the room?
• What will happen during the colonoscopy?
• How long will the procedure take?
• Will it be painful?
• Will I receive anesthesia (drugs that cause loss of feeling or put a person to sleep)?
• What are the risks associated with having a colonoscopy?
• What if I don't have this examination?
• Will I need to avoid any activities after the colonoscopy?
• When will I learn the results?
• Who will explain the results to me?
• What other tests will be necessary if the test results show cancer?
  

Preparing for the procedure

When you schedule the examination, you will get detailed instructions on how to prepare for your colonoscopy.

Review with your doctor or nurse what you need to do to prepare for your colonoscopy, and whether you should take your regular medications that day. In addition, tell your doctor about all medications you are taking and any drug allergies or medical conditions you have.

Because your colon must be empty, you will need to be on a diet of clear liquids for one to three days before the procedure. This diet means eating only foods such as fat-free bouillon or broth, black coffee, strained fruit juice, and gelatin.

In addition to the liquid diet, you will need to take a laxative or give yourself an enema the day or night before the colonoscopy. If your doctor prescribes a laxative, it will either be given as a pill or as a powder that you will mix with water before drinking. In either form, the laxative will make you use the bathroom frequently so that your bowel will be cleansed before the examination.

You will be asked to review and sign a consent form that states you understand the risks of having the colonoscopy and agree to have the test done. Talk with your doctor about any concerns you have about the colonoscopy.

During the procedure

A colonoscopy usually takes 30 to 60 minutes to complete. Before the procedure begins, you will need to change into a hospital gown. You will be given pain medication and a sedative through an intravenous (IV) line in your arm. This will help you relax and reduce the discomfort you might otherwise feel from the colonoscopy. You may feel a slight stinging where the IV needle is inserted.

You will lie on your side on an examining table in a private room with a sheet draped over your body. As the doctor guides the colonoscope through the curves of your colon, you may need to change your position slightly to allow better access. The colonoscope inflates your colon by blowing air into it; this provides the doctor a better view of the colon lining. Though rare, there is a risk of the colonoscope puncturing the colon wall and surgery may be required to repair the perforation (hole).

Removing a polyp or taking a biopsy from the colon usually does not cause pain. However, bleeding may occur at the site of a biopsy or where a polyp is removed. The doctor can stop the bleeding using tools passed through the colonoscope.

Generally, the pain medicine and sedative you receive before the colonoscopy should limit pain you may feel during the procedure. However, you may feel cramping; taking slow, deep breaths may ease this discomfort. You may also feel discomfort from lying still for an extended time.

After the procedure

You will stay at the facility where you had the colonoscopy for up to two hours while the effects of the sedative wear off. You will need a ride home, so bring someone with you or make arrangements for a ride before the procedure. You can expect to resume your normal activities the day after your colonoscopy. If you feel severe abdominal pain or have a fever, bloody bowel movements, dizziness or weakness, call your doctor immediately.

AACR: Designer T Cells Attack Prostate Cancer

DENVER, April 21 -- Reprogrammed immune cells could become targeted "killing machines" against prostate cancer, a researcher said here.

In the early stages of a phase I study, these reprogrammed T cells sharply reduced the levels of prostate specific antigen (PSA) in two patients with metastatic prostate cancer, according to Richard Junghans, M.D., Ph.D., of the Roger Williams Medical Center in Providence, R.I.

Within a few weeks of the infusion of the engineered cells, one patient's PSA level had fallen by half and the other's by 75%, Dr. Junghans reported at the annual meeting of the American Association for Cancer Research.

T cells, Dr. Junghans told reporters, are the "perfect killing machines" when faced with a cell infected with a virus. "We have to fool the T cells into thinking that the cancer has a virus infection," he said.

To do that, he and colleagues isolate a patient's T cells from a blood sample and use genetic engineering techniques to make them sensitive to a molecule that only occurs in prostate cancer -- prostate specific membrane antigen, or PSMA.

Over a period of weeks, the modified cells are amplified in culture. Meanwhile the patient undergoes chemotherapy to knock down his remaining lymphocytes, creating "hematopoietic space" for the engineered T cells.

Finally, he said, the cells are infused into the patient and begin attacking cells that express PSMA. A marker for that activity, Dr. Junghans said, is the level of prostate specific antigen.

The falling levels of PSA in the two patients treated so far were obtained despite the low dose of cells they were given -- about a billion each.

The researchers plan to test that dose in one more patient and then escalate the dose -- first to 10 billion in six patients and then to 100 billion in another six.



In the two patients treated so far, the falling PSA levels appeared to have bottomed without reaching zero -- possibly because the methods used to activate them caused them to enter a resting state without completely eradicating the cancer cells, Dr. Junghans said.

With the higher doses, he said, he hopes to see PSA levels fall all the way to zero.

"We are very hopeful that when we get to higher doses," he said, "all those activated (cells) may get us to 100% suppression before they go to the resting state."

Dr. Junghans said the redirected T cells are a "brave new world" for cancer treatment. "I predict the FDA will have approved one of these designer T-cell constructs -- if not this one, then another one -- as standard therapy in the next five or so years," he said.

Dr. Junghans' approach is a new twist on ideas that have been around for "two decades or more," said Louis Weiner, M.D., of Washington's Lombardi Cancer Center, who was not part of the research.

"What Dr. Junghans and colleagues have done is to really combine two critical elements" -- redirecting the T cells and creating space for them by chemotherapy, Dr. Weiner said.

He said while the idea is intriguing and the early results promising, "at the end of the day, we will need properly conducted efficacy trials."

But "the early returns are sufficiently encouraging that I certainly hope they continue doing the work," he said.

Note: This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Dr. Junghans did not report support or conflicts.

By Michael Smith, North American Correspondent, MedPage Today
Published: April 21, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

Primary source: American Association for Cancer Research
Source reference: Junghans RP, et al "Phase I trial of anti-PSMA designer T cells in prostate cancer" AACR 2009; Abstract 5662.