A Possible Prostate Cancer Cure: A Newly Discovered Route For Testosterone To Reach The Prostate

Varicocele has only recently been shown to be a bilateral disease, the primary cause for male infertility and low testosterone level. It has now for the first time been discovered to be the cause of enlargement of the prostate and for the development of prostatic cancer as well. Also, for the first time in the published medical literature, it has been proven that super-selective venography and sclerotherapy (Gat Goren Technique) may reverse early localized prostate cancer and reduce prostate volume in benign prostate hyperplasia (BPH).

Read more at Medical News Today.

Height And Risk Of Prostate Cancer In The Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial

The correlation between obesity and risk of prostate cancer (CaP) to include the progression of CaP has been an area of significant investigation. Greater height has also been proposed to be a risk factor for CaP, due to increased levels of bioavailable insulin-like growth factors (IGFs) or androgens, or genetic predisposition. This relationship is supported in some but not all studies. In the online edition of the British Journal of Cancer, Dr. Ahn and colleagues used the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial to explore this association.

Read more at Medical News Today.

Potential association of type 2 diabetes genes with prostate cancer

Scientists have identified six new genes which play a role in the development of type 2 diabetes, and among the group is the second gene known to also play a role in prostate cancer.

The new findings bring the total number of genes or genomic regions implicated in diabetes to 16, said Laura Scott, assistant research scientist in the Department of Biostatistics. Researchers from the University of Michigan were one of three teams of scientists in Europe and North America that led the multi-group collaboration. The findings, which were published today in the journal Nature Genetics, provide new insights into the mechanisms which are usually responsible for the control of glucose, or sugar, levels in the blood, and to the derangements that can result in type 2 diabetes, which impacts more than 170 million people worldwide.

One of the newly discovered genes, which goes by the name of JAZF1, contains a separate variant that has recently been shown to play a role in prostate cancer, and is the second gene that appears to play a role in both conditions. The first identified overlap between genes for prostate cancer and type 2 diabetes was with HNF1B, which is also involved in an early onset form of diabetes discovered at U-M in an unrelated study, called Maturity Onset Diabetes of the Young (MODY). In HNF1B, the same variant that is associated with increased risk of diabetes is associated with decreased risk of prostate cancer. In JAZF1, the diabetes and prostate cancer variants reside in different parts of the gene and there is no known relationship between them.

"Some of these genes for type 2 diabetes might be involved in diseases other than prostate cancer, in fact there is already a known overlap with heart disease in another genomic region? Scott said. "We have about 25,000 genes, and we've found a very small number by genome wide studies, so to have the same genomic regions come up in studies of different diseases is actually pretty interesting."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"The remarkable recent progress in identifying regions of the genome that increase risk to diabetes---from 3 to 16 in only a year---will help us unravel the complex basis diabetes and may suggest new and better tailored methods to prevent or treat this disease.," said U-M's Michael Boehnke, the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, one of the three lead groups in the study.

The researchers in this project set out to find differences in the genetic code that contribute to individual differences in susceptibility to disease. Previous efforts from these groups and others identified ten genes contributing to type 2 diabetes risk.

University of Michigan

An Apple Peel a Day Might Keep Cancer at Bay

An apple a day keeps the doctor away? Or, what appears to be more accurate: An apple peel a day might help keep cancer at bay, according to a new Cornell study.

Cornell researchers have identified a dozen compounds -- triterpenoids -- in apple peel that either inhibit or kill cancer cells in laboratory cultures. Three of the compounds have not previously been described in the literature.

"We found that several compounds have potent anti-proliferative activities against human liver, colon and breast cancer cells and may be partially responsible for the anti-cancer activities of whole apples," says Rui Hai Liu, Cornell associate professor of food science. Liu is affiliated with Cornell's Institute of Comparative and Environmental Toxicology and is senior author of the study, which is online and published this month in the Journal of Agricultural and Food Chemistry.

In previous Cornell studies, apples had been found not only to fight cancer cells in the laboratory but also to reduce the number and size of mammary tumors in rats. The Cornell researchers now think that the triterpenoids may be doing much of the anti-cancer work.

"Some compounds were more potent and acted differently against the various cancer cell lines, but they all show very potent anti-cancer activities and should be studied further," said Liu.

With co-author Xiangjiu He, a Cornell postdoctoral researcher, Liu analyzed the peel from 230 pounds of red delicious apples from the Cornell Orchard and isolated their individual compounds. After identifying the structures of the promising compounds in the peel, the researchers tested the pure compounds against cancer cell growth in the laboratory. In the past, Liu has also identified compounds called phytochemicals -- mainly flavonoids and phenolic acids -- in apples and other foods that appear to be have anti-cancer properties as well, including inhibiting tumor growth in human breast cancer cells.

"We believe that a recommendation that consumers to eat five to 12 servings of a wide variety of fruits and vegetables daily is appropriate to reduce the risks of chronic diseases, including cancer, and to meet nutrient requirements for optimum health," said Liu.

Cornell University

Stem cells provide clues to cancer spread

Scientists have made a breakthrough in understanding how cancers spread in what could lead to new ways of beating the disease. The University of Manchester study used embryonic stem (ES) cells to investigate how some tumours are able to migrate to other parts of the body, which makes the treatment of cancer much more difficult.

Dr Chris Ward, in the University’s Faculty of Medical and Human Sciences, studied a crucial change that makes cancer cells able to start moving and spread into other tissues.

Normal cells, as well as early cancer cells, are called epithelial cells because they bind tightly to each other forming stable layers of tissue. However, as a tumour becomes more advanced, some of the cells change to become ‘mesenchymal’.

Mesenchymal cells do not bind to each other, forming more disorganised tissues in which the cells can move around. Since this crucial change -- known as the epithelial-mesenchymal transition, was first observed in the early embryo, Dr Ward theorised that embryonic stem cells might undergo a similar process.

Dr Ward, whose findings are published in the journal Molecular Biology of the Cell, said: "We have shown that ES cells spontaneously change in a manner that is remarkably similar to the epithelial-mesenchymal transition. They lose the proteins that cells use to bind to each other and have other protein alterations that are characteristic of spreading cancer cells.

"Since ES cells can be grown in the laboratory where they keep the characteristics of the cells in the early embryo they can be studied in detail. By studying these ES cells we have already identified a novel component of this transition process. We expect the use of ES cells will lead to the identification of other unknown factors involved in cancer cell spread, hopefully leading to new avenues for cancer therapy."

Read full story in Machines Like Us

Role of TRPM8 in the development of prostate cancer

Recent studies have indicated that the protein known as TRPM8 plays an important role in prostate cancer: high levels of TRPM8 have been found in prostate carcinoma compared to normal prostate epithelial cells, and TRPM8 has been suggested as a specific marker and therapeutic target in prostate cancer. However, the regulation of and changes in TRPM8 during prostate cancer progression have remained unclear.

In normal prostate epithelium, cells coexist in many stages of development/differentiation – progressing from stem cells to mature luminal cells. Disrupted or dysregulated differentiation and proliferation are major causes of cancer. In a study appearing online on May 17 in advance of publication in the June print issue of the Journal of Clinical Investigation, Natalia Prevarskaya from Université des Sciences et Technologies de Lille, France, show that only mature, differentiated human prostate primary epithelial luminal cells express functional plasma membrane TRPM8 (PM-TRPM8) and that prostate cancer cells possessed higher PM-TRPM8 levels than normal cells. However, endoplasmic reticulum TRPM8 (ER-TRPM8) retained it’s function as a calcium release channel, independent of the differentiation state of the cell, and may be an important factor in controlling the growth of prostate cancer cells. The authors hypothesize that the constant activity of ER-TRPM8 may be the result of the expression of a truncated form of TRPM8. The authors suggest that specific inhibition of ER-TRPM8 or PM-TRPM8 may prove to be of therapeutic use in the treatment of prostate cancer, depending on the stage of the tumor.

Journal of Clinical Investigation

It's never too late to get it back! Aging interrupted

Much research has shown that reduced calorie intake can increase health and longevity. Professor Stephen Spindler (University of California) and his collaborators* have discovered that reducing calorie intake later in life can still induce many of the health and longevity benefits of life-long calorie reduction. Importantly, this also includes anti-cancer effects. They are using this knowledge to establish a novel screening technique to find drugs which mimic this longevity effect. “Right now, there are no authentic “anti-ageing drugs” capable of extending the lifespan of healthy people. The technique we have developed allows us to screen a relatively large number of drugs in months rather than years. The hope is that these drugs will be able to extend the lifespan of healthy animals, and possibly, after further testing, healthy humans”, says Professor Spindler who will present his results at the Society for Experimental Biology’s Main Meeting in Glasgow on Monday 2nd April.

Previous research has show that mice can live up to 40% longer if they simply consume fewer calories, but a highly nutritious diet. Because people are not very good at dieting, Dr. Spindler and his colleagues would like to identify drugs which can produce the same beneficial health and longevity effects without the low calorie diet. The problem is to find a way to rapidly identify these drugs. Professor Spindler and his colleagues are examining the gene expression patterns which are induced by low calorie diets, and looking for drugs which mimic these changes. They are searching for drugs which will have these beneficial effects and slow ageing, even when they are given late in life. One drug, normally used to treat diabetic patients, seems to produce many of the beneficial effects of a low calorie diet. However, it is important to be sure that healthy people will benefit from the drug. A very low level of toxicity could interfere with the beneficial effects of such a drug, if it is taken for a lifetime.

Physiological changes associated with ageing include cell damage and the emergence of cancer cells. The most important effects of low calorie diets and longevity therapeutics given late in life may not be to prevent this damage, but instead to stimulate the body to eliminate damaged cells that may become cancerous, and to stimulate repair in damaged cells like neurons and heart cells. Low calorie diets drive the body to replace and repair damaged cells. This process usually slows down as we age, but low calorie diets make the body re-synthesise and turn over more cells – a situation associated with youth and good health. Dr. Spindler and his colleagues used their screening method to search for drugs which cause pre-cancerous and cancerous cells to commit suicide and to replace those cells with new, healthy cells. It is thought that the body does this because it normally kills some cells like damaged and rogue cancer cells to provide energy when it is starving. Then it replaces these cells when a meal is eaten.

It seems it is the total number of calories which are consumed, rather than the type of food which is the key to the effects of low calorie diets on the ageing process. However, it is known that vegetarians and fish eaters live longer than red meat eaters, and that, generally, the more fruit and vegetables in the diet, the better your health and longer your lifespan.

Source: Society for Experimental Biology.

A sweet step toward new cancer therapies

By recognizing sugars, a technique developed by University of Michigan analytical chemist Kristina Hakansson sets the stage for new cancer diagnosis and treatment options.

A growing body of evidence points to assemblies of sugars called glycans attached to proteins on cancer cell surfaces as accomplices in the growth and spread of tumors. Researchers have been keen to characterize these glycans, but traditional analytical methods have not been sufficient.

Now, Hakansson's research group has demonstrated that their technique can be used to identify and structurally characterize glycans. Their work is described in the April 15 issue of the journal Analytical Chemistry.

Typically, analytical chemists use mass spectrometry—a technique that accurately weighs molecules or fragments of molecules—to analyze proteins. In this process, proteins are introduced into the mass spectrometer and fragmented by heating until the weakest bonds break. "It's the 'shake-it-til-it-breaks' approach," Hakansson said.

Together, the masses of the various fragments provide a sort of fingerprint that reveals the genetic blueprint from which the protein was built—information that helps researchers confirm the protein's identity. This works fine as long as the protein has not been modified after it was produced. But if other chemical groups such as phosphates, sulfates or sugars have been added, the identification method breaks down.

"If sugars are attached, for instance, the weakest bonds are not the bonds that hold the protein together; they're the bonds between the sugars," Hakansson said. When those bonds break, the resulting fragments don't give accurate information about either the protein's identity or the exact type and position of sugars present.

To get around that problem, researchers have used a process called electron capture dissociation (ECD) instead of the usual "shake-it-til-it breaks" method to fragment proteins. But that method requires the presence of at least two positive charges, which can be difficult to accomplish with acidic molecules, such as proteins with sulfate or phosphate groups attached.

Hakansson's group has been exploring the use of metals such as calcium and iron to carry the necessary positive charges. In a series of recently published papers, they first showed that their method can be used to selectively cleave different bonds and then demonstrated that it can be used to identify sulfate-laden proteins and to pinpoint the location of the sulfate groups on them.

In the latest research, they extended the technique to sugars, an even more challenging task.

"Sugars are not like other biomolecules," Hakansson said. "They're linked rings with lots of branches, like trees. If you cut off a branch, you don't know which part of the tree it came from." The trick is to make breaks that cut across the ring structures, rather lopping off branches. By using metals as charge carriers, the researchers were able to do just that, yielding valuable structural information.

In a project that continues to build on this line of work, Hakansson is collaborating with U-M Health System cancer surgeon Diane Simeone to investigate sugars attached to proteins in the membranes of pancreatic cancer cells.

"The work is in very early stages, but we hope that by measuring unique sugars it may be possible to develop diagnostic tools or therapeutic agents to specifically target them," Hakansson said.

Source: University of Michigan News.

Targeting tumors the natural way

By mimicking Nature's way of distinguishing one type of cell from another, University of Wisconsin-Madison scientists now report they can more effectively seek out and kill cancer cells while sparing healthy ones.

The new tumor targeting strategy, presented today (March 25) at the annual national meeting of the American Chemical Society, cleverly harnesses one of the body's natural antibodies and immune responses. "The killing agent we chose is already in us," says UW-Madison chemistry professor Laura Kiessling, who led the work with postdoctoral researcher Coby Carlson. "It's just not usually directed toward tumor cells."

In a series of cell-based experiments, the researchers' system recognized and killed only those cells displaying high levels of receptors known as integrins. These molecules, which tend to bedeck the surfaces of cancer cells and tumor vasculature in large numbers, have become important targets in cancer research.

In contrast, an established tumor-homing agent linked to the cell toxin doxorubicin destroyed cells even when they expressed very little integrin, indicating this strategy has the potential to kill cancerous and healthy cells indiscriminately.

"This study suggests that the cell recognition mode we used can direct an endogenous immune response to destroy cancer cells selectively," says Kiessling. "We think this could lead to a new class of therapeutic agents not only for cancer but also for other diseases involving harmful cells."

Cancer cells typically display higher levels of certain receptors on their surfaces than do normal cells, a fact that allows scientists to pinpoint tumor cells lurking among the body's scores of cell types. A popular approach employs a cell-binding agent, such as a monoclonal antibody, that is powerfully attracted to the target receptor and holds fast to any cell displaying it.

Although this strategy has benefits, it's not natural, says Kiessling. Cell recognition in living systems instead involves binding agents that attach only weakly to any single target receptor, and thus stick to cells only when several receptors are displayed together. These weak "multivalent" interactions cut down on cases of mistaken identity, because if the agent contacts the wrong cell type, it can be easily displaced.

The team got the idea to mimic this process from efforts to transplant pig organs into primates. The surfaces of most mammalian and bacterial cells express large amounts of a carbohydrate, called alpha-Gal in scientific shorthand, while the cells of humans and other higher primates do not. What humans and primates do produce in abundance is an antibody against the carbohydrate, called anti-Gal.

When scientists tried transplanting pig organs into primates, the anti-Gal antibodies bound to the alpha-Gal on the organ's cells, unleashing a potent immune response that caused immediate organ rejection. But true to natural cell recognition, the immune response occurs only when clusters of many alpha-Gal molecules are present for anti-Gal to bind with.

Armed with this knowledge, Kiessling's group modified an agent known to bind tightly to integrin and tethered it to alpha-Gal. When they mixed this molecule with cells displaying high levels of integrin, the agent, by attaching to the receptor, decorated the cells with large amounts of alpha-Gal. In cell cultures containing human serum, the alpha-Gal then elicited the cell-destroying immune reaction.

In cells with low concentrations of integrin, the agent still bound, but the resulting levels of alpha-Gal weren't sufficient to elicit the immune response, and the cells survived. The same wasn't true if the cell-binding agent delivered doxorubicin to cells instead: They were killed regardless of the amount of integrin they carried.

Because target receptors on cancer cells usually reside on healthy cells, too—albeit in lower numbers—therapies aimed at these receptors are always expected to have debilitating side effects. That's why Kiessling's approach holds such promise.

"What we've shown is that you don't need a receptor that's found solely on tumor cells," she says. "You just need one that's found in significantly higher numbers on cancerous cells than on normal ones."

From University of Wisconsin-Madison.

Small molecule dervived from Rb2/p130 could act as cancer therapeutic

A small molecule derived from the spacer domain of the tumor-suppressor gene Rb2/p130 has demonstrated the ability to inhibit tumor growth in vivo and could be developed into an anti-cancer therapeutic, according to researchers at Temple University's Sbarro Institute for Cancer Research and Molecular Medicine.

The researchers reported their findings, "A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo," in the March 22 issue of the journal Oncogene (http://www.nature.com/onc). Rb2/p130 was discovered in the early 1990s by Antonio Giordano, director of the Sbarro Institute (http://www.shro.org) and the Center for Biotechnology in Temple's College of Science and Technology, who headed the study.

The researchers discovered that within Rb2/p130's spacer domain—a sequence of 212 amino acids located in the pocket or middle section of the gene—was a small portion that resembled an amino-acidic sequence contained in the protein p21, which acts as a cdk (cyclin dependent kinase) inhibitor. Cdks play a critical role in cell cycle regulation.

"What we tested was the ability of the Rb2/p130 spacer region to inhibit the kinase activity of cdk2, which is the same kinase p21 inhibits," said Giordano, one of the study's lead authors. "And to our surprise, it happened." The researchers then set about trying to reduce the spacer domain's 212 amino acids down to the smallest sequence that would still produce the same functionality as p21, explained Giordano.

"We thought we could narrow down the spacer region that contains the protein-like motif to a small portion that could be delivered as a small molecule or peptide," Giordano said.

They discovered a 39 amino-acid-long sequence, which they named Spa310. The molecule that was synthetically produced in the laboratory was introduced into mice that had been injected with tumor cells.

"Tumor growth was inhibited and the tumors began to reduce in size until they disappeared," Giordano said.

Giordano said because of the intrinsic nature of the compound, it can be easily reproduced as a biological drug in large quantities and does not require potentially dangerous means of delivery like viruses, as do most gene therapies; therefore Spa310 has a good chance to succeed as an anti-cancer therapy. For these reasons, he believes it may be easier to get approval for clinical trials.

"Fifteen years after discovering Rb2/p130, our research and hard work has led us to the discovery of this small molecule, which is a step forward in cancer research and a big step toward a cancer treatment," he said.

From Temple University.

Discovery may lead to 'smart' cancer therapies

New non-toxic and targeted therapies for metastatic breast, ovarian, and possibly other cancers may now be possible, thanks to a discovery by a team of researchers at the University of British Columbia.

In a collaboration between UBC stem cell and cancer scientists, it was found that a protein called podocalyxin – which the researchers had previously shown to be a predictor of metastatic breast cancer – changes the shape and adhesive quality of tumour cells, affecting their ability to grow and metastasize. Metastatic cancer is invasive cancer that spreads from the original site to other sites in the body.

The discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The findings were recently published online by the Public Library of Science.

"We believe we’ve found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research," says Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. "The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing "smart" molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments – very different from the standard ‘slash and burn’ chemotherapy."

The researchers found that podocalyxin significantly expands the non-adhesive face of cells, allowing individual cells to brush aside adhesion molecules situated between tumour cells. The "freed" cells then move away from the original site to form new tumours at other sites. Also, the protein causes tumour cells to sprout microvilli, or hair-like projections, that may help propel cancer cells to other sites.

In addition, when the protein expands the non-adhesive face of cells it drags along with it a second protein called NHERF-1 – a protein shown by others to be implicated in cell growth and invasion. The researchers now believe the mechanism applies to difficult-to-treat invasive breast and ovarian cancers.

"We’re now tapping into what causes the characteristic cell shape changes seen in cancerous tumours and possibly how these cells grow and metastasize. It gives us a whole new target for therapy," says Assoc. Prof. of Medical Genetics and stem cell expert Kelly McNagny, co-senior principal investigator. "If we can block the protein, we may be able to stop the spread of cells."

Post-doctoral Fellow Julie Nielsen, of UBC’s Biomedical Research Centre, and PhD student Marcia Graves of the Dept. of Cellular and Physical Sciences, were instrumental in designing and executing the research experiments, he adds.

Next steps involve advancing the research in animal models, designing antibodies to block the function of the protein and working with the UBC-based Centre for Drug Research and Development to identify new therapies to combat metastasizing cancer.

The researchers say information from this discovery may speed development of new therapies to within 10 years.

In 2006, more than 22,000 women were diagnosed with breast cancer and 5,300 died of it, according to estimates from the Canadian Breast Cancer Foundation. The Canadian Cancer Society estimates that approximately 2,300 new cases of ovarian cancer were diagnosed and about 1,600 women died from the disease in 2006.

From University of British Columbia.

Inflammation may play role in metastasis of prostate cancer

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 IkB kinasea (IKKa) 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 IKKa activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKa in their nuclei and express little or no Maspin," said Karin. He noted that a perfect correlation between nuclear accumulation of activated IKKa 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 IKKa is activated, allowing it to enter the nucleus of the cancer cell, repressing Maspin. IKKa 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 IKKa," 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 IKKa, whereas late-stage tumors contain the highest levels of active nuclear IKKa. 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 IKKa activation, may offer new therapeutic strategies for prevention of metastatic disease.

From University of California – San Diego.

Health-care inequities underscore racial disparities in prostate cancer

Improving access to and utilization of the healthcare system may benefit African-American prostate cancer patients more than educational or motivational interventions, according to a new study. Published in the April 15, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study reveals that African-American men are well educated about their risk of prostate cancer and the benefits of screening, and that socioeconomic factors that impact behavior are more important barriers to adequate care. The study finds African-American men access healthcare resources, including primary care physicians, infrequently, constrained by its limited availability, resulting in distrustful and irregular interactions.

Racial disparities in the diagnosis and outcome of prostate cancer are well documented in the U.S. Most concerning is the comparatively significantly higher mortality rate in African-American men (68.1 per 100,000 versus 27.7 per 100,000 among white men). Researchers continue to explore the reasons for this gap, but recent evidence suggests that socioeconomic, cultural, and behavioral factors play an important role. One promising hypothesis is that a lack of knowledge about prostate cancer and preventive care leads to less screening, delayed diagnosis and advanced disease.

Led by James A. Talcott, M.D., S.M. of the Massachusetts General Hospital and Harvard Medical School in Boston in conjunction with collaborators at the University of North Carolina Lineberger Comprehensive Cancer Center and Sheps Center for Health Services Research, researchers surveyed 84 African-Americans and 253 whites from North Carolina recently diagnosed with prostate cancer to better characterize the role of knowledge and attitudes, socioeconomic status, demography, and healthcare access in race and prostate cancer.

The researchers found that compared to whites, African-Americans were younger, had more underlying illness, and were at a socioeconomic disadvantage at the time of diagnosis. While the level of knowledge among this group was comparable if not better than among whites, African-Americans were more often distrustful of physicians but less likely to reject conventional Western medical treatments. African-Americans also reported having less access to healthcare resources and continuity of care, and were more likely to be uninsured or without secondary insurance and seek routine care at a public medical clinic or emergency room. In addition, they were less likely to have regular physical examinations, be seen by the same physician, and follow-up on a significant medical complaint. African-Americans were also more likely to have to request prostate cancer screening tests than whites, whose physicians were more likely to order them routinely.

"For African-American men," conclude the authors, "the main barriers to timely diagnosis and screening identified in this study arose from their constrained opportunities for health care access and utilization, absence of strong ties to a primary physician, and a probably related reduced trust of physicians."

From John Wiley & Sons, Inc.

Ask Your U.S. Representative to Sign the "Dear Colleague" Letter

Help Fund the Cure for Prostate Cancer

Please contact your Representative and ask her/him to sign the DeLauro/King "Dear Colleague" letter for fiscal year 2008, and support a $100 million appropriation for the Prostate Cancer Research Rrograms at the Department of Defense (DoD).

House members need to be asked directly by their constituents to sign this important letter. Your voice makes a difference!

The deadline for this letter is the end of the day, Thursday, March 15, so send an e-mail or call today!

Send letter by clicking here.

Members of Congress are looking for programs to eliminate entirely and/or reduce funding for in the coming year. National Prostate Cancer Coalition has partnered with the breast and ovarian cancer advocacy communities to garner broad bipartisan support for all three of the "Congressionally Directed Medical Research Programs" housed at the DoD.

Representative Peter King (R-NY) and Representative Rosa DeLauro (D-CT), are circulating a "Dear Colleague" letter urging the Defense Appropriations Subcommittee which determines the funding levels for the Congressionally Directed Medical Research Program to provide:

• Prostate Cancer Research Program: $100 million
• Ovarian Cancer Research Program: $20 million
• Breast Cancer Research Program: $150 million

Please take a moment to personalize the e-mail to your Representative to explain how prostate cancer has impacted your life. Staff members remember stories better than statistics and personalized e-mails receive more attention than form e-mails. Personalizing your communication is extremely important!

If the person you contact in the Representative's office would like more information about the letter, please direct them to Averi Pakulis in Rep. DeLauro's office at (202) 225-3661, Kerry Ann Watkins in Rep. King's at (202) 225-7896, or Susan Stoner at the National Prostate Cancer Coalition at (202) 303-3104.

A "Dear Colleague" letter is a tool for members of Congress to build support for a program or particular legislative proposal. Any member of the House of Representatives can sign-on and after numerous signatures are collected, the final letter will be delivered to the House Military Quality of Life Appropriations Subcommittee.

Far more mutations than thought involved in cancer

A painstaking scan of the DNA of tumor cells shows hundreds of previously unsuspected genes are involved in cancer, researchers said on Wednesday in a finding that offers new ways to fight the disease.

They found more than 1,000 different mutations in just one family of genes taken from 200 samples of breast, stomach, colorectal and other common tumors. Other groups of genes also are involved in cancer.

"We find evidence for approximately 100 new cancer genes," Dr. Mike Stratton, co-leader of the Cancer Genome Project at the Sanger Institute in Cambridge, Britain, told reporters.

He said 120 of the mutations in these genes are believed to be "driver" mutations that directly contribute to the development of cancer.

To fully understand cancer, scientists will have to catalog, in detail, every genetic mistake involved in that cancer, they said. "The data presented in this paper provide a rational 'road map' for approaching such a task," they wrote.

Read full story at Yahoo News

How common viruses can turn cells cancerous

Common viruses may play a bigger role in cancer than anyone thought.

It is well known that certain viruses can trigger specific cancers. Human papillomavirus, for example, causes around 93 per cent of cancers of the cervix. Now Dominik Duelli and Yuri Lazebnik at Cold Spring Harbor Laboratory in New York and colleagues have found evidence for how they might do it.

Full Story >>