In a new study in PLoS Medicine, Samir Hanash and colleagues from Fred Hutchinson Cancer Research Center in Seattle report the identification of proteins that appear in increased numbers at an early stage of pancreatic tumor development in a mouse model and may be a useful tool in detecting early tumors in humans.

Using a well-characterized mouse model of pancreatic cancer the researchers identified a panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse and tested them in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel of proteins discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 months prior to the development of symptoms and clinical diagnosis of pancreatic cancer.

Although further validation will be needed, these results indicate that mouse models of cancer, in combination with in-depth proteomic analysis, could help identify candidate markers in human cancer and potentially be used for early detection, say the researchers

Source: Public Library of Science

Faca VM, Song KS, Wang H, Zhang Q, Krasnoselsky AL, et al. (2008) A mouse to human search for plasma proteome changes associated with pancreatic tumor development. PLoS Med 5(6): e123.

Tobacco smokers who eat three servings of fruits and vegetables per day and drink green or black tea may be protecting themselves from lung cancer, according to a first-of-its-kind study by UCLA cancer researchers.

UCLA researchers found that smokers who ingested high levels of natural chemicals called flavonoids in their diet had a lower risk of developing lung cancer, an important finding since more than 90 percent of lung cancers are caused by tobacco smoking.

The study was published this month in the journal CANCER.

“What we found was extremely interesting, that several types of flavonoids are associated with a reduced risk of lung cancer among smokers,” said Dr. Zuo-Feng Zhang, a researcher at UCLA’s Jonsson Cancer Center and a professor of public health and epidemiology. “The findings were especially interesting because tobacco smoking is the major risk factor for lung cancer.”

Flavonoids are water-soluble plant pigments that have antioxidant and anti-inflammatory properties, both of which can counteract damage to tissues. For the UCLA study, researchers looked at 558 people with lung cancer and 837 people who did not have lung cancer and analyzed their dietary history.

Researchers found that study participants who ate foods containing certain flavonoids seemed to be protected from developing lung cancer. Zhang said the flavonoids that appeared to be the most protective included catechin, found in strawberries and green and black teas, kaempferol, found in Brussels sprouts and apples, and quercetin, found in beans, onions and apples.

So should smokers run out and stock up on the teas, apples, beans and strawberries? Quitting smoking is the best course of action, Zhang said, but eating more fruits and vegetables and drinking more black and green teas won’t hurt.

“Since this study is the first of its type, I would usually be hesitant to make any recommendations to people about their diet,” Zhang said. “We really need to have several larger studies with similar results to confirm our finding. However, it’s not a bad idea for everyone to eat more fruits and vegetables and drink more tea.”

Zhang said flavonoids protect against lung cancer by blocking the formation of blood vessels that tumors develop so they can grow and spread, a process called angiogenesis. They also stop cancer cells from growing, allowing for naturally programmed cell death, or apoptosis, to occur.

The antioxidant properties found in the flavonoids also may work to counteract the DNA damaging effects of tobacco smoking, Zhang said, explaining why they affected the development of lung cancer in smokers but not in non-smokers.

“The naturally occurring chemicals may be working to reduce the damage caused by smoking,” Zhang said.

The next step, Zhang said, are laboratory-based studies of flavonoids on cell lines and animal models to determine how they are protecting smokers from developing lung cancer. And in addition to larger studies to confirm these findings, other studies need to be done to see if the protective effects of flavonoids extend to other smoking-related cancers, such as bladder, head and neck and kidney cancers.

Zhang and his team also plan to study which types of fruits and vegetables have the highest levels of the flavonoids found to be helpful in this study and what the optimal number of servings per day might be to provide the greatest protection.

Source: University of California - Los Angeles

Josh says:

I unfortunately can’t find the paper, as there are a lot of journals called “Cancer” and the paper may or may not actually be available yet. This is just yet another study that demonstrates how good for you flavinoids are. I remember another study that said flavinoids cause an immune response, which may be why they’re helpful for preventing disease.

New research suggests that the form of tomato product one eats could be the key to unlocking its prostate cancer-fighting potential, according to a report in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research.

“Processing of many edible plants through heating, grinding, mixing or drying dramatically increases their nutrition value, including their cancer prevention potential. It appears that the greatest protective effect from tomatoes comes by rehydrating tomato powder into tomato paste,” said Valeri V. Mossine, Ph.D., research assistant professor of biochemistry at the University of Missouri.

The protective effect of tomato products against prostate cancer has been suggested in many studies, but researchers remain uncertain about the exact mechanisms. Mossine and colleagues demonstrated that FruHis, an organic carbohydrate present in dehydrated tomato products, exerts a strong protective effect.

Researchers divided rats into groups of 20 and fed them a control diet or a diet that included tomato paste, tomato powder or tomato paste plus additional FruHis. All animals were then injected with prostate cancer-causing chemicals.

Animals fed the tomato paste plus FruHis diet had the longest survival from cancer at 51 weeks compared with 50 weeks in the tomato powder group, 45 weeks in the tomato paste alone group and 40 weeks in the control group.

On post-mortem exam, prostate tumors were found in 10 percent of the rats that had been given a combination of tomato paste and FruHis, compared with 30 percent of animals in the tomato powder group, 25 percent in the tomato paste alone group and 60 percent in the control group.

Mossine said the protective effect of tomato-based products was restricted to prostate tumors, which is consistent with other research on tomatoes and cancer. Incidence of other tumors was too small to examine.

In vitro, Mossine and colleagues evaluated the anti-cancer properties of FruHis and 14 other D-fructose amino acids and found that FruHis in a concentrated form protected against DNA damage known to lead to prostate cancer. When combined with lycopene, FruHis stopped cancerous cell growth more than 98 percent of the time.

“Before this study, researchers attributed the protective effect of tomatoes to ascorbic acid, carotenoids, or phenolic compounds,” Mossine said. “FruHis may represent a novel type of potential dietary antioxidant. Experiments like these suggest that a combination of FruHis and lycopene should be investigated as a potential therapeutic anti-tumor agent, not just a prevention strategy.”

Although Mossine cautioned against drawing broad conclusions from this animal study, he said, “the result may introduce an additional intrigue into an ongoing dispute over the beneficial effects of dietary lycopene and tomato products in lowering the risk of prostate cancer. Human trials are certainly warranted.”

Source: American Association for Cancer Research

Josh says:

The paper is not currently available. I wonder how long it will take for FruHis to be available as a supplement or added to multivitamins. It certainly should be easy enough to mass produce.

Using a breakthrough technology, researchers led by a Weill Cornell Medical College scientist have pinpointed the hormone estrogen as a key player in about half of all prostate cancers.

Estrogen-linked signaling helps drive a discrete and aggressive form of the disease caused by a chromosomal translocation, which in turn results in the fusion of two genes.

“Fifty percent of prostate cancers harbor a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors,” explains study senior author Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College. Dr. Rubin is also attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

“Interfering with this gene fusion — or its downstream molecular pathways — will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so,” he says.

The findings are published in the May 27 online edition of the Journal of the National Cancer Institute. Dr. Rubin conducted the study while at the Brigham and Women’s Hospital and in collaboration with Dr. Todd Golub and other members of the Broad Institute of MIT and Harvard, in Cambridge, Mass. His team is now continuing this line of research at Weill Cornell.

Dr. Rubin, along with researchers at the University of Michigan, first discovered and described the common fusions between the TMPRSS2 and ETS family member genes subset of prostate cancer in the journal Science in 2005. “The discovery showed that these malignancies occur after an androgen (male hormone)-dependent gene fuses with an oncogene — a type of gene that causes cancer,” he explains.

Experts have long understood that male hormones help spur prostate cancer — in fact, androgen-deprivation therapy is a first-line treatment against the disease. And yet the disease can progress despite androgen reduction, suggesting that other pathways might be at work.

“So, we wanted to learn more — what is the genetic and molecular ‘fingerprint’ of this aggressive subset of prostate tumor”" Dr. Rubin says.

Answering that question required the analysis of 455 prostate cancer samples from trials in Sweden and the United States that were conducted as far back as the mid-1970s.

“These samples were placed in fixative and not frozen, so we needed new methods of retrieving the genetic information,” Dr. Rubin says. To do so, his team led by co-lead authors Dr. Sunita Setlur and Dr. Kirsten Mertz developed an innovative technology for effectively “reading” the gene transcription profiles hidden in the samples.

“That led us to perform the largest gene-expression microarray analysis yet conducted in prostate cancer research, amassing information on more than 6,000 genes,” Dr. Rubin says. “This allowed us to obtain a robust, 87-gene expression ’signature’ that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies.”

A close analysis of the signature yielded a surprise: that estrogen-dependent molecular pathways appear to play a crucial role in regulating (and encouraging) this aggressive subset of prostate cancer.

While estrogen is typically thought of as a “female” hormone, men produce it as well.

“Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG transcript, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells,” Dr. Rubin explains.

The finding could have implications for prostate cancer research, including drug development. According to Dr. Rubin, “We now believe that agents that dampen estrogen activity (ER-beta antagonists) could inhibit fusion-positive prostate cancers. Alternatively, any intervention that boosts estrogen activity (ER-alpha) might also give a boost to these aggressive malignancies.”

Research into just why fusion-positive prostate cancers are so aggressive — and potential molecular drug targets to help curb that aggression — will continue under Dr. Rubin’s direction at Weill Cornell, in collaboration with members of his group and with computational biologist Dr. Francesca Demichelis.

“The technological achievement of using fixed samples that were up to 30 years old is significant,” Dr. Rubin says. “In the future, we hope to explore banked tissues from clinical trials to help understand why they failed. This should lead to insight for designing the next trial.”

Source: New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Sunita R. Setlur, Kirsten D. Mertz, Yujin Hoshida, Francesca Demichelis, Mathieu Lupien, Sven Perner, Andrea Sboner, Yudi Pawitan, Ove Andrén, Laura A. Johnson, Jeff Tang, Hans-Olov Adami, Stefano Calza, Arul M. Chinnaiyan, Daniel Rhodes, Scott Tomlins, Katja Fall, Lorelei A. Mucci, Philip W. Kantoff, Meir J. Stampfer, Swen-Olof Andersson, Eberhard Varenhorst, Jan-Erik Johansson, Myles Brown, Todd R. Golub, and Mark A. Rubin. Estrogen-Dependent Signaling in a Molecularly Distinct Subclass of Aggressive Prostate Cancer. Journal of the National Cancer Institute Advance Access published on May 27, 2008. doi:10.1093/jnci/djn150

Josh says:

This has a lot of potential to help prostate cancer patients. Knowing that we should also try to inhibit estrogen and estrogen production in these patients is a novel strategy and hopefully will help save a lot of lives.

Combining natural organic atoms with metal complexes, scientists at The Wistar Institute have developed a new type of enzyme inhibitor capable of blocking a biochemical pathway that plays a key role in cancer development.

Based on studies in human melanoma cells, the research paves the way for developing new ways to treat cancer by dampening the overactive enzyme activity that leads to uncontrolled tumor growth.

Details of the study, to be published in the May 16 issue of the journal ACS Chemical Biology, show how small-molecule inhibitors can be designed to target a family of signaling proteins, called phosphatidyl-inositol-3-kinases, or PI3Ks. … Continue Reading »

Studies of how cancer cells spread have led to a surprising discovery about the creation of cells with adult stem cell characteristics, offering potentially major implications for regenerative medicine and for cancer treatment.

Some cancer cells acquire the ability to migrate through the body by re-activating biological programs that have lain dormant since the embryo stage, as the lab of Whitehead Member Robert Weinberg has helped to demonstrate in recent years. Now scientists in the Weinberg lab have shown that both normal and cancer cells that are induced to follow one of these pathways may gain properties of adult stem cells, including the ability to self-renew. … Continue Reading »

While researching new ways to stop the progression of cancer, researchers at the University of Oklahoma Health Sciences Center, have discovered a compound that has shown to prevent cancer in the laboratory. The research appears in the journal Gene Regulation and Systems Biology.

The compound, which still faces several rounds of clinical trials, successfully stopped normal cells from turning into cancer cells and inhibited the ability of tumors to grow and form blood vessels. If successful tests continue, researchers plan to create a daily pill that would be taken as a cancer preventive. … Continue Reading »

Researchers at the OU Cancer Institute have identified a new gene that causes cancer. The ground-breaking research appears in Nature’s cancer journal Oncogene.

The gene and its protein, both called RBM3, are vital for cell division in normal cells. In cancers, low oxygen levels in the tumors cause the amount of this protein to go up dramatically. This causes cancer cells to divide uncontrollably, leading to increased tumor formation.

Researchers used new powerful technology to genetically “silence” the protein and reduce the level of RBM3 in cancerous cells. The approach stopped cancer from growing and led to cell death. The new technique has been tested successfully on several types of cancers – breast, pancreas, colon, lung, ovarian and prostate. … Continue Reading »