Strep bacteria may treat pancreatic cancer (Reuters Health - 18/04/2008)

In mice implanted with human pancreatic cancer tumors, injecting live Streptococcus bacteria, similar to those that cause strep throat, directly into the 
tumors caused the tumors to shrink and die, German scientists report. "The utilization of live bacteria," as a danger signal, Dr. Claudia Maletzki told Reuters Health, "obviously has great potential for activating the immune system." Given the poor prognosis of patients with advanced pancreatic cancer, "novel" interventions 
are "imperative," Maletzki and colleagues at the University of Rostock note. In culture experiments, the researchers established that streptococcal bacterium known as S. 
pyogenes could mediate severe injury to pancreatic cancer cells. The team went on to examine the efficacy of S. pyogenes in a mouse model of aggressive pancreatic cancer known to have an intrinsic insensitivity to existing anti-cancer agents. They found that a single application of the live bacteria resulted in complete regression or 
death of the pancreatic tumors. In addition to direct destructive activity, they observed a helpful tumor-specific immune response, with generation of tumor-specific cells. "We think that patients suffering from tumors with very bad prognosis could substantially benefit from such alternative treatments stimulating the immune system," Maletzki said.

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Red wine compound may kill pancreatic cancer cells (Reuters Health -14/04/2008) 

A compound found in the skin of red grapes and red wine may help induce pancreatic cancer cells to malfunction and die, a lab study has found. The compound, called resveratrol, is produced by certain plants as part of their defense 
arsenal against pathogens. A handful of foods, including raspberries, blueberries and peanuts, contain resveratrol, but it is most abundant in the skin of red grapes and, therefore, red wine. In the new study, researchers at the University of Rochester Medical Center in New York treated human pancreatic cancer cells with resveratrol, either alone or in combination with radiation. They found that the wine compound disrupted the activity of the cancer cells' mitochondria, energy-producing centers needed for cells to function. Resveratrol also impaired certain cancer-cell proteins that thwart chemotherapy by pumping drugs out of the cell. In combination with radiation, but not alone, the compound bumped up the production of cell-damaging substances called reactive oxygen species -- potentially making the cancer 
cells more destructible.

And, in fact, cancer cells treated with the combination were more likely to self-destruct, the study found. "While additional studies are needed, this research indicates that resveratrol has a promising future as part of the treatment for cancer," lead investigator Dr. Paul Okunieff said in a university statement. He and his colleagues report the findings in the journal Advances in Experimental Medicine and 
Biology. What the results mean for cancer patients is not yet clear. Resveratrol is available in over-the-counter supplements, but there is no evidence that taking them aids cancer treatment. People undergoing cancer treatment should also not take any supplement without discussing it with their doctor first. Okunieff noted, however, that drinking wine is not always off limits for cancer patients -- that is, doctors do not advise moderate drinkers who already drink wine to stop doing so while they 
are undergoing treatment. Okunieff and his colleagues also point out that they used a relatively high dose of resveratrol, 50 micrograms per milliliter; the concentration found in red wine varies widely by type, but some wines have resveratrol levels as high as 30 micrograms per milliliter. However, no one yet knows whether resveratrol from red wine would affect tumors in the body the same way it does cancer cells in a lab dish.

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Molecular Marker May Help Identify Pancreatic Cancer, And Possibly Predict Survival Time (HealthCare - 5/05/2007)

Preliminary research suggests that the expression pattern of microRNA (a short RNA molecule) may be useful in differentiating between chronic pancreatitis and pancreatic cancer and may be able to distinguish long and short term survival time for patients with pancreatic cancer, according to an article in the May 2 issue of JAMA. Pancreatic cancer is a lethal disease, with the annual deaths nearly equaling the incidence of 33,000 in the United States, according to background information in the article. In humans, aberrant expression of miRNAs contributes to carcinogenesis by promoting the expression of proto-oncogenes (a normal gene that has the potential to become an oncogene [a gene that can cause a cell to become malignant]) or by inhibiting the expression of tumor suppressor genes. MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids; nucleic acids are present in all living cells). The role of miRNAs in ductal adenocarcinoma (malignant tumor) of the pancreas is not clear.

Mark Bloomston, M.D., of Ohio State University, Columbus, Ohio, and colleagues conducted a series of experiments to identify the pattern of miRNA expression in pancreatic adenocarcinoma to attempt to differentiate pancreatic cancer from benign pancreatic tissue and any differences in survival associated with certain miRNA expression. Study specimens were obtained at a National Cancer Institute-designated comprehensive cancer center from patients with ductal adenocarcinoma of the pancreas (n = 65) or chronic pancreatitis (n = 42) 
(January 2000-December 2005). RNA was harvested from resected pancreatic cancers and benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens and subsequent miRNA was analyzed to identify associations with certain tissue types and prognosis.

"We have identified-we believe for the first time-a global expression pattern of miRNAs that can differentiate ductal adenocarcinomas of the pancreas from normal pancreas and chronic pancreatitis with 95 percent accuracy," the authors write. "A subgroup of 6 miRNAs was able to distinguish long-term [greater than 24 months] survivors with node-positive disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor survival (midpoint, 14.3 months vs. 26.5 months)." "The present report contributes to the growing understanding of the role of miRNAs in oncogenesis and describes the global expression patterns of miRNAs in pancreatic adenocarcinoma. As we and other laboratories continue to identify the expression patterns of various solid tumors, the application of this knowledge may be broad. Such patterns may be able to be used to direct therapy in patients with metastatic tumors of unknown primary neoplasms or to help discriminate between benign and malignant neoplasms that would 
otherwise be indeterminate by routine histologic and immunohistochemical analysis." "More importantly, data such as ours, in which it is possible to begin to differentiate between patients with better or worse prognoses, may help guide the clinician when determining who should or should not receive aggressive therapy. Aside from these diagnostic and prognostic examples of how miRNA expression patterns can be used clinically, the ability of miRNAs to affect multiple genes in various pathways make them a logical target for investigation of novel antitumoral therapies. However, these preliminary data will first need to be validated in other 
studies," the authors write.

In an accompanying editorial, Scott A. Waldman, M.D., Ph.D., of Thomas Jefferson University, Philadelphia, and Andre Terzic, M.D., Ph.D., of Mayo Clinic, Rochester, Minn., comment on the findings of Bloomston and colleagues. "In the context of these exciting observations in a disease characterized by a dismal prognosis, should clinical oncologists and cancer geneticists begin to apply miRNA profiling to 
establish stratification of risk or define therapeutic targets in patients with pancreatic cancer? Although the analyses of Bloomston et al provide an initial glimpse into the future of clinical oncology, they reflect the beginning of the continuum integrating discovery, development, regulatory review, and the evidence basis of medicine required to translate advanced technology into clinical practice, a framework that has largely been ignored in the field of biomarkers. Indeed, while biomarkers represent the envisioned future for individualized management of patients with cancer, their potential has yet to be realized."

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Skin Rash Actually Signifies Better Outcomes For Pancreatic And Lung Cancer Patients- (ScienceDaily- 7/07/2007)


The appearance of a rash in cancer patients treated with erlotinib (Tarceva) is strongly associated with longer survival, according to researchers from the drug's developer, OSI Pharmaceuticals, Inc. This is not the first time that rash has been associated with a survival advantage with EGFR inhibitors - a class of drugs which includes erlotinib, cetuximab, panitumumab and others designed to block overproduction of the epidermal growth factor receptor - but it is the most detailed analysis to date. The study, published in the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, reports that for patients taking Tarceva who developed a moderate to severe rash, survival without progression of disease was 245 percent longer than in patients who had a mild rash or none at all. In fact, in the majority of cases, the more severe the rash, the longer a patient's cancer was held in check, researchers found. This rash, which often looks like acne, can be unpleasant enough for some people to consider discontinuing treatment, but "it is important for physicians and patients to understand that this a positive event because it means there is likely to be a better clinical outcome," said the lead author, Bret Wacker, MS Director of Biostatistics at OSI Pharmaceuticals, Inc. "Further studies are needed to both identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy." 

Although few patients dropped out of the large Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer due to the rash, Wacker said he fears those who are taking Tarceva outside of a clinical trial may be likely to stop treatment. "Some patients are stopping treatment because of the rash, yet those are the ones who are most likely to benefit," Wacker said. "This is a critical problem and rather than permanently discontinue treatment, patients should talk to their doctor about an effective and proactive strategy to manage the rash while continuing Tarceva therapy." According to the researchers, these rashes can be controlled with mild steroids or antibiotics, and in most cases, they will improve with treatment. They are believed to be due to an inflammatory response as a result of EGFR inhibition in skin tissue, Wacker said. 

The analysis looked at two placebo-controlled, double-blind, randomized, Phase III clinical trials testing Tarceva in advanced non-small cell lung cancer and pancreatic cancer - studies which led to approval of the agent for treating both cancers. Wacker and his team excluded patients who died in the first month after starting the study because they may not have had time to develop the rash or the rash may have been under-reported in these ill patients. Of the 673 patients in the lung cancer study, called BR.21, and in the Tarceva-treated group, 81 percent developed a rash, the majority of which was grade 2 (The study graded rashes from 1, relatively mild, to 4, severe). The researchers found that the presence of any rash correlated with overall and progression-free survival and that these correlations increased with the grade of rash. Specifically, Tarceva-treated patients who did not develop a rash survived a median of 3.3 months, compared to 7.1 months for those with a grade 1 rash, and 11.1 months for patients with more severe, grade 2 rashes. They also found, however, that 18 percent of patients treated with a placebo also developed a rash, and that overall survival in these patients was also significantly longer (a median of 8.2 months compared to 4.7 months), compared to placebo patients who didn't develop a rash. "We don't know why some patients treated with a placebo developed a rash, but it could be due to the strength of their immune system, and that is why they survived longer," Wacker said. 

In the second clinical trial (known as PA.3) that tested Tarceva and the chemotherapy drug gemcitabine against a placebo drug and gemcitabine in 521 patients with advanced pancreatic cancer, 71 percent of patients using Tarceva/gemcitabine developed a rash, compared with 30 percent of patients in the placebo group. This increased rate of rashes in the placebo group makes some sense, Wacker said, because rashes are known to occur with use of gemcitabine chemotherapy. But, unlike the BR.21 study, these pancreatic cancer patients with rashes in the placebo group did not experience an increase in survival compared to placebo group patients without a rash. In the Tarceva treatment group, only a more severe rash of grade 2 or higher was associated with increased survival. Patients with a grade 2 rash survived a median of 10.8 months, compared to treated patients with no rash (5.4 months) or a grade 1 rash (5.7 months). "These different results may be associated with the addition of gemcitabine with Tarceva, or the lower dose of Tarceva in this study, but we just don't know," he said. Wacker points out that lack of a rash doesn't necessarily mean that patients will not benefit from Tarceva. "A small percentage of patients who didn't develop a rash still had relatively long survival," he said. "But, still, overall, patients who don't develop a rash don't do as well as those who do."  

The study was funded by OSI Pharmaceuticals, Inc. 

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Pancreatic cancer test uses light- (UPI- 1/08/2007)


U.S. researchers using novel light-scattering techniques have found evidence that early stage pancreatic cancer causes detectable small intestine changes.
The easily monitored marker may allow early detection of a disease known for having few obvious symptoms, said a team of engineers from Northwestern University in Evanston, Ill., and physicians from Evanston-Northwestern Healthcare. The technique produces an optic fingerprint from the altered tissue and enhances data for a clearer diagnosis. Researchers scanned tissue samples from 19 people already diagnosed with pancreatic cancer and 32 without the disease. The researchers said they were able to properly distinguish patients with cancer at an accuracy approaching 100 percent and the clearest results came from patients in the earliest stages of the disease. The technological breakthrough causes light to penetrate the cells most affected by cancer without hitting deeper unaffected cells and to scan cell structures on the scale of nanometers, smaller than a doctor can see with a microscope.

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Protein Gives Clues to Pancreatic Cancer- When pp32 is gone, a tumor-spurring gene goes to work, researchers say- (HealthDay- 19/10/2007)

Researchers say they've identified a protein that could play a key role in the development of pancreatic cancer. According to a team at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, the protein -- called pp32 -- is a tumor-blocker than normally inhibits a cancer-causing gene called K-ras.
However, pp32 is absent in the most aggressive form of pancreatic cancer, the researchers said. More research is required, but pp32 could eventually become a marker for this deadly form of pancreatic cancer and a potential drug target. In laboratory experiments, the Jefferson team found that when pp32 is absent, mutations in the K-ras gene take over and turn cells cancerous. Adding pp32 to pancreatic cancer cells with K-ras mutations slowed the growth of the fast-growing cells. The researchers concluded that the loss of pp32 may be a key event in determining the aggressiveness of pancreatic cancer. The study was published online in the journal Modern Pathology.

"If we are able to learn more about this molecule, this may be a potential target that we could turn on in aggressive types of pancreatic cancers," team leader Jonathan Brody, assistant professor of surgery, said in prepared statement. "In theory, if we could find a way to upregulate this molecule in these pancreatic cancers, we may be able to arrest these fast-growing cancer cells as we did in experiments in this study. As we understand its molecular interactions, we could also somehow find the things that regulate it and extend our molecular understanding of this devastating disease." Previous research had also suggested a link between pp32 and prostate and breast cancer.

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High Insulin Levels Linked to Pancreatic Cancer- (HealthDay- 13/12/2007) 

Elevated blood levels of insulin do more than increase diabetes risk, they may also increase odds for pancreatic cancer. New research found that male smokers with the highest post-fasting blood insulin levels had double the risk of pancreatic tumors. "We had known that there was a pretty consistent association between diabetes and glucose intolerance and pancreatic cancer, but the reason for that association has been somewhat controversial," explained study author Rachael Stolzenberg-Solomon, an investigator in the nutritional epidemiology branch at the National Cancer Institute. "Some people feel that diabetes is a risk factor for pancreatic cancer, while some clinicians think some cases of diabetes are the result of latent pancreatic cancer."

This study's findings, said Stolzenberg-Solomon, support the hypothesis that the high levels of insulin that occur during the early stages of diabetes may promote the growth of pancreatic cancer cells. The findings appear in the Dec. 14 issue of the Journal of the American Medical Association. More than 32,000 Americans will be diagnosed with pancreatic cancer this year and most will die because the disease is usually detected far too late, according to the American Cancer Society (ACS). Cigarette smoking is responsible for almost one in three cases of pancreatic cancer, according to the ACS.

Because many pancreatic cancers aren't found until the later stages of the disease, the prognosis for this type of cancer is grim. Five-year survival rates range between 4 percent and 15 percent, depending on how far the disease has spread at the time of diagnosis. The current research culled data from a large Finnish study on more than 29,000 male smokers aged between 50 and 69 years at the start of the study. From the pool of 29,000, the researchers found 169 cases of pancreatic cancer that occurred after the fifth year of follow-up.

One reason the researchers only looked at cancers that occurred after five years of follow-up was to better assess if early diabetes might be contributing to the cancer. They could assess this because they had blood samples from each man to measure glucose and insulin levels. The researchers also randomly selected 400 men from the larger sample to act as controls.

Men with the highest levels of insulin in their blood and men with clinically diagnosed diabetes had double the risk of pancreatic cancer, compared to men with low levels of insulin and no history of diabetes. "This is the first study to show that insulin levels are increased with the risk of pancreatic cancer," said Eric Jacobs, a senior epidemiologist for the American Cancer Society.

Jacobs was quick to point out, however, that insulin injected for the treatment of diabetes is not being implicated as a risk factor for pancreatic cancer in this study. The suspected mechanism behind the increase in risk is that "pancreatic cells are exposed to a lot of insulin because insulin is produced in the pancreas. People with diabetes inject insulin into other locations, so the pancreatic cells aren't exposed to as much insulin," Jacobs explained.

Both Stolzenberg-Solomon and Jacobs said that this study's findings likely apply to women and nonsmokers as well. The findings suggest that increasing levels of physical activity might help prevent pancreatic cancer, along with reducing your risk of diabetes and other serious illnesses, according to Jacobs.
"Exercising more can help reduce levels of insulin," said Jacobs.

"While our study needs to be confirmed, it has potentially important implications for nutrition and pancreatic cancer prevention strategies," said Stolzenberg-Solomon. "Lose weight, increase your physical activity and maybe make other changes to your diet, like eat less saturated fat. These changes impact other cancers and other chronic disease," she said.

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Gene therapy tested in pancreatic cancer studies- (Yahoo News- 15/11/2007)

Gene therapy to block the blood supply to tumors could provide a promising new strategy for treating pancreatic cancer, Chinese scientists said on Tuesday. In test tube experiments and studies in mice they found the therapy suppressed the formation of new blood vessels, cutting off the nutrient supply needed to grow and spread in the body, although it had little direct effect on the cancerous cells.

In a report in the journal Gut, Dr Yao-Zong Yuan, of Shanghai Second Medical School, said although more research was needed "gene therapy may be a potent strategy to treat many malignant tumors, including pancreatic cancer."
Pancreatic cancer is an extremely difficult cancer to treat because often by the time it is diagnosed it has already spread in the body. About 216,000 new cases are diagnosed worldwide each year. Surgery is the most effective treatment but the majority of patients die within one year of diagnosis.

The Chinese scientists inserted a gene that produces a protein called vasostatin into a virus, or vector, to deliver it to the cancerous cells.In the test tube experiments, 72 hours after the cancerous cells were infected with the genetically modified virus the scientists said vasostatin was active. The gene therapy also curbed the growth of pancreatic tumors in the mice. The causes of pancreatic cancer, which usually occurs in people over 60 years old, are unknown. About 30 percent of cases are attributable to smoking.

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