Pancreatic Cancer 

Obesity ups a woman's pancreatic cancer risk-study (Reuters-15/07/2008)  

Obese women who carry most of their extra weight around the stomach are 70 percent more likely to develop pancreatic cancer, an international team of researchers reported on Tuesday. The findings suggest are some of the first evidence that the link between obesity and pancreatic cancer is as strong in women as in men, Juhua Luo of Sweden's Karolinska Institute and colleagues reported in the British Journal of Cancer. "We found that the risk of developing pancreatic cancer was significantly raised in obese postmenopausal women who carry most of their excess weight around the stomach," she said in a statement. "Obesity is a growing and largely preventable problem, so it's important that women are aware of this major increase in risk." Pancreatic cancer is the fifth leading cause of cancer death worldwide. It accounts for only about 2 percent of the cancers diagnosed each year but the first-year survival rate is less than 5 percent, according to Johns Hopkins University in Baltimore. Until now, smoking and chronic pancreatitis were the most well established risk factors for the disease in men and women, with much of the evidence also pointing to a stronger obesity link for men. As part of a large study known as the Women's Health Initiative, Luo and colleagues followed more than 138,000 menopausal women in the United States for more than seven years to investigate the links between obesity and pancreatic cancer. They found that 251 women developed the disease, and of these, 78 had the highest waist-to-hip ratios. After factoring in other risk factors, this was 70 percent more than the 34 women with the lowest excess stomach weight who got pancreatic cancer.

The findings also suggest that excess weight around the stomach may better predict the disease than the traditional Body Mass Index, or BMI, measurement for obesity, the researchers said. They also suggested that obesity could increase the risk of pancreatic cancer by affecting insulin levels, and that diabetes may also play a role. Obesity is one of the main risk factors for diabetes. "We know that carrying a high proportion of abdominal fat is associated with increased levels of insulin, so we think this may cause the link between obesity and pancreatic cancer," the researchers said. Several studies have shown that obesity raises the risk of several types of cancer including breast and colon as well as heart disease and other conditions.

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Nanoparticle Stops Cancer From Spreading (HealthDay News-11/07/2008)

California researchers say they have developed molecular "smart bombs" that stop pancreatic and kidney cancer from spreading in mice while causing fewer side effects and damage to healthy surrounding tissues than traditional chemotherapy. A team from the University of California, San Diego, designed a "nanoparticle" anti-cancer drug delivery system that zooms in on a protein marker called integrin avB3, which is found on the surface of certain tumor blood vessels. The marker is tied to the development of new blood vessels and malignant tumor growth. While the system had little impact on primary tumors, it halted the metastasis of pancreatic and kidney cancers throughout the bodies of mice. Cancer metastasis normally is much harder to treat than the primary tumor, and it usually leads to the patient's death. The findings were published in this week's online issue of the Proceedings of the National Academy of Sciences. According to the report, the system works with a lower dose of chemotherapy because it attacks the cancer with such precision. In most chemo treatments, the destruction of healthy tissue is a side effect as it floods the body with cancer-killing toxins. "We were able to establish the desired anti-cancer effect while delivering the drug at levels 15 times below what is needed when the drug is used systemically," study leader David Cheresh, vice chairman of pathology at UCSD, said in a university news release. "Even more interesting is that the metastatic lesions were more sensitive to this therapy than the primary tumor." 

UCSD engineers and oncologists together designed the nanoparticle -- a microscopic particle made of lipid-based polymers -- to work with the cancer-killing drug doxorubicin. "Doxorubicin is known to be an effective anti-cancer drug but has been difficult to give patients an adequate dose without negative side effects," Cheresh said. "This new strategy represents the first time we've seen such an impact on metastatic growth, and it was accomplished without the collateral damage of weight loss or other outward signs of toxicity in the patient." "Traditional cancer therapies are often limited or non-effective over time, because the toxic side effects limit the dose we can safely deliver to the patient," he said. "This new drug delivery system offers an important advance in treating metastatic disease." 

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Combination treatment safe for pancreatic cancer (Yahoo News-6/06/2008) 

Treating pancreatic cancer with a combination of treatments prior to surgery is safe and may be beneficial for patients, according to a new study. Led by by Dr. A. James Moser of the University of Pittsburgh Cancer Institute (UPCI) researchers presented data at the 44th annual meeting of the American Society of Clinical Oncology (ASCO). The preliminary study showed that patients with pancreatic cancer benefited from treatment with a combination of chemotherapy, biotherapy and radiation to shrink tumors before undergoing surgery. "The results from the first phase of this two-phase trial are encouraging," said Moser, who is co-director of the Pancreatic Cancer Center at the University of Pittsburgh School of Medicine. "Patients who receive surgery for pancreatic cancer tend to have better outcomes than those who don't, and this treatment allows us to reduce the tumor size prior to surgery." In the small study designed primarily to test safety, the researchers evaluated a combination treatment using the chemotherapy drug gemcitabine ( Gemzar®) with the targeted biotherapy drug, bevacizumab (Avastin®), and radiation therapy in patients with operable pancreatic cancer. Among the first 14 patients, 10 of the patients were considered eligible for surgery following the combination treatment. The incidence of serious adverse events following surgery was not increased in these patients, and several demonstrated significant shrinkage of their tumors before surgery. Given the evidence of tumor-shrinkage from the initial treatment, Moser and his colleagues are enrolling patients for the second stage of the study to further evaluate the effectiveness of the treatment. 

Each year, about 33,000 individuals in the U.S. are diagnosed with pancreatic cancer. It is difficult to diagnose early because symptoms are both rare and varied, and often don't occur until the disease has progressed. Because of this, patients diagnosed with pancreatic cancer typically have a poor prognosis, underscoring the importance of new treatment options. 

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Pancreatic Cancer Biomarkers Found (HealthDay News-13/06/2008) 

Five proteins linked to early development of pancreatic cancer have been identified by U.S. researchers, who said the finding is a step forward in efforts to develop a blood test to detect this type of cancer in the early stages, when cure rates are highest. 
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"Our team identified, for the first time, protein changes associated with early-stage pancreatic tumor development in genetically engineered mice that were also found to be associated with the presence of disease in humans at an early, pre-symptomatic stage," senior author Dr. Samir Hanash, of the Fred Hutchinson Cancer Research Center in Seattle, said in a prepared statement. They first identified the five proteins in mice with a precancerous condition called pancreatic intraepithelial neoplasma. The condition, if left untreated, eventually progresses to full-blown pancreatic cancer. The researchers then looked for the same proteins in blood samples from 13 people with asymptomatic, early-stage pancreatic cancer. The study was published in this week's issue of the online journal PLoS Medicine.

If this five-biomarker panel can be developed into a commercial screening test, it may prove particularly useful when combined with a currently available test that measures levels of a pancreatic cancer biomarker called CA19.9. Eighty percent of newly diagnosed pancreatic cancer patients have elevated levels of CA19.9, which is not linked to early-stage disease with symptoms. The researchers suggested that combined use of the five-biomarker panel and the CA19.9 test may greatly improve detection of early-stage pancreatic cancer before the onset of symptoms and may also help distinguish between cancer and pancreatitis, a noncancerous, inflammatory condition. Pancreatic cancer is the fourth leading cause of cancer death in the United States. It has a five-year survival rate of only 3 percent. Because there are no symptoms in the early stages, most patients aren't diagnosed until the cancer has spread beyond the pancreas. This is a major reason for the poor long-term survival rates.

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Studies Show New Screening Techniques Could Improve Survival Rates (Yahoo News-20/05/2008)

Tests Detect Pancreatic Cancer Earlier
For people at high risk of pancreatic cancer, innovative approaches to screening and surveillance are helping to catch tumors earlier, when they're more treatable. The tests are already available at many major academic medical centers throughout the country. Researchers hope the new findings will help increase testing of high-risk patients who can gain the most benefit -- typically people whose relatives have had pancreatic cancer. Currently, most people survive only months from diagnosis; only 4% survive five years. The reason: Pancreatic cancer symptoms typically don't develop until the cancer has spread beyond the pancreas and surgical removal of the cancer is no longer possible, says Mark P. Callery, MD, associate professor of surgery at Harvard Medical School and chief of the division of general surgery at Beth Israel Deaconess Medical Center. Early detection can mean improved survival, and "now we're finding that with screening of people at high risk -- those with first- or second-degree relatives with the cancer -- we may have an impact on outcomes," Callery says. If detected early, when still confined to the pancreas, the five-year survival rate can be as high as 33%. Callery moderated a media briefing to discuss the findings at Digestive Disease Week 2008 in San Diego. An estimated 37,680 people in the U.S. will be diagnosed with pancreatic cancer in 2008, according to the American Cancer Society. About 34,290 Americans will die of the disease, making it the fourth deadliest cancer.

Ultrasound Plus X-Rays Detect Cancer Earlier
In one new study, a combination of ultrasound and specialized X-rays helped to detect the cancer earlier in people with two or more family members with pancreatic cancer. The findings are important because at least 10% of pancreatic cancer is inherited, says Teresa A. Brentnall, MD, associate professor of medicine at the division of gastroenterology at the University of Washington in Seattle. First, the patients were given an endoscopic ultrasound, which involves passing a thin, flexible tube (endoscope) into a patient's gastrointestinal tract. A tiny ultrasound probe at its tip produces high-energy sound waves (ultrasound) that create images of surrounding tissue. "It gives us a really nice view of the pancreas. We can find tiny lesions that are the earliest signs of pancreatic cancer," Brentnall says. Patients with abnormal findings on the endoscopic ultrasound were then offered specialized X-rays of the ducts that carry bile from the liver or gallbladder to the small intestine. Sometimes pancreatic cancer causes these ducts to narrow and block or slow the flow of bile. "The ducts should normally be nice and smooth. But in people with precancerous changes, they become bumpy and irregular," Brentnall tells WebMD.
If both tests were abnormal, patients were offered surgery to have their pancreas removed. None of 20 patients who had the operation developed pancreatic cancer during an average follow-up of seven years. Without the surgery, these patients would have had a high risk of developing incurable cancer, she says. However, the surgery is not without risks of its own. Without a pancreas, you don't produce insulin to regulate your blood sugar, causing you to develop insulin-dependent diabetes.

Blood Test Plus Ultrasound Detects Cancer
In a second study, researchers found that a combination of endoscopic ultrasound and a blood test for a tumor marker called CA19-9 helped to detect pancreatic cancer at an earlier stage in high-risk people. So far, 272 people ages 50 to 80 with at least one first-degree relative who had the disease have been screened with the combination in the ongoing study. In addition to family history, "age is another factor we can use to target people for screening," says researcher Richard Zubarik, MD, associate professor of medicine and chief of endoscopy at Fletcher Allen Health Care in Burlington, Vt. More than 90% of people who develop pancreatic cancer are over age 50, he tells WebMD. CA 19-9 is often produced by pancreatic cancers, and its level is elevated in more than 90% of pancreatic cancer patients. It's typically used to gauge how well a treatment is working in those already diagnosed with pancreatic cancer. The cost to detect one case of pancreatic cancer was just over $14,000, and the cost to detect precancerous abnormal cell growth was about $11,000.  "If we use this protocol, we can detect cancer at an early stage," Zubarik says.

Heavy Drinking, Smoking Raises Pancreatic Cancer Risk
Also at the meeting, researchers reported that heavy smokers and drinkers are at risk of developing the cancer much earlier than is typical. The more tobacco and alcohol one consumes, the younger the age at which the disease tends to strike, and beer drinkers may be at particularly high risk, they say. While previous studies have shown that smoking tobacco and drinking alcohol are risk factors for pancreatic cancer, "we didn't know if risk increased with dose," says Michelle A. Anderson, MD, assistant professor of medicine at the University of Michigan in Ann Arbor. To find out, she and colleagues studied data on about 450 pancreatic cancer patients enrolled in an international patient registry. The study showed that "the more a person smoked or drank, the younger the onset of the cancer, and that of the two, drinking has a worse effect," Anderson says.

Among the findings:
People who drank more than three drinks a day were diagnosed with pancreatic cancer at an average age of 60 vs. 67.3 for teetotalers. 
Heavy smokers developed the cancer about two years earlier than people who didn't smoke or drink: 64.9 years old vs. 66.7 years old. Heavy smokers were defined as people who smoked 21 or more pack-years in a lifetime, or the equivalent of at least one pack a day for 21 years. 
Beer drinkers tended to develop pancreatic cancer at an earlier age than those who preferred wine or hard liquor. While the finding could have been due to chance, Anderson tells WebMD that she believes that the link will hold up when larger numbers of people are studied. 
The median age of onset for patients who drank only beer was 62.2 compared with 68.2 for those drinking other types of alcohol. 
Heavy Drinking, Smoking Raises Pancreatic Cancer Risk 
Anderson says that regardless of their choice of beverage, heavy drinkers and smokers may want to talk to their doctors about pancreatic cancer screening. "Normally you wouldn't think about screening a 55-year-old with no family history. But if they're a heavy drinker or smoker, you may want to do it earlier," she says.

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Protein found to shield pancreatic cancer cells from self-destruction(Yahoo News-20/04/2007)

An over expressed protein protects human pancreatic cancer cells from being forced to devour themselves, removing one of the body's natural defenses against out-of-control cell growth, researchers at The University of Texas M. D. Anderson Cancer Center report in the March issue of Molecular Cancer Research. The protein tissue transglutaminase, known by the abbreviation TG2, previously has been found by researchers at M. D. Anderson and elsewhere to be overexpressed in a variety of drug-resistant cancer cells and in cancer that has spread from its original organ (metastasized). "In general, you rarely see overexpression of TG2 in a normal cell," says Kapil Mehta, Ph.D., professor in the M. D. Anderson Department of Experimental Therapeutics, who began 10 years ago studying TG2 as an inflammatory protein. Mehta and colleagues in the past year have connected TG2 overexpression to drug-resistant and metastatic breast cancer, pancreatic cancer and melanoma.

Expression of TG2 is tightly regulated in a healthy cell, Mehta says, and is temporarily increased in response to certain hormones or stress factors. "However, constitutive expression of this protein in a cancer cell helps confer protection from stress-induced cell death," Mehta says. "We are developing TG2 as a pharmaceutical target and are now working with a mouse model to that end." The mechanisms by which TG2 might promote drug-resistance and metastasis have remained elusive, the researchers note. In this paper, the M. D. Anderson team shows in lab experiments that inhibiting the protein in pancreatic cancer cells leads to a form of programmed cell suicide called autophagy, or self-digestion. TG2 was inhibited in two separate ways. First, the researchers blocked another protein known to activate TG2. Secondly, they also directly targeted TG2 with a tiny molecule known as small interfering RNA tailored to shut down expression of the protein. In both cases, the result was a drastic reduction of TG2 expression (up to 94 percent) and telltale signs of autophagy in the cancer cells, which became riddled with cavities called vacuoles. When autophagy occurs, a double membrane forms around a cell organ, or organelle. This autophagosome then merges with a digestive organelle called a lysosome and everything inside is consumed, leaving the vacuole and a residue of digested material. If enough of this happens, the cell dies.

Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics and study co-author, notes that the research also shows that the self-consuming cell death prevented by TG2 is independent of a prominent molecular pathway also known to regulate autophagy called the mammalian target of rapamycin. "Targeting TG2, or its activating protein PKC, or both, presents a novel and potentially effective approach to treating patients with pancreatic cancer," Lopez-Berestein said. Research in the mouse model remains in the early stages, the researchers caution. The researchers also show that the TG2 pathway also is separate from another, better known, form of programmed cell death called apoptosis. Apoptosis, like autophagy, is a normal biological defense mechanism that systematically destroys defective cells by forcing them to kill themselves. In apoptosis, the cells die via damage to their nucleus and DNA, with other cellular organelles preserved. Autophagy kills by degrading those other organelles while sparing the nucleus. Mehta's lab reported in a Cancer Research paper last September that TG2 overexpression also activates a protein called nuclear factor-kB known to play a role in regulating cell growth, metastasis and apoptosis. This pathway, Mehta explained, could make TG2 an attractive target for other forms of cancer as well.

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ImClone’s Drug Fails in Pancreatic Cancer Study (BLOOMBERG NEWS-11/04/2007)

ImClone Systems said yesterday that its cancer drug Erbitux failed to help pancreatic cancer patients live longer in a study, a setback for the company’s plan to expand the market for its only product. The research was testing whether Erbitux, given with chemotherapy, extends survival of patients with cancer that has spread from the pancreas. ImClone and its partner, the Bristol-Myers Squibb Company, announced the results in a statement yesterday. ImClone counted on positive results to help win Food and Drug Administration approval for the new use. Erbitux, which had $1.1 billion in 2006 sales, was accepted as a treatment for colon cancer in 2004 and won F.D.A. clearance for head and neck cancer last year. The study’s researchers, along with ImClone and Bristol-Myers, plan to review the results. “Pancreatic cancer is extremely tough to treat, and there was some hope on the part of some people” that Erbitux would be effective, said Brian Rye, an analyst with Janney Montgomery Scott in Philadelphia. “If it would have worked, the upside would have been greater than the downside is now.”

“In the wake of recent successes Erbitux has had, we think the future is still very bright for Erbitux,” said Mr. Rye, who rates the shares a buy. “We do expect 2007 to gain momentum in colorectal cancer and other indications still to come.”  ImClone has not given up on Erbitux’s use in pancreatic cancer and plans additional tests, including a study testing a combination of Erbitux and Avastin and chemotherapy against the disease, the company said. ImClone is the co-marketer of Erbitux with Bristol-Myers in the United States and receives about 39 percent of the drug’s sales through the partnership. The study, involving more than 700 pancreatic cancer patients, was conducted by the Southwest Oncology Group, a cancer-research network sponsored by the National Cancer Institute.

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Multiple Studies Demonstrate the Use of Hyperthermia Therapy in . Treating Pancreatic Cancer (Yahoo News-24/04/2008)

Business Wire US0556621003 BSD Medical Corporation (NASDAQ:BSDM) today began to report highlights from 204 abstracts summarizing presentations at the International Congress on Hyperthermic Oncology (ICHO) conducted this month in Munich, Germany. This conference is the combined meeting of the European Society for Hyperthermic Oncology (ESHO), the U.S. Society of Thermal Medicine (STM) and the Asian Society for Hyperthermic Oncology (ASHO). This press release deals with a summary of four presentations made on the use of hyperthermia therapy in the quest for better treatment of pancreatic cancer. Pancreatic cancer treatment with hyperthermia therapy was a subject of keen interest at ICHO, as researchers in different parts of the world reported their independent results in this effort. Pancreatic cancer is the fourth leading cause of cancer death in men and women, with 37,170 new cases projected in the United States this year by the American Cancer Society, and 33,370 deaths from the disease. Even a small benefit from a new treatment is important for patients faced with this deadly form of cancer. While the use of hyperthermia therapy in treating some other forms of cancer has been heavily researched, little has been known about the potential of the therapy in treating pancreatic cancer patients, a cancer for which better treatment is urgently needed.

The Verona Study Fifty-seven pancreatic cancer patients were accrued between 2000 and 2006 in a study conducted by the Department of Radiotherapy of the University of Verona in Italy. Eleven patients were lost at follow up, leaving 46 evaluable patients. Patients were divided into groups A and B.
Group A consisted of 25 patients who received chemotherapy and hyperthermia plus radiation (or chemotherapy alone in the case of 5 patients affected by distant metastases wherein radiation was excluded).
Group B consisted of 21 patients (none of whom had metastatic disease) who received chemotherapy and radiation without hyperthermia.
At 24 months, 9 patients (36%) were alive in group A, compared to 4 patients (19%) who were alive in group B.
Chemotherapy was well tolerated in both groups, with no more toxicity in group A.
The study concluded that hyperthermia is a promising therapeutic modality in the treatment of locally advanced pancreatic cancer, that it does not increase acute or late toxicity of combined treatment, and that it seems to enhance the efficacy of both chemotherapy plus radiation and chemotherapy alone with metastatic disease, as 5 patients with distant metastases were included in group A. The Munich Study Researchers associated with the University of Munich, Germany, reported results after treating 22 pancreatic patients in a very difficult stage of the disease (19 metastatic and 3 with locally advanced pancreatic cancer).
Using a combination of gemcitabine plus cisplatin as their chemotherapy drugs combined with hyperthermia therapy, the treatment reached their target for improvement, and based on these data a randomized first-line phase III clinical trial has been initiated.

A number of cancer research institutions with BSD-2000 systems have agreed to participate in this government sponsored phase III study. Kyoto Studies This study conducted at the Kyoto Prefectural University of Medicine in Japan was a retrospective analysis of patients with advanced inoperable pancreatic cancer who were treated with the sequential combination of chemotherapy (gemcitabine) plus hyperthermia therapy between 2004 and 2007. Patients treated with gemcitabine alone between December 2003 and April 2005 were allocated as a control group (historical control). Patients in the experimental group received gemcitabine plus hyperthermia therapy. The disease control rate was 57.1% for the experimental group and 14.3% for patients treated with gemcitabine alone (historical control). The one-year overall survival for the control group was 30%, compared to 49% for the experimental group that received hyperthermia therapy. The study concluded that this combination therapy could be a potential first-line treatment for patients with advanced pancreatic cancer. A second Kyoto study was also presented, designed to identify some of the mechanisms whereby hyperthermia therapy works in combination 

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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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