Protein May Indicate Pancreatic Cancer Risk

A protein that dwindles in response to obesity and a sedentary lifestyle may one day help doctors predict which people are at increased risk for pancreas cancer, new research by Dana-Farber Cancer Institute and collaborating researchers indicates.

In a report in the Aug. 15 issue of Cancer Research, the researchers observed that, in a large study group, people with the lowest blood levels of a protein called IGFBP-1 were twice as likely to develop pancreas cancer as those with higher levels. Though much work remains to determine if the protein -- whose acronym stands for insulin-like growth factor binding protein-1 -- is a reliable indicator of pancreas cancer risk, the finding adds to the scientific understanding of how the disease develops.

"The levels of insulin and another circulating hormone, insulin-like growth factor or IGF, are modified by obesity and sedentary lifestyle, and there is evidence that these hormones may stimulate the growth of pancreas cancer cells," said the study's lead author, Brian Wolpin, MD, of Dana-Farber. "When IGF binds to proteins like IGFBP-1, there may be less IGF available to bind to pancreas cancer cells and promote their growth. We wanted to determine whether IGFBP-1 levels in the blood were linked to pancreas cancer risk".

The researchers measured circulating IGFBP-1 levels in a select group of participants in four large, ongoing health studies: the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. They collected blood samples from 573 participants and, four or more years later, checked IGFBP-1 levels in the samples of 144 people who developed pancreas cancer and 429 who did not.

They observed that the quarter of the group whose IGFBP-1 levels were lowest had twice the risk of developing pancreas cancer of those in the top three quarters. The connection became even stronger over time: Among cases diagnosed at least eight years after blood collection, those in the bottom quarter of IGFBP-1 levels had nearly three-and-a-half times the pancreas cancer risk of those in the upper quarters.

The risk may be elevated because higher amounts of IGFBP-1 are able to "soak up" more IGF, leaving less available to spur pancreas cancer cell growth, or because IGFBP-1 has some cancer-blocking properties of its own, said Wolpin, who is also an instructor in medicine at Harvard Medical School. Another possibility is that other molecules may be involved, for which IGFBP-1 acts as an intermediary.

"It's known that a variety of proteins are affected by obesity and sedentary lifestyle," he added. "Studies are exploring whether a subset of these may play a role in the risk of developing pancreas cancer. More research is also needed on how alterations in insulin and proteins in the IGF family alter the risk of this difficult disease".

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Treatment of pancreatic adenocarcinoma

Medicineworld.org: Treatment of pancreatic adenocarcinoma


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Pancreatic ductal adenocarcinoma (PDAC) is a highly cancerous digestive tumor with a very poor prognosis. Hypoxia-inducible transcription factor-1a (HIF-1a) is involved in cancerous progression in a number of solid tumors, including PDAC, upregulation of HIF-1a accelerates PDAC progression, but the exact regulatory mechanisms of HIF-1ain PDAC has not been unequivocally addressed. Recently, an increasing number of studies reported that toll-like receptors (TLRs) were upregulated in epithelial malignancies and involved in tumor progression, but whether TLRs, such as TLR4, is expressed on PDAC cells remains unknown. In immune-related cells, TLR signal pathway may induce expression of HIF-1a, but it is also still unclear whether there exists some association between TLR4 and HIF-1a in tumor microenviroment, such as PDAC.

A research article to be published on June 21, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by He-Shui Wu, MD, from Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, used real time polymerase chain reaction and immunohistochemistry, to detect TLR4, NF-?B p65 and HIF-1a expression in 65 cases of PDAC tissues and 38 cases of corresponding adjacent tissues.

Their study revealed that TLR4, NF-?B p65 and HIF-1a were overexpressed in PDAC. The expression of TLR4 and HIF-1a was linked to tumor size, lymph node metastasis, venous invasion and pathological stage. Furthermore, the expression of TLR4 was positively correlated with expression of HIF-1a. Thus, TLR4 appears to be a novel marker for the progression and prognosis of PDAC, and may provide a new strategy for therapeutic intervention in the therapy of patients with PDAC in the future.

Based on these results and prior reports, the authors speculated that active TLR4 signal pathway appears to be partly involved in up-regulating HIF-1a in PDAC tumor microenviroment via NF-?B pathway, and promoted progression of PDAC. These results demonstrated a new view of molecules involved in regulatory mechanism of HIF-1a and thus may provide new therapeutic targets for PDAC.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly cancerous digestive tumor with a very poor prognosis. Hypoxia-inducible transcription factor-1and#945; (HIF-1and#945;) is involved in cancerous progression in a number of solid tumors, including PDAC, upregulation of HIF-1and#945; accelerates PDAC progression, but the exact regulatory mechanisms of HIF-1and#945;in PDAC has not been unequivocally addressed. Recently, an increasing number of studies reported that toll-like receptors (TLRs) were upregulated in epithelial malignancies and involved in tumor progression, but whether TLRs, such as TLR4, is expressed on PDAC cells remains unknown. In immune-related cells, TLR signal pathway may induce expression of HIF-1and#945;, but it is also still unclear whether there exists some association between TLR4 and HIF-1and#945; in tumor microenviroment, such as PDAC.
Medicineworld.org: Treatment of pancreatic adenocarcinoma

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The War on Cancer Continues

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Report finds progress has been made fighting some, but not all, malignancies

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Gene Mutation May Be Key to Familial Pancreatic Cancer

THURSDAY, Dec. 29 (HealthDay News) -- Individuals may face a higher hereditary risk for developing pancreatic cancer if they carry abnormalities in the so-called "ATM" gene, new research reveals.

The finding, reported in an upcoming issue of Cancer Discovery, stems from genetic-sequencing work conducted among 166 pancreatic cancer patients. For comparative purposes, 190 other individuals who did not have pancreatic cancer also underwent sequencing.

The study was led by Alison Klein, an associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and director of the National Familial Pancreas Tumor Registry.

Noting that 10 percent of pancreatic cancer patients are from families in which more than one member has battled the disease, Klein pointed out in a news release from the American Association for Cancer Research that "there was significant reason to believe this clustering was due to genetics."

But she added that no previous effort had "been able to find the causative genes that explained the cluster of pancreatic cancer for a majority of these families."

Among the pancreatic cancer patients examined, four were found to have the ATM gene mutation. By contrast, none of the healthy individuals who were sequenced carried the abnormality, according to the report.

Ultimately, the finding could lead to the development of a new screening option for a disease that kills 95 percent of patients within five years of diagnosis, according to the release. Though endoscopy is under study as another possible screening tool, there are as yet no other recommended screening alternatives for the number four cause of cancer-related death.

More information

For more on pancreatic cancer, visit the U.S. National Library of Medicine.

SOURCE: American Association for Cancer Research, news release, Dec. 29, 2011

Copyright © 2011 HealthDay. All rights reserved.

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New Drug Developed To Target And Destroy Tumor Cells Successful In Mouse Model Of Pancreatic Cancer

Main Category: Pancreatic Cancer
Article Date: 21 Oct 2012 - 0:00 PDT Current ratings for:
New Drug Developed To Target And Destroy Tumor Cells Successful In Mouse Model Of Pancreatic Cancer

A new drug created at the University of Minnesota may hold the answer to defeating pancreatic cancer, according to results published in the prestigious journal Science Translational Medicine.

The study is based on successful outcomes in a mouse model - results researchers expect to carry over to human patients when the drug potentially begins human trials in 2013.

The drug, Minnelide, is a type of injectable chemotherapy designed to target tumor cells. The drug works by inhibiting a heat shock protein, HSP 70, which has been proven to aid the growth of tumor cells. By stopping HSP 70 from working, Minnelide disperses the cells integral to the tumor's growth and the cancer disintegrates.

The drug is based on patented technology designed in the labs of Ashok Saluja, Ph.D., professor and vice chair of research in the University of Minnesota Medical School's Department of Surgery, Selwyn Vickers, M.D., chairman of the Department of Surgery, and Gunda Georg, Ph.D., director of the Institute for Therapeutics Discovery and Development in the College of Pharmacy. Bruce Blazar, M.D., director of the Center for Translational Medicine, also partnered on this project.

Pancreatic cancer is the most lethal of all cancers. This year alone, more than 44,000 Americans will be diagnosed with the disease and the median survival time following a pancreatic cancer diagnosis is just six months.

"A diagnosis of pancreatic cancer is incredibly grim. There is no good way to treat or cure this particular type of cancer," said Saluja, who holds the Eugene C. and Gail V. Sit Chair in Pancreatic and Gastrointestinal Cancer Research, "and the best options currently available offer just six weeks of added survival. It is far from tackling the real problem which is that pancreatic cancer tumor cells make survival proteins, rendering them increasingly difficult to defeat."

In 2007, Saluja and his collaborators discovered pancreatic cancer cells have too much HSP 70, which protects cells from dying. Because of this excess protein, pancreatic cancer cells are difficult to target with drugs, meaning the logical next step in fighting the cancer was to determine how to inhibit HSP 70 in these tumor cells.

Saluja found that triptolide, a compound derived from plants in China, worked to halt the development of HSP 70 in tumor cells, but because triptolide is not water soluble, it was still difficult to administer to patients. The Institute for Therapeutics Discovery and Development at the University of Minnesota, in collaboration with the Saluja lab, worked to make triptolide water soluble. They named their drug Minnelide as a nod to the compound from which it was derived, triptolide, and its discovery location, the University of Minnesota.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject.
The University of Minnesota holds the patent on the modifying factors that create Minnelide from triptolide. It has been licensed to Minneamrita Therapeutics LLC for production.

Funding for this research was provided by NIH grants R01CA124723 and R01 CA170496, as well as the Katherine and Robert Goodale Foundation and the Hirshberg Foundation.

University of Minnesota Academic Health Center

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Pancreatic Cancer Risk May Be Reduced By High Dietary Antioxidant Intake

Editor's Choice
Main Category: Pancreatic Cancer
Also Included In: Cancer / Oncology;  Nutrition / Diet
Article Date: 23 Jul 2012 - 16:00 PDT Current ratings for:
Pancreatic Cancer Risk May Be Reduced By High Dietary Antioxidant Intake

Individuals can significantly reduce their risk of developing pancreatic cancer by increasing their dietary intake of the antioxidant vitamins C, E, and selenium, say researchers who are leading the Norfolk arm of the European Prospective Investigation of Cancer (EPIC) study.

The study, published in the journal Gut, states that 1 in 12 of these cancers might be prevented if the association turns out to be casual.

More than a 250,000 people die each year around the world due to pancreatic cancer. In the UK, 7,500 people are diagnosed with the disease each year.

Only 5% of patients with pancreatic cancer survive beyond 5 years, say the researchers. Risk factors of the disease include, smoking, type 2 diabetes, and diet.

The team analyzed the health of more than 23,500 adults who participated in the Norfolk arm of the EPIC study between 1993 and 1992. Patients were aged 40 to 74 years old.

?? All study participates filled out a food diary tracking the types and amounts of food the consumed during a 7 day period. In addition, they detailed the methods they used to prepare the food.

The team then matched each entry in the food diary to one of 11,00 food items. They then used a specially designed computer program called DINER in order to calculate the nutrient values.

According to the researchers, 49 people developed pancreatic cancer within 10 years of participating in the study, and this figure increased to 86 people by 2010. On average, they survived six months after being diagnosed with pancreatic cancer.
br> ?? The nutrient intakes of participants diagnosed with the disease were compared with those of almost 4,000 healthy individuals in order to see if there were any differences.

?? According to the researchers, weekly intake of selenium in the top 25% of consumption roughly reduced their risk of developing pancreatic cancer by 50% compared with those whose intake was in the bottom 25%.

In addition, patients were 67% less likely to develop the disease if their intake of vitamins C, Em and selenium was in the top 25% of consumption. ??

The researchers note that antioxidants may neutralize free radicals and curb genetically programmed influences, as well as stimulating the immune system response.

They explained:

"Other trials using antioxidant supplements have not produced such encouraging results, but this may be because food sources of these nutrients may behave differently from those found in supplements. If a causal association is confirmed by reporting consistent findings from other epidemiological studies, then population based dietary recommendations may help prevent pancreatic cancer."

Written by Grace Rattue ??
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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Oral Bacteria Associated With Pancreatic Cancer Risk

Main Category: Pancreatic Cancer
Also Included In: Dentistry;  Infectious Diseases / Bacteria / Viruses
Article Date: 20 Sep 2012 - 1:00 PDT Current ratings for:
Oral Bacteria Associated With Pancreatic Cancer Risk

Pancreatic cancer is highly lethal and difficult to detect early. In a new study, researchers report that people who had high levels of antibodies for an infectious oral bacterium turned out to have double the risk for developing the cancer. High antibody levels for harmless oral bacteria, meanwhile, predicted a reduced pancreatic cancer risk.

A new study finds significant associations between antibodies for multiple oral bacteria and the risk of pancreatic cancer, adding support for the emerging idea that the ostensibly distant medical conditions are related.

The study of blood samples from more than 800 European adults, published in the journal Gut, found that high antibody levels for one of the more infectious periodontal bacterium strains of Porphyromonas gingivalis were associated with a two-fold risk for pancreatic cancer. Meanwhile, study subjects with high levels of antibodies for some kinds of harmless "commensal" oral bacteria were associated with a 45-percent lower risk of pancreatic cancer.

"The relative increase in risk from smoking is not much bigger than two," said Brown University epidemiologist Dominique Michaud, the paper's corresponding author. "If this is a real effect size of two, then potential impact of this finding is really significant."

Pancreatic cancer, which is difficult to detect and kills most patients within six months of diagnosis, is responsible for 40,000 deaths a year in the United States.

Several researchers, including Michaud, have found previous links between periodontal disease and pancreatic cancer. The Gut paper is the first study to test whether antibodies for oral bacteria are indicators of pancreatic cancer risk and the first study to associate the immune response to commensal bacteria with pancreatic cancer risk. The physiological mechanism linking oral bacteria and pancreatic cancer remains unknown, but the study strengthens the suggestion that there is one.

"This is not an established risk factor," said Michaud, who is also co-lead author with Jacques Izard, of the Forsyth Institute and Harvard University. "But I feel more confident that there is something going on. It's something we need to understand better."

Izard, a microbiologist, said the importance of bacteria in cancer is growing. "The impact of immune defense against both commensals and pathogenic bacteria undeniably plays a role," he said. "We need to further investigate the importance of bacteria in pancreatic cancer beyond the associated risk."

Prospective, controlled study

To conduct their research, Michaud and Izard drew on medical records and preserved blood samples collected by the Imperial College-led European Prospective Investigation into Cancer and Nutrition Study, a massive dataset of more than 500,000 adults in 10 countries. Detailed health histories and blood samples are available from more than 380,000 of the participants.

From that population, the researchers found 405 people who developed pancreatic cancer, but no other cancer, and who had blood samples available. The researchers also selected 416 demographically similar people who did not develop pancreatic cancer for comparison.

The researchers blinded themselves to which samples came from cancer patients and which didn't during their analysis of the blood, which consisted of measuring antibody concentrations for 25 pathogenic and commensal oral bacteria. In their study design and analysis they controlled for smoking, diabetes, body mass index, and other risk factors.

An important element of the study design was that date of the blood samples preceded the diagnosis of pancreatic cancer by as much as a decade, meaning that the significant difference in antibody levels were likely not a result of cancer.

Instead, the underlying mechanisms that link Porphyromonas gingivalis to pancreatic cancer could be causal, Michaud said, although much more research is needed to understand this association.

Meanwhile, the researchers speculate, the association of high levels of antibodies for commensal bacteria and pancreatic cancer, may indicate an innate, highly active immune response that is protective against cancer.

"Genetic determinants of immune surveillance clearly play a critical role in pancreatic cancer development," the authors wrote. "Consequently, it is plausible that elevated levels of antibodies to oral bacteria in individuals serve as a marker for a genetically stronger immune response, providing protection against carcinogenesis."

Michaud, who studies cancer risk factors generally, continues to investigate the association between oral bacteria and pancreatic cancer in collaboration with Izard.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject. Possible clue to a hard-to-diagnose cancer: http://news.brown.edu/files/imagecache/ursa_feature_image/article_images/Periodontic1.jpg
The National Cancer Institute was the primary funder of the study.
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Soft drink consumption and pancreatic cancer

Consuming two or more soft drinks per week increased the risk of developing pancreatic cancer by nearly twofold compared to individuals who did not consume soft drinks, according to a report in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Although relatively rare, pancreatic cancer remains one of the most deadly, and only 5 percent of people who are diagnosed are alive five years later.

Mark Pereira, Ph.D., senior author on the study and associate professor in the School of Public Health at the University of Minnesota, said people who consume soft drinks on a regular basis, defined as primarily carbonated sugar-sweetened beverages, tend to have a poor behavioral profile overall.

However, the effect of these drinks on pancreatic cancer may be unique.

"The high levels of sugar in soft drinks may be increasing the level of insulin in the body, which we think contributes to pancreatic cancer cell growth," said Pereira.

For the current study, Pereira and colleagues followed 60,524 men and women in the Singapore Chinese Health Study for 14 years. During that time, there were 140 pancreatic cancer cases. Those who consumed two or more soft drinks per week (averaging five per week) had an 87 percent increased risk compared with individuals who did not.

No association was seen between fruit juice consumption and pancreatic cancer.

Pereira said that these results from Singapore are likely applicable to the United States.

"Singapore is a wealthy country with excellent health care. Favorite pastimes are eating and shopping, so the findings should apply to other western countries," said Pereira.

Susan Mayne, Ph.D., associate director of the Yale Cancer Center and professor of epidemiology at the Yale School of Public Health, said these study results are intriguing but have some key limitations that should be considered in any interpretation.

"Although this study found a risk, the finding was based on a relatively small number of cases and it remains unclear whether it is a causal association or not. Soft drink consumption in Singapore was associated with several other adverse health behaviors such as smoking and red meat intake, which we can't accurately control for," said Mayne, an editorial board member of Cancer Epidemiology, Biomarkers & Prevention.

Pereira points out that the findings are biologically plausible, held up in non-smokers, remained similar after taking other dietary habits into account and are consistent with findings in Caucasian populations.

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Herbal extra to against pancreatic cancer

An herb recently found to kill pancreas cancer cells also appears to inhibit development of pancreas cancer as a result of its anti-inflammatory properties, as per scientists from the Kimmel Cancer Center at Jefferson. The data were presented at the AACR 100th Annual Meeting 2009 in Denver. (Abstract #494).

Thymoquinone, the major constituent of the oil extract from a Middle Eastern herbal seed called Nigella sativa, exhibited anti-inflammatory properties that reduced the release of inflammatory mediators in pancreas cancer cells, as per Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at the Jefferson Medical College of Thomas Jefferson University and a member of the Jefferson Pancreatic, Biliary & Related Cancers Center.

Nigella sativa seeds and oil are used in traditional medicine by a number of Middle Eastern and Asian countries. It helps treat a broad array of diseases, including some immune and inflammatory disorders, Dr. Arafat said. Prior studies have also shown it to have anti-cancer effects on prostate and colon cancers.

Based upon their previously published findings that thymoquinone inhibits histone deacetylases (HDACs), Dr. Arafat and her colleagues compared the anti-inflammatory properties of thymoquinone and trichostatin A, an HDAC inhibitor that has previously shown to ameliorate inflammation-associated cancers.

The scientists used pancreatic ductal adenocarcinoma (PDA) cells, some of which were pretreated with the cytokine TNF-alpha to induce inflammation. Thymoquinone almost completely abolished the expression of several inflammatory cytokines, including TNF-alpha, interleukin-1beta, interleukin-8, Cox-2 and MCP-1, an effect that was more superior to the effect of trichostatin A.

The herb also inhibited the activation and synthesis of NF-kappaB, a transcription factor that has been implicated in inflammation-associated cancer. Activation of NF-kappaB has been observed in pancreas cancer and appears to be a factor in pancreas cancer's resistance to chemotherapeutic agents. When animal models of pancreas cancer were treated with thymoquinone, 67 percent of the tumors were significantly shrunken, and the levels of proinflammatory cytokines in the tumors were significantly reduced.

Inflammation has been implicated in the development of several solid tumor malignancies. Chronic pancreatitis, both hereditary and sporadic, is linked to the risk of developing pancreas cancer.

"These are very exciting and novel results," Dr. Arafat said. "Not only patients with chronic pancreatitis could benefit from this, but also several other groups with risk of development or recurrence of pancreas cancer, such as high-risk family members and post-surgical patients. These potent effects show promise for the herb as a potential preventive and therapeutic strategy for pancreas cancer. More importantly, the herb and oil are safe when used moderately, and have been used for thousands of years without reported toxic effects".

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Pancreatic Cancer Discovery Offers New Hope For Patients

Editor's Choice
Main Category: Pancreatic Cancer
Also Included In: Cancer / Oncology
Article Date: 25 Oct 2012 - 12:00 PDT Current ratings for:
Pancreatic Cancer Discovery Offers New Hope For Patients

A set of mutated genes responsible for causing pancreatic cancer have been discovered by Australian researchers and revealed in a new study published in the journal Nature.

This is the first time a collaboration of the world's best experts has been carried out to determine the genetic factors that influence 50 different types of cancer.

According to the report, pancreatic cancer accounts for more deaths than any other major type of cancer. Survival rates have not improved over the last 40 years, acting as the fourth-leading cause of death from cancer. Common symptoms of pancreatic cancer include: NauseaVomiting Appetite LossPain in the upper part of the stomach (abdomen), which can spread to the backUnusual weight lossDiabetes mellitus or high levels of blood sugarDepression Trosseau sign (when blood clots pop up out of nowhere in the deep veins of a person's extremities, superficial veins anywhere on the body, or in the portal blood vesselsExperts noted that early pancreatic cancer sometimes does not come with any symptoms what-so-ever. According to previous research, pancreatic cancer patients' lives can be saved if they visit more experienced hospitals and facilities.

The international team of more than 100 researchers was led by Professor Sean Grimmon, from the Institute for Molecular Bioscience (IMB) at The University of Queensland, and Professor Andrew Biankin from The Kinghorn Cancer Centre at Garvan Institute of Medical Research / St. Vincent's Hospital in Sydney.

The experts sequenced the genomes from 100 pancreatic tumors and analyzed them in comparison with non-cancerous tissue to discover which genetic alterations may have caused the cancer.

Grimmon said:

"We found over 2,000 mutated genes in total, ranging from the KRAS gene, which was mutated in about 90 per cent of samples, to hundreds of gene mutations that were only present in 1 or 2 per cent of tumors. So while tumors may look very similar under the microscope, genetic analysis reveals as many variations in each tumor as there are patients. This demonstrates that so-called 'pancreatic cancer' is not one disease, but many, and suggests that people who seemingly have the same cancer might be to be treated quite differently."

Biankin commented that in the future, independent diagnoses and treatment plans for each patient will be the "norm". He said, "In this study, we found a set of genes, the axon guidance pathway, that is frequently damaged in pancreatic cancer patients and is associated with potentially poorer outcomes for those patients. It is a new marker of pancreatic cancer that can be used to direct prognoses and treatments."

Biankin continued: "'Personalized medicine', where the molecular profile of a patient is matched to the best treatment, is the way the world is moving for many diseases, not just cancer. The challenge now will be moving from population healthcare and a 'one drug fits all' model to personalized healthcare. First, we must take the time to develop the necessary genetic knowledge and implement health systems to translate that knowledge effectively."

The Professors noted that the Australian Pancreatic Cancer Genome Initiative, which involves over 20 hospitals and research facilities, of more than 200 nurses, surgeons, pathologists, and experts, played a large part in their study.

Professor Warwick Anderson, from the National Health and Medical Research Council of Australia, which funded the study with a $27.5 million grant, said: "NHMRC is proud to have been the major funding contributor to this research, and I am delighted that breakthroughs have been made in understanding the genetic basis of this disease. This positive outcome is evidence of NHMRC supporting the very best research and researchers, and the importance of our involvement in strong national and international collaborations. The ultimate goal of our funding is healthier citizens, both in Australia and overseas, and this research will certainly lead to a better understand of this issue."

Written by Christine Kearney
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our pancreatic cancer section for the latest news on this subject. "Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes" Andrew Biankin, Sean Grimmon, et.al.
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posted by Kevin on 29 Oct 2012 at 7:47 am

Although this is definitely good news, the time something of real benefit comes out of it usually takes years, dare to say decades. My wife, 30-years old, she is suffering from this terrible disease. Just wish that more research is invested into it as much as any other form of cancer...Good luck with your wife Susanta

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posted by Susanta Kumar Das on 27 Oct 2012 at 6:44 am

We expect the outcome will delight the Patients. I am a badluck husband of a young 34 yeared pancreatic wife.
Presently she is undergoing treatment and 3rd stage of Chemotherapy is continue. Doctor diagonsis this position was not operable, only Chemothery (Paraplatin 450ml)may save her life.

Any new finding in this regards may comunicate to my mail ID. This may save her life.

Susanta Kumar Das

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'Pancreatic Cancer Discovery Offers New Hope For Patients'

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Popular Diabetes Drug Might Cut Pancreatic Cancer Risk: Study

TUESDAY, Jan. 31 (HealthDay News) -- A new Swiss-American study indicates that long-term use of the popular diabetes medication metformin may lower the risk of developing pancreatic cancer, at least among women.

The researchers also found that the long-term use of another class of diabetes medications known as sulfonylureas was associated with a "substantial" bump in pancreatic risk and long-term insulin use was linked to a bump in pancreatic cancer risk in men.

"This result is somewhat unexpected," the team wrote in its paper, which is published in the Jan. 31 online issue of The American Journal of Gastroenterology.

Pancreatic cancer is the fourth most deadly cancer in the United States, with an overall survival rate of less than 5 percent, even though it is fairly rare, according to the U.S. National Institutes of Health.

The researchers noted that previous research has suggested that metformin may lower the risk for other cancers, breast and ovarian cancer in particular.

To explore metformin's protective potential against pancreatic cancer, the team sifted through drug prescription, diagnostic, hospitalization and fatality information that had been collected by the British "General Practice Research Database." The data also included significant demographic information, such as smoking, alcohol use and body mass index.

The team honed in on statistics regarding nearly 2,800 patients (all under the age of 90) who had been diagnosed with pancreatic cancer for the first time between 1995 and 2009. Data concerning almost 16,600 patients who did not have pancreatic cancer was used as a comparison.

The result: Short-term use of metformin or sulfonylureas and/or insulin had no appreciable impact on pancreatic cancer risk.

However, long-term use of each of these medications did appear to have a sizeable impact on pancreatic cancer risk among diabetics. While female patients saw their risk go down with metformin treatment and up with sulfonylureas, male patients saw their risk go up with insulin.

Dr. Michael Choti, a professor of surgery and oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, stressed the "importance of trying to identify causes for a devastating disease that is often diagnosed late."

"Over the years, many groups have tried to look at a variety of risk factors, dietary and other things, and there have been some reports over the years," he noted. "But nothing has really panned out well. So this is indeed an interesting study."

"But it's also important to say," Choti added, "that while these could be associations, we cannot really say that what we have here is a cause-and-effect. Pancreatic cancer is a multi-factorial disease. So, while it makes sense conceptually that these drugs could have an impact on the pancreas, which is a metabolic organ, it's still too early to be sure what's happening. And it's too early to recommend metformin as a preventive therapy for pancreatic cancer."

"So this is interesting and important," he said. "But it's not definitive."

More information

For more on pancreatic cancer, visit the U.S. National Library of Medicine.

SOURCES: Michael Choti, M.D., professor, surgery and oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore; Jan. 31, 2012, The American Journal of Gastroenterology, online

Copyright © 2012 HealthDay. All rights reserved.

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Balancing Quality And Quantity Of Life For Pancreatic Cancer Patients

Main Category: Pancreatic Cancer
Article Date: 27 Aug 2012 - 0:00 PDT Current ratings for:
Balancing Quality And Quantity Of Life For Pancreatic Cancer Patients

Every year, nearly 45,000 Americans are diagnosed with pancreatic cancer. The odds against those stricken by the disease are truly dismal; pancreatic cancer almost always kills within two years after diagnosis, no matter how it is treated. Even aggressive intervention with chemotherapy, radiation or surgery rarely yields more than an extra month to a year of survival, depending on the stage of the disease.

This raises a tough question: should patients who know they are going to die soon spend a substantial amount of what little time they have left undergoing aggressive and difficult treatment - treatment likely to bring them only a brief period of additional life?

"It's about balancing quality and quantity of life, really," said Dr. Casey Boyd, a University of Texas Medical Branch at Galveston surgery resident and lead author of a paper analyzing the problem in Annals of Surgical Oncology. "For pancreatic cancer we know the quantity of life is short, so maximizing the quality of life is important - and the best way we can do that is to give patients concrete data that they can look at and use in their treatment decisions."

Boyd and her colleagues approached the issue by drawing on the National Cancer Institute's Surveillance, Epidemiology and End Results database, examining SEER records for 25,476 pancreatic cancer patients and focusing on two factors that directly affect patients' lives: hospital days and days spent in medical care. (Hospital days were days spent as hospital inpatients, while medical care days included days in the hospital as well as other days on which the patient visited a physician, underwent a diagnostic test, or received a treatment).

"This study is the first to bring together hospital and medical care days in pancreatic cancer patients with stage, treatment and survival, and it gives us a quantitative look at the whole experience of a patient with pancreatic cancer," Boyd said. "We hope that physicians can use the information in this paper to give patients what they need to make critical decisions."

For example, Boyd said, a doctor could draw on the paper to counsel a patient with metastatic pancreatic cancer - the most common and deadly type. "The physician could say, if you have chemotherapy you may live four to six weeks longer, but a lot of that time you're going to be in the hospital, or getting a test, or getting a needle poked in your arm for your chemotherapy," she said. "Some patients may say, I want that, I want the most life that you can give me."

Others, she noted, might make a different choice if given an accurate picture of the treatment experience.

"They might say, it's not really worth it to me - it's a few extra weeks, but they may be miserable weeks," Boyd said. "They may decide not to have any treatment and maybe just have hospice, or just spend time with their family."

The ability to help patients make such difficult decisions was the main goal of the study, according to Boyd.

"Really, this paper is about empowering the patient," she said. "We want to provide them with the information they need to make their own personalized treatment decisions."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject. Other authors of the Annals of Surgical Oncology article include medical student Daniel Branch, assistant professor Kristin Sheffield, biostatistician Yimei Han, associate professor Yong-Fang Kuo, Sealy Center on Aging director Dr. James Goodwin and associate professor Dr. Taylor Riall. Support for this research was provided by the NCI; the Office of Research, Development and Information, Centers for Medicare & Medicaid Services; Information Management Services Inc.; the SEER program; and the Cancer Prevention Research Institute of Texas.
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Earlier Onset Of Pancreatic Cancer Likely In Those Who Smoke And Drink Heavily

Main Category: Pancreatic Cancer
Also Included In: Smoking / Quit Smoking;  Alcohol / Addiction / Illegal Drugs
Article Date: 03 Oct 2012 - 0:00 PDT Current ratings for:
Earlier Onset Of Pancreatic Cancer Likely In Those Who Smoke And Drink Heavily

Those who smoke and drink heavily may develop pancreatic cancer at an earlier age than those who don't, according to a study led by a University of Michigan Health System gastroenterologist.

In the study, published in the American Journal of Gastroenterology, heavy smokers with pancreatic cancer were diagnosed around age 62 and heavy drinkers at age 61 - almost a decade earlier than the average age of 72.

Smoking is a strong risk factor for pancreatic cancer and alcohol has been shown to cause oxidative damage to the pancreas, which sets the stage for the inflammatory pathways that can lead to cancer.

The findings only indicate these habits can lead to developing pancreatic cancer earlier in life.

The study of 811 pancreatic cancer patients from the multicenter, international database Pancreatic Cancer Collaborative Registry does not prove the habits caused cancer.

The study does make a step toward understanding at what age screening for pancreatic cancer should begin - once widespread screening is available.

"As screening programs are developed, an understanding of how personal features influence the age of presentation will be important to optimize the timing of those screenings," says lead study author and gastroenterologist Michelle Anderson, M.D., assistant professor of internal medicine at the University of Michigan Health System. Detecting pancreatic cancer early is difficult and contributes to the poor survival rates. By the time pancreatic cancer is diagnosed, it is frequently at an advanced stage and has spread to other organs.

Currently there are no tests available to easily find it in people who do not have symptoms. In the study, heavy smokers were defined as those who had more than a pack per day, and heavy drinking was measured at more than 39 grams a day, or about three average drinks per day.

Beer drinkers presented with pancreatic cancer earlier than those who drank other types of alcohol, such as wine or hard liquor although when adjusted for the amount of alcohol consumed, the type of alcohol did not affect the age of presentation.

The good news is that the harmful effects of heavy drinking and smoking can be resolved . After 10 years, former smokers and drinkers who quit their habits faced no extra risk of earlier diagnosis.

The registry used for the study gathers information on patients with pancreatic cancer and those at high-risk for developing pancreatic cancer.

Patient data was collected from University of Nebraska Medical Center, Omaha, Neb.; University of Genoa, Italy; Creighton University School of Medicine, Omaha, Neb.; University of Pittsburgh Medical Center; NorthShore University Health System, Evanston, Ill.; University of Chicago, Chicago, Ill.; University of Alabama at Birmingham, Ala.; and the University of Michigan Health System, Ann Arbor, Mich.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject. Funding: This work was supported by the following grants: NIH K23 DK082097, NCI T32 CA 083654, NIH R01 CA140940, and Italian Ministry of Health DGRST.4/4235-P1.9.A.B.
Reference: "Alcohol and Tobacco Lower the Age of Presentation in Sporadic Pancreatic Cancer in a Dose-Dependent Manner: A Multicenter Study," American Journal of Gastroenterology.
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New pancreas tumor registry

Charles J. Yeo, M.D., Samuel D. Gross Professor and Chair, Department of Surgery at Jefferson Medical College of Thomas Jefferson University, announces the establishment of the new Jefferson Pancreas Tumor Registry (JPTR).

"The purpose of the registry is to further study whether pancreas cancer occurs more frequently in families with a history of the disease," said Dr. Yeo, who is the principal investigator of JPTR. "It will also be used to determine the environmental and occupational risk factors to which pancreas cancer patients have been exposed."

The JPTR modeled after the National Familial Pancreas Tumor Registry is a longitudinal study in which participants may engage in long-term follow-up and receive information regarding scientific and epidemiological breakthroughs in pancreas cancer.

Participants are asked to complete a detailed questionnaire and may be asked to submit a blood sample and/or cheek swab. The questionnaires are designed to elicit the family health history of a patient with pancreas cancer or a non-affected family member, and to document exposure to occupational and environmental factors, such as residential radon, asbestos and second-hand tobacco smoke.

Research has shown that certain rare genetic conditions are linked to an increased risk of pancreas cancer, including familial breast-ovary cancer, familial melanoma, familial colon cancer, hereditary pancreatitis and Peutz-Jegher's syndrome (a rare hereditary condition that results in gastrointestinal polyps). "While we have not identified a causative gene yet to allow predictive testing for pancreas cancer, we can offer risk assessments and surveillance via imaging, blood tests and endoscopic ultrasound for patients with a strong family history of pancreas cancer," added Dr. Yeo.

Such high risk patients may be referred to a Jefferson gastroenterologist to discuss the pros and cons of invasive surveillance. The goal is to diagnose pancreas cancer earlier, when more therapy options are available. For persons who do develop pancreas cancer, Jefferson physicians may use the results of genetic testing to select the most effective treatment. Targeted treatment for pancreas cancer is becoming a reality, in part due to recent discoveries made in the laboratory of Jonathan Brody, Ph.D., assistant professor, Department of Surgery at Jefferson Medical College of Thomas Jefferson University, where molecular studies have clearly indicated survival advantages with the use of targeted chemotherapy.

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Smoking increases risk of metastatic pancreatic cancer

Smoking has once again been implicated in the development of advanced cancer. Exposure to nicotine by way of cigarette smoking may increase the likelihood that pancreatic ductal adenocarcinoma will become metastatic, as per scientists from the Kimmel Cancer Center at Jefferson. Their study was reported in the August edition of the journal Surgery
The culprit behind the increased metastasis potential may be an isoform (variant type) of a protein called osteopontin, as per Hwyda Arafat, M.D. Ph.D., an associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University and a member of the Jefferson Pancreatic, Biliary & Related Cancers Center.

Nicotine promotes the expression osteopontin, and high levels of osteopontin have been reported in pancreatic ductal carcinoma (PDA). Dr. Arafat and her research team analyzed PDA samples and confirmed that the isoform, called OPNc, was also expressed on invasive PDA lesions. Prior studies have shown that OPNc is expressed in several invasive cancers, and supports metastatic behavior.

The scientists correlated OPNc expression with the patients' smoking history. OPNc expression was found on 87 percent of the invasive PDA lesions analyzed, of which 73 percent were from smokers. The OPNc expression also correlated with higher expression levels of osteopontin. Precancerous lesions expressed no OPNc.

"This is the first time a relationship between nicotine and OPNc expression has been identified," Dr. Arafat said. "These data are very exciting because now we can evaluate OPNc as a prognostic and diagnostic marker of invasive PDA lesions. "Because of the lower expression levels of OPNc in non-smokers, OPNc appears to be regulated by nicotine, which is another novel finding of this study. The exact role of OPNc in PDA remains to be defined, but it could provide a unique potential target to control pancreas cancer aggressiveness, particularly in people who smoke cigarettes".

Pancreas cancer is the fourth-leading cause of cancer death in the country, taking 34,000 lives a year. Only four percent of individuals with pancreas cancer live for five years after diagnosis.

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Did you know?
Smoking has once again been implicated in the development of advanced cancer. Exposure to nicotine by way of cigarette smoking may increase the likelihood that pancreatic ductal adenocarcinoma will become metastatic, as per scientists from the Kimmel Cancer Center at Jefferson. Their study was reported in the August edition of the journal Surgery

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Hepatitis B exposure and pancreatic cancer

HOUSTON - In a first-of-its-kind finding, scientists at The University of Texas M. D. Anderson Cancer Center have discovered that exposure to the hepatitis B virus (HBV) may increase the risk of pancreas cancer.

The study, reported in the Oct. 1 edition of the Journal of Clinical Oncology, also suggests that patients with this lethal form of cancer treated with chemotherapy may face danger of reactivation of their HBV.

Pancreas cancer is diagnosed in 37,000 people in the United States each year, and more than 34,000 people die of the disease annually, as per the American Cancer Society. It is often diagnosed in the late stages and is particularly perplexing because few risk factors are known.
Manal Hassan, M.D., Ph.D.

Credit: M. D. Anderson Cancer Center

"If this study is validated, it will give us more information about the risk factors of pancreas cancer and possibly even help prevent it in some cases," said lead author Manal Hassan, M.D., Ph.D., assistant professor in M. D. Anderson's Department of Gastrointestinal Medical Oncology.

HBV and hepatitis C virus (HCV) are major global health problems, affecting about 2 percent of the population worldwide. In the United States 1.25 million people have chronic HBV, while 3.2 million have chronic HCV. These systemic viruses can harm the body in a variety of ways, including traveling through the bloodstream and damaging tissues throughout the body.

The word "hepatitis" means "inflammation of the liver," and prior research has shown HBV and HCV are major causes of liver cancer. Little is known about their roles in other cancers. However, the proximity of the liver to the pancreas and the fact the pancreas and liver share common blood vessels and ducts make the pancreas a potential target for hepatitis viruses.

While this is the first study to examine whether exposure to HBV and HCV increases risk for pancreas cancer, other research has indicated chronic HBV infection may impair pancreatic function and that HBV may replicate in the pancreas, Hassan said.

In this study, which began in 2000, 476 M. D. Anderson patients with early pancreas cancer were identified. Additionally, 879 people without pancreas cancer were matched with the patients by age, gender and race. All participants were interviewed for demographic and risk factors information.

Then scientists tested the blood of all participants for the presence of HCV and HBV antibodies, which indicate past exposure to HCV and HBV.

The prevalence of past exposure to HBV was significantly higher (7.6 percent) in people with pancreas cancer than in healthy people (3.2 percent). However, exposure to HCV was not significantly different in the two groups.

In addition, the study confirmed previously reported risk associations of cigarette smoking, history of diabetes and a family history of pancreas cancer.

People exposed to HBV may develop occult, or hidden, HBV infection. In these cases, the M. D. Anderson scientists say, there is a potential for reactivation of HBV during chemotherapy, the most common therapy for pancreas cancer. Chemotherapy may suppress the immune system, leading to viral replication of the HBV, the scientists explained.

"If these results are validated, physicians might want to test pancreas cancer patients for HBV before administering chemotherapy," said senior author James Abbruzzese, M.D., professor and chair of M. D. Anderson's Department of Gastrointestinal Medical Oncology and associate medical director of the Gastrointestinal Center. "Reactivation of HBV could potentially cause liver damage and even liver failure".

Scientists stress these early results need to be studied further and plan to collaborate with other institutions to compare results among other populations and people who are actually infected with the virus. If they are confirmed, these results may offer new insight into pancreas cancer, possibly even preventing some cases in the future.

"We are working hard to try to understand the factors that are risks to developing pancreas cancer, especially modifiable risks," Abbruzzese said. "If these results are confirmed, people who are at risk might be able to help prevent pancreas cancer by getting an HBV vaccine".

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Study Identifies Components Responsible For Therapy-Blocking Solid Stress, Suggests Therapeutic Cancer Strategies

Main Category: Pancreatic Cancer
Also Included In: Lung Cancer;  Breast Cancer
Article Date: 24 Sep 2012 - 1:00 PDT Current ratings for:
Study Identifies Components Responsible For Therapy-Blocking Solid Stress, Suggests Therapeutic Cancer Strategies

It's a high-pressure environment within solid tumors. Abnormal blood and lymphatic vessels cause fluids to accumulate, and the uncontrolled proliferation of cancer cells within limited space leads to the buildup of what is called solid stress. Both types of pressure can interfere with the effectiveness of anticancer treatments, but while strategies have been developed that reduce fluid pressures, little has been known about the impact of solid stress or potential ways to alleviate it. Now a Massachusetts General Hospital (MGH) research team has identified factors that contribute to solid stress within tumors, suggesting possible ways to alleviate it, and has developed a simple way to measure such pressures.

"Traditionally cancer research has focused on cancer cells and, more recently, on the biochemical microenvironment of tumors," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study in the Proceedings of the National Academy of Sciences. "Our work shows that the physical or mechanical microenvironment plays an equally important role in tumor progression and treatment resistance."

Jain and his colleagues have been leaders in understanding the impact of elevated fluid pressures that make it difficult for drugs to enter and permeate tumors. Their work showed that fluid pressures are relieved when antiangiogenesis drugs normalize the abnormal blood vessels characteristically found within solid tumors, improving the effectiveness of other anticancer therapies. But that approach can only work if vessels have not been squeezed shut by solid stress in surrounding tissues. In recent studies Jain's team showed that solid stress also increases the invasiveness of cancer cells.

The current study was designed to develop techniques that measure solid stress in tumors, to identify factors that contribute to the generation of this solid stress and to determine whether previously compressed blood vessels would open when stress-inducing components were depleted. Based on predictions from mathematical models, the MGH-based team developed a remarkably simple way to measure solid stress within tumor tissues.

In experiments using both tumors experimentally grown in mice and tumors removed from human patients, the researchers found that, when a solid tumor is cut in two, each segment begins to swell along the sliced surface, releasing stored solid stress. In contrast, when a sample of normal tissue is cut in two, the separated halves of tissue retain their size and shape (links to video files below). Measuring the extent of shape relaxation along with other mechanical properties of tumor tissue enabled calculation of the amount of solid stress within a tumor sample.

Sample of breast tumor grown in mouse expands after cutting, releasing solid stress *

Sample of normal mouse kidney tissue, showing no change in shape after cutting **

Additional experiments utilizing the newly developed technique identified several components that contribute to increased solid stress within tumors, including the proliferation not only of cancer cells but also of fibroblasts and other components of the tumor's extracellular matrix. In pancreatic tumors implanted into mice, the researchers showed that inhibition of a pathway leading to the growth of fibroblasts reduced solid stress associated with tumor growth and opened up compressed blood and lymphatic vessels, which could both relieve fluid pressure and improve the delivery of chemotherapy drugs.

The authors note that their results may explain why the use of antiangiogenesis drugs has not improved treatment of highly fibrotic tumors - including dangerous pancreatic, lung and breast cancers - and suggest that a strategy targeting both aspects of intratumor pressure should be explored. "Now that we have seen how tumors exploit physical forces to facilitate progression and treatment resistance, we need to learn how to tame these fluid and solid forces to improve treatment outcomes," says Jain, the Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School. "We urgently need to identify safe pharmaceutical agents that reduce solid stress and then add them judiciously to current treatments."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our pancreatic cancer section for the latest news on this subject. * http://www.pnas.org/content/suppl/2012/08/29/1213353109.DCSupplemental/sm01.mov
** http://www.pnas.org/content/suppl/2012/08/29/1213353109.DCSupplemental/sm02.mov
Co-lead authors of the PNAS paper are Triantafyllos Stylianopoulos, PhD, and John D. Martin of the Steele Laboratory. Additional co-authors are Vikash Chauhan, Saloni Jain, Benjamin Diop-Frimpong, Yves Boucher, PhD, and Lance Munn, PhD, Steele Lab; Nabeel Bardeesy, PhD, MGH Center for Cancer Research; Barbara Smith, MD, MD, and Cristina Ferrone, MD, MGH Department of Surgery; and Francis J. Horniceki, MD, PhD, MGH Orthopaedic Oncology. The study was supported by grants from the National Institutes of Health and the Department of Defense.
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New therapies promising some against pancreatic cancer

Tuesday, June 19, HealthDay News)-giving four weeks of a specific drug before chemotherapy improved response rates in a small group of patients with advanced pancreatic cancer, report researchers at the University of Michigan.

The results are "very, very preliminary", said Dr. Jay Brooks, Chairman of Hematology and Oncology at the Ochsner of Baton Rouge, Louisiana, health system but you can show "a minimum of at least progress in the understanding of the biology of the disease. Pancreatic cancer is incredibly difficult to treat cancer".

The findings were presented Tuesday during a press conference at the American Association for the Conference on cancer research on cancer of the pancreas in Lake Tahoe, Nevada

The drug, GDC-0449, directs the signaling pathway Sonic Hedgehog, which lights up when cancer is present.

Activation of the pathway seems to contribute to the healing characteristics of pancreatic cancer, which makes it more difficult for chemotherapy drugs penetrate and do their job.

The hypothesis of the researchers who giving GDC-0449 before chemotherapy can improve the effectiveness of chemotherapy and its initial results indicate that it may be the case.

GDC is already used for basal cell carcinoma advanced under the name of Erivedge (vismodegib).

Twenty-one patients with previously untreated metastatic pancreatic cancer received four weeks of GDC, given in pill form once a day, and then chemotherapy with the drug Gemcitabine.

Biopsies taken both before the GDC and three weeks later showed reduction of the tumor in five patients, while other four patients achieved disease «stable», which means that the tumor was not declining or growing.

The drug was most effective in patients who initially had high levels of expression of Hedgehog.

Hedgehog levels are especially high in cancer cells. Is human trafficking, "a subset of cells identified in many cancers, including cancer of the pancreas, which is believed not only to boost the growth of tumor but that are also particularly resistant to standard chemotherapy and radiation therapies," explained the study author Dr. Edward Kim, a medical oncologist at the cancer center integral of the University of Michigan in Ann Arbor.

"I think this trial here is a step back in the right direction to find exactly what is happening. I would say that reading the summary response rate was very high. It means that you would normally see a 5 or 9% chance of getting a response to Gemcitabine, and here in this situation I think that at least 23 percent, 25 percent, "said the President of the Conference Dr. Daniel Von Hoff, medical Chief and distinguished professor at the Translational Genomics Research Institute and Professor of medicine at the clinic Mayo in Rochester"", Minn. "went beyond what would normally be expected".

"I'm very interested in seeing the final outcome of this," said Von Hoff. "The good news is that these inhibitors of Hedgehog does not add any substantial toxicity any".

A second study presented at the Conference, this one done in mice, found a protein which makes cells to stubbornly refuse to respond to the treatment of pancreatic cancer.

Blocking the protein, known as RLIP76, in mice with cancer of the pancreas to "complete regression" in tumors, said the lead author of the study Dr. Sanjay Awasthi, Professor of medical oncology Endocrinology and therapeutic research and diabetes and metabolism at the city of Hope Cancer Center in Duarte, California.

RLIP76 transports chemicals killer of chemotherapy drugs and radiation out cells until they can do their job. It tends to be more RLIP76 in cancer cells of the pancreas that in human cells healthy.

Beating later RLIP76 levels also seemed have antidiabetic effects, as these mice showed decreases in the blood sugar, cholesterol and triglycerides.

Awasthi said that he and his colleagues expect to move forward with this molecule, possibly as a medicine against diabetes and cancer to.

Awasthi is the founder of Terapio, the company that manufactures the RLIP76 recombinant protein to treat poisoning by radiation. Terapio is not involved with any application of the protein to treat cancer.

Papers presented at medical meetings normally are considered preliminary until published in a magazine.

More information

The U.S. National Cancer Institute has more about cancer of the pancreas.

SOURCES: Dr. Jay Brooks, Chairman of Hematology / Oncology, Ochsner, Baton Rouge, Louisiana; health system May 19, 2012, the press conference with medical oncologist Edward Kim, M.D., Ph.d., centro integral de cancer the University of Michigan, Ann Arbor, Michigan; Sanjay Awasthi, M.D., Professor, medical oncology and therapeutic research and diabetes, Endocrinology and metabolism, city of Hope Cancer Center, Duarte, California; Daniel D. Von Hoff, M.D., physician in Chief and distinguished Professor, Institute of Translational Genomics Research and Professor of medicine, Mayo Clinic, Rochester, Minn.

Copyright © 2010 HealthDay. All rights reserved.

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vitamin B6. B12 and folate, may decrease pancreatic cancer risk

Scientists exploring the notion that certain nutrients might protect against pancreas cancer observed that lean individuals who got most of these nutrients from food were protected against developing cancer. The study also suggests this protective effect does not hold true if the nutrients come from vitamin supplements.

As per a research findings reported in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research, researchers combined data from four large studies and observed that people who were at or below normal body weight decreased their risk for developing pancreas cancer if they took in high levels of vitamin B6, vitamin B12, and folate from food. The study determined that their risk was 81 percent, 73 percent, and 59 percent lower, vitamin B6, vitamin B12, and folate respectively, compared with participants who did not eat as much of these nutrients or who weighed more. As per the researchers, that was the only statistically significant finding from the study, which is the largest yet to look at these nutrients and pancreas cancer risk.

All we can say is that a person who has reason to be concerned about their risk of developing this cancer, which is relatively rare but quite deadly, should maintain a normal weight and eat their fruit and vegetables, said the studys lead investigator, Eva Schernhammer, M.D., Dr.P.H., an assistant professor of medicine at Harvard Medical School.

The scientists also say that they uncovered another interesting trend - that some people who received these nutrients from multivitamin pills had an increased risk of developing the disease. As per the researchers, individuals who said they used multivitamins, and whose blood showed traces of these nutrients, had a 139 percent increased relative risk of developing pancreas cancer.

This is a preliminary, but intriguing, finding because it suggests that something in the vitamins may fuel pancreas cancer growth, Dr. Schernhammer said.

This isnt the first study to suggest that folate, and vitamin B6 and B12 - so called one carbon nutrients - are protective against pancreas cancer if they come from food, but not if they come from multivitamins, Dr. Schernhammer said.

One large Finnish study found one carbon food nutrients were linked to a decreased risk of developing pancreas cancer, but that vitamin pills were not helpful. Two other large American studies also found the food nutrients to be protective, but that vitamin use was linked to a higher, yet non-significant risk of developing the cancer.

In this study, scientists combined four large prospective cohort studies, The Womens Health Initiative, and three from the Harvard School of Public Health: the Nurses Health Study, the Health Professionals Follow-up Study, and the Physicians Health Study. From this large database, they performed a prospective nested case-control study to examine plasma concentrations of the nutrients from participants who had donated blood and answered questionnaires about their food intake and vitamin use before any cancer developed. Their analysis included 208 pancreas cancer cases and 623 cancer-free control cases.

No one knows why vitamin pills may not help ward off cancer, or why, in this study, it might have a deleterious effect, Dr. Schernhammer said, but some research in animals suggests that if there is a dormant tumor, folate and other similar vitamins may stimulate growth. That might be particularly true if a person did not take in enough of these nutrients consistently through diet, and then suddenly started taking multivitamins in an effort to become healthy, she said.

People believe that dietary intake of these nutrients reflects a lifelong healthy eating habit, and in those cases, these nutrients may be protective, but they could have an opposite effect if they are used in a person with an occult cancer, Dr. Schernhammer said. It might all depend on whether a person is cancer-free at the time they start using these nutrients.

The same kind of association has been found with use of soy, which is an estrogen-rich food, she said. Women who have eaten soy all their lives, such as people in Asia, have a reduced risk of developing breast cancer, but some studies have observed that increased soy intake in women who have not eaten it before appears to be harmful.

The scientists say their study cannot definitively say that one carbon nutrients either pose a benefit or a hazard to most people, but they note that it is the best analysis that can be performed outside of a randomized clinical trial.

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Potential To Improve Human Cancer Studies Using Novel Pig Model

Main Category: Melanoma / Skin Cancer
Also Included In: Pancreatic Cancer;  Biology / Biochemistry
Article Date: 26 Jul 2012 - 1:00 PDT Current ratings for:
Potential To Improve Human Cancer Studies Using Novel Pig Model

A naturally occurring line of immunodeficient pigs can support the growth of human tumors injected under their skin, offering a promising new large animal model for studying human cancers and testing new drugs and treatment strategies. The ability of human melanoma cells and pancreatic carcinoma cells to grow in these pig models is described in an article in BioResearch Open Access, a new bimonthly peer-reviewed open access journal from Mary Ann Liebert, Inc.. The article is available free online at the BioResearch Open Access website.*

Mathew Basel and colleagues, Kansas State University (Manhattan, KS) and Iowa State University (Ames), highlight the advantages that pig disease models offer, as they are anatomically and physiologically more closely related to humans than traditional rodent animal models. As a result, findings from studies in large animal models such as pigs are more likely to translate into similar outcomes in humans. The authors present their findings in the article "Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs." **

"This novel animal model has the potential to become a highly useful model in cancer research studies, in addition to providing significant opportunities for drug discovery and other translational applications," says Editor-in-Chief Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

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Hepatitis B does not increase pancreatic cancer risk

A Henry Ford Hospital study observed that hepatitis B does not increase the risk for pancreas cancer and that only age is a contributing factor.

The results contradict a prior study in 2008 that suggested a link between pancreas cancer and prior hepatitis B infection. Hepatitis B is an inflammation of the liver caused by a viral infection.

Study results will be presented at the American Association for the Study of Liver Diseases' Annual Meeting in Boston.

Using data from Henry Ford Health System, physicians looked at more than 74,000 patients who were tested for hepatitis B between 1995 and 2008. In the overall analysis, only age was found to be a significant predictor for pancreas cancer.

"We looked at the occurence rate of pancreas cancer among hepatitis B-infected patients over a 13-year period and observed that we could not confirm a higher risk for those with a prior exposure to hepatitis B, as a previous study suggested," says Jeffrey Tang, M.D., gastroenterologist at Henry Ford Hospital and main author of the study.

"When other factors are considered such as age, race, sex, HIV status, and the presence of diabetes only older age and presence of diabetes proved significant, whereas previous exposure to hepatitis B was no longer an important variable".

As per the National Cancer Institute, more than 35,000 people in the U.S. die of pancreas cancer each year and 42,000 new cases are diagnosed. The survival rates for patients with pancreas cancer are poor.

An estimated 800,000 to 1.4 million people have chronic hepatitis B infection, as per the Centers for Disease Control and Prevention. In 2007, an estimated 43,000 people in the United States were newly infected with hepatitis B, eventhough a number of cases are not reported because a number of people do not have symptoms.

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Genes and pancreatic cancer

Abnormalities in genes that repair mistakes in DNA replication may help identify people who are at high risk of developing pancreas cancer, a research team from The University of Texas M. D. Anderson Cancer Center reports in the Jan. 15 issue of Clinical Cancer Research
Defects in these critical DNA repair genes may act alone or in combination with traditional risk factors known to increase an individual's likelihood of being diagnosed with this very aggressive type of cancer.

"We consider DNA repair to be the guardian of the genome," said main author Donghui Li, Ph.D., professor in the Department of Gastrointestinal Medical Oncology at M. D. Anderson. "If something is wrong with the guard, the genes are more readily attacked by tobacco carcinogens and other damaging agents".

With this in mind, Li and her colleagues set out to identify DNA repair genes that could act as susceptibility markers to predict pancreas cancer risk. In a case-control study of 734 patients with pancreas cancer and 780 healthy individuals, they examined nine variants of seven DNA repair genes. The repair genes under investigation were: LIG3, LIG4, OGG1, ATM, POLB, RAD54L and RECQL.

The scientists looked for direct effects of the gene variants (also called single nucleotide polymorphisms) on pancreas cancer risk as well as potential interactions between the gene variants and known risk factors for the disease, including family history of cancer, diabetes, heavy smoking, heavy alcohol consumption and being overweight.

The M. D. Anderson team observed that the risk of developing pancreas cancer was 77 percent lower among individuals with the variant form of the LIG3 gene (LIG3 G-39A AA). In contrast, people who carried the variant form of the ATM gene (ATM D1853N AA) were more than twice as likely to develop the disease as those without the genetic variation.

When the researchers examined possible interactions between gene variants and known risk factors, they found no significant interplay between the abnormal DNA repair genes and smoking, heavy alcohol consumption or excess body weight. However, two of the gene variants (ATM D1853N and LIG4 C54T) did interact with diabetes to affect pancreas cancer risk.

For example, in comparison to non-diabetics with the ATM D1853N GG genotype, diabetics carrying the ATM D1853N GA/AA genotypes had more than triple the risk of developing pancreas cancer. Similarly, in comparison to non-diabetics with the LIG4 CC genotype, diabetics with the LIG4 CT/TT genotype had more than double the risk of developing the disease.

Li noted that the ultimate goal of this research is to identify high-risk individuals for closer scrutiny and follow up.

"We know that people with diabetes have a higher risk of developing pancreas cancer, but we don't know who will actually develop the disease and who will not," Li said. "The same is true for smokers. But we can't do Computerized axial tomography scans on every diabetic or every smoker.

"We need to develop biomarkers that will enable us to do a quick genetic test on a diabetic patient, heavy smoker or someone with a family history of pancreas cancer," she continued. "We could then do a screening test, identify those with the highest risk, and monitor them more closely".

U.

nderstanding the role of variant DNA repair genes in the development and prognosis of pancreas cancer would also give scientists more insight into their functional significance. This increased knowledge should promote the development of new therapeutic strategies to target these abnormal genes.

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