Pancreatic Cancers: Chemotherapy Plus Synthetic Compound Provides Potent Anti-Tumor Effect

Human pancreatic cancer cells dramatically regress when treated with chemotherapy in combination with a synthetic compound that mimics the action of a naturally occurring "death-promoting" protein found in cells, researchers at UT Southwestern Medical Center have found.



The research, conducted in mice, appears in today's issue of Cancer Research and could lead to more effective therapies for pancreatic and possibly other cancers, the researchers said.



"This compound enhanced the efficacy of chemotherapy and improved survival in multiple animal models of pancreatic cancer," said Dr. Rolf Brekken, associate professor of surgery and pharmacology and the study's senior author. "We now have multiple lines of evidence in animals showing that this combination is having a potent effect on pancreatic cancer, which is a devastating disease."



In this study, Dr. Brekken and his team transplanted human pancreatic tumors into mice, then allowed the tumors to grow to a significant size. They then administered a synthetic compound called JP1201 in combination with gemcitabine, a chemotherapeutic drug that is considered the standard of care for patients with pancreatic cancer. They found that the drug combination caused regression of the tumors.



"There was a 50 percent regression in tumor size during a two-week treatment of the mice," Dr. Brekken said. "We also looked at survival groups of the animals, which is often depressing in human therapeutic studies for pancreatic cancer because virtually nothing works. We found not only significant decrease in tumor size, but meaningful prolongation of life with the drug combination."



The drug combination was also effective in an aggressive model of spontaneous pancreatic cancer in mice.



The compound JP1201 was created in 2004 by UT Southwestern researchers to mimic the action of a protein called Smac. The researchers discovered Smac in 2000 and found that this protein plays a key role in the normal self-destruction process present in every cell.



Cell death, or apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or is no longer needed for normal growth and development. In cancer cells, this self-destruct mechanism is faulty and lead to breaks in the cell-death cascade of events. The synthetic Smac, or Smac mimetic, developed at UT Southwestern inhibits these breaks, allowing the cell to die.



"In essence, we're inhibiting an inhibitor," Dr. Brekken said. "And we're allowing the apoptotic cascade to kick off, resulting in the death of cancer cells."



UT Southwestern researchers are using Smac mimetics in breast and lung cancer research, as well. Dr. Brekken said the next step is to develop a compound based on JP1201 that can be tested in humans in clinical trials.



Other UT Southwestern researchers involved in the study included lead author Dr. Sean Dineen, surgery resident; Dr. Christina Roland, surgery resident; Rachel Greer, student research assistant in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; Juliet Carbon, senior research associate in surgery and in the Hamon Center; Jason Toombs, research assistant in surgery and in the Hamon Center; Dr. Puja Gupta, a pediatric hematology/oncology fellow; Dr. Noelle Williams, associate professor of biochemistry; and Dr. John Minna, director of the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and of the Hamon Center.



The research was supported by Susan G. Komen for the Cure and Joyant Pharmaceuticals, a Dallas-based company and UT Southwestern spinoff that is developing medical applications of Smac-mimetic compounds.



Source:

Connie Piloto


UT Southwestern Medical Center

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Returning Troops Benefit From Innovative Virtual Reality Exposure Therapy

An article published in a forthcoming issue of the Journal of Traumatic Stress is one of the first to provide evidence of the effectiveness of exposure therapy with active duty military service members suffering from posttraumatic stress disorder (PTSD). The study shows that virtual reality exposure therapy resulted in significant reductions in PTSD symptoms after an average of seven treatment sessions. Additionally, 62 % of patients reported clinically meaningful, reliable change in PTSD symptoms.



During the treatment the soldier repeatedly revisits the memory, and through the use of their imagination they safely access emotions related to the original traumatic experience. Revisiting the memory while safely emotionally engaged, reduces anxiety, and allows the engagement process to be comfortably repeated. Lead author Dr. Greg Reger, "We know that lengthy military deployments in stressful environments with exposure to multiple, potentially traumatic events can lead to the desire to emotionally 'unplug.' By using multi-sensory virtual reality that can be customized in real time, the provider can help activate the memory with relevant sights, sounds, vibrations, even scents that resemble aspects of the event that is haunting them."



A clinical trial with Vietnam veterans and World Trade Center survivors has shown that virtual exposure therapy is an innovative and effective form of treatment. The current research extends those findings to the population of military service members returning from deployments to Iraq or Afghanistan with PTSD.



Reger, "It is possible that virtual reality exposure therapy would provide a more appealing treatment option to a young, technologically savvy generation of service members and veterans. In addition, it is possible that a treatment option like virtual reality exposure would be viewed by some service members as less stigmatizing than traditional treatment approaches. If accurate, virtual reality exposure therapy might provide us with the opportunity to treat service members and veterans who may not otherwise seek help."



Source:

Bethany Carland-Adams

Wiley-Blackwell

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NPA Issues Oral Methotrexate SOP, UK

The NPA has produced a resource to help members, in England and Wales, review their dispensing procedures in order to minimise the risks associated with oral methotrexate therapy. The resource comprises a template Standard Operating procedure (SOP) for the supply of oral methotrexate and guidance notes.


The model NPA SOP incorporates the National Patient Safety Agency (NPSA) guidance from Patient Safety Alert 13 - Improving Compliance with Oral Methotrexate Guidelines. The NPA's SOP and guidance notes draws on the areas specific to community pharmacy.


Ruth Wakeman, NPA Information Department Manager said: "The guidance notes and SOP on supply of oral methotrexate help provide all the necessary information in a straightforward format. It is important for members to ensure that they are complying with the NPSA advice."


'Supplying Oral Methotrexate' can be downloaded from the NPA website npa/members. Although applicable directly to England and Wales, the SOP resource may also be of interest to pharmacy contractors from Scotland and Northern Ireland. All NPA SOPs and information materials can be found within the NPA Document Store area.

National Pharmacy Association

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Risk Of Death Not Reduced By Flu Shot

The widely-held perception that the influenza vaccination reduces overall mortality risk in the elderly does not withstand careful scrutiny, according to researchers in Alberta. The vaccine does confer protection against specific strains of influenza, but its overall benefit appears to have been exaggerated by a number of observational studies that found a very large reduction in all-cause mortality among elderly patients who had been vaccinated.



The results will appear in the first issue for September of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.



The study included more than 700 matched elderly subjects, half of whom had taken the vaccine and half of whom had not. After controlling for a wealth of variables that were largely not considered or simply not available in previous studies that reported the mortality benefit, the researchers concluded that any such benefit "if present at all, was very small and statistically non-significant and may simply be a healthy-user artifact that they were unable to identify."



"While such a reduction in all-cause mortality would have been impressive, these mortality benefits are likely implausible. Previous studies were likely measuring a benefit not directly attributable to the vaccine itself, but something specific to the individuals who were vaccinated - a healthy-user benefit or frailty bias," said Dean T. Eurich,Ph.D. clinical epidemiologist and assistant professor at the School of Public Health at the University of Alberta. "Over the last two decades in the United Sates, even while vaccination rates among the elderly have increased from 15 to 65 percent, there has been no commensurate decrease in hospital admissions or all-cause mortality. Further, only about 10 percent of winter-time deaths in the United States are attributable to influenza, thus to suggest that the vaccine can reduce 50 percent of deaths from all causes is implausible in our opinion."



Dr. Eurich and colleagues hypothesized that if the healthy-user effect was responsible for the mortality benefit associated with influenza vaccination seen in observational studies, there should also be a significant mortality benefit present during the "off-season".



To determine whether the observed mortality benefits were actually an effect of the flu vaccine, therefore, they analyzed clinical data from records of all six hospitals in the Capital Health region in Alberta. In total, they analyzed data from 704 patients 65 years of age and older who were admitted to the hospital for community-acquired pneumonia during non-flu season, half of whom had been vaccinated, and half of whom had not. Each vaccinated patient was matched to a non-vaccinated patient with similar demographics, medical conditions, functional status, smoking status and current prescription medications.



In examining in-hospital mortality, they found that 12 percent of the patients died overall, with a median length of stay of approximately eight days. While analysis with a model similar to that employed by past observational studies indeed showed that patients who were vaccinated were about half as likely to die as unvaccinated patients, a finding consistent with other studies, they found a striking difference after adjusting for detailed clinical information, such as the need for an advanced directive, pneumococcal immunizations, socioeconomic status, as well as sex, smoking, functional status and severity of disease. Controlling for those variables reduced the relative risk of death to a statistically non-significant 19 percent.



Further analyses that included more than 3,400 patients from the same cohort did not significantly alter the relative risk. The researchers concluded that there was a difficult to capture healthy-user effect among vaccinated patients.



"The healthy-user effect is seen in what doctors often refer to as their 'good' patients - patients who are well-informed about their health, who exercise regularly, do not smoke or have quit, drink only in moderation, watch what they eat, come in regularly for health maintenance visits and disease screenings, take their medications exactly as prescribed - and quite religiously get vaccinated each year so as to stay healthy. Such attributes are almost impossible to capture in large scale studies using administrative databases," said principal investigator Sumit Majumdar, M.D., M.P.H., associate professor in the Faculty of Medicine & Dentistry at the University of Alberta.



The finding has broad implications:
For patients: People with chronic diseases such as chronic respiratory diseases e.g. chronic obstructive pulmonary disease, immuno-compromised patients, healthcare workers, family members or friends who take care of elderly patients and others with greater exposure or susceptibility to the influenza virus should still be vaccinated. "But you also need to take care of yourself. Everyone can reduce their risk by taking simple precautions," says Dr. Majumdar. "Wash your hands, avoid sick kids and hospitals during flu season, consider antiviral agents for prophylaxis and tell your doctor as soon as you feel unwell because there is still a chance to decrease symptoms and prevent hospitalization if you get sick - because flu vaccine is not as effective as people have been thinking it is."


For vaccine developers: Previously reported mortality reductions are clearly inflated and erroneous - this may have stifled efforts at developing newer and better vaccines especially for use in the elderly.


For policy makers: Efforts directed at "improving quality of care" are better directed at where the evidence is, such as hand-washing, vaccinating children and vaccinating healthcare workers.

Finally, Dr. Majumder said, the findings are a reminder to researchers that "the healthy-user effect is everywhere you don't want it to be."



###



Source: Keely Savoie


American Thoracic Society

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Nutraceuticals And Prostate Cancer Prevention: A Current Review

UroToday - Nutraceutical is a new term in prostate cancer research that relates to nutritional or wholistic treatments. Nutraceuticals generally refer to isolated compounds, usually from plant matter, that are unmodified with demonstrated benefit against chronic disease or cancer. A high percentage of patients at risk for prostate cancer or already diagnosed with the disease are interested in alternative therapies such as nutraceuticals. With the highly prevalent nature of PCa and its latent clinical effects, there is intense interest in prevention strategies.


Furthermore, now that many urology practices carry a significant number of patients on active surveillance, mechanisms to retard the disease are a priority. 5 alpha reductase inhibitor therapy is one approach in such patients, but use of these drugs comes at the price of significant side effects and cost. Nutraceutical compounds are generally inexpensive and rarely have any adverse effects unless used at exceedingly high doses.


The most notable nutraceutical compounds examined in prostate cancer prevention are vitamin D, vitamin E, selenium, lycopene, soy, and green tea. Aside from vitamin E, the data on these compounds is largely retrospective and in many cases contradictory. As a consequence, most of these compounds have been ruled out as effective agents against PCa despite a lack of good evidence for their ineffectiveness. Some are still under investigation and new nutraceuticals such as pomegranate are in the cue with over 30 randomized control trials registered in the area of nutraceuticals.


Of these compounds, soy has the most compelling evidence for benefit, albeit moderate in strength, in both primary prevention and patients on active surveillance. Some promising results are also available for green tea and pomegranate. However, we feel that many of the other compounds should not be ruled out based on contradictory low quality case-control studies. The future of these compounds is uncertain, but interest remains high.


We hope future studies will be higher quality in the form of randomized control trials to avoid the confusion of countless contradictory case-control studies. Our review of nutraceuticals in prostate cancer prevention comprehensively surveys the literature on these compounds with discussions on and newer promising compounds.


Greg Trottier, Peter J. Bostrom, Nathan Lawrenstchuk and Neil E. Fleshner as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.


UroToday - the only urology website with original content global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
www.urotoday


Copyright © 2010 - UroToday

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Preliminary Evaluation Of Reliability And Criterion Validity Of Actiwatch-Score

Restoration of normal physical activity is a primary objective of most chronic pain rehabilitative interventions,
yet few clinically practical objective measures of activation exist. We evaluated the measurement properties of the Actiwatch-Score (AW-S). We conducted separate trials to examine concordance between units when worn concurrently at the same and different body sites and to compare the AW-S with a validated optical three-dimensional motion-tracking system. The data indicate that the AW-S has excellent interunit reliability and good criterion validity, but its intersite reliability varies with activity type. These results suggest that this device, and those like it, warrants further investigation and is likely to yield valuable data regarding the optimal application of this technology.




The Journal of Rehabilitation Research and Development (JRRD) has been a leading research journal in the field of rehabilitation medicine and technology for over 40 years. Formerly the Bulletin of Prosthetics Research, JRRD debuted in 1983 to include cross-disciplinary findings in rehabilitation. JRRD, a scientifically indexed journal, publishes original research papers, review articles, as well as clinical and technical commentary from U.S. and international researchers on all rehabilitation research disciplines.


JRRD publishes in both print and electronic formats, increasing the journal's dissemination from a hard copy circulation of 8,000 to 2.3 million Web downloads in 2005. Currently, there are over 1,000 peer-reviewed articles available in electronic format and free for downloading. JRRD will initiate an archiving program in 2005 to make all issues of JRRD and the Bulletin of Prosthetics Research available online.


Journal of Rehabilitation Research and Development

Now Available Online and in Print: www.rehab.research.va

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Pollen.com Introduces New Features To Help Allergy Sufferers

Responding to numerous user requests, Pollen, one of the most visited allergy web sites, announced the addition of two new features, Pollen History and Two-City Comparison, to its popular site for people who suffer from seasonal allergies. Pollen, a division of SDI , has also added a shopping feature for those who wish to comparison-shop for anti-allergenic products.


Pollen History provides a 30-day allergy index history by zip code. The proprietary index assigns a weighted value to key factors such as the pollen count, weather, and wind speed and direction. Visitors can use the chart to track whether allergy conditions are increasing or decreasing over time. In the near future, the site will introduce a 90-day look-back, which will be the most extensive pollen history available on the web.


The launch of Pollen History has generated rave reviews from users. One mother wrote in, "This helps me so much! My daughter is not yet 2 and she is suffering from asthma symptoms. When she has a flare-up, I look on here to see if there is a connection with the pollen levels."


The Two-City Comparison Chart, not found on any other web site, allows Pollen visitors to compare the pollen intensity in their own area with that of another location for the next four days by plugging in the two zip codes. The chart that pops up displays bar graphs showing the pollen severity levels in the two locations for each day.


"When people with allergies travel on business, vacation, or relocate, they want to know how the expected pollen levels in other areas compare with what they're currently experiencing," explains Glenn Connery, manager of the application development/web group for SDI. "Our Two-City Comparison helps people plan their medication use and their outdoor activities a little better. The comparison feature has also been used by parents whose children have allergies and are going away to college in a different city."


Pollen will soon expand both Pollen History and Two-City Comparison to include breakdowns of specific pollen sources such as trees, plants, and grasses.


Site visitors can already get more information on pollen-emitting flora by clicking on the icon for Pollen Library. This feature provides data and photos for more than 1100 plant species, searchable by county for all 48 contiguous states in the U.S.


The new "Allergy Buyers Club" feature allows Pollen users to shop online for a wide range of allergy relief and healthy home products, including air purifiers, dehumidifiers, water filters, furnace filters, vacuum cleaners and hypoallergenic bedding.


Pollen, one of the top allergy sites in both Google and Yahoo rankings, reaches more than 200 million people annually. These include over 30 million people who visit the site directly, and 170 million who access Pollen features through radio and TV station websites across the U.S., as well as weather, health and wellness sites.


Over the past decade, Pollen has continuously improved its methodology and created new features to further benefit people with allergies. Many of these ideas have come from users who provide feedback on the site.


"This is a user-driven service," Connery says. "We're fortunate to have such an interested and involved audience, and we try to respond to their suggestions by providing the features that they want. Their feedback really makes a difference in the usefulness of the site."


About Pollen


Pollen, a division of SDI, has been supplying important information to many millions of people with allergic conditions for nearly 10 years. Among its free services are charts of current and predicted pollen levels, pollen histories, e-mail alerts, and educational materials on how to manage seasonal allergies.


About SDI


Since 1982, SDI has been delivering the most innovative healthcare data products and analytic services on the market to the pharmaceutical, biotech, healthcare, medical device, and consumer packaged goods industries. SDI is a leading provider of de-identified patient-level data, as well as real-time localized disease and treatment surveillance and modeling data. SDI takes a consultative approach to designing the best analyses for its clients, combined with expert study execution and analytical expertise to produce superior insights. Its current roster of client companies in the pharmaceutical/biotech sector includes all of the top 20 firms. For more information, call 610.834.0800 or visit survdata.


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