An experimental drug combination may provide “a new weapon against pancreatic cancer”, BBC News has reported.
In a search for new ways to fight the aggressive cancer, scientists combined an existing chemotherapy drug called gemcitabine with an experimental chemical called MRK003. The chemical can block the actions of a protein called "gamma secretase" that plays a range of roles in the body. To test the effect of this combination they gave the mixture to mice genetically engineered to develop pancreatic cancer. They found that that the mice survived 26 days with the combination treatment, compared with just nine days when given an inactive dummy drug. Cancer Research UK reports that a human trial of gemcitabine combined with another gamma secretase blocker are now underway.
Pancreatic cancer often has a poor prognosis as it’s usually only diagnosed at an advanced stage, by which time it is resistant to many conventional treatments. It is the fifth most common cause of cancer death in the UK, and patients with metastatic disease (where the cancer has spread survive between two and six months on average.
This animal study has reported promising results for a new form of combination therapy. However, there are limits to what can be learnt from animal tests, so the results of the current clinical trial will provide a much clearer indication of how safe or successful this regime is for treating patients.
Where did the story come from?
The study was carried out by researchers from the Cancer Research UK Cambridge Research Institute, Cambridge University and Merck Research Laboratories, USA. It was funded by the University of Cambridge and Cancer Research UK, the Li Ka Shing Foundation and Hutchison Whampoa Limited, the UK National Institute for Health Research, Cambridge Biomedical Research Centre and the collaborative research programme at Merck, a pharmaceutical company. The study was published in the peer-reviewed Journal of Experimental Medicine.
This story was covered by the BBC and Metro. The coverage was accurate and explained that the drug is part of an ongoing phase I/II clinical trial.
What kind of research was this?
This study examined the use of an experimental drug in a mouse model of pancreatic cancer and on cells grown in the laboratory. Animal models of disease provide a useful way to test what might happen if human patients were given a particular drug. Although the animal models don’t necessarily reflect what would happen in humans, they can be invaluable in exploring the properties of potential treatments. The mouse model in this research has already been used to test several pancreatic cancer drugs, with researchers finding that it accurately modelled the responses seen in patients with the condition.
This is the ideal study design for preliminary trials of new drugs. Drugs need to be well-tolerated and effective in the laboratory and in animals before trials on humans can happen.
What did the research involve?
The researchers took mice that modelled the main subtype of pancreatic cancer, called pancreatic ductal adenocarcinoma. This type accounts for around 90% of pancreatic cancer cases. The researchers wanted to test a novel drug called MRK003, a type of “inhibitor” that blocks the gamma secretase pathway. Gamma secretase is involved in a signalling pathway between cells, which is disrupted in many cancers.
To test their theory, the researchers looked at the effect of several treatment regimes involving MRK003, administering it alone or in combination with a drug called gemcitabine that is already clinically used to treat pancreatic cancer. In particular, the researchers looked at:
- the way treatment affected the expression of certain markers that are characteristic of pancreatic cancer
- the effect on mice survival
- the effect on the tumour cells
What were the basic results?
The researchers found that MRK003 could reduce the expression of certain pancreatic cancer markers. When given alone, MRK003 had no effect on the survival of pancreatic cancer model, but when given in combination with gemcitabine the median survival time of the mice was significantly increased, from nine days when given a placebo to 26 days when given MRK003 and gemcitabine in combination (p=0.002 . The researchers found that combination treatment promotes tumour cell death and suppresses tumour growth.
How did the researchers interpret the results?
The researchers concluded that this research supports the further investigation of gamma secretase inhibitors (drugs such as MRK003 in combination with gemcitabine for the treatment of patients with pancreatic ductal adenocarcinoma.
Conclusion
Patients diagnosed with pancreatic cancer can have a poor outlook, as the disease is aggressive and often advanced by the time it produces any symptoms. Despite being a relatively rare form of cancer (with around 7,800 cases diagnosed each year , it’s the fifth most common cause of cancer death in the UK. Patients with metastatic disease (where the cancer has spread have a median survival of between two and six months.
Given the current poor outlook for pancreatic cancer patients, there is a real need for new treatment options for the condition. This experimental study, although only in mice, has produced positive results for the combination therapy involving a gamma secretase inhibitor and gemcitabine. Gemcitabine is an established treatment for pancreatic cancer, but it currently attains only modest survival results.
The combination treatment was found to promote the death of tumour cells and suppress tumour growth, and increased survival time to 26 days (compared to nine days with a placebo .
These are exciting early results in an area with a clear need for better treatments. However, it will take the results of further clinical trials, such as the phase I/II clinical trial currently underway, to tell how successful or safe this regime is for treating patients.
Analysis by Bazian
Links To The Headlines
Pancreatic cancer: Trial drug MRK003 shows promise. BBC News, February 21 2012
Drugs mixture offers new hope in pancreatic cancer fight. Metro, February 21 2012
Links To Science
Cook N, Frese KK, Bapiro TE et al. Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. The Journal of Experimental Medicine, February 20 2012
“Not sleeping enough can damage your immune system and make you ill,” according to the Daily Mail.
This somewhat sweeping statement is based purely on an animal study looking at how mice body clocks affected their immune systems. The study found that levels of an infection-detecting protein called TLR9 fluctuated throughout the day and that the exact level of this protein influenced how effective a vaccine was in mice. It also influenced the mice’s response to a type of serious infection.
Differences between man and mouse mean more research will be needed to determine if these findings apply to humans. If they do, then it may be possible that certain vaccinations could be administered at specific times of day to make them more effective. However, this approach would need to be tested in humans to be sure that it actually made a meaningful difference to the effectiveness of the vaccines.
The immune system is a complex area, and while this research shed some light on one aspect of the body’s immunity and its ties to the body clock, there’s still much to learn.
Where did the story come from?
The study was carried out by researchers from Yale University School of Medicine and the Howard Hughes Medical Institute in the US. It was funded by the US National Institutes of Health and published in the peer-reviewed scientific journal, Immunity.
When reporting this study both BBC News and the Daily Mail stated that this research was in mice, and gave good summaries of the findings. However, the Mail’s headline claimed that “not sleeping enough can damage your immune system and make you ill”, which the current research does not support. The results of this research in mice should not be interpreted as providing proof that amount of sleep affects illness in humans.
What kind of research was this?
This was animal research looking at exactly how the body clock affects the function of the immune system in mice. The researchers say that previous studies have shown that certain immune system functions and chemicals vary naturally in relation to light and daily rhythms in humans and mice. They say that studies have also suggested that disruptions to normal daily rhythms, such as jet lag or sleep deprivation, may also affect the immune system.
This type of early research will usually use animals such as mice to carry out in-depth investigation of the interaction of basic biological functions, which might be difficult to carry out in humans. Generally, it’s only once researchers have built up a picture of these interactions in mice that they can then carry out further studies to test the findings in humans.
What did the research involve?
The researchers first looked at a group of mice genetically engineered to have defective body clocks and a group of normal mice to identify any differences between the two groups in how their white blood cells (immune cells responded to invading microorganisms. They found that the differences identified related to a protein called Toll-like receptor 9 (TLR9 . This protein recognises DNA from bacteria and viruses, and plays a role in signalling to the immune system to mount an attack on these invading organisms. The researchers then looked at whether the production and function of TLR9 in normal mice varies throughout the day as a result of the body clock cycle (known as the “circadian cycle” .
The researchers then gave mice vaccinations containing molecules that would activate TLR9 and looked at whether mice responded differently to the vaccine according the time of the day it was given. They also looked at whether time of day affected how mice responded to being infected with bacteria in a process known to involve TLR9. The method used involves allowing bacteria from the mouse’s intestines to invade its body cavity. This leads to a condition called sepsis, a strong inflammatory immune system response throughout the body that is harmful to the mice.
What were the basic results?
The researchers found that levels of the protein TLR9 in mice did fluctuate naturally through the day, peaking at set times over a 24-hour cycle.
They found that when they gave mice vaccines that would activate TLR9, the vaccination produced a greater immune response if given at a time of day when TLR9 levels were at their highest. The researchers found that if the mice were infected at a time when TLR9 was at its highest, the mice showed worse signs of sepsis and died earlier than mice infected at the time when TLR9 was at its lowest.
How did the researchers interpret the results?
The researchers concluded that their findings showed a direct link between the body clock and one aspect of the immune system in mice. They said that this may have important implications for how vaccination and immune-system-related therapies are administered in humans.
They also noted that some studies have found that people with sepsis are more likely to die between 2am and 6am. They say that further studies are needed to determine if this may be related to levels of TLR9, and if so whether giving certain therapies during this period could reduce this risk.
Conclusion
This study identifies one way in which the body clock and immune system interact in mice, via a protein called TLR9. The researchers found that fluctuations in this protein throughout the day influenced how effective a certain form of vaccination was in mice, and also influenced the mice’s response to one type of serious infection.
Differences between the species mean more research is needed to determine if these findings also apply to humans. If they do, then vaccinations could be given at specific times of day when they would be most effective. However, this theory needs testing in humans to ensure that it makes a meaningful difference to the effectiveness of the vaccine.
There has also been media speculation that researchers could develop infection-fighting drugs based on these findings. However, this suggestion is premature as researchers first need to confirm that the mechanism identified in this study also applies in humans. Even if it is confirmed, it would still take a great deal of research to develop and test a drug that could capitalise on it.
It’s also worth remembering just how complex the immune system is, and although this research improves our understanding of one aspect (how it is affected by the body clock there is still much to learn.
Analysis by Bazian
Links To The Headlines
Body clock 'alters' immune system. BBC News, February 17 2012
Not sleeping enough can damage your immune system and make you ill, says study. Daily Mail, February 17 2012
Links To Science
Silver AC, Arjona A, Walker WE, Fikrig E. The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity. Immunity, February 17 2011
Slaughter specically asked the companies to breakdown what percentage of the food they sell is raised "without any antibiotics," raised with antibiotics only for "therapeutic reasons," or raised with "routine use of antibiotics" -- information that consumers often have no way of knowing. The list of companies that received the letter was varied, including: Burger King, Cargill, YUM! Brands, Costco, Bon Appetit Management Company, Kraft, McDonald's and Whole Foods.
"Very simply, consumers have a right to know what's in their food," said Slaughter. "It's like that old commercial, 'where's the beef?' We just want to know, 'what's in the beef?' The US is facing a growing public health crisis in the form of antibiotic-resistant bacteria, and information about how these companies are contributing to its rise or resolution should be available to consumers."
Antibiotic-resistance is not just an issue that rallies sustainable agriculture advocates -- who have long argued against drug use in food animal production -- the issue is increasingly tied to foodborne illness outbreak headlines.
Last year, the United States had the most outbreaks ever of antibiotic-resistant Salmonella tied to meat and poultry, according to Slaughter's office. Last summer, the largest Class I meat recall on record was initiated after Cargill ground turkey was linked to a nationwide drug-resistant Salmonella Heidelberg outbreak tied to 136 illnesses and one death.
"Decades of research has shown that the practice of routinely feeding antibiotics to swine, cows, and chickens harms human health by contributing to diseases that fail drug treatment," the letter continued. "A National Academy of Sciences report stated that 'a decrease in the inappropriate use of antimicrobials in human medicine is not enough [to slow the increase in antibiotic resistance]. Substantial efforts must be made to decrease inappropriate misuse in animals and agriculture as well."
The most recent estimates show around 80 percent of all antibiotics sold annually are used in food animal production.
The only microbiologist serving in Congress, Slaughter challenged companies to tout examples of lessening antibiotic use.
"There are some who would have us believe that we must pump our food up with antibiotics to keep prices low and affordable," she said. "But the food industry has proven success stories and leaders who understand the benefits that come from raising and serving antibiotic-free meat. It is not incompatible for us to have healthy and affordable food."
The
letter asks companies to respond in detail to Congresswoman Slaughter's office by June 15.
And as if the old adage needed more proof that political movements always end up eating their own, Mr. Taylor's nemesis is MoveOn, the left-of-center group that got its start trying to retain President Clinton after his sexual liaison with Monica Lewinsky.
Taylor, currently deputy commissioner for foods at the U.S. Food and Drug Administration (FDA , did not get on MoveOn's bad side for anything as nefarious as that.
He did however do a 15-month stint as vice president for public policy for Monsanto, leaving the corporation that has been called one of America's ten most innovative companies, in January 2000. If Taylor's obituary were written now, it's not his short time at Monsanto that would get much attention. It would be his two longer periods of public service. At USDA during the Clinton Administration, he was the top administrator for the Food Safety and Inspection Service that first banned E. coli O157:H7 from beef.
And at FDA, he put his skills with Congress to work to get the Food Safety Modernization Act passed by Congress and he now in charge of implementation.
Still, a loose coalition of genetic engineering (GE opponents, raw milk advocates, organic farmers and the like has voiced objections to Taylor since he joined the Obama Administration. They point to other stints in
Taylor's resume where they claim he had ties to Monsanto.
A petition went up months ago, but only after MoveOn adopted Taylor's removal as a pet cause has the effort "gone viral." It has so far collected about 420,000 signatures.
Now, however, some of the nation's best known food safety and consumer advocates are trying to see if they can get MoveOn to back down.
"We acknowledge that Monsanto symbolizes a lot of things that many people (including some of us don't like about modern, industrial agriculture. But Mr. Taylor's resume is not reducible to his work at that company," the signers wrote MoveOn.
"It is far more relevant that in the Clinton Administration he headed the Food Safety and Inspection Service at the U.S. Department of Agriculture, where he stood up to the meat industry and fought for strict controls that help keep E. coli and other pathogens out of meat and poultry. Since joining the Obama Administration, Taylor has been working extraordinarily hard to transform the FDA from a reactive agency that chases down foodborne?illness outbreaks after people fall ill, to a proactive public?health?based agency focused on preventing foods from becoming contaminated in the first place."
"We are confident that his leadership, formerly at USDA and now at FDA, has and will continue to reduce the number of Americans sickened, hospitalized, and killed by foodborne pathogens."
Signing on to the
public letter are:
-Michael F. Jacobson, Ph.D., Executive Director Center for Science in the Public Interest
-Shaun Kennedy, Director, National Center for Food Protection and Defense Director, Partnerships and Programs, College of Veterinary Medicine Assistant Professor, Veterinary Population Medicine University of Minnesota
-William D. Marler, Esq. Marler Clark, The Food Safety Law Firm
-J. Glenn Morris, M.D., Director, Emerging Pathogens Institute University of Florida
-Michael Rodemeyer, Lecturer, Department of Science, Technology and Society University of Virginia, Former Executive Director, Pew Initiative on Food and Biotechnology
-Donald W. Schaffner, Ph.D., Extension Specialist in Food Science and Professor Director of the Center for Advanced Food Technology Rutgers University
-Deirdre Schlunegger Chief Executive Officer STOP Foodborne Illness
-Carol L. Tucker?Foreman, Distinguished Fellow, The Food Policy Institute Consumer Federation of America, Former Assistant Secretary of Agriculture
On the other side, Atlanta' s Frederick Ravid is the author of the petition calling for Taylor's removal. He posted it on
SignOn.org in August. MoveOn sent it out on Feb. 6 to its five million members, spiking sign-ups.
Taylor's supporters have pointed out that Ravid 's claims that biotech foods contribute to various types of cancers are without scientific merit.
Taylor has removed himself from making any policies having to do with GE foods.
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