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Thursday, 23 February 2012

Drug combo may fight pancreas cancer

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.

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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.

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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.�

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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

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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.

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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.

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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

Source: http://www.nhs.uk/news/2012/02February/Pages/pancreatic-cancer-mrk003-drug-combination.aspx

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Is immune system linked to the body clock?

?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.

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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.

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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.

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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.

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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.

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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.

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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

Source: http://www.nhs.uk/news/2012/02February/Pages/circadian-rhythm-and-infection-immunity.aspx

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Migraine increases risk of depression

A study of 36,000 women found those who had either suffered from different types of migraine in the past, or continued to experience episodes, were at a 36 per cent higher risk of developing depression over 14 years.

All those who enrolled in the study, conducted by researchers at the University of California, Los Angeles (UCLA), had never being diagnosed with depression.

Over the 14 years they were followed on average, almost 4,000 developed the mental illness.

The researchers found the 6,500 women with current or past migraine were at a higher risk.

Those with a condition called migraine with aura appeared to be at a higher risk still (43 per cent) than those who had migraine without aura (29 per cent), although the difference was not statistically significant.

Dr Tobias Kurth, of Brigham and Women's Hospital in Boston, Mass., said: "We hope our findings will encourage doctors to speak to their migraine patients about the risk of depression and potential ways to prevent depression."

He and colleagues are to present their findings at the American Academy of Neurology's annual conference in New Orleans in April.

The study could not draw any conclusions about any possible link between migraine and depression in men because it only looked at women.

Source: http://telegraph.feedsportal.com/c/32726/f/568409/s/1cdb9309/l/0L0Stelegraph0O0Chealth0Chealthnews0C90A9860A30CMigraine0Eincreases0Erisk0Eof0Edepression0Bhtml/story01.htm

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Does a daily dose of dhal dispel dementia?

The Daily Mail reported today that ?eating a curry once (or twice) a week could stave off dementia.?

Sadly, this mouth-watering headline is not a good representation of the research. The study in question tested the effects of curcumin (a chemical found in the spice turmeric) on fruit flies. It found that curcumin improved lifespan and activity in some genetically engineered fruit fly models of Alzheimer?s disease. However, some other fruit flies, including the normal fruit flies, those eating actually died more quickly.

This type of study is essential for the initial testing of chemicals that may be of some benefit to humans. Chemicals showing beneficial effects and sufficient safety in animal studies need to be tested in humans before we can know what their true effects on a disease are. However, the promising effects of many chemicals seen in animals are not replicated in humans.

Despite what the papers have reported, this study cannot tell us whether a weekly curry will stave off Alzheimer?s disease or other forms of dementia.

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Where did the story come from?

The study was carried out by researchers from Link�ping University in Sweden.

It was funded by The Knut and Alice Wallenberg Foundation, Alice and Georg Olsson, The Swedish Foundation for Strategic Research, ?Hj�rnfonden? (the Brain Foundation), The Swedish Research Council, the Gustaf V Foundation, and the European Union FP-7 Health project LUPAS.

The study was published in the peer-reviewed scientific journal Public Library of Science One.

The Daily Mail reported that the study was in fruit flies (Drosophila melanogaster) and used the chemical curcumin. However,�the newspaper's�headline suggesting that eating a curry once or twice a week may stave off dementia is not representative of this research.

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What kind of research was this?

This was an animal study looking at the effect of the chemical curcumin on fruit fly models of Alzheimer?s disease. Curcumin is found in turmeric, a spice commonly used in curry recipes such as korma and jalfrezi. Previous studies have suggested that curacumin may help reduce the build-up of toxic amyloid beta that occurs in the brain of people with Alzheimer?s disease.

Animal models of human diseases are used in the initial testing of chemicals that may be beneficial to humans. It is easier and safer to do these early tests in animals in the laboratory than in humans. These models replicate specific aspects of the disease in question, but due to differences between species, do not fully represent the human condition.

As fruit flies are not mammals like humans, any chemicals found to show promise would then also need to be tested in a mammal species such as mice. Although certain chemicals may be effective and safe when tested on mammals, they then need to be tested in humans to see if they are really beneficial to us�as well as�safe to use.

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What did the research involve?

The researchers used fruit flies that had been genetically engineered to replicate (to a certain extent) what happens in the brains of people with Alzheimer?s disease. They used five different types of fruit flies engineered to produce different sections of the protein amyloid beta or another protein called tau. Both of these proteins build up and form abnormal insoluble deposits called plaques and tangles in the brains of people with Alzheimer?s disease. These fruit flies are less active than normal ones of the same age, and have a shortened lifespan.

The researchers carried out various experiments where they fed the genetically engineered and normal fruit flies different amounts of curcumin. They looked at the effect of the curcumin on the fruit flies? activity and lifespan compared to the same types of flies not fed curcumin. They also looked at how curcumin affected the build-up of amyloid beta in the brains of the flies.

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What were the basic results?

The researchers found that the effect of curcumin on lifespan depended on the concentration of curcumin used and the type of fly being tested:

increasing concentrations of curcumin reduced lifespan in normal (control) fruit flies
two of the five Alzheimer?s model fly strains also died sooner with high curcumin dose
three of the Alzheimer?s model fly strains lived longer with the low and intermediate doses of curcumin, although this was still shorter than the lifespan of the normal untreated flies

The greatest effect of curcumin observed was a 75% increase in lifespan with an intermediate dose of curcumin ? from fewer than 10 days to more than 15 days on average, in one of the Alzheimer?s fruit fly models.

As all the different types of flies got older they became less active. Again, the effect of curcumin depended on the type of fruit fly tested:

curcumin reduced activity slightly in normal flies
curcumin had no effect on the activity one of the Alzheimer?s model fly strains
the other four Alzheimer?s model fly strains all showed some increase in activity with curcumin, but the extent of the increase varied

The Alzheimer?s model fruit fly strain that showed the greatest increase in lifespan did not show the greatest increase in activity.

The researchers found that curcumin did not decrease the build up of insoluble deposits of amyloid beta in the brains of the fruit flies. However, curcumin sped up the soluble amyloid beta sticking together to form larger bundles called fibrils.

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How did the researchers interpret the results?

The researchers concluded that curcumin reduces the toxic effects of amyloid beta or tau protein in the brains of genetically engineered fruit fly models of Alzheimer?s disease.

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Conclusion

Curcumin is found in the bright yellow spice turmeric, which is commonly used in curries. This study has shown that curcumin can improve lifespan and activity in some genetically engineered fruit fly models of Alzheimer?s disease.

It is worth noting that this effect was not seen in all of the genetically engineered fruit fly models of Alzheimer?s disease, and that some fruit flies, including the normal ones, actually showed reduced lifespan with curcumin.

Chemicals showing beneficial effects and sufficient safety in animal studies�also�need to be tested in humans before we can know what their true effects on a disease are. Sadly, the promising effects of many chemicals seen in animals are not replicated in humans.

Despite what the papers have reported, this study cannot tell us whether a weekly curry will stave off Alzheimer?s or any other forms of dementia. However, it is worth noting that a high-fat diet is associated with some forms of dementia.

Analysis by Bazian.

Links To The Headlines

Hot new tip... eating a curry once (or twice) a week could stave off dementia, say scientists. Daily Mail, February 16 2012

Having a curry could help ward off dementia. The Daily Telegraph, February 16 2012

Links To Science

Caesar I, Jonson M,�Nilsson KPR, et al. Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila. Public Library of Science One. Published online February 13 2012

Source: http://www.nhs.uk/news/2012/02February/Pages/a-curry-a-week-staves-off-dementia.aspx

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Breastfeeding And Caffeine Consumption

Main Category: Women's Health / Gynecology
Also Included In: Nutrition / Diet;��Sleep / Sleep Disorders / Insomnia;��Pediatrics / Children's Health
Article Date: 23 Feb 2012 - 0:00 PST

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Babies are not able to metabolize or excrete caffeine very well, so a breastfeeding mother's consumption of caffeine may lead to caffeine accumulation and symptoms such as wakefulness and irritability, according to an interview with expert Ruth Lawrence, MD, published in Journal of Caffeine Research, a peer-reviewed journal from Mary Ann Liebert, Inc. The interview is available on the Journal of Caffeine Research website.*

Caffeine is found in a wide range of products in addition to coffee, tea, and chocolate, including soft drinks, sports drinks, and some over-the-counter medications. In a provocative discussion with Dr. Ruth Lawrence, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Jack E. James, PhD, Editor-in-Chief of Journal of Caffeine Research, asks a variety of probing questions. Is there a safe level of caffeine intake while breastfeeding? Are there potential long-term effects of caffeine exposure on development and intellect? Can a baby whose mother consumed caffeine during pregnancy experience withdrawal if she then abstains from caffeine while breastfeeding? Dr. Lawrence bases her responses on the scientific and medical evidence related to caffeine exposure in breastfed babies, and distinguishes between what is and what is not well understood in this developing field of study.

"Usually a mother, particularly if she is breastfeeding, is cautioned to limit her caffeine intake," says Dr. Lawrence, who is Editor-in-Chief of the peer-reviewed journal Breastfeeding Medicine. After giving birth, mothers "should consume all things in moderation and try to avoid the excesses that might really add up to a lot of caffeine."

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