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Monday, April 16, 2012

Colon Cancer - New Mechanism Discovered

Editor's Choice
Main Category: Colorectal Cancer
Also Included In: GastroIntestinal / Gastroenterology
Article Date: 16 Apr 2012 - 14:00 PDT

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Researchers from the Case Western Reserve University School of Medicine have discovered a new mechanism by which colon cancer develops. Whilst concentrating on 'junk DNA' i.e. DNA segments located between genes, the team found a set of master switches (gene enhancer elements) that turn key genes on and off. An alteration in the expression of these genes leads to colon cancers. To describe these master switches, the team has named them Variant Enhancer Loci or 'VELs'.

The team points out that VELs are not mutations in the actual DNA sequence, but changes in proteins that bind to DNA. This form of alteration is also known as 'epigenetic' or 'epimutations'. The finding is significant, given that such epimutations can potentially be reversed.

Over a 3-year period, the team systematically recorded the locations of hundreds of thousands of gene enhancer elements in DNA from normal and cancerous colon tissues and identified key target VELs that were different between the two tissue types.

Senior researcher, Peter Scacheri, PhD, assistant professor of Genetics and Genome Sciences at the School of Medicine and member of Case Comprehensive Cancer Center at Case Western Reserve University states:

"What is particularly interesting is that VELs define a 'molecular signature' of colon cancer. Meaning, they are consistently found across multiple independent colon tumor samples, despite the fact that the tumors arose in different individuals and are at different stages of the disease. The set of common VELs govern a distinct set of genes that go awry in colon cancer."

Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics in the Division of Hematology-Oncology at the School of Medicine and member of Case Comprehensive Cancer Center, who is also an oncologist at the University Hospitals Seidman Cancer Center, and whose team collaborated on the study, adds:

"The VELs signature is notable because it cuts through the complexity of the many genes that are changed in colon cancer, to identify genes that are direct targets of alterations on chromosomes. The key next step will be to determine whether we can use VELs for 'personalized medicine,' to molecularly define distinct groups of colon cancers that differ in their clinical behavior, and to enable selection of specific drugs that will best treat a given colon tumor."

Aside from discovering that VELs are a 'signature' of colon cancer, the team also demonstrated that VELs contain genetic variants that govern which people will be likely to suffer from colon cancer. This indicates that individual differences within VELs may play an important part in establishing different people's susceptibility to colon cancer.

Lead author, Batool Akhtar-Zaidi, PhD candidate in Dr. Scacheri's lab explains:

"Epigenetics has transformed the way we think about genomes. The genetic code isn't just a series of As, Ts, Gs, and Cs strung together. Epigenetic 'marks' on DNA tell genes when, where, and how much to turn on or off to keep cells healthy. When this epigenetic machinery is disrupted, as we see with VEL events, this can tip the balance to cancer."

Written By Petra Rattue
Copyright: Medical News Today
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Indian Mothers In Canada More Likely To Have Male Offspring

Editor's Choice
Main Category: Pregnancy / Obstetrics
Also Included In: Sexual Health / STDs
Article Date: 16 Apr 2012 - 14:00 PDT

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According to a new study published in the CMAJ (Canadian Medical Association Journal), mothers who were born in India, but now live in Canada, are considerably more likely to give birth to boys as their second or third births than Canadian women.

Dr. Joel Ray of the St. Michael's Hospital and University of Toronto remarks:

"Our findings raise questions about why there are more male liveborns than female liveborns among Indian couples who have had two or more previous babies."

In a male:female ratio study, researchers from St. Michael's Hospital and the University of Toronto examined 766,688 single live births in Ontario between 2002 and 2007. The births were categorized by the mother's country or region of birth, revealing that 486,599 babies were born to Canadian mothers, 58,505 to European mothers, 31,978 to Indian mothers and 23,818 to Chinese mothers, whilst 18,971 babies were born to mothers originating from the rest of East Asia, as well as 18,018 Pakistani mothers and 3,663 Korean mothers.

The investigators also considered the fathers country of birth and calculated the male:female ratio of live births by country or region and on how many previous deliveries the mother already had, i.e. 0, 1, 2, 3 or more.

The findings showed that the male:female ratio for most women was 1.05 and remained unchanged, regardless of the number of previous births, yet for Indian and South Korean women with previous children, the likelihood of giving birth to a male child was substantially higher, and even higher than that for Indian-born women with more than one previous child.

According to earlier research in India and a study that examined Canadian census data for South Asian and East Asian immigrants, the patterns of a higher male:female ratios are associated with having more children, in particular, if the previous children were girls.

The authors conclude:

"Whether this difference in sex ratios was the result of prenatal sex selection should be determined by direct study of practices of sex-selected preimplantation and pregnancy termination among individuals from various world regions. In addition, an analysis of the duration of residence in Canada, access to fertility care, family income and parental preferences would be of value in describing factors that might influence prenatal sex selection."

The study was limited in terms of only including single births, with no consideration to any sex selection in multiple pregnancies from fertility treatments. The researchers were also unable to determine the sex of older siblings from the same mother.

Written By Petra Rate
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Sepsis Common In USA Hospitals, Unawareness High

Editor's Choice
Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 16 Apr 2012 - 14:00 PDT

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According to a 2010 survey, 66% of Americans had never heard of the word 'sepsis', and of the remaining third who had, 35% had no idea what it meant. The result is shocking considering that sepsis is the leading cause of mortality in U.S. hospitals, with 750,000 patients and over 250,000 deaths each year. The most dangerous form of sepsis, i.e. severe sepsis and septic shock has a combined mortality rate of 30 to 35%.

Sepsis poses a healthcare crisis that is becoming pandemic in the U.S. and worldwide. The Global Sepsis Alliance defined sepsis last year for what it represents, i.e. a worldwide medical emergency and possibly the leading cause of death worldwide, which kills tens of millions every year.

Even though the situation is very serious indeed, there is still not one FDA-approved drug on the market today which can treat severe sepsis and septic shock. In late 2011, Eli Lilly withdrew Xigris from the U.S. market, due to efficacy and safety problems, which highlighted the urgent need for new efficient and cost-effective treatments. Another drug, Eritorin (Eisai) intended for the use of severe sepsis, failed the efficacy test in its phase III trial, whilst Agennix AG stopped its Phase II/III trial of talactoferrin in February 2012 because of safety issues.

Canadian and U.S. researchers are currently participating in EUPHRATES, a late-stage North American multi-center clinical study, which is evaluating whether a combination therapeutic/diagnostic (theranostic) can improve patient survival in those with severe sepsis and septic shock. EUPHRATES is the first study assessing a theranostic for the diagnosis and treatment of sepsis. It also differs from other studies insofar that it applies principles of personalized medicine to identify and treat a specific subgroup of the patient population that has the highest risk of mortality.

Earlier studies have demonstrated that elevated endotoxin levels in the blood, a condition known as endotoxemia, can be a potent trigger of the "sepsis cascade", i.e. the physiological chain of events that may ultimately result in organ failure and death. About half of all patients with severe sepsis, which is around 125,000 patients, have endotoxemia.

The theranostic substance in the EUPHRATES study consists of Endotoxin Activity Assay (EAA') and Toraymyxin'. EAA' is an FDA-cleared rapid diagnostic that measures endotoxin levels in the blood, whilst Toraymyxin' is a therapeutic hemoperfusion device that removes endotoxin from the bloodstream and is already approved in 18 countries and has safely treated over 80,000 patients. However, in the U.S., Toraymyxin is still an investigational device. JAMA published interim results of a Phase II study in 2009, which demonstrated that Toraymyxin, when added to conventional therapy, substantially reduced 28-day mortality in patients with severe sepsis and septic shock, unlike patients who only received conventional therapy. The trial was terminated early because of these positive results, and a Phase III pivotal multi-center study has been launched in the U.S. and Canada.

If the EUPHRATES trial should prove successful, the potential first effective treatment would mean a major breakthrough in an area of unmet medical need and it would change the way in which most patients are currently treated for sepsis.

Written By Petra Rattue

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Sunday, April 15, 2012

Tree Nut Consumption Associated With Better Diet Quality In Children And Adults

Main Category: Nutrition / Diet
Also Included In: Heart Disease; Cholesterol
Article Date: 15 Apr 2012 - 0:00 PDT

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In a study published in Nutrition Research, researchers looked at the association of out-of-hand nut (OOHN) consumption with nutrient intake, diet quality and the prevalence of risk factors for cardiovascular disease and metabolic syndrome in both children and adults. Consumers of OOHN, including tree nuts (almonds, Brazil nuts, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts), had higher intakes of energy, monounsaturated and polyunsaturated fats (the good fats) and dietary fiber, and lower intakes of carbohydrates, cholesterol and sodium than non-consumers.

"Adult consumers also had a 19% decreased risk of hypertension and a 21% decreased risk of low high-density lipoprotein (HDL - -the good cholesterol) levels - both risk factors for metabolic syndrome and cardiovascular disease," stated Carol O'Neil, PhD, MPH, RD, lead author on the paper and Professor at Louisiana State University Agricultural Center.

The study looked at 24,385 individuals aged 2+ years participating in the 1999-2004 National Health and Nutrition Examination Surveys (NHANES). Intake was from 24-hour recall data and OOHN consumers were defined as those who consumed at least ¼ ounce of nuts per day, solely as nuts and not as part of products (i.e., in breads, cereals and bars.)

According to Dr. O'Neil, "We decided to look at OOHN specifically because this shows an individual's conscious decision to consume nuts, which may be associated with a desire for a healthier lifestyle." Interestingly, the percent of OOHN consumers increased with age: 2.1% ± 0.3%, 2.6% ± 0.3%, 6.5% ± 0.5%, and 9.6% ± 0.5% of those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years, respectively. The two latter groups were combined into a single group of consumers aged 19+ years for subsequent analyses.

"In all of the age groups, although energy intake was higher in OOHN consumers than non-consumers, neither weight nor body mass index (BMI) was higher. This suggests that OOHN consumers are better able to balance energy intake with energy output than non-consumers," stated Dr. O'Neil. This research comes on the heels of another study by the same authors, published in the Journal of the American College of Nutrition, which showed that tree nut consumers specifically (ages 19+) had lower body weight, as well as lower BMI and waist circumference compared to non-consumers. The mean weight, BMI, and waist circumference were 4.19 pounds, 0.9kg/m2 and 0.83 inches lower in consumers than non-consumers, respectively.

"These new data, along with previous research, show once again that nuts can and should play an important role in a healthy diet," adds Maureen Ternus, M.S., R.D., Executive Director of the International Tree Nut Council Nutrition Research & Education Foundation (INC NREF). "With current nut consumption well below the recommended 1.5 ounces of nuts per day (in the FDA qualified health claim for nuts and heart disease) people should be encouraged to grab a handful of nuts every day. Eat them as a snack or throw some on yogurt, salad or oatmeal."

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Biomarkers May Predict Chemo-Resistant Breast Cancers

Featured Article
Academic Journal
Main Category: Breast Cancer
Also Included In: Cancer / Oncology; Blood / Hematology
Article Date: 15 Apr 2012 - 6:00 PDT

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Researchers at the University of Hull in the UK have identified a family of proteins that could potentially be used as biomarkers to predict resistance to chemotherapy in estrogen receptor-positive (ER-positive) breast cancer patients.

In an "in press" issue of their study published online in the Journal of Proteomics on 3 April, lead researcher Dr Lynn Cawkwell and colleagues explain how they discovered a number of potential biomarkers for resistance to epirubicin, docetaxel and other chemo drugs.

Resistance to chemotherapy is a big problem in the treatment of some types of cancer.

Without a means to predict whether chemo will work, some patients with resistant cancers undergo much hardship: suffering the side effects of ineffective chemo options without the benefits, plus they lose valuable time until an effective therapy is found.

So a major goal in cancer research is to predict how particular cancers might respond, and one way to do this is to test for particular proteins or biomarkers.

"Unfortunately, a reliable test has not yet been developed to achieve this [for ER-positive breast cancer]. We hope our work can help to bring us a step closer," Cawkwell told the press.

Some scientists working in this field use cell lines to try and track down biomarkers, but Cawkwell's team used clinical breast tumour tissue samples taken from patients, which she says helped them gain a "more accurate representation of what is relevant in real-life diseases".

For their study, Cawkwell and colleagues also used two "high-throughput processes", one based on antibodies and the other using mass spectrometry, to identify candidate biomarker proteins.

Using these to conduct "comparative proteomic experiments", they identified 132 unique proteins that were significantly differently expressed (more than two-fold) in chemo-resistant samples, 57 of which were identified in at least two experiments, they write.

Five of the proteins in the 57 candidates belong to the 14-3-3 protein family (namely the "isoforms" theta/tau, gamma, epsilon, beta/alpha and zeta/delta), and have previously been associated with chemotherapy resistance in breast cancer.

The team says their findings confirm the 14-3-3 protein family as a strong candidate for a predictive test for chemo-resistance.

The team is now working on showing how these proteins might be used as biomarkers to predict chemo-resistant ER-positive breast cancers. Cawkwell said:

"If we're correct, we hope that by testing for these proteins, doctors will be able to anticipate a patient's response to different chemotherapies, and decide which course of treatment is most appropriate for them."

The team is also investigating radiotherapy resistance in a number of different cancers.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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"Pilot and feasibility study: comparative proteomic analysis by 2-DE MALDI TOF/TOF MS reveals 14-3-3 proteins as putative biomarkers of response to neoadjuvant chemotherapy in ER-positive breast cancer"; Victoria C. Hodgkinson, Vijay Agarwal, Dalia ELFadl, John N. Fox, Penelope L. McManus, Tapan K. Mahapatra, Peter J. Kneeshaw, Philip J. Drew, Michael J. Lind, Lynn Cawkwell; Journal of Proteomics, In Press, Uncorrected Proof, Available online 3 April 2012; DOI: 10.1016/j.jprot.2012.03.049; Link to Abstract.
Addtitional sources: University of Hull. Please use one of the following formats to cite this article in your essay, paper or report:

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Saturday, April 14, 2012

Treating Head Injury Without Surgery By Monitoring Pressure

Editor's Choice
Main Category: Neurology / Neuroscience
Article Date: 14 Apr 2012 - 8:00 PDT

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The pressure inside patient's skull can rise due to brain tumors and head trauma, including concussion. The elevated pressure inside the brain can destroy brain tissue or cut off the brain's blood supply. Being able to monitor the pressure inside the brains of affected people could help physicians in establishing the best possible treatment. However, the procedure is extremely invasive, as it requires drilling a hole into the patient's skull and is therefore only performed in patients who are severely injured. ''

A novel, less risky technique, described in the April 11 issue of Science Translational Medicine, could enable doctors to measure brain pressure in patients with less severe or milder head injuries, who would benefit from close monitoring.

Researchers at MIT's Research Laboratory of Electronics (RLE) developed the novel technique based on a computer model of the way blood flows through the brain. Based on the model, researchers are able to calculate brain pressure from two less invasive measurements, i.e. arterial blood pressure and an ultrasound measurement of the velocity of blood flow through the brain. This approach allows physicians to constantly monitor any changes in brain pressure, as well as being alerted of problems that may build up slowly.

Intracranial pressure (ICP), or the pressure in the brain, can become elevated because of excessive blood or cerebrospinal fluid building up, a brain tumor or swelling of the brain.

Until now, neurosurgeons had to drill a hole in the skull and insert a catheter into the brain tissue, or a fluid-filled cavity within the brain, in order to measure the pressure within the brain. According to study conducted by co-author George Verghese, a Henry Ellis Warren Professor of Electrical Engineering at MIT, the risk of infection or brain damage outweighs the benefits of this procedure, which is therefore only undertaken in only the most critically ill patients.

Verghese, whose lab concentrates on using computer models of human physiology to interpret patient data, explains:

"There's a much larger patient population for whom physicians would like this measurement, but the invasiveness stops them from obtaining it." ''

Lead author Faisal Kashif, a postdoc in Verghese's lab, designed a computer model in his PhD thesis, which links arterial blood pressure and blood flow through the brain to pressure within the brain.

Kashif's model calculates ICP by calculating the blood flow through the brain, which is caused by the difference in pressure between the blood entering the brain and the pressure inside the brain (ICP). Given that t'he pressure of blood entering the brain cannot be measured directly, the MIT team used radial arterial pressure as a proxy measurement, which was obtained by inserting a catheter at the wrist before using their blood flow model to compensate for the difference in location. ''

Because it is possible to measure peripheral arterial pressure continuously and non-invasively by using a finger cuff, comparable to an arm cuff used for measuring blood pressure, the team is now examining whether data obtained in this way is sufficiently accurate enough to be used in their model.

They confirmed the accuracy of their technique by using data their collaborator Marek Czosnyka obtained a few years ago from patients with traumatic brain injury, which turned out to be one of the few data sets that included all necessary measurements, together with the proper time stamps. The MIT team received Czosnyka's data on radial arterial blood pressure and ultrasound blood flow velocity and used these numbers in their model to calculate an estimated ICP before sending the figures back to Czosnyka to compare. ''

The test revealed that the MIT results were marginally less precise, compared with those obtained from the best invasive procedures. However, they proved to be similar to other invasive procedures still in clinical use, as well as to some less invasive tried techniques.

James Holsapple, chief of neurosurgery at Boston Medical Center remarks:

"It's a holy grail of clinical neurosurgery to find a noninvasive way to measure pressure. It would be a big step if we could get our hands on something reliable."''

He continues saying that the new MIT approach is promising and adds that the next significant step would be to incorporate the technology into a system that would be easy to use for hospital staff and which could record data over many hours or days. '

'The MIT team and Vera Novak of Beth Israel Deaconess Medical Center (BIDMC) in Boston are currently collaborating with doctors at BIDMC to test their approach on patients in the neurosurgical intensive care unit. ''

Verghese declares:

"It's still at the validation stage. To convince people that this works, you need to build up more [data] than we currently have. Our hope is that once it's been validated on additional sorts of patients, where you're able to show that you can match what the invasive measurement is, people will have confidence in starting to apply it to patients who are currently not getting monitored. That's where we see the big potential."

Senior author, Thomas Heldt, a research scientist in RLE states that once the data collection and model have manifested themselves sufficiently, the team hopes to test different patient populations, for instance athletes with concussions, or soldiers who experienced explosions to identify ways in which the extent of injury can be determined and whether or not it would be safe for individuals to return to work. ''Given that NASA has observed signs of elevated ICP in some astronauts and is now looking for new ways of measuring their ICP would open another avenue to apply the system.

'Written By Petra Rattue
Copyright: Medical News Today
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Restoring Heart Muscle Function With Pelvic Bone Stem Cells

Editor's Choice
Main Category: Stem Cell Research
Also Included In: Heart Disease
Article Date: 14 Apr 2012 - 8:00 PDT

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Researchers from the Orlando Health Heart Institute are exploring how to restore tissue and improve heart function after muscle damage from heart attacks with stem cells from pelvic bone marrow, as it may improve the heartbeat.

The ORMC's leading researcher for the clinical trial, Vijaykumar S. Kasi, MD, PhD, an interventional cardiologist, director, Cardiovascular Research, explains:

"The thought is the body may use itself to heal itself. Because stem cells are immature cells they have the potential to develop into new blood vessels and preserve cardiac muscle cells. By infusing certain stem cells into the area of the heart muscle that has been damaged from a heart attack, tissue can be preserved and heart function restored."

The PreSERVE-AMI Study assesses the efficacy and safety of infusing stem cells obtained from a patient's bone marrow into the artery in the heart, which may have caused the heart attack in patients who received a stent to open the blocked artery after a specific heart attack history, such as STEMI.

A ST-Segment Elevation Myocardial Infarction (STEMI) is a critical type of heart attack that occurs due to the blood supply to the heart being blocked for a prolonged period of time, which affects a large area of the heart muscle and causes changes in the blood levels of key chemical markers.

The national, randomized, double blinded and placebo controlled study will involve approximately 160 patients, at about 34 sites, to evaluate the efficacy and safety of infusing stem cells obtained from a patient's bone marrow into the artery in the heart that may have caused the heart attack.

The surgeons will first insert a catheter into an incision in the patient's groin. Guided by an x-ray camera, the doctors will then position the catheter in the location of the heart artery where the stent was placed, before inflating a balloon within the stent and infusing either AMR-001, a cell therapy product comprised of stem cells taken from the patient's own bone marrow, or a placebo into the affected area.

Before the infusion is made, the patients undergo various tests, including an electrocardiogram, a cardiac MRI and a cardiac nuclear test. After the patient has received all screenings required, the doctors will perform a mini-bone marrow procedure, in which they remove stem cells from the bone marrow of the patient's pelvic bone with a special needle. The stem cells are subsequently processed in preparation for infusion. The bone marrow of patients randomized to receive placebo will be frozen and stored in case they require bone marrow for any reason.

Dr. Kasi announces:

"We are excited to participate in innovative clinical trials as part of our continued efforts to play a vital role in future solutions to improve patient outcomes. Heart disease remains the No.1 killer of men and women in our country."

Finding effective treatment approaches is one step towards achieving more heart healthy communities worldwide.

Kasi concludes:

"Severe heart failure, often the end result of large or multiple heart attacks, is a major health care challenge, impacting more than five million people in the United States and costing more than $35 billion annually. Stem cell therapy is part of the movement from treatment to cure and has the potential to overcome limitations and expenses of heart transplants and offers hope for patients who are desperately praying for another chance at life."

Written By Petra Rattue
Copyright: Medical News Today
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