The wiring diagram of the cellular computer: all five factors must be in their correct state in order to trigger cell death. (Illustration: Benenson Y. & R. Weiss)

Researchers led by ETH professor Yaakov Benenson and MIT professor Ron Weiss have successfully incorporated a diagnostic biological “computer” network in human cells. this network recognizes certain cancer cells using logic combinations of five cancer-specific molecular factors, triggering cancer cells destruction.

Yaakov (Kobi) Benenson, Professor of Synthetic Biology at ETH Zurich, has spent a large part of his career developing biological computers that operate in living cells. his goal is to construct biocomputers that detect molecules carrying important information about cell wellbeing and process this information to direct appropriate therapeutic response if the cell is found to be abnormal.

Now, together with MIT professor Ron Weiss and a team of scientists including post-doctoral scholars Zhen Xie and Liliana Wroblewska, and a doctoral student Laura Prochazka, they made a major step towards reaching this goal. in a study that has just been published in Science, they describe a multi-gene synthetic “circuit” whose task is to distinguish between cancer and healthy cells and subsequently target cancer cells for destruction. this circuit works by sampling and integrating five intracellular cancer-specific molecular factors and their concentration. The circuit makes a positive identification only when all factors are present in the cell, resulting in a highly precise cancer detection. Researchers hope that it can serve a basis for very specific anti-cancer treatments.

The scientists tested the gene network in two types of cultured human cells: cervical cancer cells, called HeLa cells, and normal cells. when the genetic bio-computer was introduced into the different cell types, only HeLa cells, but not the healthy ones, were destroyed.

Extensive groundwork was required to achieve this result. Benenson and his team had to first find out which combinations of molecules are unique to HeLa cells. they looked among the molecules that belong to the class of compounds known as microRNA (miRNA) and identified one miRNA combination, or profile, that was typical of a HeLa cell but not any other healthy cell type.

Finding the profile was a challenging task. in the human body there are about 250 different healthy cell types. in addition, there are numerous variants of cancer cells, of which hundreds can be grown in the laboratory. still greater is the diversity of miRNA: between 500 to 1000 different species have been described in human cells. “Each cell type, healthy or diseased, has different miRNA molecules switched on or off,” says Benenson.

Creating a miRNA “profile” is not unlike finding a set of symptoms to reliably diagnose a disease: “One symptom alone, such as fever, can never characterize a disease. The more information is available to a doctor, the more reliable becomes his diagnosis,” explains the professor, who came to ETH from Harvard University a year and a half ago. The researchers have therefore sought after several factors that reliably distinguish HeLa cancer cells from all other healthy cells. it turned out that a combination of only five specific miRNAs, some present at high levels and some present at very low levels, is enough to identify a HeLa cell among all healthy cells.

“The miRNA factors are subjected to Boolean calculations in the very cell in which they are detected. The biocomputer combines the factors using logic operations such as AND and NOT, and only generates the required outcome, namely cell death, when the entire calculation with all the factors results in a logical TRUE value,” says Benenson. Indeed, the researchers were able to demonstrate that the network works very reliably in living cells, correctly combining all the intracellular factors and giving the right diagnosis. this, according to Benenson, represents a significant achievement in the field.

In a next step, the team wants to test this cellular computation in an appropriate animal model, with the aim to build diagnostic and therapeutic tools in the future. this may sound like science fiction, but Benenson believes that this is feasible. However, there are still difficult problems to solve, for example the delivery of foreign genes into a cell efficiently and safely. Such DNA delivery is currently quite challenging. in particular this approach requires temporary rather than permanent introduction of foreign genes into the cells, but the currently available methods, both viral and chemical, are not fully developed and need to be improved.

“We are still very far from a fully functional treatment method for humans. this work, however, is an important first step that demonstrates feasibility of such a selective diagnostic method at a single cell level,” said Benenson.

more information: “Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells,” by Z. Xie et al. Science (2011). dx.doi.org/ … ence.1205527

Provided by Swiss Federal Institute of Technology

Summary This study attempted to explore a possible relationship between various parameters of blood cholesterol and a risk of bowel cancer. The cholesterol parameters studied included total cholesterol, high density lipoprotein (HDL) cholesterol (or “good” cholesterol) and other molecules known as lipoproteins. Results showed that the risk of colon cancer was reduced when there was a rise of HDL and a lipoprotein called apoA. this relationship did not hold true for cancer of the rectum however. The authors conclude, “These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.”

Introduction Over the years, many studies have shown that a rise in different types of blood cholesterol may contribute to an increased risk of colon and rectal cancer. However, results from these studies have not always been consistent. Also, there has been little evidence that shows whether lipoproteins and HDL cholesterol are protective in bowel cancer. Studies have speculated that cholesterol in the body can cause several pathological processes that may give rise to bowel cancer. Similarly the risk of high blood cholesterol — especially the bad components like triglycerides, total cholesterol, etc.– is raised by bad lifestyle habits, like too much fatty food consumption, obesity, lack of exercise and alcoholism. this study was planned to explore the benefits that high good cholesterol can provide in protecting against bowel cancer.

Methodology * for this study a total of 520,000 people were followed from 10 different countries from Western Europe. * among these people a total of 1,238 cases of bowel cancer that affected either the rectum or the colon were detected. for each of these cases, matching people with the same age, sex and region, but without cancer, were selected for analysis. * for both the set of cancer-affected people and matching controls, a complete analysis of other parameters like weight, smoking, alcohol consumption, duration of physical exercise, dietary habits, educational status, etc., were recorded. Blood was taken for examination of various cholesterol parameters.

Results/Key findings * Preliminary analysis revealed that those with bowel cancer weighed more than normal, exercised less and had a higher level of education. * HDL was highly correlated with apoA levels but LDL (or “bad” cholesterol) was highly correlated with apoB, another type of lipoprotein. Results showed that a high level of good cholesterol and lipoprotein apoA meant a reduced risk of cancer of the colon.  this beneficial relationship of HDL and apoA did not translate over to cancer of the rectum. * On following the patients for more than two years, the benefits of HDL cholesterol remained, while that of apoA was not found.

Next steps/Shortcomings Authors agree that one of the shortcomings of this study was the one point examination of the blood cholesterol levels. they admit that effects of rising or falling levels of cholesterol on risk of bowel cancer were not explored. they admit that some of the cases of cancer may have been a silent disease at the start of the study and this may have altered their dietary patterns. Finally, the authors write that this study was conducted over a short period of time and longer studies are warranted.

Conclusion this study’s “findings show that high concentrations of serum HDL are associated with a lower risk of colon cancer.” Authors agree that the short duration of this study should be kept in perspective before coming to concrete conclusions. Long-term benefits of HDL cholesterol need to be studied in detail. this is, however, the first large study on bowel cancer and the benefits of HDL cholesterol and apoA that, no matter how small, cannot be overruled. The authors suggest that apart from modification and stoppage of other risk factors for bowel cancer — like an improper diet, smoking, alcoholism, lack of exercise and obesity — raising HDL cholesterol may also be considered as an intervention.

For More Information: Blood Lipid and Lipoprotein Concentrations and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Publication Journal: Gut, March 2011 By Fränzel J. B. van Duijnhoven; H. Bas Bueno-De-Mesquita; National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, and the University Medical Center, Utrecht, The Netherlands

*FYI Living Lab Reports Are Summaries of the Original Research.

Public release date: 20-Mar-2011 [ | E-mail | Share ] Contact: Marty Rayaray6@partners.org617-726-0274Massachusetts General Hospital

Measuring the levels of small molecules in the blood may be able to identify individuals at elevated risk of developing type 2 diabetes as much as a decade before symptoms of the disorder appear. In a report receiving advance online release in Nature Medicine, a team led by Massachusetts General Hospital (MGH) researchers describes finding that levels of five amino acids not only indicated increased diabetes risk in a general population but also could differentiate, among individuals with traditional risk factors such as obesity, those most likely to actually develop diabetes.

“These findings could provide insight into metabolic pathways that are altered very early in the process leading to diabetes,” says lead author Thomas Wang, MD, of the MGH Cardiovascular Research Center (CVRC) and Division of Cardiology. “They also raise the possibility that, in selected individuals, these measurements could identify those at highest risk of developing diabetes so that early preventive measures could be instituted.”

New technologies to measure levels of metabolites — small molecules produced by metabolic activities and released into the bloodstream — are giving investigators increased insight into an individual’s metabolic status. Since the diagnosis of type 2 diabetes marks the culmination of a years-long breakdown of the body’s system for metabolizing glucose, the ability to detect that breakdown at a stage when lifestyle changes could halt the process may significantly reduce the incidence of the disease. Known risk factors such as obesity and elevated glucose levels often signify that diabetes actually is present, so earlier identification of at-risk individuals is critical to more effective preventive measures, the authors note.

Some earlier studies had found elevated levels of certain amino acids in individuals who are obese or have insulin resistance, a condition that precedes full-blown type 2 diabetes. but no previous study examined whether levels of these or other metabolites predicted the future development of diabetes in currently healthy individuals. The current study began with an analysis of data from the Framingham Offspring Study, which follows a group of adult children of participants in the original Framingham Heart Study. Out of 2,400 study participants who entered the study in 1991 and 1995, about 200 developed type 2 diabetes during the following 12 years. using the baseline blood samples, the research team measured levels of 61 metabolites in 189 participants who later developed diabetes and 189 others — matched for age, sex and diabetes risk factors such as obesity and fasting glucose levels — who remained diabetes free.

This analysis found that elevations in five amino acids — isoleucine, leucine, valine, tyrosine and phenylalanine — were significantly associated with the later development of type 2 diabetes. several of these amino acids were the same ones found in smaller studies to be elevated in individuals with obesity or insulin resistance, and other evidence has suggested they may directly affect glucose regulation. The association of levels of these five amino acids with future diabetes development was replicated in 326 participants in the Malmo Diet and Cancer Study.

The investigators then found that measuring combinations of several metabolites, as opposed to a single amino acid, improved risk prediction. Overall, in individuals closely matched for traditional risk factors for type 2 diabetes, those with the highest levels of the three most predictive amino acids had a four to five times greater risk of developing diabetes than did those with the lowest levels.

“Several groups have suggested that these amino acids can aberrantly activate an important metabolic pathway involved in cellular growth or can somehow poison the mitochondria that provide cellular energy,” says Robert Gerszten, MD, director of Clinical and Translational Research for the MGH Heart Center, the paper’s senior author. “From a clinical perspective, we need to see if these markers, which we found using data from only about 1,000 individuals, do identify truly high-risk individuals who should be triaged to early preventive treatment and intensive lifestyle interventions. Additional basic investigations can reveal if these metabolites play a role in the process leading to diabetes and if there are ways we can stop the damage.” Gerszten and Wang are both associate professors of Medicine at Harvard Medical School.

These studies were performed in close collaboration with Clary Clish, PhD, director of Metabolite Profiling of the Broad Institute. Additional co-authors of the Nature Medicine report are Susan Cheng, MD, Elizabeth McCabe, MS, and Gregory Lewis, MD, MGH Cardiology; Eugene Rhee, MD, MGH Renal Unit; Vamsi Mootha, MD, and Jose Florez, MD, PhD, MGH Center for Human Genetic Research and the Broad Institute; Martin Larson, ScD, Ramachandran Vasan, MD, Christopher O’Donnell,MD, and Caroline Fox, MD, MPH, Framingham Heart Study; Paul Jacques, DSc, Tufts University; Celine Fernandez and Olle Melander, MD, PhD, Lund University, Malmo, Sweden; and Stephen Carr, PhD, and Amanda Souza, Broad Institute..

The study was supported by grants from the National Institutes of Health, the Leducq Foundation, the Donald W. Reynolds Foundation, and the American Heart Association. The Framingham Heart Study of the National, Heart, Lung and Blood Institute and Boston University is supported by a contract from the National Institutes of Health.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, reproductive biology, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

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Inflammation of the Colon

Most inflammatory bowel diseases occur within the intestinal walls of the colon. the worst part of this disease is that its so hard to access and try to heal because it is always an internal bowel problem. There are different medications that try to attempt to stop the inflammation from getting worse, and Asacol is one of them. the ulcerative colitis pill Asacol works by releasing its medicine only once it reaches the colon walls. Most of the other medications on the market release their medicine much too early and end up becoming in-effective once the remaining molecules reach the colon.

Longterm Ulcerative Colitis Treatment

The Asacol 5-ASA medication is not just a temporary fix for ulcerative colitis, it can also be a long term treatment that patients can use the rest of their lives. the polls are always almost covered by health insurance, and patients usually can tolerate the medication with very little side effects. unfortunately, when patients stop taking their medicine, there is a much greater chance of the colitis symptoms coming back quickly.

Breakthrough on cystic fibrosis 1 step closer as new research alliance formed( McGill University ) McGill University and GlaxoSmithKline PLC have signed a collaboration agreement to develop a potential breakthrough approach to treat cystic fibrosis, a fatal genetic disease. the trans-Atlantic effort between researchers from McGill’s Faculty of Medicine and their GSK collaborators in the UK, will focus on developing molecules that could treat the disease by correcting the …

Local SportsCancer is a disease that touches nearly every American in some way. It can seemingly come out of thin air and almost instantaneously changes someone’s life the second they’re affected by the disease.

Family Promotes Kawasaki Disease Awareness3,000 people – mostly children – are diagnosed annually.

Family Promotes Kawasaki Disease Awareness3,000 people – mostly children – are diagnosed annually.

Dealing with blight and ways to prevent it“I have a disease on my tomato plants. I compared it to pictures on the Internet and it looks like blight. am I going to lose them all? “My housemates have tomatoes planted next to these. mine are in pots I can move. will mine infect theirs?”

Time: Thursday, January 27th, 2011 at 10:36 pm

Researchers have been able to detect “markers” in the blood that identify the disease three to five years before any memory loss occurs.

The breakthrough means that treatment for the disease could be started before irreversible brain damage has been caused – dramatically slowing down progression.

The same technology could also make it easier to spot other disease such as Parkinson’s and hard-to-detect cancers, said the researchers.

Around 750,000 people in the UK suffer from dementia, more than half of whom have Alzheimer’s.

At present the only way for sure to know if someone has suffered from the condition is to carry out a brain examination after their death.

Scientists have long been trying to discover ways of detect antibodies, chemicals and other substances in the blood that identify the body is fighting the condition.

But this has proved elusive until now.

In the new study, scientists at the Scripps Research Institute in Florida, have come up with a new approach by manufacturing thousands of molecules in different shapes – known as peptoids -designed to react with antibodies.

This suggests these antibodies are unique to the condition.

Further tests on six patients and laboratory mice showed that it was 93 per cent accurate and could eventually be used to detect the condition up to five years in advance.

Professor Thomas Kodadek, who led the research, said tests on thousands more patients was needed to test the accuracy of the test.

“If this works in Alzheimer’s disease, it suggests it is a pretty general platform that may work for a lot of different diseases,” he said.

Experts described the research as exciting but cautioned that it is still in the early stages.

Dr Susanne Sorensen, head of research at the Alzheimer’s Society, said: “This is a refreshing new approach to diagnosing Alzheimer’s disease which holds promise.

“Early diagnosis is very important and a simple non-invasive blood test for Alzheimer’s disease would be invaluable.

“However, this research is in the early stages and more investigation is needed to find out it if it can be developed in to a reliable and practical test for the future.

“As a million people develop dementia in the next 10 years we urgently need more funding to find reliable tests for the diseases that cause dementia.”

Dr Bryce Vissel, head of research into neurodegenerative diseases at the Garvan Institute in Australia, said: “This exciting study has significant implications for advancing understanding and treatments of diseases like multiple sclerosis and Alzheimer’s disease.

“This is a step towards being able to develop better treatments because we may now be able to identify people early in the disease and test drugs on them before the disease is too advanced.

“Perhaps even more importantly, the study offers a new approach to identify disease markers in the blood which could have significant implications for accurately diagnosing a range of diseases.”

The research was published in the journal Cell.

Cystic fibrosis creates a sticky mucus in the lungs of sufferers making breathing almost impossible. A new drug, Denufosol, has been shown to keep the lungs clear in children and young adults. This is a large breakthrough for this often deadly disease.

Cystic fibrosis is a disorder that is caused by the inability of ion sodium chloride molecules to pass through cells correctly. This new drug is an ion channel regulator.

Initial tests show that children with limited symptoms are benefiting the most from this new therapy. Cystic fibrosis is a progressive disease that continues to distress lung and digestive functions. while physical therapy has been successful for helping patients move the mucus through their system, the mucus often causes infections in the lungs because it is a perfect breeding ground for bacteria.

Denufosol is a very important step to overcoming this disease. unlike other medications for CF, this treats a cause of the disorder, not simply the symptoms.

Trials will continue to see how effect the drug will be for people with more advanced stages of the disease. to date, the results were based only on children that had very limited symptoms. the drug is taken through inhalation three times a day.