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Archive - 2012

September 23rd

Harvard Researchers Engineer Highly Versatile “Origami” Fluorescent Barcodes

Much like the checkout clerk uses a machine that scans the barcodes on packages to identify what customers bought at the store, scientists use powerful microscopes and their own kinds of barcodes to help them identify various parts of a cell, or types of molecules at a disease site. But their barcodes only come in a handful of "styles," limiting the number of objects scientists can study in a cell sample at any one time. Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have created a new kind of barcode that could come in an almost limitless array of styles -- with the potential to enable scientists to gather vastly more vital information, at one given time, than ever before. The method harnesses the natural ability of DNA to self-assemble, and was reported on September 24, 2012 in the online issue of Nature Chemistry and in the October 2012 print issue of the same journal. "We hope this new method will provide much-needed molecular tools for using fluorescence microscopy to study complex biological problems," says Dr. Peng Yin, Wyss core faculty member and study co-author who has been instrumental in the DNA origami technology at the heart of the new method. Fluorescence microscopy has been a tour de force in biomedical imaging for the last several decades. In short, scientists couple fluorescent elements -- the barcodes -- to molecules they know will attach to the part of the cells they wanted to investigate. Illuminating the sample triggers each kind of barcode to fluoresce at a particular wavelength of light, such as red, blue, or green -- indicating where the molecules of interest are. However, the method is limited by the number of colors available -- three or four -- and sometimes the colors get blurry.

September 21st

Natural Killer Cells May Be a Key to Variation in Lung Cancer Susceptibility

Why do many heavy smokers evade lung cancer while others who have never lit up die of the disease? The question has vexed scientists for decades. Now, new research at Washington University School of Medicine in St. Louis suggests a key immune cell may play a role in lung cancer susceptibility. Working in mice, they found evidence that the genetic diversity in natural killer cells, which typically seek out and destroy tumor cells, contributes to whether or not the animals develop lung cancer. The research was published in the September 1, 2012 issue of Cancer Research. “Overall, humans are genetically very similar, but their immune systems are incredibly diverse,” explains senior author Alexander Krupnick, M.D., a thoracic surgeon at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “Our findings add to the growing body of evidence suggesting that innate differences in immunity may determine not only a person’s susceptibility to colds but also to lung cancer.” Based on the findings in mice, Dr. Krupnick says he and his colleagues are now studying whether humans have a similar genetic diversity in their natural killer cells. As part of a new clinical study, they’re analyzing the blood of heavy smokers with and without lung cancer and never-smokers with and without lung cancer to look for differences. “We want to know whether heavy smokers who don’t get lung cancer have natural killer cells that are somehow better at destroying newly developing lung cancer cells,” says Dr. Krupnick, associate professor of surgery. “And, by comparison, do patients who have never smoked but develop lung cancer have weak natural killer cells?” For the mouse study, the scientists evaluated three groups of mice with varying susceptibilities to lung tumors.

September 20th

Small RNAs Key to Plant Inheritance of Acquired Traits

During embryonic development in humans and other mammals, sperm and egg cells are essentially wiped clean of chemical modifications to DNA called epigenetic marks. They are then held in reserve to await fertilization. In flowering plants, the scenario is dramatically different. Germ cells don't even appear until the post-embryonic period – sometimes not until many years later. When they do appear, only some epigenetic marks are wiped away; some remain, carried over from prior generations – although until now little was known about how or to what extent. "What we did know," says Professor and HHMI-GBMF Investigator Rob Martienssen, Ph.D., of Cold Spring Harbor Laboratory (CSHL), "was that epigenetic inheritance – the inheritance by offspring of chemical "tags" present in parental DNA that modify the expression of genes – is much more widespread in plants than in animals." In new research published online on September 20, 2012 in the journal Cell, Dr. Martienssen and colleagues show that genome reprogramming through these epigenetic mechanisms is guided by small RNAs and is passed on to the next generation. It has long been known that in plants, as the male germline pollen grains develop, they give rise to two sperm cells, and a structure called the vegetative nucleus, also known as the "nurse cell" because it provides energy and nourishment to the sperm cells. The DNA in germ cells can exist in two dramatically different states: in one, it is very densely packed and essentially inaccessible to the cellular machinery that enables individual genes to be "expressed." In the other, in which the packing is much looser, genes can be expressed.

September 17th

Underlying Mechanism of Taxane Chemotherapy for Prostate Cancer Treatment

The power of taxane-based chemotherapy drugs are misunderstood and potentially underestimated, according to researchers at Weill Cornell Medical College writing in the September 15, 2012 issue of Cancer Research. Most physicians and investigators believe that taxane chemotherapy (paclitaxel, docetaxel, and cabazitaxel) just does one thing -- stop a cancer cell from dividing -- but the team of Weill Cornell scientists have revealed it acts much more powerfully and broadly, especially against prostate cancer. "Taxanes are one of the best class of chemotherapy drugs that we can use to treat our cancer patients, but while they are effective against a wide range of tumors, they don't work in all of them, and often patients become resistant," says the study's senior investigator, Dr. Paraskevi Giannakakou, an associate professor of pharmacology in medicine and pharmacology and director of laboratory research for the Division of Hematology and Medical Oncology at Weill Cornell. "However, our new understanding of the precise action of taxanes in a cancer cell may help us overcome drug insensitivity or acquired resistance to the drugs and design therapies that can be used in combination with them to improve cancer control." In their report, the researchers stress that investigators must shift their attention away from taxane's function during cell division to the drugs' effects on halting the everyday movement of proteins and protein-to-protein communication within cancer cells -- and to understanding how and why a cancer cell can still survive.

Breath Analysis Could Aid Diagnosis of Pulmonary Nodules

A pilot study, published in the October 2012 issue of the International Association for the Study of Lung Cancer's (IASLC) Journal of Thoracic Oncology, showed that breath testing could be used to discriminate between benign and malignant pulmonary nodules. The study looked at 74 patients who were under investigation for pulmonary nodules and attended a referral clinic in Colorado between March 2009 and May 2010. Researchers from Israel and Colorado collected exhaled breath from each patient, analyzing the exhaled volatile organic compounds using gas chromatography with mass spectrometry and information from chemical nanoarrays, which have been developed by Professor Hossam Haick and his colleagues in the Technion-Israel Institute of Technology. The patients also underwent a bronchoscopy, wedge resection, and/or lobectomy, whichever was required for final diagnosis. Nodules that either regressed or remained stable over a 24-month period were considered benign. The two techniques accurately identified that 53 pulmonary nodules were malignant and 19 were benign. Furthermore, the nanoarrays method discriminated between adenocarcinoma and squamous cell carcinoma and between early versus advanced disease. This kind of testing could help solve some of the problems computed tomography screening has created. While low-dose CT screening has reduced the mortality rate by 20 percent, many people have to undergo invasive procedures only to find out their pulmonary nodules are not cancerous. The false positive rate is 96 percent. This testing could serve as a secondary screener for patients who were found to have pulmonary nodules after CT screening. Authors say, "the reported breath test in this study could have significant impact on reducing unnecessary investigation and reducing the risk of procedure-related morbidity and costs.

Chloride Channel Study Offers New Hope for Asthma Sufferers

A new study that identifies ways to reduce the factors that lead to an asthma attack gives hope to asthma sufferers. A University of California-San Francisco (UCSF) researcher and his colleagues believe they have found a way to help asthma sufferers by impeding the two most significant biological responses that lead to an asthma attack. Asthma, a respiratory disorder that causes shortness of breath, coughing, and chest discomfort, results from changes in the airways that lead to the lungs. It affects 18.7 million adults and 7.0 million children in the U.S., according to the Centers for Disease Control and Prevention. In a paper published online on September 17, 2012 in the PNAS, researchers from UCSF, Johns Hopkins University, and Duke University demonstrate that a specific calcium-activated chloride channel holds valuable clues to reducing two biological processes that contribute to the severity of asthma. These channels regulate airway secretions and smooth muscle contraction, the two major factors that lead to an asthma attack. "Maybe if we could inhibit both of these processes by blocking this one channel, then we could affect the two symptoms of asthma," said senior author Jason Rock, Ph.D., assistant professor in the UCSF Department of Anatomy. Normally, humans have few mucus-producing cells but asthma sufferers have an elevated number of these cells in the lining of the tubes that lead to the lungs. Asthmatics also have an abnormal amount of smooth muscle surrounding the airway tubes. Even the slightest stimulus can cause these to contract. "The overabundance of mucus plugging the airways combined with hyper-contractility of the smooth muscle – when the tubes get really small – make it difficult to move air in or out," Dr. Rock said. "A lot of people equate that with breathing through a straw." Dr.

September 16th

Whole-Genome Scan Helps Determine Best Treatment for Neuroblastoma

A whole-genome scan to identify large-scale chromosomal damage can help doctors choose the best treatment option for children with neuroblastoma, one of the most common types of childhood cancer, finds an international collaboration jointly led by The Institute of Cancer Research, London. The researchers called for all children diagnosed with neuroblastoma worldwide to have a whole-genome scan as a standard part of their treatment. Neuroblastoma, a cancer of the developing nervous system, is sometimes very treatable but other forms are highly aggressive, making the disease overall one of the leading causes of death from childhood cancer. As intense treatments can carry life-long side-effects, identifying the form is crucial in giving an accurate prognosis and deciding the most appropriate care. Scientists examined the medical records of 8,800 neuroblastoma patients from around the world and found that several large-scale genetic faults were strongly linked to survival rates, and that a whole-genome scan would therefore be more effective at predicting prognosis than tests for individual genetic factors. The study was published online on September 13, 2012 in the British Journal of Cancer. Senior author Professor Andy Pearson, Cancer Research UK professor of paediatric oncology at The Institute of Cancer Research and a paediatric consultant at The Royal Marsden NHS Foundation Trust, said: "Our study has found that every single patient diagnosed with neuroblastoma should have a whole genome assessment. The technology required to carry out these scans has become much more widely available and cheaper over recent years, and we believe most diagnostic labs in developed countries worldwide should have this capacity.

September 5th

Landmark Advances in Understanding Regulation and Organization of Human Genome

The Human Genome Project produced an almost complete order of the 3 billion pairs of chemical letters in the DNA that embodies the human genetic code — but little about the way this blueprint works. Now, after a multi-year concerted effort by more than 440 researchers in 32 labs around the world, a more dynamic picture gives the first holistic view of how the human genome actually does its job. During the new study, researchers linked more than 80 percent of the human genome sequence to a specific biological function and mapped more than 4 million regulatory regions where proteins specifically interact with the DNA. These findings represent a significant advance in understanding the precise and complex controls over the expression of genetic information within a cell. The findings bring into much sharper focus the continually active genome in which proteins routinely turn genes on and off using sites that are sometimes at great distances from the genes themselves. They also identify where chemical modifications of DNA influence gene expression and where various functional forms of RNA, a form of nucleic acid related to DNA, help regulate the whole system. "During the early debates about the Human Genome Project, researchers had predicted that only a few percent of the human genome sequence encoded proteins, the workhorses of the cell, and that the rest was junk. We now know that this conclusion was wrong," said Eric D. Green, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI), a part of the National Institutes of Health. "ENCODE has revealed that most of the human genome is involved in the complex molecular choreography required for converting genetic information into living cells and organisms." The NHGRI organized the research project producing these results; it is called the Encyclopedia of DNA Elements or ENCODE.

September 4th

Pretreatment PET/CT Scan of Lymph Nodes Predicts Recurrence in Type of Breast Cancer

Disease-free survival for invasive ductal breast cancer (IDC) patients may be easier to predict with the help of F-18-fludeoxyglucose positron emission tomography (PET)/computed tomography (CT) scans, according to research published online on June 29, 2012 in The Journal of Nuclear Medicine and scheduled for print publication in the September issue of the same journal. New data, obtained by researchers in Korea, show that high maximum standard uptake value (SUVmax) of F-18-FDG in the lymph nodes prior to treatment could be an independent indicator of disease recurrence. “Many studies have revealed that breast cancer patients with axillary lymph node metastasis have a significantly poorer prognosis than those without nodal metastases,” noted Sang-Woo Lee, M.D., Ph.D., one of the authors of the current article. “However, the prognostic value of F-18-FDG uptake in metastatic axillary lymph nodes with PET/CT has not been investigated in IDC patients,” he added. In this study, researchers followed 65 female patients with IDC who had undergone pretreatment F-18-FDG PET/CT and who had pathologically confirmed axillary lymph node involvement without distant metastases. Factors such as age, TNM (tumor, lymph node, and metastases) stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and SUVmax for the primary-tumor and axillary lymph nodes were analyzed. Patients underwent treatment and were followed for a range of 21-57 months (median of 36 months). Among the patients, 53 were disease-free and 12 had disease recurrence during the follow-up period. While both the primary-tumor and nodal SUVmax were higher in patients with recurrence, the nodal SUVmax was significantly higher.

September 3rd

Targeting Inflammation to Treat Depression

Researchers at Emory University have found that a medication that inhibits inflammation may offer new hope for people with difficult-to-treat depression. The study was published September 3, 2012 in the online version of Archives of General Psychiatry. "Inflammation is the body's natural response to infection or wounding,” says Andrew H. Miller, M.D., senior author for the study and professor of Psychiatry and Behavioral Sciences at Emory University School of Medicine. "However, when prolonged or excessive, inflammation can damage many parts of the body, including the brain." Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation. The study employed infliximab, one of the new biologic drugs used to treat autoimmune and inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. A biologic drug copies the effects of substances naturally made by the body's immune system. In this case, the drug was an antibody that blocks tumor necrosis factor (TNF), a key molecule in inflammation that has been shown to be elevated in some depressed individuals. Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment.