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Archives for February 2013

The Institute for Systems Biology and AB SCIEX Partner to Help Make Medical Care More Predictive and Personalized

Medical care is expected to become more personalized and better able to help prevent the onset of diseases in the future, thanks to groundbreaking research into P4 medicine underway by world-renowned scientists at the Institute for Systems Biology, including National Medal of Science award winner Leroy Hood, MD, PhD., and ISB proteomics research director, Robert Moritz, PhD., and now supported by a new collaboration with AB SCIEX, a global leader in analytical technology.

ISB and AB SCIEX have signed a multi-year agreement to collaborate on the development of methods and technology in proteomics mass spectrometry with the goal to redefine biomarker research and complement genomics through fully comprehensive quantitative proteomics analysis. This will help advance the development of a new approach to medical care.

ISB’s concept of P4 medicine promises to provide deep insight into disease mechanisms on the path to develop medical care that is predictive, personalized, preventive and participatory (the four “P”s) – a pioneering vision that requires a combination of analytical tools, workflows, databases, collaborations and computational strategies.

“With breakthroughs in translating research into clinical relevance, P4 medicine is expected to enable the creation of a virtual cloud of billions of data points around each individual as the basis for straightforward predictions about health and disease,” said Dr. Hood, ISB president and co-founder. In December, he was named a recipient of the National Medal of Science, which is the highest honor the President of the United States can bestow on a scientist, in recognition of visionary work for the advancement of science.

Led by Dr. Hood, ISB’s groundbreaking research is being accelerated by SWATH™ Acquisition, a data-independent acquisition (DIA) mass spectrometry workflow that can quantify virtually all detectable peptides and proteins in a complex sample – all in a single analysis.

“Quantifying enormous numbers of protein analytes at the same time is a critical need to accelerate P4 medicine and the democratization of proteomics, a revolution that is akin to the sequencing of the genome and the democratization of DNA,” added Dr. Hood. “SWATH is a game-changing technique that essentially acts as a protein microarray and is the most reproducible way to generate comprehensive quantitation of the entire proteome. It generates a digital record of the entire proteome that can be mined retrospectively for years to come.”

ISB’s know-how in systems biology and informatics will support the development of SWATH libraries, similar to its highly regarded SRMAtlas project for the human proteome, pioneered by Rob Moritz and his collaborators, and the proteomes of other clinically-relevant organisms. “With complete proteome-wide libraries, ISB provides the basis to support comprehensive SWATH analysis,” said Dr. Moritz, ISB Proteomics Research Director.

Committed to an open policy of sharing data and methods, ISB will make the SWATH libraries available to the global scientific community to accelerate the use of SWATH for other biological research. Utilizing the depth in proteomics technology development and underpinned by the extensive proteomics computational resources in data interpretation tools, standards initiatives and database development under the leadership of Dr. Moritz, ISB will develop new SWATH technologies and tools to enable the community to quickly adopt comprehensive quantitative proteome analysis.

“Having the proteomics data standardized across laboratories and across samples really enables us to quantitate entire proteomes at a level that hasn’t been done before,” said Dr. Moritz. “We aim to define markers that can predict whether a patient will respond to a certain treatment or not, and applying SWATH will play a big part in taking our advancements to another level. Not only can we now complement the breadth of genomics, but we will have the much-needed libraries and software development going forward to make data-sharing quite easier and standardized.”

As a trusted partner with academic researchers, AB SCIEX has formed this strategic alliance with Dr. Hood, Dr. Moritz and their distinguished ISB colleagues through the AB SCIEX Academic Partnership Program to help broaden the availability of new technologies to researchers delving into omics research around the world.

“What ISB does with SWATH will set a new benchmark in proteomics research,” said Rainer Blair, President of AB SCIEX. “Our collaboration with ISB will help drive SWATH into the mainstream of analytical science and make comprehensive, reproducible and simplified omics data more accessible to biologists around the world.”

ISB will be using the AB SCIEX TripleTOF® 5600± System and an Eksigent ekspert™ nano-LC 400 System as the instrument platforms on which to conduct the protein identification and quantitation. The TripleTOF 5600+ System provides the high speed necessary for SWATH Acquisition. TripleTOF technology combines high speed and high sensitivity with high resolution and accurate mass. ISB also plans to use SelexION™ technology, a recent advancement in differential ion mobility, in the future to advance its research.

Source: Institute for Systems Biology

Investment in a Quebec Public-private Partnership to Support the Use of Personalized Medicine Solutions in the Treatment of Cancer Patients

The Government of Québec announced today a $10 million investment in the Personalized Medicine Partnership for Cancer (PMPC). This public-private partnership will be focused on establishing an integrated approach for the development and implementation of clinical biomarkers and other personalized healthcare solutions to improve the outcome and cost-efficiency of healthcare services provided to cancer patients in the province of Québec and abroad. The investment, to be disbursed over a 4 year period, will be supplemented with $11.1 million of funding from the private sector partners, for a total project value of $21.1 million.

The PMPC will be under the leadership of Caprion Proteome Inc., a Montreal-based biotech company specializing in the discovery and development of protein-based diagnostic biomarkers. The other partners will include the Québec Clinical Research Organization in Cancer (Q-CROC), a multidisciplinary network of clinicians, academic scientists and other members of the medical community involved in clinical and translational cancer research, as well as private partners Oncozyme Pharma Inc., Pfizer Canada Inc., Sanofi Canada Inc. and TELUS Health.

As part of the projects supported through this partnership, state-of-the-art genomic, proteomic, bioinformatic and information technology platforms will be implemented to develop and deploy novel biomarkers and targeted therapeutic strategies in the healthcare system for the treatment of lung, colon and breast cancers: “The sequence of our genome or the profile of the proteins in our blood can be used to accurately predict disease progression or treatment outcome. Our partnership will integrate advanced technology platforms with clinical research to accelerate the development and clinical deployment of novel personalized healthcare solutions. Caprion has pioneered such strategies for years, and with our partners, we are committed to delivering tangible results to provide more targeted diagnosis and treatments for cancer,” said Martin LeBlanc, President and Chief Executive Officer of Caprion Proteome.

Personalized medicine has been coined to describe the use of specific patient information gathered from tumour, blood or other specimens to characterize disease subtype and select the optimal treatment. “The rapid progress in clinical research enables us to decipher the underpinnings of cancer and to develop specific diagnostic tools and targeted drugs to treat specific subtypes of common cancers such as lung, colon or breast. It is critical that these new tools and medicines be deployed for the benefit of patients across Québec,” said Gerald Batist, Professor of Oncology at McGill University and Co-director of the Q-CROC and Director of the Segal Cancer Center at the Jewish General Hospital. “While technology has been progressing rapidly, it will be critical to prepare our healthcare system to integrate the wealth of new molecular information and educate professionals in the practice of personalized medicine,” he added.

The PMPC project stemmed from the Stratégie québécoise de la recherche et de l’innovation (SQRI) that was created by the Government of Québec to advance knowledge and accelerate the deployment of innovative personalized medicine solutions to the bedside. The partnership, in collaboration with the Ministère de la santé et des services sociaux (MSSS), was also built to strengthen the cooperation between the private and the public research sectors including academic healthcare institutions and universities.

Source: PR Newswire

Molecules Generated that Can Halt Metastasis of Colon Cancer

A Basque research consortium has managed to halt the progress of colon cancer and its metastasis in the liver in an experimental model with mice. This advance, that may open a new path for the future treatment of such pathologies, has been achieved by creating molecules which interfere with the adhesion of tumour cells to other cells of the organism. In this way, the molecules halt both the growth of the tumour and the dissemination of the tumour to and its proliferation in other organs.

The research, published in the prestigious North American Journal of Medicinal Chemistry, is based on a previous work by researchers at the University of the Basque Country (UPV-EHU) which had described a series of molecules which reduced the metastasis of melanoma (a serious variety of skin cancer) in mice. That research opened up the possibility of generating new molecules with this activity in other types of cancer and following a similar strategy, something which has been achieved in this, later research, applied to colon cancer and its metastasis of the liver.

The Basque research consortium is made up of the CIC bioGUNE biociences research centre, the UPV/EHU, the Institute of Genetics and a Molecular and Cell Biology (IGBMC) in Strasbourg (France), and the Ikerchem spin-off Enterprise. Moreover, researchers from the Rocasolano Chemical-Physical Institute, from the CSIC (the Spanish Council for Scientific Research) and from the Novartis Institute for Biomedical Research took part.

“In this project we first designed inhibitors to cell adhesion involved in the metastasis of murine melanomas, and then undertook the chemical synthesis of these molecules, testing their biological potential and activity. What was surprising was that our calculations predicted that, by introducing relatively small changes, we would be able to generate new molecules with the capacity to inhibit cell adhesion involved in another type of cancer. This prediction was confirmed by the experiments, suggesting that these techniques of chemical design and synthesis could be extended to other related therapeutic targets”, stated Dr. Fernando Cossío, UPV/EHU professor and co-founder of Ikerchem S. L., as well as President of the Executive Committee of Ikerbasque.

“Besides its relevance in the control of cancer and metastasis, this research highlights that, in the Basque Country, there are research teams at academic centres and in companies with the necessary experience and skill to tackle multidisciplinary projects of biomedical relevance, combining synthetic and computational chemistry with the structural analysis of the mechanism and the biological validation of the molecules generated”, stated Dr. Francisco Blanco, Ikerbasque lecturer and researcher at CIC bioGUNE.

Impact of cancer and metastasis

Cancer is the second cause of human mortality and its incidence increases with age. Thanks to progress in the early diagnosis and control of detected tumours, enhancing the rate of survival has been achieved and, in this sense, it is believed that further progress can be made in these two aspects of the disease.

Currently 90 % of deaths from cancer are produced by the reappearance of the original tumour in another part of the body, a process known as metastasis. This process consists of a cancerous cell of the original tumour passing through the body of the patient and lodging in another organ, generating a new tumour.

The colon is not the organ with the greatest cancer mortality rate, but it gives rise to metastasis of the liver, which is. In fact the liver is the organ where metastasis of tumours originatng in other parts of the body is more frequent. This is because the liver acts as a filter for the blood and the lymph and so cancerous cells flowing in these fluids can be trapped therein.
The lethal danger arising from the migration of cancerous cells throughout the body is what drives researchers in the quest for therapies to halt metastasis.

Study: Design, Synthesis, and Functional Evaluation of Leukocyte Function Associated Antigen-1 Antagonists in Early and Late Stages of Cancer Development

Source: Basque

New Evidence for Link Between Depression and Heart Disease

A Loyola University Medical Center psychiatrist is proposing a new subspecialty to diagnose and treat patients who suffer both depression and heart disease. He’s calling it “Psychocardiology.”

In his most recent study, Angelos Halaris, MD, PhD, and colleagues found that an inflammatory biomarker, interleukin-6, was significantly higher in the blood of 48 patients diagnosed with major depression than it was in 20 healthy controls. Interleukin-6 has been associated with cardiovascular disease. Halaris presented findings at a joint congress of the World Psychiatric Association and International Neuropsychiatric Association in Athens, Greece. At the congress, Halaris formally proposed creation of a new Psychocardiology subspecialty.

Forty to 60 percent of heart disease patients suffer clinical depression and 30 to 50 percent of patients who suffer clinical depression are at risk of developing cardiovascular disease, Halaris said.

Stress is the key to understanding the association between depression and heart disease. Stress can lead to depression, and depression, in turn, can become stressful.

The body’s immune system fights stress as it would fight a disease or infection. In response to stress, the immune system produces proteins called cytokines, including interleukin-6. Initially, this inflammatory response protects against stress. But over time, a chronic inflammatory response can lead to arteriosclerosis (hardening of the arteries) and cardiovascular disease.

It’s a vicious cycle: depression triggers a chronic inflammation, which leads to heart disease, which causes depression, which leads to more heart disease.

Clinical depression typically begins in young adults. “Treating depression expertly and vigorously in young age can help prevent cardiovascular disease later on,” Halaris said.

Physicians often work in isolation, with psychiatrists treating depression, and cardiologists treating cardiovascular disease. Halaris is proposing that psychiatrists and cardiologists work together in a multidisciplinary Psychocardiology subspecialty.

A Psychocardiology subspecialty would raise awareness among physicians and the public. It would forge closer working relationships between psychiatrists and cardiologists. It would formalize multidisciplinary teams with the requisite training and expertise to enable early detection of cardiovascular disease risk in psychiatric patients and psychiatric problems in heart disease patients. And it would provide continuing education to physicians in the safe and correct use of medications in cardiac patients who have psychiatric disorders.

“It is only through the cohesive interaction of such multidisciplinary teams that we can succeed in unravelling the complex relationships among mental stress, inflammation, immune responses and depression, cardiovascular disease and stroke,” Halaris said.

Source: EurekAlert!

Hopkins Scientists Create Method To Personalize Chemotherapy Drug Selection

In laboratory studies, scientists at the Johns Hopkins Kimmel Cancer Center have developed a way to personalize chemotherapy drug selection for cancer patients by using cell lines created from their own tumors. If the technique is successful in further studies, it could replace current laboratory tests to optimize drug selection that have proven technically challenging, of limited use, and slow, the researchers say.

Oncologists typically choose anticancer drugs based on the affected organs’ location and/or the appearance and activity of cancer cells when viewed under a microscope. Some companies offer commercial tests on surgically removed tumors using a small number of anticancer drugs. But Anirban Maitra, MBBS, professor of pathology and oncology at the Johns Hopkins University School of Medicine, says the tissue samples used in such tests may have been injured by anesthetic drugs or shipping to a lab, compromising test results.

By contrast, he says “our cell lines better and more accurately represent the tumors, and can be tested against any drug library in the world to see if the cancer is responsive.”

The Johns Hopkins scientists developed their test-worthy cell lines by injecting human pancreatic and ovarian tumor cells into mice genetically engineered to favor tumor growth. Once tumors grew to one centimeter in diameter in the mice, the scientists transferred the tumors to culture flasks for additional studies and tests with anticancer drugs.

In one experiment, they successfully pinpointed the two anticancer drugs from among more than 3,000 that were the most effective in killing cells in one of the pancreatic cancer cell lines. A report on the success was published online Jan. 22 in the journal Clinical Cancer Research.

The new method was designed to overcome one of the central problems of growing human tumor cell lines in a laboratory dish — namely the tendency of noncancerous cells in a tumor to overgrow cancerous ones, says James Eshleman, M.D., Ph.D., professor of pathology and oncology and associate director of the Molecular Diagnostics Laboratory at Johns Hopkins. As a consequence, it has not been possible to conventionally grow cell lines for some cancers. Still other cell lines, Eshleman says, don’t reflect the full spectrum of disease.

To solve the problem of overcrowding by noncancerous cells, Maitra and Eshleman bred genetically engineered mice that replace the noncancerous cells with mouse cells that can be destroyed by chemicals, leaving pure human tumor cells for study.

“Our technique allows us to produce cell lines where they don’t now exist, where more lines are needed, or where there is a particularly rare or biologically distinctive patient we want to study,” says Eshleman.

In its proof of concept research, the Johns Hopkins team created three pancreatic ductal adenocarcinoma cell lines and one ovarian cancer cell line. They then tested one of the pancreatic cancer cell lines (called Panc502) against the Johns Hopkins Drug Library of 3,131 drugs, identifying tumor cells most responsive to the anticancer drugs digitoxin and nogalamycin.

For 30 days, they watched the effects in living mice of the two drugs and a control medicine on tumors grown from implanted cells derived from Panc502 and an additional pancreatic cell line, Panc410. They measured the size of tumors twice a week. Both drugs demonstrated more activity in reducing the tumor appearance and size in Panc502 than in Panc410, supporting the notion that the cell line technology may better predict sensitivity to the two drugs.

The investigators have given one type of their genetically engineered mice to The Jackson Laboratory in Bar Harbor, ME, a mouse genetics research facility, for breeding and distribution to other laboratories and are looking to partner with a company to distribute two other types.

Study co-authors were Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Collins A. Karikari, Georg Feldmann, Li Hua, Mihoko Kamiyama, F. William Schuler, Ming-Tseh Lin, Robert M. Beaty, Balasubramanyam Karanam, Hong Liang, Michael E. Mullendore, Guanglan Mo, Manuel Hidalgo, Elizabeth Jaffee, Ralph H. Hruban, Richard B. S. Roden, Antonio Jimeno, and Jun O. Liu, of Hopkins; and H. A. Jinnah of Emory University School of Medicine in Atlanta.

The work was supported by the National Institutes of Health, National Cancer Institute (CA130938, CA62924 and CA122581), the Sol Goldman Pancreatic Cancer Research Center, the Stewart Trust Fund, the Lustgarten Foundation, the Mary Lou Wootton Pancreatic Pancreatic Cancer Research Fund, the Michael Rolfe Pancreatic Cancer Foundation and the HERA Foundation.

Rauenzahn, Maitra and Eshleman may receive royalty payments if the mice are licensed, and Eshleman is an advisory board member for Roche Molecular Diagnostics. These relationships have been disclosed and are under the management of the Johns Hopkins University School of Medicine Conflict of Interest Committee.

Source: Johns Hopkins Medicine