BreakThrough Digest Medical News |
- Promising new drug target for inflammatory lung diseases
- Human genome far more active than thought
- Multi-functional anti-inflammatory/anti-allergic developed by Hebrew University researcher
- Possible new therapy for the treatment of a common blood cancer
| Promising new drug target for inflammatory lung diseases Posted: 05 Sep 2012 09:00 PM PDT The naturally occurring cytokine interleukin-18, or IL-18, plays a key role in inflammation and has been implicated in serious inflammatory diseases for which the prognosis is poor and there are currently limited treatment options. Therapies targeting IL-18 could prove effective against inflammatory diseases of the lung including bronchial asthma and chronic obstructive pulmonary disease (COPD), as described in a review article published in Journal of Interferon & Cytokine Research (http://www.liebertpub.com/jir), a peer-reviewed publication from Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com). The article is available free online at the Journal of Interferon & Cytokine Research website. (http://www.liebertpub.com/jir)
Tomotaka Kawayama and coauthors from Kurume University School of Medicine, Fukuoka, Japan, University of Ryukyus, Okinawa, Japan, and Frederick National Laboratory for Cancer Research, Frederick, MD, review the growing evidence to support the important role IL-18 has in inflammation and how it may help to initiate and worsen inflammatory disorders such as arthritis, dermatitis and inflammatory diseases of the bowel and immune system. In the article “Interleukin-18 in Pulmonary Inflammatory Diseases” (http://online.liebertpub.com/doi/full/10.1089/jir.2012.0029) they describe the potential benefits of therapies aimed at blocking the activity of IL-18 to treat inflammatory lung disease. “This review provides an interesting and thorough summary of the biology and potential application of IL-18 in the setting of inflammatory pulmonary disease,” says Co-Editor-in-Chief Thomas A. Hamilton, PhD, Chairman, Department of Immunology, Cleveland Clinic Foundation. ### About the Journal Journal of Interferon & Cytokine Research (http://www.liebertpub.com/jir), led by Co-Editors-in-Chief Ganes C. Sen, PhD, Chairman, Department of Molecular Genetics, Cleveland Clinic Foundation, and Thomas A. Hamilton, PhD, is an authoritative peer-reviewed journal published monthly in print and online that covers all aspects of interferons and cytokines from basic science to clinical applications. Journal of Interferon & Cytokine Research is the official journal of the International Society for Interferon and Cytokine Research. Complete tables of content and a sample issue (http://online.liebertpub.com/toc/jir/31/6) may be viewed online at the Journal of Interferon & Cytokine Research website. (http://www.liebertpub.com/jir) About the Publisher
Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Viral Immunology, AIDS Research and Human Retroviruses, and DNA and Cell Biology. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 70 journals, books, and newsmagazines is available at Mary Ann Liebert, Inc., publishers website. (http://www.liebertpub.com).
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| Human genome far more active than thought Posted: 05 Sep 2012 09:00 PM PDT
The GENCODE Consortium expects the human genome has twice as many genes than previously thought, many of which might have a role in cellular control and could be important in human disease. This remarkable discovery comes from the GENCODE Consortium, which has done a painstaking and skilled review of available data on gene activity.
Among their discoveries, the team describe more than 10,000 novel genes, identify genes that have ‘died’ and others that are being resurrected. The GENCODE Consortium reference gene catalogue has been one of the underpinnings of the larger ENCODE Project and will be essential for the full understanding of the role of our genes in disease. The GENCODE Consortium is part of the ENCODE Project that, today, publishes 30 research papers describing findings from their nearly decade-long effort to describe comprehensively all the active regions of our human genome. ENCODE was launched in 2003 after the completion of the Human Genome Project, and brought together an international group of scientists tasked with identifying and describing all functional regions of the human genome sequence. “We have uncovered a staggering array of genes in our genome, simply because we can examine many genomes in a detail that was not possible a decade ago,” says Dr Jennifer Harrow, GENCODE principle investigator from the Wellcome Sanger Institute. “As sequencing technology improves, so we have much more data to explore. “But our work remains a skilled effort to annotate correctly our human genome ? or, more precisely, our human genomes, for each of us differ. These vast texts of genetic information will not give up their secrets easily. GENCODE has made amazing strides to enable immediate access of its reference gene set by other researchers.” The team more accurately described the genes that contain the genetic code to make proteins: they found 20,687 such protein-coding genes, a value that has not changed greatly from previous work. The new set captures far more of the alternative forms of these genes found in different cell types. More significant are their findings on genes that do not contain genetic code to make proteins ? non-coding genes ? and the graveyard of supposedly ‘dead’ genes from which some are emerging, resurrected from the catalogue of pseudogenes. They mapped and described 9,277 long non-coding genes, a relatively new type that acts, not through producing a protein, but directly through its RNA messenger. Long non-coding RNAs derived from these genes can play a significant part in human biology and disease, but they remain only poorly understood. The new map of such genetic components gives researchers more avenues to explore in their quest to understand human biology and human disease. Remarkably, the team think their job is not complete and believe that there may be another 10,000 of these genes yet to be uncovered. “Our initial work from the Human Genome Project suggested there were around 20,000 protein-coding genes and that value has not changed greatly,” says Professor Roderic Guigo, GENCODE principle investigator from Centre for Genomic Regulation, Barcelona. “However GENCODE has shown that long non-coding RNAs are far more numerous and important than previously thought” “The limited knowledge we have of the class of long non-coding RNAs suggests they might play a major role in regulating the activity of other genes. If this is generally true of this group, we have much more to explore than we imagined.” As dramatic, GENCODE has catalogued for the first time a set of more than 11,000 pseudogenes by examining the entire human genome. There is some emerging evidence that many of these genes, too, might have some biological activity. The GENCODE team predict that at least 9% of pseudogenes may be active with some controlling the activity of other genes. Pseudogenes have been implicated in many biological activities, such as the prevention of certain elements known to be involved in the development of cancer. “At the announcement of the Human Genome Project draft sequence, we emphasized this was the end of the beginning, that ‘at present most genes – probably tens of thousands – remain a mystery’”, says Dr Tim Hubbard, lead principle investigator of GENCODE from the Wellcome Trust Sanger Institute. “Today, we describe many thousands of genes for the first time.” “If the Human Genome Project was the baseline for genetics, ENCODE is the baseline for biology, and GENCODE are the parts that make the human biological machine work. Our list is essential to all those who would fix the human machine.” The GENCODE human reference set will be updated every three months to ensure that models are continually refined and assessed based on new experimental data deposited in the public databases. ### Notes to Editors Publication Details
Publication details can be found at http://www.genome.gov/10005107 Funding
The GENCODE Consortium was supported by the National Institutes of Health, USA, and the Wellcome Trust. Participating Centres
Selected Websites
GENCODE consortium website details consortium members, and data releases. http://www.gencodegenes.org/ Ensembl genome browser, which is part of the GENCODE consortium and displays the GENCODE human reference set http://www.ensembl.org/ The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. Contact: Aileen Sheehy |
| Multi-functional anti-inflammatory/anti-allergic developed by Hebrew University researcher Posted: 05 Sep 2012 09:00 PM PDT
A synthetic, anti-inflammatory and anti-allergic family of drugs to combat a variety of illnesses while avoiding detrimental side effects has been developed by a Hebrew University of Jerusalem researcher.
The researcher is Saul Yedgar, who is the Walter and Greta Stiel Professor of Heart Studies at the Institute for Medical Research Israel-Canada at the Hebrew University Faculty of Medicine. Inflammatory/allergic diseases affect billions of people worldwide, and treatments for these conditions are a major focus of the pharmaceutical industry. The most common drugs currently used to treat these numerous diseases are steroids, which are potent but are associated with severe side effects. These include metabolic changes (weight gain, increased blood pressure, diabetes), organ-specific effects (glaucoma, cataracts, bone fragility), and even psychotrophic side effects (depression, psychosis). For decades, alternatives, such as biological NSAIDs (non-steroidal alternative anti-inflammatory drugs) have been the focus of the pharmaceutical industry. The resulting drugs have been commercially successful, but have not produced genuine alternatives to steroids due to their limitations. Synthetic NSAIDs are less potent and have their own serious side effects, including cardiovascular disorders, stomach bleeding and respiratory disorders. The biological drugs are costly and, must be injected and have rare but very severe side effects. Inflammatory/allergic diseases present different symptoms affecting different organs, such as skin inflammations (dermatitis, psoriasis); airway injury and allergy (asthma, cystic fibrosis, allergic rhinitis); osteoarthritis and rheumatoid arthritis; intestinal inflammation (ulcerative colitis, Crohn’s disease); central nervous system inflammation (multiple sclerosis), as well as atherosclerosis and cancer metastasis. What they have in common is that all of them share biochemical mechanisms. A key one among them is the action of an enzyme family (PLA2) that initiates the production of a cascade of pro-inflammatory mediators involved in the induction and propagation of the diverse inflammatory diseases. In Prof. Yedgar’s lab at the Hebrew University, he and his associates have designed and constructed an entirely novel synthetic generation of drugs that control the PLA activity and the subsequent cascade of pro-inflammatory mediators, thereby providing multi-functional, anti-inflammatory drugs (MFAIDs). MFAIDs have shown excellent safety and were found efficient in treating diverse inflammatory/allergic conditions in animal models, using different ways of administration ? oral, rectal, intravenous, inhaled and injected. These conditions included sepsis, inflammatory bowel diseases, asthma and central nervous system inflammation. In particular, in two clinical studies MFAIDs have been shown to be safe and efficient in treating contact dermatitis, when incorporated into skin cream, and allergic rhinitis, when administered as a nasal spray. This platform technology has been exclusively licensed from the Hebrew University through the university’s Yissum Technology Transfer Company to Morria Biopharmaceuticals PLC (a British company), which is currently developing these drugs to treat inflammatory diseases of the airways (hay-fever, cystic fibrosis), the skin (eczema), the eye (conjunctivitis) and the gut (colitis, Crohn’s disease). For his groundbreaking work, Prof. Yedgar was one of the winners of this year’s Kaye Innovation Awards at the Hebrew University. The Kaye Awards have been given annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential which will benefit the university and society. The awards were presented this year during the annual meeting of the Hebrew University Board of Governors. Contact: Jerry Barach |
| Possible new therapy for the treatment of a common blood cancer Posted: 04 Sep 2012 09:00 PM PDT Research from Karolinska Institutet in Sweden shows that sorafenib, a drug used for advanced cancer of the kidneys and liver, could also be effective against multiple myeloma. The disease is one of the more common forms of blood cancer and is generally incurable.
“Recently developed drugs, like bortezomib, have increased the survival rate for people with this serious and complex disease,” says study leader Theocharis Panaretakis, docent of experimental oncology. “Having said this, the heterogeneity of the disease progression, the treatment response and the development of resistance to administered drugs which leads to the relapse of nearly all patients, has compelled us to find new and better treatments.” Myeloma is only found in adults; it is uncommon before the age of 40, and most patients are over 60 years when diagnosed. The disease can lie dormant in the body for many years, but only becomes life-threatening and requires treatment once the patient has begun to exhibit symptoms. The myeloma cells are mainly located in the bone marrow, and since this is where blood cells are produced, their presence seriously disrupts regular blood production. Malignant cancer cells or tumours can also accumulate outside the bone marrow, hence the term “multiple”. A common effect of multiple myeloma is osteoporosis, and as a consequence patients develop intense back pain as their vertebrae become compressed as well as bone fractures. Other symptoms are anaemia, fatigue, renal failure and, often, a greater susceptibility to infection. The current study, which is published in the scientific journal Cancer Research, was conducted on cell samples from humans and mice (cell lines). Almost all myleoma patients, seen at Karolinska University Hospital, were previously untreated. The researchers show how sorafenib induces cell death in human myeloma cell lines in a laboratory environment by preventing a certain kind of protein-level activity, an effect that also was achieved when the myeloma cells had developed a resistance to bortezomib. They also tested sorafenib in live mice and found that the drug either prevented or delayed the course of the disease. All in all, the researchers maintain that their results support the use of sorafenib in combination with other drugs in the treatment of multiple myeloma. Research groups from Uppsala University and Belgium were also involved in the study. The project was financed by the Swedish Cancer Society, the Swedish Research Council, the Cancer Society in Stockholm and the Åke Wiberg Foundation. ### Publication: ‘Sorafenib has potent anti-tumor activity against multiple myeloma in vitro, ex vivo and in vivo, in the 5T33MM mouse model’, Pedram Kharaziha, Hendrik De Raeve, Charlotte Fristedt, Qiao Li, Astrid Gruber, Per Johnsson, Georgia Kokaraki, Maria Panzar, Edward Laane, Anders Österborg, Boris Zhivotovsky, Helena Jernberg-Wiklund, Dan Grandér, Fredrik Celsing, Magnus Björkholm, Karin Vanderkerken, Theocharis Panaretakis, Cancer Research, online first 4 September 2012, doi: 10.1158/0008-5472.CAN-12-0658. Read the abstract: http://goo.gl/RnJrG For further information, please contact:
Theocharis Panaretakis, docent
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