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Nanotechnology Used to Target Drug Delivery to Glioblastoma Cells

Great discoveries do sometimes come in small packages. Few know that better than Ann-Marie Broome (at left in photo), Ph.D., who feels nanotechnology holds the future of medicine with its ability to deliver powerful drugs in tiny, designer packages. Her latest research finds the perfect application - targeting cancerous brain tumor cells. Results from her recent paper, published in the March 2016 issue of the international journal Nanomedicine - Future Medicine, found that a lipid nanocarrier engineered to be small enough to get past the blood-brain barrier could be targeted to deliver a chemotherapeutic drug more efficiently to tumor cells in the brain. The article is titled "Delivery of a Drug Cache to Glioma Cells Overexpressing Platelet-Derived Growth Factor Receptor Using Lipid Nanocarriers.” In vivo studies showed specific uptake and increased killing in glial cells, so much so that Dr. Broome initially questioned the results. "I was very surprised by how efficiently and well it worked once we got the nanocarrier to those cells," she said, explaining that initial results were so promising that she had her team keep repeating the experiments, using different cell lines, dosage amounts, and treatment times. Researchers and clinicians are excited because it potentially points the way to a new treatment option for patients with certain conditions, such as glioblastoma multiforme (GBM), the focus of this study. Glioblastoma multiforme is a devastating disease with no curative options due to several challenges, said Dr. Broome, who is the Director of Molecular Imaging of the Medical University of South Carolina's Center for Biomedical Imaging and Director of Small Animal Imaging of Hollings Cancer Center.

Scientists Resolve Crystal Structure of Zika Virus Replicase at 1.8-Angstroms; Possible Basis for Anti-Viral Drug Design

A team led by researchers from Tianjin University (People’s Republic of China) has solved the structure of the Zika virus helicase, which is a key target for antiviral development. The research is published online in May 12, 2016 in Springer's journal Protein & Cell. The open-access article is titled “The Crystal Structure of Zika Virus Helicase: Basis for Antiviral Drug Design.” The Zika virus (ZIKV) can cause microcephaly and other severe birth defects. However, as there are currently no effective vaccines or therapies available to contain ZIKV infection, ZIKV remains a significant challenge to public health. All viruses seem to need a helicase for replication. The ZIKV helicase is a motor enzyme that can convert energy from nucleoside triphosphate to unwind-double stranded nucleic acids. This is an essential step for viral replication. By targeting ZIKV helicase with small-molecule inhibitors, it might be possible to stop viral replication and prevent disease. The scientists have successfully obtained an image at 1.8 angstroms of the ZIKV helicase. This high-resolution image of the ZIKV key enzyme may help scientists develop drugs to treat the ZIKV disease. The image here is from the article in Protein & Cell and is also reproduced in the press release. (Credit: Protein & Cell). Please see either the article or the press release to view a larger version of this image.

[Press release] [Protein & Cell article]

Plant Cell Wall Development Revealed in Space & Time

Scientists have mapped changes in the composition of plant cell walls over space and time, providing new insights into the development and growth of all plants. The work represents a first step towards precision-breeding to enhance the properties of plant-based products such as timber and biofuels. Conducted by an international research team using the model laboratory plant Arabidposis, the study was published online on May 19, 2016 in the journal Current Biology. The article is titled “Regulation of Meristem Morphogenesis by Cell Wall Synthases in Arabidopsis.” The cell wall is a defining feature of plant cells, providing essential functions like strength and mechanical support to plant tissues. The cell wall is also associated with cellular function, including enabling the plant to grow and to sense and respond to developmental cues and environmental stresses such as pathogen invasion. Plant cell walls are also the main component of plant biomass, our only renewable bioenergy resource, and are consumed by humans as a component of food - dietary fiber. "Despite their importance to society, we currently know very little about how these walls are built and refined during plant development" said study co-author Dr. Monika Doblin from the ARC Centre of Excellence in Plant Cell Walls situated within the School of Biosciences at the University of Melbourne in Australia. "We used three sophisticated techniques to generate a spatiotemporal map of plant cell wall development in the shoot apical meristem (SAM), the structure that gives rise to all above-ground tissues in plants," added Dr. Doblin.

Discovery in Dogs of Candidate Genes for Three Rare Human Diseases

Professor Hannes Lohi's research group at the University of Helsinki in Finland has discovered three novel canine genes for Caffey, Raine, and van den Ende-Gupta syndromes. Research reveals close similarities of the canine models of human rare disorders and highlights the potential of comparative research approach for the development of rare disease diagnostics and treatments. Gene discoveries will also benefit veterinary diagnostics and breeding programs. The study was published in the open-access journal PLOS Genetics on May 17, 2016. The article is titled “Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, Ende-Gupta, and Raine Syndromes.” Genetic research in dogs revealed the causes of hyperostosis in Terrier breeds, dental hypomineralization in Border Collie, and previously undescribed skeletal syndrome in Wire Fox Terriers. The latter two syndromes were described for the first time in this study. Hyperostosis in Terriers has been described before, but the genetic cause was found here. Gene discoveries helped to identify and name the conditions and link them to human rare disorders. The study unraveled a novel candidate gene for human Caffey disease, a condition that causes facial swelling and other symptoms. Gene discovery for canine craniomandibular osteopathy (CMO) is of particular interest. The disease is known as infantile hyperostosis in human and belongs to a group of self-limiting and difficult-to-diagnose swelling syndromes. The group found a novel physiologically relevant candidate gene, SLC37A2, and have initiated mutation screenings in human Caffey patients, explains lead author, Marjo Hytönen., Ph.D. SLC37A2 is a glucose-phosphate transporter, and its defect suggests an impaired glucose homeostasis in developing bone, leading to hyperostosis.

Final Talks, Clinical & Scientific Summaries, Awards Mark Final Day of ISEV 2016 Annual Meeting in Rotterdam; Long-Time Leader Jan Lötvall Steps Down & Australia’s Andy Hill Named New ISEV President; ISEV 2017 Scheduled for Toronto

Saturday’s closing half-day session of the International Society for Extracellular Vesicles (ISEV 2016) annual meeting was rich with exciting new science, as well as recognition for some of the extraordinary work presented throughout the course of the four-day conference (May 4-7) in Rotterdam, the Netherlands. The meeting closed with outgoing ISEV president Jan Lötvall handing over the reins of leadership to Andy Hill (photo), Head of the Department of Biochemistry & Genetics at La Trobe University in Australia, and the announcement that the ISEV 2017 annual meeting would be held in Toronto, Canada. Prior to those announcements, short clinical and scientific wrap-ups of the meeting were given, respectively, by Peter Quesenberry, MD, Professor of Oncology & Medicine at the medical school of Brown University in the USA and Alise Weaver, MD, PhD, Professor of Cancer Biology & Cell and Developmental Biology at the Vanderbilt University Medical Center, also in the USA. The fabulous work of the ISEV’s international local organizing committee, under the leadership of Hungary’s Edit Buzás, was also lauded. Awards were also presented for exceptional oral and poster presentations given at the meeting. It was also announced that an online course on EVs would be made available by the ISEV later in May. The final morning of the meeting had begun with three simultaneous Experts Meet sessions on the biofluids blood, milk, and urine. These were followed by three simultaneous sessions featuring late-breaking oral presentations. Highlights of these sessions included one talk on how exosomes might play a role in the repair of spinal cord injury and another on a possible role for EVs in infections caused by non-enveloped viruses such as the mengovirus, a picorna virus.

Plenary Address on Immuno Cell-Cell Interactions Highlights Friday Session of International Society for Extracellular Vesicles (ISEV 2016) Annual Meeting in Rotterdam

The plenary address of Friday’s session of the International Society for Extracellular Vesicles annual meeting (ISEV 2016) in Rotterdam was delivered by the eminent immunologist and cell biologist Francisco Sanchez-Madrid, PhD, and was titled “Immune Cell-Cell Communication: Mechanisms of MicroRNA and Protein Sorting into Exosomes.” Dr. Sanchez-Madrid is Professor at the Universidad Autonoma de Madrid and Head of the Immunology Department at the La Princesa Hospital in Madrid. His address to the 800+ attendees in the filled amphitheater focused on two main topics: the exosome-driven transfer of genetic and mitochondria constituents through immune synapses [an immune synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as an effector T-cell or natural killer cell; an immune synapse is also defined as a temporary membrane structure formed between immune cells in contact so as to effect communication], and the mechanisms of miRNA and protein sorting in exosomes. He first reported that there is unidirectional transfer of miRNA-loaded exosomes from activated T-cells at the immune synapse. He then showed evidence that mtDNA-binding proteins are contained in these exosomes, and, in fact, next-gen sequencing demonstrated that the entire mitochondrial genome is present in some of the exosomes. He then investigated whether mtDNA might trigger a signaling response in recipient cells. He noted that there is a potential role of T-cell exosomes as inhibitors of the innate immune response. Dr. Sanchez-Madrid then turned to a discussion of miRNA and protein sorting into exosomes.

Eminent Virologist Robert Gallo Delivers Plenary Address to ISEV 2016 Rotterdam Meeting from Hospital

In an extraordinary moment, world-renowned virologist Robert Gallo, MD, one of Thursday’s International Society for Extracellular Vesicles (ISEV) 2016 scheduled plenary speakers addressed the over 800 attendees in Rotterdam by video recording from a hospital in the United States where he Is being treated for an infection. Dr. Gallo was originally scheduled to participate on site with another world-class virologist, Leonid Margolis, PhD, in the ISEV’s second plenary session “Learning from the Best: Viruses and EVs.” Also speaking at this plenary was Shilpa Buch, PhD, Professor at the University of Nebraska Medical Center. Dr. Gallo’s scientific accomplishments are legendary and legion. He led critical work to identify HIV as the cause of AIDS and also to develop a simple blood test for the virus that was an absolutely critical advance in the fight against this dread disease. In the period 1980-1990, Dr. Gallo was the most cited scientist in the world. He is one of a select few scientists ever to be recognized with two Lasker awards. The fact that a scientist of such immense accomplishment chose to speak to the ISEV 2016 meeting attendees is a profound indication of how significant work on EVs has become. In fact, early in his remarks Dr. Gallo described EVs as an “exciting new field” and “another way of communication that may have impact all through medicine.” Dr. Gallo very briefly outlined some of his seminal work with human retroviruses with the thought that this work might guide the new efforts to investigate and characterize EVs, which have many similarities to retroviruses.

Plenary Session on Cancer Opens Fifth International Society for Extracellular Vesicles (ISEV 2016) Annual Meeting in Rotterdam

On Wednesday morning May 4, the International Society for Extracellular Vesicles (ISEV) opened its fifth annual meeting (ISEV 2016) in Rotterdam with a plenary session featuring presentations by two giants in cancer research. Klaus Pantel, MD, PhD, Professor and Director of the Department of Tumor Biology at the University Medical Center Hamburg-Eppendorf, spoke on “Liquid Biopsy in Cancer,” and David Lyden (photo), MD, PhD, Professor at Weill Cornell Medical College in New York City, spoke on “The Systemic Effects of Exosome-Mediated Metastasis.” The packed house gallery of nearly 800 meeting attendees was not disappointed. Dr. Pantel, a long-time metastasis researcher, spoke on the urgent need for techniques such as non-invasive liquid biopsies--using circulating tumor cells (CTCs), cell-free DNA (cfDNA), miRNAs, and/or exosomes--to provide effective tools for screening and early detection of cancer, for cancer prognoses, for stratifying and monitoring cancers, for revealing markers of minimum residual disease, and for the identification of therapeutic targets and the understanding of resistance mechanisms, as well as possible guides to effective interventions. With regard to early detection, Dr. Pantel noted that studies have shown that there is an increase in exosome number in patients with ovarian cancer, which is a very aggressive cancer. In addition, recent work has suggested that glypican-1 cancer exosomes are an early indicator of pancreatic cancer. He further noted that contrary to current dogma, his group had found CTCs from glioma patients in the circulation outside the brain. He noted that although these CTCs do not cause metastasis in the glioma patients, they can cause cancer in those receiving transplants from such patients. Dr.

Well-Attended Two-Track Education Day Precedes Opening of International Society for Extracellular Vesicles (ISEV 2016) Annual Meeting in Rotterdam May 4-7

As in the past, this year’s International Society for Extracellular Vesicles (ISEV 2016) annual meeting featured a pre-meeting education day to bring interested parties up to speed on extracellular vesicles (EVs), particularly on key recent developments. For the first time, however, the full-day effort was divided into two parallel sessions: “Novel Developments of Isolation and Characterization of Extracellular Vesicles” and “Extracellular Vesicle Therapeutics.” The two tracks, coupled with the outstanding attendance by 400 scientists and students on May 3, 2016, are yet another indication of the tremendous recent growth of the EV field. The Education Day was held at the De Doelen International Congress Center in the heart of Rotterdam, the Netherlands, and this venue will also be the site for the ISEV 2016 meeting running from Wednesday, May 4- Saturday, May 7. An attendance of over 800 is expected for the ISEV 2016 meeting. The education session on novel development of isolation and characterization of EVs, began, perhaps appropriately, with a discussion by Cecilia Lasser on a highly impressive educational tool that will become available to everyone a little later in May. The tool is a Massive Online Open Course (MOOC) on EVs. The online course will seek to provide a highly useful informative resource with the basics of EVS described in presentations by world leaders in the field. Among the subjects covered initially will be a historical introduction, presence of EVs in bodily fluids, a description of the biogenesis of EVs, different methods of isolation, and different approaches to characterization and quantification. When launched later in May, the MOOC can be accessed at the following URL: https://www.coursera.org.

JSR Establishes Life Sciences Division to Expand into Bioprocessing and Diagnostic and Research Products, Including Liquid Biopsy Products (e.g., ExoCap™ Kit for Exosomes)

On April 18, 2016, JSR Corporation announced the formation and establishment of its Life Sciences Division, JSR Life Sciences (JLS). The newly formed JLS has been established as a business unit for parent company, Tokyo-based JSR Corporation, a company with more than 50 years of success in material and polymer chemistries including marketing latex and magnetic beads to life sciences and diagnostic companies worldwide. Eric R. Johnson will lead the global operation for the Life Sciences business and assume responsibility of all operations as Senior Executive Officer of JSR Corporation and Head of the Life Sciences Division. In that capacity he will lead JLS in integrating the global operations of the US, Europe, Asia, and Japan. “We know that we need to engage experts and markets outside of Japan and we see the US and Europe as key regions for the growth of our life sciences businesses,” said Mitsunobu Koshiba, President and Representative Director of JSR Corporation. “Assigning Johnson as the head of JLS is a strategic move that will facilitate our going beyond traditional markets to drive growth for JSR.” The company is leveraging its material and polymer expertise to expand into the life sciences industry in the two major industry categories of bioprocessing and diagnostic and research products. In bioprocessing, JLS focuses on large-scale purification and chromatography products, including the recent launch of Amsphere™ A3, a protein A chromatography resin for downstream processing. In 2015, JSR expanded its capabilities through the acquisition of a majority stake in contract development and manufacturing organization KBI Biopharma, Inc. In diagnostics and research products, JLS has established a liquid biopsies business that recently launched ExoCap™ Kit for the isolation and purification of exosomes from plasma or serum.

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