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# News

Orange lichens are source for potential anticancer drug

An orange pigment, found in lichens and rhubarb, called parietin may have potential as an anti-cancer drug, scientists at Winship Cancer Institute of Emory University have discovered.
The results were published in Nature Cell Biology on October 19.
Parietin, also known as physcion, could slow the growth of and kill human leukemia cells obtained directly from patients, without obvious toxicity to human blood cells, the authors report. The pigment could also inhibit the growth of human cancer cell lines, derived from lung and head and neck tumors, when grafted into mice.
A team of researchers led by Jing Chen, PhD, discovered the properties of parietin because they were looking for inhibitors for the metabolic enzyme 6PGD (6-phosphogluconate dehydrogenase). 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. Researchers have already found 6PGD enzyme activity increased in several types of cancer cells.
"This is part of the Warburg effect, the distortion of cancer cells’ metabolism," says Chen, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. "We found that 6PGD is an important metabolic branch point in several types of cancer cells."
This work represents a collaboration among three laboratories at Winship led by Chen, Sumin Kang, PhD, assistant professor of hematology and medical oncology, and Jun Fan, PhD, assistant professor of radiation oncology. Co-first authors are postdoctoral fellows Ruiting Lin, PhD, and Changliang Shan, PhD, and former graduate student Shannon Elf, PhD, now at Harvard.
The Winship team obtained cancer cells from a patient with acute lymphoblastic leukemia, and found doses of physcion/parietin that could kill half the leukemia cells in culture within 48 hours, while the same doses left healthy blood cells unscathed. A more potent derivative of the pigment called S3 could cut the growth of a lung cancer cell line by a factor of three over 11 days, when the cells were implanted into mice.
Although 6PGD inhibitors appear to be nontoxic to healthy cells, more toxicology studies are needed, both to assess potential side effects and to see whether people with inherited conditions would be more sensitive to the drugs. Parietin is present in some natural food pigments, but has not been tested as a drug in humans.
The research at Emory was supported by the Winship Cancer Institute, the National Cancer Institute, the Department of Defense, the Charles Harris Run for Leukemia and the Georgia Research Alliance. Some co-authors of the paper are employees of Cell Signaling Technology Inc.
Emory Health Sciences

3-D printed parts from some commercial devices toxic to zebrafish embryos

The recent boom in 3-D printing has driven innovations in fields as disparate as haute couture and medical implants. But little is known about the safety of the materials used. In a new study in ACS’ journal Environmental Science & Technology Letters, scientists showed that some 3-D printed parts are highly toxic to zebrafish embryos. Their findings could have implications not only for aquatic life but also for hobbyists, manufacturers and patients.

In 2012, the market for 3-D printing was worth $288 million, according to an analysis by Canalys, Inc. By 2018, its value is projected to soar to$16.2 billion. The driver for this market has largely been use in medical applications, but with prices dropping for 3-D printers, more hobbyists and small businesses are expected to adopt the technology. Some research has already raised concerns that the printed materials might cause inflammatory or allergic reactions in patients. But little work has been done to explore their potential effects on an organism’s overall health and development. William H. Grover and colleagues wanted to fill that void.

The researchers exposed zebrafish embryos to discs printed by two kinds of commercial 3-D printers: fused deposition modeling (FDM) printers and stereolithography (STL) printers. Among other problems, the embryos exposed to either type of disc showed lower survival, reduced lengths and decreased hatching rates compared to the controls. In addition, all embryos exposed to STL-printed parts had malformations and died within seven days. The researchers found that treating 3-D printed pieces with ultraviolet (UV) light for 30 minutes on each side seemed to reduce some side effects. They conclude that safe disposal strategies for 3-D printed products and waste materials are needed to protect aquatic life.
American Chemical Society

Virginia Tech Carilion Research Institute scientists gain insight in cause of Alzheimer’s symptoms

Virginia Tech Carilion Research Institute scientists have uncovered a mechanism in the brain that could account for some of the neural degeneration and memory loss in people with Alzheimer’s disease.
The researchers, together with scientists at the University of Alabama at Birmingham School of Medicine, discovered that a common symptom of Alzheimer’s disease – the accumulation of amyloid plaques along blood vessels – could be disrupting blood flow in the brain. The results have been published in the journal Brain.
“We’ve always been interested in how glial cells interact with blood vessels,” said Harald Sontheimer, director of the Center for Glial Biology in Health, Disease, and Cancer at the Virginia Tech Carilion Research Institute and senior author of the paper. “Astrocytes are the most populous cell type in the brain and even outnumber neurons.”
Sontheimer also noted the importance of astrocyte function in the brain.
“Astrocytes serve many support functions, such as shuttling nutrients from blood vessels to nerve cells or removing their waste products,” said Sontheimer, who is also the I. D. Wilson Chair in Virginia Tech’s College of Science. “They also control the diameter of blood vessels to assure proper nutrient and oxygen delivery to the brain and maintenance of the blood-brain barrier. In response to injury and disease, however, astrocytes become reactive and change many of their supportive properties.”
Sontheimer’s team discovered that the astrocytes’ blood flow regulation is disrupted by plaques formed of misfolded proteins around blood vessels. In a healthy brain, amyloid protein fragments are routinely broken down and eliminated.
The presence of amyloid proteins around blood vessels in the brain is a hallmark of Alzheimer’s disease, yet it wasn’t understood if the proteins did any harm. Now, Sontheimer’s team has found that they do.
“We found that amyloid deposits separated astrocytes from the blood vessel wall,” said Stefanie Robel, a research assistant professor at the Virginia Tech Carilion Research Institute and a coauthor of the paper. “We also found that these amyloid deposits form an exoskeleton around the blood vessels, a kind of cast that reduces the pliability of the vessels.”
The exoskeleton is known as a vascular amyloid. Its inelasticity might result in lower blood flow, which could account for Alzheimer’s symptoms, such as memory lapses, impaired decision-making, and personality changes.
“Vascular amyloid may be the culprit in Alzheimer’s disease symptoms, especially considering that the amyloid exoskeleton might limit the supply of oxygen and glucose to the brain regions that need them most,” Sontheimer said. “This could also explain the cognitive decline in people with Alzheimer’s disease, as the disease is associated with reduced cerebral blood flow.”
While the scientists don’t fully understand the role of vascular amyloid in Alzheimer’s disease, they now have a possible therapeutic target to study.
“It may be helpful to remove the deposits to allow for appropriate blood flow,” Robel said. “The problem is we don’t know. It might be harmful to remove vascular amyloid at late stages of the disease; maybe they’re actually holding the vessels together.”
The researchers’ next step will be to examine blood vessels once the amyloid deposits are removed.
“Vascular amyloid is strangling the blood vessels,” Sontheimer said. “By removing them, maybe we’ll be able to restore blood flow regulation. Perhaps it’ll turn out vascular amyloid is preventing further degeneration. Whatever the case, we’ll certainly learn something new.”
The Virginia Tech Carilion Research Institute joins the life science, physical science, computational science, informatics, engineering, and social science strengths of Virginia Tech with the medical education expertise of the Virginia Tech Carilion School of Medicine and the medical practice experience of Carilion Clinic.
Virginia Tech

RAPID EVAPORATION SOLUTIONS FOR NATURAL PRODUCT EXTRACTION
Genevac reports on how their Rocket Synergy automated evaporator systems are replacing rotary evaporators as the tool of choice for rapid and sample-safe evaporation of natural product extracts. Working with natural products to derive potential pharmaceutical drug candidates or to identify new flavours and fragrances has a reputation of being very difficult. Sample collection, preparation, extraction, and drying are extremely labour intensive and not easily reproducible from a process standpoint. The traditional bottleneck in the natural product pipeline has been the drying of solvent extracted samples. Historically natural product researchers have used rotary evaporators to remove solvent from the extract, a tedious process that sometimes can take days per sample. Recently researchers have found the unique design of the Rocket Synergy used in conjunction with Genevac SampleGenie™ technology has allowed them to dry down samples in just 1-2 hours under low vacuum and low temperature conditions which do affect the integrity of the sample. The Rocket Synergy is able to dry or concentrate up to six flasks, each containing a maximum of 450ml of solvent, or 18 ASE® vials, with no user intervention or attention. To extend operational versatility the Rocket Synergy flask rotor may be quickly removed and replaced with a stainless steel vessel allowing unattended automated batch processing of up to 5 litres per run. It has been found that a single Rocket Synergy evaporator is capable of replacing several rotary evaporators, saving valuable bench space and improving your productivity.
www.genevac.com/naturalproducts

UNDERTAKING HEATED EXPERIMENTS IN NMR TUBES
Asynt has developed DrySyn NMR Heating Blocks to enable safe, effective and uniform heating of up to 10 NMR tubes on a conventional hotplate stirrer. This new DrySyn unit allows you to use standard NMR tubes as a reaction vessel for applications including catalyst screening experiments and reaction monitoring as well as studying broad peaks, temperature dependent solubility issues and conformational changes. Unlike heating in problematic oil baths, using a DrySyn NMR Heating Blocks allows you to analyse the contents of your NMR tube almost immediately without removal of residual oil on the outside of the glassware. To compliment the DrySyn NMR heating blocks, Asynt also offer an affordable range of NMR tubes and a Liquid Nitrogen Generator for NMR spectrometers to keep liquid helium cool and prevent boil off. The DrySyn heating block range is a safe and productive alternative to oil baths and heating mantles. The system offers clean, safe synthesis for single or multiple reactions. Compatible with any magnetic hotplate stirrer, DrySyn heating blocks provide rapid temperature ramping to over 300 ºC. All DrySyn heating blocks are manufactured in the UK with a chemical and solvent resistant clear anodised finish to ensure long trouble-free operation.

POST PURIFICATION SAMPLE HANDLING
Genevac, specialists in solvent removal, have developed a suite of proprietary technological solutions to facilitate post purification sample handling, including reformatting. For labs undertaking purification using Normal Phase HPLC, SFC or Flash chromatography – removal of organic solvents can be simply, productively and safely carried out in a Genevac centrifugal evaporator (EZ-2, ROCKET, Rocket Synergy or HT Series III). Where the nature of the sample being concentrated can lead to solvent bumping (e.g. natural products) - Genevac's DriPure® technology is proven to completely eliminate this troublesome and time-consuming problem. The evaporation of aqueous acetonitrile (or methanol / ethanol) fractions resulting from Reverse Phase HPLC is a widely carried out application on many Genevac evaporator systems. A multiple stage method has been developed for the EZ-2 evaporator to remove the organic solvent without freezing the water, remove the water, and then dry any remaining stubborn solvent. Alternatively, the unique LyoSpeed™ fast lyophilisation method can be used in Genevac HT series evaporators to produce dry (solvent-free) powders from samples that previously could only be produced as gums and oils. Recent advances in condenser technology, in particular the high power -75°C cold trap, available on HT Series III and Rocket Synergy evaporators, has led to significant advances in lyophilisation success rates. During post purification handling - samples typically need to be reformatted from fraction tubes or flasks, into a small vial for compound storage. For this specific time consuming task, Genevac developed SampleGenie™ technology. SampleGenie™ enables a large volume to be dried (or lyophilised) directly into a small storage vial in a fraction of the time taken by traditional evaporation methods that require you to reformat samples from a flask or multiple tubes into a vial.
www.genevac.com/purification

IMPROVING SUB-AMBIENT REACTION REPRODUCIBILITY
The DrySyn Snowstorm MULTI from Asynt provides a simple and highly effective way to perform multiple reactions in parallel across a large temperature range including sub-ambient chemistries such as organometallic syntheses and controlled rate crystallisation studies down to -60°C. Sub-ambient reactions have traditionally been difficult to undertake reproducibly on a small to medium scale. The DrySyn Snowstorm MULTI is able to accommodate up to 12 vials or three 100ml round bottom flasks offering sub ambient reactions in parallel without the need for jacketed reaction vessels, or ice baths. Operating with a suitable chiller / circulator, a DrySyn SnowStorm MULTI provides accurate, stable temperature control down to -60°C and up to +150°C. Being able to maintain a sub-ambient temperature, sometimes for significant periods, is important for reaction reproducibility. The DrySyn SnowStorm MULTI connects to an external chiller unit and holds temperatures at a set-point for as long as is required. Setting temperature ramping profiles is also possible on the DrySyn Snowstorm MULTI which is important in crystallisation studies.
www.asynt.com/product/drysynsnowstormreactor/

ABBVIE'S COMMITMENT TO ONCOLOGY DEMONSTRATED AT THE 57TH AMERICAN SOCIETY OF HEMATOLOGY ANNUAL MEETING
AbbVie presented data from clinical trials evaluating the company's oncology portfolio during the 57th American Society of Hematology Annual Meeting (ASH), December 5-8, in Orlando, Fla. Notably, data scheduled for presentation include results from studies of venetoclax, an investigational oral B-cell lymphoma-2 (BCL-2) inhibitor, in chronic lymphocytic leukemia (CLL) and other hematological malignancies. Additionally, researchers presented data from studies of ibrutinib (IMBRUVICA®), an inhibitor of Bruton's tyrosine kinase (BTK), as a single-agent and in combination with other therapies in several hematologic malignancies, including CLL, mantle cell lymphoma (MCL), follicular lymphoma (FL), multiple myeloma (MM) and diffuse large B-cell Lymphoma (DLBCL). "The breadth and depth of the data we are presenting at ASH underscore our commitment to developing treatment options for people affected by blood cancers" said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "We have made significant progress in advancing our deep and robust pipeline and are excited to share the results of some of our key clinical trials".
Meeting abstracts are available at http://www.hematology.org/Annual-Meeting/Abstracts/.
www.abbvie.com

DR. REDDY'S ANNOUNCES THE COMPLETION OF FONDAPARINUX INTELLECTUAL PROPERTY PURCHASE

Dr. Reddy's Laboratories has announced that it has completed the purchase of worldwide exclusive intellectual property rights for Fondaparinux sodium, its generic anti-coagulant drug from its Australian partner, Alchemia Limited. Earlier, the company had signed a term sheet for this transaction in September, 2015. Alchemia’s shareholders approved the sale of Fondaparinux at the Company’s annual general meeting held on 10 November 2015, post which Dr. Reddy’s and Alchemia have executed a purchase and sale agreement, together with various patent assignment deeds. Alchemia has received USD 17.5 million from Dr. Reddy’s as consideration for the sale. The agreement is effective July, 2015.
www.drreddys.com

EUR 60 MILLION INVESTMENT FOR SALTIGO
Specialty chemicals company LANXESS is investing around EUR 60 million in the expansion of the Leverkusen production facilities of Saltigo GmbH – a leading supplier in the field of exclusive synthesis. The biggest single investment in Saltigo since it was founded as a fine chemicals company in 2006 should sustainably strengthen the LANXESS subsidiary’s market position. “Once again this year, we have many projects in the pipeline and see further growth potential” says Saltigo Managing Director Wolfgang Schmitz. This is why the LANXESS subsidiary is significantly expanding its multi-purpose production facilities in the Central Organics Pilot Plant (ZeTO). “This expansion will further expand our flexibility and also ensure in the future that Saltigo remains optimally positioned in the dynamic custom manufacturing market” adds Schmitz. “In the crop protection segment alone we anticipate annual market growth of 3 percent on average through 2025 despite weaker demand at the moment. To grow with our customers, we are expanding synthesis capacities for custom manufacturing in the ZeTO by around a third” says Schmitz. A part of these future capacities is already contractually secured. Saltigo will use a large share of this investment to add further reactors to its existing multi-purpose facilities and to construct two new solids isolation and drying lines. In addition, it will ensure an even more efficient raw material and solvent supply of the production facilities through the installation of a new container warehouse next to the plant. Planning also leaves scope for further expansion of this storage capacity. The complete facility will be equipped with a modern new process control system to combine the highest possible qualitative requirements with maximum productivity. The construction launch is scheduled for the middle of next year, while production should start at the end of 2017. The expansion should create 10 new jobs.
www.saltigo.com