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News Article | May 16, 2017
Site: www.prweb.com

Genedata, a leading provider of advanced software solutions for R&D, today announced its global Genedata Screener User Group Meetings, which will be held in Boston, Cambridge/UK, Shanghai, and Tokyo. These forums give Genedata Screener users the opportunity to share best practices in screening data analysis and learn about the latest advances in screening technologies and applications. They also enable customers to network with scientists and informaticians from some of the world’s premier pharmaceutical companies, academic research institutions, and contract research organizations. Scientists and researchers from Agios Pharmaceuticals, AstraZeneca, Biogen, Broad Institute, Constellation Pharmaceuticals, Daiichi Sankyo, EMD Serono, Evotec, MRC Technology, and UCB are among attendees at this year’s global User Group Meetings. “Screener User Group Meetings are valuable knowledge-sharing events,” said Suvarna Khare-Pandit, a research scientist with Vertex Pharmaceuticals. “Agenda topics are comprehensive and balanced, giving you insights into how other researchers are using Screener. These meetings are a great opportunity to network with my peers and the Genedata Screener team.” At the Boston User Group Meeting (UGM), Khare-Pandit will deliver a presentation on how Vertex uses Genedata Screener for assay validation and compound screening with high-content image data analysis. Customer Collaboration Key to Innovation “Close collaborations and regular discussions with customers are part of the Genedata DNA,” said Dr. Othmar Pfannes, CEO of Genedata. “This level of engagement enables us to acquire a deeper understanding of our customers’ requirements so that we can continuously develop better solutions that keep us at the frontier of science and technology.” Regional and accessible, Genedata Screener UGMs promote dialogue between screening sciences and data sciences. They also provide an opportunity to share insights on current and future functionality in Genedata Screener. For example, Relay Therapeutics will detail how it uses Genedata Screener in the cloud to enhance collaborative research and screening data analysis. Other presentations will address Genedata Screener applications in areas such as Automated Patch Clamp (APC), Compound Combination Screening, High Content Screening (HCS), and Surface Plasmon Resonance (SPR). Editorial Note: The following are among the customer presentations that will be featured at global UGMs: About Genedata Genedata transforms data into intelligence with innovative software solutions and domain-specific consulting services that automate complex, large-scale experimental processes and enable organizations to maximize the ROI from their R&D. Founded in 1997, Genedata is headquartered in Switzerland and has offices in Germany, the UK, Japan, and the US. http://www.genedata.com. Follow Genedata on LinkedIn Disclaimer The statements in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties, including risks associated with uncertainties related to contract cancellations, developing risks, competitive factors, uncertainties pertaining to customer orders, demand for products and services, development of markets for the Company's products and services. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to release publicly the result of any revisions to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. All product and service names mentioned are the trademarks of their respective companies.


MRC Technology and Biocartis initiate development of liquid biopsy test for breast cancer Partnership aimed at the development of molecular diagnostic assays on Biocartis' fully automated Idylla(TM) platform London (UK) / Mechelen (Belgium), 7 June 2017 - MRC Technology ('MRCT'), a medical research charity, and Biocartis Group NV ('Biocartis' or the 'Company'), an innovative molecular diagnostics company (Euronext Brussels: BCART), today announced a partnership to develop selected molecular diagnostic tests for use on Biocartis' fully automated Idylla(TM) platform. MRCT aims to move promising medical research forward into patient treatments and diagnostics and has been involved in helping deliver a number of therapies including Keytruda® (pembrolizumab, marketed by MSD) which is an important immunotherapy treatment for various cancers. Under the terms of the agreement, Biocartis and MRCT will jointly develop selected molecular diagnostic tests for use on the fully automated Idylla(TM) platform. For each selected test, MRCT will act as a development contractor, whereas Biocartis will be responsible for the commercialization of the tests under its own label. Financial details of the partnership are not disclosed. The first test to be developed under the partnership is a liquid biopsy test aimed at monitoring of metastatic breast cancer patients for resistance to hormone therapy. This is an important first step in the breast cancer menu that Biocartis is developing, and has a clear strategic fit within the Company's focus on liquid biopsy testing. One in eight women is diagnosed with breast cancer in her lifetime, according to the World Health Organization. This makes it the most common cancer among women worldwide[1] but early diagnosis can improve the survival rate[2]. Consequently, breast cancer is currently the largest cancer diagnostics market in the world[3], expected to account for USD 13.1bn by 2020[4]. As such, it represents an important segment for Biocartis to enter, next to its current focus on melanoma, lung and colorectal cancer. Erwin Sablon, Head of R&D and Alliance Management at Biocartis, commented: "Building partnerships with third parties to accelerate the expansion of our menu of molecular diagnostic tests is a key element in our strategy. We are very pleased to be partnering with MRCT, an organization that has clearly shown the ability to convert promising medical research into solutions for patients. MRCT has an experienced team in place and we are confident that together we can successfully develop a range of high quality tests for the Idylla(TM) platform, beginning with this first test for breast cancer." Michael A. Dalrymple, PhD, MBA, Director, Diagnostics & Science Foresight MRCT, reacted: "We are excited to partner with Biocartis on test development for the Idylla(TM) platform, which we believe can impact the way molecular diagnostics for oncology is done today. This resonates well with our focus of translating medical innovation into viable and accessible treatments and diagnostics that patients can benefit from. Breast cancer has an enormous impact on many lives every day and we see this assay as an important project to start our partnership with." Within its melanoma and colorectal cancer menu, Biocartis already launched three liquid biopsy assays[5] (available for research use only), detecting a large set of actionable mutations directly from 1 ml of blood plasma each. The fourth liquid biopsy assay, the Idylla(TM) ctEGFR Mutation Assay, adding to Biocartis' lung cancer test menu, is expected to be launched in H2 2017. About MRC Technology MRC Technology is an independent life science medical research charity committed to improving positive patient outcomes everywhere. As a champion for human health, MRC Technology partners with academic, biotechnology, pharmaceutical and charity organisations to move promising medical research forward into viable and accessible patient treatments. As a self-funded charity, income is reinvested to support translating research from the bench to patient. MRC Technology offers commercialization and IP management skills and diagnostic and drug discovery expertise, specializing in small molecules and therapeutic antibodies. www.mrctechnology.org. MRC Technology's work has helped to develop four drugs (Keytruda®, Actemra®, Tysabri® and Entyvio®) and a test for antimicrobial resistance. About Biocartis  Biocartis (Euronext Brussels: BCART) is an innovative molecular diagnostics (MDx) company providing next generation diagnostic solutions aimed at improving clinical practice for the benefit of patients, clinicians, payers and industry. Biocartis' proprietary MDx Idylla(TM) platform is a fully automated sample-to-result, real-time PCR (Polymerase Chain Reaction) system that offers accurate, highly reliable molecular information from virtually any biological sample in virtually any setting. Biocartis launched the Idylla(TM) platform in September 2014. Biocartis is developing and marketing a rapidly expanding test menu addressing key unmet clinical needs in oncology and infectious diseases. These areas represent respectively the fastest growing and largest segments of the MDx market worldwide. Today, Biocartis offers nine oncology tests and two infectious disease tests. More information: www.biocartis.com Press Photo Library available here. Follow us on Twitter: @Biocartis_. Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors' current expectations and projections concerning future events such as the Company's results of operations, financial condition, liquidity, performance, prospects, growth, strategies and the industry in which the Company operates. By their nature, forward-looking statements involve a number of risks, uncertainties, assumptions and other factors that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties, assumptions and factors could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward-looking statements contained in this press release regarding past trends or activities are not guarantees of future performance and should not be taken as a representation that such trends or activities will continue in the future.  In addition, even if actual results or developments are consistent with the forward-looking statements contained in this press release, those results or developments may not be indicative of results or developments in future periods. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person's officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release. [1] Source: World Cancer Research Fund International, http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/breast-cancer-statistics, last consulted on 17 May 2017. [2] Source: http://www.nationalbreastcancer.org/breast-cancer-facts, last consulted on 15 May 2017. [3] Source: GrandView Research, "Cancer Diagnostics Market Analysis By Type (Laboratory Tests, Genetic Tests, Imaging, Endoscopy), By Application (Breast, Lung, Liver, Cervical, Colorectal, Skin), By Region, And Segment Forecasts, 2014 - 2025", http://www.grandviewresearch.com/industry-analysis/cancer-diagnostics-market,  last consulted on 15 May 2017. [4] Source: MarketsandMarkets, "Cancer Diagnostics Market by Technology (ELISA, ELFA, PCR, NGS, Immunohistochemistry, Microarray, Imaging (MRI, CT, PET, Ultrasound, Mammography), Biopsy), by Application (Breast Cancer, Lung Cancer, Colorectal Cancer, Melanoma) - Forecast to 2020", 2015. [5] The Idylla(TM) ctBRAF Mutation Assay, the Idylla(TM) ctKRAS Mutation Assay and the Idylla(TM) ctNRAS-BRAF-EGFR S492R Mutation Assay are Research Use Only (RUO) and not for use in diagnostic procedures.


Leeper A.D.,University of Edinburgh | Farrell J.,MRC Technology | Williams L.J.,University of Edinburgh | Thomas J.S.,University of Edinburgh | And 4 more authors.
Biomaterials | Year: 2012

We developed a three-dimensional assay prepared from primary breast cancer tissue and quantified tumor response to tamoxifen therapy. Freshly harvested breast cancer biopsies obtained at the time of curative surgical resection were fragmented and embedded into collagen I cushions. Changes in proliferation, apoptosis and tumor volume in response to tamoxifen treatment were quantified using image analysis software and optical projection tomography. Individual and collective invasion of epithelial cells into the surrounding collagen I was observed over the course of the experiment using phase contrast light microscopy and histopathological methods. Addition of tamoxifen to preparations derived from ER+ tumors demonstrated a range of response as measured by proliferative and apoptotic markers. In keeping with published data, tamoxifen reduced the percentage of apoptotic cells expressing cleaved caspase-3 (p = 0.02, Poisson regression analysis). Tamoxifen also reduced residual epithelial volume in ER+ tumors (p = 0.001, Mann-Whitney test), but not in ER low/- tumors (p = 0.78). Changes in tumor volume, as measured by optical projection tomography, allowed stratification into responsive and non-responsive tumors. The model mirrors observations of breast cancer response and histopathological changes to tamoxifen in neo-adjuvant trials. This assay provides a method of screening a battery of therapeutics against individual cancers, informing subsequent design of neo-adjuvant trials. © 2011 Elsevier Ltd.


Miller T.C.R.,University of Cambridge | Rutherford T.J.,University of Cambridge | Birchall K.,MRC Technology | Chugh J.,MRC Technology | And 2 more authors.
ACS Chemical Biology | Year: 2014

The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygos PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the BCL9 HD1 domain. Here, we report the first use of fragment-based screening by NMR to identify small molecules that block protein-protein interactions by a PHD finger. This led to the discovery of a set of benzothiazoles that bind to a cleft emanating from the PHD-HD1 interface, as defined by X-ray crystallography. Furthermore, we discovered a benzimidazole that docks into the H3K4me specificity pocket and displaces the native H3K4me peptide from the PHD finger. Our study demonstrates the ligandability of the Pygo-BCL9 complex and uncovers a privileged scaffold as a template for future development of lead inhibitors of oncogenesis. © 2014 American Chemical Society.


Smith H.,University of Dundee | Liu X.-Y.,Nanyang Technological University | Dai L.,Nanyang Technological University | Goh E.T.H.,University of Dundee | And 12 more authors.
Biochemical Journal | Year: 2011

Mammalian Pellino isoforms are phosphorylated by IRAK (interleukin receptor associated kinase) 1/IRAK4 in vitro, converting them into active E3 ubiquitin ligases. In the present paper we report a striking enhancement in both transcription of the gene encoding Pellino 1 and Pellino 1 protein expression when murine BMDMs (bone-marrow-derived macrophages) are stimulated with LPS (lipopolysaccharide) or poly(I:C). This induction occurs via a TRIF [TIR (Toll/interleukin-1 receptor)-domain-containing adaptor-inducing interferon-β]-dependent IRAK-independent pathway and is prevented by inhibition of the IKK [IκB(inhibitor of nuclear factor κB) kinase]-related protein kinases, TBK1 {TANK [TRAF (tumour-necrosis-factor- receptor-associated factor)-associated nuclear factor κB activator]-binding kinase 1} and IKK?. Pellino 1 is not induced in IRF3 (interferon regulatory factor 3) -/- BMDMs, and its induction is only reduced slightly in type 1 interferon receptor -/- BMDMs, identifying Pellino 1 as a new IRF3-dependent gene. We also identify Pellino 1 in a two-hybrid screen using IKKε as bait, and show that IKKε/TBK1 activate Pellino 1 in vitro by phosphorylating Ser 76, Thr 288 and Ser 293. Moreover, we show that the E3 ligase activity of endogenous Pellino 1 is activated in LPS- or poly(I:C)-stimulated macrophages. This occurs more rapidly than the increase in Pellino 1 mRNA and protein expression, is prevented by the inhibition of IKKε/TBK1 and is reversed by phosphatase treatment. Thus IKKε/TBK1mediate the activation of Pellino 1's E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists. © The Authors Journal compilation © 2011 Biochemical Society.


Clark K.,University of Dundee | Peggie M.,University of Dundee | Plater L.,University of Dundee | Sorcek R.J.,Boehringer Ingelheim Pharmaceuticals | And 6 more authors.
Biochemical Journal | Year: 2011

Members of the IKK {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase} family play a central role in innate immunity by inducing NF-κB- and IRF [IFN (interferon) regulatory factor]-dependent gene transcription programmes required for the production of pro-inflammatory cytokines and IFNs. However, the molecular mechanisms that activate these protein kinases and their complement of physiological substrates remain poorly defined. Using MRT67307, a novel inhibitor of IKKε/TBK1 (TANK {TRAF [TNF (tumour-necrosis-factor)-receptor-associated factor]-associated NF-κB activator}-binding kinase 1) and BI605906, a novel inhibitor of IKKβ, we demonstrate that two different signalling pathways participate in the activation of the IKK-related protein kinases by ligands that activate the IL-1 (interleukin-1), TLR (Toll-like receptor) 3 and TLR4 receptors. One signalling pathway is mediated by the canonical IKKs,which directly phosphorylate and activate IKKε and TBK1, whereas the second pathway appears to culminate in the autocatalytic activation of the IKK-related kinases. In contrast, the TNFα-induced activation of the IKK-related kinases is mediated solely by the canonical IKKs. In turn, the IKK-related kinases phosphorylate the catalytic subunits of the canonical IKKs and their regulatory subunit NEMO (NF-κB essential modulator), which is associated with reduced IKKα/β activity and NF-κB-dependent gene transcription. We also show that the canonical IKKs and the IKK-related kinases not only have unique physiological substrates, such as IκBα, p105, RelA (IKKα and IKKβ) and IRF3 (IKKε and TBK1), but also have several substrates in common, including the catalytic and regulatory (NEMO and TANK) subunits of the IKKs themselves. Taken together, our studies reveal that the canonical IKKs and the IKK-related kinases regulate each other by an intricate network involving phosphorylation of their catalytic and regulatory (NEMO and TANK) subunits to balance their activities during innate immunity. © The Authors Journal compilation © 2011 Biochemical Society.


De La Roche M.,University of Cambridge | Rutherford T.J.,University of Cambridge | Gupta D.,University of Cambridge | Veprintsev D.B.,University of Cambridge | And 4 more authors.
Nature Communications | Year: 2012

Wnt/β-catenin signalling controls development and tissue homeostasis. Moreover, activated β-catenin can be oncogenic and, notably, drives colorectal cancer. Inhibiting oncogenic β-catenin has proven a formidable challenge. Here we design a screen for small-molecule inhibitors of β-catenin's binding to its cofactor BCL9, and discover five related natural compounds, including carnosic acid from rosemary, which attenuates transcriptional β-catenin outputs in colorectal cancer cells. Evidence from NMR and analytical ultracentrifugation demonstrates that the carnosic acid response requires an intrinsically labile α-helix (H1) amino-terminally abutting the BCL9-binding site in β-catenin. Similarly, in colorectal cancer cells with hyperactive β-catenin signalling, carnosic acid targets predominantly the transcriptionally active ('oncogenic') form of β-catenin for proteasomal degradation in an H1-dependent manner. Hence, H1 is an 'Achilles' Heel' of β-catenin, which can be exploited for destabilization of oncogenic β-catenin by small molecules, providing proof-of-principle for a new strategy for developing direct inhibitors of oncogenic β-catenin. © 2012 Macmillan Publishers Limited. All rights reserved.


Forfar R.,MRC Technology | Lu Z.-L.,Xi'an Jiaotong - Liverpool University
Journal of Biological Chemistry | Year: 2011

Recent crystal structures of G protein-coupled receptors (GPCRs) show the remarkable structural diversity of extracellular loop 2 (ECL2), implying its potential role in ligand binding and ligand-induced receptor conformational selectivity. Here we have applied molecular modeling and mutagenesis studies to the TM4/ECL2 junction (residues Pro 174(4.59)-Met 180(4.66)) of the human gonadotropin-releasing hormone (GnRH) receptor, which uniquely has one functional type of receptor but two endogenous ligands in humans. We suggest that the above residues assume an α-helical extension of TM4 in which the side chains of Gln 174(4.60) and Phe 178(4.64) face toward the central ligand binding pocket to make H-bond and aromatic contacts with pGlu 1 and Trp 3 of both GnRH I and GnRH II, respectively. The interaction between the side chains of Phe 178(4.64) of the receptor and Trp 3 of the GnRHs was supported by reciprocal mutations of the interacting residues. Interestingly, alanine mutations of Leu 175(4.61), Ile 177(4.63), and Met 180(4.66) decreased mutant receptor affinity for GnRH I but, in contrast, increased affinity for GnRH II. This suggests that these residues make intramolecular or intermolecular contacts with residues of transmembrane (TM) domain 3, TM5, or the phospholipid bilayer, which couple the ligand structure to specific receptor conformational switches. The marked decrease in signaling efficacy of I177A and F178A also indicates that IIe 177(4.63) and Phe 178(4.64) are important in stabilizing receptor-active conformations. These findings suggest that the TM4/ECL2 junction is crucial for peptide ligand binding and, consequently, for ligand-induced receptor conformational selection. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


News Article | December 7, 2016
Site: www.latimes.com

Researchers in Spain have taken a key step in unraveling one of nature’s most malignant mysteries: How do cancerous tumor cells that establish a beachhead in one organ strike out in search of new territory to colonize? And more important, how might they be stopped? Some answers to those questions came Wednesday in a study published in the journal Nature. In a series of experiments using human oral cancer cells implanted in mice, scientists at Barcelona's Institute for Research in Biomedicine focused on a single protein that sits on the surface of some cancer cells. Known only as CD36, this protein helps usher a key energy source — fatty acids — into the cell for use as fuel. The presence of CD36 on a cell’s surface was revealing. Amid millions of cells that make up a tumor, only a very small number are equipped with this telltale fatty acid receptor. Within groups of oral cancer cells transferred from humans to mice, these were among the first to break free of their beachhead in search of new territory, the scientists found. They functioned as cancer’s expeditionary forces, plying the body’s bloodstream or lymphatic tissue to find new sites to conquer. And they were not limited to oral cancers:  The same fat-metabolizing proteins appear to play a key role in spurring metastasis in ovarian, bladder and lung cancers, and possibly others. The researchers, led by stem cell biologist Salvador Aznar Benitah, used this finding to develop two experimental antibody treatments capable of disarming CD36. Ideally, these armies of cloned immune cells would knock out CD36 and deny the expansionist cancer cells the means, or perhaps just the impetus, to wander beyond their place of origin. It worked. Among the mice implanted with human cancer cells, those that got an infusion of cloned antibodies every three days showed no metastases, even though the cancer cells had established themselves firmly inside the lab animals’ mouths. When mice whose cancer had already metastasized got daily infusions of the antibodies, their lymph node metastases shrunk by 80% to 90%. And in 15% to 20% of these mice, the antibodies brought about complete remission. The new findings suggest that fatty acids — dietary fats that are plentiful in all modern human diets and ubiquitous in Western diets — play an outsize role in promoting cancer’s spread. When mice were fed a high-fat diet and seeded with human cancer cells, they developed more and larger lymph node metastases. And researchers found one type of fat that encouraged metastasis with particular effectiveness. The researchers bathed human oral cancer cells in palmitic acid — a type of fat widely added to modern processed food — and injected the treated cells into the tongues of mice. The animals’ original tumors did not change in size. But the size and frequency of lymph node metastases increased markedly. Indeed, 10% of the affected mice saw their cancer spread to the lung, a very rare metastasis for this type of cancer. The finding that dietary fats and large stores of excess fat contribute to cancer’s spread is not new. University of Chicago cancer researcher Ernst Lengyel and his colleagues discovered in 2011 that dietary fat was a key promoter of metastasis in ovarian cancer. Lengyel, who wasn’t involved in the new research, called the Nature paper “fantastic.” But he cautioned that it is far too early for cancer patients to halt their consumption of fat in a bid to prevent their disease from spreading. “You can take away from this paper that cancer cells depend on the nutrients in their environment,” Lengyel said. But, he added, “fatty acids have very important roles for normal cells and also help immune cells to protect the body from the tumor.” So cutting consumption of all fats could be harmful, he said. The findings are striking, given that 90% of the world’s 7.6 million cancer deaths each year come after a cancer has metastasized. Benitah said his team is working with a London-based medical research charity, MRC Technology, to identify human versions of the mouse antibodies that have shown such promise in blocking cancer’s spread. The work of identifying those human antibodies, and of beginning to test them in humans, is expected to take up to 10 years, Benitah said. However, with a few lucky breaks, antibodies capable of knocking out CD36 in human cells could be found in just three or four years, he said. “Science is much tougher than many people might think. We constantly have negative results and failure,” Benitah said. But his lab’s four-year quest to find a way to block the spread of cancer has given him some “magical moments,” he said, and “this is what we’re here for.” Follow me on Twitter @LATMelissaHealy and "like" Los Angeles Times Science & Health on Facebook. Click here for a Spanish version of this story States with background checks of those who buy guns and bullets also have fewer school shootings Explosives detector works 16 times better when it can ‘sniff’ like a dog Here's something Americans disagree about that has nothing to do with partisan politics: food


News Article | December 7, 2016
Site: www.eurekalert.org

A study headed by Salvador Aznar Benitah, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona), and published today in Nature identifies metastasis-initiating cells through a specific marker, namely the protein CD36. This protein, which is found in the membranes of tumour cells, is responsible for taking up fatty acids. CD36 activity and dependence on lipid (fat) metabolism distinguish metastasis-initiating cells from other tumour cells. The researchers discovered the metastatic CD36+ cells in samples from patients with oral cancer with different degrees of aggressiveness, provided as part of a collaboration with the Hospital Vall d'Hebrón de Barcelona. In the mouth tumours analysed, very few cells were found to have metastasis-initiating capacity. The addition of CD36 expression to tumours that did not cause metastasis made them become metastatic. Furthermore, the researchers have demonstrated that the effect exerted by CD36 on metastasis is the same for melanoma cells and luminal breast cancer cells. Likewise, statistical analyses of samples from patients reveal that the metastasis of ovarian, bladder and lung cancer are also dependent on CD36. "Although we have not yet tested this in all tumour types, we can state that CD36 is a general marker of metastatic cells, the first marker I know of that is generally specific to metastasis," says Salvador Aznar Benitah, head of the Stem Cell and Cancer Lab at IRB Barcelona. "We can now obtain metastatic cells in the laboratory. This will allow us to trace them and to study, for example, their distribution in the tumour, where they anchor when they leave it, or why they are so sensitive to fat, among other questions," adds the first author of the study Gloria Pascual. Dr. Aznar-Benitah pointed that "We expect this study to have a big impact on the scientific community and to further advances in metastasis research, and we hope to be able to validate the potential of CD36 as an anti-metastasis treatment. Things like this don't happen every day." Given the involvement of lipid metabolism in metastasis and the function of CD36 in this process, the next logical question for the researchers was: does fat intake have a direct effect on metastasis? The researchers provided mice with a high-fat diet (15% more fat that normal, equivalent to what a so-called "cafeteria diet"). They then inoculated them with a type of oral cancer, which in standard dietary conditions would lead to 30% of the animals developing metastasis. Strikingly, under the high-fat diet and thus with a greater amount of lipids in blood, around 80% of the mice developed many more and larger metastases. They also tested the effect of a specific fatty acid, palmitic acid, on metastasis. This plant-derived fatty acid is the main component of palm oil, and in lower proportions, of coconut and other oils, and is used in many kinds of processed food. The researchers treated the oral tumours with palmitic acid for two days and then injected them into mice on a standard diet,.An increase from 50 to 100% was observed in the frequency of the metastatic tumour. That is to say, all the mice developed metastasis in a CD36-dependent manner. "In mice inoculated with human tumour cells, there appears to be a direct link between fat intake and an increase in metastatic potential through CD36. More studies are needed to unravel this intriguing relationship between diet and metastasis, above all because industrialised countries are registering an alarming increase in the consumption of saturated fats and sugar," warns Aznar Benitah. "Fat is necessary for the function of the body, but uncontrolled intake can have an effect on health, as already shown for some tumours such as colon cancer, and in metastasis, as we demonstrate here," explains the researcher. The study demonstrates the anti-metastatic effect of blocking the CD36 protein, both in immunodepressed mice and in mice with intact immune systems. Figures were similar for all tests. The inhibition of CD36 when the animals were inoculated with the tumour cells completely eliminated their metastatic potential. In addition, the administration of CD36-blocking antibodies to mice with already established metastases led to total removal of the metastases in 20% of the animals, while for the others it brought about a dramatic reduction of 80-90% in the number of metastatic foci and their size. The mice tolerated the treatment in the therapeutic window required to achieve an anti-metastasis effect and no intolerable side-effects were observed in autopsies, and blood and tissue analyses. IRB Barcelona has applied for IP protection of the results, and the researchers are working with MRC Technology in the UK to co-develop new antibody-based therapeutics against CD36 that are suitable for treatment of patients in a range of cancers. If the development of the novel therapeutic was successful, a new product could be available in 5-10 years. The study has been possible thanks to the collaboration of the Service of Oral and Maxillofacial Surgery, the Service of Pathology Anatomy and the biobank of the Hospital Vall d'Hebrón de Barcelona, with the participation of Coro Bescós and Juan Antonio Hueto from the Vall d'Hebron Institut de Recerca (VHIR). The study is thus the result of collaboration between basic and clinical research and it aims to transform research results into useful treatments for patients. This work has been supported by the Fundació La Marató de TV3, two project grants from the World Wide Cancer Research of the UK, and Fundación Botín and Banco Santander, through Santander Universidades. Furthermore, the laboratory is supported by funding from the European Research Council, the Ministry of Science and Innovation, and the Generalitat de Catalunya (Government of Catalonia).

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