News Article | February 22, 2017
What can’t graphene do? You can scratch “detect cancer” off of that list. By interfacing brain cells onto graphene, University of Illinois at Chicago (UIC) researchers have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, noninvasive tool for early cancer diagnosis. “This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine. “Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry says. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface. “The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry says, referring to a powerful workhorse technique that is routinely used to study graphene. The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry says, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons. “The electric field around the cell pushes away electrons in graphene’s electron cloud,” he says, which changes the vibration energy of the carbon atoms. The change in vibration energy can be pinpointed by Raman mapping with a resolution of 300 nanometers, he says, allowing characterization of the activity of a single cell. The study, reported in the journal ACS Applied Materials & Interfaces, looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumor glioblastoma multiforme. The technique is being studied in a mouse model of cancer, with results that are “very promising,” Berry says. Experiments with patient biopsies would be further down the road. “Once a patient has brain tumor surgery, we could use this technique to see if the tumor relapses,” Berry says. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.” The same technique may also work to differentiate between other types of cells or the activity of cells. “We may be able to use it with bacteria to quickly see if the strain is Gram-positive or Gram-negative,” Berry says. “We may be able to use it to detect sickle cells.” Last year, Berry and other coworkers introduced nanoscale ripples in graphene, causing it to conduct differently in perpendicular directions, useful for electronics. They wrinkled the graphene by draping it over a string of rod-shaped bacteria, then vacuum-shrinking the germs. “We took the earlier work and sort of flipped it over,” Berry says. “Instead of laying graphene on cells, we laid cells on graphene and studied graphene’s atomic vibrations.” Co-authors on the study are Bijentimala Keisham and Phong Nguyen of UIC chemical engineering and Arron Cole of UIC neurosurgery.
News Article | February 15, 2017
Baconfest Chicago Responds to Report of U.S. Bacon Shortage, Urges Calm to Bacon Nation As Ohio Pork Council Reports on 50-Year Low in Bacon Supplies, Promises “No Turkey Bacon” at Upcoming Baconfest Chicago, March 31 & April 1 As U.S. bacon reserves hit a 50-year low, according to the Ohio Pork Council, Baconfest Chicago Co-founder Seth Zurer releases an official statement. Baconfest Co-founder “After encouraging mass consumption of bacon at Baconfest and offering an unlimited supply of bacon delights over the last eight years, I can’t help but feel responsible for this shortage in our national bacon reserves.” Zurer went on to say, “Pork farmers we all need you. America needs you. I challenge you to step it up. Don’t let your country down.” Baconfest is one of Chicago’s top-shelf festivals providing a unique showcase for bacon talent from Food Network stars, Michelin honored chefs (Stars and Bib-Gourmands!) and James Beard nominees, side by side with beloved local chefs on the rise. The two-day event will feature over 150 restaurants, highlighting 40 - 50 of the best chefs in the city at each of the three sessions. For a complete list of participating 2017 Baconfest restaurants, please visit this page. "There will be plenty of bacon at Baconfest,” said Zurer. “I have already been in touch with our sponsors at Nueske’s and can confirm we have an abundance of reserves -- 8,000 pounds of bacon ready for Baconfest #9. We are the Fort Knox of bacon. I will assure all our bacon lovers it is pure pork belly gold. No turkey bacon (whatever that is). I promise no facon!” Nueske’s knows bacon and they’ve been perfecting their Applewood smoked bacon since 1882. As the official Baconfest Chicago bacon supplier, Marketing Director Megan Dorsch urged calm: “Don’t panic. We’ve got bacon. It’s delicious and we’ll feed it to the bacon-lovers of Bacon Nation in Chicago.” Tickets are on sale now for the 9th annual Baconfest held on March 31 and April 1 at the UIC Forum located at 725 West Roosevelt. Tickets are available at baconfestchicago.com/ticket and are $100 for General Admission and $200 for VIP. All ticket holders get access to their selected General Admission session, including unlimited bacon dishes from 40-50 chefs as well as seven drink tickets good for beer, wine, and cocktails. VIP ticket holders are allowed one hour of early access to the session selected, with no crowds and unfettered access to bacon pleasure. ###
News Article | October 28, 2016
VANCOUVER, BC--(Marketwired - October 27, 2016) - Excelsior Mining Corp. (TSX VENTURE: MIN) ( : 3XS) ( : EXMGF) ("Excelsior" or the "Company") is pleased to announce the results of the Company's Annual General Meeting of Shareholders held on October 27 in Vancouver (the "AGM"), including the approval of the US$14 million financing. Excelsior is also pleased to provide an update on the permitting process for the Gunnison Copper Project in Cochise County, Arizona ("Gunnison Project"). On September 29, 2016, Excelsior announced a US$14 million Private Placement and Royalty financing (the "Financing") with an affiliate of Greenstone Resources L.P. ("Greenstone") (See Excelsior News Release September 29, 2016). This Financing required approval from the Company's shareholders and the Company confirms that at the AGM shareholders (excluding Greenstone) approved a resolution permitting the Company to proceed with the Financing. The Company is working to satisfy all of the outstanding closing conditions associated with the Financing. Assuming all closing conditions are satisfied, the Company intends to close the Financing during the first half of November 2016. Shareholders at the AGM also passed resolutions approving the election of the nominees listed in the management information circular for the AGM, the re-appointment of the Company's auditors and amendments to the Company's stock option plan. Excelsior has been working with the Arizona Department of Environmental Quality ("ADEQ") towards the issuance of the Aquifer Protection Permit ("APP") for the Gunnison Copper Project. As part of the ADEQ's technical review process, Excelsior received a "Comprehensive Request for Information" from the ADEQ on June 17, 2016. Since this time, Excelsior's permitting team has worked diligently to provide a detailed response to the ADEQ's request and this has now been successfully submitted. This represents a major milestone in the advancement of Excelsior's APP application. In parallel, Excelsior is working towards the issuance of the Underground Injection Control ("UIC") Permit with the US Environmental Protection Agency ("EPA"). The UIC permit application is under technical review and the Company is pleased with the current EPA process. Excelsior expects draft permits to be issued for public review in early 2017. Excelsior considers its permitting timetable to be on schedule and the Company anticipates initial production from the Gunnison Project in 2018. Commenting on this news, Rebecca Sawyer, VP Sustainability, said, "The ADEQ and the EPA continue to demonstrate their proficiency as we move into the advanced stages of the permitting process. We remain confident that the efficiency of the state and federal permitting procedures, combined with the straightforward aspects of the Gunnison Copper Project, will result in the timely issuance of operating permits that ensure compliance with environmental standards." Excelsior Mining "The Copper Solution Company" is a mineral exploration and development company that is advancing the Gunnison Copper Project in Cochise County, Arizona. The project is an advanced staged, low cost, environmentally friendly in-situ recovery copper extraction project that is scheduled for commercial production in 2018. Further information about the Gunnison Copper Project can be found in the technical report filed on SEDAR at www.sedar.com entitled: "Gunnison Copper Project, NI 43-101 Technical Report, Prefeasibility Study Update" dated effective January 28, 2016. Excelsior's technical work on the Gunnison Copper Project is supervised by Stephen Twyerould, Fellow of AUSIMM, President & CEO of Excelsior and a Qualified Person as defined by National Instrument 43-101. Mr. Twyerould has reviewed and approved the technical information contained in this news release. For more information on Excelsior, please visit our website at www.excelsiormining.com. ON BEHALF OF THE EXCELSIOR BOARD "Stephen Twyerould" President & CEO This news release contains "forward-looking information" concerning anticipated developments and events that may occur in the future. Forward-looking information contained in this news release includes, but is not limited to, statements with respect to: (i) the closing of the Financing; (ii) the commencement of commercial production from the Gunnison Project; (iii) the timelines associated with the permitting process; (iv) the issuance of permits for the Gunnison Project; and (v) the ability to mine the Gunnison Project using in-situ recovery mining techniques. In certain cases, forward-looking information can be identified by the use of words such as "plans", "expects" or "does not expect", "is expected", "budget", "scheduled", "estimates", "forecasts", "intends", "anticipates" or "does not anticipate", or "believes", or variations of such words and phrases or state that certain actions, events or results "may", "could", "would", "might" or "will be taken", "occur" or "be achieved" suggesting future outcomes, or other expectations, beliefs, plans, objectives, assumptions, intentions or statements about future events or performance. Forward-looking information contained in this news release is based on certain factors and assumptions regarding, among other things, the estimation of mineral resources and mineral reserves, the realization of resource and reserve estimates, copper and other metal prices, the timing and amount of future exploration and development expenditures, the estimation of initial and sustaining capital requirements, the estimation of labour and operating costs, the availability of necessary financing and materials to continue to explore and develop the Gunnison Project in the short and long-term, the progress of exploration and development activities, the receipt of necessary regulatory approvals, the completion of the permitting process, the estimation of insurance coverage, and assumptions with respect to currency fluctuations, environmental risks, title disputes or claims, and other similar matters. While the Company considers these assumptions to be reasonable based on information currently available to it, they may prove to be incorrect. Forward looking information involves known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of the Company to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information. Such factors include risks inherent in the exploration and development of mineral deposits, including risks relating to changes in project parameters as plans continue to be redefined including the possibility that mining operations may not commence at the Gunnison Project, risks relating to variations in mineral resources and reserves, grade or recovery rates resulting from current exploration and development activities, risks relating to the ability to access infrastructure, risks relating to changes in copper and other commodity prices and the worldwide demand for and supply of copper and related products, risks related to increased competition in the market for copper and related products and in the mining industry generally, risks related to current global financial conditions, uncertainties inherent in the estimation of mineral resources, access and supply risks, reliance on key personnel, operational risks inherent in the conduct of mining activities, including the risk of accidents, labour disputes, increases in capital and operating costs and the risk of delays or increased costs that might be encountered during the development process, regulatory risks, including risks relating to the acquisition of the necessary licenses and permits, financing, capitalization and liquidity risks, including the risk that the financing necessary to fund the exploration and development activities at the Gunnison Project may not be available on satisfactory terms, or at all, risks related to disputes concerning property titles and interest, environmental risks and the additional risks identified in the "Risk Factors" section of the Company's reports and filings with applicable Canadian securities regulators. Although the Company has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking information, there may be other factors that cause actions, events or results not to be as anticipated, estimated or intended. Accordingly, readers should not place undue reliance on forward-looking information. The forward-looking information is made as of the date of this news release. Except as required by applicable securities laws, the Company does not undertake any obligation to publicly update or revise any forward-looking information. Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release, and no securities regulatory authority has either approved or disapproved of the contents of this release.
News Article | February 15, 2017
People who eat a gluten-free diet may be at risk for increased exposure to arsenic and mercury - toxic metals that can lead to cardiovascular disease, cancer and neurological effects, according to a report in the journal Epidemiology. Gluten-free diets have become popular in the U.S., although less than 1 percent of Americans have been diagnosed with celiac disease - an out-of-control immune response to gluten, a protein found in wheat, rye and barley. A gluten-free diet is recommended for people with celiac disease, but others often say they prefer eating gluten-free because it reduces inflammation - a claim that has not been scientifically proven. In 2015, one-quarter of Americans reported eating gluten-free, a 67 percent increase from 2013. Gluten-free products often contain rice flour as a substitute for wheat. Rice is known to bioaccumulate certain toxic metals, including arsenic and mercury from fertilizers, soil, or water, but little is known about the health effects of diets high in rice content. Maria Argos, assistant professor of epidemiology in the UIC School of Public Health, and her colleagues looked at data from the National Health and Nutrition Examination Survey searching for a link between gluten-free diet and biomarkers of toxic metals in blood and urine. They found 73 participants who reported eating a gluten-free diet among the 7,471 who completed the survey, between 2009 and 2014. Participants ranged in age from 6 to 80 years old. People who reported eating gluten-free had higher concentrations of arsenic in their urine, and mercury in their blood, than those who did not. The arsenic levels were almost twice as high for people eating a gluten-free diet, and mercury levels were 70 percent higher. "These results indicate that there could be unintended consequences of eating a gluten-free diet," Argos said. "But until we perform the studies to determine if there are corresponding health consequences that could be related to higher levels of exposure to arsenic and mercury by eating gluten-free, more research is needed before we can determine whether this diet poses a significant health risk." "In Europe, there are regulations for food-based arsenic exposure, and perhaps that is something we here in the United States need to consider," Argos said. "We regulate levels of arsenic in water, but if rice flour consumption increases the risk for exposure to arsenic, it would make sense to regulate the metal in foods as well." Catherine Bulka of UIC; Matthew Davis of the University of Michigan; Margaret Karagas of Dartmouth University; and Habibul Ahsan of the University of Chicago are co-authors on the paper. This research was supported by National Institutes of Health grants R01 ES024423, R21 ES024834, R01 CA107431, P42 ES010349 and T32 HL125294.
News Article | November 3, 2016
Two widely prescribed antibiotics -- chloramphenicol and linezolid -- may fight bacteria in a different way from what scientists and doctors thought for years, University of Illinois at Chicago researchers have found. Instead of indiscriminately stopping protein synthesis, the drugs put the brakes on the protein synthesis machinery only at specific locations in the gene. Ribosomes are among the most complex components in the cell, responsible for churning out all the proteins a cell needs for survival. In bacteria, ribosomes are the target of many important antibiotics. The team of Alexander Mankin and Nora Vazquez-Laslop has conducted groundbreaking research on the ribosome and antibiotics. In their latest study, published in the Proceedings of the National Academy of Sciences, they found that while chloramphenicol and linezolid attack the catalytic center of the ribosome, they stop protein synthesis only at specific checkpoints. "Many antibiotics interfere with the growth of pathogenic bacteria by inhibiting protein synthesis," says Mankin, director of the UIC Center for Biomolecular Sciences and professor of medicinal chemistry and pharmacognosy. "This is done by targeting the catalytic center of the bacterial ribosome, where proteins are being made. It is commonly assumed that these drugs are universal inhibitors of protein synthesis and should readily block the formation of every peptide bond." "But -- we have shown that this is not necessarily the case," said Vazquez-Laslop, research associate professor of medicinal chemistry and pharmacognosy. A natural product, chloramphenicol is one of the oldest antibiotics on the market. For decades it has been useful for many bacterial infections, including meningitis, plague, cholera and typhoid fever. Linezolid, a synthetic drug, is a newer antibiotic used to treat serious infections -- streptococci and methicillin-resistant Staphylococcus aureus (MRSA), among others -- caused by Gram-positive bacteria that are resistant to other antibiotics. Mankin's previous research established the site of action and mechanism of resistance to linezolid. While the antibiotics are very different, they each bind to the ribosome's catalytic center, where they were expected to inhibit formation of any peptide bond that links the components of the protein chain into a long biopolymer. In simple enzymes, an inhibitor that invades the catalytic center simply stops the enzyme from doing its job. This, Mankin said, had been what scientists had believed was also true for antibiotics that target the ribosome. "Contrary to this view, the activity of chloramphenicol and linezolid critically depends on the nature of specific amino acids of the nascent chain carried by the ribosome and by the identity of the next amino acid to be connected to a growing protein," Vazquez-Laslop said. "These findings indicate that the nascent protein modulates the properties of the ribosomal catalytic center and affects binding of its ligands, including antibiotics." Combining genomics and biochemistry has allowed the UIC researchers to better understand how the antibiotics work. "If you know how these inhibitors work, you can make better drugs and make them better tools for research," said Mankin. "You can also use them more efficiently to treat human and animal diseases."
News Article | February 15, 2017
Probiotics may hold part of the key to treating ALS. New research led by Kansas City University of Medicine and Biosciences(KCU) scientist Jingsong Zhou, PhD and Jun Sun, PhD of University of Illinois at Chicago (UIC) found an imbalance of bacteria in the digestive tract may contribute to the progression of Amyotrophic Lateral Sclerosis (ALS). Their preliminary research suggests probiotics could be a potential therapy for the disease. The study which appears in the journal Clinical Therapies, found evidence that targeting gut microbiota with natural bacteria products was successful in alleviating ALS progression in animal models. https://www.ncbi.nlm.nih.gov/pubmed/28129947 ALS is a fatal disease with progressive loss of motor neurons. The only current treatment approved by the US Food and Drug Administration extends life by just a few months. “Due to the severe and rapidly progressing neuromuscular symptoms, the majority of study on ALS has focused on neurodegeneration,” said Zhou. “We hope that our published studies will draw attention from the research field, encouraging more investigators to consider ALS as a systemic disorder by evaluating the potential contributors outside of the nervous system.” While Zhou and her colleagues are encouraged by what they believe is a solid step forward, Zhou says the work is still in the preliminary stages. “There is a lot to do before we can translate the basic research to finally treat ALS patients,” Zhou said. Robert White, PhD, dean of the KCU College of Biosciences said Zhou and her colleagues are contributing crucial knowledge about the devastating disease. “This research represents a significant and innovative approach to understanding and treating ALS,” said White. “Dr. Zhou is a nationally recognized researcher in this field, and we are delighted to have her at KCU.” Funding for the research came from one of 58 ALS Association grants totaling $11.6 million, which was raised through the international Ice Bucket challenge. About Kansas City University The Kansas City University of Medicine and Biosciences (KCU), founded in 1916, is a fully accredited, private not-for-profit university with a College of Biosciences and a College of Osteopathic Medicine. The College of Osteopathic Medicine is the oldest medical school in Kansas City, Mo., and the largest in the state. KCU is the second-leading producer of physicians for both the states of Missouri and Kansas. KCU will open a second medical school in Joplin, Mo., in 2017 to help address the growing need for primary care physicians in the region’s rural communities.
News Article | December 20, 2016
What can’t graphene do? You can scratch “detect cancer” off of that list. By interfacing brain cells onto graphene, researchers at the University of Illinois at Chicago have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, noninvasive tool for early cancer diagnosis. “This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering at UIC, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine. “Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry says. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface. “The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry says, referring to a powerful workhorse technique that is routinely used to study graphene. The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry says, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons. “The electric field around the cell pushes away electrons in graphene’s electron cloud,” he says, which changes the vibration energy of the carbon atoms. The change in vibration energy can be pinpointed by Raman mapping with a resolution of 300 nanometers, he says, allowing characterization of the activity of a single cell. The study, reported in the journal ACS Applied Materials & Interfaces, looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumor glioblastoma multiforme. The technique is now being studied in a mouse model of cancer, with results that are “very promising,” Berry says. Experiments with patient biopsies would be further down the road. “Once a patient has brain tumor surgery, we could use this technique to see if the tumor relapses,” Berry says. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.” The same technique may also work to differentiate between other types of cells or the activity of cells. “We may be able to use it with bacteria to quickly see if the strain is Gram-positive or Gram-negative,” Berry says. “We may be able to use it to detect sickle cells.” Earlier this year, Berry and other coworkers introduced nanoscale ripples in graphene, causing it to conduct differently in perpendicular directions, useful for electronics. They wrinkled the graphene by draping it over a string of rod-shaped bacteria, then vacuum-shrinking the germs. “We took the earlier work and sort of flipped it over,” Berry says. “Instead of laying graphene on cells, we laid cells on graphene and studied graphene’s atomic vibrations.” Co-authors on the study are Bijentimala Keisham and Phong Nguyen of UIC chemical engineering and Arron Cole of UIC neurosurgery.
News Article | March 2, 2017
Blocking a protein found on the surface of ovarian cancer cells could prevent or reduce the spread of the disease to other organs, according to new research at the University of Illinois at Chicago. The American Cancer Society estimates that 22,440 women in the U.S. will receive a new diagnosis of ovarian cancer this year. About 15,000 will die from the disease, which ranks fifth in cancer deaths among women and No. 1 among cancers of the female reproductive system. It is often diagnosed in a late stage, after the cancer has spread to other organs, making it incurable to currently available treatment options. "The greatest barrier to our ability to treat cancer in this stage is that we know very little about the molecules that cause the disease to spread," said Maria Barbolina, associate professor of biopharmaceutical sciences and lead researcher of the study. "The goal of our research is to identify key molecules that govern metastasis and use them as targets for the development of new drugs." Barbolina and her colleagues hypothesized that biomolecules successfully targeted with drugs in other cancers might also be targets in metastatic ovarian cancer. In earlier research, Barbolina discovered that a fractalkine receptor -- a protein found on the cell surface -- is expressed in the majority of ovarian cancer cases. It could help the cancer spread to other organs throughout the body when stimulated by another protein that binds to it. In her latest findings, published in the journal Oncogene, Barbolina demonstrated in a mouse model that by lowering production of the fractalkine receptor, tumors did not metastasize to nearby sites of the peritoneal wall, bowel or liver. Nearly a third of all cancer drugs target G protein-coupled receptors, of which fractalkine is one, so "we reasoned that blocking it may prevent or reduce ovarian cancer metastasis, because it's expressed in 64 percent of metastatic ovarian carcinoma specimens," Barbolina said. Symptoms of ovarian cancer include bloating, pelvic or abdominal pain, feeling of fullness, or urinary tract complaints. The cancer mainly develops in older women, after menopause -- about half are 63 or older. A woman's lifetime risk of getting ovarian cancer is about one in 75. The research was funded by the National Cancer Institute (grant number CA160917) and Ovarian Cancer Research Foundation Liz Tilberis Scholar Award. Co-authors of the study include Hilal Gurler Main, Jia Xie and Goda Muralidhar of the UIC College of Pharmacy, and pathologists Osama Elfituri, Haoliang Xu and Andre Kajdacsy-Balla of the UIC College of Medicine.
News Article | November 8, 2016
Researchers at the University of Illinois at Chicago have identified a new way to block the action of genetic mutations found in nearly 30 percent of all cancers. Mutations in genes for the RAS family of proteins are present in nearly 90 percent of pancreatic cancers and are also highly prevalent in colon cancer, lung cancer and melanoma, the most dangerous kind of skin cancer. The group of proteins include three members, K-RAS, H-RAS and N-RAS. The prevalence of RAS mutations in human cancers and the dependence of tumors on RAS for survival has made a RAS a prime target for cancer research and drug discovery. Scientists and drug developers have long studied RAS oncogenes hoping to find a new treatment for cancer, but they have not yet been able to identify drugs that safely inhibit the oncogene's activity. John O'Bryan, associate professor of pharmacology in the UIC College of Medicine, led a team of researchers that took a different approach to studying RAS, and discovered that a synthetic binding protein they call "NS1 monobody," which they created in the lab, can block the activity of the RAS proteins. "We did not look for a drug or specifically for an inhibitor," said O'Bryan, who is also a member of the University of Illinois Cancer Center and holds an appointment at the Jesse Brown VA Medical Center in Chicago. "We used monobody technology, a type of protein-engineering technology, to identify regions of RAS that are critical for its function." Unlike conventional antibodies, monobodies are not dependent on their environment and can be readily used as genetically encoded inhibitors, O'Bryan said. "The beauty of the technology is that when a monobody binds a protein, it usually works as an inhibitor of that protein," he said. Monobodies were developed by Shohei Koide, a co-author on the study who is professor of biochemistry and molecular pharmacology at New York University. They have been used to target a diverse array of proteins that include enzymes and receptors. The researchers found that the NS1 monobody binds to an area of the RAS protein molecule that was not previously known to be important for its oncogenic activity. NS1 strongly inhibits oncogenic K-RAS and H-RAS function by blocking the ability of the protein to interact with an identical one to form a molecular pair. NS1 does not affect N-RAS. O'Bryan says the findings, published in the journal Nature Chemical Biology, provide important insight into long-standing questions about how RAS proteins function in cells. These insights may help guide the development of new therapeutic approaches to treating cancer by interfering with mutant RAS function in cancer cells. "Development of effective RAS inhibitors represents a 'holy grail' in cancer biology," O'Bryan said. "We now have a powerful tool we can use to further probe RAS function. While future studies and trials are needed before these findings can be leveraged outside the lab, this study provides new insight into how we can potentially inhibit RAS to slow tumor growth."
News Article | March 1, 2017
A chemical found in tumors may help stop tumor growth, according to a new study. Researchers at the University of Illinois at Chicago report that increasing expression of a chemical cytokine called LIGHT in mice with colon cancer activated the immune system's natural cancer-killing T-cells and caused primary tumors and metastatic tumors in the liver to shrink. LIGHT is an immune-stimulating chemical messenger previously found to have low levels of expression in patients with colon cancer metastases. The results are published in Cancer Research. Colon cancer is the second-leading cause of cancer-related death in the U.S. and, despite advances in treatment, long-term survival of patients with liver metastases is rare. "For most patients with colon cancer that has spread to the liver, current treatments are palliative and not curative," says Dr. Ajay Maker, associate professor of surgery in the UIC College of Medicine and corresponding author on the paper. "And while studies have suggested that immunotherapy may be a promising approach for advanced cancers, the use of such treatments for advanced gastrointestinal metastases have not yet been very successful." Maker, a surgical oncologist, says that this study is exciting because it looks at an immunotherapy intervention for a previously unresponsive gastrointestinal cancer. The intervention, he says, essentially trains the immune system to recognize and attack the tumor, and to protect against additional tumor formation--a significant issue in colon cancer. Maker and his colleagues established colon cancer tumors in a mouse model, in which the animals had an intact and unedited immune system. Once tumors were sizable, the mice were randomized into two groups--one group had the cytokine LIGHT turned on in the tumors, and the other served as a control group for comparison. Tumors exposed to LIGHT showed an influx of T-cells that resulted in rapid and sustained diminishment in size, even after expression of the cytokine stopped. In mice with liver metastases, expression of LIGHT similarly provoked a potent immune response that resulted in a significant decrease in tumor burden. "We demonstrated that delivery of a therapeutic immune-stimulating cytokine caused T-cells to traffic to tumors and to become activated tumor-killing cells," Maker said. "This activity is especially exciting because it resulted in a profound anti-tumor immune response without any other chemotherapy or intervention. The treatment manipulates our natural defenses to fight off the tumor in the same way it has been trained to attack other foreign invaders in our body." "Not only did we find that LIGHT expression promoted tumor regression, upon further study we also identified the specific type of T-cell -- CD8 -- that was responsible for shrinking the tumor," Maker said. "These findings are powerful and have great clinical potential." Co-authors on the paper are Guilin Qiao, Jianzhong Qin, Nicholas Kunda, Jed Calata, Dolores Mahmud, Peter Gann and Bellur Prabhakar of UIC; Yang-Xin Fu of the University of Texas Southwestern; and Steven Rosenberg of the National Cancer Institute. The study was funded by grant number K08CA190855 from the National Cancer Institute, one of the National Institutes of Health.