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News Article | February 14, 2017
Site: www.chromatographytechniques.com

A breakthrough trial at the University of Minnesota testing a new UMN-developed drug resulted in improved survival rates for dogs diagnosed with a cancer called hemangiosarcoma (HSA). The results were published today in the journal Molecular Cancer Therapeutics. “This is likely the most significant advance in the treatment of canine HSA in the last three decades,” said study co-author Jaime Modiano, professor in the University of Minnesota College of Veterinary Medicine and member of the Masonic Cancer Center, University of Minnesota. Canine HSA is a common, aggressive, incurable sarcoma. It is remarkably similar to angiosarcoma, which affects humans. Both cancers typically spread before diagnosis and the survival time for affected patients is extremely short, even with aggressive treatment. Only 50% of humans diagnosed with angiosarcoma live longer than 16 months and the prognosis for dogs with HSA is similarly dire: less than 50% will survive 4-6 months and only about 10% will be alive one-year after their diagnosis. The study tested a drug called eBAT, invented by study senior author Daniel Vallera, professor at the University of Minnesota Medical School and Masonic Cancer Center. “eBAT was created to specifically target tumors while causing minimal damage to the immune system. HSA is a vascular cancer, meaning it forms from blood vessels. eBAT was selected for this trial because it can simultaneously target the tumor and its vascular system,” said Vallera. Traditional cancer treatments have side effects that can be very hard on patients. “In this trial we aimed for a sweet spot by identifying a dose of eBAT that was effective to treat the cancer, but caused no appreciable harm to the patient. Essentially we’re treating the cancer in a safer and more effective way, improving quality of life and providing a better chance at survival,” lead study author Antonella Borgatti, associate professor with the University of Minnesota College of Veterinary Medicine said. eBAT was tested on 23 dogs of various breeds, both large and small, with HSA of the spleen. Dogs received three treatments of eBAT after surgery to remove the tumor and before conventional chemotherapy. The drug treatment improved the 6-month survival rate to approximately 70%. Furthermore, five of the 23 dogs that received eBAT treatment lived more than 450 days. The positive results for canine patients, the similarities between this cancer and angiosarcoma in humans, and the fact that many other tumor types can be targeted by eBAT, make a strong case for translating this drug into clinical trials for human cancer patients. The researchers want these results to bring hope to those touched by this disease. “This drug was invented, developed, manufactured, and tested and showed positive results at the University of Minnesota. We would also like this drug to achieve positive outcomes for humans here,” Modiano said. “The ultimate goal for all of us is to create a world in which we no longer fear cancer,” Modiano said. This project is an example of the remarkable progress that is being made through collaborations among the multiple colleges and schools within the University of Minnesota’s Academic Health Center. Funding was provided by many sources, including various foundations and individuals along with the National Institutes of Health, showing the broad interest in identifying cures for these devastating cancers.


Bottom Line: Survivors of melanoma were more likely to limit exposure to the sun than people who had never had the disease, but some still reported seeking out suntans and getting sunburns. Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research. Author: Rachel Isaksson Vogel, PhD, an assistant professor in the Department of Obstetrics, Gynecology and Women's Health at the University of Minnesota. Background: Incidence of melanoma, the deadliest form of skin cancer, has risen steadily for the past 30 years. Melanoma is now the sixth most common cancer in the United States, with an estimated 76,380 cases diagnosed in 2016, according to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Ultraviolet radiation from the sun has been proven to cause melanoma. How the Study Was Conducted and Results: In this study, Vogel and colleagues compared sun exposure and protection behaviors in long-term melanoma survivors with those who had never had the disease, asking participants about the amount of time they had spent outdoors in the summer, and about sun protection methods such as wearing sunscreen, staying in the shade, wearing hats, and intentionally tanning. Participants were also asked to report the number of red or painful sunburns they had experienced in the past year, and whether they had used a tanning bed or booth in the past year. The study comprised 724 melanoma survivors and 660 controls. All were between the ages of 25 and 59, and the survivors had been diagnosed with invasive cutaneous melanoma between July 2004 and December 2007. Overall, Vogel said, the survivors were more likely to report optimal sun protection behaviors than those in the control group. Some highlights: However, the study revealed suboptimal behaviors in some melanoma survivors. Nearly 20 percent said they had gotten sunburned in the previous year, and on weekend days, sun exposure was roughly equal between the two groups, with 74.8 percent of the survivors and 79.7 percent of the controls spending more than two hours outside. Author Comment: "At a time when rates of many cancer types are declining, the rising incidence of melanoma is worrisome," Vogel said. "People who have survived melanoma are at high risk of another diagnosis, so reducing exposure to the sun is really crucial." Vogel said that in conversations with individuals diagnosed with melanoma, many survivors expressed a desire to "just live their lives," playing with their children, exercising, and socializing outdoors. She said that in most cases, the participants had been diagnosed with stage 1 disease, when melanoma is often easily treated and has a five-year survival rate of 98 percent. "Because an early-stage melanoma diagnosis and treatment was likely a fairly minor experience for most survivors, they might not understand how serious an illness this is," Vogel said. "Survivors of melanoma have a nearly nine-fold risk of developing melanoma again, and they can reduce that risk if they make sun protection a priority." Limitations: Vogel noted that one limitation of the study is that data on second primary melanomas--a new diagnosis at a different site than the initial diagnosis-- were not available for all participants. Also, she said, it is possible that some subjects over-reported their sun protection behaviors. Funding & Disclosures: This study was funded by a grant from the Masonic Cancer Center of the University of Minnesota's Internal Grants Program, as well as a grant from the National Cancer Institute. Vogel declares no conflicts of interest. About the American Association for Cancer Research Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with nearly 19,500 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www. . To interview Rachel Isaksson Vogel, contact Julia Gunther at julia.gunther@aacr.org or 215-446-6896.


News Article | February 15, 2017
Site: www.eurekalert.org

A breakthrough trial at the University of Minnesota testing a new UMN-developed drug resulted in improved survival rates for dogs diagnosed with a cancer called hemangiosarcoma (HSA). The results were published today in the journal Molecular Cancer Therapeutics. "This is likely the most significant advance in the treatment of canine HSA in the last three decades," said study co-author Jaime Modiano, V.M.D., Ph.D. professor in the University of Minnesota College of Veterinary Medicine and member of the Masonic Cancer Center, University of Minnesota. Canine HSA is a common, aggressive, incurable sarcoma. It is remarkably similar to angiosarcoma, which affects humans. Both cancers typically spread before diagnosis and the survival time for affected patients is extremely short, even with aggressive treatment. Only 50% of humans diagnosed with angiosarcoma live longer than 16 months and the prognosis for dogs with HSA is similarly dire: less than 50% will survive 4-6 months and only about 10% will be alive one-year after their diagnosis. The study tested a drug called eBAT, invented by study senior author Daniel Vallera, Ph.D., professor at the University of Minnesota Medical School and Masonic Cancer Center. "eBAT was created to specifically target tumors while causing minimal damage to the immune system. HSA is a vascular cancer, meaning it forms from blood vessels. eBAT was selected for this trial because it can simultaneously target the tumor and its vascular system," said Vallera. Traditional cancer treatments have side effects that can be very hard on patients. "In this trial we aimed for a sweet spot by identifying a dose of eBAT that was effective to treat the cancer, but caused no appreciable harm to the patient. Essentially we're treating the cancer in a safer and more effective way, improving quality of life and providing a better chance at survival," lead study author Antonella Borgatti, D.V.M., M.S., associate professor with the University of Minnesota College of Veterinary Medicine said. eBAT was tested on 23 dogs of various breeds, both large and small, with HSA of the spleen. Dogs received three treatments of eBAT after surgery to remove the tumor and before conventional chemotherapy. The drug treatment improved the 6-month survival rate to approximately 70%. Furthermore, five of the 23 dogs that received eBAT treatment lived more than 450 days. The positive results for canine patients, the similarities between this cancer and angiosarcoma in humans, and the fact that many other tumor types can be targeted by eBAT, make a strong case for translating this drug into clinical trials for human cancer patients. The researchers want these results to bring hope to those touched by this disease. "This drug was invented here at the University of Minnesota, developed here, manufactured here, tested here and showed positive results here. We would also like this drug to achieve positive outcomes for humans here," Modiano said. "The ultimate goal for all of us is to create a world in which we no longer fear cancer," Modiano said. This project is an example of the remarkable progress that is being made through collaborations among the multiple colleges and schools within the University of Minnesota's Academic Health Center. Funding was provided by many sources, including various foundations and individuals along with the National Institutes of Health, showing the broad interest in identifying cures for these devastating cancers. The College of Veterinary Medicine improves the health and well-being of animals and people by providing high-quality veterinary training, conducting leading-edge research, and delivering innovative veterinary services. The University of Minnesota Medical School, with its two campuses in the Twin Cities and Duluth, is a leading educator of the next generation of physicians. Our graduates and the school's 3,370 faculty and affiliate physicians and scientists advance patient care, discover biomedical research breakthroughs with more than $177 million in sponsored research annually, and enhance health through world-class patient care for the state of Minnesota and beyond. Visit http://www. to learn more.


Off-the-Shelf Natural Killer Cell Therapy Being Developed to Complement Standard-of-Care Monoclonal Antibody Treatment for Cancer First-of-Kind Product Candidate to be Manufactured from an Engineered Induced Pluripotent Stem Cell Line Intellectual Property Covering Compositions of Novel CD16 and Chimeric Antigen Receptors Exclusively Licensed SAN DIEGO, Feb. 27, 2017 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today an expansion of its research collaboration with the Regents of the University of Minnesota (UMN) to initiate the clinical translation of a first-of-kind product candidate, an off-the-shelf targeted natural killer (NK) cell cancer immunotherapy derived from an engineered induced pluripotent stem cell (iPSC) line. The Company plans to produce the product candidate from a single iPSC that is first genetically engineered to express a high-affinity, non-cleavable CD16 (hnCD16) receptor and then is clonally-expanded to generate a master engineered pluripotent cell line. Similar to master cell lines used for the manufacture of therapeutic antibodies, a master engineered pluripotent cell line can be used to repeatedly create clonal populations of effector cells to enable off-the-shelf treatment of many thousands of patients. Preclinical production runs have shown that a single iPSC can yield a homogeneous population of over one million iPSC-derived NK (iNK) cells. “Using induced pluripotent stem cells, which possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body, is a first-of-kind approach that enables tremendous product development optionality for the Company. Our first announced iPSC-derived cell product candidate, a natural killer cell incorporating CD16 as the targeting element, is derived from a master pluripotent cell line. This line serves as the backbone into which we have engineered other targeting and functional elements, such as chimeric antigen receptors, and from which we can derive effector cells including NK and T cells,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “We look forward to working closely with the FDA and regulatory authorities in other territories in 2017 to advance our revolutionary approach for off-the-shelf cellular immunotherapy into clinical development.” NK cells have been proven to play a major role in cancer immunotherapy including antibody-dependent cellular cytotoxicity (ADCC), which involves targeting of tumor cells by monoclonal antibodies for the treatment of breast, head and neck, colorectal and certain blood cancers. Activation of NK cells through CD16, a receptor that can bind to antibody-coated tumor cells, unleashes potent NK cell-mediated anti-tumor responses including direct lysis of target cells and cytokine secretion for adaptive immune cell recruitment. The Company’s hnCD16 receptor, which is licensed exclusively from UMN, incorporates two unique modifications designed to enhance the anti-tumor activity of NK cells. The receptor has been modified to augment its binding affinity to certain monoclonal antibodies, and also to prevent its shedding from the surface of NK cells upon activation which can otherwise diminish effector function. In preclinical studies, the Company has shown that its hnCD16-iNK cell product candidate exhibits potent and persistent anti-tumor activity in vitro and in vivo in multiple tumor cell recognition and killing assays: The collaboration is being led by renowned NK cell biologist Jeffrey S. Miller, M.D., Deputy Director of the Masonic Cancer Center, University of Minnesota. The Company has exclusively licensed from UMN foundational intellectual property covering compositions of a modified CD16 as well as certain chimeric antigen receptors and of immune cells expressing such receptors, and also maintains an option to exclusively license all intellectual property arising from research and development activities under the collaboration. In addition to its collaboration with UMN, Fate Therapeutics has also partnered with Memorial Sloan Kettering Cancer Center for the development of off-the-shelf T-cell product candidates using engineered iPSCs. Research and development activities are being led by Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair at Memorial Sloan Kettering Cancer Center. About Fate Therapeutics, Inc. Fate Therapeutics is a biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders. The Company's hematopoietic cell therapy pipeline is comprised of NK- and T-cell immuno-oncology programs, including off-the-shelf product candidates derived from engineered induced pluripotent cell lines, and immuno-regulatory programs, including product candidates to prevent life-threatening complications in patients undergoing hematopoietic cell transplantation and to promote immune tolerance in patients with autoimmune disease. Its adoptive cell therapy programs are based on the Company's novel ex vivo cell programming approach, which it applies to modulate the therapeutic function and direct the fate of immune cells. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com. Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the impact, benefits, timing, and conduct of the partnership between the Company and UMN, as well as the capabilities, expertise, and responsibilities of each, and the therapeutic potential of any cellular immunotherapies developed under the partnership. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the success, cost, and timing of research and product development activities under the collaboration, the risk of cessation or delay of any development activities under the collaboration for a variety of reasons, including any inability to develop or manufacture off-the-shelf NK cell products, and the risk that any off-the-shelf NK cell therapies developed under the collaboration may not be suitable for therapeutic applications and may not provide the anticipated therapeutic benefits. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time the Company’s other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.


News Article | November 2, 2016
Site: www.eurekalert.org

MINNEAPOLIS (Nov. 2, 2016) - The Masonic Cancer Center, University of Minnesota is hosting its 7th Annual Cancer Research Symposium today and tomorrow, Nov. 2-3, at TCF Bank Stadium. With the goal of celebrating 25 years of research innovation, discovery, and collaborations, the 2-day event will feature internationally recognized cancer researchers and doctors, many of who currently work or have trained at the Masonic Cancer Center, as well as current trainee presenters that represent the vision of tomorrow. Together, these researchers and trainees will share the work they've explored in many areas of cancer research that have changed lives and move us in new directions. "We're extremely excited to welcome back such esteemed cancer research experts to Minneapolis," said Dr. Douglas Yee, M.D., director of the Masonic Cancer Center. "Their trainee experience here at the Masonic Cancer Center--and the profound research they have led across the country--is invaluable and has made the fight to end cancer more attainable. We hope this motivational event will spur new ideas and collaborations toward developing new research." Dr. Yee will deliver the opening remarks on Nov. 2, followed by a keynote address by one of the National Cancer Institute's Outstanding Investigators, Thomas Kensler, Ph.D., professor of Pharmacology and Chemical Biology at University of Pittsburgh's School of Medicine and Johns Hopkins Bloomberg School of Public Health. Focal points of the symposium include presentations given by Masonic Cancer Center alumni who now work as investigators all over the United States. Topics that will be covered include everything from exercise rehabilitation after breast cancer, to the science of surviving cancer--lessons learned from cancer survivors, to taking apart the complex interactions that influence the evolution of cancer genomes. Collaborations will be highlighted through engaging presentations, as well as on-site poster sessions that feature graduate students and postdoctoral research trainees sharing their most current cancer research findings. "The Masonic Cancer Center, University of Minnesota is proud to bring together a scientifically diverse group of cancer researchers in an environment where they can foster new collaborations and generate new, innovative, and novel ideas," said Dr. Yee. "This event will also allow our graduate students and postdoctoral research trainees an opportunity to see what researchers around the United States are working on, and the types of studies and clinical trials they build on as they work to advance their own research careers." For more information on the 7th Annual Cancer Research Symposium, including a complete list of sponsors and speakers, please visit the symposium event page. Masonic Cancer Center, University of Minnesota is a Comprehensive Cancer Center designated by the National Cancer Institute. For more than 25 years, researchers, educators, and care providers have worked to discover the causes, prevention, detection, and treatment of cancer and cancer-related disease. Learn more about the Masonic Cancer Center at cancer.umn.edu.


News Article | December 19, 2016
Site: www.eurekalert.org

Unprecedented images of cancer genome-mutating enzymes acting on DNA provide vital clues into how the enzymes work to promote tumor evolution and drive poor disease outcomes. These images, revealed by University of Minnesota researchers, provide the first ever high-resolution pictures of molecular complexes formed between DNA and the human APOBEC3A and APOBEC3B enzymes. The research is published today online in Nature Structural and Molecular Biology. The DNA mutating enzymes called APOBECs are a major source of mutation in breast, lung, cervical, head/neck and many other cancer types. "These enzymes normally function to protect us from viral infections," said Reuben Harris, Ph.D., investigator of the Howard Hughes Medical Institute and professor of Biochemistry, Molecular Biology, and Biophysics, member of the Masonic Cancer Center, and associate director of the Institute of Molecular Virology, University of Minnesota. "However, these enzymes can become misregulated in cancer cells and cause mutations in our own genomic DNA. These mutations fuel tumor evolution and promote poor clinical outcomes such as drug resistance and metastasis." With an imaging technique called x-ray crystallography, which uses a high energy x-ray beam to visualize the atomic details of molecules, researchers were able to see an unexpected mode of DNA binding activity. A unique U-shaped DNA conformation and defined pockets for the target cytosine and the adjacent thymine base explains the specific mutation signature left behind by the enzyme interacting with tumor DNA. "Our crystal structures and corroborating biochemical experiments show how APOBEC3A and APOBEC3B engage DNA substrates," said Hideki Aihara, Ph.D., associate professor in the department of Biochemistry, Molecular Biology and Biophysics and member of the Institute of Molecular Virology and the Masonic Cancer Center at the University of Minnesota. "These structures show an unexpected mode of DNA engagement with a sharply bent DNA strand and flipped-out nucleotides. Our findings were surprising, but actually make a lot of sense and explain many previous observations about this family of proteins." The DNA-binding mechanism suggests ways to block enzyme activity in cancer, which could slow the rate at which tumors evolve. Inhibiting APOBEC activity could make current anti-cancer therapies more effective. Work continues to take and analyze additional portraits of these enzymes with different DNA substrates and to devise strategies for enzyme inhibition. Funding for this work is provided by grants from the National Institutes of Health (R01-GM118000, R35-GM118047, R01-GM110129, R21-CA206309, DP2-OD007237, P41-GM103426), the National Science Foundation (CHE060073N), the Prospect Creek Foundation and the Masonic Cancer Center, University of Minnesota. Harris is the Margaret Harvey Schering Land Grant Chair for Cancer Research at the University of Minnesota, and an Investigator of the Howard Hughes Medical Institute. College of Biological Sciences faculty conduct research in all areas of biology from molecules to ecosystems with applications in medicine, environment, and biotechnology. The college offers seven undergraduate majors and five graduate programs. Our highly competitive undergraduate program attracts some of the brightest students at the University of Minnesota. Visit cbs.umn.edub to learn more. Masonic Cancer Center, University of Minnesota is a Comprehensive Cancer Center designated by the National Cancer Institute. For more than 25 years, researchers, educators, and care providers have worked to discover the causes, prevention, detection, and treatment of cancer and cancer-related disease. Learn more about the Masonic Cancer Center at cancer.umn.edu. The University of Minnesota Medical School, with its two campuses in the Twin Cities and Duluth, is a leading educator of the next generation of physicians. Our graduates and the school's 3,370 faculty and affiliate physicians and scientists advance patient care, discover biomedical research breakthroughs with more than $177 million in sponsored research annually, and enhance health through world-class patient care for the state of Minnesota and beyond. Visit http://www. to learn more.


PubMed | University of Minnesota, From the Animal Cancer Care and Research Program and the Masonic Cancer Center
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015

We previously identified two distinct molecular subtypes of osteosarcoma through gene expression profiling. These subtypes are associated with distinct tumor behavior and clinical outcomes. Here, we describe mechanisms that give rise to these molecular subtypes. Using bioinformatic analyses, we identified a significant association between deregulation of the retinoblastoma (RB)-E2F pathway and the molecular subtype with worse clinical outcomes. Xenotransplantation models recapitulated the corresponding behavior for each osteosarcoma subtype; thus, we used cell lines to validate the role of the RB-E2F pathway in regulating the prognostic gene signature. Ectopic RB resets the patterns of E2F regulated gene expression in cells derived from tumors with worse clinical outcomes (molecular phenotype 2) to those comparable with those observed in cells derived from tumors with less aggressive outcomes (molecular phenotype 1), providing a functional association between RB-E2F dysfunction and altered gene expression in osteosarcoma. DNA methyltransferase and histone deacetylase inhibitors similarly reset the transcriptional state of the molecular phenotype 2 cells from a state associated with RB deficiency to one seen with RB sufficiency. Our data indicate that deregulation of RB-E2F pathway alters the epigenetic landscape and biological behavior of osteosarcoma.

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