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News Article | December 12, 2016
Site: www.eurekalert.org

A major challenge in truly targeted cancer therapy is cancer's suppression of the immune system. Northwestern University synthetic biologists now have developed a general method for "rewiring" immune cells to flip this action around. "Right now, one of the most promising frontiers in cancer treatment is immunotherapy -- harnessing the immune system to combat a wide range of cancers," said Joshua N. Leonard, the senior author of the study. "The simple cell rewiring we've done ultimately could help overcome immunosuppression at the tumor site, one of the most intransigent barriers to making progress in this field." When cancer is present, molecules secreted at tumor sites render many immune cells inactive. The Northwestern researchers genetically engineered human immune cells to sense the tumor-derived molecules in the immediate environment and to respond by becoming more active, not less. This customized function, which is not observed in nature, is clinically attractive and relevant to cancer immunotherapy. The general approach for rewiring cellular input and output functions should be useful in fighting other diseases, not just cancer. "This work is motivated by clinical observations, in which we may know why something goes wrong in the body, and how this may be corrected, but we lack the tools to translate those insights into a therapy," Leonard said. "With the technology we have developed, we can first imagine a cell function we wish existed, and then our approach enables us to build -- by design -- a cell that carries out that function." Currently, scientists and engineers lack the ability to program cells to exhibit all the functions that, from a clinical standpoint, physicians might wish them to exhibit, such as becoming active only when next to a tumor. This study addresses that gap, Leonard said. Leonard, who focuses on integrating synthetic biology into medicine, is an associate professor of chemical and biological engineering at the McCormick School of Engineering. He is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The research comes out of a rich collaboration that Leonard's team has with clinical oncologists, immunologists and basic cancer researchers at Northwestern University Feinberg School of Medicine as well as other synthetic biologists. The study, to be published Dec. 12 by the journal Nature Chemical Biology, provides details of the first synthetic biology technology enabling researchers to rewire how mammalian cells sense and respond to a broad class of physiologically relevant cues. Kelly A. Schwarz, a graduate student in Leonard's research group, is the study's first author. "This work is exciting because it addresses a key technical gap in the field," Schwarz said. "There is great promise for using engineered cells as programmable therapies, and it is going to take technologies such as this to truly realize that goal." Starting with human T cells in culture, the research team genetically engineered changes in the cells' input and output, including adding a sensing mode, and built a cell that is relevant to cancer immunotherapy. Specifically, the engineered cells sense vascular endothelial growth factor (VEGF), a protein found in tumors that directly manipulates and in some ways suppresses the immune response. When the rewired cells sense VEGF in their environment, these cells, instead of being suppressed, respond by secreting interleukin 2 (IL-2), a protein that stimulates nearby immune cells to become activated specifically at that site. Normal unmodified T cells do not produce IL-2 when exposed to VEGF, so the engineered behavior is both useful and novel. This work was carried out in cells in culture, and the technology next will be tested in animal studies. While Leonard's team has initially focused on the application of this cell programming technology to enabling cancer immunotherapy, it can be readily extended to distinct cellular engineering goals and therapeutic applications. Leonard's "parts" are also intentionally modular, such that they can be combined with other synthetic biology innovations to write more sophisticated cellular programs. "To truly accelerate the rate at which we can translate scientific insights into treatments, we need technologies that let us rapidly try out new ideas, in this case by building living cells that manifest a desired biological function," said Leonard, who also is a founding member of the Center for Synthetic Biology and a member of the Chemistry of Life Processes Institute. "Our technology also provides a powerful new tool for fundamental research, enabling biologists to test otherwise untestable theories about how cells coordinate their functions in complex, multicellular organisms," he said. Related to this research, Leonard was an invited conferee at a special meeting held in October, "Systems and Synthetic Biology for Designing Rational Cancer Immunotherapies," as part of President Obama and Vice President Biden's Cancer Moonshot Initiative. The paper is titled "Rewiring Human Cellular Input-Output Using Modular Extracellular Sensors." In addition to Leonard and Schwarz, other authors are Nichole M. Daringer and Taylor B. Dolberg, both of Northwestern.


News Article | November 10, 2016
Site: www.marketwired.com

Editors: An online press kit is available at www.NCCN.org/justbagit As part of its mission to improve the quality, effectiveness, and efficiency of cancer care so that patients can live better lives, the National Comprehensive Cancer Network® (NCCN®) today announced the launch of Just Bag It: The NCCN Campaign for Safe Vincristine Handling. This campaign encourages health care providers to adopt a policy to always dilute and administer vincristine in a mini IV-drip bag to prevent a deadly medical error. Vincristine is a chemotherapy agent, widely used in patients with Leukemia or Lymphoma, which should be administered intravenously, or directly into the patient's vein. When it enters the blood, it is highly effective at blocking the growth of cancer by preventing cells from separating. However, vincristine is a neurotoxin that causes peripheral neuropathy when given intravenously and profound neurotoxicity if given into the spinal fluid, which flows around the spinal cord and brain. Many patients who receive vincristine have a treatment regimen that includes other chemotherapy drugs that are administered intrathecally, or injected into the spinal fluid with a syringe. If vincristine is mistakenly administered into the spinal fluid, it is uniformly fatal, causing ascending paralysis, neurological defects, and eventually death. In 2005, NCCN Chief Executive Officer Robert W. Carlson, MD, a medical oncologist, witnessed such a tragedy with a 21 year-old patient with Non-Hodgkin's Lymphoma named Christopher Wibeto. Wibeto was transferred to Carlson's care after receiving incorrectly administered vincristine at another hospital. Carlson watched the young man go from having a likely curable condition to deteriorating and dying within four days. Motivated by this tragic experience, Carlson spearheaded a national effort to address this deadly error when he arrived at NCCN, enlisting the help of its Best Practices Committee, which is dedicated to improving cancer treatment protocols. To ensure that vincristine is always administered properly, NCCN has issued guidelines advising health care providers to always dilute and administer vincristine in a mini IV-drip bag and never use a syringe to administer the medication. This precaution renders it impossible to accidentally administer the medication into the spinal fluid and greatly decreases the chances of improper dosage. All 27 NCCN Member Institutions have adopted policies in line with these guidelines, which are also recommended by the Institute for Safe Medication Practices, the Joint Commission, the World Health Organization, and the Oncology Nursing Society. "We are proud of this achievement and grateful for the support and participation of our Member Institutions in reaching this goal," Carlson said. "Our efforts will not stop here. We challenge all medical centers, hospitals, and oncology practices around the nation and the world to implement this medication safety policy so this error never occurs again." Surveys issued by the Institute for Safe Medication Practices (ISMP) show that over time, more hospitals have adopted a policy to always bag vincristine. According to ISMP data, the number of hospitals that have fully implemented the policy across their practice nearly doubled between February 2014 and February 2016. Earlier surveys indicated a similar increase between 2005 and 2012. Still, only about half of all respondents indicated that they have implemented the policy in all treatment settings, indicating that there is a long way to go. With 125 known cases of accidental death in the U.S. and abroad since the inception of vincristine use in the 1960s, this error is relatively rare. Still, it is unique in its level of mortality. Improvements in practice over the years, including manufacturer- and pharmacist-issued warning labels, have reduced the number of deaths, but the error continues to occur. Diluting vincristine into a mini IV-drip bag may entail a change in practice for some providers, but it is well worth the outcome of avoiding preventable deaths, according to Michael Cohen, RPh, MS, FASHP, President of ISMP. "One more life taken is one too many," Cohen said. "We are glad an organization of NCCN's influence has stepped up to bring this issue to national attention. Ending this devastating error should be a priority for all of us who care for and advocate on behalf of patients and their families." Some health care providers may associate the use of an IV bag with a heightened risk of extravasation, or the leaking of a chemotherapy drug into the tissue surrounding the intravenous administration site. But research shows that the risk of extravasation is extremely low. [1] "The Just Bag It campaign is the latest of NCCN's long-standing efforts to improve the safe use of drugs in cancer care," said F. Marc Stewart, MD, Medical Director of the Seattle Cancer Care Alliance and Member of the Fred Hutchinson Cancer Research Center, Professor of Medicine at University of Washington, and Co-Chair of the NCCN Best Practices Committee. "For more than 15 years, the Best Practices Committee has worked to ensure the highest standards of safety for patients." In 2008, the Best Practices Committee led the charge for NCCN to begin publishing Chemotherapy Order Templates (NCCN Templates®), which detail the most common regimens for many cancers and highlight safety parameters. These resources enable practitioners to standardize patient care, reduce medication errors, and anticipate and manage adverse events. There are more than 1,500 NCCN Templates® for 86 cancer types, and they are used by more than 10,000 subscribers. For more information about Just Bag It: The NCCN Campaign for Safe Vincristine Handling, or to report that a medical facility has adopted a vincristine policy, visit www.NCCN.org/JustBagIt. The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 of the world's leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT. [1] ISMP. Death and neurological devastation from intrathecal vinca alkaloids: Prepared in syringes = 120; Prepared in minibags = 0. ISMP Medication Safety Alert! 2013;18(18):3. The following files are available for download:


News Article | December 12, 2016
Site: phys.org

"Right now, one of the most promising frontiers in cancer treatment is immunotherapy—harnessing the immune system to combat a wide range of cancers," said Joshua N. Leonard, the senior author of the study. "The simple cell rewiring we've done ultimately could help overcome immunosuppression at the tumor site, one of the most intransigent barriers to making progress in this field." When cancer is present, molecules secreted at tumor sites render many immune cells inactive. The Northwestern researchers genetically engineered human immune cells to sense the tumor-derived molecules in the immediate environment and to respond by becoming more active, not less. This customized function, which is not observed in nature, is clinically attractive and relevant to cancer immunotherapy. The general approach for rewiring cellular input and output functions should be useful in fighting other diseases, not just cancer. "This work is motivated by clinical observations, in which we may know why something goes wrong in the body, and how this may be corrected, but we lack the tools to translate those insights into a therapy," Leonard said. "With the technology we have developed, we can first imagine a cell function we wish existed, and then our approach enables us to build—by design—a cell that carries out that function." Currently, scientists and engineers lack the ability to program cells to exhibit all the functions that, from a clinical standpoint, physicians might wish them to exhibit, such as becoming active only when next to a tumor. This study addresses that gap, Leonard said. Leonard, who focuses on integrating synthetic biology into medicine, is an associate professor of chemical and biological engineering at the McCormick School of Engineering. He is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The research comes out of a rich collaboration that Leonard's team has with clinical oncologists, immunologists and basic cancer researchers at Northwestern University Feinberg School of Medicine as well as other synthetic biologists. The study, to be published Dec. 12 by the journal Nature Chemical Biology, provides details of the first synthetic biology technology enabling researchers to rewire how mammalian cells sense and respond to a broad class of physiologically relevant cues. Kelly A. Schwarz, a graduate student in Leonard's research group, is the study's first author. "This work is exciting because it addresses a key technical gap in the field," Schwarz said. "There is great promise for using engineered cells as programmable therapies, and it is going to take technologies such as this to truly realize that goal." Starting with human T cells in culture, the research team genetically engineered changes in the cells' input and output, including adding a sensing mode, and built a cell that is relevant to cancer immunotherapy. Specifically, the engineered cells sense vascular endothelial growth factor (VEGF), a protein found in tumors that directly manipulates and in some ways suppresses the immune response. When the rewired cells sense VEGF in their environment, these cells, instead of being suppressed, respond by secreting interleukin 2 (IL-2), a protein that stimulates nearby immune cells to become activated specifically at that site. Normal unmodified T cells do not produce IL-2 when exposed to VEGF, so the engineered behavior is both useful and novel. This work was carried out in cells in culture, and the technology next will be tested in animal studies. While Leonard's team has initially focused on the application of this cell programming technology to enabling cancer immunotherapy, it can be readily extended to distinct cellular engineering goals and therapeutic applications. Leonard's "parts" are also intentionally modular, such that they can be combined with other synthetic biology innovations to write more sophisticated cellular programs. "To truly accelerate the rate at which we can translate scientific insights into treatments, we need technologies that let us rapidly try out new ideas, in this case by building living cells that manifest a desired biological function," said Leonard, who also is a founding member of the Center for Synthetic Biology and a member of the Chemistry of Life Processes Institute. "Our technology also provides a powerful new tool for fundamental research, enabling biologists to test otherwise untestable theories about how cells coordinate their functions in complex, multicellular organisms," he said. Related to this research, Leonard was an invited conferee at a special meeting held in October, "Systems and Synthetic Biology for Designing Rational Cancer Immunotherapies," as part of President Obama and Vice President Biden's Cancer Moonshot Initiative.


News Article | November 15, 2016
Site: www.marketwired.com

Providing access to NCCN Templates® through Cerner's PowerChart Oncology™ will help practitioners make informed treatment decisions based on up-to-date, standard protocols FORT WASHINGTON, PA--(Marketwired - November 15, 2016) - The National Comprehensive Cancer Network® (NCCN®) is collaborating with Cerner to integrate the NCCN Chemotherapy Order Templates (NCCN Templates®) into PowerChart Oncology™, the oncology-specific solution within Cerner's electronic health record (EHR), as electronic chemotherapy protocols for use by health care providers. NCCN Templates® will be available for PowerChart Oncology users in 2017. "We are collaborating with Cerner to provide practitioners with access to evidence-based treatment protocols at the point of care to help provide patients with the most up-to-date regimens possible for their specific diagnoses," said Dr. Robert W. Carlson, CEO, NCCN. As part of the integration, Cerner's EHR will link to NCCN.org, providing end-user access to NCCN Templates and the corresponding NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), helping practitioners make treatment decisions based on up-to-date, evidence-based standard protocols. "At Cerner, we constantly work to provide solutions that support the oncology care team as they make the best treatment decisions possible. Our collaboration with NCCN will further this mission by providing clinicians with direct access to the evidence-based NCCN Chemotherapy Order Templates in their PowerChart Oncology workflow," said Susan Stiles, Oncology solution executive at Cerner. "We have always recommended that clients use NCCN Guidelines® and NCCN Templates and now they will be integrated into PowerChart Oncology. This will help providers follow the most up-to-date treatment plans and be more available to focus on what is most important, their patients." The information contained in the NCCN Templates is based on the NCCN Guidelines. NCCN Templates include chemotherapy and immunotherapy regimens with literature support, supportive care agents, monitoring parameters and safety instructions. A goal of the NCCN Templates is to enhance patient safety by empowering health care providers to standardize patient care, reduce medical errors, and anticipate and manage adverse events. NCCN continues to expand the library of chemotherapy order templates to work toward improved safe and effective use of drugs and biologics in cancer care. For more information about NCCN Templates, visit NCCN.org/templates. Cerner's health information technologies connect people, information and systems at more than 25,000 provider facilities worldwide. Recognized for innovation, Cerner solutions assist clinicians in making care decisions and enable organizations to manage the health of populations. The company also offers an integrated clinical and financial system to help health care organizations manage revenue, as well as a wide range of services to support clients' clinical, financial and operational needs. Cerner's mission is to contribute to the systemic improvement of health care delivery and the health of communities. Nasdaq: CERN. For more information about Cerner, visit cerner.com, read our blog at blogs.cerner.com, connect with us on Twitter at twitter.com/cerner and on Facebook at facebook.com/cerner. Our website, blog, Twitter account and Facebook page contain a significant amount of information about Cerner, including financial and other information for investors. The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 of the world's leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT. The following files are available for download:


As published in JNCCN, a recent project out of Canada shows that programs identifying stress and distress in patients with cancer increase health care professionals' confidence and awareness of patient-centeredness; outcomes are influenced by site-based navigators and practice size FORT WASHINGTON, PA--(Marketwired - November 01, 2016) - As many as 60 percent of patients with cancer report distress following a cancer diagnosis, and this stress can have significant impacts on patients' well-being, resulting in psychosocial problems, physical side effects, and dissatisfaction with their health care. To examine the impact of distress on patients and health care professionals (HCPs), Linda Watson, PhD, RN, CancerControl Alberta, Alberta Health Services, led the implementation of screening for distress (SFD) as a new standard of care across 17 provincial cancer care sites. More than 250 HCPs across cancer care facilities in Alberta, Canada, participated in educational sessions and adopted this standard of practice. Dr. Watson and Dr. Rie Tamagawa, a senior researcher in provincial practices, found that HCPs who participated in this educational program and utilized SFD routinely reported improved confidence in detecting patient distress and increased awareness of the importance of a patient-centered approach to care. The study, "The Effects of a Provincial-Wide Implementation of Screening for Distress on Health Care Professionals' Confidence and Understanding of Patient-Centered Care in Oncology", is published in the October issue of JNCCN - Journal of the National Comprehensive Cancer Network. Complimentary access to the article is available until December 15, 2016 at JNCCN.org. "Distress can be caused by a variety of issues, concerns, or symptoms, but how distress is experienced and what underlies a person's distress is unique to each person and changes over time. The SFD helps clinicians identify distressed patients and their issues, concerns, or symptoms driving their distress. This project has demonstrated that through clinical review and targeted response to the patient priority issue, improved clinical outcomes and patient experiences can be achieved," said Dr. Watson. For Dr. Watson's quality improvement project, the SFD intervention was implemented as a standard of care at all cancer care facilities in Alberta over a 10-month period. HCPs at all sites completed educational sessions prior to implementation of this new practice. HCPs also completed surveys before and after implementation. Results of the project illustrated a significant increase in participants' confidence in identifying, assessing, and managing distress, as well as their awareness of person-centered care principles following the implementation. HCPs at smaller community cancer centers reported greater person-centered awareness as compared to HCPs at larger tertiary sites throughout the study. HCPs at those smaller sites identified more benefits from the SFD intervention relative to HCPs at the larger sites. This variance, Dr. Tamagawa reports, is likely because smaller, more remote cancer centers have patient navigation as part of their model of care and physicians are treating multiple tumor types. These are likely to contribute to personable patient-provider relationships. The benefits of the SFD was more salient for HCPs taking care of multiple tumor types, suggesting that such intervention is well adopted by physicians who practice as generalist model of care. On the other hand, physicians from larger centers tend to be single-tumor specialists at hospitals that do not employ patient navigation programs -- these participants reported lower awareness in person-centeredness in general, and the SFD intervention potentially posed an additional workload. Prior to adequate SFD training and with less time for patient relationship-building, physicians often lack confidence in their ability to identify and treat patient distress in a timely manner. The study highlighted that SFD intervention can help build this confidence and awareness of person-centered care delivery regardless of the types of care facilities. In Alberta, Dr. Watson shared, "We have found that utilizing a SFD tool that spans the physical, emotional, social, spiritual, practical, and informational domains has been helpful as it reflects the whole patient experience. It has been our experience that using a tool that helps the patient to specify their particular area of concern facilitates meaningful interventions." "Patient distress has received little attention from clinicians, but can have a large impact on patient quality of life. As such, screening for distress will become increasingly important in clinical practices, so information on its implementation is useful for practitioners," said Jimmie C. Holland, MD, Wayne R. Chapman Chair in Psychiatric Oncology, Memorial Sloan Kettering Cancer Center, and Chair of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Distress Management. Complimentary access to the article is available until December 15, 2016 at JNCCN.org. About JNCCN - Journal of the National Comprehensive Cancer Network More than 24,000 oncologists and other cancer care professionals across the United States read JNCCN-Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about best clinical practices, health services research, and translational medicine. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside Press. Visit JNCCN.org. To inquire if you are eligible for a FREE subscription to JNCCN, visit http://www.nccn.org/jnccn/subscribe.asp About the National Comprehensive Cancer Network The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 of the world's leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT. The following files are available for download:


As reported in JNCCN, a recent study from McGill University shows that while opioid use increases during treatment in older patients with breast cancer, most do not continue use into survivorship; however, use of anxiolytics and antidepressants remains high in survivors FORT WASHINGTON, PA--(Marketwired - November 21, 2016) - A new McGill University study published in the November issue of JNCCN - Journal of the National Comprehensive Cancer Network found that most patients with breast cancer aged 65 and older use psychotropic and opioid medications during active treatment and often in the first year of survivorship, despite this population's vulnerability to adverse events. According to the authors, this study highlights the need for a multidimensional approach to distress and anxiety that includes comprehensive psychological intervention. The study, "Psychotropic and Opioid Medication Use in Older Patients with Breast Cancer across the Care Trajectory: A Population-Based Cohort Study," is available free-of-charge until February 28, 2017 on JNCCN.org. According to principle investigator, Ari Meguerditchian, MD, MSc, FRCS, Assistant Professor in the Departments of Surgery and Oncology, and member of the Clinical and Health Informatics Research Group at McGill University, "Women over 65 represent the fastest growing segment of breast cancer survivors. The fact that so many of them need mediations for anxiety, depression, and distress even after active cancer care highlights the fact that we know so little about the specific needs of these patients." The researchers followed more than 19,500 women, 65 years or older, diagnosed with incident, non-metastatic breast cancer in Quebec, Canada, and analyzed the use of anxiolytics, antidepressants, antipsychotics, and opioids from precancer baseline through active care and into first-year survivorship. The most prescribed drugs within the population were anxiolytics and antidepressants. Although the percentage of patients on opioids and antipsychotics was lower than the other drugs, with 16.2 percent of patients using antipsychotics and 25 percent using opioids, the authors noted a marked increase in use of opioids and antipsychotics-4.5- and 7-fold, respectively-from baseline to active care. More than 50 percent of women studied used anxiolytics during care-an increase from 36 percent at baseline-and the vast majority of those women (44.4 percent) continued use of the medication into first-year survivorship. Moreover, use of antidepressants among the cohort was 22.4 percent, with 22.3 percent continuing use into survivorship. Dr. Meguerditchian further noted, "Chronic use of these drugs is related to an increased risk of adverse events among these women, notably medication-related falls and injuries. Many studies suggest that this segment of the population is over-medicated." Conversely, the authors saw a notable drop-off in use of antipsychotics and opioids in first-year survivorship. This is likely due, at least in part, to the fact that antipsychotics and opioids are used to treat physical side effects of treatment, such as extreme nausea and pain, which decrease dramatically after treatment. Anxiolytics and antidepressants, on the other hand, are generally prescribed to combat the psychological aspects of diagnosis and treatment such as distress and anxiety, which have an extended effect on the patient. "Our findings raise important questions about the lasting psychological impact of cancer, such as uncertainty of recurrence, family hardships, etc. Are we supporting our older patients as they move to survivorship? How can we best address their needs?" said Dr. Meguerditchian. According to Crystal Denlinger, MD, FACP, Chief, GI Medical Oncology, and Associate Professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, "This study represents an important overview of high-risk medication use in a vulnerable population, namely older breast cancer survivors. The fact that women increase their use of psychotropic and opioid medications during treatment is not surprising due to the current treatment of nonmetastatic breast cancer (ie, surgery and cytotoxic chemotherapy), but the trend toward continued use into survivorship warrants further evaluation as to cause. Given the current campaign to curb opioid abuse in the general population, understanding the reasons for use of these medications and development of better interventions to address underlying causes is critical to ensuring the best outcomes for this, and potentially other, patient populations." About JNCCN - Journal of the National Comprehensive Cancer Network More than 23,000 oncologists and other cancer care professionals across the United States read JNCCN-Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about best clinical practices, health services research, and translational medicine. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside Press. Visit JNCCN.org. To inquire if you are eligible for a FREE subscription to JNCCN, visit http://www.nccn.org/jnccn/subscribe.asp About the National Comprehensive Cancer Network The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 of the world's leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The NCCN Member Institutions are: Fred & Pamela Buffett Cancer Center, Omaha, NE; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Mayo Clinic Cancer Center, Phoenix/Scottsdale, AZ, Jacksonville, FL, and Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UC San Diego Moores Cancer Center, La Jolla, CA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Colorado Cancer Center, Aurora, CO; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Wisconsin Carbone Cancer Center, Madison, WI; Vanderbilt-Ingram Cancer Center, Nashville, TN; and Yale Cancer Center/Smilow Cancer Hospital, New Haven, CT. 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News Article | October 24, 2016
Site: www.medicalnewstoday.com

Northwestern Medicine scientists have discovered circadian clocks in muscle tissue that control the muscle's metabolic response and energy efficiency depending on the time of day. The finding in mice sheds light on the time-of-day differences in muscle's ability to adapt to exercise and use oxygen for energy. Muscle cells are more efficient during an organism's normal waking hours, the study found. All cells in the body, including those in muscle, contain a clock that regulates how cells adapt to changes in the environment and activity across the 24-hour day. "Oxygen and the internal clock are doing a dance together inside muscle cells to produce energy, and the time of day determines how well that dance is synchronized," said senior author Dr. Joseph Bass. "The capacity for a cell to perform its most important functions, to contract, will vary according to the time of day." More research is needed before the finding can be translated into workout advice. "We're not saying we can tell athletes when they should work out," Bass said, "but in the future, perhaps, you may be able to take advantage of these insights to optimize muscle function." Bass is the Northwestern Medicine chief of endocrinology, metabolism and molecular medicine, and director of the Center for Diabetes and Metabolism at Northwestern University Feinberg School of Medicine. He also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Clara Bien Peek, the first author and a research assistant professor, spearheaded the work on muscle and timing. The paper has been published in the journal Cell Metabolism. The research has implications beyond muscle cells because oxygen response is important in all cells. In particular, the deprivation of oxygen is a key factor in heart attacks and in cancer, in which the depletion of oxygen curiously enables cancer cells to grow. In the research, scientists performed studies in mice, which were exercised on a treadmill at different times of day, as well as in isolated muscle fibers in which the circadian clock was genetically mutated. The scientists analyzed mouse muscle tissues and muscle fibers for expression of genes that are important for exercise. In this way, they determined the impact of deregulation of the circadian clock on muscle fibers in terms of how muscle processes fuel, like sugar and fat, when oxygen levels are low. "When we manipulated the clock genetically, we noticed there were profound abnormalities in the muscle," Bass said. "That set us on a course to understand how the inner muscle clock is important in regulating how well the muscle cell can mobilize energy." When mice, which are nocturnal, are exercised during the night, their muscles are better at turning on genes to help them adapt to exercise, scientists found. Since these genes also exist in humans, this suggests humans may also be able to respond better to exercise during the daytime. The muscle clocks control the metabolic response by interacting with proteins called HIFs that change metabolism when oxygen concentrations get too low in order to allow muscle cells to continue to make energy. Normally when we rest or do low-level exercise, our muscles consume oxygen to make energy. When we start to sprint or exercise strenuously, we consume oxygen faster and quickly run out. That's when the dip in oxygen triggers HIFs and signals muscles to switch to sugar for energy - which in turn increases lactic acid. Turning off the muscle clock prevented the normal capacity of exercise to induce sugar consumption and generation of lactic acid. These findings suggest that better exercise capacity may be tied to specific times of day. "In the future, we may discover new ways to manipulate the oxygen response of the cell by resetting the clock," said Bass, who also holds the Charles F. Kettering Professorship of Medicine at Feinberg. He noted drugs are available that can manipulate the internal clock in cells. "If we can optimize muscle function, " he said, "it's also a critical step in understanding how to impact glucose metabolism in diabetes." Diabetes is characterized by a failure of muscle to consume glucose, which in turn controls blood sugar levels. Strengthening the muscle clock may provide a new way to eliminate excess glucose and treat diabetes. The scientists tested their theories about the internal clock in muscle cells because those cells are particularly dependent on oxygen for contraction and metabolism. "We wanted to determine the rules that interconnect clocks with the physiological use of oxygen," Bass said. "We believe that studying muscle can provide us with the rules of how clocks govern response to oxygen, and we would like to test these principles in a variety of conditions." The study was supported by National Institutes of Health grants R01DK090625, R01DK100814 and K01DK105137-02 from the National Institute of Diabetes and Digestive and Kidney Diseases and grant P01AG011412 from the National Institute on Aging. Lynn Sage Cancer Research Foundation and others also supported the study. Article: Circadian Clock Interaction with HIF1α Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle, Clara Bien Peek, Daniel C. Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J. Tsai, Nicolle A. Bonar, Maureen R. McNulty, Kathryn Moynihan Ramsey, Joseph Bass, Cell Metabolism, doi: 10.1016/j.cmet.2016.09.010, published 20 October 2016.


News Article | February 27, 2017
Site: www.eurekalert.org

CHICAGO --- Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive pediatric brain tumor. The tumor is always fatal and primarily strikes children under 10 years old. Every year, about 300 children under the age of 10 years old in the U.S. develop a tumor referred to as diffuse intrinsic pontine glioma (DIPG). "This tumor kills every single kid who gets DIPG within one year. No one survives," said the study's first author, Andrea Piunti, a postdoctoral fellow in Shilatifard's lab in biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine. The study will be published February 27 in Nature Medicine. "To the best of our knowledge, this is the most effective molecule so far in treating this tumor," said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Pediatrics and the chair of biochemistry and molecular genetics at Feinberg. "Every other therapy that has been tried so far has failed." Radiation therapy only prolongs patients' survival by a few months, he noted. Shilatifard's lab previously identified the pathway via which this mutation causes cancer in studies with fruit flies, which was published in Science a few years ago. He and colleagues believed the pathway would be a good target to thwart the tumor and pushed forward with their molecular studies. Shilatifard and Piunti collaborated with C. David James, Dr. Rintaro Hashizume, Dr. Craig Horbinski, Dr. Rishi Lulla and Dr. Amanda Saratsis at Northwestern Medicine. Lulla, a pediatric neuro-oncologist, and Saratis, a pediatric neurosurgeon, respectively, are also at the Ann & Robert H. Lurie Children's Hospital of Chicago. The scientists also are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. In a study with Hashizume's group, they demonstrated mice in the experiment, which had the drug delivered through their abdomen, had an increased survival of 20 days, which is a long time in the life of a mouse, Piunti said. Now the team at Northwestern Medicine and Lurie Children's is working on delivering the drug to the brain stem to see if the effect will be more potent and effective. To test the molecule, scientists took tumor cell lines from a pediatric patient that was untreated and injected those cells into the brain stem of a mouse. The human tumor engrafted in the brain of the mouse. The mouse was then treated with the molecule while scientists monitored the tumor. The molecule stopped the growth of the tumor cells and forced them to turn into other types of cells, known as differentiation, thereby halting its growth. This molecule detaches proteins, known as bromodomain proteins, from their binding to a mutant protein, the histone H3K27M, which is present in more than 80 percent of these tumors. While the molecule itself is not yet available commercially, another similar class of molecules, BET inhibitors, is being tested in clinical trials for pediatric leukemia and other types of tumors. These could be used in a clinical trial for the pediatric tumor, Piunti said. The collaborative environment at Northwestern made the discovery possible, Shilatifard said. "This work could not have been done anywhere in the world except Northwestern Medicine, because of all the scientists and physicians who have been recruited here during the past five years and how they work together to link basic scientific research to the clinic," Shilatifard said. "This discovery is the perfect example of how we take basic science discoveries and translate them to cure diseases at Northwestern Medicine." Shilatifard's other Northwestern collaborators are Marc Morgan, Elizabeth Bartom, Stacy Marshall, Emily Rendleman, Quanhong Ma, Yoh-hei Takahashi, Ashley Woodfin, Alexander Misharin, Nebiyu Abshiru and Neil Kelleher. The research was supported by grants RO1NS093079 and R35CA197569 from the National Cancer Institute of the National Institutes of Health.


News Article | November 3, 2016
Site: www.eurekalert.org

Combination therapy utilizing two approved immunotherapy drugs for cancer treatment may cause rare and sometimes fatal cardiac side effects linked to an unexpected immune response. In a study led by Vanderbilt University Medical Center (VUMC) investigators and published in the Nov. 3 issue of The New England Journal of Medicine, researchers describe two cases of acute and unexpected fatal myocarditis (inflammation of the heart muscle) that occurred in melanoma patients following treatment with a combination of ipilimumab and nivolumab. Both drugs are FDA-approved immune checkpoint inhibitors which stimulate an anti-tumor response in cancer patients. Ipilimumab is an anti-cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti-programmed death-1 (PD-1) antibody. The use of these immune checkpoint inhibitors, especially in combination using two such therapies, has enhanced the treatment of several types of malignancy. Common side effects of these agents such as inflammation of the skin, colon, liver, endocrine glands and lung, are thought to arise from off-target activation of T cells in the immune system. In the two study cases, a 65-year-old woman and a 63-year-old man, both with metastatic melanoma, were hospitalized nearly two weeks after initiation of the combination therapy. Javid Moslehi, M.D., assistant professor of Medicine, director of the Cardio-Oncology Program at VUMC and corresponding author of the study, said both patients had seemingly mild symptoms at the time of hospitalization. "The patients came with rather vague symptoms including fatigue and muscle aches. What made us take notice, however, were blood tests for cardiac damage that were extremely elevated and the electrocardiograms (EKG) that were abnormal in both cases. The problems quickly advanced such that the patients each needed a pacemaker to control the heart's electrical activity. The degree of cardiac arrhythmia was striking," Moslehi explained. "Even aggressive combinations of these immune therapies are usually well tolerated with very selective activity against the tumor instead of self," said study first author Douglas Johnson, M.D., M.S.C.I., assistant professor of Medicine and clinical director of Melanoma. "But we occasionally observe these cases of wildly dysregulated autoimmune activation." Johnson said VUMC physicians quickly treated the patients with high-dose corticosteroids (methylprednisolone). Despite aggressive treatment, both patients died from myocarditis. The two similar cases stimulated a cross-disciplinary effort at VUMC to investigate the mechanisms of toxicity and potential treatments for patients with such rare reactions. The investigators collaborated with colleagues at Harvard Medical School, Johns Hopkins School of Medicine, and Bristol-Myers Squibb, the company that makes both drugs. Justin Balko, Pharm.D., Ph.D., assistant professor of Medicine and Cancer Biology and leader of Molecular Oncology in the Center for Cancer Targeted Therapies at Vanderbilt-Ingram Cancer Center (VICC), said on autopsy and biopsy of the cardiac tissue it was clear that there was an immune reaction to the heart. VUMC pathologists found robust T cell and macrophage infiltrates. Importantly, there were shared populations of T cells infiltrating the myocardium which were identical to those present in tumor and skeletal muscle. "One hypothesis based on the data is that essentially the body is seeing the heart and muscle tissue as foreign, just like the tumor," Balko said. "This gives us a starting point to develop a model to see how consistent this is with other cases as they appear and once we have that model, determine the right way to intervene so that we can keep other patients safe." Study authors said global data reveal that myocarditis has occurred in less than one percent of patients treated with the ipilimumab/nivolumab combination therapy to date, suggesting this is a rare, potentially fatal T cell-driven drug reaction. Johnson suggested "presumably the treatment strategy would involve high-dose steroids and possibly other intensive immune-suppressive drugs, as well. The best regimen is unclear at this point." Other investigators on the study include Margaret Compton, Yaomin Xu, Mellissa Hicks, Matthew Alexander, Tyler Bloomer, Jason Becker, David Slosky, Elizabeth Phillips, Mark Pilkinton, Laura Craig-Owens, Robert Hoffman, and Dan Roden, VUMC; Igor Puzanov, VUMC and Roswell Park Cancer Institute, Buffalo, New York; Jeffrey Sosman, VUMC and Robert H. Lurie Comprehensive Cancer Center, Evanston, Illinois; Spyridon Chalkias, Igor Koralnik, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Joshua Gorham, Jonathan Seidman, Harvard Medical School, Boston; Benjamin Olenchock, Christine Seidman, Brigham and Women's Hospital, Boston; Janis Taube, Luis Diaz, Robert Anders, Johns Hopkins University School of Medicine, Baltimore, Maryland; Nina Kola, Gregory Plautz, Daniel Reshef, Jonathan Deutsch, Bristol-Myers Squibb, New York City; and Raquel Deering, Neon Therapeutics, Cambridge, Massachusetts. The authors have received funding from the Bready Family Foundation, NIH/NCI (6R00CA181491), VICC ambassadors, the VICC Breast Cancer Specialized Program of Research Excellence (SPORE) grant (P50 CA098131),and the National Comprehensive Cancer Network Young Investigator Award.

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