The Case Comprehensive Cancer Center is comprised of over 370 members, who span 32 departments of the Schools of Medicine, Nursing, Dentistry, Engineering, Applied Social Sciences, and the College of Arts and Sciences at Case Western Reserve University (CWRU), located at CWRU, University Hospitals Case Medical Center (UHCMC), Cleveland Clinic, and MetroHealth Medical Center (MHMC).
Case Western Reserve University scientists have discovered that a protein called Kruppel-like Factor 4(KLF4) controls mitochondria-the "power plants" in cells that catalyze energy production. Specifically, they determined KLF4's pivotal role through its absence-that is, the mitochondria malfunction without enough of the protein, which in turn leads to reduced energy. This decline is particularly problematic in the heart because lower energy can lead to heart failure and death.
The researchers' findings appear in the August edition of The Journal of Clinical Investigation (JCI). In addition to an article detailing the research, the edition also features a First Author Perspective piece from Xudong Liao, an assistant professor of medicine in the area of cardiovascular medicine at Case Western Reserve University School of Medicine.
"Xudong made the observation several years ago that mice lacking KLF4 in the heart developed profound heart failure in response to stress," said senior author Mukesh Jain, the Ellery Sedgwick Jr. Chair and Distinguished Scientist, director of the Case Cardiovascular Research Institute, and member of the Case Comprehensive Cancer Center. "In this most recent research, he looked into the mechanisms for why the heart had failed so quickly and made the exciting observation that KLF4 controls major aspects of the mitochondrial biology." [more]
Treatment with low-molecular-weight heparin (LMWH) is as safe and effective as warfarin in cancer patients with acute symptomatic venous thromboembolism (VTE), according to new findings.
Compared with warfarin, the LMWH tinzaparin (Innohep, LEO Pharma) did not significantly reduce the composite primary outcome of recurrent VTE, and it was not associated with reductions in overall mortality or major bleeding.
However, the risk for clinically relevant nonmajor bleeding events was significantly lower with tinzaparin (49 of 449 patients) than with warfarin (69 of 451 patients); the hazard ratio (HR) was 0.58 (P = .004). Findings from the CATCH study, initially presented last year at the annual meeting of the American Society of Hematology, as reported by Medscape Medical News were published in the August 18 issue of JAMA. "We haven't had a larger confirmation until now," explained senior author Alok Khorana, MD, a medical oncologist at the Cleveland Clinic and member of the Case Comprehensive Cancer Center. [more]
Researchers have shown that magnetic resonance imaging (MRI) can detect the earliest signs of breast cancer recurrence and fast-growing tumors. Their approach detects micrometastases, breakaway tumor cells with the potential to develop into dangerous secondary breast cancer tumors elsewhere in the body. The approach may offer an improved way to detect early recurrence of breast cancer in women and men. The work was completed at Case Western Reserve University (CWRU), Cleveland and was funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health.
The study, published online in the Aug. 12, 2015, issue of Nature Communications, was led by Zheng-Rong Lu, PhD, CWRU M. Frank Rudy and Margaret Domiter Rudy Professor of biomedical engineering and an expert in molecular imaging for cancer and other diseases. More>
Jeremy Rich, MD, Chair of the Department of Stem Cell Biology & Regenerative Medicine in Cleveland Clinic's Lerner Research Institute, has been awarded the National Cancer Institute's prestigious Outstanding Investigator Award and will receive $6.7 million over seven years for his research laboratory. The National Cancer Institute awards these select grants to established scientists who have exceptional records of accomplishment and whose research shows great promise for future medical breakthroughs.
"This is an amazing honor and opportunity," Dr. Rich said. "We are just now beginning to comprehend the unique biology of brain cancer stem cells, and this substantial award will push us years ahead in finding new treatments for glioblastoma." More>
Dr. Charis Eng, the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine, and Hannah Wang, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University School of Medicine, are recipients of a Doris Duke Charitable Foundation Clinical Research Mentorships grant. This competitive award program supports the development of a mentoring relationship between a medical student interested in becoming a future researcher, and a clinical scientist previously funded through the foundation. More>
Researchers say their adoptive immunotherapy study ("T Cells Derived From Human Melanoma Draining Lymph Nodes Mediate Melanoma-specific Antitumor Responses In Vitro and In Vivo in Human Melanoma Xenograft Model"), published in the July/August issue of Journal of Immunotherapy, demonstrates that T cells derived from lymph nodes of patients with melanoma can be expanded in number and activated in the laboratory for intravenous administration in the treatment of patients. Led by Julian Kim, MD, chief medical officer at UH Seidman Cancer Center and member of the Case Comprehensive Cancer Center, the team has developed a technique to generate large numbers of activated T cells which can be transferred back into the same patient to stimulate the immune system to attack the cancer. More>
Case Western Reserve University researcher Mehmet Koyuturk, an associate professor of electrical engineering and computer science, was awarded a $1.3 million grant from NIH to help develop open-source software to store biomedical data and make this mountain range of information handy. His was one of 15 proposals to win grants under the NIH Big Data to Knowledge (BD2K) initiative. More>
An algorithm dubbed ENVE could be the Google for genetic aberrations -- and it comes from Case Western Reserve researchers Kishore Guda and Vinay Varadan.
Remember the World Wide Web before the famed search engine? The web offered extraordinary amounts of information, but no consistently reliable way to secure relevant results.
Cancer researchers at Case Western Reserve encountered a comparable conundrum when considering reams of data about the body that new technological advances provide -- how could they tell what parts of the information actually offer value. In this instance, the goal was to distinguish between distracting or even misleading material and evidence worthy of action.
Their answer -- as well as remarkable findings involving genetic characteristics of African Americans with colon cancer -- appears this week in the journal Genome Medicine.
Case Western Reserve researchers already demonstrated that a single protein plays a pivotal role in the use of nutrients by major organs that allow for the burning of fat during exercise or regulating the heart's contractile and electrical activity. Now they have found a new benefit of Kruppel-like Factor 15 (KLF15) -- keeping the body in metabolic balance.
The discovery, which highlights how KLF15 affects the availability of nutrients in the body, may also have significant implications for scientists' ability to understand ways that the body metabolizes different medications. The findings appeared last month in the journal Nature Communications.
"It's important to understand how nutrients are acquired, how they are made available to tissues, how they are used, and how disease alters the dynamics of the process," said Mukesh K. Jain, MD, Ellery Sedgwick Jr. Chair & Distinguished Scientist and director of the Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. More>
Cleveland Clinic researchers have discovered for the first time that a metabolite of an FDA-approved drug for metastatic prostate cancer, abiraterone (Abi), has more anti-cancer properties than its precursor. The research was published online June 1 in Nature.
Nima Sharifi, MD, co-Leader of the Case Comprehensive Cancer Center GU Malignancies Program, found that abiraterone, a steroid inhibitor, is converted into the more physiologically active D4A (Δ4-abiraterone) in both patients and animal models with prostate cancer who take the drug. Furthermore, they found that D4A is more effective than abiraterone at killing aggressive prostate cancer cells, suggesting that some patients may benefit from direct treatment with D4A. More>
Recurrence scores based on a 16-gene assay accurately predicted clinical outcomes in patients with surgically treated clear cell renal cell carcinoma, according to study results.
Surgery or ablation represent curative options for patients with stage I to III clear cell renal cell carcinoma, but about 30% of patients with localized disease will relapse, according to study background. Clinicians frequently use clinical and pathological parameters to determine the probability of recurrence.
"The current methods we use to assess recurrence can certainly be improved," Brian Rini, MD, associate professor of medicine in the department of urology at the Cleveland Clinic and a HemOnc Today Editorial Board member, told HemOnc Today. "Researchers have utilized a similar testing method to predict breast cancer recurrence." Dr. Rini is co-leader of the Case Comprehensive Cancer Center GU Malignancies Program. More>
Andrew Sloan, MD, a Case Comprehensive Cancer Center brain surgeon and neurosurgery professor at CWRU is among the primary authors of a new approach to classifying tumors that could lead to significant improvements in their diagnosis and treatment. The research and recommendations appear online June 10 in The New England Journal of Medicine.
Dr. Sloan, Director of the Brain Tumor and Neuro-Oncology Center at University Hospitals Case Medical Center, said the new classification system has the potential to provide far more accurate assessments of brain tumors known as low and intermediate grade gliomas (LGGs) - which in turn could enhance patients' outcomes.
Scientists and physicians from Cleveland and 43 other federally designated cancer centers used molecular and genetic analysis to develop an approach that reduces the role of individual observers' assessments of the tumors' appearance. Co-authors on the study include Cancer Center members Drs. Gene Barnett and Jill Barnholtz-Sloan. More >
Researchers at Case Western Reserve and UT Southwestern Medical Center this week announced that they have taken significant steps toward turning this once-improbable idea into a vivid reality. In a study published in the June 12 edition of Science, they detail how a new drug repaired damage to the colon, liver and bone marrow in animal models - even going so far as to save the lives of mice who otherwise would have died in a bone marrow transplantation model.
"We are very excited," said Sanford Markowitz, MD, PhD, the Ingalls Professor of Cancer Genetics at the university's School of Medicine, medical oncologist at University Hospitals Case Medical Center's Seidman Cancer Center, and co-leader of the Cancer Genetics Program at the Case Comprehensive Cancer Center. "We have developed a drug that acts like a vitamin for tissue stem cells, stimulating their ability to repair tissues more quickly. The drug heals damage in multiple tissues, which suggests to us that it may have applications in treating many diseases."
The study was truely a collaborative effort with research being performed by many Cancer Center members, including Case CCC Director Dr. Stan Gerson, Drs. Fabio Cominelli, Mark Chance and Stephen Fink and former Case CCC Director Dr. James K.V. Willson, now director of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center. More >
Case Western Reserve University nurse scientist Amy Zhang, PhD who has long examined quality-of-life issues in cancer patients, wondered whether depression in African-American cancer patients has been under-recognized for treatment.
Accurately assessing depression in cancer patients is difficult in general because the physical symptoms of cancer and depression-low energy, lack of sleep and loss of appetite-are so similar.
“African-American cancer patients are often sicker and have more severe physical symptoms,” said Zhang, an associate professor at Case Western Reserve’s Frances Payne Bolton School of Nursing. “So I wanted to see if something was missing in how and what we were asking patients.” More>
Case Western Reserve Scientists Collaborate with China's Lanzhou University Investigators in Exploring the Dual Compound Strategy.
The concept was simple: If two compounds each individually show promise in preventing colon cancer, surely it's worth trying the two together to see if even greater impact is possible.
In this instance, Case Western Reserve cancer researcher Li Li, MD, PhD, could not have been more prescient.
New England Journal of Medicine - Mar 5, 2015
The POEMS/S0230 impressive results were published in NEJM this past week.
As PI on the SWOG randomized study of 257 premenopausal women with operable hormone-receptor-negative breast cancer receiving standard chemotherapy with or without the GnRH agonist goserelin, Dr Halle Moore was able to demonstrate improved protection against ovarian failure and therefor improved prospects for fertility.
The impact of this research was articulated by Dr Stan Gerson; " I think more than anything is to remember how rare out work changes the practice of medicine and this will do so."
A team of researchers at Case Western Reserve University (CWRU) assisted in a study that uncovered previously unknown segments of DNA shared by African American family members who have breast cancer. The study was led by Dr. Heather Ochs-Balcom from the University of Buffalo, a former postdoc of Dr. Robert Elston.
African American women have different incidence of breast cancer as compared to European American women, in particular the distribution of the known subtypes of breast cancer are different between these groups. Treatment decisions and clinical outcomes are tightly coupled with breast cancer subtype designation.
For the study, Dr. Ochs-Balcom recruited African American women with breast cancer and their family members. Sophisticated statistical analysis was conducted by the team at CWRU and the Case Comprehensive Cancer Center, including Xiangqing Sun, Yanwen Chen, Jill Barnholtz-Sloan and Robert Elston. Using this analysis, Dr. Ochs-Balcom was able to find novel genetic variants for these families not previously described in European American families with breast cancer. More>
Anant Madabhushi, PhD of the CWRU Department of Biomedical Engineering, Center for Computational Imaging and Personalized Diagnostics, and Case Comprehensive Cancer Center has been unanimously elected to the National Cancer Institute's Quantitative Imaging Network (QIN) on account of his ongoing NCI funded grant R01CA136535-01, Software to facilitate multimode, multi-scale fused data for Pathology and Radiology.
The Quantitative Imaging Network (QIN) grows from the NCI program announcement "Quantitative Imaging for Evaluation of Responses to Cancer Therapies". The network is designed to promote research and development of quantitative imaging methods for the measurement of tumor response to therapies in clinical trial settings, with the overall goal of facilitating clinical decision making. Projects include the appropriate development and adaptation/implementation of quantitative imaging methods, imaging protocols, and software solutions/tools (using existing commercial imaging platforms and instrumentation) and application of these methods in current and planned clinical therapy trials. The projects are focusing on imaging-derived quantitative measurements of responses to drugs and/or radiation therapy, and/or image-guided interventions (IGI).
As an Associate member of the QIN, Dr. Madabhushi will attend quarterly meetings in Washington, DC and will be contributing his expertise and tools being developed in computational imaging and radiology-pathology data fusion as part of R01CA136535-01 to the consortium.
In a new study, researchers explored ways to treat life-threatening blood cancers in a less toxic way. They worked to wipe out cancer cells in the blood without destroying healthy surrounding cells. Yogen Saunthararajah, MD, who treats cancer patients at Cleveland Clinic, led the study. Dr. Saunthararajah, Co-leader of the Developmental Therapeutics Program and Professor, Hematologic Oncology and Blood Disorders, explains how the new approach works by comparing it to a popular arcade game.
"The way the medicine works is like the game Whac-a-Mole™. You have a mallet and you're only getting the moles that happen to be in a particular phase of their growth cycle. You don't want a huge mallet because you're just going to damage the golf green. You want a little mallet and you want to keep on whacking regularly," Dr. Saunthararajah says.
In the same way, the new treatment involves using an existing drug but in a more targeted, repetitive way. The idea is to use more and smaller doses, as though the drug were the mallet you use to strike the cancer cells. More>
Dr. Nima Sharifi, Associate Professor of Cancer Biology at the Cleveland Clinic Lerner College of Medicine of CWRU and Co-Leader of the Case Comprehensive Cancer Center GU Malignancies Program, is one of six people to receive a Challenge Award from the Prostate Cancer Foundation (PCF). These multi-year awards support cross-disciplinary teams of research scientists to advance the treatment of lethal prostate cancer.
According to a PCF press release, Dr. Sharifi's project will develop an FDA-approved prognostic test to identify patients with genetic mutations that predispose them to treatment resistance. An inherited mutation in 3βHSD1 increases the body's production of male hormones, leading to poor clinical outcomes when patients are treated with androgen deprivation therapy. Dr. Sharifi's work will be translated into a new diagnostic test, which may also predict the efficacy of abiraterone (Zytiga®) as an alternative treatment for these high-risk patients. This is Dr. Sharifi's third PCF award; he was named a PCF Young Investigator in 2008, and a co-investigator on a previous Challenge Award. More>
Dr. Anant Madabhushi, Professor of Biomedical Engineering and Director of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University, has been invited to serve as associate editor for the Journal of Medical Image Analysis (MedIA), one of the top international journals in computer science. Dr. Madabhushi is also a member of the Case Comprehensive Cancer Center.
The International Society for Stem Cell Research (ISSCR) has named Paul Tesar, PhD of Case Western Reserve University and the Case Comprehensive Cancer Center the Outstanding Young Investigator for 2015. The award "recognizes the exceptional achievements of an investigator in the early part of his or her independent career in stem cell research who will be honored with the award at the ISSCR Annual Meeting in Stockholm, Sweden in June 2015." More>
ASCO’s Cancer.Net is providing free access to a new educational program to help patients and their caregivers learn about clinical trials and address barriers to participation.
The video-based program, Preparatory Education About Clinical Trials (PRE-ACT), is designed to improve patients’ general knowledge and attitudes about clinical trials, and prepare them for considering participation if this option is available. The program was tested with more than 1,200 patients in a phase III randomized clinical trial.
Cancer.Net licensed the program from the Case Western Reserve University, in Cleveland, Ohio, where the program was developed by ASCO member Neal J. Meropol, MD, of the Seidman Cancer Center at University Hospitals Case Medical Center, through a grant from the National Cancer Institute. Dr. Meropol began designing PRE-ACT with a team of colleagues when he was a faculty member at Fox Chase Cancer Center in Philadelphia, PA. More>
Case Comprehensive Cancer Center researchers have identified new gene mutations unique to colon cancers in African Americans the population with the highest incidence and death rates of any group for this disease.
This discovery – namely, that colorectal cancers appear different on a molecular level in African Americans – offers new hope for these patients. With this groundbreaking knowledge, scientists now will seek to develop treatments that target the distinct nature of the disease in African Americans – and, they hope, begin to reduce the devastation disproportionately wrought on this population.
The findings, published in the Jan. 12 edition of PNAS (Proceedings of the National Academy of Sciences), only became possible because of technological advances in gene sequencing and computational analysis. The study that revealed this invaluable information ultimately involved review of 1.5 billion bits of data. More>
Clark Distelhorst, MD, PhD, Professor in the Division of Hematology/Oncology at CWRU and University Hospitals Case Medical Center (UHCMC), was recently named a 2015 Harrington Scholar-Innovator by the Harrington Discovery Institute (HDI) at UHCMC. Dr. Distelhorst is one of 11 outstanding physician-scientists in the nation to receive the award, which provides funding and drug development to help bring their research from basic discovery to clinical introduction.
As a recipient of this award, Dr. Distelhorst will receive up to $700,000 over two years to support his research on blood cancer. In addition, he along with his fellow Scholar-Innovators will be given access to HDI's Innovation Support Center, which includes a renowned group of industry experts charged with helping guide drug development. More>
Shaveta Vinayak, MD, Assistant Professor in the Division of Hematology/Oncology at CWRU and UHCMC, was honored as the inaugural Becky Hennessy Endowed Master Clinician in Breast Cancer Genomics. This endowment recognizes Dr. Vinayak's excellence in patient care and accomplishments, dedication, and clinical research focus on genomic approaches to breast cancer treatment.
A study conducted by the Gliogene Consortium, an international consortium of researchers, has identified for the first time a gene associated with familial glioma,providing new support that certain people may be genetically predisposed to the disease. Study authors found an increased risk of cancer associated with mutations in the POT1 gene. The findings were published last week in the Journal of the National Cancer Institute.
"This discovery is tremendously exciting, as we have known for years that a small subset of families have multiple people with gliomas, yet we have not understood the potential causes," commented study collaborator, Dr. Jill Barnholtz-Sloan. "This new paper sheds light on a potential cause for some of these families." Dr. Barnholtz-Sloan, Associate Director for Bioinformatics at the Case Comprehensive Cancer Center and Associate Professor in the Division of General Medical Sciences (Oncology) at CWRU, recruited families to the study and is the Ohio Principal Investigator for the Gliogene Consortium. More>
Huiping Liu, MD, PhD, Assistant Professor of Pathology at Case Western Reserve University School of Medicine, was named a Mt. Sinai Health Care Foundation Scholar. The Mt. Sinai Health Care Foundation Scholars Program has assisted the CWRU School of Medicine in attracting young, highly promising research stars in order to build its basic science departments.
Dr. Liu came to CWRU from the University of Chicago, where she worked on microRNAs in human breast cancer in their Transitional Chicago Fellows Program. Currently, she is the primary investigator on a Case Comprehensive Cancer Center pilot genomics study on RNA sequencing of breast cancer stem cells. More >
Justin Lathia, PhD, of the Department of Cellular and Molecular Medicine at Cleveland Clinic's Lerner Research Institute and member of the Case Comprehensive Cancer Center, was recently honored with a Distinguished Scientist Award from the Sontag Foundation. The award is given to young scientists whose research is likely to improve the quality of life of patients with brain cancer. It includes a $600,000 award over four years for a brain-cancer-related research project. Dr. Lathia will use the funds to study how cancer stem cells, a population of cells that drive tumor growth and resistance to therapy, interact with the immune system in glioblastoma, the deadliest type of brain tumor. More >
Ahmad Khalil, PhD, Assistant Professor of Genetics and Genome Sciences at the CWRU School of Medicine and member of the Case Comprehensive Cancer Center, was selected to speak at the 16th Chinese-American Kavli Frontiers of Science symposium. The symposium, co-sponsored by the Chinese Academy of Sciences and the U.S. National Academy of Sciences, was held in Beijing October 11-13.
Analisa DiFeo, PhD, studies epithelial ovarian cancer (EOC), one of the most lethal gynecological malignancies. Her research focuses on identifying genetic aberrations critical to the development of drug resistance and ovarian cancer progression. The genetic changes she finds will serve as novel biomarkers of ovarian cancer therapeutic response and/or innovative targeted molecular therapies that can work alone or in conjunction with current treatment options. Member Spotlight: Analisa DiFeo
A common Asian spice and cancer-hampering molecules show promise in slowing the progression of mesothelioma, a cancer of the lung's lining often linked to asbestos. Scientists from Case Western Reserve University and the Georg-Speyer-Haus in Frankfurt, Germany, demonstrate that application of curcumin, a derivative of the spice turmeric, and cancer-inhibiting peptides increase levels of a protein inhibitor known to combat the progression of this cancer. Their findings appeared in the August 14 online edition Clinical Cancer Research; the print version of the article appeared October 1. "Mesothelioma is a disease that continues to have a significant burden worldwide, and the treatment option is really suboptimal. We must find better ways to treat it," said senior author Afshin Dowlati, MD, Professor of Medicine – Hematology/Oncology, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. "We now understand the mechanisms that drive cell proliferation and growth in malignant mesothelioma."
Last week, Mark Griswold, PhD, Professor of Radiology, was awarded the CWRU School of Medicine Medal for Excellence in Health Science Innovation, one of its highest honors, to recognize his extraordinary dedication and accomplishments.
Michael A. Vogelbaum MD, PhD has been appointed to the Brain Malignancy Steering Committee of the National Cancer Institute. This committee functions to review and prioritize adult and pediatric phase II and phase III clinical trials submitted for NCI funding. Dr. Vogelbaum also currently serves as the Co-Chair of the Brain Site Committee and Chair of the Neurosurgery Subcommittee at NRG Oncology, one of four adult clinical trials groups in the NCI's National Clinical Trials Network (NCTN).
Dr. Jill Barnholtz-Sloan, Associate Professor of General Medical Sciences (Oncology) at CWRU and Associate Director for Bioinformatics at the Case Comprehensive Cancer Center, has been invited to serve as a member of the Pediatric Brain Tumor Foundation Research Advisory Network (RAN). As a member of RAN, Dr. Barnholtz-Sloan joins a group of North American leaders in pediatric brain tumor research and clinical care. More >
Dr. Hillard Lazarus, Professor in the Division of Hematology/Oncology at CWRU and University Hospitals Case Medical Center, received a July 2014 CTSC Core Utilization Pilot Award for his project, Pre-Clinical Model Using Pluristem Administration For Delayed Engraftment After Hematopoietic Cell Transplant. Clinical and Translational Science Collaborative (CTSC) of Case Western Reserve University Core Utilization pilot program