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News Article | May 22, 2017
Site: www.eurekalert.org

COLUMBUS, Ohio -- A new study shows that so-called "light" cigarettes have no health benefits to smokers and have likely contributed to the rise of a certain form of lung cancer that occurs deep in the lungs. For this new study, researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) and five other universities/cancer centers examined why the most common type of lung cancer, called adenocarcinoma, has increased over the last 50 years, rather than decreasing as smokers have been able to quit. Other types of lung cancer have been decreasing in relationship to fewer people smoking, but not lung adenocarcinoma. Because of this, lung adenocarcinoma is now the most common type of lung cancer. Results confirm what tobacco-control researchers have suspected for years: There is no health benefit to high-ventilation (light) cigarettes - long marketed by the tobacco industry as a "healthier" option - and these cigarettes have actually have caused more harm. Holes in cigarette filters were introduced 50 years ago and were critical to claims for low-tar cigarettes "This was done to fool smokers and the public health community into thinking that they actually were safer," says Peter Shields, MD, deputy director of the OSUCCC - James and a lung medical oncologist. "Our data suggests a clear relationship between the addition of ventilation holes to cigarettes and increasing rates of lung adenocarcinoma seen over the past 20 years. What is especially concerning is that these holes are still added to virtually all cigarettes that are smoked today." The U.S. Food and Drug Administration (FDA) was given the authority to regulate the manufacture, distribution and marketing of tobacco products through the Family Smoking Prevention and Tobacco Control Act in 2009. Current regulations ban tobacco companies from labeling and marketing cigarettes as "low tar" or "light." Study authors, however, say that given this new data, the FDA should take immediate action to regulate the use of the ventilation holes, up to and including a complete ban of the holes. "The FDA has a public health obligation to take immediate regulatory action to eliminate the use of ventilation holes on cigarettes," adds Shields. "It is a somewhat complicated process to enact such regulations, but there is more than enough data to start the process. We believe that such an action would drive down the use and toxicity of conventional cigarettes, and drive smokers to either quit or use less harmful products. There are some open questions about unintended consequences for enacting a ban, which provides for an important research agenda." A team made up of lung oncology, public health and tobacco regulation researchers conducted a comprehensive, multi-faceted analysis of existing literature that included chemistry and toxicology studies, human clinical trials and epidemiological studies of both smoking behavior and cancer risk. They studied scientific publications in the peer-reviewed literature and internal tobacco company documents. Researchers hypothesized that the higher incidence rates of lung adenocarcinoma were attributable to the filter ventilation holes, which allow smokers to inhale more smoke that also has higher levels of carcinogens, mutagens and other toxins. "The filter ventilation holes change how the tobacco is burned, producing more carcinogens, which then also allows the smoke to reach the deeper parts of the lung where adenocarcinomas more frequently occur," explains Shields. To date, all the scientific evidence involves the adverse impact of adding ventilation, but not removing it. Additional research is needed to confirm that the addictiveness of the cigarette or toxic exposures from cigarettes would not increase with elimination of the ventilation holes. The OSUCCC - James and researchers at the University of Minnesota, Roswell Park Cancer Institute, Virginia Tech, Harvard University and Medical University of South Carolina are conducting additional research to reconcile human biomarkers studies and smoke distribution/exposure in the lung. Funding for this research comes from the National Cancer Institute and Food and Drug Administration Center for Tobacco Products. Coauthors include OSUCCC - James researchers Min-Ae Song, PhD, Micah Berman, JD, Theodore Brasky, PhD, and Casper Woroszylo, PhD; Neal Benowitz, MD, University of California-San Francisco; Michael Cummings, PhD, Medical University of South Carolina; Dorothy Hatsukami, PhD, University of Minnesota; Vaughan Rees, PhD, Harvard University; Richard O'Connor, PhD, Roswell Park Cancer Institute; and Catalin Marian, PhD, of Victor Babes University of Medicine and Pharmacy (Romania). The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. Learn more at cancer.osu.edu.


News Article | May 22, 2017
Site: www.eurekalert.org

A new study shows that so-called "light" cigarettes have no health benefits to smokers and have likely contributed to the rise of a certain form of lung cancer that occurs deep in the lungs. For this new study, researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) and five other universities/cancer centers examined why the most common type of lung cancer, called adenocarcinoma, has increased over the last 50 years, rather than decreasing as smokers have been able to quit. Other types of lung cancer have been decreasing in relationship to fewer people smoking, but not lung adenocarcinoma. Because of this, lung adenocarcinoma is now the most common type of lung cancer. Results confirm what tobacco-control researchers have suspected for years: There is no health benefit to high-ventilation (light) cigarettes - long marketed by the tobacco industry as a "healthier" option - and these cigarettes have actually have caused more harm. Holes in cigarette filters were introduced 50 years ago and were critical to claims for low-tar cigarettes "This was done to fool smokers and the public health community into thinking that they actually were safer," says Peter Shields, MD, deputy director of the OSUCCC - James and a lung medical oncologist. "Our data suggests a clear relationship between the addition of ventilation holes to cigarettes and increasing rates of lung adenocarcinoma seen over the past 20 years. What is especially concerning is that these holes are still added to virtually all cigarettes that are smoked today." The U.S. Food and Drug Administration (FDA) was given the authority to regulate the manufacture, distribution and marketing of tobacco products through the Family Smoking Prevention and Tobacco Control Act in 2009. Current regulations ban tobacco companies from labeling and marketing cigarettes as "low tar" or "light." Study authors, however, say that given this new data, the FDA should take immediate action to regulate the use of the ventilation holes, up to and including a complete ban of the holes. "The FDA has a public health obligation to take immediate regulatory action to eliminate the use of ventilation holes on cigarettes," adds Shields. "It is a somewhat complicated process to enact such regulations, but there is more than enough data to start the process. We believe that such an action would drive down the use and toxicity of conventional cigarettes, and drive smokers to either quit or use less harmful products. There are some open questions about unintended consequences for enacting a ban, which provides for an important research agenda." A team made up of lung oncology, public health and tobacco regulation researchers conducted a comprehensive, multi-faceted analysis of existing literature that included chemistry and toxicology studies, human clinical trials and epidemiological studies of both smoking behavior and cancer risk. They studied scientific publications in the peer-reviewed literature and internal tobacco company documents. Researchers hypothesized that the higher incidence rates of lung adenocarcinoma were attributable to the filter ventilation holes, which allow smokers to inhale more smoke that also has higher levels of carcinogens, mutagens and other toxins. "The filter ventilation holes change how the tobacco is burned, producing more carcinogens, which then also allows the smoke to reach the deeper parts of the lung where adenocarcinomas more frequently occur," explains Shields. To date, all the scientific evidence involves the adverse impact of adding ventilation, but not removing it. Additional research is needed to confirm that the addictiveness of the cigarette or toxic exposures from cigarettes would not increase with elimination of the ventilation holes. The OSUCCC - James and researchers at the University of Minnesota, Roswell Park Cancer Institute, Virginia Tech, Harvard University and Medical University of South Carolina are conducting additional research to reconcile human biomarkers studies and smoke distribution/exposure in the lung. Funding for this research comes from the National Cancer Institute and Food and Drug Administration Center for Tobacco Products. Coauthors include OSUCCC - James researchers Min-Ae Song, PhD, Micah Berman, JD, Theodore Brasky, PhD, and Casper Woroszylo, PhD; Neal Benowitz, MD, University of California-San Francisco; Michael Cummings, PhD, Medical University of South Carolina; Dorothy Hatsukami, PhD, University of Minnesota; Vaughan Rees, PhD, Harvard University; Richard O'Connor, PhD, Roswell Park Cancer Institute; and Catalin Marian, PhD, of Victor Babes University of Medicine and Pharmacy (Romania).


News Article | May 3, 2017
Site: www.eurekalert.org

COLUMBUS, Ohio - More than half of breast cancer patients (57 percent) undergoing mastectomy lack the necessary medical knowledge to make a high-quality decision about reconstructive surgery that aligns with their personal goals, suggesting a trend toward overtreatment, according to a new study conducted by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). "High-quality" decisions were defined as those that demonstrated adequate medical knowledge of treatment choices - including associated risks - and that also matched with the patient's specific goals and preferences for choosing whether or not to pursue reconstructive surgery. Researchers say shared decision-making tools are needed to help women make decisions based on a full understanding of treatment choices and associated risks alongside their personal goals for surgery. Researchers report the findings online first in the medical journal JAMA Surgery May 3, 2017. In this observational, single-institution study, researchers sought to evaluate the quality of 126 adult breast cancer patients' decisions about breast reconstruction after mastectomy. All patients had stage I-III invasive ductal/lobular breast cancer, ductal carcinoma in situ (DCIS) or were having preventive mastectomies. The majority of patients (73 percent) had early-stage disease. Researchers measured study participants' medical knowledge about mastectomy and mastectomy with reconstruction -- for example, effects of surgery on appearance and associated risks. They also measured individual preferences of what mattered most to patients. Key preference factors included breast appearance/shape post treatment, length of recovery time and risk for complications. "We found that less than half of the women had adequate medical knowledge about breast reconstruction and made a choice that aligned with their personal preferences. This is very concerning to us, because it means that some women did not get the treatment they truly preferred, and quite a few had more treatment than they preferred," says Clara Lee, MD, principal investigator of the study and a breast reconstructive surgeon at The OSUCCC - James. Lee holds a dual associate professor appointment in the colleges of medicine and public health at Ohio State. "Many women were quite concerned about complication risks, but they didn't actually know how high the risk was. This may explain some of the overtreatment that we saw," she adds. Researchers found that only 43 percent of the patients in the study demonstrated an understanding of at least half of the important facts about reconstruction and made a choice that was consistent with their preferences. Understanding of surgical complications was particularly low, with only 14 percent of patients demonstrating strong knowledge of associated risks. "As breast cancer providers, we need to talk about the pros and cons of surgery to help women make treatment choices. Shared decision-making between the surgeon and patient would be particularly useful for this decision. We need to connect patients with decision aids to help them really think through what is most important to them," Lee adds. Collaborators in this National Cancer Institute-funded study include Allison Deal, MD, and Ruth Huh, BA, of Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill; Michael Pignone, MD, MPH, of University of Texas at Austin; and Peter Ubel, MD, of Duke University. "The interesting thing is that these findings are not unique to breast reconstruction," adds Pignone, study coauthor and chair of the Department of Internal Medicine at the Dell Medical School at The University of Texas at Austin. "In other places where we've looked at decision quality, we see gaps in patients' understanding of key information and poor alignment between the things they care most about and the treatments that they choose. It means that we need to do a much better job of providing decision support to patients, so that the care they get is, ultimately, the care they want." Lee and colleagues in Ohio State's colleges of engineering, communication and public health are working on a study to evaluate treatment decisions in early-stage breast cancer patients to assess how communication with their providers affects their decision-making. This ongoing study examines patients' knowledge, preferences, and expectations about future well-being. Information from this study is expected to help clinicians develop tools to aid patients in making an informed decision about their care. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. Learn more at cancer.osu.edu.


News Article | May 3, 2017
Site: www.eurekalert.org

More than half of breast cancer patients (57 percent) undergoing mastectomy lack the necessary medical knowledge to make a high-quality decision about reconstructive surgery that aligns with their personal goals, suggesting a trend toward overtreatment, according to a new study conducted at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). "High-quality" decisions were defined as those that demonstrated adequate medical knowledge of treatment choices -- including associated risks -- and that also matched with the patient's specific goals and preferences for choosing whether or not to pursue reconstructive surgery. Researchers say shared decision-making tools are needed to help women make decisions based on a full understanding of treatment choices and associated risks alongside their personal goals for surgery. Researchers report the findings online first in the medical journal JAMA Surgery May 3, 2017. In this observational, single-institution study, researchers sought to evaluate the quality of 126 adult breast cancer patients' decisions about breast reconstruction after mastectomy. All patients had stage I-III invasive ductal/lobular breast cancer, ductal carcinoma in situ (DCIS) or were having preventive mastectomies, and the majority (73 percent) had early-stage disease. Researchers measured study participants' medical knowledge about mastectomy and mastectomy with reconstruction -- for example, effects of surgery on appearance and associated risks. They also measured individual preferences of what mattered most to patients. Key preference factors included breast appearance/shape post treatment, length of recovery time and risk for complications. "We found that less than half of the women had adequate medical knowledge about breast reconstruction and made a choice that aligned with their personal preferences. This is very concerning to us, because it means that some women did not get the treatment they truly preferred, and quite a few had more treatment than they preferred," says Clara Lee, MD, principal investigator of the study and a breast reconstructive surgeon at The OSUCCC - James. Lee holds a dual associate professor appointment in the colleges of medicine and public health at Ohio State. "Many women were quite concerned about complication risks, but they didn't actually know how high the risk was. This may explain some of the overtreatment that we saw," she adds. Researchers found that only 43 percent of the patients in the study demonstrated an understanding of at least half of the important facts about reconstruction and made a choice that was consistent with their preferences. Understanding of surgical complications was particularly low, with only 14 percent of patients demonstrating strong knowledge of associated risks. "As breast cancer providers, we need to talk about the pros and cons of surgery to help women make treatment choices. Shared decision-making between the surgeon and patient would be particularly useful for this decision. We need to connect patients with decision aids to help them really think through what is most important to them," Lee adds. Collaborators in this National Cancer Institute-funded study include Allison Deal, MD, and Ruth Huh, BA, of Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill; Michael Pignone, MD, MPH, of University of Texas at Austin; and Peter Ubel, MD, of Duke University. Lee and colleagues in Ohio State's colleges of engineering, communication and public health are working on a study to evaluate treatment decisions in early-stage breast cancer patients to assess how communication with their providers affects their decision-making. This ongoing study examines patients' knowledge, preferences, and expectations about future well-being. Information from this study is expected to help clinicians develop tools to aid patients in making an informed decision about their care. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. Learn more at cancer.osu.edu.


News Article | December 8, 2016
Site: www.prweb.com

Mike Gardner, President and CEO of third-party logistics provider Kane Is Able, Inc. (KANE -- http://www.kaneisable.com) was awarded the 2016 “Fearless Fundraiser” award by Pelotonia, an organization that runs fundraising bike tours to fight cancer. Pelotonia announced the award at the Pelotonia 2016 Check Celebration on Wednesday, November 9th at Express Live, an indoor-outdoor concert venue in downtown Columbus, OH. Mike’s efforts raised close to $70,000 in funds for cancer research this past year. Susie Pattison, Director of Rider Recruitment and Stewardship for Pelotonia, stated, “Mike set a high bar for all of our other participants! We are so grateful for his enthusiasm for this year’s campaign.” Pelotonia directs 100 percent of every dollar raised by participants to cancer research at The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, and Richard J. Solove Research Institute. Upon receiving the award, Mike said, “A few years ago, my dad was diagnosed with colon cancer. Through surgery, excellent medical care, prayers, and the support of family and friends, he continues to be in remission. Pelotonia is an amazing experience that combines physical challenge, philanthropy and community involvement. These are central tenets in my own life. I am proud to support one of the premier cancer centers in the country – one mile, and one dollar, at a time. Additionally, I’d like to thank the Kane family and our great KANE associates across the country, who have given generously to this cause.” Founded in 2008, Pelotonia was established with the objective to fund life‐saving cancer research. Pelotonia’s ride weekend is a three‐day experience that includes a weekend of cycling, entertainment and volunteerism. In its first seven rides, Pelotonia has raised more than $100 million for cancer research. About Kane Is Able Kane Is Able is a third-party logistics provider that helps manufacturers and their retail partners efficiently and effectively distribute goods throughout the United States. KANE’s value-added logistics services include retail consolidation, nationwide warehousing and distribution, contract packaging, fulfillment, and transportation solutions.


News Article | March 2, 2017
Site: www.biosciencetechnology.com

A new study by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) has identified a mechanism by which cancer cells develop resistance to a class of drugs called fibroblast growth factor receptor (FGFR) inhibitors. Published in the journal Molecular Cancer Therapeutics, the study also found that use of a second inhibitor might improve the effectiveness of these drugs by possibly preventing resistance, and it recommends that clinical trials should be designed to include a second inhibitor. FGFR inhibitors are a new family of targeted agents designed to inhibit the action of the fibroblast growth factor receptor, which is often overexpressed in lung, bladder, biliary and breast cancers. "Understanding how drug resistance develops can help in the design of new agents or strategies to overcome resistance," says principal investigator Sameek Roychowdhury, MD, PhD, assistant professor of medicine and of pharmacology in the Division of Medical Oncology at the OSUCCC - James. "Our paper demonstrates in a laboratory model how cancer can evade this class of therapy, and it provides insights into how clinical trials for these therapies could be further developed to overcome the problem of drug resistance," he adds. The laboratory study by Roychowdhury and his colleagues induced resistance to the FGFR inhibitor BGJ398 in lung- and bladder-cancer cells after long-term exposure to the agent. The researchers then found that, while the drug continued to inhibit FGFR activity in the resistant cells, its inhibition of FGFR signaling had no appreciable effect on the cells' survival. Examining other molecules in the FGFR pathway, the researchers found that a regulatory protein called Akt remained highly active, even during FGFR inhibition. Akt, a key regulator of cell biology, is directly involved in cell proliferation, cell survival and cell growth. Furthermore, they found that by inhibiting Akt they could significantly slow cell proliferation, cell migration and cell invasion in the lung cancer and bladder cancer cells. "Fibroblast growth factor receptor inhibitors are new therapies being developed in clinical trials for patients whose cancer cells have genetic alterations in this family of genes," says Roychowdhury, a member of the OSUCCC - James Translational Therapeutics Program. "We believe our findings will help improve this therapy for lung, bladder and other cancers."


News Article | August 22, 2016
Site: www.biosciencetechnology.com

New research links specific inherited genetic differences (alterations) to an increased risk for eye (uveal) melanoma, a rare form of melanoma that arises from pigment cells that determine eye color. Roughly 2,500 people are diagnosed with uveal melanoma in the United States annually. Previous clinical data suggests uveal melanoma is more common in Caucasians and individuals with light eye coloration; however, the genetic mechanisms underlying this cancer's development were largely unknown. In this new study -- co-authored by ophthalmologic pathologist and cancer geneticist Mohamed Abdel-Rahman, M.D., Ph.D., of The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and cancer geneticist Tomas Kirchhoff, Ph.D., of the Perlmutter Cancer Center of NYU School of Medicine - scientists report the first evidence of a strong association between genes linked to eye color and development of uveal melanoma. Reported data suggests that inherited genetic factors associated with eye and skin pigmentation could increase a person's risk for uveal melanoma. Abdel-Rahman, Kirchhoff and team report their findings in the medical journal Scientific Reports. "This is a very important discovery that will guide future research efforts to explore the interactions of these pigmentary genes with other genetic and environmental risk factors in cancers not linked to sun exposure, such as eye melanoma. This could provide a paradigm shift in the field. Our study suggests that in eye melanoma the pigmentation difference may play a direct cancer-driving role, not related to sunlight protection," says Abdel-Rahman. Unlike other solid tumors, there has been limited progress in understanding the contribution of genetic risk factors to the development of uveal melanoma, researchers say, primarily due to the absence of comprehensive genetic data from patients as the large sample cohorts for this rare cancer type have not been available for research. To overcome these limitations, researchers analyzed samples from more than 270 patients with uveal melanoma, most of whom were treated at Ohio State. Because there is a known clinical connection between eye melanoma and skin cancer, in this study researchers sought to determine whether there were commonly shared genetic factors between both diseases, as the inherited genetic risk of skin melanoma has been more extensively explored in previous medical literature. The team analyzed 29 inherited genetic mutations previously linked with skin melanoma to determine if there was an associated risk of uveal melanoma. This analysis revealed that five genetic mutations were significantly associated with uveal melanoma risk. The three most significant genetic associations occurred in a genetic region that determines eye color. "Genetic susceptibility to uveal melanoma has been traditionally thought to be restricted only to a small groups of patients with family history. Now our strong data shows the presence of novel genetic risk factors associated with this disease in a general population of uveal melanoma patients," says Kirchhoff. "But this data is also important because it indicates -- for the first time -- that there is a shared genetic susceptibility to both skin and uveal melanoma mediated by genetic determination of eye color. This knowledge may have direct implications in the deeper molecular understanding of both diseases," adds Kirchhoff. Researchers expect the data presented in this study to fuel the formation of large national and international research consortiums to conduct comprehensive, systematic analysis of inherited (germline) genome data in large cohorts of uveal melanoma patients. "This type of collaboration is critically needed to dissect additional modifying genetic risk factors that may be uveal melanoma specific. This has important consequences not only for the prevention or early diagnosis of the disease but potentially for more improved therapies for at-risk patients," says Kirchhoff. "Federal funding will be crucial to support research of rare cancers such as eye melanoma as it is likely, as shown in this study, that the impact of such research will extend across the different cancer types," adds Abdel-Rahman.


Other factors -- such as weight loss, a healthy diet and ceasing to smoke -- remain the top risk-reduction strategies both for developing cancer and premature cancer-related deaths COLUMBUS, Ohio - Regular use of over-the-counter non-steroidal inflammatory drugs (NSAIDs) such as aspirin and ibuprofen is associated with an increased risk of dying in patients diagnosed with Type 1 endometrial cancers, according to a new population-based study led by The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). In this observational study, a multi-institutional team of cancer researchers sought to understand the association of regular NSAID use and the risk of dying from endometrial cancer among a cohort of more than 4,000 patients. They found that regular NSAID use was associated with a 66 percent increased risk of dying from endometrial cancer among women with Type 1 endometrial cancers, a typically less-aggressive form of the disease. The association was statistically significant among patients who reported past or current NSAID use at the time of diagnosis, but it was strongest among patients who had used NSAIDs for more than 10 years in the past but had ceased use prior to diagnosis. Use of NSAIDs was not associated with mortality from typically more aggressive, Type 2 cancers. "There is a increasing evidence that chronic inflammation is involved in endometrial cancer and progression and recent data suggests that inhibition of inflammation through NSAID use plays a role," says Theodore Brasky, PhD, co-lead author of the study and a cancer epidemiologist with the OSUCCC - James. "This study identifies a clear association that merits additional research to help us fully understand the biologic mechanisms behind this phenomenon. Our finding was surprising because it goes against previous studies that suggest NSAIDs can be used to reduce inflammation and reduce the risk of developing or dying from certain cancers, like colorectal cancer." Researchers point out that information about specific dosages and NSAID use after surgery was not available in the current study, which represents a significant limitation. "We are continuing to analyze the biologic mechanisms by which inflammation is related to cancer progression in this specific cohort of patients," adds Ashley Felix, PhD, co-lead author of the study and cancer epidemiologist with the OSUCCC - James and College of Public Health. They report their findings in the Dec. 16, 2016, issue of the Journal of the National Cancer Institute. "These results are intriguing and worthy of further investigation," says David Cohn, MD, gynecologic oncology division director at the OSUCCC - James and co-author of the study. "It is important to remember that endometrial cancer patients are far more likely to die of cardiovascular disease than their cancer so women who take NSAIDs to reduce their risk of heart attack -- under the guidance of their physicians -- should continue doing so. While these data are interesting, there is not yet enough data to make a public recommendation for or against taking NSAIDS to reduce the risk of cancer-related death." Cohn says any woman concerned about the risks of long-term NSAID use should consult with her physician. For this study, researchers analyzed information from 4,374 endometrial cancer patients who previously participated in a national clinical trial (NRG Oncology/GOG 210). All of the women were eligible for surgery and had not undergone prior surgery or radiation at the time of enrollment. Participants were followed for an average of five years after enrollment. Study participants were asked at the beginning of the study to complete a questionnaire prior to surgery to capture information about previous and current NSAID use including aspirin, non-aspirin NSAIDs (ibuprofren, naproxen, indomethacin, piroxicam, sulinadac) and COX-2 inhibitors. Researchers collected information about duration of use -- ranging from less than one year to more than 10 years -- and whether that use was previous or current. Daily frequency of NSAID use, NSAID dosage, and use after surgery were not available. Researchers also collected clinical data (cancer stage, pathology, and treatment), demographic data (age, race, annual income, education) and information about established endometrial cancer risk factors, including body weight/height, reproductive and menstrual characteristics, history of hormone therapy, smoking status and other medical conditions. Researchers used regression models to statistically account for the influence of these additional factors on the association between NSAID use and endometrial cancer mortality. Funding for this research comes from grants to the NRG/Gynecologic Oncology Group (CA 27469, CA 37517, 1 U10 CA180822 and U10 CA180868); National Cancer Institute and National Institutes of Health. Additional collaborators in this study include Louise A. Brinton, PhD, of the National Cancer Institute; D. Scott McMeekin, MD, and Joan Walker, MD, of the University of Oklahoma; David Mutch, MD, and Premal Thaker, MD, Washington University School of Medicine; William Creasman, MD, Medical University of South Carolina; Richard Moore, MD, Women and Infants Hospital/Brown University; Shashikant Lele, MD, and John Boggess, MD, University of North Carolina; Saketh Guntupalli, MD, University of Colorado Cancer Center; Levi Downs, MD, University of Minnesota; Christa Nagel, MD, Case Western Reserve University; Michael Pearl, MD, State University of New York; Olga Ioffe, MD; University of Maryland; and Shamshad Ali, Roswell Park Cancer Institute. More than 60,000 women are diagnosed with endometrial cancer in the United States annually, making it the fourth most common cancer in women and sixth leading cause of cancer death. The cancer begins in the lining of the uterus and grows outward to surrounding organs. Type 1 tumors are less aggressive and are typically confined to the uterus at the time of diagnosis, whereas Type 2 tumors tend to be aggressive and are at greater risk of spreading. The disease is most common in women over age 60. Aside from aging, excess body weight, diabetes, certain hormone therapies, a family history of endometrial cancer or personal history of endometrial hyperplasia, breast cancer or ovarian cancer are associated with increased risk of the disease. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program's 306-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, please visit cancer.osu.edu.


News Article | March 2, 2017
Site: www.eurekalert.org

Columbus, Ohio - A new study by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) has identified a mechanism by which cancer cells develop resistance to a class of drugs called fibroblast growth factor receptor (FGFR) inhibitors. Published in the journal Molecular Cancer Therapeutics, the study also found that use of a second inhibitor might improve the effectiveness of these drugs by possibly preventing resistance, and it recommends that clinical trials should be designed to include a second inhibitor. FGFR inhibitors are a new family of targeted agents designed to inhibit the action of the fibroblast growth factor receptor, which is often overexpressed in lung, bladder, biliary and breast cancers. "Understanding how drug resistance develops can help in the design of new agents or strategies to overcome resistance," says principal investigator Sameek Roychowdhury, MD, PhD, assistant professor of medicine and of pharmacology in the Division of Medical Oncology at the OSUCCC - James. "Our paper demonstrates in a laboratory model how cancer can evade this class of therapy, and it provides insights into how clinical trials for these therapies could be further developed to overcome the problem of drug resistance," he adds. The laboratory study by Roychowdhury and his colleagues induced resistance to the FGFR inhibitor BGJ398 in lung- and bladder-cancer cells after long-term exposure to the agent. The researchers then found that, while the drug continued to inhibit FGFR activity in the resistant cells, its inhibition of FGFR signaling had no appreciable effect on the cells' survival. Examining other molecules in the FGFR pathway, the researchers found that a regulatory protein called Akt remained highly active, even during FGFR inhibition. Akt, a key regulator of cell biology, is directly involved in cell proliferation, cell survival and cell growth. Furthermore, they found that by inhibiting Akt they could significantly slow cell proliferation, cell migration and cell invasion in the lung cancer and bladder cancer cells. "Fibroblast growth factor receptor inhibitors are new therapies being developed in clinical trials for patients whose cancer cells have genetic alterations in this family of genes," says Roychowdhury, a member of the OSUCCC - James Translational Therapeutics Program. "We believe our findings will help improve this therapy for lung, bladder and other cancers." This work was supported by funding from the American Society of Clinical Oncology, the American Cancer Society, the Prostate Cancer Foundation, Fore Cancer Research, American Lung Association and Pelotonia. Other Ohio State researchers involved in this study were Jharna Datta, Senthilkumar Damodaran, Hannah Parks, Cristina Ocrainiciuc, Jharna Miya, Lianbo Yu, Elijah P. Gardner, Eric Samorodnitsky, Michele R. Wing, Darshna Bhatt, John Hays and Julie W. Reeser. The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 47 National Cancer Institute-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs sponsored by the NCI. As the cancer program's 308-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors and with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care. For more information, please visit cancer.osu.edu.


Caronia L.M.,Ohio State University | Phay J.E.,The Surgical Center | Shah M.H.,Solove Research Institute
Clinical Cancer Research | Year: 2011

BRAF, a cytoplasmic serine-threonine protein kinase, plays a critical role in cell signaling as an activator within the mitogen-activated protein kinase (MAPK) pathway. The most common BRAF mutation is the V600E transversion, which causes constitutive kinase activity. This mutation has been found in a multitude of human cancers, including both papillary thyroid cancer (PTC) and papillary-derived anaplastic thyroid cancer (ATC), in which it initiates follicular cell transformation. With such a high frequency of BRAF mutations in PTC (44%) and PTC-derived ATC (24%), research in BRAF V600E detection for diagnostic purposes has shown high sensitivity and specificity for tumor cell presence. BRAF V600E in PTC has also provided valuable prognostic information, as its presence has been correlated with more aggressive and iodine-resistant phenotypes. Such findings have initiated research in targeting oncogenic BRAF in cancer therapeutics. Although multiple phase II clinical trials in patients with iodine-refractory metastatic PTC have shown significant efficacy for sorafenib, a first-generation BRAF inhibitor, the mechanism by which it mediates its effect remains unclear because of multiple additional kinase targets of sorafenib. Additionally, preclinical and clinical studies investigating combination therapy with agents such as selective (PLX 4032) and potent (BAY 73-4506 and ARQ 736) small-molecule BRAF inhibitors and MAP/extracellular signalregulated kinase (ERK) kinase inhibitors (AZD6244) hold great promise in the treatment of BRAF V600Ecancers and may eventually play a powerful role in changing the clinical course of PTC and ATC. ©2011 AACR.

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