Newswise — Researchers at Johns Hopkins Medicine report new evidence that immune cells infected with a latent form of human immunodeficiency virus (HIV) are able to proliferate, replenishing the reservoir of virus that is resistant to antiretroviral drug therapy. Although HIV can be controlled with therapy in most cases, the proliferation of such reservoir cells pose a persistent barrier to developing a cure for HIV, researchers say.  “We knew before that the reservoir is very long lived,” says Robert Siliciano, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine, “but what we didn’t know was how the reservoir was maintained. Now it is clear that these cells aren’t just sitting there but are dividing and replenishing themselves.” A report on the new research, published March 24 in the Journal of Experimental Medicine, says resting CD4+ T cells not only make up the latent reservoir of HIV in those infected, but also have the potential to reactivate the production of active virus throughout the body. In the study, Siliciano and his team collected latently infected HIV cells from the blood of 12 patients with HIV on long-term antiretroviral therapy. After growing the CD4+ T cells in the laboratory, the investigators exposed them to four rounds of chemicals designed to stimulate cell division and proliferation. After each round of stimulation, the cell population was split into two separate groups and allowed to grow, one serving as a control and the other used to repeat the process. Following each stimulation, the researchers also measured whether the cells were releasing HIV. Previously, Siliciano explains, researchers suspected that such cells could not proliferate without releasing the active form of HIV. Although some cells did release HIV during the first stimulation, the subsequent stimulations of each cell line also released more virus, suggesting that some of the latently infected cells divided without releasing the infectious virus and maintained the ability to do so in subsequent stimulations.   The researchers then sequenced the genomes of the viruses. They speculated that if the viruses in subsequent stimulations from each patient were genetically identical, that would tell them the HIV they detected originated from cell division, rather than from independent infections because of HIV’s high genetic mutation rate. “When you sequence HIV from a patient, you typically get a huge variety of HIV viruses that are genetically different. Looking at the viruses we grew out, there was much less diversity. In fact, the sequences were mostly identical throughout the series of stimulations. We think that strongly suggests that what we are seeing is a single cell proliferating and copying the HIV DNA along with it,” Siliciano says. Siliciano’s team found that these kinds of viral copies were so common they could find multiple cells carrying the same variant of HIV in a single blood sample. “For this to be possible, the reservoir must be mostly composed of these cellular clones.” In the future, Siliciano and his team say they will search for specific factors that cause these cells to proliferate and to develop new techniques that allow them to study whether the location of the HIV genome in the cell’s DNA affects this process. More than 1.2 million people in the U.S. are living with HIV and one in eight of them are unaware that they are infected, according to the Centers for Disease Control and Prevention. Stigma and discrimination around HIV is still a major challenge to reaching and treating infected people, so the CDC estimates that only half of infected people have their virus under control with consistent treatment. However, the number of new HIV cases has fallen significantly since the 1990s and with improved awareness and improved treatments, the life expectancy of people infected with HIV is close to that of the general population. “Treatments now are so good,” Siliciano says, “that if we are able to eliminate the reservoir, we could cure HIV.” Other researchers involved in this study include Nina Hosmane, Kyungyoon Kwon, Katherine Bruner, Adam Capoferri, Subul Beg, Ya-Chi Ho and Janet Siliciano of the Johns Hopkins University School of Medicine, Daniel Rosenbloom of the Columbia University Medical Center and Brandon  Keele of the Fredrick National Laboratory for Cancer Research. This work was supported by the National Institute of Allergy and Infectious Diseases Extramural Activities Martin Delaney CARE and DARE Collaboratories (AI096113 and 1UI9AI096109), an ARCHE Collaborative Research Grant from the Foundation for AIDS Research (amfAR 108165-50-RGRL), The Johns Hopkins Center for AIDS Research (P30AI094189), the National Institutes of Health (43222), the Howard Hughes Medical Institute, the Bill and Melinda Gates Foundation, and the National Cancer Institute and National Institutes of Health (HHSN261200800001E).
Newswise — With a number of high-profile cases of prescription medication prices suddenly skyrocketing, people naturally start to wonder if perhaps some government control over the price of drugs might be a good idea. However, due to the high risk and high cost of developing new drugs, it’s possible that capping the amount of money that can be made from them would suppress development of new therapeutics. “If we have price controls, on the one hand, it seems like a good thing for the consumer,” said Mansoor A. Khan, RPh, PhD, professor and vice dean of the Texas A&M Irma Lerma Rangel College of Pharmacy College Station campus, “but, on the other hand, why would companies spend in excess of two billion dollars and wait 10 or more years to develop a drug if they can’t make a huge profit? That’s the balance we need to strike.” Adding to the risk is the possibility that drugs might be pulled from the market before they can make any money at all, and as many as 80 percent of the drugs that are sold don’t recover the amount of money spent on their development completely, according to Khan. At the same time, some blockbuster drugs manage to make billions of dollars, and that helps encourage drug companies to continue to create new medications. “It’s an extremely high-risk, but highly profitable business,” he said. Khan sees the approval of generics and competition in the market as being key to driving down costs. “We have a very good system in place in the United States to allow generic drugs after a certain number of years of exclusivity,” said Khan, who was director of the Division of Product Quality Research at the Food and Drug Administration (FDA) before joining Texas A&M. “About 88 percent of prescriptions are generic, and those manufacturers are able to copy the formulas of the original drug and avoid the extensive safety and efficacy clinical trials in patient populations, which means the medication becomes very inexpensive.” However, that’s only if the system works properly, and it doesn’t always. “Some brand products have been around a long time—and their exclusivity has long since expired—but there are still no generics,” Khan said. “That’s something the FDA needs to deal with more effectively.” One reason for the lack of generics is that sometimes a brand name drug company will file a citizen petition with the FDA, saying that manufacture of the drug is risky and complicated and that if generics are allowed, they may cause problems. “Generic approvals get delayed because of these petitions, and the FDA may ask the generic company to do additional testing or need extended multiple cycle of responses,” Khan said. These citizen petitions and response cycle times have the potential to delay timely access to generic medications. Generally, generics don’t have to undergo a lot of clinical pharmacodynamics studies or animal safety testing; they simply must show that their product has pharmaceutical equivalence and bioequivalence with the original drug—which provide an indication that it is also therapeutically equivalent. However, when the drug is something that is not absorbed into the body in sufficient quantities to be detected in the blood, bioequivalence can be difficult to prove. This is generally the case for locally acting antibiotics and anti-inflammatory drugs in the gastrointestinal tract, products topically applied to the skin or ocular products because their concentrations are not significant enough in the blood to measure and quantitate. Regulations do exist to do bioequivalence by in vitro laboratory studies, but there are not many published and peer-reviewed studies to show and validate what those in vitro studies are. Still, there are ways to approach the problem if the brand name drug company is insisting on further testing. “The regulations do provide a window, it’s just that a scientific determination needs to be made,” Khan said. “If the generic is made exactly the same as the brand, then you can test its stability and release in the different environments that exist in the human body, and if the release of the drug is the same or very similar as the brand, then we propose that it is very likely they will behave similarly in a human being.” A precedence of this approval by in vitro procedures without clinical bioequivalence studies is provided by the approval of locally acting vancomycin antibiotic capsules. Additionally, many generic products are made outside the United States. Inspections of those facilities are difficult and more complicated than inspection of domestic facilities. “Foreign facility inspections need to be streamlined and should be on par with the frequency of domestic inspections,” Khan said. “If they are not streamlined to ensure a consistently good quality generic product quality, we may see more problems of drug shortages with unexpected post-market failures.” Khan sees bringing the industry back to the United States as a required remedy, but says we need many more trained professionals. “Pharmaceutical and biotech industry might create 350,000 new jobs in the next ten years with regulatory reforms, according to Steven Ubl, the head of Pharmaceutical Research and Manufacturing Association, or PhRMA, but we don’t have anywhere near that number of people trained in the pharmaceutical sciences,” Khan said. “We have to be self-sufficient and shouldn’t depend on drugs manufactured elsewhere, and there is a tremendous opportunity here for education and training.” To that end, approval for master’s and doctorate programs in the College of Pharmacy is in the works, and Khan hopes students can begin taking classes in the fall of 2018. Collaboration is also key. “We need to bring our Health Science Center, engineering, veterinary medicine, AgriLife, life sciences and other programs together and have incentives for a multidisciplinary approach,” he said. “If people work together, there is no doubt they can bring down the cost with more efficient manufacturing processes, novel products and a more streamlined regulatory process.” “We cannot go on like this forever—some of these medications are just so expensive,” Khan added, “but if we avoid the greed displayed by some that have been identified in the media recently, and work together as a nation, there is no reason we cannot dramatically cut down on the price.”
Newswise — MINNEAPOLIS – Hospitals vary widely in how often they transition people with strokes from active treatment to comfort or hospice care within 48 hours after they get to the hospital, according to a new study published in the May 24, 2017, online issue of Neurology® Clinical Practice, an official journal of the American Academy of Neurology. “End-of-life and palliative care plays an important role with stroke, since the death rate is high, yet there has been limited data on the transition from treatment to comfort care,” said study author Shyam Prabhakaran, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago. For the study, researchers looked at data on 963,525 people hospitalized for stroke in 1,675 hospitals over a four-year period. Of those people, 54,794 were given an order for early comfort measures only. Researchers found overall 5.6 percent of people were transitioned to early comfort measures only, but the percentage varied widely by hospital, from just 0.6 percent of those with stroke in some hospitals up to 37.6 percent in others. Transitioning people to early comfort measures only did decline over the four-year period of 2009 to 2013, from 6.1 percent to 5.4 percent. Researchers also found that people who were transitioned earliest to comfort care were more likely to have had an intracerebral or subarachnoid hemorrhage than an ischemic stroke. Intracerebral hemorrhage, a bleeding stroke, is when a blood vessel bursts inside the brain. Subarachnoid hemorrhage is when it bursts in the area between the brain and the tissues that cover it. Ischemic stroke is when there is a blockage of blood flow to the brain. People with the bleeding types of stroke are more likely to die or have disability than people with ischemic strokes. Further analysis found the following factors were independently associated with orders for early comfort measures only: older age, female sex, white race, Medicaid and self-pay or no insurance, arrival by ambulance, arrival during off-hours and being unable to walk. For stroke type, 19 percent of people with intracerebral hemorrhage received early comfort measures only, compared to 13 percent of those with subarachnoid hemorrhage and 3 percent of those who had an ischemic stroke. “The use of early comfort care varies widely between hospitals and is influenced by stroke type as well as the characteristics of both the hospitals and the people who are hospitalized,” Prabhakaran said. “Future studies are needed to better define how such decisions are made.” Prabhakaran noted that comfort care is different than do not resuscitate orders, which do not limit the use of intensive stroke treatments. Limitations of the study include being unable to evaluate level of consciousness, to see brain scans of the extent of injury from stroke and other factors that could affect the patients’ prognosis. Robert G. Holloway, MD, MPH, of the University of Rochester Medical Center in New York and a Fellow of the American Academy of Neurology, said in an accompanying editorial, “Severe stroke is a common event often close to one’s death that unleashes a series of intense conversations among doctors, patients and families about what health states are acceptable or unacceptable and what makes life worth living. This study gives us insights into how these transitions are happening and will stimulate discussion about how we can improve this process to help ensure that care is high quality and consistent with the patient’s goals.” To learn more about stroke, visit The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 32,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.
Newswise — PHILADELPHIA— A new strategy – an injectable antibody – for lowering blood lipids and thereby potentially preventing coronary artery disease and other conditions caused by the build-up of fats, cholesterol, and other substances on the artery walls, is supported by findings from two new studies from researchers in the Perelman School of Medicine at the University of Pennsylvania. The new approach targets a protein called ANGPTL3, a regulator of enzymes that clear triglycerides and other fat molecules from the blood. Research in recent years has hinted that inherited mutations in the ANGPTL3 gene that disable its function can decrease triglyceride, LDL cholesterol and HDL cholesterol levels. As reported in a paper published online today in the New England Journal of Medicine, researchers from Penn Medicine, Regeneron Pharmaceuticals, and a group of international collaborators studied ANGPTL3 in both humans and mice. They found that blocking ANGPTL3 activity with an investigative injectable antibody, known as evinacumab, reduced triglycerides by up to 76 percent and lowered LDL cholesterol 23 percent in human study participants, and largely reversed signs of atherosclerosis in a mouse models. Researchers also included a human genetics study of approximately 188,000 people, which found that carriers of mutations that disable ANGPTL3 had nearly 40 percent fewer incidents of coronary artery disease as compared to those with fully functioning ANGPTL3.  “In the clinic, I treat many patients with very high triglycerides, but our current medications aren’t lowering triglycerides enough in many cases. I’m delighted at the prospect of a new treatment that’s a lot more potent, all the more because it lowers LDL at the same time,” said study co-author Richard L. Dunbar, MD, assistant professor of Cardiovascular Medicine and member of Penn’s Division of Translational Medicine and Human Genetics. “It’s very reassuring to see that people with this genetic defect actually seem to be protected from heart disease. I think that really bodes well for a therapeutic that’s targeting the ANGPTL3 pathway.” In a separate study, published in the March issue of the Journal of the American College of Cardiology (JACC) researchers from Penn Medicine, Harvard Medical School, Washington University in St. Louis, and nine other institutions, who also studied humans and mice, reported on a similar set of findings. Among these was the discovery from another large population sample that carriers of ANGPTL3-inactivating mutations had a 34 percent lower rate of coronary artery disease compared to non-carriers. “We used different lines of evidence to show that ANGPTL3 deficiency is associated with a reduced risk of coronary artery disease,” said study co-author Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. “But ultimately we were able to identify that fact that carriers of this genetic mutation did in fact experience a benefit – with little other health risk.” A beneficial gene defect The trial of research on ANGPTL3 as a potential target for atherosclerosis prevention began over a decade ago when scientists reported on two cases of familial hypolipidemia, a rare inherited condition involving abnormally low blood levels of cholesterol and triglycerides. Most cases of familial hypolipidemia are linked to other gene mutations that cause liver and digestive problems, but in members of this American family with the condition, Musunuru found mutations in the gene for ANGPTL3, and no associated health problems. In the NEJM study from Dunbar and colleagues, the antibody had similar effects in an initial clinical trial in 83 people, lowering the blood levels of triglycerides measured after fasting by about 75 percent at the highest dose, and lowering LDL cholesterol by about 30 percent. Statins and other drugs are already widely used to lower LDL cholesterol, but there are fewer options for lowering triglycerides. “For treating high triglyceride levels there’s really nothing out there that’s quite this potent, so that’s where I expect this new approach to have its greatest therapeutic benefit,” Dunbar said. Hypertriglyceridemia, a condition in which fasting triglyceride levels are greater than 150 mg/dL, is estimated to affect at least tens of millions of American adults. It is associated with coronary artery disease and other forms of atherosclerosis, and can lead to potentially fatal inflammation of the pancreas. In principle, the strategy of targeting ANGPTL3 could have an even broader use in treating atherosclerosis in the general population. The researchers found that in a mouse model of atherosclerosis, treatment with evinacumab reduced the area of atherosclerotic lesions by 39 percent. The population study findings, including those from the JACC study, suggest that even the partial inactivation of ANGPTL3—carriers typically have one mutant copy of the gene and one working copy—may be powerfully protective against coronary artery disease, which has long been one of the leading causes of death in developed countries. In the JACC study, for example, carriers of inactivating ANGPTL3 mutations had only a 17 percent reduction in triglycerides on average. But that modest reduction was associated with a 34 percent reduction in coronary artery disease risk. Moreover, Musunuru and his colleagues found that the people in their sample with the lowest blood levels of ANGPTL3 had a 35 percent lower rate of heart attacks compared to those with the highest ANGPTL3 levels. Dunbar noted that the population study findings probably have lain to rest a lingering concern about targeting ANGPTL3, namely its effect in lowering not just LDL and triglycerides but also the so-called “good cholesterol,” known as HDL cholesterol. “If lowering HDL were a major concern, then I don’t think we would have seen the evidence of overall benefit that we did in this study,” he said. The two studies together suggest that single copies of inactivating ANGPTL3 mutations are found in roughly one of every 250 people of European descent, whereas people with mutations in both copies of the gene—as in the family studied by Musunuru and colleagues—are much rarer. According to Dunbar, the next logical step would be to take evinacumab into larger clinical trials to study its safety, effectiveness, and optimal dosing. “The effect of even a single dose lasts for several months, and it’s plausible that with multiple doses we would see an even deeper and more sustained effect,” he said. Additional Penn authors on the NEJM study include Scott Damrauer, MD, Aeron Small, and Daniel J. Rader MD, and the Journal of the American College of Cardiology study include Xiao Wang, PhD, Daniel J. Rader, MD, and Danish Saleheen, MBBS, PhD. Funding sources for the studies detailed in this press release included grants from the National Heart, Lung, and Blood Institute (NHLBI) (R01HL131961), (K08HL114642), (R01HL118744), (R01HL127564) and (R21HL120781) and Regeneron Pharmaceuticals. Editor’s Note:  Dunbar has received grant support from and consulted for Regeneron Pharmaceuticals, Inc. ###
Newswise — Global leaders in cancer research have called for the worldwide sharing of cancer data to save lives. The Global Alliance for Genomics and Health argue how the ‘freeing of data’ for a disease that knows no borders will enable researchers to find better treatments that increase survival and improve quality of life  for cancer patients Professor Mark Lawler at the Centre for Cancer Research and Cell Biology (CCRCB) at Queen’s University Belfast and lead author of the study said: “Current restrictions on data sharing across borders limit the data that can be used by researchers to carry out a comprehensive analysis of cancer. “This is particularly pertinent when researching rare types of cancer. If data is limited to a particular region or country, low patient numbers can make clinical research impossible. But it can also pose challenges with common cancers such as breast cancer, which is made up of different subtypes. We need as much information as possible to help develop new diagnostic tests and treatments for these different subtypes.” Charles Sawyers of the Memorial Sloan-Kettering Cancer Center in New York and co-author of the paper said: “If we get this right, we can really use the data to help us in our aspiration to improve outcomes in this deadly disease.” Taking the lives of over 8.5 million people every year, cancer is a global challenge demanding a global response. The paper, published in the New England Journal of Medicine (NEJM) was conducted by a coalition of world leading cancer experts under The Global Alliance for Genomics and Health and led by Queen’s University Belfast. World-leading cancer researchers highlight the urgent need to foster a more collaborative culture, to work together and share data for the benefit of cancer patients around the world. Professor Lawler said: “Such an aspiration depends on both effective collaboration as well as dedicated resources. We hope that our call for a ‘global cancer knowledge network’ energises the community to act decisively and provide the resources to embed data sharing for the benefit of cancer patients globally. If we do, then big data really can save lives.” “Our experience shows that patients want to get involved to make a positive difference so we need to help them to do that.” Recently, a group of patients with a rare gene mutation called ROS 1 that can cause different cancers came together online, frustrated about the lack of progress in the treatment of their disease. The online group involving over 130 individuals from eleven different countries approached a disease foundation and they are now involved in the first steps of developing a clinical trial that targets the particular genomic abnormality that causes their disease.  Professor Lawler added: “We are working with the disease foundation to help make this clinical trial a reality. This exemplifies why accessing data is so vital to enable researchers to carry out their work and ultimately to help patients.”  Margaret Grayson, a breast cancer survivor and Chair of the patient group, the Northern Ireland Cancer Research Consumer Forum explained: “Research is vital to improve the quality of life as well as life expectancy for cancer patients. Many patients will be more than willing to get involved and share their clinical information to bring us one step closer to tackling this global health issue.”     The paper, ‘Sharing Clinical and Genomic Data on Cancer – The Need for Global Solutions’ is being published in the New England Journal of Medicine (NEJM) on 25 May.
Newswise —  WASHINGTON, DC─ African Americans with sleep apnea and insomnia are rarely diagnosed with either problem, even when the severity of the two sleep disorders are likely to affect their health, according to new research presented at the ATS 2017 International Conference. “African Americans experience a disproportionate burden of numerous health problems, including obesity, diabetes, hypertension and cardiovascular disease, all of which have been shown to be associated with sleep,” said lead study author Dayna A. Johnson, PhD, MPH, MS, MSW, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School. “It seems plausible that sleep apnea and insomnia are important risk factors contributing to these health disparities.” Dr. Johnson and her colleagues studied data of 825 African Americans who underwent a sleep study as part of the Jackson (Miss.) Heart Study, which is funded by the National Institutes of Health and is the largest single-site prospective investigation of cardiovascular disease in African Americans undertaken. The average age of those undergoing the home sleep study was 63 years, and two-thirds of the participants were women. The researchers defined sleep apnea, which produces pauses in breathing, based on the apnea-hypopnea index (AHI), which measures the number of pauses that occur per hour of sleep. An AHI >5 was considered mild; an AHI >15, moderate; and an AHI >30, severe.  The researchers used the Women’s Health Initiative (WHI) Insomnia Rating Scale, a commonly used assessment of perceived insomnia symptoms, to define insomnia. Participants with a score >10 were considered to have insomnia. Participants were asked if a physician had told them that they suffered from either of the disorders. The study found that three of every four participants had sleep apnea: 38.4 percent had mild sleep apnea; 21.3 percent had moderate sleep apnea; and 15.8 percent had severe sleep apnea. But only 2.1 percent of those with sleep apnea reported that a physician diagnosed the condition. Higher body mass index, hypertension, diabetes, being male and being older were all associated with sleep apnea and its severity. The study also found that more than 2 in 10 participants suffered from insomnia. But only 6.7 percent of them reported a physician diagnosis. According to Dr. Johnson, the prevalence of both sleep apnea and insomnia in the study population was higher than would be expected in the general population of adults of a similar age. “There is a disturbingly high prevalence of undiagnosed sleep disorders in our study population of African Americans,” she said. “It is important to investigate the reasons for this high prevalence as well as investigate interventions targeted at increasing awareness and screening for sleep disorders.” Because treating these sleep disorders “could drastically improve quality of life and reduce the burden of subsequent adverse health outcomes,” Dr. Johnson added, clinicians need to identify patients at risk of these sleep disorders and encourage them to undergo sleep studies. In addition, although public awareness of sleep apnea is growing, efforts targeting the most at-risk populations may be warranted. Dr. Johnson said that study findings from the Jackson, Miss., metropolitan area may not apply to African Americans living elsewhere. “African Americans living in Jackson, Mississippi, may not be representative of all African Americans due to differences in risk factors that may be related to geography,” she said. Contact for Media: Dayna A. Johnson, PhD, MPH, MS, MSW, ###
Newswise — Among 12- to 17-year-olds who have never used tobacco products, nearly half were considered receptive to tobacco marketing if they were able to recall or liked at least one advertisement, report a coalition of behavioral scientists in a new national study. Receptivity to tobacco ads is associated with an increased susceptibility to smoking cigarettes in the future.Led by researchers at University of California San Diego Moores Cancer Center and Dartmouth’s Norris Cotton Cancer Center, the researchers analyzed data from the Population Assessment of Tobacco and Health (PATH) Study, which included interviews with 10,751 adolescents who reported having never used any type of tobacco product. Risk to use a tobacco product in the future was the researchers’ main point of interest. The findings are published in the May 22 issue of Pediatrics."Tobacco marketing restrictions differ by product with only e-cigarettes allowed to be advertised on television,” said John P. Pierce, PhD, Professor Emeritus in the Department of Family Medicine and Public Health at UC San Diego School of Medicine and Moores Cancer Center and lead author on the study. "Previous studies have linked receptivity to cigarette advertising with susceptibility to smoke cigarettes among youth. What we’re seeing in this study is that even being receptive to marketing of non-cigarette tobacco products, including e-cigarettes, is associated with susceptibility to smoke cigarettes.”In this analysis of the first wave of data from the PATH Study, respondents were considered susceptible to tobacco or committed to never using these products based on responses to three questions assessing their curiosity about the product, intention to try it in the near future, and likely response if a best friend were to offer them the product. Only those with the strongest rejection to all three questions were categorized as committed to never use. All others were susceptible. This index has been validated in multiple studies.Participants were shown 20 tobacco ads chosen randomly from 959 ads representing all available recent commercials used in print, direct mail, internet or television advertisements. Each respondent was asked initially to name his or her favorite tobacco ad and then shown a random set of five ads for each of the following products: cigarettes, e-cigarettes, cigars and smokeless products. For each ad presented, they were asked if they had seen the ad in the past 12 months and whether they liked the ad. Aided recall was classified as low receptivity while image-liking or favorite ad was considered to be higher.A high proportion of under-aged adolescents in the United States are still exposed to tobacco advertising. The study found that 41 percent of 12- to 13-year-olds, and about half of both 14- to 15-year-olds and 16- to 17-year-olds were receptive to any type of tobacco advertising. "Six of the top 10 most recognized tobacco ads by adolescents were for e-cigarettes, four of which were aired on TV," said James Sargent, MD, director of the C. Everett Koop Institute at Dartmouth and co-author. "The PATH Study will continue to track these adolescents who have not used tobacco and will be able to identify if receptivity to marketing for different tobacco products during wave 1 of the study — particularly e-cigarette marketing — increases cigarette smoking one or two years later."Receptivity to advertising was highest for e-cigarettes with 28 to 33 percent across age groups, followed by 22 to 25 percent for cigarettes and 15 to 21 percent for cigars. E-cigarette advertising is of interest to researchers because of its presence on television and because showing people vaping is very similar to showing people smoking, said Pierce. The proportion who were susceptible to using tobacco products increased with the level of receptivity. Fifty percent of respondents considered to have low receptivity, 65 percent who were moderately receptive and 87 percent of youth who were deemed highly receptive were susceptible to use tobacco products.“Cigarette smoking is still a major problem and a major cause of lung cancer and other diseases,” said Pierce. “We’ve had big declines in the number of people who initiated smoking, but it is important that we maintain that reduction.”Co-authors include: Martha White, David R. Strong, Eric Leas, Madison Noble, Dennis Trinidad, Karen Messer, UC San Diego; Nicolette Borek, David B. Portnoy, Blair N. Coleman, US Food and Drug Administration; Victoria R. Green, National Institutes of Health and Kelly Government Solutions; Annette R. Kaufman, National Cancer Institute; Cassandra A. Stanton, Westat and Georgetown University Medical Center; Maansi Bansal-Travers, Andrew Hyland, Roswell Park Cancer Institute; Jennifer Pearson, Johns Hopkins University and Schroeder Institute for Tobacco Research and Policy Studies at Truth Initiative; Meghan B. Moran, Johns Hopkins University; and Charles Carusi, Westat. This research was funded by the National Institute on Drug Abuse, National Institutes of Health, and the Food and Drug Administration, Department of Health and Human Services, under a contract to Westat, which collected data using Audio-Computer-Assisted Self Interviews. ###
Newswise — LOS ANGELES – New research from the Keck School of Medicine of the University of Southern California (USC) shows new promise in the fight against one of the most lethal forms of cancer. Studies in mice with a mutation present in 90 percent of pancreatic cancer patients (the KRAS mutation) indicate that expressing only half the amount of the glucose-regulated protein GRP78 is enough to halt the earliest stage of pancreatic cancer development. The study, funded in part by the National Institutes of Health, suggests that because the protein is required for “switching” healthy pancreatic cells that produce enzymes to digest food into potentially cancerous cells, reducing the amount of this protein delays pancreatic cancer development and prolongs survival. The study, published online on May 16 in the Proceedings of the National Academy of Sciences of the United States of America, is the first to establish the pivotal role of the protein in pancreatic cancer. “Cancer cells are addicted to high levels of GRP78 for cancer development and growth. Our hope is that partially reducing or inactivating the protein by therapeutic agents could one day be an effective complementary therapy for pancreatic cancer and other cancers, while sparing other healthy organs,” said Amy Lee, PhD, professor of biochemistry and molecular medicine at the Keck School and the Judy and Larry Freeman Chair in Basic Science Research at the USC Norris Comprehensive Cancer Center. Lee, who was the first scientist to clone human GRP78, has since dedicated much of her research to investigating the protein’s role in cancer progression and treatment. For her scientific contributions, Lee was honored by a MERIT award from the National Cancer Institute and elected as Fellow of the American Association for the Advancement of Science. “As developing drugs directly targeting the KRAS genetic mutation has been challenging, we are thrilled these findings indicate that we can attack KRAS-driven pancreatic cancer through an entirely new method,” Lee said. GRP78 is a stress-inducible protein that folds newly synthesized proteins and performs quality control in the endoplasmic reticulum (an essential component of human cells). During stress, a fraction of GRP78 is shipped out to the cell surface to perform additional growth and survival functions. Cancer cells, particularly those that survive treatment, typically undergo more stress than healthy cells, resulting in increased levels of GRP78 to help the cancer cells survive, grow and develop therapeutic resistance. A number of studies across cancer types have shown a relationship between highly elevated levels of the protein and increased risk for cancer recurrence or decreased survival. With GRP78 emerging as an attractive anti-cancer target, there is active development of potential treatments that can inhibit GRP78 activity or expression, including some that are in early-phase clinical trials with promising results. Certain food and herbs, including green tea and soy, contain natural compounds that can suppress the protein, Lee said. Patients and physicians alike are eager for more effective treatments for pancreatic cancer, as it is among the deadliest forms of cancer. According to the American Cancer Society, more than 53,600 people will be diagnosed with pancreatic cancer this year, and more than 43,000 people will die from the disease. The five-year survival rate for early stage pancreatic cancer is only 12 percent, compared to 100 percent for breast cancer and prostate cancer and 92 percent for colon cancer. “Translating any basic science discovery into clinical practice is a long process that requires substantial resources,” Lee said. “But given the notorious difficulties of treating KRAS-mutation related cancers, particularly in a disease as devastating as pancreatic cancer, this research provides hope and a novel approach. I am excited to put our theories to test in the clinical setting.” ###
Newswise — The Valley Heart and Vascular Institute in Ridgewood, NJ, has been selected as 1 of just 10 hospitals – and the only hospital in New Jersey – to participate in a nationwide study investigating a minimally invasive aortic valve replacement procedure for individuals with aortic stenosis. The first-of-its-kind clinical trial, led by Medstar Washington Hospital Center in Washington, D.C., aims to evaluate the use of transcatheter aortic valve replacement (TAVR), a minimally invasive procedure, in aortic stenosis patients who are at low risk for conventional open-heart surgery. TAVR is not yet approved by the FDA for use in this population.  TAVR has already been established as a treatment option for intermediate- and high-risk patients. The trial is now open and will be enrolling 200 patients over a 24-month period. It will be non-randomized, meaning individuals who qualify will be selected to undergo the TAVR procedure instead of open-heart surgery.  "TAVR has already been shown to extend lives and improve the quality of life for intermediate- and high-risk patients who just a few years ago may not have had an alternative to open-heart surgery,” said John Goncalves, M.D., Director of Cardiac Surgery at The Valley Hospital and Surgical Director of Valley’s TAVR Program. “This is an exciting study to be a part of because it may potentially prove the effectiveness of TAVR for low-risk patients and open the door for others to qualify for this minimally invasive procedure in the future.” TAVR is a procedure used to treat aortic stenosis, a life-threatening condition that occurs when blood flow is obstructed due to the narrowing of the aortic valve, one of the valves in the heart. Using TAVR, the heart team can replace a diseased aortic heart valve in a less-invasive manner than with open-heart surgery. The procedure requires only a small incision in the groin, through which an expandable heart valve is placed into the body and up to the heart via a catheter-based delivery system. Studies have shown that patients achieve better outcomes when undergoing TAVR than with medication alone. “We are honored to be recognized for our expertise and experience with the TAVR procedure,” said Dr. Goncalves. “Clinical trials like this are critical to our work providing the highest quality and most innovative care for our patients.” Individuals interested in making an appointment for an evaluation to see if they are a candidate for this study are encouraged to contact Jaclyn Chomsky, D.N.P., Valve Coordinator at Valley, at 201-447-8378 or
Newswise — Social media is more than a way to connect with friends, access news or information, or watch entertaining videos. It’s now a proven method of conducting medical research. Researchers in the Urology department at Beaumont Hospital, Royal Oak, Michigan collaborated with the Interstitial Cystitis Association to use social media to recruit research volunteers for a study leading to the development of a new urine biomarker for the diagnosis of interstitial cystitis. IC causes recurring pelvic pain, pressure or discomfort in the bladder and pelvic region, often associated with urinary frequency and urgency. In extreme cases, patients with IC may urinate 60 times a day or more. The social media research exceeded expectations. Within just two weeks, 454 women and men from 46 states participated in the study, watching a YouTube video and completing an online survey. Qualified participants were sent a prepaid return shipping container to provide a urine sample. The container included preservatives to maintain protein and nucleic acid in the urine at room temperature. Analysis of the samples led to the discovery of three proteins that were highly statistically different for research participants with IC with ulcer versus those without ulcer. This was then used in a machine-learning program to accurately classify patients with the disease. The research was presented May 13 at the American Urological Association meeting in Boston, the largest meeting of urologic specialists in the world. IC is a disease that affects more than 12 million people in the U.S. and currently does not have a single, objective laboratory test for diagnosis. Laura Lamb, Ph.D., urology research scientist at Beaumont, said “Our goal was to develop a simple urine-based test that identifies IC patients with bladder pain syndrome who have ulcerative IC and a bladder permeability defect. The test had to be developed and validated in a large number of samples collected beyond the referral area of our single academic medical center.” Participants were recruited through a collaboration with the Interstitial Cystitis Association, which has an active presence across several social media platforms. “IC is ideal for social media research,” said Kenneth Peters, M.D., chief of Urology, Beaumont, Royal Oak. “The IC community is a motivated patient group because of their poor quality of life. They are relatively younger compared to patients with other chronic diseases; as such, they may be more comfortable and familiar with the internet and social media.” The use of social media is an emerging approach for medical researchers to rapidly collect, process and interpret data, generating support for medical advances that would otherwise be impossible due to research funding constraints and the large number of participants needed for medical research. Michael Chancellor, M.D., director of Neurourology at Beaumont, Royal Oak, predicts that, “As the research community discovers this new role of social media, medical research may no longer be confined to academic centers, but will be a collaboration of key stakeholders across the world.” “Our study achieved diversity in sample source collection from across the U.S. and engaged many national stakeholders using social media,” said Dr. Chancellor. “And the outcome of the study is significant - the development of a bladder permeability risk score that is the first validated urine biomarker test for interstitial cystitis/bladder pain syndrome.” The research was supported with funding from the Taubman Family through the Taubman Interstitial Cystitis Research Program. # # #