1 HEALTH.GOV.AU 12/07/2012 HPV vaccine extended to boys In a world first, Australian schoolboys will be able to get the successful Gardasil vaccine, which will protect them against developing a range of cancers and bolster the effectiveness of this vaccine in women. Starting next school year, the Gillard Government will fund the vaccine for 12 and 13-year-old boys through school-based programs under the National Immunisation Program. Year 9 boys will also be able to get the vaccine at school under a catch-up program for the next two years. Minister for Health Tanya Plibersek said providing the HPV vaccine to boys would protect them and increase the effectiveness of the vaccination program for girls. "Every parent wants their child to be healthy and that is why the Australian Government is delivering the best protection we have against HPV related cancer through this vaccine," said Ms Plibersek. "By building on Australia's world-class immunisation program, we're stopping preventable HPV related disease and cancers, and that makes a difference to the quality of life of our families. "Already the HPV vaccine has had an impact significantly reducing the number of lesions that lead to cervical cancer amongst women in the vaccinated age group. It is estimated that a quarter of new infections will be avoided by extending the vaccine to boys," said Ms Plibersek. An Australian innovation, the vaccine protects against four important genotypes of the human papillomavirus (HPV). The HPV vaccination program for boys is expected to cost $21.1 million over four years. This will include an information campaign, a vaccine register and monitoring of adverse reactions. Ms Plibersek said the Pharmaceutical Benefits Advisory Committee had recommended last year that the HPV vaccination program be extended to boys following a review of its cost effectiveness. She said the Australian Government would work with all states and territories to implement the boys' vaccination program in high schools. WASHINGTON UNIVERSITY - ST.LOUIS 12/07/2012 Noninvasive imaging technique may help kids with heart transplants By Julia Evangelou Strait Cardiologists at Washington University School of Medicine in St. Louis have developed a noninvasive imaging technique that may help determine whether children who have had heart transplants are showing early signs of rejection. The technique could reduce the need for these patients to undergo invasive imaging tests every one to two years. The new method is described online in the Journal of Heart and Lung Transplantation. The invasive imaging test, a coronary angiogram,
2 involves inserting a catheter into a blood vessel and injecting a dye to look for dangerous plaque on the walls of arteries feeding blood to the heart. This plaque build-up indicates coronary artery disease and is a sign that the body may be rejecting the new heart. Since pediatric heart transplant patients are at high risk of developing coronary artery disease, doctors monitor their arteries on a regular basis. But recurring angiograms become problematic. "Many of these children have undergone so many operations, we have lost access to their big blood vessels," says Charles E. Canter, MD, professor of pediatrics. "Sometimes it's impossible to do catheterization procedures on them." Based on experience imaging other types of inflammation in arteries, senior author Samuel A. Wickline, MD, professor of medicine, and his colleagues, including Canter and medical student Mohammad H. Madani, a Doris Duke Clinical Research Fellow, examined whether they could assess coronary artery disease in these children using magnetic resonance imaging (MRI). In this case, the MRI was enhanced with a commonly used contrast agent called gadolinium that is injected into the arteries. Gadolinium is not radioactive and makes areas of inflamed arteries and heart muscle show up brighter on an MRI. "The brighter it is, the more it is associated with coronary artery disease," Canter says. The study included 29 heart transplant patients and eight healthy children who served as controls. The transplant patients underwent standard coronary angiograms as part of their normal care. They also had MRIs of the coronary arteries to examine whether the noninvasive method correlated with the degree of coronary artery disease found in the angiograms. The eight children who served as controls only had MRI scans. The researchers assessing the MRI results were blinded to the results of the transplants patients' angiograms. While all of the transplant patients' angiograms showed evidence of plaque build-up, in only six of them was it severe enough for a diagnosis of coronary artery disease. These six patients had the brightest coronary arteries on the MRI scans, compared to both the transplant patients without coronary disease and the healthy controls. Still, the 23 transplant patients without diagnosed coronary disease had significantly brighter arteries than the healthy participants. Such evidence demonstrates the need to continue monitoring these patients. Although the brightness of the arteries on MRI correlated well with a diagnosis of coronary artery disease, gadolinium can be toxic to the kidney, Canter points out. This means the technique can't be used for patients with poor kidney function. Furthermore, clear images with MRI are difficult in very young children because of their high heart rates. In this study, no participant was younger than age 10. Nevertheless, Canter sees a possible future place for this technique in helping to monitor the progress of coronary artery disease in transplant patients. "The results of this pilot study were very promising," Canter says. "But we need to look at more patients. We're in the process of developing a bigger study to confirm and refine the results. I think eventually this could be used as a screening technique, not so much to eliminate, but to reduce the number of angiograms." MEDWIRE-NEWS.MD 13/07/2012 More reason to restrict hormone therapy during menopause By Piriya Mahendra PLoS One7(7): e40260 Researchers have found further evidence to show that menopausal hormone therapy (MHT) increases the risk for high blood pressure (BP) in postmenopausal women. The association between the MHT use and high BP diminished
3 with increasing age, which shows that age is a significant predictor for the development of high BP, comment the authors in PLoS One. Joanne Lind (University of Western Sydney, New South Wales, Australia) and team found that MHT use was associated with a 59% increased risk for high BP in women younger than 56 years of age, a 58% increased risk for those aged years, and a 26% increased risk for those aged years. However, in women aged 71 years and older, there was no significant association between MHT use and high BP. Moreover, there was no statistically significant difference in the odds for having high BP between past and current users of MHT in any age group. The duration of MHT use was significantly associated with the risk for having high BP, with women who had used MHT for longer time periods having greater increases in risk. Indeed, among women younger than 56 years who had used MHT for less than 2 years, the risk for high BP was increased 0.07%, whereas for those who had used it for more than 10 years, the risk was increased more than threefold. The findings of the current study, conducted in 43,405 postmenopausal women, are in line with current US Food and Drug Administration recommendations that MHT should be limited to the shortest possible duration consistent with treatment goals. However, previous studies have shown conflicting results, with some supporting the use of MHT in reducing the risk for cardiovascular disease, and some showing it to increase risk."women who require MHT should be closely monitored as they may represent a population of women with subclinical cardiovascular disease, and BP should be monitored after treatment ceases," caution the authors. "Furthermore, high BP should be conveyed as a health risk for people considering MHT use." INSTITUT NATIONAL DU CANCER 13/07/2012 Le grand programme de sequençage des genomes tumoraux produit ses premiers resultats Des analyses approfondies du ge'nome de 21 tumeurs du sein et de 24 tumeurs du foie dressent un paysage ine'dit des mutations implique'es dans le de'veloppement des cancers. Pre'sente au cœur de chacune de nos cellules, la mole'cule d'adn est une longue suite de quatre bases azote'es (A, C, G, T). Au cours du processus de de'veloppement d'une tumeur, les cellules cance'reuses acquièrent des mutations de l'adn, par exemple une "lettre" C est remplace'e par un T : ces mutations sont qualifie'es de "somatiques" par diffe'rence avec les mutations germinales transmises aux enfants par leurs parents. Grâce aux progrès des techniques de se'quençage et d'analyse du ge'nome, il est de'sormais possible, par comparaison entre l'adn de cellules tumorales et l'adn de cellules sanguines, de dresser tre's pre'cise'ment le catalogue de ces mutations somatiques dans les divers types de tumeurs. C'est l'objectif initial d'un grand programme, dont l'institut national du cancer (INCa) est membre, l'international Cancer Genome Consortium (ICGC). Mises a' la disposition de la communaute' scientifique, les donne'es accumule'es par l'icgc doivent ensuite permettre de donner du sens aux mutations identifie'es, le but ultime e'tant d'e'laborer de nouvelles strate'gies dans la pre'vention, le diagnostic ou le traitement des cancers. Lance' en 2008, l'icgc implique, pour chaque type tumoral, un processus complexe auquel participent de nombreux acteurs: patients, me'decins, ge'ne'ticiens et
4 bioinformaticiens travaillant sur de puissants outils d'analyse du ge'nome. Les premiers re'sultats de l'icgc viennent d'être publie's pour deux types tumoraux sur lesquels l'inca est engage'(1) : les tumeurs du sein et du foie. Mene's par de nombreux chercheurs europe'ens, les travaux sur les tumeurs du sein ont fait l'objet de deux articles dans la prestigieuse revue Cell: le premier livre une "photographie" des mutations somatiques tandis que le second tente de reconstruire le "film" des e've'nements qui ont abouti a' cette "photographie". Ces re'sultats s'appuient sur une profondeur ine'gale'e du se'quençage des ge'nomes de 21 tumeurs. Pour aborder le problème de l'he'te'roge'néité des cancers, le génome de l'une d'entre elles, en particulier, a e'te' analyse' 188 fois! Après avoir dresse' un catalogue brut des mutations individuelles, les chercheurs se sont demande' s'ils pouvaient identifier des re'gularite's au sein de cet oce'an de donne'es : par exemple, en observant le contexte d'apparition des modifications de l'enchaînement des bases ou "fautes d'orthographe" de l'adn, c'est-a'-dire en lisant le texte constitue' par les lettres situe'es a' proximite' imme'diate des mutations observe'es. Pour y parvenir, ils ont adapte' a' leurs besoins un logiciel qui, dans sa version initiale, servait a' la reconnaissance automatique de visages sur des photographies. Et, de fait, ils ont repe're' cinq "signatures" qui, chacune, correspond probablement a' un processus biologique diffe'rent. Les chercheurs ont pu relier l'une de ces signatures a' un processus qui, pre'ce'demment, a e'te' implique' dans la cance'rogenèse. Pour les quatre autres, le travail d'interpre'tation reste a' faire, ce qui ouvre de nouvelles pistes de recherche. Par ailleurs, les chercheurs ont mis en e'vidence un nouveau phe'nomène, qu'ils ont appele' kataegis (orage, en grec) pour de'crire l'apparition simultane'e, ou très rapide, de groupes de mutations dans une re'gion de l'adn. Une première analyse suggère qu'une certaine famille d'enzymes serait implique'e dans ce processus mais, la' aussi, les me'canismes pre'cis restent a' e'lucider. Pour reconstituer le film des e've'nements ayant engendre' toutes ces mutations, les chercheurs ont emprunte' des concepts a' la ge'ne'tique des populations. Dans la vision classique du de'veloppement des cancers, l'accumulation de mutations somatiques confère un avantage se'lectif a' une population de cellules qui, progressivement, envahit toute la tumeur. Or, de nombreux travaux montrent qu'en re'alite', les tumeurs sont he'térogènes et qu'elles contiennent un mélange de populations cellulaires en compe'tition. Dans le processus actuellement utilise' pour le se'quençage d'un ge'nome de grande taille, tel que le ge'nome humain, celui-ci se pre'sente sous la forme d'un grand nombre de fragments d'adn. Dans le cas d'un ge'nome tumoral, ces fragments proviennent de diffe'rentes cellules issues de l'e'chantillon analyse'. Leur e'tude permet donc d'e'valuer le degre' d'he'te'roge'ne'ite' de la tumeur. Les chercheurs ont d'abord commence' par analyser les donne'es produites par le très profond se'quençage d'une tumeur. Puis, a' l'aide d'algorithmes sophistique's de ge'ne'tique des populations, ils ont tente' de reconstruire l'arbre "ge'ne'alogique" des cellules tumorales. Ils ont ensuite répété ce processus sur les vingt autres tumeurs pour confirmer leurs re'sultats. Comme les chercheurs l'avaient anticipe', chaque tumeur semble bien être forme'e de différentes sous-populations cellulaires issues d'un "ancêtre commun", unique pour chaque patiente, tandis qu'une population cellulaire semble dominante, repre'sentant au moins la moitie' du volume tumoral. Les chercheurs en ont de'duit le sce'nario suivant du de'veloppement d'un cancer du sein: pendant un certain temps, la tumeur est forme'e de petites colonies cellulaires pre'sentant de subtiles diffe'rences jusqu'a' ce que, pour des raisons encore inconnues, l'une d'entre elles prenne le dessus, entre en croissance rapide et finisse par provoquer des symptômes. Une observation comple'mentaire s'ave're cruciale : les mutations essentielles semblent apparaître tre's tôt au cours de la vie d'une tumeur.
5 Puisque ces mutations sont pre'sentes sur le tronc de l'arbre "ge'ne'alogique" tumoral, les strate'gies the'rapeutiques ciblant les produits de ces mutations conservent donc toutes leurs promesses. Publie'e dans la revue Nature Genetics, l'e'tude sur les tumeurs du foie a e'te' re'alise'e par une e'quipe française dirige'e par Jessica Zucman-Rossi (Unite' Inserm 674). Pre'leve'es sur des patients atteints d'un carcinome he'patocellulaire souvent associe' a' une forte consommation d'alcool, 24 paires d'e'chantillons de tissu tumoral et de tissu sain ont e'te' analysées dans le cadre du programme ICGC. Dans un premier temps, l'analyse a notamment permis d'identifier quatre nouveaux gènes qui, jusqu'a' pre'sent, n'avaient jamais e'té implique's dans les tumeurs hépatiques. Puis une analyse fonctionnelle mene'e sur une centaine de tumeurs complémentaires a montre' que, d'un point de vue physiologique, certaines mutations e'taient spécifiques de la cause identifiée dans la transformation (alcool, virus C) et alte'raient plusieurs voies de signalisation distinctes, en inactivant des fonctions de suppression des tumeurs ou en activant des fonctions oncoge'niques. Ces travaux ouvrent des pistes de recherche pour le de'veloppement de the'rapies ciblant les produits de ces alte'rations nouvellement identifie'es. NICHD.NIH.GOV 13/07/2012 Federal report shows drops in infant mortality, preterm birth rates Annual statistics compilation notes increases in poverty, drop in secure parental employment The infant mortality rate, the preterm birth rate, and the adolescent birth rate all continued to decline, average mathematics scores increased for 4th and 8th grade students, the violent crime victimization rate among youth fell, as did the percentage of young children living in a home where someone smoked, according to the federal government's annual statistical report on the well-being of the nation's children and youth. However, the percentage of children living in poverty increased, and the percentage of children with at least one parent employed full time, year-round decreased, the report said These and other findings are described in America's Children in Brief: Key National Indicators of Well-Being, The report was compiled by the Federal Interagency Forum on Child and Family Statistics, a working group of 22 federal agencies that produce and use data on issues related to children and families. The report uses the most recently available and reliable official federal statistics to describe the family and social environment, economic circumstances, health care, physical environment and safety, behavior, education, and health of America's children and youth. "This year's report contains good news about newborns, said Alan E. Guttmacher, M.D., Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. "Fewer infants were born preterm and fewer died in the first year of life." The report notes that infants born preterm or of low birth weight are at high risk of early death and long-term health and developmental problems. "The findings in this report, drawn from many outstanding data systems across the federal spectrum, allow us to track key progress in the fight against many major public health threats, such as meningitis, for example," said Edward Sondik, Ph.D., Director of the Centers for Disease Control and Prevention's National Center for Health Statistics. "The report shows that in the last five years there has been more than
6 a five-fold increase in the percent of adolescents who have received the vaccination that helps prevent meningococcal disease - a serious bacterial illness and leading cause for the most dangerous form of meningitis." The Forum alternates publishing a detailed report, America's Children: Key National Indicators of Well-Being, with a summary version that highlights selected indicators. This year, the Forum is publishing America's Children in Brief; it will publish the more detailed report in New to this year's report is a figure showing the percentage of children in race groups constituting less than 10 percent of the population (American Indian and Alaska Native, Asian, Native Hawaiian and Other Pacific Islander, or two or more races). This detailed figure is available only online It supplements figure 1 in this year's brief, which shows the percentage of children by race and Hispanic origin. Also new is a revised figure showing the percentages of high school graduates who completed selected mathematics and science coursework (Figure 13). Among the findings in this year's report: A drop in births to adolescents, from 20 per 1,000 girls ages 15 to 17 (2009) to 17 per 1,000 (2010, preliminary data) A drop in the proportion of infants born before 37 weeks' gestation (preterm), from 12.2 percent (2009) to 12.0 percent (2010, preliminary data) A drop in deaths before the first birthday, from 6.4 per 1,000 births (2009) to 6.1 per 1,000 births (2010, preliminary data) A drop in the percentage of children from birth to 17 years of age living with at least one parent employed year round full time, from 72 percent (2009) to 71 percent (2010) A rise in the proportion of children from birth to 17 years of age living in poverty, from 21 percent (2009) to 22 percent (2010) A drop in the percentage of children from birth to 17 years of age living in households classified by the U.S. Department of Agriculture as food insecure, from 23 percent (2009) to 22 percent (2010) An increase in vaccination coverage with one dose or more of the meningococcal conjugate vaccine for adolescents ages 13-17, from 12 percent (2006) to 63 percent (2010) A drop in the proportion of youth ages who were victims of serious violent crimes, from 11 per 1,000 youth ages (2009) to 7 per 1,000 (2010) A drop in the percentage of children, birth to 6 years of age, living in a home where someone smoked regularly, from 8.4 percent (2005) to 6.1 percent (2010) An increase of one point in the average mathematics scores for both 4th and 8th graders from 2009 to 2011 A drop in the percentage of youth ages neither enrolled in high school or college nor working, from 9 percent (2010) to 8 percent (2011) A rise in the percentage of children from birth to 17 years of age living in counties in which levels of one or more air pollutants were above allowable levels, from 59 percent (2009) to 67 percent (2010) An audio file of the news briefing on the 2012 America's Children Report is available and a transcript. AMERICAN PHARMACIST ASSOCIATION 13/07/2012 West Nile virus and other arboviruses continue to cause severe illness in the United States In 2011, 871 cases of nationally notifiable arboviral diseases, excluding dengue, were reported to CDC, 712 of which were caused by West Nile virus. West Nile virus (WNV) and other arthropod-borne viruses (arboviruses) continue to cause outbreaks and severe illness in many Americans, according to a CDC report
7 in the July 13 Morbidity and Mortality Weekly Report (MMWR). During 2011, 871 cases of nationally notifiable arboviral diseases (excluding dengue) were reported to CDC. The agency reported the following numbers of cases: WNV: 712 La Crosse virus: 130 Powassan virus: 16 St. Louis encephalitis virus: 6 Eastern equine encephalitis virus: 4 Jamestown Canyon virus: 3 A total of 624 (72%) of these cases were classified as neuroinvasive disease, corresponding to a national incidence of 0.20 per 100,000 population. Bites from infected mosquitoes and ticks are the primary cause of arbovirus transmission to humans. Most arboviruses occurring in the United States, CDC stated, are maintained in transmission cycles between arthropods and vertebrate hosts (usually birds or small mammals). Human-to-human transmission can occur via blood transfusion and organ transplantation. Most cases of human arboviral infections are asymptomatic. According to CDC, symptomatic infections most often manifest as systemic febrile illness and less commonly as neuroinvasive disease. No cases of arboviral disease were reported for Alaska, Hawaii, Maine, New Hampshire, Oregon, or Washington during Nationally, the incidence of neuroinvasive WNV disease was 0.16 per 100,000 population, with the highest rates reported in the District of Columbia (1.62), Mississippi (1.04), Nebraska (0.76), and Arizona (0.76). More than one-half (51%) of WNV neuroinvasive disease cases were reported in five states: California (110 cases), Arizona (49), Michigan (32), Mississippi (31), and New York (28). Patients with WNV disease had a median age of 57 years (range 7 96), and 424 (60%) were male. Neuroinvasive WNV disease incidence increased with age; the highest incidence was among individuals 70 years or older. The median age of patients who died was 74 years (range 32 96). Late August 2011 was the peak for WNV disease, with 663 (93%) cases having illness onset during July to September. Overall, 547 (77%) people were hospitalized with WNV disease, 43 (6%) of whom died. Among 486 patients with WNV neuroinvasive disease, 273 (56%) had encephalitis, 183 (38%) meningitis, and 30 (6%) acute flaccid paralysis. Of the 30 patients with acute flaccid paralysis, 28 (93%) also had encephalitis or meningitis. CDC noted that because no specific treatments exist for arboviral diseases, prevention is critical to reducing the effect of these illnesses. Preventive measures suggested by the agency include use of repellents, wearing protective clothing, repairing or installing screens, eliminating tall grass and standing water near homes, and initiating community-level insect control programs. Posted by Joe Sheffer E-CANCER NEWS 15/07/2012 Immunostimulatory nanoparticles enhance tumour immunotherapy by ecancer reporter Clare Sansom Many recently developed therapies for cancer rely on stimulating the patient's immune system to attack the tumour, rather than doing so directly. Immunotherapy is a primary treatment option for malignant melanoma, an aggressive solid tumour that is often refractory to surgery, radiation and chemotherapy. However, only a minority of melanoma patients have durable complete responses when treated with the immuno-stimulatory cytokine, interleukin-2 (IL-2). One important reason for this is the ability of tumour cells to secrete chemicals that suppress the immune system, including transforming growth factor-b (TGF-b), into their micro-environment. As the dose of IL-2 is limited by toxicity,
8 scientists are investigating methods of increasing its half-life in circulation. Tarek Fahmy and his co-workers, all based at Yale University, New Haven, Connecticut, USA have now designed a novel system for the sustained delivery of a combination of IL-2 with an inhibitor of TGF-b receptor signalling to the site of a solid tumour. This system, which the researchers have termed a "nanolipogel" (nlg) particle, comprises a spherical core of degradable hydrogel, approximately 120nm in diameter, surrounded by a lipid bilayer. It is possible to encapsulate both therapeutic proteins and small-molecule drugs within the particle core. The test system used for the nlg particles involved a combination of IL-2 with the commercially available TGF-b receptor inhibitor, SB It is always a challenge to release protein and small-molecule drugs in combination, as proteins are significantly more water-soluble than, for example, a typical receptor blocker. However, Fahmy and co-workers were able to show that both the cytokine and the inhibitor were released from the nlg particles in a more sustained fashion than from either liposomes or more conventional PLGA nanoparticles. Furthermore, no significant toxicities were observed when empty nlg particles were administered to healthy mice, and administration of fluorescence-labelled particles showed the particles accumulating mainly in the lungs, liver and kidneys. The liver and the lungs are two of the main sites of metastasis from primary melanoma. Next, the researchers tested the nlg particles loaded with both cytokine and inhibitor in a mouse model of malignant melanoma. As a control experiment, mice bearing subcutaneous melanomas were treated with weekly doses of both IL-2 and SB505124, and little or no effect on tumour growth was observed. Some delay in tumour growth was noticed when either the cytokine or the inhibitor was delivered alone using the nlg system, and a more striking reduction occurred with the simultaneous delivery of both drugs in nanolipogel particles. The survival time of mice treated with both drugs delivered using nlgs was also significantly increased over treatment with either a single nlg-delivered drug or both drugs delivered systemically, and there was also a significant decrease in the number of metastases. Fluorescence labelling was then used to discover the main sites of accumulation of the drug-loaded nano-particles in mice bearing subcutaneous melanomas and in similar mice with lung metastases. The nlg particles were found to accumulate in the tumours and the areas surrounding them in both types of mice. Finally, the researchers sought to elucidate the immunostimulatory mechanisms through which this combination of cytokine and inhibitor prevent tumour growth by probing various parameters of the innate and adaptive immune systems in the mice. They found an increase in the number and activity of natural killer (NK) cells and in the infiltration of CD8+ T-cells at the tumour sites of treated mice. Taken together, these results provide a proof of the concept that simultaneous, sustained delivery of IL-2 with a TGF-b receptor inhibitor in nlg particles can promote NK-mediated anti-tumour immune responses and so shrink tumours. As the lipid used to form the outer surface of the particles has already been approved by the FDA as safe for use in humans, it is possible that a very similar drug delivery system may ultimately enter clinical use. Source: Park, J., Wrzesinski, S.H., Stern, E. and 15 others (2012). Combination delivery of TGF inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nature Materials, published online ahead of print 15 July doi: /nmat3355
9 AMERICAN ACADEMY OF PEDIATRICS 16/07/2012 Playing on several sports teams reduces obesity risk in teens esearchers involved in the study, "Influence of Sports, Physical Education, and Active Commuting to School on Adolescent Weight Status" in the August 2012 issue of Pediatrics (published online July 16) conducted telephone surveys with 1,718 New Hampshire and Vermont high school students to determine their level of sports participation, other forms of physical activity, and height and weight status. Teens who played on three or more sports teams in the past year were 27 percent less likely to be overweight and 39 percent less likely to be obese compared with teens who did not play on any sports team. Active commuting, such as riding a bike or walking to school, was not significantly related to overweight status, but it was associated with a reduced likelihood of obesity. Physical education classes for teens appeared to have little impact on weight status. The study suggests that high school sports participation, which involves regular practices and competitions, reduces overweight and obesity because participation involves moderate to strenuous activity levels. Study authors conclude that increasing opportunities for all teens, regardless of athletic ability, to participate in sports should be a priority in obesity prevention efforts. ESMO.ORG 16/07/2012 The first study to investigate the role of interleukin-9 in melanoma tumor immunity High expression of a cell-signalling molecule, interleukin-9, in immune cells inhibits melanoma growth Researchers from Brigham and Women's Hospital (BWH) have made a groundbreaking discovery that will shape the future of melanoma therapy. The team, led by Dr Thomas Kupper, chair of the BWH Department of Dermatology, and Rahul Purwar, PhD, found that high expression of a cell-signalling molecule, known as interleukin-9, in immune cells inhibits melanoma growth. Their findings were published online in the July 8, 2012 issue of Nature Medicine. After observing mice without genes responsible for development of an immune T helper cell 17 (TH17), researchers found that these mice had significant resistance to melanoma tumor growth, suggesting that blockade of the TH17 cell pathway favoured tumor inhibition. The researchers also noticed that the mice expressed high amounts of interleukin-9. A new finding paves the way for future studies that will assess the role of interleukin-9 and TH9 cells in human cancer therapy These were unexpected results, which led to examine a possible contribution of interleukin-9 to cancer growth suppression. The researchers next treated melanoma-bearing mice with T helper cell 9 (TH9), an immune cell that produces interleukin-9. They saw that these mice also had a profound resistance to melanoma growth. This is the first reported finding showing an anti-tumor effect of TH9 cells. Moreover, the researchers were able to detect TH9 cells in both normal human blood and skin, specifically in skin-resident memory T cells and memory T cells in peripheral blood mononuclear cells. In contrast, TH9 cells were either absent or present at very low levels in human melanoma. This new finding paves the way for future studies that will assess the role of interleukin-9 and TH9 cells in human cancer therapy. Immunotherapy of cancer is coming of age, and there have been exciting recent results in patients
10 with melanoma treated with drugs that stimulate the immune system. The researchers hope that their results will also translate to the treatment of melanoma patients, but much work still needs to be done. According to the researchers, other cell-signalling molecules have been used in treating melanoma; however, this study is the first to investigate the role of interleukin-9 in melanoma tumor immunity. This research was supported by the United States National Institutes of Health (R01 AI-41707, R01 AI , P50 CA , R01-AR , R03-MH and Z01-ES ) and The Skin Cancer Foundation. NEWS-MEDICAL.NET 16/07/2012 Study determines optimal screening strategy for gastric or stomach cancer A new study has determined how often people should get screened for gastric or stomach cancer in high-risk regions of the world. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings could help reduce deaths from gastric cancer, which is the second most common cause of cancer-related mortality. Although the incidence of gastric cancer has decreased substantially in the western part of the world, the disease is still common in areas such as Eastern Asia, including Korea, Japan, and China. Gastric cancer patients' prognosis strongly depends on the stage of the disease, or how advanced it is, at the time of diagnosis. In other words, early detection and treatment can save lives. Gastric cancer screening is often done by upper endoscopy-using a tiny camera at the end of a long, flexible tube to look at the upper digestive system. To see how often this screening technique should be done to detect gastric cancer at an early stage, Il Ju Choi, MD, PhD, of the National Cancer Center in Korea, and his colleagues studied 2,485 patients who had been diagnosed with gastric cancer at their institution. The researchers divided the patients into the following seven groups based on the interval between the endoscopy that detected gastric cancer and the endoscopy that preceded it: one year, two years, three years, four years, five years, more than five years, and never-screened. Currently, screening every two years is recommended in Korea for individuals who are aged 40 years or older. The investigators found that gastric cancer stages were similar for screening intervals between one and three years; however, the cancer stage at diagnosis was significantly higher at screening intervals of four years or more. "The optimal screening strategy appears to be every three years. Gastric cancers are likely to become more advanced before detection with screening intervals that are longer than three years, but screening more frequently than every three years does not appear to be more beneficial," said Dr. Choi. "The exception is if you have a family member with gastric cancer. In that case, you may need to undergo upper endoscopy screening more frequently than every three years," he added. Patients with a family history of gastric cancer were more likely to have a higher stage at diagnosis if they had a three-year interval rather than a one-year interval.