Oncolytic Virotherapy as Emerging Immunotherapeutic Modality: Potential of Parvovirus H-1

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evidence indicates that intratumoral (it) or intravenous (iv) injections of replicative oncolytic viruses such as herpes simplex-, pox-, parvo- or adenoviruses may also reactivate the human immune system. By generating tumor cell lysates in situ, oncolytic viruses overcome cellular tumor resistance mechanisms and induce immunogenic tumor cell death resulting in the recognition of newly released tumor antigens.This is in particular the case of the oncolytic parvovirus H-1 (H-1PV) which is able to kill human tumor cells and stimulate an antitumor immune response through increased presentation of tumor-associated antigens, maturation of dendritic cells and release of proinflammatory cytokines. Current research and clinical studies aim to assess the potential of oncolytic virotherapy and its combination with immunotherapeutic agents or conventional treatments to further induce effective antitumoral immune responses

Susceptibility to collagen-induced arthritis is modulated by TGFβ responsiveness of T cells

The objective of our study was to determine the regulatory effects that endogenous transforming growth factor β (TGFβ) exerts on T cells in the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in transgenic mice expressing a dominant negative TGFβ type II receptor in T cells under the control of the human CD2 promoter. Clinical and histological arthritis scores were determined and experiments on disease induction and the healing phase of disease were performed. The proliferation and cytokine production of draining lymph node cells in vitro were analyzed. Transgenic mice were more susceptible to induction of CIA. The overall incidence was higher in transgenic mice than in wild-type mice (57% vs 35%, P < 0.05). Affected transgenic animals displayed a significantly higher clinical (4.5 ± 0.6 vs 1.67 ± 0.19, P = 0.001) and histological arthritis score (8.01 ± 0.9 vs 4.06 ± 1.1, P < 0.05). Draining lymph node cells of transgenic mice secreted more tumor necrosis factor α and IFNγ and proliferated more vigorously in response to collagen type II and upon CD3/CD28 costimulation in vitro. Therefore, the regulation of T cells by endogenous TGFβ is important for the maintenance of joint integrity after arthritis induction. Defects in TGFβ-signalling as a susceptibility factor for rheumatoid arthritis may warrant further investigation

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus

Genome-wide association study of germline variants and breast cancer-specific mortality

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10

Portal Vein Thrombosis Is Associated with an Increased Incidence of Depression and Anxiety Disorders

Portal vein thrombosis (PVT) is a severe disease that adversely affects patients’ well-being. Data on the influence of PVT on the occurrence of depression or anxiety disorders are lacking. This study aimed to explore the impact of PVT on the incidence of depression and anxiety disorders diagnoses in a large German primary care cohort over a ten-year period. Patients with PVT were matched to non-PVT individuals by age, sex, yearly consultation frequency, index year and comorbidities in a 1:5 ratio. The primary outcome of the study was the incidence of depression and anxiety disorders. The relationship between PVT and both depression and anxiety disorders was investigated using Cox regression models. We compared 547 patients with PVT with 2735 matched individuals without PVT. Within 5 years of the index date, 17.4% of patients with PVT and 9.3% of non-PVT individuals were diagnosed with depression (p p = 0.002). On regression analyses, PVT was positively associated with incident depression (HR 2.01, 95% CI 1.53–2.64, p p = 0.001). Regarding depression, this association remained significant in women as well as in men. There was no association between PVT and the incidence of anxiety disorders in women. In conclusion, PVT is associated with the development of depression and anxiety disorders. However, further prospective studies are needed to confirm our findings before definitive recommendations can be made

Portal vein thrombosis is associated with an increased risk of bone fractures.

BackgroundPortal vein thrombosis (PVT) is a rare but severe disease that often leads to portal hypertension-related complications. It is well-known that patients with portal hypertension associated with liver cirrhosis are at increased risk for bone fractures, however data on the impact of PVT on fracture risk are lacking.AimsThis study aimed to explore the impact of PVT on the incidence of bone fractures in a large German primary care cohort.MethodsPatients with PVT were extensively matched to non-PVT individuals in a 1:5 ratio. The primary outcome of the study was the incidence of any bone fracture.ResultsThis study included 596 patients with PVT and 2,980 non-PVT individuals. During five years of follow-up, the cumulative incidence of bone fractures was significantly higher in PVT patients (n = 87, 13.6%) than in those without PVT (n = 186, 6.7%) (pConclusionsPVT is independently associated with a higher incidence of bone fractures. Patients with PVT should be critically evaluated for fracture risk and preventive measures should be considered