Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Abstract: Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective. Treatment of established tumors with MeVac FmIL-12 achieved 90% complete remissions. Profiling of the tumor immune microenvironment revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL-12 ensuring potent early natural killer and effector T cell activation as well as upregulation of the effector cytokines IFN-gamma and TNF-alpha. CD8+ T cells were found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery and elucidate mechanisms of successful immunovirotherapy.
    Type of Publication: Journal article published
    PubMed ID: 28507792
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CANCER ; human ; MODEL ; MODELS ; SUPPORT ; COHORT ; EPIDEMIOLOGY ; EXPOSURE ; RISK ; RISKS ; MARKER ; RISK-FACTORS ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; CARE ; HEALTH ; AGE ; WOMEN ; SWEDEN ; RISK FACTOR ; INDIVIDUALS ; CHILDREN ; SERUM ; REGRESSION ; HUMAN CHORIONIC-GONADOTROPIN ; preeclampsia ; PREGNANCY ; BIRTH ; USA ; INCREASED RISK ; RISK-FACTOR ; FETAL ; CONFIDENCE ; 2ND TRIMESTER ; HYPEREMESIS GRAVIDARUM ; MOTHER ; TRANSIENT INCREASE
    Abstract: Background: Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone, proposed to be involved in the protective effect against breast cancer afforded to mothers who bear children. In comparison with normal pregnancies, Down syndrome pregnancies are characterized by further elevated hCG concentrations from late first trimester to the middle of the second trimester. This study aimed to compare the risk of breast cancer in women who gave birth to a child with Down syndrome (as a marker of elevated hCG exposure) with that of women who had only unaffected children. Methods: The study cohort included all mothers of live-born children in Norway and Sweden from 1967-1973 through 2004. During the study period, 54,063 women developed breast cancer; 5330 children with Down syndrome were born and 139 breast cancer cases were diagnosed in their mothers. We fitted Cox proportional hazards regression models to obtain relative risks of breast cancer, adjusted for risk factors for breast cancer, such as overall parity and age at births. Results: Mothers of Down syndrome children were at 23% increased risk to develop breast cancer (95% confidence interval = 4%-46%). The risk increase was limited to women who had a Down syndrome child after age 30, and seemed to be confined to women whose cancer was diagnosed before age 50. Conclusions: Study results do not support the hypothesis of a protective effect of elevated pregnancy hCG on maternal breast cancer. (Epidemiology 2009;20: 584-589)
    Type of Publication: Journal article published
    PubMed ID: 19451822
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; BLOOD ; carcinoma ; COHORT ; cohort studies ; cohort study ; RISK ; ASSOCIATION ; HEALTH ; WOMEN ; OBESITY ; PROSPECTIVE COHORT ; COLORECTAL-CANCER ; SWEDEN ; CARCINOMAS ; body mass index ; REGRESSION ; ASSOCIATIONS ; WEIGHT ; BODY-SIZE ; GROWTH-FACTOR-I ; metabolic syndrome ; blood pressure ; SERUM-LEVELS ; prospective ; CORONARY HEART-DISEASE ; INCREASED RISK ; CANCERS ; CANCER-RISK ; CIRCULATING LEVELS ; C-PEPTIDE ; BODY-MASS ; endometrial neoplasms ; journals ; AGED NORWEGIAN MEN ; metabolic syndrome X
    Abstract: The authors examined the association between the metabolic syndrome and risk of incident endometnal and fatal uterine corpus cancer within a large prospective cohort study Approximately 290,000 women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, systolic and diastolic blood pressure, and circulating levels of glucose, total cholesterol, and tnglycendes Relative risks were estimated using Cox proportional hazards regression. The metabolic syndrome was assessed as a composite z score, as the standardized sum of z scores for body mass index, blood pressure, glucose, cholesterol, and tnglycendes. A total of 917 endonnetnal carcinomas and 129 fatal cancers were identified Increased risks of incident endometnal carcinoma and fatal uterine corpus cancer were seen for the metabolic syndrome factors combined, as well as for individual factors (except for cholesterol) The relative risk of endometnal carcinoma for the metabolic syndrome was 1.37 (95% confidence interval 1 28, 1 46) per 1-unit increment of z score The positive associations between metabolic syndrome factors (both individually and combined) and endometrial carcinoma were confined to the heaviest women. The association between the metabolic syndrome and endometnal carcinoma risk seems to go beyond the risk conferred by obesity alone, particularly in women with a high body mass index
    Type of Publication: Journal article published
    PubMed ID: 20219764
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: POPULATION ; ASSOCIATION ; SCHIZOPHRENIA ; PERVASIVE DEVELOPMENTAL DISORDERS ; INDIVIDUALS ; SPECTRUM DISORDERS ; Copy number variation ; GENETIC ARCHITECTURE ; NEUROPSYCHIATRIC CONDITIONS ; PTEN MUTATIONS
    Abstract: Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P 〈 5 x 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P 〈 5 x 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C
    Type of Publication: Journal article published
    PubMed ID: 20663923
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: EXPRESSION ; POPULATION ; RISK ; GENE ; POLYMORPHISMS ; SCHIZOPHRENIA ; COPY NUMBER ; SNP ; NEURONS ; MENTAL-RETARDATION ; GENOME-WIDE ASSOCIATION ; GLUTAMATE-RECEPTOR-6 GENE ; LINKAGE ANALYSES ; RUNS
    Abstract: Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (round 90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
    Type of Publication: Journal article published
    PubMed ID: 21996756
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: cohort study ; EPIDEMIOLOGY ; HEPATOCELLULAR-CARCINOMA ; hepatocellular carcinoma ; UNITED-STATES ; DIABETES-MELLITUS ; ALCOHOL-CONSUMPTION ; INCIDENCE RATES ; VIRUS-INFECTION ; metabolic syndrome ; US ADULTS ; REGRESSION DILUTION ; INTERNATIONAL TRENDS ; intrahepatic cholangiocarcinoma ; TOTAL SERUM-CHOLESTEROL
    Abstract: Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24-1.58), mid blood pressure 2.08 (0.95-4.73), blood glucose 2.13 (1.55-2.94) cholesterol 0.62 (0.51-0.76) and serum triglycerides 0.85 (0.65-1.10). The RR per one unit increment of the MetS z-score was 1.35 (1.12-1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
    Type of Publication: Journal article published
    PubMed ID: 21805476
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: FOLLOW-UP ; COHORT ; MORTALITY ; BLOOD-PRESSURE ; DIABETES-MELLITUS ; METAANALYSIS ; BODY-MASS INDEX ; CUTANEOUS MALIGNANT-MELANOMA ; BASAL-CELL CARCINOMA ; REGRESSION DILUTION
    Abstract: Background Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Objectives To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). Methods During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. Results Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1.17, 95% confidence interval (CI) 1.04-1.31 and HR 1.18, 95% CI 1.03-1.36, respectively] and fatal MM cases among women (HR 2.39, 95% CI 1.58-3.64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0.02) and there was a trend with triglyceride concentration (P-trend 0.09). Conclusion These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.
    Type of Publication: Journal article published
    PubMed ID: 22530854
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: EXPRESSION ; COMBINATION ; antibody ; MELANOMA ; SAFETY ; CANCER-IMMUNOTHERAPY ; RESCUE ; IPILIMUMAB ; CHEMOVIROTHERAPY
    Abstract: We hypothesized that the combination of oncolytic virotherapy with immune checkpoint modulators would reduce tumor burden by direct cell lysis and stimulate antitumor immunity. In this study, we have generated attenuated Measles virus (MV) vectors encoding antibodies against CTLA-4 and PD-L1 (MV-aCTLA-4 and MV-aPD-L1). We characterized the vectors in terms of growth kinetics, antibody expression, and cytotoxicity in vitro. Immunotherapeutic effects were assessed in a newly established, fully immunocompetent murine model of malignant melanoma, B16-CD20. Analyses of tumor-infiltrating lymphocytes and restimulation experiments indicated a favorable immune profile after MV-mediated checkpoint modulation. Therapeutic benefits in terms of delayed tumor progression and prolonged median overall survival were observed for animals treated with vectors encoding anti-CTLA-4 and anti-PD-L1, respectively. Combining systemic administration of antibodies with MV treatment also improved therapeutic outcome. In vivo oncolytic efficacy against human tumors was studied in melanoma xenografts. MV-aCTLA-4 and MV-aPD-L1 were equally efficient as parental MV in this model, with high rates of complete tumor remission (〉 80%). Furthermore, we could demonstrate lysis of tumor cells and transgene expression in primary tissue from melanoma patients. The current results suggest rapid translation of combining immune checkpoint modulation with oncolytic viruses into clinical application.Molecular Therapy (2014); doi:10.1038/mt.2014.160.
    Type of Publication: Journal article published
    PubMed ID: 25156126
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: CANCER ; carcinoma ; COHORT ; EPIDEMIOLOGY ; RISK ; OBESITY ; HUMAN-PAPILLOMAVIRUS ; cholesterol ; METAANALYSIS ; VULVAR CANCER ; COMPLETENESS ; REGRESSION DILUTION ; COFACTORS ; MetS ; rare gynecological cancers
    Abstract: Background: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. Materials and methods: The Metabolic syndrome and Cancer project cohort includes 288 834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. Results: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). Conclusion: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors
    Type of Publication: Journal article published
    PubMed ID: 20966183
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: CANCER ; GROWTH-FACTOR ; carcinoma ; COHORT ; EPIDEMIOLOGY ; RISK ; RISK-FACTORS ; score ; WOMEN ; OBESITY ; cervical cancer ; HUMAN-PAPILLOMAVIRUS ; SQUAMOUS-CELL CARCINOMA ; adenocarcinoma ; UTERINE CERVIX ; PROJECT ; metabolic syndrome ; COMPLETENESS ; REGRESSION DILUTION ; CONOR ; Squamous cell ; Metabolic factors
    Abstract: Background. Little is known about the association between metabolic risk factors and cervical cancer carcinogenesis. Material and methods. During mean follow-up of 11 years of the Me-Can cohort (N = 288,834) 425 invasive cervical cancer cases were diagnosed. Hazard ratios (HRs) were estimated by the use of Cox proportional hazards regression models for quintiles and standardized z-scores (with a mean of 0 and a SD of 1) of BMI, blood pressure, glucose, cholesterol, triglycerides and MetS score. Risk estimates were corrected for random error in the measurements. Results. BMI (per 1SD increment) was associated with 12%, increase of cervical cancer risk, blood pressure with 25% and triglycerides with 39%, respectively. In models including all metabolic factors, the associations for blood pressure and triglycerides persisted. The metabolic syndrome (MetS) score was associated with 26% increased corrected risk of cervical cancer. Triglycerides were stronger associated with squamous cell carcinoma (HR 1.48; 95% CI, 1.20-1.83) than with adenocarcinoma (0.92, 0.54-1.56). Among older women cholesterol (50-70 years 1.34; 1.00-1.81), triglycerides (50-70 years 1.49, 1.03-2.16 and 〉= 70 years 1.54, 1.09-2.19) and glucose (〉= 70 years 1.87, 1.13-3.11) were associated with increased cervical cancer risk. Conclusion. The presence of obesity, elevated blood pressure and triglycerides were associated with increased risk of cervical cancer.
    Type of Publication: Journal article published
    PubMed ID: 22330614
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...