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  • Articles  (197)
  • DKFZ Publication Database  (80)
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  • Articles  (197)
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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  51. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie; 20060910-20060914; Leipzig; DOC06gmds056 /20060901/
    Publication Date: 2006-09-25
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Abstract: Background: Previous studies suggest that a stable end-product of prostaglandin E2, the urinary metabolite PGE-M, is associated with colorectal cancer, and 1 study of relatively small sample size found an association with gastric cancer among women. In the present study we further investigate the PGE-M, Helicobacter pylori, and gastric cancer association. Methods: The present analysis included 359 prospectively ascertained gastric cancer cases and 700 individually matched controls from the Shanghai Women's and Men's Health Studies. Urinary PGE-M was measured by a liquid chromatography/tandem mass spectrometric method. Seropositivity to 15 H. pylori recombinantly expressed fusion proteins was detected by H. pylori multiplex serology. Results: Adjusting for H. pylori, increasing PGE-M was associated with higher risk of gastric cancer (quartile 4 vs 1: odds ratio [OR], 1.76 [95% confidence interval {CI}, 1.17-2.66], Ptrend = .004). This association remained after excluding those diagnosed within 2 years from sample collection (OR, 1.73 [95% CI, 1.12-2.65], Ptrend = .007). However it was no longer present among individuals with 10 or more years of follow-up (2-4.9 years: OR, 3.15 [95% CI, 1.11-8.91]; 5-9.9 years: OR, 2.23 [95% CI, 1.22-4.06]; 〉/=10 years: OR, 0.73 [95% CI, .31-1.70]). Compared to H. pylori-negative individuals with below-median PGE-M levels, H. pylori-positive individuals with above-median PGE-M levels had a 5-fold increase in the odds of gastric cancer (OR, 5.08 [95% CI, 2.47-10.43]). Conclusions: In China, higher PGE-M levels may indicate an increased risk of gastric cancer independent of the risk conferred by H. pylori infection status, particularly for cancers diagnosed within 10 years of sample collection.
    Type of Publication: Journal article published
    PubMed ID: 28402440
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie; 20180603-20180606; Münster; DOCP010 /20180618/
    Publication Date: 2018-06-19
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
    Keywords: CELLS ; EXPRESSION ; IRRADIATION ; proliferation ; carcinoma ; CELL ; COMBINATION ; Germany ; human ; EXPOSURE ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; LINES ; MICE ; MARKER ; CONTRAST ; SKIN ; E7 ; papillomavirus ; ALPHA ; TRANSGENIC MICE ; LESIONS ; NUMBER ; MOUSE SKIN ; LINE ; MARKERS ; p53 ; human papillomavirus ; HPV ; E6 ; BENIGN ; HUMAN KERATINOCYTES ; HUMAN-PAPILLOMAVIRUS ; keratin ; squamous cell carcinoma ; SQUAMOUS-CELL CARCINOMAS ; CLUSTERS ; P53 MUTATIONS ; HIGH-LEVEL ; CLUSTER ; MUTANT P53 ; CELL CARCINOMA ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; LEVEL ; P63 ; E6 PROTEINS ; EPIDERMAL-CELLS ; E6 and E7 ; granular layer ; HPV 20 ; CESSATION ; E7 PROTEIN ; EARLY ADAPTIVE RESPONSES ; ULTRAVIOLET-B-LIGHT
    Abstract: The functional role of UV irradiation, in combination with the E6 and E7 proteins of the cutaneous human papillomavirus (HPV) types in the malignant conversion of benign papillomatous lesions, has not been elucidated. Transgenic SKH-hr1 hairless mice expressing HPV-20 and HPV-27 E6 and E7 proteins in the suprabasal compartment were generated and exposed to chronic UV irradiation. Histological and immunohistochemical examination of skin samples revealed enhanced proliferation of the epidermal layers and papilloma formation in both transgenic strains in comparison to what was observed with nontransgenic mice. Squamous cell carcinoma developed in the HPV-20 E6/E7 transgenic line as well as in the HPV-27 E6/E7 transgenic line. Several weeks after cessation of UV-B exposure, enhanced proliferation, as measured by BrdU incorporation, was maintained only in HPV-20 transgenic skin. Keratin 6 expression was increased in the transgenic mice throughout all cell layers. Expression of the differentiation markers involucrin and loricrin was reduced and disturbed. p63 alpha expression was differentially regulated with high levels of cytoplasmic expression in clusters of cells in the granular layer of the skin in the transgenic lines 20 weeks after cessation of UV-B exposure, in contrast to uninterrupted staining in the nontransgenic lines. p53 was expressed in clusters of cells in nontransgenic and HPV-27 transgenic mice, in contrast to an even distribution in a higher number of cells in HPV-20 transgenic animals
    Type of Publication: Journal article published
    PubMed ID: 16971438
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  • 5
    Keywords: CANCER ; POPULATION ; RISK ; PROTEIN ; INFECTION ; ASSOCIATION ; antibodies ; PLASMA ; PREVALENCE ; GASTRIC-CANCER ; RANDOMIZED-TRIAL ; FOOD FREQUENCY QUESTIONNAIRE ; ABSORPTION ; ALPHA-TOCOPHEROL ; SUPPLEMENTATION ; SOUTHERN COMMUNITY COHORT ; CAROTENE CONCENTRATIONS
    Abstract: High prevalence of Helicobacter pylori (H. pylori), the leading cause of gastric cancer, and low levels of micronutrients have been observed in many developing countries, and the question remains as to the whether an association between the 2 exists. The present study seeks to further our understanding of this potential connection in the Southern Community Cohort Study, representing a low-income population in the United States. Blood levels of antibodies to H. pylori proteins were assessed by multiplex serology for a sample of 310 African American and white participants, ages 40 to 79 years. Blood collected at baseline was also assayed for levels of carotenoids, tocopherols, retinol, and folate. Multivariate linear regression was used to calculate least-squares mean micronutrient levels within groups defined by H. pylori status. The mean serum levels of all micronutrients assayed were lower among H. pylori+ individuals than H. pylori- individuals, significantly for beta-carotene, folate, and retinol (decreases of 27.6%, 18.6%, and 9.7%, respectively). Individuals who were seropositive to the virulent CagA+ H. pylori strains had even lower mean levels of micronutrients, particularly beta-carotene, folate, total carotenoids, and retinol (decreases of 38.9%, 19.1%, 17.0%, and 11.7%, respectively, compared with H. pylori- individuals). However, dietary micronutrient levels as derived from a food frequency questionnaire did not vary between groups defined by H. pylori status. These results provide support for the hypothesis that H. pylori infection impairs nutrient absorption and suggest a need for future studies to explore the role of H. pylori infection on nutrition and gastric cancer risk in this high-risk population.
    Type of Publication: Journal article published
    PubMed ID: 21436385
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  • 6
    Keywords: PROTEINS ; INFECTION ; CARCINOGENESIS ; antibody ; ADENOCARCINOMAS ; multiplex serology ; CAGA ; ERADICATION ; SHANGHAI WOMENS HEALTH
    Abstract: Background: Helicobacter pylori is the leading risk factor for gastric cancer, yet only a fraction of infected individuals ever develop neoplasia. Methods: To identify potential predictive biomarkers, we assessed the association of 15 antibodies to H. pylori proteins and gastric cancer in a nested case-control study. Blood levels of antibodies were assessed using multiplex serology for 226 incident cases and 451 matched controls from the Shanghai Men's Health Study. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Seropositivity to four (Omp, HP0305, HyuA, and HpaA) proteins was associated with a 1.5- to 3-fold increased risk for gastric cancer. When exCIuding cases diagnosed within 2 years of study enrollment, seropositivity to two additional proteins (CagA and VacA) showed significant associations with risk. Compared with individuals with three or fewer seropositive results to the six virulent proteins identified in this population, individuals with four to five seropositive results were at a 2-fold increased risk (OR, 2.08; 95% CI, 1.31-3.30) and individuals seropositive to all six proteins had a 3.5-fold increase in risk (OR, 3.49; 95% CI, 2.00-6.11) for gastric cancer. Among individuals diagnosed at least 2 years after study enrollment, these associations were even stronger (ORs, 2.79 and 4.16, respectively). Conclusions: Increasing number of seropositives to six H. pylori proteins may be a risk marker for distal gastric cancer in China. Impact: In a population with a 90% prevalence of CagA-positive H. pylori infection, assessment of additional virulent H. pylori proteins might better identify individuals at high risk for gastric cancer.
    Type of Publication: Journal article published
    PubMed ID: 23035179
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  • 7
    Keywords: GENE-EXPRESSION ; MOUSE ; MUTATIONS ; C-KIT ; ROLES ; proto-oncogene ; TUMOR-BEARING MICE ; HEMATOPOIETIC STEM ; TYROSINE KINASE RECEPTOR ; W-LOCUS
    Abstract: Mast cell-deficient Kit(W-sh) "sash" mice are widely used to investigate mast cell functions. However, mutations of c-Kit also affect additional cells of hematopoietic and nonimmune origin. In this study, we demonstrate that Kit(W-sh) causes aberrant extramedullary myelopoiesis characterized by the expansion of immature lineage-negative cells, common myeloid progenitors, and granulocyte/macrophage progenitors in the spleen. A consistent feature shared by these cell types is the reduced expression of c-Kit. Populations expressing intermediate and high levels of Ly6G, a component of the myeloid differentiation Ag Gr-1, are also highly expanded in the spleen of sash mice. These cells are able to suppress T cell responses in vitro and phenotypically and functionally resemble myeloid-derived suppressor cells (MDSC). MDSC typically accumulate in tumor-bearing hosts and are able to dampen immune responses. Consequently, transfer of MDSC from naive sash mice into line 1 alveolar cell carcinoma tumor-bearing wild-type littermates leads to enhanced tumor progression. However, although it can also be observed in sash mice, accelerated growth of transplanted line 1 alveolar cell carcinoma tumors is a mast cell-independent phenomenon. Thus, the Kit(W-sh) mutation broadly affects key steps in myelopoiesis that may have an impact on mast cell research.
    Type of Publication: Journal article published
    PubMed ID: 23636054
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  • 8
    Keywords: INFECTION ; ASSOCIATION ; multiplex serology
    Abstract: Helicobacter pylori (H. pylori) seropositivity has been inconsistently associated with pancreatic cancer. We, therefore, investigated the association between H. pylori seropositivity and pancreatic cancer in a case-control study nested within Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of Finnish male smokers. Pancreatic cancer cases (n = 353) and control subjects (n = 353) were matched on date of baseline serum collection, age at randomization, and follow-up time (up to 23.9 years). We used a multiplex serology assay to determine the sero-status of antibodies against 15 H. pylori-specific antigens in fasting serum samples. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Neither targeted H. pylori antigens in serum nor the combination of all was associated with development of pancreatic cancer (combination of all: OR, 0.85; 95% CI, 0.49-1.49). Our results suggest that H. pylori is not a risk factor for pancreatic cancer.
    Type of Publication: Journal article published
    PubMed ID: 24089457
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  • 9
    Keywords: FOLLOW-UP ; EPIDEMIOLOGY ; PROTEINS ; INFECTION ; cancer risk ; glutathione-S-transferase ; multiplex serology ; FOOD-CONSUMPTION HABITS ; EARLY-CHILDHOOD ; GASTRIC EPITHELIAL-CELLS
    Abstract: BACKGROUND: Helicobacter pylori infection that is usually acquired in childhood and lasts for lifetime is mostly asymptomatic but associated with severe gastrointestinal disease including cancer. During chronic infection, the gastric mucosa is histologically changing. This forces H. pylori to permanent adaptation in its gastric habitat by expression of different proteins which might be reflected in distinctive antibody patterns. METHODS: To characterize dynamics of the immune response to H. pylori we analysed 1797 sera of a cross-sectional study representative for the German population (age range 1-82 years) with multiplex serology, a fluorescent bead-based antibody binding assay that allows simultaneous and quantitative detection of antibodies. Fifteen recombinant, affinity-purified H. pylori proteins (UreA, GroEL, Catalase, NapA, CagA, CagM, Cagdelta, HP0231, VacA, HpaA, Cad, HyuA, Omp, HcpC and HP0305) were used as antigens. RESULTS: H. pylori seroprevalence (positivity for at least three antigens) was 48% and increased with age from 12% in children 〈15 years to 69% in females and 90% in males 〉65 years. Prevalences were highest (〉83%) for Omp, VacA and GroEL. For 11 proteins, seroprevalence was higher in males than females (P 〈 0.05) from age 55 onwards. For all antigens, the median prevalence increase per age decade was stronger in males (8.4%, range 3.8-12.9%) than females (6.1%, range 3.4-10.8%). However, among seropositives the median number of antigens recognized increased from children 〈15 years to individuals 〉65 years stronger in females (P = 0.02). Antibody reactivities to GroEL, HyuA, CagM, Catalase, NapA and UreA also increased stronger in females (average 1.7-fold/decade, SD 0.5) than in males (1.5-fold/decade, SD 0.4). CONCLUSION: H. pylori antibody response accumulates qualitatively and quantitatively with age. This may reflect a lifelong stimulation of the immune response by chronically active infection.
    Type of Publication: Journal article published
    PubMed ID: 24782915
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  • 10
    Keywords: INDUCED APOPTOSIS ; SQUAMOUS-CELL CARCINOMA ; EPIDERMODYSPLASIA-VERRUCIFORMIS ; E6 PROTEINS ; NONMELANOMA SKIN-CANCER ; HUMAN-PAPILLOMAVIRUS TYPES ; SUN EXPOSURE ; BASAL-CELL ; CUTANEOUS HUMAN PAPILLOMAVIRUSES ; BETA-HUMAN PAPILLOMAVIRUSES
    Abstract: Organ transplant recipients (OTR) have an increased risk of developing keratinocyte carcinomas (KC). The aim of this study was to correlate infection with human papillomaviruses (HPV) belonging to the beta genus (Beta-PV) at transplantation with later development of KC. In a cohort study, sera collected between one year before and one year after transplantation of OTR transplanted between 1990 and 2006 were tested for antibody responses against the L1 capsid antigen of Beta-PV and other HPV genera (Gamma-, Mu-, Nu-, Alpha-PV) using multiplex serology. The OTR were followed for a maximum of 22 years. Cox regression models with KC, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) as outcome variables were used. Sixty out of 445 OTR had developed KC: 14 developed only SCC, 24 only BCC and 22 both types of KC. The time-dependent hazard ratio to develop either or both types of KC, adjusted for age, sex and transplanted organ, in OTR tested Beta-PV seropositive around time of transplantation compared to Beta-PV seronegative OTR was 2.9 (95%CI 1.3-6.4). The hazard ratio for SCC was 2.9 (95%CI 0.99-8.5) and for BCC 3.1 (95%CI 1.2-8.0). There was also an association between Mu-PV seropositivity and KC, but there were no significant associations between other HPV genera tested and KC. A positive seroresponse for Beta-PV around transplantation significantly predicted the development of KC in OTR up to 22 years later, providing additional evidence that infection with Beta-PV plays a role in KC carcinogenesis.Journal of Investigative Dermatology accepted article preview online, 27 October 2014. doi:10.1038/jid.2014.456.
    Type of Publication: Journal article published
    PubMed ID: 25347116
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