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Search Results: 1 - 10 of 266073 matches for " Claus K H?gdall "
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YKL-40 tissue expression and plasma levels in patients with ovarian cancer
Estrid VS Hgdall, Merete Ringsholt, Claus K Hgdall, Ib Jarle Christensen, Julia S Johansen, Susanne K Kjaer, Jan Blaakaer, Lene Ostenfeld-M?ller, Paul A Price, Lise H Christensen
BMC Cancer , 2009, DOI: 10.1186/1471-2407-9-8
Abstract: YKL-40 protein expression was determined by immunohistochemistry in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients.YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor cell expression was higher in OC than in borderline tumors (p = 0.001), and associated with FIGO stage (p < 0.0001) and histological subtype (p = 0.0009). Positive YKL-40 expression (≥ 5% staining) was not associated with reduced survival. Plasma YKL-40 was also higher in patients with OC than in patients with borderline tumors (p < 0.0001), and it was positively correlated to serum CA-125 (p < 0.0001) and FIGO stage (p = 0.0001). Univariate Cox analysis of plasma YKL-40 showed association with overall survival (p < 0.0001). Multivariate Cox analysis, including plasma YKL-40, serum CA125, FIGO stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40–3.25, p = 0.0004).YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic biomarker in patients with OC.YKL-40 (chitinase-3-like-1) is a highly conserved protein [1] and a member of "mammalian chitinase-like proteins" [1,2]. The protein is expressed in many types of cancer cells (dbest NCBI database), and elevated plasma levels are predictive of poor prognosis in patients with different types of cancer [2-8]. The highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival [2-8]. Furthermore, plasma YKL-40 has provided independent information on prognosis over clinical characteristics and biomarkers, such as serum CA-125, LDH, PSA, CEA, and HER2 [2-8]. It has been suggested that YKL-40 is associated with cancer cell prolife
Circulating Antinuclear Antibodies in Patients with Pelvic Masses Are Associated with Malignancy and Decreased Survival
Niels H. H. Heegaard, Mikkel West-N?rager, Julia T. Tanassi, Gunnar Houen, Lotte Nedergaard, Claus Hgdall, Estrid Hgdall
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030997
Abstract: Background Circulating autoantibodies occur more frequently in cancer patients than in patients without cancer. Methods and Findings We examined sera from patients referred for pelvic mass symptoms to a tertiary university clinic. A total of 127 were diagnosed with epithelial ovarian cancer while 386 had a benign condition. A screen for IgG anti-nuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells confirmed a highly significant overrepresentation of ANA in the cancer group where 40% had detectable (i.e., a titer ≥160) ANA compared with less than 12% in the benign group. The overrepresentation of ANA in the cancer group persisted (p<0.0001) after matching the age-profile of the benign group with the ovarian cancer group. Only 19 out of 127 patients in the age-matched benign subgroup were positive for ANA corresponding to an 85% specificity at 40% sensitivity of ANA as the only marker for malignancy. No correlation of ANA positivity in either group with specific bands in immunoblots could be demonstrated even though immunoblot positivity was clearly increased in the malignant group (41% vs. 3%). The presence, strength, and type of ANA did not correlate with serum CA-125 values or with staging, and ANA outcome did not contribute with independent diagnostic information. However, survival was significantly shorter in ANA-positive compared with ANA-negative cancer patients and patients with CA-125 below the median CA-125 value in the cancer group had a significantly decreased survival when positive for ANA. ANA status made no difference in the group with CA-125 values above the median. Also, there was a significant correlation between speckled ANA-strength and histological tumor grade. Conclusions Circulating antibodies are a promising source for new biomarkers in cancer. Characterization of epitope specificities and measurements of consecutive samples will be important for further elucidating the role of ANA in evaluating ovarian cancer patients.
Polymorphisms in Stromal Genes and Susceptibility to Serous Epithelial Ovarian Cancer: A Report from the Ovarian Cancer Association Consortium
Ernest K. Amankwah, Qinggang Wang, Joellen M. Schildkraut, Ya-Yu Tsai, Susan J. Ramus, Brooke L. Fridley, Jonathan Beesley, Sharon E. Johnatty, Penelope M. Webb, Georgia Chenevix-Trench, Australian Ovarian Cancer Study Group , Laura C. Dale, Diether Lambrechts, Frederic Amant, Evelyn Despierre, Ignace Vergote, Simon A. Gayther, Aleksandra Gentry-Maharaj, Usha Menon, Jenny Chang-Claude, Shan Wang-Gohrke, Hoda Anton-Culver, Argyrios Ziogas, Thilo D?rk, Matthias Dürst, Natalia Antonenkova, Natalia Bogdanova, Robert Brown, James M. Flanagan, Stanley B. Kaye, James Paul, Ralf Bützow, Heli Nevanlinna, Ian Campbell, Diana M. Eccles, Beth Y. Karlan, Jenny Gross, Christine Walsh, Paul D. P. Pharoah, Honglin Song, Susanne Krüger Kj?r, Estrid Hgdall, Claus Hgdall, Lene Lundvall, Lotte Nedergaard, Lambertus A. L. M. Kiemeney, Leon F. A. G. Massuger, Anne M. van Altena, Sita H. H. M. Vermeulen, Nhu D. Le, Angela Brooks-Wilson, Linda S. Cook, Catherine M. Phelan, Julie M. Cunningham, Celine M. Vachon, Robert A. Vierkant, Edwin S. Iversen, Andrew Berchuck, Ellen L. Goode, Thomas A. Sellers, Linda E. Kelemen
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0019642
Abstract: Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≥0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≤0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.
Association between Common Germline Genetic Variation in 94 Candidate Genes or Regions and Risks of Invasive Epithelial Ovarian Cancer
Lydia Quaye, Jonathan Tyrer, Susan J. Ramus, Honglin Song, Eva Wozniak, Richard A. DiCioccio, Valerie McGuire, Estrid Hgdall, Claus Hgdall, Jan Blaakaer, Ellen L. Goode, Joellen M. Schildkraut, Douglas F. Easton, Susanne Krüger-Kjaer, Alice S. Whittemore, Simon A. Gayther, Paul D. P. Pharoah
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005983
Abstract: Background Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. Methods We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA. Results After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment-wise test for association (P-heterogeneity = 0.051; P-trend = 0.068). Conclusion These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs.
Charge-screening role of $c$-axis atomic displacements in YBa$_2$Cu$_3$O$_{6+x}$ and related superconductors
E. S. Bozin,A. Huq,Bing Shen,H. Claus,W. K. Kwok,J. M. Tranquada
Physics , 2015,
Abstract: The importance of charge reservoir layers for supplying holes to the CuO$_2$ planes of cuprate superconductors has long been recognized. Less attention has been paid to the screening of the charge transfer by the intervening ionic layers. We address this issue in the case of YBa$_2$Cu$_3$O$_{6+x}$, where CuO chains supply the holes for the planes. We present a simple dielectric-screening model that gives a linear correlation between the relative displacements of ions along the $c$ axis, determined by neutron powder diffraction, and the hole density of the planes. Applying this model to the temperature dependent shifts of ions along the $c$ axis, we infer a charge transfer of 5-10% of the hole density from the planes to the chains on warming from the superconducting transition to room temperature. Given the significant coupling of $c$-axis displacements to the average charge density, we point out the relevance of local displacements for screening charge modulations and note recent evidence for dynamic screening of in-plane quasiparticles. This line of argument leads us to a simple model for atomic displacements and charge modulation that is consistent with images from scanning-tunneling microscopy for underdoped Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$.
Long QT Interval in Turner Syndrome – A High Prevalence of LQTS Gene Mutations
Christian Trolle, Kristian H. Mortensen, Lisbeth N. Pedersen, Agnethe Berglund, Henrik K. Jensen, Niels H. Andersen, Claus H. Gravholt
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069614
Abstract: Objectives QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Methods Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett’s (bQTc) and Hodges’s formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. Results The mean hQTc in women with Turner syndrome (414.0±25.5 ms) compared to controls (390.4±17.8 ms) was prolonged (p<0.001) and did not change over time (416.9±22.6 vs. 415.6±25.5 ms; p = 0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2±24.8 vs. 407.6±25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). Conclusion There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. Clinical Trial Registration NCT00624949. https://register.clinicaltrials.gov/prs/?app/action/SelectProtocol/sid/S0001FLI/s?electaction/View/ts/3/uid/U000099E.
Studies on Two Exoenzymes Which Lyse Wine-Spoiling Bacteria  [PDF]
Patrick Sebastian, Harald Claus, Helmut K?nig
Advances in Microbiology (AiM) , 2014, DOI: 10.4236/aim.2014.49059

Microorganisms play an important role in the conversion of grape juice into wine. Different species of yeast are mainly responsible for the production of ethanol. Lactic acid bacteria also occur regularly in must or wine. They are mostly undesirable due to their capacity to produce wine-spoiling compounds. Especially strains of Lactobacillus brevis are able to produce biogenic amines as well as precursors of ethyl carbamate and different off-flavours (N-heterocycles, volatile phenols). By excessive formation of acetic acid some lactobacilli may even induce slow/stuck grape juice fermentations. In conventional winemaking, additions of sulphite or lysozyme are used to inhibit the growth of spoilage microorganisms. There is a strong interest in finding alternatives, because of the reduced activity of lysozyme in the wine milieu, a limited growth-inhibiting activity against lactic acid bacteria, and some health risks described regarding the application of sulphite. We found that a culture supernatant of Streptomyces albidoflavus B 578 lysed all bacteria previously isolated from must and wine samples (Acetobacter sp., Lactobacillus sp., Leuconostoc sp., Oenococcus oeni, Pediococcus sp., Staphylococcus sp.) including 35 strains of L. brevis. Two bacteriolytic

A Highly Sensitive Quantitative Real-Time PCR Assay for Determination of Mutant JAK2 Exon 12 Allele Burden
Lasse Kj?r, Maj Westman, Caroline Hasselbalch Riley, Estrid Hgdall, Ole Weis Bjerrum, Hans Hasselbalch
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033100
Abstract: Mutations in the Janus kinase 2 (JAK2) gene have become an important identifier for the Philadelphia-chromosome negative chronic myeloproliferative neoplasms. In contrast to the JAK2V617F mutation, the large number of JAK2 exon 12 mutations has challenged the development of quantitative assays. We present a highly sensitive real-time quantitative PCR assay for determination of the mutant allele burden of JAK2 exon 12 mutations. In combination with high resolution melting analysis and sequencing the assay identified six patients carrying previously described JAK2 exon 12 mutations and one novel mutation. Two patients were homozygous with a high mutant allele burden, whereas one of the heterozygous patients had a very low mutant allele burden. The allele burden in the peripheral blood resembled that of the bone marrow, except for the patient with low allele burden. Myeloid and lymphoid cell populations were isolated by cell sorting and quantitative PCR revealed similar mutant allele burdens in CD16+ granulocytes and peripheral blood. The mutations were also detected in B-lymphocytes in half of the patients at a low allele burden. In conclusion, our highly sensitive assay provides an important tool for quantitative monitoring of the mutant allele burden and accordingly also for determining the impact of treatment with interferon-α-2, shown to induce molecular remission in JAK2V617F-positive patients, which may be a future treatment option for JAK2 exon 12-positive patients as well.
Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization for Low and High Throughput HER2 Genetic Testing
Tim S. Poulsen,Maiken L. M. Espersen,Vibeke Kofoed,Tanja Dabetic,Estrid Hgdall,Eva Balslev
International Journal of Breast Cancer , 2013, DOI: 10.1155/2013/368731
Abstract: The purpose was to evaluate and compare 5 different HER2 genetic assays with different characteristics that could affect the performance to analyze the human epidermal growth factor 2 (HER2) gene copy number under low and high throughput conditions. The study included 108 tissue samples from breast cancer patients with HER2 immunohistochemistry (IHC) results scored as 0/1+, 2+, and 3+. HER2 genetic status was analysed using chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). Scoring results were documented through digital image analysis. The cancer region of interest was identified from a serial H&E stained slide following tissue cores were transferred to a tissue microarrays (TMA). When using TMA in a routine flow, all patients will be tested for HER2 status with IHC followed by CISH or FISH, thereby providing individual HER2 results. In conclusion, our results show that the differences between the HER2 genetic assays do not have an effect on the analytic performance and the CISH technology is superior to high throughput HER2 genetic testing due to scanning speed, while the IQ-FISH may still be a choice for fast low throughput HER2 genetic testing. 1. Introduction Human Epidermal growth factor Receptor 2 (HER2) expression is investigated routinely on all breast cancer cases to make the therapeutic decisions for patients with breast cancer. The American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) recommendations for HER2 status testing are first immunohistochemical (IHC) staining and secondary to perform genetic HER2 testing on tissues scored as borderline cases (2+) found by IHC [1]. Ratio-based dual color HER2 gene amplification assays are commercially available from a multiple vendors using either fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH), where the various tests have differing characteristics (Table 1). The HER2/neu labeled part of the dual color HER2 genetic assays is in all cases DNA based, while the centromere reference part can either be an DNA probe or an peptide nucleic acids (PNA) probe. The direct labeling of the different FISH probes from Dako and ZytoVision uses red (TexasRed), orange (Rhodamine), or green (FITC) fluorocrome, while the CISH-based assays give rise to either red, green, or blue chromogenic precipitation. Various strategies for blocking of nonspecific probe binding and detection systems have been implemented into the different HER2 genetic assays. ZytoVison uses repeat-free oligonucleotides and thereby does not need
Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model
Sanjay Tiwari, Jan H Egberts, Olena Korniienko, Linda K?hler, Anna Trauzold, Claus C Glüer, Holger Kalthoff
BMC Medical Imaging , 2011, DOI: 10.1186/1471-2342-11-15
Abstract: In the first experiment, primary orthotopic pancreatic tumor growth was measured with Infliximab treatment. In the second experiment, orthotopic tumors were resected ten days after inoculation of tumor cells and tumor recurrence was measured following Infliximab treatment. Tumor progression was evaluated using 3D high resolution sonography.Sonography measurement of tumor volume in vivo showed inhibitory effect of Infliximab on primary tumor growth in both non-resected and resected models. Measurement of the dynamics of tumor growth by sonography revealed that in the primary tumor Infliximab is effective against established tumors while in the resection model, Infliximab is more effective at an early stage following tumor resection. Infliximab treatment is also effective in inhibiting tumor growth growth as a result of tumor cell contamination of the surgical field.Clinical application of Infliximab is feasible in both the neoadjuvant and adjuvant setting. Infliximab is also effective in slowing the growth of tumor growth under the peritoneum and may have application in treating peritoneal carcinomatosis. Finally the study demonstrates that high resolution sonography is a sensitive imaging modality for the measurement of pancreatic tumor growth.Pancreatic cancer is the fourth leading cause of cancer death. It is characterized by high metastasis, uncontrolled proliferation and resistance to almost all current therapies. Consequently the prognosis of this disease is poor. Surgery is the only curative treatment option and is often followed up with adjuvant systemic chemotherapy and/or radiation. However, only about 10% of patients can be surgically treated and for those patients where surgery cannot remove the entire tumor, chemotherapy with or without radiation therapy is the best option [1]. The median survival rate following curative resection is less than 21 months and for non-surgical intervention the five year survival rate is about 4% [2]. More effective drug the
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