LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 12

Search options

  1. Book ; Thesis: Assessment of new avenues of screening for colorectal cancer based on novel molecular blood and stool tests

    Hundt, Sabrina

    2009  

    Author's details vorgelegt von Sabrina Hundt
    Language English
    Size VIII, 116 Bl., Ill., graph. Darst., 30 cm
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Heidelberg, Univ., Diss., 2009
    HBZ-ID HT016284935
    Database Catalogue ZB MED Medicine, Health

    Kategorien

  2. Article ; Online: SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

    Löhr, Mario / Härtig, Wolfgang / Schulze, Almut / Kroiß, Matthias / Sbiera, Silviu / Lapa, Constantin / Mages, Bianca / Strobel, Sabrina / Hundt, Jennifer Elisabeth / Bohnert, Simone / Kircher, Stefan / Janaki-Raman, Sudha / Monoranu, Camelia-Maria

    International journal of molecular sciences

    2022  Volume 23, Issue 7

    Abstract: Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum ... ...

    Abstract Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and
    MeSH term(s) Adrenal Cortex Neoplasms ; Adrenocortical Carcinoma ; Brain Neoplasms/metabolism ; Glioblastoma/metabolism ; Glioma/metabolism ; Humans ; Isocitrate Dehydrogenase/genetics ; Mutation ; Sterol O-Acyltransferase/metabolism
    Chemical Substances Isocitrate Dehydrogenase (EC 1.1.1.41) ; Sterol O-Acyltransferase (EC 2.3.1.26) ; sterol O-acyltransferase 1 (EC 2.3.1.26)
    Language English
    Publishing date 2022-03-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23073726
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: SOAT1

    Mario Löhr / Wolfgang Härtig / Almut Schulze / Matthias Kroiß / Silviu Sbiera / Constantin Lapa / Bianca Mages / Sabrina Strobel / Jennifer Elisabeth Hundt / Simone Bohnert / Stefan Kircher / Sudha Janaki-Raman / Camelia-Maria Monoranu

    International Journal of Molecular Sciences, Vol 23, Iss 3726, p

    A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

    2022  Volume 3726

    Abstract: Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum ... ...

    Abstract Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH -mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.
    Keywords SOAT1 ; glioblastoma ; astrocytoma ; IDH1 / 2 ; lipid droplets ; mitotane ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  4. Article ; Online: Sensitivity estimates of blood-based tests for colorectal cancer detection: impact of overrepresentation of advanced stage disease.

    Tao, Sha / Hundt, Sabrina / Haug, Ulrike / Brenner, Hermann

    The American journal of gastroenterology

    2011  Volume 106, Issue 2, Page(s) 242–253

    Abstract: A large number of blood-based markers have been proposed for early detection of colorectal cancer (CRC). Their sensitivity for detecting CRC has mostly been evaluated in clinical settings, and found to be higher in more advanced stages compared with ... ...

    Abstract A large number of blood-based markers have been proposed for early detection of colorectal cancer (CRC). Their sensitivity for detecting CRC has mostly been evaluated in clinical settings, and found to be higher in more advanced stages compared with earlier stages of the disease. The aim of this study is to estimate the overall sensitivity of blood-based markers expected in screening settings, where the proportion of advanced stages is typically lower than in clinical settings. A systematic literature review was performed on studies evaluating sensitivity and specificity of blood-based markers for early detection of CRC. For each study, overall sensitivity expected in screening settings was estimated by weighting stage-specific sensitivities according to the stage distribution of CRC expected in the screening setting. The latter was derived from 12,605 CRC cases diagnosed in the German screening colonoscopy program during 2003-2007. Overall, 73 studies evaluating 55 blood-based markers were identified. Adjusted sensitivity was lower than reported sensitivity in 120 (90%) evaluations of different markers. Median absolute reduction in sensitivity after adjustment was 9.0% (interquartile range: 4.0-13.0) units, whereas median relative reduction was 19.5% (interquartile range: 11.3-33.3%). Blood-based markers for CRC detection reported from clinical settings showed higher sensitivities than expected in the screening setting in most cases, mainly due to substantially higher proportions of advanced stage cancers. Adjustment of sensitivity to the stage distribution expected in the screening setting is crucial to obtain realistic and comparable estimates of sensitivities.
    MeSH term(s) Biomarkers/blood ; Colorectal Neoplasms/blood ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/pathology ; Hematologic Tests/methods ; Humans ; Mass Screening ; Neoplasm Staging ; Sensitivity and Specificity
    Chemical Substances Biomarkers
    Language English
    Publishing date 2011-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 390122-1
    ISSN 1572-0241 ; 0002-9270
    ISSN (online) 1572-0241
    ISSN 0002-9270
    DOI 10.1038/ajg.2010.393
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Inter-test agreement and quantitative cross-validation of immunochromatographical fecal occult blood tests.

    Brenner, Hermann / Haug, Ulrike / Hundt, Sabrina

    International journal of cancer

    2010  Volume 127, Issue 7, Page(s) 1643–1649

    Abstract: Immunochromatographical fecal occult blood tests were shown to have higher sensitivity for detecting colorectal neoplasms than the commonly used guaiac-based test. However, positivity rates, sensitivity and specificity vary widely. We aimed to assess the ...

    Abstract Immunochromatographical fecal occult blood tests were shown to have higher sensitivity for detecting colorectal neoplasms than the commonly used guaiac-based test. However, positivity rates, sensitivity and specificity vary widely. We aimed to assess the reasons for this heterogeneity. Six dichotomous (qualitative) immunochromatographical tests were used in the same stool samples, taken before cathartic bowel preparation, from 1,330 participants of the German colonoscopy screening program. Positivity rates were determined, and inter-test agreement beyond chance was quantified by kappa coefficients (kappa). In addition, kappa coefficients were expressed in relation to their maximum possible values given differences in test positivity rates (kappa/kappa(max)). Furthermore, the distribution of fecal hemoglobin concentration was assessed by an additional quantitative test in participants classified as clearly positive, borderline positive or clearly negative according to the qualitative tests. Positivity rates strongly varied from 6.4 to 46.8%. As a result, overall agreement between tests was only poor to moderate, with kappa ranging from 0.14 to 0.61. However, apart from the different positivity rates, agreement was mostly very high, with kappa/kappa(max) ranging from 0.53 to 1.00, and exceeding 0.70 in 12 of 15 cases. Distribution of fecal hemoglobin concentrations in the various categories strongly varied across tests. The observed patterns suggest that the strongly different positivity rates essentially reflect different cutoff levels of tests with otherwise very high inter-test agreement. Definition of cutoffs is a critical issue in the application of immunochromatographical tests and should be redefined for several of these tests.
    MeSH term(s) Adenoma/blood ; Adenoma/diagnosis ; Adenoma/immunology ; Aged ; Colonic Polyps/blood ; Colonic Polyps/diagnosis ; Colonic Polyps/immunology ; Colorectal Neoplasms/blood ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/immunology ; Female ; Guaiac ; Humans ; Immunologic Tests ; Intestinal Polyps/blood ; Intestinal Polyps/diagnosis ; Intestinal Polyps/immunology ; Male ; Middle Aged ; Neoplasms/blood ; Neoplasms/diagnosis ; Neoplasms/immunology ; Occult Blood ; Reproducibility of Results
    Chemical Substances Guaiac (9000-29-7)
    Language English
    Publishing date 2010-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.25154
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Sex differences in performance of fecal occult blood testing.

    Brenner, Hermann / Haug, Ulrike / Hundt, Sabrina

    The American journal of gastroenterology

    2010  Volume 105, Issue 11, Page(s) 2457–2464

    Abstract: Objectives: Immunological and guaiac-based fecal occult blood tests (iFOBTs and gFOBTs) are widely used for early detection of colorectal cancer (CRC). We aimed to assess potential sex differences in performance of iFOBTs and gFOBT in the screening ... ...

    Abstract Objectives: Immunological and guaiac-based fecal occult blood tests (iFOBTs and gFOBTs) are widely used for early detection of colorectal cancer (CRC). We aimed to assess potential sex differences in performance of iFOBTs and gFOBT in the screening setting.
    Methods: The sensitivity, specificity, and positive and negative predictive values for detection of advanced colorectal neoplasms (CRC or advanced adenoma) were assessed by sex for a range of cutpoints of a quantitative iFOBT (RIDASCREEN Hemoglobin), six qualitative iFOBTs, and a gFOBT (HemOccult) among 1,157 male and 1,167 female participants of the German screening colonoscopy program (mean age: 63.0 and 62.0 years, respectively).
    Results: The prevalence of advanced colorectal neoplasms was much higher among men (13.5%) than among women (7.5%). At any cutpoint of the quantitative iFOBT, and for all qualitative iFOBTs and the gFOBT, the sensitivity and positive predictive value were substantially higher, and specificity and negative predictive value were substantially lower among men than among women. At the cutpoint of 2 μg/g stool given by the manufacturer of the quantitative iFOBT, sensitivity, specificity, and the positive and negative predictive values were 47.6, 85.0, 33.0, and 91.3% among men, and 30.7, 89.5, 19.3, and 94.1% among women (P value for sex differences 0.001, 0.002, 0.004, and 0.019, respectively). Sex differences in predictive values were mostly explained by sex differences in the prevalence of advanced colorectal neoplasms.
    Conclusions: There are major sex differences in the performance of fecal occult blood testing, which might require careful attention in the interpretation of test results, and in the design, modeling, and evaluation of CRC screening strategies.
    MeSH term(s) Adenoma/diagnosis ; Aged ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Early Detection of Cancer/methods ; Feces/chemistry ; Female ; Guaiac ; Humans ; Male ; Middle Aged ; Occult Blood ; Predictive Value of Tests ; Sensitivity and Specificity ; Sex Characteristics
    Chemical Substances Guaiac (9000-29-7)
    Language English
    Publishing date 2010-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390122-1
    ISSN 1572-0241 ; 0002-9270
    ISSN (online) 1572-0241
    ISSN 0002-9270
    DOI 10.1038/ajg.2010.301
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Quantitative immunochemical fecal occult blood testing for colorectal adenoma detection: evaluation in the target population of screening and comparison with qualitative tests.

    Haug, Ulrike / Hundt, Sabrina / Brenner, Hermann

    The American journal of gastroenterology

    2010  Volume 105, Issue 3, Page(s) 682–690

    Abstract: Objectives: Quantitative and qualitative immunochemical fecal occult blood tests (FOBTs) have been proposed for noninvasive colorectal cancer screening, but comparative evaluation is lacking. The aim of this study was to determine the diagnostic ... ...

    Abstract Objectives: Quantitative and qualitative immunochemical fecal occult blood tests (FOBTs) have been proposed for noninvasive colorectal cancer screening, but comparative evaluation is lacking. The aim of this study was to determine the diagnostic accuracy of two (quantitative) enzyme-linked immunosorbent assay (ELISA)-based immunochemical FOBTs for identifying colorectal adenomas in the target population of screening and to compare the results with six (qualitative) immunochromatographic FOBTs, previously evaluated in the same study participants using the same stool samples.
    Methods: A total of 1,319 participants of screening colonoscopy at average risk for colorectal neoplasia (mean age 63 years; age range 31-86 years; 50% men) were recruited prospectively from January 2006 to December 2007 in collaboration with 20 gastroenterological practices in Germany. Fecal hemoglobin and hemoglobin-haptoglobin levels were measured using an automated ELISA (RIDASCREEN). Test performance characteristics at different cutoff values were derived by comparing the results of stool testing with the results of colonoscopy in a blinded manner.
    Results: A total of 130 participants (10%) had an advanced adenoma. The area under the receiver-operating characteristic curve with regard to advanced adenomas was 0.68 (0.65-0.71) for hemoglobin and 0.64 (0.61-0.67) for hemoglobin-haptoglobin (P=0.034). At a specificity of approximately 95%, the sensitivity (95% confidence interval) for advanced adenomas was 33% (25-42%) for hemoglobin and 24% (17-32%) for hemoglobin-haptoglobin, respectively. The sensitivity for hemoglobin was very close to sensitivities of the six qualitative FOBTs at (strongly divergent) levels of specificity observed for the latter.
    Conclusions: ELISA-based measurement of hemoglobin was superior to hemoglobin-haptoglobin, but showed a similar sensitivity for advanced adenomas compared with (qualitative) immunochromatographic FOBTs at defined levels of specificity. Compared with the latter, its quantitative nature offers advantages in terms of transparency and flexibility regarding the positivity threshold (e.g., specificity can be oriented toward available colonoscopy resources or personal risk profiles) and in terms of a higher level of standardization regarding test analysis and interpretation.
    MeSH term(s) Adenoma/diagnosis ; Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Colorectal Neoplasms/diagnosis ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Humans ; Immunoassay/methods ; Male ; Mass Screening/methods ; Middle Aged ; Occult Blood ; Predictive Value of Tests ; ROC Curve ; Sensitivity and Specificity
    Language English
    Publishing date 2010-03
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390122-1
    ISSN 1572-0241 ; 0002-9270
    ISSN (online) 1572-0241
    ISSN 0002-9270
    DOI 10.1038/ajg.2009.668
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection.

    Hundt, Sabrina / Haug, Ulrike / Brenner, Hermann

    Annals of internal medicine

    2009  Volume 150, Issue 3, Page(s) 162–169

    Abstract: Background: Different immunochemical fecal occult blood tests (FOBTs) have been proposed for noninvasive colorectal cancer screening. Large-scale, colonoscopy-based screening studies that allow evaluation of these tests for the detection of precursor ... ...

    Abstract Background: Different immunochemical fecal occult blood tests (FOBTs) have been proposed for noninvasive colorectal cancer screening. Large-scale, colonoscopy-based screening studies that allow evaluation of these tests for the detection of precursor lesions are scarce.
    Objective: To determine and compare performance characteristics of 6 qualitative immunochemical FOBTs for identifying colorectal adenomas among adults who attended screening colonoscopy examinations.
    Design: Prospective screening study from January 2006 to December 2007.
    Setting: 20 gastroenterology practices in Germany that did screening colonoscopy.
    Patients: 1319 participants at average risk for colorectal neoplasia who were undergoing screening colonoscopy (mean age, 63 years; 50% men).
    Measurements: 6 different qualitative immunochemical FOBTs were done with stool samples collected before bowel preparation for colonoscopy. Performance characteristics (sensitivity, specificity, predictive values, and likelihood ratios) of tests were measured by comparing test results with findings on colonoscopy. Technicians who read the tests were blinded to colonoscopy results, and colonoscopists were blinded to FOBT results.
    Results: Overall, 405 participants (31%) had an adenoma and 130 participants (10%) had an advanced adenoma. Performance characteristics varied widely among tests. For the 2 best-performing tests (immoCARE-C [CAREdiagnostica, Voerde, Germany] and FOB advanced [ulti med, Ahrensburg, Germany]), the sensitivity for detection of advanced adenomas was 25% (95% CI, 18% to 34%) and 27% (CI, 20% to 35%), respectively; specificity was 97% (CI, 95% to 98%) and 93% (CI, 91% to 95%); and the positive likelihood ratio was 3.5 (CI, 2.2 to 5.4) and 2.5 (CI, 1.9 to 3.5).
    Limitation: The study differed from real-life conditions in that stool samples were not directly dissolved in a buffer-filled vial; instead, a small container was used and stool was frozen before testing.
    Conclusion: Qualitative immunochemical FOBTs could be an option for future colorectal cancer screening because they showed better performance characteristics for precursor lesions than guaiac-based FOBTs and are practical for mass screening. However, given the large differences in diagnostic performance among tests, careful evaluation of the different test variants is important.
    Funding: The German Research Foundation (Deutsche Forschungsgemeinschaft) within the framework of a PhD program (Graduiertenkolleg 793).
    MeSH term(s) Adenoma/diagnosis ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Early Detection of Cancer ; Female ; Guaiac ; Humans ; Immunohistochemistry/methods ; Indicators and Reagents ; Male ; Middle Aged ; Occult Blood ; Predictive Value of Tests ; Specimen Handling
    Chemical Substances Indicators and Reagents ; Guaiac (9000-29-7)
    Language English
    Publishing date 2009-01-19
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 336-0
    ISSN 1539-3704 ; 0003-4819
    ISSN (online) 1539-3704
    ISSN 0003-4819
    DOI 10.7326/0003-4819-150-3-200902030-00005
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article: Blood markers for early detection of colorectal cancer: a systematic review.

    Hundt, Sabrina / Haug, Ulrike / Brenner, Hermann

    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

    2007  Volume 16, Issue 10, Page(s) 1935–1953

    Abstract: Background: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on ... ...

    Abstract Background: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on the analysis of blood specimens may overcome this problem. The purpose of this review was to give an overview of published studies on blood markers aimed at the early detection of CRC and to summarize their performance characteristics.
    Method: The PUBMED database was searched for relevant studies published until June 2006. Only studies with more than 20 cases and more than 20 controls were included. Information on the markers under study, on the underlying study populations, and on performance characteristics was extracted. Special attention was given to performance characteristics by tumor stage.
    Results: Overall, 93 studies evaluating 70 different markers were included. Most studies were done on protein markers, but DNA markers and RNA markers were also investigated. Performance characteristics varied widely between different markers, but also between different studies using the same marker. Promising results were reported for some novel assays, e.g., assays based on SELDI-TOF MS or MALDI-TOF MS, for some proteins (e.g., soluble CD26 and bone sialoprotein) and also for some genetic assays (e.g., L6 mRNA), but evidence thus far is restricted to single studies with limited sample size and without further external validation.
    Conclusions: Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions.
    MeSH term(s) Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Genetic Markers/genetics ; Humans ; Neoplasm Proteins/blood ; Neoplasm Proteins/genetics ; Neoplasm Staging ; Neoplasms/blood ; Neoplasms/diagnosis ; Neoplasms/genetics ; Neoplasms/pathology ; Predictive Value of Tests
    Chemical Substances Biomarkers, Tumor ; Genetic Markers ; Neoplasm Proteins
    Language English
    Publishing date 2007-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1153420-5
    ISSN 1055-9965
    ISSN 1055-9965
    DOI 10.1158/1055-9965.EPI-06-0994
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Conference proceedings: Blood markers for early detection of colorectal cancer. A systematic review

    Hundt, Sabrina / Haug, Ulrike / Brenner, Hermann

    2007  , Page(s) 07gmds572

    Event/congress Kongress Medizin und Gesellschaft 2007; Augsburg; ; Medizinischer Dienst der Krankenversicherung in Bayern; 2007
    Keywords Medizin, Gesundheit ; colorectal cancer ; CRC ; early detection ; serum marker ; biomarker
    Publishing date 2007-09-06
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    Database German Medical Science

    More links

    Kategorien

To top