Grabe, Niels

[["dc.bibliographiccitation.firstpage","4193"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Annals of Surgical Oncology"],["dc.bibliographiccitation.lastpage","4201"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Kahlert, Christoph"],["dc.contributor.author","Gaitzsch, Eva"],["dc.contributor.author","Steinert, Gunnar"],["dc.contributor.author","Mogler, Carolin"],["dc.contributor.author","Herpel, Esther"],["dc.contributor.author","Hoffmeister, Michael"],["dc.contributor.author","Jansen, Lina"],["dc.contributor.author","Benner, Axel"],["dc.contributor.author","Brenner, Hermann"],["dc.contributor.author","Chang-Claude, Jenny"],["dc.contributor.author","Rahbari, Nuh"],["dc.contributor.author","Schmidt, Thomas"],["dc.contributor.author","Klupp, Fee"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Lahrmann, Bernd"],["dc.contributor.author","Koch, Moritz"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Büchler, Markus"],["dc.contributor.author","Weitz, Juergen"],["dc.date.accessioned","2022-04-29T14:53:50Z"],["dc.date.available","2022-04-29T14:53:50Z"],["dc.date.issued","2012-12"],["dc.description.abstract","Aldehyde dehydrogenase 1A1 (ALDH1A1) has been described as a cancer stem cell marker and as a regulator of cellular chemoresistance. Therefore, ALDH1A1 has been suggested as potential biomarker to stratify patients into different risk categories for a \"personalized\" therapy approach. We have investigated the prognostic role of ALDH1A1 in primary colorectal cancer and its value in predicting response to chemotherapy in metastatic colorectal cancer."],["dc.identifier.doi","10.1245/s10434-012-2518-9"],["dc.identifier.pmid","22878609"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107119"],["dc.language.iso","en"],["dc.relation.eissn","1534-4681"],["dc.relation.issn","1068-9265"],["dc.title","Expression analysis of aldehyde dehydrogenase 1A1 (ALDH1A1) in colon and rectal cancer in association with prognosis and response to chemotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e24116"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","OncoImmunology"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Spille, Anna"],["dc.contributor.author","Lerchl, Tina"],["dc.contributor.author","Brand, Karsten"],["dc.contributor.author","Herpel, Esther"],["dc.contributor.author","Welte, Stefan"],["dc.contributor.author","Keim, Sophia"],["dc.contributor.author","Lahrmann, Bernd"],["dc.contributor.author","Klupp, Fee"],["dc.contributor.author","Kahlert, Christoph"],["dc.contributor.author","Weitz, Jürgen"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jaeger, Dirk"],["dc.contributor.author","Zoernig, Inka"],["dc.date.accessioned","2022-04-29T14:52:41Z"],["dc.date.available","2022-04-29T14:52:41Z"],["dc.date.issued","2013-04-01"],["dc.description.abstract","The immune system plays an important role in shaping the clinical course of colorectal cancer (CRC). However, it is still unclear how the immune infiltrates of primary CRC lesions and distant metastases by immune effector cells are related to each other. To address this issue, we quantified CD3+, CD8+ and granzyme B+ lymphocytes in primary CRC samples and corresponding liver metastases. This analysis showed that the prognostic predictions that can be drawn from the infiltration of immune cells in primary CRCs and their metastases are heterogeneous. To investigate whether such heterogeneity would also be observed within CRC hepatic metastases, the density of the immune infiltrate and cytokine production were assessed in opposite sides of the same metastatic lesion. In addition, tumor-infiltrating lymphocytes were assessed in sequential sections of the same metastatic lesion, with a spacing of 30 μm. In summary, consistent cell counts and cytokine levels were detected within the same lesion. The study of a case of synchronous metastases, however, suggested that different metastatic lesions within the same patient may be heterogeneous, perhaps indicating a major impact for local causes on tumor infiltration by immune cells. In summary, our study demonstrates a consistent degree of heterogeneity between primary tumors and hepatic metastases but an excellent intra-lesional homogeneity. These findings may be of key importance for patient stratification and the development of personalized strategies against CRC."],["dc.identifier.doi","10.4161/onci.24116"],["dc.identifier.pmid","23734335"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107103"],["dc.language.iso","en"],["dc.relation.issn","2162-4011"],["dc.title","Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","593"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","OncoImmunology"],["dc.bibliographiccitation.lastpage","599"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Keim, Sophia"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Spille, Anna"],["dc.contributor.author","Lahrmann, Bernd"],["dc.contributor.author","Brand, Karsten"],["dc.contributor.author","Herpel, Esther"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jäger, Dirk"],["dc.contributor.author","Halama, Niels"],["dc.date.accessioned","2022-04-29T14:53:05Z"],["dc.date.available","2022-04-29T14:53:05Z"],["dc.date.issued","2012-08-01"],["dc.description.abstract","The role of the immune system in the course of colorectal cancer has been elucidated in the last decade. While quantification of immune cell infiltrates within the resected specimen at diagnosis has a clear power to estimate the prognosis of the patient, the role of infiltrating immune cells within the metastatic situation and especially within the metastatic lesion itself requires further detailed analyses. Recent analyses of infiltrates in colorectal cancer liver metastases revealed a role for the infiltrate density not only for prognosis but also in the prediction of treatment response. This not only broadens the view on these infiltrates and indicates a systematic role of the local immunological microenvironment, but also raises the question how these infiltrates change during repeated courses of treatment (i.e., resection, chemotherapy, etc.). To address this question, sequential lung or sequential liver metastases of colorectal cancer patients were analyzed using whole slide image quantification after immunohistochemical staining against CD3, CD8, FOXP3, CD68 and Granzyme B. The clinical data and interventions were associated with each individual patient and the metastatic lesions. The resulting cell densities reveal a heterogeneous profile: after successful treatment of a metastatic lesion, the recurrent lesion can still have the same immunophenotype with similar cell distributions. In a situation of a favorable immune cell profile, this profile can return and apparently convey a similar favorable course throughout the disease. But also the opposite was found: the recurrent metastatic lesion could have a different profile with alterations in specific immune cell subsets over time. Further analyses are required to elucidate the different patterns and their associations to the treatment, the tumor cell phenotype and other dynamic factors. However, it is clear from this data however, that there is an immune cell plasticity that needs to be analyzed for individual patients."],["dc.identifier.doi","10.4161/onci.20179"],["dc.identifier.pmid","22934251"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107109"],["dc.language.iso","en"],["dc.relation.issn","2162-4011"],["dc.title","Sequential metastases of colorectal cancer: Immunophenotypes and spatial distributions of infiltrating immune cells in relation to time and treatments"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5670"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","5677"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Michel, Sara"],["dc.contributor.author","Kloor, Matthias"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Benner, Axel"],["dc.contributor.author","Spille, Anna"],["dc.contributor.author","Pommerencke, Thora"],["dc.contributor.author","von Knebel, Doeberitz Magnus"],["dc.contributor.author","Folprecht, Gunnar"],["dc.contributor.author","Luber, Birgit"],["dc.contributor.author","Feyen, Nadine"],["dc.contributor.author","Martens, Uwe M."],["dc.contributor.author","Beckhove, Philipp"],["dc.contributor.author","Gnjatic, Sacha"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Herpel, Esther"],["dc.contributor.author","Weitz, Juergen"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jaeger, Dirk"],["dc.date.accessioned","2022-04-29T14:55:08Z"],["dc.date.available","2022-04-29T14:55:08Z"],["dc.date.issued","2011-09-01"],["dc.description.abstract","Analysis of tumor-infiltrating lymphocytes (TIL) in primary human colorectal cancer (CRC) by in situ immunohistochemical staining supports the hypothesis that the adaptive immune response influences the course of human CRC. Specifically, high densities of TILs in the primary tumor are associated with good prognosis independent of other prognostic markers. However, the prognostic role of TILs in metastatic CRC lesions is unknown, as is their role in response or resistance to conventional chemotherapy. We analyzed the association of TIL densities at the invasive margin of CRC liver metastases with response to chemotherapy and progression-free survival in a set of 101 large section samples. High-resolution automated microscopy on complete tissue sections was used to objectively generate cell densities for CD3, CD8, granzyme B, or FOXP3 positive immune cells. A predictive scoring system using TIL densities was developed in a training set and tested successfully in an independent validation set. TIL densities at the invasive margin of liver metastases allowed the prediction of response to chemotherapy with a sensitivity of 79% and specificity of 100%. The association of high density values with longer progression-free survival under chemotherapy was statistically significant. Overall, these findings extend the impact of the local immune response on the clinical course from the primary tumor also to metastatic lesions. Because detailed quantification of TILs in metastatic lesions revealed a strong association with chemotherapy efficacy and prognosis, we suggest that the developed scoring system may be used as a predictive tool for response to chemotherapy in metastatic CRC."],["dc.identifier.doi","10.1158/0008-5472.CAN-11-0268"],["dc.identifier.pmid","21846824"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107139"],["dc.language.iso","en"],["dc.relation.eissn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","795"],["dc.bibliographiccitation.lastpage","795"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Spille, Anna"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Brand, Karsten"],["dc.contributor.author","Falk, Christine"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jäger, Dirk"],["dc.date.accessioned","2022-04-29T14:54:49Z"],["dc.date.available","2022-04-29T14:54:49Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1158/1538-7445.AM2011-795"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107134"],["dc.relation.conference","AACR 102nd Annual Meeting 2011"],["dc.relation.eventend","2011-04-06"],["dc.relation.eventlocation","Orlando, FL"],["dc.relation.eventstart","2011-04-02"],["dc.relation.ispartof","Proceedings"],["dc.title","Abstract 795: Patterns of T-cell distribution at the invasive margin of colorectal cancer liver metastases: Downstream recruitment of T cells and spatial heterogeneity"],["dc.type","conference_paper"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","396"],["dc.bibliographiccitation.lastpage","396"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Keim, Sophia"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jaeger, Dirk"],["dc.date.accessioned","2022-04-29T14:54:45Z"],["dc.date.available","2022-04-29T14:54:45Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1158/1538-7445.AM2012-396"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107133"],["dc.relation.conference","AACR 103rd Annual Meeting 2012"],["dc.relation.eventend","2012-04-04"],["dc.relation.eventlocation","Chicago, IL"],["dc.relation.eventstart","2012-03-31"],["dc.relation.ispartof","Proceedings"],["dc.title","Abstract 396: Sequential metastases of colorectal cancer: Treatment, immunophenotypes and spatial distributions of infiltrating immune cells"],["dc.type","conference_paper"],["dc.type.internalPublication","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","62"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","OncoImmunology"],["dc.bibliographiccitation.lastpage","66"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Jaeger, Dirk"],["dc.date.accessioned","2022-04-29T14:52:46Z"],["dc.date.available","2022-04-29T14:52:46Z"],["dc.date.issued","2012-01-01"],["dc.description.abstract","Analysis of the local immunological microenvironment in colorectal cancer lesions yielded prognostic markers. Harnessing these insights for clinical application however requires the use of sophisticated technology and algorithms, especially the robust and reproducible quantification of immune cells. These technologies are available and will allow individualized treatment decisions beyond the current standard."],["dc.identifier.doi","10.4161/onci.1.1.18460"],["dc.identifier.pmid","22720213"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107104"],["dc.language.iso","en"],["dc.relation.issn","2162-4011"],["dc.title","The local immunological microenvironment in colorectal cancer as a prognostic factor for treatment decisions in the clinic: The way ahead"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1169"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cytometry. Part A"],["dc.bibliographiccitation.lastpage","1176"],["dc.bibliographiccitation.volume","77"],["dc.contributor.author","Lahrmann, Bernd"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Westphal, Kathi"],["dc.contributor.author","Ernst, Claudia"],["dc.contributor.author","Elsawaf, Zeinab"],["dc.contributor.author","Sinn, Peter"],["dc.contributor.author","Bosch, Franz X."],["dc.contributor.author","Dickhaus, Hartmut"],["dc.contributor.author","Jäger, Dirk"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Grabe, Niels"],["dc.date.accessioned","2022-05-02T08:59:46Z"],["dc.date.available","2022-05-02T08:59:46Z"],["dc.date.issued","2010-12"],["dc.description.abstract","Tissue microarrays (TMAs) represent an important approach for the high-throughput cellular analysis of large numbers of tissue samples on one single slide in research related to diagnostics and oncology. Whole-slide imaging now enables full scanning and subsequent image analysis of such TMAs. In contrast to automatically spotted RNA microarrays, TMAs are fabricated manually and mechanically by arranging hundreds of tissue cores in a single paraffin block. This procedure frequently results in quality problems severely hampering the later automatic image analysis of TMAs after whole-slide imaging. We therefore set out to (a) determine the extent of these quality issues in exemplary TMAs and (b) to develop a robust gridding method to identify the logical position coordinates of each TMA core on a virtual TMA slide. We present the first robust method identifying these coordinates by shifting a template grid over all cores of the TMA (template matching) and thereby measuring in how far the grid matches a predefined list of cores on the virtual TMA Slide. Analysis of 20 TMAs from Breast Cancer as well as 40 Head-and-Neck Cancer showed that frequent TMA layout issues comprise low staining, debris, core displacement, nonuniform background, missing cores, and rotated subarrays. On this highly demanding test comprising chromogen as well as fluorescence stained TMAs, our template matching method achieved an excellent position analysis. Of 8900 cores, 8864 (99.59%) were assigned properly. In all 60 slides of the test set, no localization error occurred. The automatic grid analysis of TMAs after whole-slide imaging is highly demanding and requires dedicated algorithms. We demonstrate such a method and evaluate its performance. © 2010 International Society for Advancement of Cytometry."],["dc.identifier.doi","10.1002/cyto.a.20949"],["dc.identifier.pmid","20662092"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107542"],["dc.language.iso","en"],["dc.relation.eissn","1552-4930"],["dc.relation.issn","1552-4922"],["dc.title","Robust gridding of TMAs after whole-slide imaging using template matching"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","138"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","151"],["dc.bibliographiccitation.volume","136"],["dc.contributor.author","Zörnig, Inka"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Lorenzo Bermejo, Justo"],["dc.contributor.author","Ziegelmeier, Claudia"],["dc.contributor.author","Dickes, Elke"],["dc.contributor.author","Migdoll, Alexander"],["dc.contributor.author","Kaiser, Iris"],["dc.contributor.author","Waterboer, Tim"],["dc.contributor.author","Pawlita, Michael"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Ugurel, Selma"],["dc.contributor.author","Schadendorf, Dirk"],["dc.contributor.author","Falk, Christine"],["dc.contributor.author","Eichmüller, Stefan B."],["dc.contributor.author","Jäger, Dirk"],["dc.date.accessioned","2022-05-02T08:59:23Z"],["dc.date.available","2022-05-02T08:59:23Z"],["dc.date.issued","2015-01-01"],["dc.description.abstract","Distribution, patterns and prognostic impact of spontaneous antibody responses against different tumor-associated antigens (TAAs) in malignant melanoma patients are unknown so far and were investigated in this study for the first time in a large cohort at different stages of the disease, identifying new prognostic biomarkers for malignant melanoma. Serum samples from 365 melanoma patients (97 Stage I melanoma patients, 87 Stage II, 92 Stage III and 89 Stage IV) and 100 age and gender matched healthy control donors were analyzed. Samples were drawn at the time of diagnosis (Stages I-III) or at time of diagnosis of distant metastasis (Stage IV). Applying a novel multiplex assay, humoral immune responses against 29 TAAs were determined and the association between response and patient survival was investigated. Antibody responses were mainly found in melanoma patients and all tested antigens elicited immune responses in all disease stages. Antibody responses against single antigens were either associated with poor prognosis and/or shorter progression-free survival (PFS) or had no influence. While in Stages I-III significant associations were observed between an antibody response and overall survival or PFS, among Stage IV patients, no significant association was found. Multivariate analyses identified specific humoral immune responses as prognostic factors independently of age, chemotherapy and immunotherapy. Antibody responses against specific TAA in Stage I-III melanoma patients correlate with poor prognosis and/or shorter PFS. These results may help to design clinical studies in order to evaluate the potential of these responses as prognostic serological biomarkers."],["dc.identifier.doi","10.1002/ijc.28980"],["dc.identifier.pmid","24839182"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107537"],["dc.language.iso","en"],["dc.relation.eissn","1097-0215"],["dc.relation.issn","0020-7136"],["dc.title","Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","678"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","689"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Halama, Niels"],["dc.contributor.author","Braun, Monika"],["dc.contributor.author","Kahlert, Christoph"],["dc.contributor.author","Spille, Anna"],["dc.contributor.author","Quack, Christian"],["dc.contributor.author","Rahbari, Nuh"],["dc.contributor.author","Koch, Moritz"],["dc.contributor.author","Weitz, Jürgen"],["dc.contributor.author","Kloor, Matthias"],["dc.contributor.author","Zoernig, Inka"],["dc.contributor.author","Schirmacher, Peter"],["dc.contributor.author","Brand, Karsten"],["dc.contributor.author","Grabe, Niels"],["dc.contributor.author","Falk, Christine S."],["dc.date.accessioned","2022-04-29T14:55:04Z"],["dc.date.available","2022-04-29T14:55:04Z"],["dc.date.issued","2011-02-15"],["dc.description.abstract","Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells in CRC tissue is unclear. The contribution of intratumoral cytokines and chemokines in shaping the composition of the inflammatory lymphocytic infiltrate is also unclear."],["dc.identifier.doi","10.1158/1078-0432.CCR-10-2173"],["dc.identifier.pmid","21325295"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107138"],["dc.language.iso","en"],["dc.relation.eissn","1557-3265"],["dc.relation.issn","1078-0432"],["dc.title","Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]