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  1. Book ; Thesis: Onkolytische H-1-Parvoviren in Kombination mit ionisierender Strahlung

    Hartkopf, Andreas

    Untersuchung zytotoxischer Effekte in Zellkulturen humaner Glioblastome

    2007  

    Author's details vorgelegt von Andreas Hartkopf
    Subject code 616.994
    Language German
    Size VII, 116 S. : Ill., graph. Darst., 30 cm
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Heidelberg, Univ., Diss., 2009
    HBZ-ID HT016637182
    Database Catalogue ZB MED Medicine, Health

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  2. Article: Endocrine-Resistant Breast Cancer: Mechanisms and Treatment.

    Hartkopf, Andreas D / Grischke, Eva-Maria / Brucker, Sara Y

    Breast care (Basel, Switzerland)

    2020  Volume 15, Issue 4, Page(s) 347–354

    Abstract: Background: Endocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and ... ...

    Abstract Background: Endocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and markers of endocrine-resistant breast cancer. In addition, current and future strategies to overcome endocrine resistance are discussed.
    Summary: Several molecular mechanisms of endocrine resistance have been identified, including alterations in the ESR1 gene or in the PIK3CA/mTOR pathway. Meanwhile, CDK4/6, mTOR, and PI3K inhibition have shown to improve the efficacy of endocrine treatment and new promising approaches are being developed.
    Key message: Overcoming primary or acquired resistance to endocrine treatment remains a major challenge. Since the molecular mechanisms of endocrine resistance are manifold, optimal combination and sequencing strategies will have to be developed in the future.
    Language English
    Publishing date 2020-07-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2202236-3
    ISSN 1661-3805 ; 1661-3791
    ISSN (online) 1661-3805
    ISSN 1661-3791
    DOI 10.1159/000508675
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Clinical Trials of Oncolytic Viruses in Breast Cancer.

    Carter, Mary E / Koch, André / Lauer, Ulrich M / Hartkopf, Andreas D

    Frontiers in oncology

    2021  Volume 11, Page(s) 803050

    Abstract: Breast cancer is the second most common kind of cancer worldwide and oncolytic viruses may offer a new treatment approach. There are three different types of oncolytic viruses used in clinical trials; (i) oncolytic viruses with natural anti-neoplastic ... ...

    Abstract Breast cancer is the second most common kind of cancer worldwide and oncolytic viruses may offer a new treatment approach. There are three different types of oncolytic viruses used in clinical trials; (i) oncolytic viruses with natural anti-neoplastic properties; (ii) oncolytic viruses designed for tumor-selective replication; (iii) oncolytic viruses modified to activate the immune system. Currently, fourteen different oncolytic viruses have been investigated in eighteen published clinical trials. These trials demonstrate that oncolytic viruses are well tolerated and safe for use in patients and display clinical activity. However, these trials mainly studied a small number of patients with different advanced tumors including some with breast cancer. Future trials should focus on breast cancer and investigate optimal routes of administration, occurrence of neutralizing antibodies, viral gene expression, combinations with other antineoplastic therapies, and identify subtypes that are particularly suitable for oncolytic virotherapy.
    Language English
    Publishing date 2021-12-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.803050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Precision Immunotherapy Utilizing Adapter CAR-T Cells (AdCAR-T) in Metastatic Breast Cancer Leads to Target Specific Lysis.

    Önder, Cansu E / Moustafa-Oglou, Moustafa / Schröder, Sarah M / Hartkopf, Andreas D / Koch, André / Seitz, Christian M

    Cancers

    2023  Volume 16, Issue 1

    Abstract: A frequent symptom of metastasized breast cancer (BC) includes the development of malignant pleural effusion (MPE), which contains malignant cells derived from the primary tumor site. The poor prognosis of MPE in metastasized BC indicates the necessity ... ...

    Abstract A frequent symptom of metastasized breast cancer (BC) includes the development of malignant pleural effusion (MPE), which contains malignant cells derived from the primary tumor site. The poor prognosis of MPE in metastasized BC indicates the necessity for dependable precision oncology and the importance of models representing the heterogenous nature of metastatic BC. In this study, we cultured MPE-derived metastatic tumor cells from four advanced BC patients using organoid technology. We assessed the expression of tumor-associated antigens on MPE-derived organoid lines by flow cytometry (FC). Based on an individual antigen expression pattern, patient-derived organoids were treated with adapter CAR-T cells (AdCAR-T) and biotinylated monoclonal antibodies targeting CD276, HER2, EGFR, TROP2, or EpCAM. Co-culture assays revealed specific organoid lysis by AdCAR-T depending on individual antigen expression patterns. Our results demonstrate that MPE-derived organoids can serve as a reliable tool for assessing the efficacy of AdCAR-T on metastatic BC in a patient-individualized manner. This approach could potentially be applied in a preclinical setting to instruct therapy decisions. Further, our study demonstrates the feasibility of precision immunotherapy utilizing AdCAR-T to target patient-individualized antigen patterns.
    Language English
    Publishing date 2023-12-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16010168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Advancing Cancer Therapy Predictions with Patient-Derived Organoid Models of Metastatic Breast Cancer.

    Önder, Cansu E / Ziegler, Teresa J / Becker, Ronja / Brucker, Sara Y / Hartkopf, Andreas D / Engler, Tobias / Koch, André

    Cancers

    2023  Volume 15, Issue 14

    Abstract: The poor outcome of metastasized breast cancer (BC) stresses the need for reliable personalized oncology and the significance of models recapitulating the heterogeneous nature of BC. Here, we cultured metastatic tumor cells derived from advanced BC ... ...

    Abstract The poor outcome of metastasized breast cancer (BC) stresses the need for reliable personalized oncology and the significance of models recapitulating the heterogeneous nature of BC. Here, we cultured metastatic tumor cells derived from advanced BC patients with malignant ascites (MA) or malignant pleural effusion (MPE) using organoid technology. We identified the characteristics of tumor organoids by applying immunohistochemistry and mutation analysis. Tumor organoids preserved their expression patterns and hotspot mutations when compared to their original metastatic counterpart and are consequently a well-suited in vitro model for metastasized BC. We treated the tumor organoids to implement a reliable application for drug screenings of metastasized cells. Drug assays revealed that responses are not always in accord with expression patterns, pathway activation, and hotspot mutations. The discrepancy between characterization and functional testing underlines the relevance of linking IHC stainings and mutational analysis of metastasized BC with in vitro drug assays. Our metastatic BC organoids recapitulate the characteristics of their original sample derived from MA and MPE and serve as an invaluable tool that can be utilized in a preclinical setting for guiding therapy decisions.
    Language English
    Publishing date 2023-07-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15143602
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.

    Volmer, Léa L / Önder, Cansu E / Volz, Barbara / Singh, Anjali R / Brucker, Sara Y / Engler, Tobias / Hartkopf, Andreas D / Koch, André

    International journal of molecular sciences

    2023  Volume 24, Issue 18

    Abstract: Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a ... ...

    Abstract Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a clinical routine level, the characterization of DTCs and in vitro drug testing on DTCs are of great interest. Therefore, biobanking methods, as well as novel approaches to DTC isolation, need to be developed. In this study, we established a protocol for the biobanking of BM samples and evaluated a microfluidic-based separation system (Parsortix
    Language English
    Publishing date 2023-09-11
    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/ijms241813930
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy.

    Carter, Mary E / Hartkopf, Andreas D / Wagner, Anna / Volmer, Léa L / Brucker, Sara Y / Berchtold, Susanne / Lauer, Ulrich M / Koch, André

    Frontiers in molecular biosciences

    2022  Volume 9, Page(s) 826302

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2022.826302
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Image-guided metabolomics and transcriptomics reveal tumour heterogeneity in luminal A and B human breast cancer beyond glucose tracer uptake.

    Yang, Qianlu / Deng, Sisi / Preibsch, Heike / Schade, Tim-Colin / Koch, André / Berezhnoy, Georgy / Zizmare, Laimdota / Fischer, Anna / Gückel, Brigitte / Staebler, Annette / Hartkopf, Andreas D / Pichler, Bernd J / la Fougère, Christian / Hahn, Markus / Bonzheim, Irina / Nikolaou, Konstantin / Trautwein, Christoph

    Clinical and translational medicine

    2024  Volume 14, Issue 2, Page(s) e1550

    Abstract: Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated.: Methods: We investigated in an ... ...

    Abstract Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated.
    Methods: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach.
    Results: [
    Conclusion: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [
    MeSH term(s) Humans ; Female ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Fluorodeoxyglucose F18/metabolism ; Gene Expression Profiling ; Acetates ; Serine ; Lipids
    Chemical Substances Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Acetates ; Serine (452VLY9402) ; Lipids
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2697013-2
    ISSN 2001-1326 ; 2001-1326
    ISSN (online) 2001-1326
    ISSN 2001-1326
    DOI 10.1002/ctm2.1550
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.

    Seller, Anna / Tegeler, Christian M / Mauermann, Jonas / Schreiber, Tatjana / Hagelstein, Ilona / Liebel, Kai / Koch, André / Heitmann, Jonas S / Greiner, Sarah M / Hayn, Clara / Dannehl, Dominik / Engler, Tobias / Hartkopf, Andreas D / Hahn, Markus / Brucker, Sara Y / Salih, Helmut R / Märklin, Melanie

    International journal of molecular sciences

    2024  Volume 25, Issue 7

    Abstract: Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T ...

    Abstract Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.
    MeSH term(s) Humans ; Female ; Breast Neoplasms ; Carcinoma, Intraductal, Noninfiltrating ; Research Personnel ; Enzyme-Linked Immunosorbent Assay ; Health Status
    Language English
    Publishing date 2024-04-08
    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/ijms25074126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer.

    Kaidun, Polina / Holzmayer, Samuel J / Greiner, Sarah M / Seller, Anna / Tegeler, Christian M / Hagelstein, Ilona / Mauermann, Jonas / Engler, Tobias / Koch, André / Hartkopf, Andreas D / Salih, Helmut R / Märklin, Melanie

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with a poor response rate to conventional systemic treatment and high relapse rates. Members of the natural killer group 2D ligand (NKG2DL) family are expressed on ...

    Abstract Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with a poor response rate to conventional systemic treatment and high relapse rates. Members of the natural killer group 2D ligand (NKG2DL) family are expressed on cancer cells but are typically absent from healthy tissues; thus, they are promising tumor antigens for novel immunotherapeutic approaches. We developed bispecific fusion proteins (BFPs) consisting of the NKG2D receptor domain targeting multiple NKG2DLs, fused to either anti-CD3 (NKG2D-CD3) or anti-CD16 (NKG2D-CD16) Fab fragments. First, we characterized the expression of the NKG2DLs (MICA, MICB, ULBP1-4) on TNBC cell lines and observed the highest surface expression for MICA and ULBP2. Targeting TNBC cells with NKG2D-CD3/CD16 efficiently activated both NK and T cells, leading to their degranulation and cytokine release and lysis of TNBC cells. Furthermore, PBMCs from TNBC patients currently undergoing chemotherapy showed significantly higher NK and T cell activation and tumor cell lysis when stimulated with NKG2D-CD3/CD16. In conclusions, BFPs activate and direct the NK and T cells of healthy and TNBC patients against TNBC cells, leading to efficient eradication of tumor cells. Therefore, NKG2D-based NK and T cell engagers could be a valuable addition to the treatment options for TNBC patients.
    MeSH term(s) Humans ; Administration, Cutaneous ; Aggression ; Ligands ; NK Cell Lectin-Like Receptor Subfamily K/genetics ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Recombinant Fusion Proteins/therapeutic use ; Receptors, IgG ; CD3 Complex
    Chemical Substances Ligands ; NK Cell Lectin-Like Receptor Subfamily K ; Recombinant Fusion Proteins ; KLRK1 protein, human ; Receptors, IgG ; CD3 Complex
    Language English
    Publishing date 2023-08-24
    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/ijms241713156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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