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  1. Article ; Online: Repeatability and reproducibility of apparent exchange rate measurements in yeast cell phantoms using filter-exchange imaging.

    Schillmaier, Mathias / Kaika, Athanasia / Topping, Geoffrey J / Braren, Rickmer / Schilling, Franz

    Magma (New York, N.Y.)

    2023  Volume 36, Issue 6, Page(s) 957–974

    Abstract: Objectives: Development of a protocol for validation and quality assurance of filter-exchange imaging (FEXI) pulse sequences with well-defined and reproducible phantoms.: Materials and methods: A FEXI pulse sequence was implemented on a 7 T ... ...

    Abstract Objectives: Development of a protocol for validation and quality assurance of filter-exchange imaging (FEXI) pulse sequences with well-defined and reproducible phantoms.
    Materials and methods: A FEXI pulse sequence was implemented on a 7 T preclinical MRI scanner. Six experiments in three different test categories were established for sequence validation, demonstration of the reproducibility of phantoms and the measurement of induced changes in the apparent exchange rate (AXR). First, an ice-water phantom was used to investigate the consistency of apparent diffusion coefficient (ADC) measurements with different diffusion filters. Second, yeast cell phantoms were utilized to validate the determination of the AXR in terms of repeatability (same phantom and session), reproducibility (separate but comparable phantoms in different sessions) and directionality of diffusion encodings. Third, the yeast cell phantoms were, furthermore, used to assess potential AXR bias because of altered cell density and temperature. In addition, a treatment experiment with aquaporin inhibitors was performed to evaluate the influence of these compounds on the cell membrane permeability in yeast cells.
    Results: FEXI-based ADC measurements of an ice-water phantom were performed for three different filter strengths, showed good agreement with the literature value of 1.099 × 10
    Conclusions: Using ice-water and yeast cell-based phantoms, a protocol for the validation of FEXI pulse sequences was established for the assessment of stability, repeatability, reproducibility and directionality. In addition, a strong dependence of AXR on cell density and temperature was shown. As AXR is an emerging novel imaging biomarker, the suggested protocol will be useful for quality assurance of AXR measurements within a study and potentially across multiple sites.
    MeSH term(s) Saccharomyces cerevisiae ; Ice ; Reproducibility of Results ; Diffusion Magnetic Resonance Imaging/methods ; Water ; Phantoms, Imaging
    Chemical Substances Ice ; Water (059QF0KO0R)
    Language English
    Publishing date 2023-07-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1160826-2
    ISSN 1352-8661 ; 0968-5243
    ISSN (online) 1352-8661
    ISSN 0968-5243
    DOI 10.1007/s10334-023-01107-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3788: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article: Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas.

    Modena, Daniela / Moras, Maria Luisa / Sandrone, Giovanni / Stevenazzi, Andrea / Vergani, Barbara / Dasgupta, Pooja / Kliever, Andrea / Gulde, Sebastian / Marangelo, Alessandro / Schillmaier, Mathias / Luque, Raul M / Bäuerle, Stephen / Pellegata, Natalia S / Schulz, Stefan / Steinkühler, Christian

    Cancers

    2023  Volume 15, Issue 13

    Abstract: Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of ... ...

    Abstract Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing's syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.
    Language English
    Publishing date 2023-06-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15133453
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Gender-Specific Efficacy Revealed by Head-to-Head Comparison of Pasireotide and Octreotide in a Representative In Vivo Model of Nonfunctioning Pituitary Tumors.

    Gulde, Sebastian / Wiedemann, Tobias / Schillmaier, Mathias / Valença, Isabel / Lupp, Amelie / Steiger, Katja / Yen, Hsi-Yu / Bäuerle, Stephen / Notni, Johannes / Luque, Raul / Schmid, Herbert / Schulz, Stefan / Ankerst, Donna P / Schilling, Franz / Pellegata, Natalia S

    Cancers

    2021  Volume 13, Issue 12

    Abstract: Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail ... ...

    Abstract Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors' proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal
    Language English
    Publishing date 2021-06-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13123097
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Angpt2/Tie2 autostimulatory loop controls tumorigenesis.

    Karabid, Ninelia Minaskan / Wiedemann, Tobias / Gulde, Sebastian / Mohr, Hermine / Segaran, Renu Chandra / Geppert, Julia / Rohm, Maria / Vitale, Giovanni / Gaudenzi, Germano / Dicitore, Alessandra / Ankerst, Donna Pauler / Chen, Yiyao / Braren, Rickmer / Kaissis, Georg / Schilling, Franz / Schillmaier, Mathias / Eisenhofer, Graeme / Herzig, Stephan / Roncaroli, Federico /
    Honegger, Jürgen B / Pellegata, Natalia S

    EMBO molecular medicine

    2022  Volume 14, Issue 5, Page(s) e14364

    Abstract: Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. ... ...

    Abstract Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.
    MeSH term(s) Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Heterografts ; Humans ; Mice ; Neoplasm Recurrence, Local ; Pituitary Neoplasms/genetics ; Pituitary Neoplasms/metabolism ; Pituitary Neoplasms/pathology ; Rats ; Receptor, TIE-2/genetics ; Receptor, TIE-2/metabolism ; Zebrafish
    Chemical Substances ANGPT2 protein, human ; Angiopoietin-2 ; Receptor, TIE-2 (EC 2.7.10.1) ; TEK protein, human (EC 2.7.10.1)
    Language English
    Publishing date 2022-03-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202114364
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6784: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Simultaneous characterization of tumor cellularity and the Warburg effect with PET, MRI and hyperpolarized

    Hundshammer, Christian / Braeuer, Miriam / Müller, Christoph A / Hansen, Adam E / Schillmaier, Mathias / Düwel, Stephan / Feuerecker, Benedikt / Glaser, Steffen J / Haase, Axel / Weichert, Wilko / Steiger, Katja / Cabello, Jorge / Schilling, Franz / Hövener, Jan-Bernd / Kjær, Andreas / Nekolla, Stephan G / Schwaiger, Markus

    Theranostics

    2018  Volume 8, Issue 17, Page(s) 4765–4780

    Abstract: Modern oncology aims at patient-specific therapy approaches, which triggered the development of biomedical imaging techniques to synergistically address tumor biology at the cellular and molecular level. PET/MR is a new hybrid modality that allows ... ...

    Abstract Modern oncology aims at patient-specific therapy approaches, which triggered the development of biomedical imaging techniques to synergistically address tumor biology at the cellular and molecular level. PET/MR is a new hybrid modality that allows acquisition of high-resolution anatomic images and quantification of functional and metabolic information at the same time. Key steps of the Warburg effect-one of the hallmarks of tumors-can be measured non-invasively with this emerging technique. The aim of this study was to quantify and compare simultaneously imaged augmented glucose uptake and LDH activity in a subcutaneous breast cancer model in rats (MAT-B-III) and to study the effect of varying tumor cellularity on image-derived metabolic information.
    MeSH term(s) Aerobiosis ; Anaerobiosis ; Animals ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/physiopathology ; Carbon Isotopes/administration & dosage ; Disease Models, Animal ; Fluorodeoxyglucose F18/administration & dosage ; Glucose/metabolism ; Heterografts ; Image Processing, Computer-Assisted/methods ; L-Lactate Dehydrogenase/analysis ; Magnetic Resonance Imaging/methods ; Metabolic Networks and Pathways ; Neoplasm Transplantation ; Positron-Emission Tomography/methods ; Rats
    Chemical Substances Carbon Isotopes ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Carbon-13 (FDJ0A8596D) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2018-09-09
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.25162
    Database MEDical Literature Analysis and Retrieval System OnLINE

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