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Dive into the research topics where Alexandra von Baer is active.

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Featured researches published by Alexandra von Baer.


Cancer Research | 2015

Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway

Adrian von Witzleben; Lukas T. Goerttler; Ralf Marienfeld; Holger Barth; André Lechel; Kevin Mellert; Michael Böhm; Marko Kornmann; Regine Mayer-Steinacker; Alexandra von Baer; Markus Schultheiss; Adrienne M. Flanagan; Peter Möller; Silke Brüderlein; Thomas F. E. Barth

Chordomas are tumors that arise at vertebral bodies and the base of the skull. Although rare in incidence, they are deadly owing to slow growth and a lack of effective therapeutic options. In this study, we addressed the need for chordoma cell systems that can be used to identify therapeutic targets and empower testing of candidate pharmacologic drugs. Eight human chordoma cell lines that we established exhibited cytology, genomics, mRNA, and protein profiles that were characteristic of primary chordomas. Candidate responder profiles were identified through an immunohistochemical analysis of a chordoma tissue bank of 43 patients. Genomic, mRNA, and protein expression analyses confirmed that the new cell systems were highly representative of chordoma tissues. Notably, all cells exhibited a loss of CDKN2A and p16, resulting in universal activation of the CDK4/6 and Rb pathways. Therefore, we investigated the CDK4/6 pathway and responses to the CDK4/6-specific inhibitor palbociclib. In the newly validated system, palbociclib treatment efficiently inhibited tumor cell growth in vitro and a drug responder versus nonresponder molecular signature was defined on the basis of immunohistochemical expression of CDK4/6/pRb (S780). Overall, our work offers a valuable new tool for chordoma studies including the development of novel biomarkers and molecular targeting strategies.


International Journal of Oncology | 2014

Molecular profiling of chordoma

Stefanie Scheil-Bertram; Roland Kappler; Alexandra von Baer; Erich Hartwig; Michael R. Sarkar; Massimo Serra; Silke Brüderlein; Bettina Westhoff; Ingo Melzner; Birgit Bassaly; Jochen Herms; Heinz Hermann Hugo; Michael Schulte; Peter Møller

The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma.


Histopathology | 2017

H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant

Julian Lüke; Alexandra von Baer; Jordan Schreiber; Christoph Lübbehüsen; Thomas Breining; Kevin Mellert; Ralf Marienfeld; Markus Schultheiss; Peter Møller; Thomas F. E. Barth

Giant cell tumour of the bone (GCTB) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumours giant cell‐rich morphology, which overlaps with other giant cell‐containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell‐containing lesions.


Archives of Orthopaedic and Trauma Surgery | 2010

Integrated FDG-PET-CT: its role in the assessment of bone and soft tissue tumors

Mark Bischoff; Gisela Bischoff; Andreas Buck; Alexandra von Baer; Sandra Pauls; Florian Scheffold; Markus Schultheiss; Florian Gebhard; Sven N. Reske

PurposeThe purpose of this study was to evaluate prospectively, whether integrated 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography (FDG-PET-CT) is more accurate for determination musculoskeletal tumors compared with separate interpretation of CT and FDG-PET, because most of the current clinical data come from patients studied with PET.MethodsEighty patients with newly diagnosed musculoskeletal tumors underwent FDG-PET-CT. CT, FDG-PET, and FDG-PET-CT were interpreted separately to determine the performance of each imaging modality.ResultsAssuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity and accuracy for CT alone was 81, 84, 83%, for PET 71, 82, 76, and for PET-CT 80, 83 and 86%. Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 61, 100, 70%, for PET 69, 100, 79, and for PET-CT 69, 100 and 79%.ConclusionsCombined FDG-PET-CT reliably differentiates soft tissue and bone tumors from benign lesions. The value of the information provided by FDG-PET-CT for planning surgical procedures must be evaluated in further studies.


Virchows Archiv | 2004

Metachronous and multiple aneurysmal bone cysts: a rare variant of primary aneurysmal bone cysts

Stefanie Scheil-Bertram; Erich Hartwig; Silke Brüderlein; Ingo Melzner; Alexandra von Baer; Albert Roessner; Peter Möller; Michael Schulte

In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patient’s ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.


Pathology Research and Practice | 2014

Immunohistochemical and FISH analysis of MDM2 and CDK4 in a dedifferentiated extraskeletal osteosarcoma arising in the vastus lateralis muscle: Differential diagnosis and diagnostic algorithm

Alexandra von Baer; Alexander Ehrhardt; Daniel Baumhoer; Regine Mayer-Steinacker; Markus Schultheiss; Thair Abdul-Nou; Thomas Mentzel; Falko Fend; Peter Möller; Gernot Jundt; Thomas F. E. Barth

Extraskeletal osteosarcoma is a rare neoplasia within the broad differential diagnostic spectrum of calcifying intramuscular lesions. We present a case of a slowly increasing mass within the left vastus lateralis muscle. At first presentation the patient showed a partially calcified well defined mass with a diameter of 5 cm and with no direct contact to the femur. A biopsy from the periphery revealed an ossifying lesion compatible with myositis ossificans. The patient returned 18 months later with the lesion having increased to a diameter of 25 cm. The resection specimen revealed a well delimitated tumor with a central core of partially necrotic neoplastic bone. Besides, histology showed high mitotic areas with pleomorphic spindle cells and regions with cartilaginous differentiation. Immunohistochemistry demonstrated: vimentin+, CD34-, desmin-, actin-, EMA- and pancytokeratin- with focal S100 protein positivity and a Ki-67 index of 20%. Comparative genomic hybridization (CGH) revealed a gain of chromosomal material on 12q; FISH analyses for the CDK4 and MDM2 region showed high level amplifications. Consequently, a high-grade dedifferentiated extraskeletal osteosarcoma was diagnosed. In conclusion, analysis of the MDM2 and CDK4 status is a powerful and discriminating diagnostic tool to distinguish dedifferentiated extraskeletal osteosarcoma from other benign/malignant ossifying lesions in the skeletal muscle.


European Radiology | 2018

Diagnostic value of MRI-based 3D texture analysis for tissue characterisation and discrimination of low-grade chondrosarcoma from enchondroma: a pilot study

Catharina S. Lisson; Christoph G. Lisson; Kerstin Flosdorf; Regine Mayer-Steinacker; Markus Schultheiss; Alexandra von Baer; Thomas F. E. Barth; Ambros J. Beer; Matthias Baumhauer; Reinhard Meier; Meinrad Beer; Stefan Schmidt

AbstractObjectivesTo explore the diagnostic value of MRI-based 3D texture analysis to identify texture features that can be used for discrimination of low-grade chondrosarcoma from enchondroma.MethodsEleven patients with low-grade chondrosarcoma and 11 patients with enchondroma were retrospectively evaluated. Texture analysis was performed using mint Lesion: Kurtosis, entropy, skewness, mean of positive pixels (MPP) and uniformity of positive pixel distribution (UPP) were obtained in four MRI sequences and correlated with histopathology. The Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were performed to identify most discriminative texture features. Sensitivity, specificity, accuracy and optimal cut-off values were calculated.ResultsSignificant differences were found in four of 20 texture parameters with regard to the different MRI sequences (p<0.01). The area under the ROC curve values to discriminate chondrosarcoma from enchondroma were 0.876 and 0.826 for kurtosis and skewness in contrast-enhanced T1 (ceT1w), respectively; in non-contrast T1, values were 0.851 and 0.822 for entropy and UPP, respectively. The highest discriminatory power had kurtosis in ceT1w with a cut-off ≥3.15 to identify low-grade chondrosarcoma (82 % sensitivity, 91 % specificity, accuracy 86 %).ConclusionMRI-based 3D texture analysis might be able to discriminate low-grade chondrosarcoma from enchondroma by a variety of texture parameters.Key Points• MRI texture analysis may assist in differentiating low-grade chondrosarcoma from enchondroma. • Kurtosis in the contrast-enhanced T1w has the highest power of discrimination. • Tools provide insight into tumour characterisation as a non-invasive imaging biomarker.


Scientific Reports | 2017

HOXA7 , HOXA9 , and HOXA10 are differentially expressed in clival and sacral chordomas

Daniela Jäger; Thomas F. E. Barth; Silke Brüderlein; Angelika Scheuerle; Beate Rinner; Adrian von Witzleben; André Lechel; Patrick Meyer; Regine Mayer-Steinacker; Alexandra von Baer; Markus Schultheiss; Christian Rainer Wirtz; Peter Möller; Kevin Mellert

Chordomas are rare tumours of the bone arising along the spine from clivus to sacrum. We compared three chordoma cell lines of the clivus region including the newly established clivus chordoma cell line, U-CH14, with nine chordoma cell lines originating from sacral primaries by morphology, on genomic and expression levels and with patient samples from our chordoma tissue bank. Clinically, chordomas of the clivus were generally smaller in size at presentation and patients with sacral chordomas had more metastases and more often recurrent disease. All chordoma cell lines had a typical physaliphorous morphology and expressed brachyury, S100-protein and cytokeratin. By expression analyses we detected differentially expressed genes in the clivus derived cell lines as compared to the sacral cell lines. Among these were HOXA7, HOXA9, and HOXA10 known to be important for the development of the anterior-posterior body axis. These results were confirmed by qPCR. Immunohistologically, clivus chordomas had no or very low levels of HOXA10 protein while sacral chordomas showed a strong nuclear positivity in all samples analysed. This differential expression of HOX genes in chordomas of the clivus and sacrum suggests an oncofetal mechanism in gene regulation linked to the anatomic site.


JAMA Surgery | 2013

Cystic lesions with suspected soft tissue infiltration.

Theresia Weber; Alexandra von Baer; Markus Schultheiß; Clemens Maier-Funk; Markus Luster; Thomas F. E. Barth; Bernhard O. Boehm

In April 2010, a 19-year-old soccer player presented with a 4-week history of pain after a tap against his right knee. Medical and family histories were unremarkable and no abnormalities were found on physical examination. A radiograph of the right knee showed osteolytic lesions in the distal femur and the head of the tibia. On magnetic resonance imaging, the epiphyseal lesions were visualized as cystic and nonsclerotic and extended to the articular surface of the distal femur and proximal tibia (Figure 1). Soft tissue extension was suspected from the tibia. Laboratory test results showed normal blood cell count, renal function, and concentration of C-reactive protein. Aneurysmatic bone cysts were suspected and a biopsy was performed. Histopathological examination detected spindle cell infiltrates with hemorrhages, fragmented trabecular bone, and numerous osteoclastic giant cells proliferating at a rate of 10% suggesting an aggressive giant cell lesion. Since it was still not determined whether the lesions were malignant, flourodeoxyglucose F 18positron emission tomography/computed tomographywasperformedand foundadditional lesions in the left distal femur and the leftmandible. Biopsyof themandible showed the same type of tissue as seen in the right femur and tibia. Quiz at jamasurgery.com A B


The Journal of Nuclear Medicine | 2000

Grading of Tumors and Tumorlike Lesions of Bone: Evaluation by FDG PET

Michael Schulte; Doris Brecht-Krauss; Berno Heymer; Albrecht Guhlmann; Erich Hartwig; Michael R. Sarkar; Christoph G. Diederichs; Alexandra von Baer; Jörg Kotzerke; Sven N. Reske

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Peter Møller

University of Copenhagen

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