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16. Correlation of inflammatory and proangiogenic cytokines from undiluted vitreous samples with spectral domain OCT scans, in untreated branch retinal vein occlusion

Author

Pfister M, Rothweiler F, Michaelis M, Cinatl J Jr, Schubert R, Koch FH, and Koss MJ

Subjects
Ophthalmology, RE1-994
Abstract

Marcel Pfister,1,4 Florian Rothweiler,2 Martin Michaelis,2 Jindrich Cinatl Jr,2 Ralf Schubert,3 Frank H Koch,1 Michael J Koss1,4 1Department of Ophthalmology, Goethe University, Frankfurt, Germany; 2Department of Virology, Goethe University, Frankfurt, Germany; 3Department of Pediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe University, Frankfurt, Germany; 4Doheny Eye Institute, University of Southern California, Los Angeles, CA, USA Purpose: To assess the levels of inflammatory and angiogenic cytokines in undiluted vitreous from treatment-naïve patients with macular edema secondary to nonischemic branch retinal vein occlusion (BRVO), with flow cytometric bead array (CBA) and to correlate the results with subjective and multiple spectral-domain optical coherence tomography (SD-OCT) parameters. Methods: A total of 43 eyes from 43 patients (mean age 69.7 years, 23 male) were divided into groups of new, "fresh" (n = 28; mean duration after onset 4.1 months) and older BRVO (n = 15; 11.6 months). Because of macular edema, these patients underwent an intravitreal therapy combining a single-site 23 g core vitrectomy with bevacizumab and dexamethasone. Undiluted vitreous was then analyzed for interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor isoform A (VEGF-A) levels with CBA and correlated with visual acuity (VA), clinical parameters of BRVO (type and perfusion status), and morphologic parameters, such as central macular thickness, central retinal thickness, thickness of the neurosensory retina, thickness of the serous retinal detachment, and the disruption of the ellipsoid line (photoreceptor inner and outer segments) and the external limiting membrane, as measured with SD-OCT. Twenty-eight undiluted vitreous samples from patients with idiopathic, nonuveitis vitreous floaters served as the controls. Results: The mean IL-6 was 23.2 pg/mL (standard deviation, ±48.8), MCP-1 was 602.6 (±490.3), and VEGF-A was 161.8 (±314.3), and this was higher than in the control group, which had a mean IL-6 of 6.2 ± 3.4 pg/mL (P = 0.17), MCP-1 of 253.2 ± 73.5 (P < 0.0000001), and VEGF-A of 7.0 ± 4.9 (P < 0.003). In all BRVO samples, IL-6 correlated positively with MCP-1 and VEGF-A (correlation coefficient r = 0.79 and r = 0.46, respectively). VEGF-A was the only cytokine to correlate significantly with SD-OCT parameters (thickness of the neurosensory retina r = 0.31; disruption of the ellipsoid line r = 0.33). In the older BRVO group, there was a positive correlation between cytokines (IL-6 with MCP-1, r = 0.77; Il-6 with VEGF-A, r = 0.68; MCP-1 and VEGF-A, r = 0.68), whereas only IL-6 correlated with MCP-1 in the fresh group (r = 0.8). Conclusion: The inflammatory markers and VEGF-A were elevated in the vitreous fluid of patients with BRVO, and these correlated with one another. VEGF-A was more often correlated with the morphologic changes assessed by SD-OCT, whereas the inflammatory markers had no significant influence on SD-OCT changes. Keywords: vitreous samples, BRVO, VEGF, MCP, IL-6, CBA, SD-OCT

Published
2013

20. Der Einfluss der Resistenz gegen Cisplatin und Osimertinib auf das Metastasierungsverhalten des penilen Plattenepithelkarzinoms

Author

Slade, K., Thomas, A., Huck, S., Vakhrusheva, O., Michaelis, M., Cinatl, J., Rothweiler, F., Haferkamp, A., Jüngel, E., and Tsaur, I.

Subjects
ddc: 610, Medicine and health
Abstract

Einleitung: Für das metastasierte Peniskarzinom (PeCa) gibt es derzeit keine kurative, erfolgreiche Behandlung und die schnell erworbene Resistenz gegen Chemotherapien verschlechtert die Prognose der Patienten dramatisch. Dennoch ist das Wissen über die genauen Resistenzmuster begrenzt. Wir [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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21. Die Reduktion von Integrin α6 durch Artesunat inhibiert das progressive Wachstum Docetaxel-resistenter Prostatakarzinomzellen

Author

Bräunig, V, Stein, L, Wüstefeld, L, Vakhrusheva, O, Markowitsch, S, Slade, K, Efferth, T, Culig, Z, Puhr, M, Michaelis, M, Cinatl, J, Haferkamp, A, and Jüngel, E

Subjects
ddc: 610, Medicine and health
Abstract

Einleitung: Therapieresistenzen stellen eines der größten Probleme in der Behandlung des fortgeschrittenen Prostatakarzinom (PCa), dem häufigsten Tumor des Mannes, dar. Neue Behandlungskonzepte werden daher dringend gesucht. Artesunat (ART) aus der Traditionellen Chinesischen Medizin [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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22. Artesunat hemmt signifikant das Metastasierungsverhalten Cisplatin-resistenter Harnblasenkarzinomzellen

Author

Vakhrusheva, O., Zhao, F., Markowitsch, S., Michaelis, M., Cinatl, J., Efferth, T., Haferkamp, A., and Jüngel, E.

Subjects
ddc: 610, Medicine and health
Abstract

Einleitung: Zur Standardtherapie des metastasierten Harnblasenkarzinom (BCa) gehört die Cisplatin-basierte Chemotherapie. Das Therapieansprechen ist jedoch limitiert, so dass es zum Rezidiv kommt oder die Erkrankung in einen invasiven bzw. systemischen Progress fortschreitet. Dafür maßgeblich [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022

40. Artesunate inhibits the progressive growth behavior of docetaxel-resistant prostate cancer cells

Author

Jüngel, E., primary, Vakhrusheva, O., additional, Erb, H.H.H., additional, Braeunig, V., additional, Markowitsch, S.D., additional, Schupp, P., additional, Slade, K.S., additional, Thomas, A., additional, Tsaur, I., additional, Puhr, M., additional, Culig, Z., additional, Cinatl Jr., J., additional, Michaelis, M., additional, Efferth, T., additional, and Haferkamp, A., additional

Published
2021
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42. Molekulare Mechanismen der Therapieresistenz zu Cisplatin und Osimertinib beim Peniskarzinom

Author

Thomas, A, Vakhrusheva, O, Cinatl, J, Rothweiler, F, Michaelis, M, Haferkamp, A, Jüngel, E, and Tsaur, I

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Die erworbene Resistenz gegenüber systemischen Therapeutika limitiert Behandlungsfortschritte bei Patienten mit metastasiertem Peniskarzinom (PeCa) erheblich. Da es sich bei PeCa um eine seltene Erkrankung handelt, ist die aktuelle Forschung bezüglich neuer vielversprechender Ansätze[zum vollständigen Text gelangen Sie über die oben angegebene URL], 61. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V.

Published
2021
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43. mTOR/Akt-Signalweg-Proteine als potentielle Biomarker beim Peniskarzinom

Author

Thomas, A., Reetz, S., Stenzel, P., Tagscherer, K., Roth, W., Vakhrusheva, O., Macher-Göppinger, S., Michaelis, M., Rothweiler, F., Cinatl, J., Haferkamp, A., Jüngel, E., and Tsaur, I.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Peniskrebs (PeCa) ist ein seltenes, aber aggressives Malignom, das sich durch ein schnelles Tumorwachstum und lymphatische Metastasierung auszeichnet. Während insbesondere das Fehlen von Biomarkern beim Peniskarzinom (PeCa) wesentlichen Behandlungsfortschritten im Wege steht, deutet[zum vollständigen Text gelangen Sie über die oben angegebene URL], 61. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V.

Published
2021

44. Shikonin aus der Traditionellen Chinesischen Medizin inhibiert das progressive Wachstum Docetaxel-resistenter Prostatakarzinome in vitro

Author

Jüngel, E, Markowitsch, S, Juetter, K, Schupp, P, Hauschulte, K, Vakhrusheva, O, Slade, K, Thomas, A, Tsaur, I, Cinatl, J, Michaelis, M, Efferth, T, and Haferkamp, A

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Das Prostatakarzinom (PCa) ist noch immer der häufigste Tumor des Mannes. Die Wirksamkeit der zugelassenen Therapeutika ist durch die Entstehung von Therapieresistenzen zeitlich limitieren. Neue Therapiekonzepte werden daher weiterhin dringend gesucht. Shikonin (SHI) aus der Traditionellen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 61. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V.

Published
2021
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48. Gene expression signature of acquired chemoresistance in neuroblastoma cells

Author

Jemaa M., Sime W., Abassi Y., Lasorsa V. A., Kohler J. B., Michaelis M., Cinatl J., Capasso M., Massoumi R., Jemaa, M., Sime, W., Abassi, Y., Lasorsa, V. A., Kohler, J. B., Michaelis, M., Cinatl, J., Capasso, M., and Massoumi, R.

Subjects
Prognosi, Nocodazole, Cell Cycle, Antineoplastic Agents, Phytogenic, Antineoplastic Agent, Gene Expression Regulation, Neoplastic, Neoplasm Protein, Neuroblastoma, Clone Cell, Vincristine, Drug Resistance, Neoplasm, Cell Line, Tumor, Cisplatin, Transcriptome, Chemoresistance, Etoposide, Human
Abstract

Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. Patients with relapsed disease have a poor prognosis despite intense treatment. In the present study, we aimed to identify chemoresistance gene expression signatures in vincristine resistant neuroblastoma cells. We found that vincristine-resistant neuroblastoma cells formed larger clones and survived under reduced serum conditions as compared with non-resistant parental cells. To identify the possible mechanisms underlying vincristine resistance in neuroblastoma cells, we investigated the expression profiles of genes known to be involved in cancer drug resistance. This specific gene expression patterns could predict the behavior of a tumor in response to chemotherapy and for predicting the prognosis of high-risk neuroblastoma patients. Our signature could help chemoresistant neuroblastoma patients in avoiding useless and harmful chemotherapy cycles.

Published
2020

49. Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma

Author

Sime W., Jemaa M., Abassi Y., Lasorsa V. A., Kohler J. B., Hansson K., Bexell D., Michaelis M., Cinatl J., Strand D., Capasso M., Massoumi R., Sime, W., Jemaa, M., Abassi, Y., Lasorsa, V. A., Kohler, J. B., Hansson, K., Bexell, D., Michaelis, M., Cinatl, J., Strand, D., Capasso, M., and Massoumi, R.

Subjects
High-Throughput Screening Assay, Animal, Cell Survival, Pyridine, Apoptosi, Mice, Nude, Xenograft Model Antitumor Assays, Antineoplastic Agent, Neuroblastoma, Mice, Small Molecule Librarie, Vincristine, Doxorubicin, Drug Resistance, Neoplasm, Cell Line, Tumor, Female, Drug Screening Assays, Antitumor, Chemoresistance, Epi-enprioline, Human
Abstract

Neuroblastoma is a childhood solid tumour originating from undifferentiated neural progenitor cells of the sympathetic nervous system. Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. In the present study, we aimed to identify novel drugs that can inhibit the growth and survival of chemoresistant neuroblastoma. High-throughput screening identified a small molecule, epi-enprioline that was able to induce apoptosis of vincristine-resistant neuroblastoma cells via the mitochondrial apoptotic pathway. Epi-enprioline reduced tumour growth in multiple preclinical models, including an orthotopic neuroblastoma patient-derived xenograft model in vivo. In summary, our data suggest that epi-enprioline can be considered as a lead compound for the treatment of vincristine-resistant neuroblastoma uncovering a novel strategy, which can be further explored as a treatment for drug-resistant neuroblastoma.

Published
2020

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