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1. γ-Cyclodextrin hydrogel for the sustained release of josamycin for potential ocular application

Author

Jennifer Huling, Stefan Oschatz, Helge Lange, Katharina Anna Sterenczak, Thomas Stahnke, Jana Markhoff, Oliver Stachs, Steffen Möller, Nasrullah Undre, Anita Peil, Anselm Jünemann, Niels Grabow, Georg Fuellen, and Thomas Eickner

Subjects
γ-cyclodextrin, glaucoma, fibrosis, josamycin, drug delivery, hydrogel, Therapeutics. Pharmacology, RM1-950
Abstract

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug’s solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ − cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.

Published
2024
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2. In Vivo Monitoring of Corneal Dendritic Cells in the Subbasal Nerve Plexus during Trastuzumab and Paclitaxel Breast Cancer Therapy—A One-Year Follow-Up

Author

Sebastian Bohn, Nadine Stache, Karsten Sperlich, Stephan Allgeier, Bernd Köhler, Andreas Bartschat, Ha-Vy Do, Christian George, Rudolf F. Guthoff, Angrit Stachs, Oliver Stachs, and Katharina Anna Sterenczak

Subjects
paclitaxel and trastuzumab, chemotherapy-induced peripheral neuropathy (CIPN), in vivo large-area confocal laser scanning microscopy (CLSM) of the cornea, breast cancer, one-year follow-up, corneal subbasal nerve plexus (SNP), Medicine (General), R5-920
Abstract

Paclitaxel and trastuzumab have been associated with adverse effects including chemotherapy-induced peripheral neuropathy (CIPN) or ocular complications. In vivo confocal laser scanning microscopy (CLSM) of the cornea could be suitable for assessing side effects since the cornea is susceptible to, i.e., neurotoxic stimuli. The study represents a one-year follow-up of a breast cancer patient including large-area in vivo CLSM of the subbasal nerve plexus (SNP), nerve function testing, and questionnaires during paclitaxel and trastuzumab therapy. Six monitoring sessions (one baseline, four during, and one after therapy) over 58 weeks were carried out. Large-area mosaics of the SNP were generated, and identical regions within all sessions were assigned. While corneal nerve morphology did not cause alterations, the number of dendritic cells (DCs) showed dynamic changes with a local burst at 11 weeks after baseline. Simultaneously, paclitaxel treatment was terminated due to side effects, which, together with DCs, returned to normal levels as the therapy progressed. Longitudinal in vivo CLSM of the SNP could complement routine examinations and be helpful to generate a comprehensive clinical picture. The applied techniques, with corneal structures acting as biomarkers could represent a diagnostic tool for the objective assessment of the severity of adverse events and the outcome.

Published
2022
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4. Evaluation of Stem Cell Marker Expression in Canine B-Cell Lymphoma Cell Lines, B-Cell Lymphoma-generated Spheres and Primary Samples

Author

Wen, Liu, Feyza, Selçuk, Barbara C, Rütgen, Mohammed, Moulay, Saskia, Willenbrock, Sabine E, Hammer, Katharina Anna, Sterenczak, Christian, Junghanss, Marion, Hewicker-Trautwein, Ingo, Nolte, and Hugo, Murua Escobar

Subjects
Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, Disease Models, Animal, Dogs, Hyaluronan Receptors, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Neoplastic Stem Cells, Animals, Humans, Lymph Nodes, Flow Cytometry
Abstract

Canine lymphoma has lately drawn focus as a model of human non-Hodgkin's lymphoma due to its spontaneous occurrence and similar biological behavior. Cells with stem cell-like characteristics are believed to play a key role in therapeutic failure. Thus, an initial characterization and the possibility of specific detection of such cells could bear significant value.Expression of 12 stem cell markers were analyzed in two canine B-cell lymphoma cell lines, their generated spheres, and in primary lymphoma samples by quantitative real-time polymerase chain reaction and partially by flow cytometry and immunocytochemistry.Expression of maternal embryonic leucine zipper kinase (Melk) was significantly higher in CLBL-1, CLBL-1M and in primary B-cell lymphoma samples compared to non-neoplastic lymph nodes. Spheres displayed a higher expression of v-myc myelocytomatosis viral oncogene homolog (Myc) and lower expression of Cd44 compared to original cell lines and primary B-cell lymphoma samples.The results suggest a potential interesting role of Melk in canine B-cell lymphoma. Furthermore, the up-regulation of Myc in serum-free-generated spheres offers interesting possibilities for functional assays characterizing the specific generated sub-population.

Published
2015

5. RAGE splicing variants in mammals

Author

Katharina Anna, Sterenczak, Ingo, Nolte, and Hugo, Murua Escobar

Subjects
Dogs, Receptor for Advanced Glycation End Products, Animals, Humans, Protein Isoforms, RNA, Messenger, Receptors, Immunologic
Abstract

The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer's disease, and several cancer types. Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases-including cancer-comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

Published
2013

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