@article{BreunFlockFeldheimetal.2023,
  author    = {Breun, Maria and Flock, Katharina and Feldheim, Jonas and Nattmann, Anja and Monoranu, Camelia M. and Herrmann, Pia and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten and Stein, Ulrike},
  title     = {Metastasis associated in colorectal cancer 1 (MACC1) mRNA expression is enhanced in sporadic vestibular schwannoma and correlates to deafness},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {16},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15164089},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362543},
  year      = {2023},
  abstract  = {Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients' clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p \< 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis.},
  language  = {en}
}
@article{VonaMazaheriLinetal.2021,
  author    = {Vona, Barbara and Mazaheri, Neda and Lin, Sheng-Jia and Dunbar, Lucy A. and Maroofian, Reza and Azaiez, Hela and Booth, Kevin T. and Vitry, Sandrine and Rad, Aboulfazl and R{\"u}schendorf, Franz and Varshney, Pratishtha and Fowler, Ben and Beetz, Christian and Alagramam, Kumar N. and Murphy, David and Shariati, Gholamreza and Sedaghat, Alireza and Houlden, Henry and Petree, Cassidy and VijayKumar, Shruthi and Smith, Richard J. H. and Haaf, Thomas and El-Amraoui, Aziz and Bowl, Michael R. and Varshney, Gaurav K. and Galehdari, Hamid},
  title     = {A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans},
  series = {Human Genetics},
  volume    = {140},
  journal   = {Human Genetics},
  number    = {6},
  issn      = {1432-1203},
  doi       = {10.1007/s00439-020-02254-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267740},
  pages     = {915-931},
  year      = {2021},
  abstract  = {Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.},
  language  = {en}
}
@article{HuettenDhanasinghHessleretal.2014,
  author    = {H{\"u}tten, Mareike and Dhanasingh, Anandhan and Hessler, Roland and St{\"o}ver, Timo and Esser, Karl-Heinz and M{\"o}ller, Martin and Lenarz, Thomas and Jolly, Claude and Groll, J{\"u}rgen and Scheper, Verena},
  title     = {In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0104564},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119375},
  pages     = {e104564},
  year      = {2014},
  abstract  = {Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.},
  language  = {en}
}