@article{LeichWeissbachKleinetal.2013,
  author    = {Leich, E. and Weißbach, S. and Klein, H.-U. and Grieb, T. and Pischimarov, J. and St{\"u}hmer, T. and Chatterjee, M. and Steinbrunn, T. and Langer, C. and Eilers, M. and Knop, S. and Einsele, H. and Bargou, R. and Rosenwald, A.},
  title     = {Multiple myeloma is affected by multiple and heterogeneous somatic mutations in adhesion- and receptor tyrosine kinase signaling molecules},
  series = {Blood Cancer Journal},
  volume    = {3},
  journal   = {Blood Cancer Journal},
  number    = {e102},
  doi       = {10.1038/bcj.2012.47},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128663},
  year      = {2013},
  abstract  = {Multiple myeloma (MM) is a largely incurable plasma cell malignancy with a poorly understood and heterogeneous clinical course. To identify potential, functionally relevant somatic mutations in MM, we performed whole-exome sequencing of five primary MM, corresponding germline DNA and six MM cell lines, and developed a bioinformatics strategy that also integrated published mutational data of 38 MM patients. Our analysis confirms that identical, recurrent mutations of single genes are infrequent in MM, but highlights that mutations cluster in important cellular pathways. Specifically, we show enrichment of mutations in adhesion molecules of MM cells, emphasizing the important role for the interaction of the MM cells with their microenvironment. We describe an increased rate of mutations in receptor tyrosine kinases (RTKs) and associated signaling effectors, for example, in EGFR, ERBB3, KRAS and MAP2K2, pointing to a role of aberrant RTK signaling in the development or progression of MM. The diversity of mutations affecting different nodes of a particular signaling network appears to be an intrinsic feature of individual MM samples, and the elucidation of intra- as well as interindividual redundancy in mutations that affect survival pathways will help to better tailor targeted therapeutic strategies to the specific needs of the MM patient.},
  language  = {en}
}
@article{DanhofSchrederStrifleretal.2015,
  author    = {Danhof, Sophia and Schreder, Martin and Strifler, Susanne and Einsele, Hermann and Knop, Stefan},
  title     = {Long-Term Disease Control by Pomalidomide-/Dexamethasone-Based Therapy in a Patient with Advanced Multiple Myeloma: A Case Report and Review of the Literature},
  series = {Case Reports in Oncology},
  volume    = {8},
  journal   = {Case Reports in Oncology},
  number    = {1},
  doi       = {10.1159/000381983},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126093},
  pages     = {189-195},
  year      = {2015},
  abstract  = {Background: Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these 'novel agents' remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement. Pomalidomide-based combination therapies are currently under investigation, but data on long-term treatment are lacking. Case Report: We present the case of a 68-year-old woman with refractory MM who received pomalidomide in combination with various drugs including anthracyclines, alkylators and proteasome inhibitors. Initially, major hematological toxicities and infectious complications including a hepatitis B virus reactivation were encountered. With careful dose adjustments and selection of combination partners, pomalidomide treatment was maintained for over 4 years and led to a sustained partial remission. In particular, the well-tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with pomalidomide was administered for >30 cycles. Conclusion: This case illustrates the value of an individualized approach to myeloma care given an increasing availability of 'novel agents'. Tailored treatment using these drugs as a backbone is essential to achieve long-lasting responses and minimize side effects.},
  language  = {en}
}
@article{SteinbrunnChatterjeeBargouetal.2014,
  author    = {Steinbrunn, Torsten and Chatterjee, Manik and Bargou, Ralf C. and St{\"u}hmer, Thorsten},
  title     = {Efficient Transient Transfection of Human Multiple Myeloma Cells by Electroporation - An Appraisal},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0097443},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119616},
  pages     = {e97443},
  year      = {2014},
  abstract  = {Cell lines represent the everyday workhorses for in vitro research on multiple myeloma (MM) and are regularly employed in all aspects of molecular and pharmacological investigations. Although loss-of-function studies using RNA interference in MM cell lines depend on successful knockdown, no well-established and widely applied protocol for efficient transient transfection has so far emerged. Here, we provide an appraisal of electroporation as a means to introduce either short-hairpin RNA expression vectors or synthesised siRNAs into MM cells. We found that electroporation using siRNAs was much more efficient than previously anticipated on the basis of transfection efficiencies deduced from EGFP-expression off protein expression vectors. Such knowledge can even confidently be exploited in "hard-to-transfect" MM cell lines to generate large numbers of transient knockdown phenotype MM cells. In addition, special attention was given to developing a protocol that provides easy implementation, good reproducibility and manageable experimental costs.},
  language  = {en}
}
@article{RauertStuehmerBargouetal.2011,
  author    = {Rauert, H. and St{\"u}hmer, T. and Bargou, R. and Wajant, H. and Siegmund, D.},
  title     = {TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76092},
  year      = {2011},
  abstract  = {The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFjBmediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFjB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival.},
  subject      = {Medizin},
  language  = {en}
}