@article{LueckerathLapaMalzahnetal.2014,
  author    = {L{\"u}ckerath, Katharina and Lapa, Constantin and Malzahn, Uwe and Samnick, Samuel and Einsele, Herrmann and Buck, Andreas K. and Herrmann, Ken and Knop, Stefan},
  title     = {18FDG-PET/CT for prognostic stratification of patients with multiple myeloma relapse after stem cell transplantation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113107},
  year      = {2014},
  abstract  = {The aim of this study was to investigate the prognostic value of 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) in 37 patients with a history of multiple myeloma (MM) and suspected or confirmed recurrence after stem cell transplantation (SCT). All patients had been heavily pre-treated. Time to progression (TTP) and overall survival (OS) were correlated to a number of different PET-derived as well as clinical parameters. Impact on patient management was assessed. Absence of FDG-avid MM foci was a positive prognostic factor for both TTP and OS (p<0.01). Presence of >10 focal lesions correlated with both TTP (p<0.01) and OS (p<0.05). Interestingly, presence of >10 lesions in the appendicular skeleton proved to have the strongest association with disease progression. Intensity of glucose uptake and presence of extramedullary disease were associated with shorter TTP (p=0.037 and p=0.049, respectively). Manifestations in soft tissue structures turned out to be a strong negative predictor for both, TTP and OS (p<0.01, respectively). PET resulted in a change of management in 30\% of patients. Our data underline the prognostic value of 18F-FDG-PET/CT in MM patients also in the setting of post-SCT relapse. PET/CT has a significant impact on patient management.},
  language  = {en}
}
@article{EbertDotterweichKrausetal.2014,
  author    = {Ebert, Regina and Dotterweich, Julia and Kraus, Sabrina and Tower, Robert J. and Jakob, Franz and Sch{\"u}tze, Norbert},
  title     = {Mesenchymal stem cell contact promotes CCN1 splicing and transcription in myeloma cells},
  doi       = {10.1186/1478-811X-12-36},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110497},
  year      = {2014},
  abstract  = {CCN family member 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), belongs to the extracellular matrix-associated CCN protein family. The diverse functions of these proteins include regulation of cell migration, adhesion, proliferation, differentiation and survival/apoptosis, induction of angiogenesis and cellular senescence. Their functions are partly overlapping, largely non-redundant, cell-type specific, and depend on the local microenvironment. To elucidate the role of CCN1 in the crosstalk between stromal cells and myeloma cells, we performed co-culture experiments with primary mesenchymal stem cells (MSC) and the interleukin-6 (IL-6)-dependent myeloma cell line INA-6. Here we show that INA-6 cells display increased transcription and induction of splicing of intron-retaining CCN1 pre-mRNA when cultured in contact with MSC. Protein analyses confirmed that INA-6 cells co-cultured with MSC show increased levels of CCN1 protein consistent with the existence of a pre-mature stop codon in intron 1 that abolishes translation of unspliced mRNA. Addition of recombinant CCN1-Fc protein to INA-6 cells was also found to induce splicing of CCN1 pre-mRNA in a concentration-dependent manner. Only full length CCN1-Fc was able to induce mRNA splicing of all introns, whereas truncated recombinant isoforms lacking domain 4 failed to induce intron splicing. Blocking RGD-dependent integrins on INA-6 cells resulted in an inhibition of these splicing events. These findings expand knowledge on splicing of the proangiogenic, matricellular factor CCN1 in the tumor microenvironment. We propose that contact with MSC-derived CCN1 leads to splicing and enhanced transcription of CCN1 which further contributes to the translation of angiogenic factor CCN1 in myeloma cells, supporting tumor viability and myeloma bone disease.},
  language  = {en}
}