Jürgen C Becker

Publications (327) View all

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  Available from: Jürgen C Becker

  Article: Type I and II IFNs inhibit Merkel cell carcinoma via modulation of the Merkel cell polyomavirus T antigens.

  Christoph Willmes, Christian Adam, Miriam Alb, Lena Völkert, Roland Houben, Jürgen C Becker, David Schrama
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  ABSTRACT: Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer associated with the Merkel cell polyomavirus (MCV). As MCC cell lines show oncogene addiction to the MCV T antigens, pharmacologic interference of the large T antigen (LTA) may represent an effective therapeutic approach for this deadly cancer. In this study, we investigated the effects of IFNs on MCC cell lines, especially on MCV-positive (MCV(+)) lines. Type I IFNs (i.e., Multiferon, a mix of different IFN-α subtypes, and IFN-β) strongly inhibited the cellular viability. Cell-cycle analysis showed increased sub-G fractions for these cells upon IFN treatment indicating apoptotic cell death; these effects were less pronounced for IFN-γ. Notably, this inhibitory effect of type I IFNs on MCV(+) MCC cell lines was associated with a reduced expression of the MCV LTA as well as an increased expression of promyelocytic leukemia (PML) protein, which is known to interfere with the function of the LTA. In addition, the intratumoral application of Multiferon resulted in a regression of MCV(+) but not MCV(-) MCCs in vivo. Together, our findings show that type I IFNs have a strong antitumor effect, which is at least in part explained by modulation of the virally encoded LTA.
  Cancer Research 03/2012; 72(8):2120-8. · 7.86 Impact Factor
• Article: Cutaneous T cell lymphoma cells are targets for immune checkpoint ligand PD-L1-specific, cytotoxic T cells.

  S Munir, G H Andersen, A Woetmann, N Odum, J C Becker, M H Andersen
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; · 8.30 Impact Factor
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  Available from: Cesare Massone

  Article: BRAF mutation analysis of only one metastatic lesion can restrict the treatment of melanoma: a case report.

  E Richtig, D Schrama, S Ugurel, I Fried, A Niederkorn, C Massone, J C Becker
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  ABSTRACT: The RAS-RAF-MEK-ERK-mitogen activated protein kinase (MAPK) pathway is a crucial signalling pathway for the growth of malignant cells. BRAF (v-Raf murine sarcoma viral oncogene homolog B1) mutations, especially V600E(1) and to a lesser extend V600K, are frequently present in melanoma.
  British Journal of Dermatology 07/2012; · 3.67 Impact Factor
• Article: Expression of the T-cell regulatory marker FOXP3 in primary cutaneous large B-cell lymphoma tumour cells.

  M Felcht, M Heck, C Weiss, J C Becker, E Dippel, C S L Müller, D Nashan, M M Sachse, J P Nicolay, N Booken, S Goerdt, C-D Klemke
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  ABSTRACT: Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response. To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome. Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P<0.05. The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P=0.0002 for CD4, P<0.0001 for FOXP3 and P=0.0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P=0.9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan-Meier analysis. High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.
  British Journal of Dermatology 04/2012; 167(2):348-58. · 3.67 Impact Factor
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  Available from: Jürgen C Becker

  Article: Activation of the PI3K/AKT pathway in Merkel cell carcinoma.

  Christian Hafner, Roland Houben, Anne Baeurle, Cathrin Ritter, David Schrama, Michael Landthaler, Juergen C Becker
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  ABSTRACT: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.
  PLoS ONE 01/2012; 7(2):e31255. · 4.09 Impact Factor