TY  - JOUR
A1  - Hagemann, Carsten
A1  - Kessler, Almuth Friederike
A1  - Wiesner, Miriam
A1  - Denner, Joachim
A1  - Kämmerer, Ulrike
A1  - Vince, Giles Hamilton
A1  - Linsenmann, Thomas
A1  - Löhr, Mario
A1  - Ernestus, Ralf-Ingo
T1  - Expression-analysis of the human endogenous retrovirus HERV-K in human astrocytic tumors
N2  - Background

The human endogenous retrovirus K (HERV-K) has been acquired by the genome of human ancestors million years ago. It is the most complete of the HERVs with transcriptionally active gag, pol and env genes. Splice variants of env, which are rec, 1.5 kb transcript and Np9 have been suggested to be tumorigenic. Transcripts of HERV-K have been detected in a multitude of human cancers. However, no such reports are available concerning glioblastomas (GBM), the most common malignant brain tumor in adults. Patients have a limited prognosis of 14.6 months in median, despite standard treatment. Therefore, we elucidated whether HERV-K transcripts could be detected in these tumors and serve as new molecular target for treatment.

Findings

We analyzed human GBM cell lines, tissue samples from patients and primary cell cultures of different passages for HERV-K full length mRNA and env, rec and 1.5 kb transcripts. While the GBM cell lines U138, U251, U343 and GaMG displayed weak and U87 strong expression of the full length HERV-K, the splice products could not be detected, despite a weak expression of env mRNA in U87 cells. Very few tissue samples from patients showed weak expression of env mRNA, but none of the rec or 1.5 kb transcripts. Primary cells expressed the 1.5 kb transcript weakly in early passages, but lost HERV-K expression with extended culture time.

Conclusions

These data suggest that HERV-K splice products do not play a role in human malignant gliomas and therefore, are not suitable as targets for new therapy regimen.
KW  - Human endogenous retrovirus
KW  - HERV-K
KW  - Glioblastoma multiforme
KW  - Astrocytic tumor
KW  - Expression
KW  - Glioblastoma cell line
KW  - PCR analysis
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110211
ER  - 
TY  - JOUR
A1  - Linsenmann, Thomas
A1  - Monoranu, Camelia M.
A1  - Vince, Giles H.
A1  - Westermaier, Thomas
A1  - Hagemann, Carsten
A1  - Kessler, Almuth F.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
T1  - Long-term tumor control of spinal dissemination of cerebellar glioblastoma multiforme by combined adjuvant bevacizumab antibody therapy: a case report
N2  - Background

Glioblastoma multiforme located in the posterior fossa is extremely rare with a frequency up to 3.4%. Compared with glioblastoma of the hemispheres the prognosis of infratentorial glioblastoma seems to be slightly better. Absence of brainstem invasion and low expression rates of epidermal growth factor receptor are described as factors for long-time survival due to the higher radiosensitivity of these tumors.

Case presentation

In this case study, we report a German female patient with an exophytic glioblastoma multiforme arising from the cerebellar tonsil and a secondary spinal manifestation. Furthermore, the tumor showed no O (6)-Methylguanine-DNA methyltransferase promotor-hypermethylation and no isocitrate dehydrogenase 1 mutations. All these signs are accompanied by significantly shorter median overall survival. A long-term tumor control of the spinal metastases was achieved by a combined temozolomide/bevacizumab and irradiation therapy, as part of a standard care administered by the treating physician team.

Conclusion

To our knowledge this is the first published case of a combined cerebellar exophytic glioblastoma with a subsequent solid spinal manifestation. Furthermore this case demonstrates a benefit undergoing this special adjuvant therapy regime in terms of overall survival. Due to the limited overall prognosis of the disease, spinal manifestations of glioma are rarely clinically relevant. The results of our instructive case, however, with a positive effect on both life quality and survival warrant treating future patients in the frame of a prospective clinical study.
KW  - Glioblastoma
KW  - Spinal dissemination
KW  - Bevacizumab
KW  - Temozolomide
KW  - Irradiation
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110536
ER  -