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Mistletoe-Based Drugs Work in Synergy with Radio-Chemotherapy in the Treatment of Glioma In Vitro and In Vivo in Glioblastoma Bearing Mice.
Schötterl, Sonja; Miemietz, Jennifer T; Ilina, Elena I; Wirsik, Naita M; Ehrlich, Ingrid; Gall, Andrea; Huber, Stephan M; Lentzen, Hans; Mittelbronn, Michel; Naumann, Ulrike.
Afiliação
  • Schötterl S; Molecular Neurooncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, Otfried-Müller-Str. 27, 72076 Tübingen, Germany.
  • Miemietz JT; Molecular Neurooncology, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, Otfried-Müller-Str. 27, 72076 Tübingen, Germany.
  • Ilina EI; Luxembourg Centre of Neuropathology (LCNP), 1 Rue Louis Rech, L-3555 Dudelange, Luxembourg.
  • Wirsik NM; NORLUX Neurooncology Laboratory, Luxembourg Institute of Health, 84 Rue Val Fleuri, L-1526 Luxembourg, Luxembourg.
  • Ehrlich I; Neurological Institute (Edinger Institute), Goethe University Frankfurt, Heinrich-Hoffmann-Str. 7, 60528 Frankfurt/Main, Germany.
  • Gall A; Learning and Memory, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, Otfried-Müller-Str. 27, 72076 Tübingen, Germany.
  • Huber SM; Learning and Memory, Hertie Institute for Clinical Brain Research and Center Neurology, University of Tübingen, Otfried-Müller-Str. 27, 72076 Tübingen, Germany.
  • Lentzen H; Department of Radiation Oncology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.
  • Mittelbronn M; MELEMA Pharma GmbH, Hamburg, Germany.
  • Naumann U; Luxembourg Centre of Neuropathology (LCNP), 1 Rue Louis Rech, L-3555 Dudelange, Luxembourg.
Article em En | MEDLINE | ID: mdl-31354846
ABSTRACT

BACKGROUND:

Extracts from Viscum album L. (VE) are used in the complementary cancer therapy in Europe for decades. VE contain several compounds like the mistletoe lectins (MLs) 1-3 and viscotoxins and also several minor ingredients. Since mistletoe lectin 1 (ML-1) has been described as the main component of VE harboring antitumor activity, purified native or recombinant ML-1 has been recently used in clinical trials. MLs stimulate the immune system, induce cytotoxicity, are able to modify the expression of cancer-associated genes, and influence the proliferation and motility of tumor cells.

OBJECTIVE:

In this study our goal was to determine anticancer effects of the VE ISCADOR Qu, of recombinant ML-1 (Aviscumine), and of native ML-1 in the treatment of glioblastoma (GBM), the most common and highly malignant brain tumor in adults. Additionally we were interested whether these drugs, used in combination with a temozolomide-(TMZ)-based radio-chemotherapy, provide synergistic effects.

METHODS:

Cell culture assays, ex vivo murine hippocampal brain slice cultures, human GBM cryosections, and a xenograft orthotopic glioblastoma mouse model were used.

RESULTS:

In cells, the expression of the ML receptor CD75s, which is also expressed in GBM specimen, but not in normal brain, correlates with the drug-induced cytotoxicity. In GBM cells, the drugs induce cell death in a concentration-dependent manner and reduce cell growth by inducing cell cycle arrest in the G2/M phase. The cell cycle arrest was paralleled by modifications in the expression of cell cycle regulating genes. ML containing drugs, if combined with glioma standard therapy, provide synergistic and additive anticancer effects. Despite not reaching statistical significance, a single intratumoral application of Aviscumine prolonged the median survival of GBM mice longer than tumor irradiation. Moreover, intratumorally applied Aviscumine prolonged the survival of GBM-bearing mice if used in combination with irradiation and TMZ for further 6.5 days compared to the radio-chemotherapy.

CONCLUSION:

Our results suggest that an adjuvant treatment of glioma patients with ML-containing drugs might be beneficial.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2019 Tipo de documento: Article