| 1. |
- Hortobágyi, Tibor, et al.
(författare)
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Pathophysiology of meningioma growth in pregnancy
- 2017
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Ingår i: Open Medicine (Poland). - : Walter de Gruyter GmbH. - 2391-5463. ; 12:1, s. 195-200
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Forskningsöversikt (refereegranskat)abstract
- Meningioma is among the most frequent brain tumours predominantly affecting elderly women. Epidemiological studies have shown that at the age of fertility the incidence is relatively low. The biological behaviour of meningioma in pregnancy is different from other meningiomas. The possible explanation is rooted in the complex physiological changes and hormonal differences during pregnancy. The increased meningioma growth observed in pregnancy is presumably the result of endocrine mechanisms. These include increase in progesterone, human placental lactogen (hPL) and prolactin (PRL) serum levels. In contrast, levels of pituitary hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG) produced by the placenta are decreasing in the mother prior to childbirth. Besides, vascular factors also play a crucial role. Peritumoral brain edema (PTBE), with well-known causative association with vascular endothelial growth factor (VEGF), can often be seen both with imaging and in the surgical specimens. Our aim is to assess published research on this topic including diagnostic and therapeutic guidelines, and to provide a clinically useful overview on the pathophysiology and biological behaviour of this rare complication of pregnancy.
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| 2. |
- Torok, Szilvia, et al.
(författare)
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Limited tumor tissue drug penetration contributes to primary resistance against angiogenesis inhibitors
- 2017
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 7:2, s. 400-412
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Tidskriftsartikel (refereegranskat)abstract
- Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly. Importantly, the highest and most homogeneous intratumoral drug concentrations have been found in sunitinib-treated animals. In another animal model, where - in contrast to the first model - vatalanib was detectable at homogeneously high intratumoral concentrations, the drug significantly reduced tumor growth and angiogenesis. In conclusion, the tumor tissue penetration and thus the antiangiogenic and antitumor potential of antiangiogenic RTKIs vary among the tumor models and our study demonstrates the potential of MALDI-MSI to predict the efficacy of unlabelled small molecule antiangiogenic drugs in malignant tissue. Our approach is thus a major technical and preclinical advance demonstrating that primary resistance to angiogenesis inhibitors involves limited tumor tissue drug penetration. We also conclude that MALDI-MSI may significantly contribute to the improvement of antivascular cancer therapies.
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