Glioma
Neuro Oncol.2013 Nov;15(11):1469-78. doi: 10.1093/neuonc/not111. Epub 2013 Oct 6.
Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions.
Schmidt L1,Kling T, Monsefi N, Olsson M, Hansson C, Baskaran S, Lundgren B, Martens U, Häggblad M, Westermark B, Forsberg Nilsson K, Uhrbom L, Karlsson-Lindahl L, Gerlee P, Nelander S.
Abstract
BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers.
METHODS: We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling.
RESULTS: Of the 5 × 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds
CONCLUSION: We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.
KEYWORDS: drug combination responses; glioblastoma stem cell cultures; glioblastoma therapy; predictive medicine
PMID: 24101737
J Nutr Biochem.2015 May;26(5):466-75.
Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis.
Huynh TT1
Abstract
Glioblastoma multiforme (GBM) is the most aggressive type characterized by relapse and resistance even with the combination of radio- and chemotherapy. The presence of glioma stem cells (GSCs) has been shown to contribute to tumorigenesis, recurrence
Copyright © 2015 Elsevier Inc. All rights reserved.
KEYWORDS: CD133+ glioma stem cells; Glucose-regulated protein, 78 kDa (GRP78); Irradiation resistance; Pterostilbene; miR-205
PMID: 25736407
CancerRes.2016 Sep 1;76(17):4970-80. doi: 10.1158/0008-5472.CAN-15-3541. Epub 2016 Jun 30.
Activation of the c-Met Pathway Mobilizes an Inflammatory Network in the Brain Microenvironment to Promote Brain Metastasis of Breast Cancer.
Xing F1, Liu Y2, Sharma S2, Wu K2, Chan MD3, Lo HW2, Carpenter RL2, Metheny-Barlow LJ3, Zhou X4, Qasem SA5, Pasche B2, Watabe K1.
Abstract
Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remain poorly understood. Here, we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL8 and CXCL1. Additionally, stimulation of IL1β secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle that generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood-brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. Cancer Res; 76(17); 4970-80. ©2016 AACR.
©2016 American Association for Cancer Research.
PMID: 27364556
Oncotarget.2016 Nov 8;7(45):73200-73215. doi: 10.18632/oncotarget.12298.
Case-specific potentiation of glioblastoma drugs by pterostilbene.
Schmidt L1,Baskaran S1, Johansson P1, Padhan N1, Matuszewski D2, Green LC3, Elfineh L1, Wee S4, Häggblad M5, Martens U5, Westermark B1, Forsberg-Nilsson K1,Uhrbom L1, Claesson-Welsh L1,Andäng M4, Sintorn IM2, Lundgren B5, Lönnstedt I1, Krona C1, Nelander S1.
Abstract
Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib
KEYWORDS: cancer therapeutics; drug repurposing; glioblastoma;
PMID: 27689322
Toxicol In Vitro.2017 Sep;43:69-75.
The effect of resveratrol, its naturally occurring derivatives
Zielińska-Przyjemska M1,Kaczmarek M2, Krajka-Kuźniak V1,Łuczak M3, Baer-Dubowska W4.
Abstract
Resveratrol (3,5,4′-trihydroxy-
Copyright © 2017. Published by Elsevier Ltd.
KEYWORDS: Apoptosis; Cell cycle; Human T98G glioblastoma cells; Rat C6 glioma cells; Stilbene derivatives; Tannic acid
PMID: 28595835