A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies

Conclusions GLPG0187 was well tolerated with a dose-proportional PK profile upon continuous infusion. No formal maximal tolerated dose could be established. GLPG0187 showed signs of target engagement with a favourable toxicity profile. However, continuous infusion of GLPG0187 failed to show signs of monotherapy efficacy.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 26 February 2020Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Meng Cheng, Zheng Wei Zhang, Xing Hu Ji, Yadi Xu, Erbao Bian, Bing Zhao
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research
e Kim Kwon Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors are shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets, we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC–MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition at...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Seol Lee Lee Nam Diffusely infiltrating gliomas (DIGs) are difficult to completely resect and are associated with a high rate of tumor relapse and progression from low- to high-grade glioma. In particular, optimized short-term culture-enriching patient-derived glioma stem cells (GSCs) are essential for customizing the therapeutic strategy based on clinically feasible in vitro drug screening for a wide range of DIGs, owing to the high inter-tumoral heterogeneity. Herein, we constructed a novel high-throughput culture condition screening platform called ‘GFSCAN’, which evaluated the cellul...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSIONS: Circ_0079593 stimulated the pathological process of glioma via acting as competing endogenous RNA to sponge miR-499a-5p. PMID: 32096160 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
The cancer stem cell hypothesis is an old idea which has been revived in recent years for many cancers, including gliomas. However, this concept has become controversial due to a series of studies with conflic...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Review Source Type: research
Conclusions: Percentage of signal recovery shows low recovery values in metastases, intermediate recovery values in glioma, and overshoot in lymphoma. PSR values show lower overlap than rCBV between lymphoma and metastases; and between high grade glioma and metastases. PSR difference is also higher than rCBV between low- and high-grade gliomas. Hence, PSR can potentially help as an additional perfusion parameter in the preoperative differentiation of these tumors.
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
Abstract The folate-modified graphene oxide (GO-FA) was successfully prepared, which had good stability and biocompatibility on rat glioma cells. The formation and composition of GO-FA were confirmed by scanning electron microscope (SEM), transmission electron microscope (TEM), fourier transform infrared spectrum (FT-IR), Raman spectra and X-ray photoelectron spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells. The experiment of GO-FA loading with temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loa...
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
AbstractBackgroundThe use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with theO6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.MethodsWe analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified ...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
In this study, we found that eriodictyol has anti-tumor activity in lung, colon, breast, pancreas, and liver cancer, and most significantly in glioma cell lines. Eriodictyol dose- and time-dependently suppresses cell proliferation, migration, and invasion in U87MG and CHG-5 glioma cells. In addition, eriodictyol induces apoptosis in U87MG and CHG-5 cells, as evaluated by flow cytometry, immunofluorescence, and Western blot. Furthermore, eriodictyol downregulates the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway in a concentration-dependent manner. Moreover, the effects of eriodictyol on the apoptosis o...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: Our results provide a transcriptional rationale for the lack of significant therapeutic benefit from temozolomide in patients with recurrent glioblastoma. Our findings imply that the spectrum of potentially effective drugs is likely to differ between newly diagnosed and recurrent glioblastomas and underscore the merits of glioblastoma stem cells as prognostic models for identifying alternative drugs and predicting drug response in recurrent glioblastoma. With the majority of recurrent glioblastomas being inoperable, glioblastoma stem cell models provide the means of compensating for the limited availability of...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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