Tumor microenvironment in treatment of glioma

Li, Guijie; Qin, Zhigang; Chen, Zhuo; Xie, Li; Ren, Wei; Zhao, Hang

doi:10.1515/med-2017-0035

Cited by 45 publications

(47 citation statements)

References 32 publications

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“…GBM patients usually have a median survival of approximately 15 months with the “Stupp” Regimen, consisting of 6 weeks of radiation with daily Temozolomide (TMZ) followed by 6 cycles of TMZ [ 2 , 3 ]. However, despite the modern therapies, GBM patients still have poor prognosis and high tumor recurrence due to the tumor resistance to chemotherapy [ 4 , 5 ]. TMZ, a DNA alkylating agent, is currently the most widely used and effective chemotherapeutic drug for GBM [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082

Pustchi

Avci

Akay

et al. 2020

IJMS

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Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased GBM survival and resistance after combined drug treatment compared to mono-cultures. These data restated the importance of 3D cell culture to mimic the tumor microenvironment for drug screening.

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Section: Introductionmentioning

confidence: 99%

“…The tumor microenvironment has a crucial role in cancer development, progression, and response to treatment [ 5 ]. The GBM microenvironment does not only contain tumor cells but also a mixture of diverse stromal cell types.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082

Pustchi

Avci

Akay

et al. 2020

IJMS

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“…Glioma microenvironment is composed by a multitude of chemokines, interleukins, growth factors, and proinflammatory small molecules. These growth factors stimulate several oncogenes such as PKB, mTOR, and STATs (Audia, Conroy, Glass, & Bhat, 2017;Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Boswellic acid has anti‐inflammatory effects and enhances the anticancer activities of Temozolomide and Afatinib, an irreversible ErbB family blocker, in human glioblastoma cells

Barbarisi

Sena

et al. 2019

Phytotherapy Research

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Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug‐resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti‐inflammatory effects analyzing p65/NF‐κB and Leukotriene B4 expression and production of interleukins and growth factors (IL‐8, IL‐6, vascular endothelial growth factor, CXCL‐12, and MMP‐9). Considering the cardiotoxicity of TMZ and anti‐EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti‐inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti‐inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.

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“…Glioblastoma represents a prototype of tumor in which the remarkable capability of communication with the microenvironment and the complex intra- and inter-tumor heterogeneity play a leading role in tumor malignancy, invasiveness and therapy failure. The interaction of tumor-glia cells is also linked with the chemoresistant phenotype of glioblastoma [ 5 ]; in particular, the hypoxic microenvironment, a common feature of this type of cancer, is strongly associated with radio- and chemoresistance by modulating different mechanisms, such as apoptosis and angiogenesis [ 6 ], expression of ATP-binding cassette (ABC) proteins [ 7 ], and functions of glioblastoma stem cells (GSCs) [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier

Ros

Gregorio

Iorio

et al. 2018

IJMS

151

130

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For glioblastoma, the tumor microenvironment (TME) is pivotal to support tumor progression and therapeutic resistance. TME consists of several types of stromal, endothelial and immune cells, which are recruited by cancer stem cells (CSCs) to influence CSC phenotype and behavior. TME also promotes the establishment of specific conditions such as hypoxia and acidosis, which play a critical role in glioblastoma chemoresistance, interfering with angiogenesis, apoptosis, DNA repair, oxidative stress, immune escape, expression and activity of multi-drug resistance (MDR)-related genes. Finally, the blood brain barrier (BBB), which insulates the brain microenvironment from the blood, is strongly linked to the drug-resistant phenotype of glioblastoma, being a major physical and physiological hurdle for the delivery of chemotherapy agents into the brain. Here, we review the features of the glioblastoma microenvironment, focusing on their involvement in the phenomenon of chemoresistance; we also summarize recent advances in generating systems to modulate or bypass the BBB for drug delivery into the brain. Genetic aspects associated with glioblastoma chemoresistance and current immune-based strategies, such as checkpoint inhibitor therapy, are described too.

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Tumor microenvironment in treatment of glioma

Cited by 45 publications

References 32 publications

Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082

Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082

Boswellic acid has anti‐inflammatory effects and enhances the anticancer activities of Temozolomide and Afatinib, an irreversible ErbB family blocker, in human glioblastoma cells

Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier

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