Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft

Dugandžija, Tihomir; Drljača, Jovana; Bulajić, Dragica; Isaković, Aleksandra; Stilinović, Nebojša; Sekulić, Slobodan; Čapo, Ivan

doi:10.1016/j.tice.2021.101557

Cited by 5 publications

(9 citation statements)

References 45 publications

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“… 24 and Ref. 25 ), and hence, are briefly outlined here. Detailed description of antibodies (manufacturer and dilution used) and primers (sequences, products’ length, and NCBI accession codes) information are given in Appendix S1 .…”

Section: Methodsmentioning

confidence: 99%

“…The U87 cells derived from human glioblastoma (ATCC HTB‐14) were used in this study. The cells were maintained in Modified Eagle Medium, as we described earlier 25 . All reagents were purchased from Capricorn Scientific GmbH.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were maintained in Modified Eagle Medium, as we described earlier. 25 All reagents were purchased from Capricorn Scientific GmbH.…”

Section: Methodsmentioning

confidence: 99%

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Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line

et al. 2022

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Aims: Many patients with glioblastoma (GBM) suffer from comorbid neurological/ psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy-associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM. Hence, it may be of interest to investigate whether DIA enhances the antitumor efficacy of TMZ in GBM cells.Methods: U87 human GBM was used to examine the effects of combined TMZ and DIA on cell viability, and the oxygen consumption within the cells, in order to evaluate mitochondrial bioenergetic response upon the treatment. Results:The cooperative index showed the presence of antagonism between TMZ and DIA, which was confirmed on long-term observation. Moreover, the level of apoptosis after the TMZ treatment was significantly decreased when administered with DIA (p < 0.001). Concomitant use of TMZ and DIA increased the basal cell respiration rate, the oxidative phosphorylation rate, and maximal capacity of mitochondrial

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line

et al. 2022

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“…Importantly, microglia/macrophages in the GBM resection zone have been suggested to function as part of a glioma stem cell niche at the tumour border [ 50 , 51 ] which is important for tumour recurrence. It is suggested that they express a distinct gene signature [ 52 ]. The supportive influence of microglial cells on glioma growth is now established beyond doubt and can even be reproduced in a xenograft model [ 52 ].…”

Section: Heterogeneity Of Cells In Tmementioning

confidence: 99%

Microglia and Brain Macrophages as Drivers of Glioma Progression

Zheng

Graeber

2022

IJMS

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Evidence is accumulating that the tumour microenvironment (TME) has a key role in the progression of gliomas. Non-neoplastic cells in addition to the tumour cells are therefore finding increasing attention. Microglia and other glioma-associated macrophages are at the centre of this interest especially in the context of therapeutic considerations. New ideas have emerged regarding the role of microglia and, more recently, blood-derived brain macrophages in glioblastoma (GBM) progression. We are now beginning to understand the mechanisms that allow malignant glioma cells to weaken microglia and brain macrophage defence mechanisms. Surface molecules and cytokines have a prominent role in microglia/macrophage-glioma cell interactions, and we discuss them in detail. The involvement of exosomes and microRNAs forms another focus of this review. In addition, certain microglia and glioma cell pathways deserve special attention. These “synergistic” (we suggest calling them “Janus”) pathways are active in both glioma cells and microglia/macrophages where they act in concert supporting malignant glioma progression. Examples include CCN4 (WISP1)/Integrin α6β1/Akt and CHI3L1/PI3K/Akt/mTOR. They represent attractive therapeutic targets.

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“…NSCLC cancer requires an expensive clinical treatment [ 7 ], so curcumin and germacrone are promising for the development of new NSCLC drugs. Preclinical studies are always useful for a prospective new drug [ 8 , 9 ]; meanwhile, the kinetics offer use as a model in preclinical research [ 10 , 11 ]. The blood pharmacokinetics and urodynamics with curcumin or germacrone in rats were reported [ 12 , 13 , 14 ], but no more studies on kinetics of curcumin and germacrone with the liver microsomes metabolism were conducted.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

Zhou

et al. 2022

Molecules

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Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions.

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Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft

Cited by 5 publications

References 45 publications

Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line

Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line

Microglia and Brain Macrophages as Drivers of Glioma Progression

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

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