Strategies of temozolomide in future glioblastoma treatment

Lee, Chooi Yeng

doi:10.2147/ott.s120662

Cited by 93 publications

(65 citation statements)

References 43 publications

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“…TMZ is a DNA-alkylating compound, which is widely applied in treating malignant tumors, including glioblastomas, pituitary adenomas, and carcinomas (44,45). Combining chemosensitizers has been shown to profoundly improve the therapeutic effect of TMZ in different tumor models.…”

Section: Combination Of a Parp Inhibitor And Tmz Suppressed Sdhb-mutamentioning

confidence: 99%

Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma

Pang

Caisová

et al. 2018

Clinical Cancer Research

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Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, and multiplicity. Transcriptomic profiling suggests that cluster I PCPGs and other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, the hypoxia signaling pathway, mitochondrial electron transport chain, and methylation status, suggesting that therapeutic regimen might be optimized by targeting these signature molecular pathways. In the present study, we investigated the molecular signatures in clinical specimens from cluster I PCPGs in comparison with cluster II PCPGs that are related to kinase signaling and often present as benign tumors. We found that cluster I PCPGs develop a dependency to mitochondrial complex I, evidenced by the upregulation of complex I components and enhanced NADH dehydrogenation. Alteration in mitochondrial function resulted in strengthened NAD metabolism, here considered as a key mechanism of chemoresistance, particularly, of succinate dehydrogenase subunit B ()-mutated cluster I PCPGs via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide, a conventional chemotherapeutic agent, not only improved cytotoxicity but also reduced metastatic lesions, with prolonged overall survival of mice with knockdown PCPG allograft. In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with mutations..

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Section: Combination Of a Parp Inhibitor And Tmz Suppressed Sdhb-mutamentioning

confidence: 99%

Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma

Pang

Caisová

et al. 2018

Clinical Cancer Research

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“…The degradation rate of PLGA can be easily tailored from days to years by tuning the lactic to glycolic acid ratio, molecular weight, and the end cap groups and thus, providing versatility in the development of microparticles to deliver different drugs where the release kinetics need to be tailored to fit the drug of interest. Because of its versatility and biosafety, PLGA has been widely used for the fabrication of TMZ‐loaded particles for the treatment of glioblastoma . There are many different methods of producing PLGA microparticles including emulsion solvent extraction/evaporation, electrospraying, and microfabrication .…”

Section: Introductionmentioning

confidence: 99%

“…Because of its versatility and biosafety, PLGA has been widely used for the fabrication of TMZ-loaded particles for the treatment of glioblastoma. 21 There are many different methods of producing PLGA microparticles including emulsion solvent extraction/evaporation, 22 electrospraying, 23 and microfabrication. 24 Among the different fabrication methods, the emulsion solvent extraction/evaporation method is the most widely used method for the fabrication of drug-loaded microparticles as it is associated with an easy and low cost setup.…”

Section: Introductionmentioning

confidence: 99%

Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide‐loaded PLGA microparticles for the treatment of glioblastoma

et al. 2019

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Glioblastoma multiforme (GBM) is the most common and invasive form of malignant brain tumors and despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with GBM still remains poor. Temozolomide (TMZ) is the chemotherapy drug that is most commonly given orally after surgical resection of these tumors. In this study, the effects of solvents (i.e., dichloromethane and acetonitrile) used for the fabrication of electrosprayed TMZ‐loaded poly(lactic‐co‐glycolic acid) (PLGA) on drug loading, loading efficiency, drug release kinetics, surface morphology, and particle size were investigated. The results from this study demonstrated that by using a larger volume of a solvent with higher polarity (i.e., acetonitrile) which allows for a higher amount of hydrophilic TMZ to dissolve into the polymer solution, higher drug loading could be achieved. However, the particles fabricated with high amount of acetonitrile, which has a lower vapor pressure, had large pores and a smaller diameter which led to an initial burst release and high cumulative release at the end of the study. An optimal combination of the two solvents is needed to result in particles with a good amount of loading and minimal initial burst release. The electrosprayed microparticles were able to illicit a cytotoxic response in U‐87 MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work indicated that electrospraying is a promising method for the fabrication of TMZ‐loaded PLGA microparticles for the treatment of GBM and solvent composition can be altered to control drug loading and release kinetics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2317–2324, 2019.

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“…Resistance to chemotherapeutics is another difficulty for malignant gliomas treatment. As the most effective medicine for malignant gliomas, the cytotoxicity of TMZ induced glioma cells apoptosis and activated multiple signaling pathway increasing glioma cells damages [43][44][45] . It has been reported that TMZ promoted ROS production in glioma tissues [46][47][48] .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-144 represses gliomas progression and elevates susceptibility to Temozolomide by targeting CAV2 and FGF7

Liu

Ren

Zhao

et al. 2020

Sci Rep

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Malignant gliomas are the most common tumor in central nervous system with poor prognosis. Due to the limitation of histological classification in earlier diagnosis and individualized medicine, it is necessary to combine the molecular signatures and the pathological characteristics of gliomas. Lots of microRNAs presented abnormal expression in gliomas and modulated gliomas development.Exploration the miRNAs profile is helpful for the diagnosis, therapy and prognosis of gliomas. It has been demonstrated that miR-144 plays important roles in solid tumors. However, the detail mechanisms remained unrevealed. In this study, we have demonstrated the level of miR-144 decreased in glioma tissues from patients, especially in gliomas with higher grades. MiR-144 was also validated have lower expression in glioma cell lines compared with cortical neuron cell by using qRT-PCR. The in vitro functional experiment indicated miR-144 improved gliomas progression through repressing proliferation, sensitizing to chemotherapeutics and inhibiting metastasis. We further identified fibroblast growth factor 7 (FGF7) and Caveolin 2 (CAV2) were target genes of miR-144 by luciferase reporter assay and western blotting. The mechanisms study suggested forced FGF7 expression elevated Akt activation and decreased reactive oxygen species (ROS) generation. The MTT and cell cycle assay indicated miR-144 suppressed glioma cells proliferation through modulating FGF mediated Akt signaling pathway. Meanwhile, miR-144 promoted Temozolomide (TMZ) induced apoptosis in glioma cells via increasing ROS production by using FACS. On the other hand, CAV2, as another target of miR-144, accelerated glioma cells migration and invasion via promoting glioma cells EMT progress. Retrieved expression of FGF7 or CAV2 rescued the proliferation and migration function mediated by miR-144. Furthermore, the in vivo experiments in PDX models displayed the anti-tumor function of miR-144, which could be retrieved by overexpression of FGF7 and CAV2. Taken together, these findings indicated miR-144 acted as a potential target against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new therapeutic strategy and prognostic indicator for gliomas.

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Strategies of temozolomide in future glioblastoma treatment

Cited by 93 publications

References 43 publications

Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma

Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma

Effects of solvent used for fabrication on drug loading and release kinetics of electrosprayed temozolomide‐loaded PLGA microparticles for the treatment of glioblastoma

MicroRNA-144 represses gliomas progression and elevates susceptibility to Temozolomide by targeting CAV2 and FGF7

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