The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma

Sordillo, Peter P.; Sordillo, Laura A.; Helson, Lawrence

doi:10.21873/anticanres.11551

Cited by 64 publications

(52 citation statements)

References 56 publications

(72 reference statements)

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“…Interestingly, indoleacetaldehyde, a product of tryptophan metabolism, was also shown to be putatively increased in the 8MGBA-TMZres media. Tryptophan metabolism disruption has been shown previously as a feature of treatment adaptation in GBM cells 15 . Consistent with our observation of increased extracellular vesicles, there was an increase in palmitic acid and stearic acid lipids in the GC-TOF-MS metabolites from the 8MBGA-TMZres cell line conditioned media ( Figure 6).…”

Section: Tmz Resistance Leads To An Increase In Intracellular Vesiclementioning

confidence: 80%

“…This was reflected in the putative increase of lipids from the LC-MS analysis. Another hit, indoleacetaldehyde, is a product of tryptophan metabolism, hyperactivation of which occurs in GBM and is thought to suppress anti-tumor immunity 15 . Extracellular lipids, stearic and palmitic acid, were also found and validated in the GC-TOF-MS analysis along with citric acid.…”

Section: Discussionmentioning

confidence: 99%

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Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Tiek

Rone

Graham

et al. 2017

Preprint

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Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard of care is the DNA alkylating agent temozolomide (TMZ), but this treatment strategy adds only ~4 months to median survival due to the rapid development of resistance. While some mechanisms of TMZ resistance have been identified, they are not fully understood. There are few effective strategies to manage therapy resistant GBM, and we lack diverse preclinical models of acquired TMZ resistance in which to test therapeutic strategies on TMZ resistant GBM. In this study, we create and characterize two new GBM cell lines resistant to TMZ, based on the 8MGBA and 42MGBA cell lines. Analysis of the TMZ resistant (TMZres) variants in conjunction with their parental, sensitive cell lines shows that acquisition of TMZ resistance is accompanied by broad phenotypic changes, including increased proliferation, migration, chromosomal aberrations and secretion of cytosolic lipids. Importantly, each TMZ resistant model captures a different facet of the "go" (8MGBA-TMZres) or "grow" (42MGBA-TMZres) hypothesis of GBM behavior. These model systems will be important additions to the available tools for investigators seeking to define molecular mechanisms of acquired TMZ resistance.. CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a

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Section: Tmz Resistance Leads To An Increase In Intracellular Vesiclementioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Tiek

Rone

Graham

et al. 2017

Preprint

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“…However, the role of m 6 A is controversial in glioblastoma. Glioblastoma is an aggressive primary brain tumour in adults and has no significant improvement in survival rate so far 46. Previous studies strongly indicated the role of m 6 A methylation in self‐renewal and tumorigenesis of glioblastoma stem cells (GSCs) 47.…”

Section: The Dual Role Of M6a Modification In Human Cancersmentioning

confidence: 99%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

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As the most abundant and reversible RNA modification in eukaryotic cells, m6A triggers a new layer of epi‐transcription. M6A modification occurs through a methylation process modified by “writers” complexes, reversed by “erasers”, and exerts its role depending on various “readers”. Emerging evidence shows that there is a strong association between m6A and human diseases, especially cancers. Herein, we review bi‐aspects of m6A in regulating cancers mediated by the m6A‐associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6A‐targeted therapies including competitive antagonists of m6A‐associated proteins may provide a new tumour intervention in the future.

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“…Moreover, it is believed that curcumin has influence on the cells’ microenvironment. In fact, this drug changes the microenvironment around the cells to one that is harmful for proliferation of cancer cells, but conducive to healthy stem cells …”

Section: Resultsmentioning

confidence: 99%

Curcumin-Loaded Starch Micro/Nano Particles for Biomedical Application: The Effects of Preparation Parameters on Release Profile

et al. 2019

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Although curcumin is highly cytotoxic against cancer cells, its hydrophobicity and fast degradation at physiological pH limit its effective practical application. To prevent such limitations, inexpensive curcumin‐loaded starch particles are synthesized in this research. Particles are prepared by water‐in‐oil (W/O) miniemulsion technique and an adsorption method is used for curcumin loading. Also, encapsulation efficiency (%EE) is improved by using pluronic F‐127 in the drug solution. Particles are characterized, swelling studies are performed, and MTT assays against human adipose mesenchymal stem cells (hAMSCs) and MG‐63 cells are utilized for investigations. Results indicate that crosslinker, surfactant, and stirring rate affect the swelling degree of bare particles as well as %EE and release profile of drug‐loaded particles. Moreover, swelling degree, %EE, and burst release are modeled by design of experiments via response surface method. Due to analysis of variance, the responses can be predicted by quadratic models within the design space. Also, cell viability studies depict that curcumin encapsulation improves its cytotoxic effect on MG‐63 cells due to its sustained release while it has no cytotoxic effect on hAMSCs. In addition, it can be concluded that curcumin sustained release plays a more crucial role on cell viability of cancer cells compared to %EE. Consequently, it can be stated that curcumin‐loaded starch particles have good potential as drug delivery systems for osteosarcoma therapy.

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The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma

Abstract: Abstract.

Cited by 64 publications

References 56 publications

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

Alterations in Cell Motility, Proliferation, and Metabolism in Novel Models of Acquired Temozolomide Resistant Glioblastoma

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Curcumin-Loaded Starch Micro/Nano Particles for Biomedical Application: The Effects of Preparation Parameters on Release Profile

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