Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model

Saga, Isako; Shibao, Shunsuke; Okubo, Jun; Osuka, Satoru; Kobayashi, Yusuke; Yamada, Sachiko; Fujita, Satoshi; Urakami, Kenichi; Kusuhara, Masatoshi; Yoshida, Kazunari; Saya, Hideyuki; Sampetrean, Oltea

doi:10.1093/neuonc/nou096

Cited by 44 publications

(59 citation statements)

References 27 publications

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“…Like many other cancers, GBM preferentially utilizes glycolysis as a key energy source regardless of oxygen supply, which is also known as "Warburg effect" [54,55]. The glycolysis in GBM also displays heterogeneity [56]. Some cases have higher levels of glycolysis, thus GBM cells are adapted to the metabolic condition lacking oxygen supply, where glycolysis meets their metabolic demands for growth and >1.06; mvFD low : ≤1.06.…”

Section: Discussionmentioning

confidence: 99%

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Chen

Shi

et al. 2018

Laboratory Investigation

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The microvascular profile has been included in the WHO glioma grading criteria. Nevertheless, microvessels in gliomas of the same WHO grade, e.g., WHO IV glioblastoma (GBM), exhibit heterogeneous and polymorphic morphology, whose possible clinical significance remains to be determined. In this study, we employed a fractal geometry-derived parameter, microvascular fractal dimension (mvFD), to quantify microvessel complexity and developed a home-made macro in Image J software to automatically determine mvFD from the microvessel-stained immunohistochemical images of GBM. We found that mvFD effectively quantified the morphological complexity of GBM microvasculature. Furthermore, high mvFD favored the survival of GBM patients as an independent prognostic indicator and predicted a better response to chemotherapy of GBM patients. When investigating the underlying relations between mvFD and tumor growth by deploying Ki67/mvFD as an index for microvasculature-normalized tumor proliferation, we discovered an inverse correlation between mvFD and Ki67/mvFD. Furthermore, mvFD inversely correlated with the expressions of a glycolytic marker, LDHA, which indicated poor prognosis of GBM patients. Conclusively, we developed an automatic approach for mvFD measurement, and demonstrated that mvFD could predict the prognosis and response to chemotherapy of GBM patients.

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Section: Discussionmentioning

confidence: 99%

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Chen

Shi

et al. 2018

Laboratory Investigation

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“…O-6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose expression level is regulated epigenetically at the gene promoter, correlates with resistance to chemotherapies (116), and renders GSCs resistant to temozolomide (62). Secretion of exosomes, activation of autophagy (117), cell metabolism (66,118), ROS production (119, 120), drug efflux (121), and microRNA expression (114,115) are also altered in GSCs and can further enhance therapeutic resistance.…”

Section: What Type Of Clone Can Initiate Tumor Recurrence?mentioning

confidence: 99%

Overcoming therapeutic resistance in glioblastoma: the way forward

Osuka¹,

Meir²

2017

Journal of Clinical Investigation

386

311

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“…Cancer stem cells possess the property of “robustness”, which refers to several biological characteristics including resistance to redox stress, the capacity to carry out rapid repair of damaged DNA, the ability to adapt to a hyperinflammatory or hyponutritious microenvironment, plasticity in the transition to transit‐amplifying cells, metabolic reprogramming, and an enhanced ability to expel anticancer drugs through ATP‐binding cassette transporters (Fig. b).…”

Section: Cancer Stem Cells and Intratumoral Heterogeneitymentioning

confidence: 99%

Therapeutic strategies targeting cancer stem cells

2015

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Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self‐renewal, and a multilineage differentiation potential. Cancer stem cells are responsible for the development of tumor cell heterogeneity, a key feature for resistance to anticancer treatments including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Furthermore, minimal residual disease, the major cause of cancer recurrence and metastasis, is enriched in CSCs. Cancer stem cells also possess the property of “robustness”, which encompasses several characteristics including a slow cell cycle, the ability to detoxify or mediate the efflux of cytotoxic agents, resistance to oxidative stress, and a rapid response to DNA damage, all of which contribute to the development of therapeutic resistance. The identification of mechanisms underlying such characteristics and the development of novel approaches to target them will be required for the therapeutic elimination of CSCs and the complete eradication of tumors. In this review, we focus on two prospective therapeutic approaches that target CSCs with the aim of disrupting their quiescence or redox defense capability.

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Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model

Cited by 44 publications

References 27 publications

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study

Overcoming therapeutic resistance in glioblastoma: the way forward

Therapeutic strategies targeting cancer stem cells

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