Pharmacologic Therapies for Malignant Glioma: A Guide for Clinicians

Soffietti, Riccardo; Bertero, Luca; Pinessi, Lorenzo; Rudà, Roberta

doi:10.1007/s40263-014-0215-x

Cited by 10 publications

(6 citation statements)

References 72 publications

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“…Neuroglioma is a primary nervous system tumor with a high rate of malignancy (1). Patients that receive surgical treatment for this disease typically have a poor prognosis, particularly those with glioblastoma multiforme (GBM), for which the average survival time is <2 years (2).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

et al. 2017

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Abstract. Long non-coding RNA (lncRNA) is a class of regulative non-coding RNA that is >200 nucleotides in length. Previous studies have demonstrated that lncRNA Fer-1-like family member 4 (FER1L4) serves regulatory roles in tumor progression; however, its clinical significance in human neuroglioma remains unclear. In the present study, data from The Cancer Genome Atlas was mined in order to investigate the association between FER1L4 expression and prognosis in patients with glioma. A short interfering (si)RNA targeting FER1L4 was transfected into U373-MG and U251 glioma cell lines, and cell viability, invasion and apoptosis were examined using CCK-8, Transwell and Annexin V-fluorescein isothiocyanate/propidium iodide assays, respectively. FER1L4 was significantly upregulated in high-grade glioma compared with low-grade glioma. Additionally, high expression of FER1L4 significantly predicted poor prognosis in patients with glioma. The expression of FER1L4 in glioma cell lines was significantly higher compared with that in normal astrocytes. Furthermore, by downregulating FER1L4 using siRNA, the invasiveness and viability of the glioma cells significantly decreased, while apoptosis significantly increased. The findings from the present study indicate that FER1L4 serves a role in the occurrence and progression of glioma, and could be used as a prognostic biomarker for this disease.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

et al. 2017

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“…Dasatinib, a kinase inhibitor that acts on members of the Src family of kinases, is well studied in glioma and has shown preclinical promise 45. Vincristine, a spindle poison, is used in combination with procarbazine and lomustine to treat high-grade glioma and has also been successful in a phase III trial for the treatment of low-grade gliomas 22,46,47. Reductions in transcript abundance probably led to the loss of low-abundance genes from the full gene signature and altered the DEGs detected, leading to the loss of these connectivity mapping connections.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with GBM undergo concurrent chemoradiotherapy with temozolomide according to the Stupp protocol and adjuvant chemotherapy 21. Patients with anaplastic glioma may undergo radiotherapy with or without chemotherapy, depending on tumor molecular profile 22. Low-grade gliomas with poor prognosis may also be considered for adjuvant treatment 23.…”

Section: Introductionmentioning

confidence: 99%

Impact of Variable RNA-Sequencing Depth on Gene Expression Signatures and Target Compound Robustness: Case Study Examining Brain Tumor (Glioma) Disease Progression

Stupnikov

O’Reilly

McInerney

et al. 2018

JCO Precision Oncology

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PurposeGene expression profiling can uncover biologic mechanisms underlying disease and is important in drug development. RNA sequencing (RNA-seq) is routinely used to assess gene expression, but costs remain high. Sample multiplexing reduces RNAseq costs; however, multiplexed samples have lower cDNA sequencing depth, which can hinder accurate differential gene expression detection. The impact of sequencing depth alteration on RNA-seq–based downstream analyses such as gene expression connectivity mapping is not known, where this method is used to identify potential therapeutic compounds for repurposing.MethodsIn this study, published RNA-seq profiles from patients with brain tumor (glioma) were assembled into two disease progression gene signature contrasts for astrocytoma. Available treatments for glioma have limited effectiveness, rendering this a disease of poor clinical outcome. Gene signatures were subsampled to simulate sequencing alterations and analyzed in connectivity mapping to investigate target compound robustness.ResultsData loss to gene signatures led to the loss, gain, and consistent identification of significant connections. The most accurate gene signature contrast with consistent patient gene expression profiles was more resilient to data loss and identified robust target compounds. Target compounds lost included candidate compounds of potential clinical utility in glioma (eg, suramin, dasatinib). Lost connections may have been linked to low-abundance genes in the gene signature that closely characterized the disease phenotype. Consistently identified connections may have been related to highly expressed abundant genes that were ever-present in gene signatures, despite data reductions. Potential noise surrounding findings included false-positive connections that were gained as a result of gene signature modification with data loss.ConclusionFindings highlight the necessity for gene signature accuracy for connectivity mapping, which should improve the clinical utility of future target compound discoveries.

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“…Despite huge progress in developing the diagnostic methods and strategies for therapy, such as radiation treatment and chemotherapy, glioma is still one of the most lethal cancer in human ( 18 , 19 ). The average survival period of patients with glioma is less than 2 years and the 5-year survival rate is no more than 3%, which ranks the lowest among all cancers ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Hepatoma‑derived growth factor functions as an unfavorable prognostic marker of human gliomas

Yang

Liang

et al. 2017

Oncol Lett

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Hepatoma-derived growth factor (HDGF) regulates various cellular processes involved in the onset and development of tumors. To evaluate the role of HDGF in human gliomas, western blotting analysis, immunohistochemistry staining and reverse transcription-quantitative polymerase chain reaction were performed to detect HDGF protein and mRNA expression levels in glioma and intractable epileptic brain tissue. Various clinicopathological characteristics, including age, gender, World health Organization grade, HDGF expression level, Karnofsky performance Status (KPS) and Ki-67 index were obtained from medical records. The correlation between HDGF expression and these clinicopathological characteristics was statistically evaluated. Following this, multivariate liner regression was used to evaluate their effect on patient survival time. HDGF expression, at the protein and mRNA levels, was observed to be more upregulated in glioma tissues compared with intractable epileptic brain tissue without tumor. Furthermore, the level of HDGF expression was positively associated with the grade of malignancy [grades II~IV, Ki-67 index ≥20% or KPS <80 (P<0.05)] and poor prognosis in glioma patients. Notably, the univariate survival analysis identified a negative correlation between HDGF-expression and survival time (P<0.01) and multivariate liner regression demonstrated that HDGF expression is an independent prognostic factor for gliomas (P=0.01). Overall, HDGF upregulation may be a crucial step in the development and invasion of glioma. Further survival analysis highlighted its prognostic value for this malignancy, implying its potential as a promising therapeutic target for gliomas.

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Pharmacologic Therapies for Malignant Glioma: A Guide for Clinicians

Cited by 10 publications

References 72 publications

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

Long non-coding RNA Fer-1-like family member 4 is overexpressed in human glioblastoma and regulates the tumorigenicity of glioma cells

Impact of Variable RNA-Sequencing Depth on Gene Expression Signatures and Target Compound Robustness: Case Study Examining Brain Tumor (Glioma) Disease Progression

Hepatoma‑derived growth factor functions as an unfavorable prognostic marker of human gliomas

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