The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas

Ajeawung, Norbert F.; Joshi, Harish C.; Kamnasaran, Deepak

doi:10.1016/j.canlet.2013.02.004

Cited by 6 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding the MF category, microtubule binding was the most influential and the drug targeted microtubule was proven effective in glioma. For example, the drug EM011 functions by disrupting microtubule dynamics and modules several oncogenic mediators causing a decrease in cell viability, proliferation and migration/invasion in the astrocytoma cell lines (Ajeawung, Joshi & Kamnasaran, 2013). For KEGG pathway enrichment analysis, cell cycle was the most significant pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma

Xiao

Liu

Peng

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background Lower grade glioma (LGG) are a heterogeneous tumor that may develop into high-grade malignant glioma seriously shortens patient survival time. The clinical prognostic biomarker of lower-grade glioma is still lacking. The aim of our study is to explore novel biomarkers for LGG that contribute to distinguish potential malignancy in low-grade glioma, to guide clinical adoption of more rational and effective treatments. Methods The RNA-seq data for LGG was downloaded from UCSC Xena and the Chinese Glioma Genome Atlas (CGGA). By a robust likelihood-based survival model, least absolute shrinkage and selection operator regression and multivariate Cox regression analysis, we developed a three-gene signature and established a risk score to predict the prognosis of patient with LGG. The three-gene signature was an independent survival predictor compared to other clinical parameters. Based on the signature related risk score system, stratified survival analysis was performed in patients with different age group, gender and pathologic grade. The prognostic signature was validated in the CGGA dataset. Finally, weighted gene co-expression network analysis (WGCNA) was carried out to find the co-expression genes related to the member of the signature and enrichment analysis of the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted for those co-expression network. To prove the efficiency of the model, time-dependent receiver operating characteristic curves of our model and other models are constructed. Results In this study, a three-gene signature (WEE1, CRTAC1, SEMA4G) was constructed. Based on the model, the risk score of each patient was calculated with LGG (low-risk vs. high-risk, hazard ratio (HR) = 0.198 (95% CI [0.120–0.325])) and patients in the high-risk group had significantly poorer survival results than those in the low-risk group. Furthermore, the model was validated in the CGGA dataset. Lastly, by WGCNA, we constructed the co-expression network of the three genes and conducted the enrichment of GO and KEGG. Our study identified a three-gene model that showed satisfactory performance in predicting the 1-, 3- and 5-year survival of LGG patients compared to other models and may be a promising independent biomarker of LGG.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma

Xiao

Liu

Peng

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…19 Other studies have shown that loss of the NF1 gene allows hyperactivation of the oncogene KRAS, 34 and a microtubule-binding drug, EM011, can decrease the expression of cancer progression genes like EGFR, mTORC1, and multiple matrix metalloproteinases. 5 The ERK/MAPK pathway represents an intriguing route of targeted therapy with drugs, such as MEK inhibitors, for patients in whom an aggressive resection is not possible or not desired. Subsets of infratentorial gangliogliomas were also found to contain either BRAF V600E mutations or KIAA1549-BRAF fusions, 6,21 suggesting a potential for targeted therapies in the future for the majority of CMTs (pilocytic astrocytomas and gangliogliomas).…”

Section: Discussionmentioning

confidence: 99%

Cervicomedullary tumors in children

McAbee

Modica

Thompson

et al. 2015

PED

View full text Add to dashboard Cite

OBJECT Cervicomedullary tumors (CMTs) represent a heterogeneous group of intrinsic neoplasms that are typically low grade and generally carry a good prognosis. This single-institution study was undertaken to document the outcomes and current treatment philosophy for these challenging neoplasms. METHODS The charts of all pediatric patients with CMTs who received treatment at St. Jude Children’s Research Hospital between January 1988 and May 2013 were retrospectively reviewed. Demographic, surgical, clinical, radiological, pathological, and survival data were collected. Treatment-free survival and overall survival were estimated, and predictors of recurrence were analyzed. RESULTS Thirty-one children (16 boys, 15 girls) with at least 12 months of follow-up data were identified. The median age at diagnosis was 6 years (range 7 months-17 years) and the median follow-up was 4.3 years. Low-grade tumors (Grade I or II) were present in 26 (84%) patients. Thirty patients underwent either a biopsy alone or resection, with the majority of patients undergoing biopsy only (n = 12, 39%) or subtotal resection (n = 14, 45%). Only 4 patients were treated solely with resection; 21 patients received radiotherapy alone or in combination with other treatments. Recurrent tumor developed in 14 children (45%) and 4 died as a result of their malignancy. A high-grade pathological type was the only independent variable that predicted recurrence. The 5- and 10-year treatment-free survival estimates are 64.7% and 45.3%, respectively. The 5- and 10-year overall survival estimate is 86.7%. CONCLUSIONS Children with CMTs typically have low-grade neoplasms and consequently long-term survival, but high risk of recurrence. Therapy should be directed at achieving local tumor control while preserving and even restoring neurological function.

show abstract

“…Thus, noscapine-specific effects towards GBN cells seem very promising but its further studies might be limited due to its relatively short half-life and poor solubility. To overcome these limits, several noscapine derivates were prepared and subsequently tested on GBM and other malignant tumor models with positive results [99][100][101][102][103].…”

Section: Mitotic Catastrophementioning

confidence: 99%

Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality

Vitovcova

Skarkova

Rudolf

et al. 2020

IJMS

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G2/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.

show abstract

The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas

Cited by 6 publications

References 49 publications

Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma

Identification and validation of a three-gene signature as a candidate prognostic biomarker for lower grade glioma

Cervicomedullary tumors in children

Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality

Contact Info

Product

Resources

About