Effect of acetylsalicylic acid and pentoxifylline (trental) on intravascular erythrocyte aggregation stimulated by arachidonic acid

Sheremet’ev, Yu. A.; Shtykhno, Yu. M.; Udovichenko, V. I.; Levin, G. Ya.

doi:10.1007/bf00830383

Cited by 1 publication

(1 citation statement)

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“…Ultimately cells will accumulate the DNA alterations leading to genomic instability and causing the cell transformation and ontogenesis [ 28 ]. Spindle microtubules are attached to chromosomes by kinetochore, which confirms the attachment and stability of microtubule status to the spindle assembly checkpoint, a signaling pathway responsible to correct chromosome segregation and modulation of CDK1 activity [ 29 , 30 ]. The canonical pathway findings suggest that the upregulation in the kinetochore-signaling pathway due to the differentially expressed genes leads to genomic and chromosomal instability, which in turn contributes to the tumor progression.…”

Section: Resultsmentioning

confidence: 87%

In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK, NEK2, and CDK1

Khedkar

Wang

Yadav

et al. 2021

IJMS

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Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease’s pathogenesis have yet to be fully elucidated. Thus, the identification of prognostic biomarkers as well as developing novel therapeutic agents for targeting these markers become relevant. Herein, we identified 264 differentially expressed genes (DEGs) common in four ovarian cancer datasets (GSE14407, GSE18520, GSE26712, GSE54388), respectively. We constructed a protein-protein interaction (PPI) interaction network with the overexpressed genes (72 genes) and performed gene enrichment analysis. In the PPI networks, three proteins; TTK Protein Kinase (TTK), NIMA Related Kinase 2 (NEK2), and cyclin-dependent kinase (CDK1) with higher node degrees were further evaluated as therapeutic targets for our novel multi-target small molecule NSC777201. We found that the upregulated DEGs were enriched in KEGG and gene ontologies associated with ovarian cancer progression, female gamete association, otic vesicle development, regulation of chromosome segregation, and therapeutic failure. In addition to the PPI network, ingenuity pathway analysis also implicate TTK, NEK2, and CDK1 in the elevated salvage pyrimidine and pyridoxal pathways in ovarian cancer. The TTK, NEK2, and CDK1 are over-expressed, demonstrating a high frequency of genetic alterations, and are associated with poor prognosis of ovarian cancer cohorts. Interestingly, NSC777201 demonstrated anti-proliferative and cytotoxic activities (GI50 = 1.6 µM~1.82 µM and TGI50 = 3.5 µM~3.63 µM) against the NCI panels of ovarian cancer cell lines and exhibited a robust interaction with stronger affinities for TTK, NEK2, and CDK1, than do the standard drug, paclitaxel. NSC777201 displayed desirable properties of a drug-like candidate and thus could be considered as a novel small molecule for treating ovarian carcinoma.

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Section: Resultsmentioning

confidence: 87%