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Inhibition of proteasome deubiquitinating activity as a new cancer therapy
Treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model, showing that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target. Expand
Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer
It is reported that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials and it is shown that all five compounds inhibit mitochondrial respiration, suggesting that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Expand
Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments
The small molecule VLX600 is identified as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues and displays tumour growth inhibition in vivo, suggesting that tumours in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function. Expand
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones fromExpand
Induction of tumor cell apoptosis by a proteasome deubiquitinase inhibitor is associated with oxidative stress.
The data show that enhanced oxidative stress and ER stress are major determinants of the strong apoptotic response elicited by the 19S DUB inhibitor b-AP15. Expand
Allelic imbalance in gene expression as a guide to cis-acting regulatory single nucleotide polymorphisms in cancer cells
This study established a process for systematic screening for cis-acting rSNPs using experimental detection of AI as an initial approach and identified differential protein binding from a nuclear extract between the SNP alleles. Expand
Abstract C84: Inhibition of proteasome deubiquitinating activity as a novel cancer therapy.
Tumor cells display enhanced sensitivity to disruptions in the ubiquitin-proteasome system making this an attractive target for the development of anti-cancer therapies. Ubiquitin-tagged substratesExpand
Polycomb Target Genes Are Silenced in Multiple Myeloma
The results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex, which resulted in gene upregulation, reduced tumor load and increased overall survival in the immunocompetent 5T33MM in vivo model. Expand
Molecular Markers for Discrimination of Benign and Malignant Follicular Thyroid Tumors
The results indicate that a small number of genes can be useful to distinguish follicular adenomas from follicular carcinomas and have the potential for molecular classification of follicular thyroid tumors and for providing improved understanding of the molecular mechanisms involved in thyroid malignancies. Expand
Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system.
This new 3-D spheroid cell culture system provides a convenient and clinically relevant model for the identification and characterization of cancer drugs for solid tumors. Expand