Project description:The investigators aim to assess the procedure time and miss rate of polyps when performing polypectomy in the colon on the way up* and down** or only on the way down**.
(* advancing the scope to the cecum, ** pulling back the scope after intubation of the cecum). Our hypothesis is that using the strategy to remove all visible polyps firstly on the way up and secondly on the way down is less time consuming and misses less polyps as with the strategy to remove polyps only on the way down.
Project description:Analysis of Drug transports as a mechanism of resistance to aurora kinase inhibition Parental and Taxol-resistant cell lines are compared for gene expression profile differences. 2 samples, fluor reversed
Project description:Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal–induced pERK rebound upregulated p38–FRA1–JUNB–CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death–predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction.
Project description:The clinical development of targeted therapies has been hampered by their limited intrinsic antitumor activity and the rapid emergence of resistance, highlighting the need to identify highly active and synergistic drug combinations. However, empirical synergistic drug screening approaches are challenging and elucidating the mechanisms that underlie such drug interactions is typically complex. Here we performed an expression based screen and network analyses to identify drugs amplyfiying the antitumor effects of NOTCH inhibition in T-ALL. These studies uncovered a novel and druggable synthetic lethal interaction between supression of protein translation and NOTCH inhibition in T-ALL. Our results illustrate the power of expression-based analyses towards the identification and functional characterization of new antitumor drug combinations for the treatment of human cancer.
Project description:Analysis of Drug transports as a mechanism of resistance to aurora kinase inhibition Parental and Taxol-resistant cell lines are compared for gene expression profile differences.
Project description:To investigate the mechanism associated with cis-platin intrinsic resistance, we established a model of early drug-tolerant persister cells by exposing lung adenocarcinoma cell lines to the drug for 24 h. Then, we analyzed the transcriptome using RNA-seq from 4 different lung adenocarcinoma cell lines.
Project description:Heroin addiction and withdrawal influence multiple physiological functions including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the immune system function and molecular inflammatory interactome particularly the cytokines and RNA regulatory network in heroin addicts undergoing withdrawal compared healthy controls.