Rabbit Anti-Human NOLC1 (a.a. 621-699) Polyclonal antibody

Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the standard first-line therapy for patients with chronic-phase CML. However, TKIs cannot eliminate quiescent leukemia stem cells (LSCs) which persist in all patients on long-term therapy and provides a reservoir for disease progression and recurrence. Many researches have confirmed that TKI-resistant LSCs compartment can be captured within CD26(+) fraction. In order to analyze distinctive biological characteristics of TKI-resistant LSCs, we isolated the CD34(+) CD38(-)CD26(+), CD34(+) CD38(-)CD26(-)and CD34(+) CD38(+) cells from 8 CML patients utilizing magnetic and flow sorting, and analyzed the global proteomic expression through high-resolution LC-MS/MS analysis. In the work, we discovered that a list of dysregulated proteins involved in energy metabolism and carcinogenesis, including PPARD, ILl-RAP, HNF, S15A2, PCLO, VA0D1, CKLF5, were extremely upregulated in the CD26(+) LSCs while some majoring in DNA mismatch repair or related to cell senescence, such as MLH3, NOLC1, were downregulated. Additionally, we verified the upregulation of PPARD in both CML patients-derived CD26(+) LSCs and donor-derived BCR-ABL1 overexpressed HSCs. These results open in turn new therapeutic avenues for targeting TKI-insensitive LSCs. (C) 2019 Elsevier Inc. All rights reserved.

Adjuvant chemotherapy has become the frequently adopted standard therapeutic approach for non-small cell lung cancer (NSCLC). However, the development of multidrug resistance (MDR) is a major obstacle contributing to the failure of chemotherapy. This study aimed to identify genes associated with MDR development that predict tumor response to chemotherapy in NSCLC. In the present study, a multidrug-resistant NSCLC cell sub-line, A549/MDR, was established from the A549/DDP cell line and characterized. The resistance index (RI) of this subline was calculated according to the IC50 of A549/MDR relative to the parental A549/DDP cells. The gene expression profiles of A549/DDP and A549/MDR were obtained using an oligonucleotide microarray (Agilent SureHyb microarray chip). The microarray results were validated by qRT-PCR and selected genes were analyzed by in vitro loss-of-function experiments. Gene expression profiling identified 921 differentially expressed genes (DEGs) according to the selection criteria, in which 541 genes were upregulated and 380 genes were downregulated in A549/MDR compared with A549/DDP cells. We found that these DEGs are involved in diverse biological processes, including ribonucleoprotein complex, drug metabolism, the Hippo signaling pathway and transcriptional misregulation. NOLC1, as one of the identified DEGs, was confirmed to be overexpressed in A549/MDR cells and its knockdown significantly enhanced the drug sensitivity of A549/MDR cells in response to multidrug treatment. Furthermore, knockdown of NOLC1 downregulated the expression levels of drug resistance-associated molecules (LRP and MDR1) in A549/MDR cells. These findings provide a new and comprehensive expression profile of MDR in NSCLC cells. Identification and validation of NOLC1 might be a promising therapeutic strategy for the management of MDR of NSCLC patients.