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1.
Eur Phys J Plus ; 138(5): 383, 2023.
Article in English | MEDLINE | ID: mdl-37192841

ABSTRACT

Air transportation systems are a foundational infrastructure for the human's society. The lack of systematic and detailed investigation on a large amount of records for air flights has blocked seriously the deep understanding of the systems. By using the American domestic passenger flight records from 1995 to 2020, we constructed the air transportation networks and calculated the betweenness and the eigenvector centralities for the airports. It is found that in terms of eigenvector centrality, 15-30% airports in the unweighted and undirected networks behave anomalous. The anomalies disappear after considering the information of link weights or directionalites. Five widely used models for air transportation networks are evaluated, results for which tell us that the spatial constraints are required to eliminate the anomalies detected by the eigenvector centrality, and provide us some references for selecting the parameters in the models. We hope the empirical benchmarks reported in this paper can stimulate much more works on theoretical models for air transportation systems.

2.
Mol Med ; 20: 390-9, 2014 Sep 08.
Article in English | MEDLINE | ID: mdl-25105301

ABSTRACT

Lapatinib, a tyrosine kinase inhibitor, is used in the treatment of advanced or metastatic breast cancer overexpressing human epidermal receptor 2 (HER2). Lapatinib can modulate the function of ATP-binding cassette (ABC) transporters (ABCB1 and ABCG2), which are the major mechanism responsible for multidrug resistance (MDR) in cancer. In this study, we investigated the effect of lapatinib on multidrug resistance-associated protein 1 (MRP1 [ABCC1]), MRP2 (ABCC2), MRP4 (ABCC4) and lung relative resistance protein (LRP) drug efflux pumps. We demonstrated that lapatinib could enhance the efficacy of conventional chemotherapeutic agents in MRP1-overexpressing cells in vitro and in vivo, but no effect in MRP2-, MPR4- and LRP-overexpressing cells. Furthermore, lapatinib significantly increased the accumulation of rhodamine 123 (Rho123) and doxorubicin (DOX) in MRP1-overexpressing cells. However, lapatinib did not alter the protein or mRNA expression levels of MRP1. Further studies showed that the level of phosphorylation of AKT and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were not altered at the indicated concentrations of lapatinib. In conclusion, lapatinib enhanced the efficacy of conventional chemotherapeutic agents in MRP1-overexpressing cells by inhibiting MRP1 transport function without altering the level of AKT or ERK1/2 phosphorylation. These findings will encourage the clinical research of lapatinib combined with conventional chemotherapeutic drugs in MRP1-overexpressing cancer patients.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Quinazolines/pharmacology , Animals , Antineoplastic Agents/therapeutic use , Biological Transport/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cisplatin/pharmacology , Doxorubicin/pharmacology , Drug Synergism , Extracellular Signal-Regulated MAP Kinases/metabolism , HEK293 Cells , Humans , Lapatinib , Mice , Mice, Nude , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , NIH 3T3 Cells , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Quinazolines/therapeutic use , Tumor Burden/drug effects , Vincristine/pharmacology , Vincristine/therapeutic use
3.
Molecules ; 19(3): 3356-75, 2014 Mar 19.
Article in English | MEDLINE | ID: mdl-24651611

ABSTRACT

Incomplete chemotherapeutic eradication of leukemic CD34⁺CD38⁻ stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our results showed that ABCB1 and ABCG2 were preferentially expressed in leukemic CD34⁺CD38⁻ cells. Nilotinib significantly enhanced the cytotoxicity of doxorubicin and mitoxantrone in CD34⁺CD38⁻ cells and led to increased apoptosis. Moreover, nilotinib strongly reversed multidrug resistance and increased the intracellular accumulation of rhodamine 123 in primary leukemic blasts overexpressing ABCB1 and/or ABCG2. Studies with ABC transporter-overexpressing carcinoma cell models confirmed that nilotinib effectively reversed ABCB1- and ABCG2-mediated drug resistance, while showed no significant reversal effect on ABCC1- and ABCC4-mediated drug resistance. Results from cytotoxicity assays showed that CD34⁺CD38⁻ cells exhibited moderate resistance (2.41-fold) to nilotinib, compared with parental K562 cells. Furthermore, nilotinib was less effective in blocking the phosphorylation of Bcr-Abl and CrkL (a substrate of Bcr-Abl kinase) in CD34⁺CD38⁻ cells. Taken together, these data suggest that nilotinib particularly targets CD34⁺CD38⁻ stem cells and MDR leukemia cells, and effectively enhances the efficacy of chemotherapeutic drugs by blocking the efflux function of ABC transporters.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Antineoplastic Agents/pharmacology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Pyrimidines/pharmacology , ADP-ribosyl Cyclase 1/metabolism , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/genetics , Animals , Antigens, CD34/metabolism , Cell Line, Tumor , Drug Resistance, Multiple/drug effects , Drug Resistance, Multiple/genetics , Drug Synergism , Fusion Proteins, bcr-abl/antagonists & inhibitors , Gene Expression , Humans , Inhibitory Concentration 50 , Leukemia , Mice , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism
4.
Biochem Pharmacol ; 85(11): 1619-25, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23583455

ABSTRACT

The side population cells characterized by the ability to transport Hoechst 33342 out of cells have been identified as cancer stem-like cells. ABCG2 is found to confer the side population (SP) phenotype, multidrug resistance (MDR) and tumor recurrence. In this study, we found secalonic acid D (SAD), a metabolite of marine-derived mangrove endophytic fungus, showed potent anticancer effect on ABCB1-, ABCC1- and ABCG2- overexpressing multidrug resistance cells by MTT assay. Furthermore, SAD could down-regulate the expression of ABCG2 and decrease the percentage of SP cells in lung cancer cells. The MTT assay showed the sorted SP cells were sensitive to SAD and we also found SAD could inhibit the sphere-forming ability of SP cells. Although SAD did not affect the expression of ABCG2 mRNA, it shortened the half-life of ABCG2 protein by activating calpain 1. These results implicated that SAD could be developed as a leading compound to target cancer stem cells and would be a promising agent to treat lung cancer patients.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Down-Regulation/drug effects , Neoplasm Proteins/metabolism , Xanthones/pharmacology , ATP Binding Cassette Transporter, Subfamily G, Member 2 , Blotting, Western , Calpain/metabolism , Cell Line, Tumor , Flow Cytometry , Humans , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
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