MARC details
000 -LEADER |
fixed length control field |
03135nam a22004937a 4500 |
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
fixed length control field |
170505s20162016 xxu||||| |||| 00| 0 eng d |
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER |
International Standard Serial Number |
1949-2553 |
040 ## - CATALOGING SOURCE |
Original cataloging agency |
Ovid MEDLINE(R) |
099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) |
PMID |
28157711 |
245 ## - TITLE STATEMENT |
Title |
The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma. |
251 ## - Source |
Source |
Oncotarget. 8(8):12576-12595, 2017 Feb 21 |
252 ## - Abbreviated Source |
Abbreviated source |
Oncotarget. 8(8):12576-12595, 2017 Feb 21 |
253 ## - Journal Name |
Journal name |
Oncotarget |
260 ## - PUBLICATION, DISTRIBUTION, ETC. |
Year |
2017 |
260 ## - PUBLICATION, DISTRIBUTION, ETC. |
Manufacturer |
FY2017 |
266 ## - Date added to catalog |
Date added to catalog |
2017-05-06 |
520 ## - SUMMARY, ETC. |
Abstract |
Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation. Reverse Phase Protein Array (RPPA) and immunoblot analyses show that both trametinib and MBZ inhibit the MAPK pathway, and cluster analysis revealed a protein cluster showing strong MBZ+trametinib - inhibited phosphorylation of MEK and ERK within 10 minutes, and its direct and indirect downstream targets related to stress response and translation, including ElK1 and RSKs within 30 minutes. Downstream ERK targets for cell cycle, including cMYC, were down-regulated, consistent with S- phase suppression by MBZ+trametinib, while apoptosis markers, including cleaved caspase-3, cleaved PARP and a sub-G1 population, were all increased with time. These data suggest that MBZ, a well-tolerated off-patent approved drug, should be considered as a therapeutic option in combination with trametinib, for patients with NRASQ61mut or other non-V600E BRAF mutant melanomas. |
546 ## - LANGUAGE NOTE |
Language note |
English |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Cell Proliferation/de [Drug Effects] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Mebendazole/pd [Pharmacology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Melanoma/pa [Pathology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Pyridones/pd [Pharmacology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
*Pyrimidinones/pd [Pharmacology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Animals |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Antinematodal Agents/pd [Pharmacology] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Cell Line, Tumor |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
GTP Phosphohydrolases |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Humans |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Immunoblotting |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Melanoma/ge [Genetics] |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Membrane Proteins |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Mice |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Protein Array Analysis |
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM |
Topical term or geographic name entry element |
Xenograft Model Antitumor Assays |
651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME |
Institution |
MedStar Franklin Square Medical Center |
657 ## - INDEX TERM--FUNCTION |
Medline publication type |
Journal Article |
700 ## - ADDED ENTRY--PERSONAL NAME |
Local Authors |
Abdussamad, Maryam |
700 ## - ADDED ENTRY--PERSONAL NAME |
Local Authors |
Zapas, John |
700 ## - ADDED ENTRY--PERSONAL NAME |
Local Authors |
Zhou, Hengbo |
790 ## - Authors |
All authors |
Abdussamad M, Atkins MB, Byers SW, Calvert V, Chen YS, Dakshanamurthy S, Fang HB, Gaur A, Petricoin EF, Rosenthal DS, Simbulan-Rosenthal CM, Zapas J, Zhou H |
856 ## - ELECTRONIC LOCATION AND ACCESS |
DOI |
<a href="https://dx.doi.org/10.18632/oncotarget.14990">https://dx.doi.org/10.18632/oncotarget.14990</a> |
Public note |
https://dx.doi.org/10.18632/oncotarget.14990 |
942 ## - ADDED ENTRY ELEMENTS (KOHA) |
Koha item type |
Journal Article |
Item type description |
Article |