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1.
EMBO Rep ; 23(2): e54260, 2022 02 03.
Article in English | MEDLINE | ID: mdl-34962350

ABSTRACT

Postdocs are at a challenging step in the career ladder and research organisations could do more to help them along the way.


Subject(s)
Career Choice , Research Personnel , Career Mobility , Humans
2.
Melanoma Res ; 27(1): 8-16, 2017 02.
Article in English | MEDLINE | ID: mdl-27776018

ABSTRACT

The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Carbazoles/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm , Glycosides/pharmacology , Melanoma/drug therapy , Melanoma/metabolism , Methylnitrosourea/analogs & derivatives , Neovascularization, Pathologic/prevention & control , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antigens, Neoplasm/genetics , Apoptosis/drug effects , CD24 Antigen/metabolism , Drug Resistance, Neoplasm/genetics , Endoglin/metabolism , Fluorescent Dyes/metabolism , Gene Expression/drug effects , Humans , Hyaluronan Receptors/metabolism , Intercellular Adhesion Molecule-1/metabolism , Male , Melanoma/blood supply , Melanoma/genetics , Methylnitrosourea/pharmacology , Middle Aged , Neoplasm Proteins/genetics , Neoplastic Stem Cells/metabolism , Nuclear Proteins/genetics , Phenotype , Phosphoprotein Phosphatases/genetics , Proto-Oncogene Proteins c-kit/metabolism , Rhodamine 123/metabolism , Tetraspanin 30/metabolism
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