Resistance to antifolates

Zhao, Rongbao; Goldman, I. David

doi:10.1038/sj.onc.1206946

Cited by 237 publications

(251 citation statements)

References 281 publications

(232 reference statements)

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“…Unfortunaltely, the resistance in cancer cells often compromises the efficacy of the anticancer therapy with MTX (Zhao and Goldman 2003). In addition, the conventional MTX delivery strategies often lead to undesirable shortcomings, such as the severe side effects associate with the treatment, including neurologic toxicity, renal failure and mucositis (Banerjee et al 2002;Rubino 2001).…”

Section: Introductionmentioning

confidence: 99%

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

et al. 2015

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The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promissing approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pHresponsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials.Outstandingly, the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-senstive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent.

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Section: Introductionmentioning

confidence: 99%

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

et al. 2015

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“…Consistently, alternative phosphorylations also have been reported to render Sp1 a transcriptional repressor. 29,30 An important mechanism of antifolate resistance in ALL 31 and other malignancies 32 is impaired antifolate transport due to loss of RFC function, 2,33 resulting from mutational inactivation 34 and/or transcriptional silencing. [9][10][11] This loss of function, as we have recently shown in multiple antifolate-resistant human leukemia cell lines with defective antifolate uptake, is due either to mutations in the RFC gene 34 or decreased RFC mRNA levels caused by a methylation-independent transcriptional silencing of the RFC gene.…”

Section: Introductionmentioning

confidence: 99%

Loss of Sp1 function via inhibitory phosphorylation in antifolate-resistant human leukemia cells with down-regulation of the reduced folate carrier

Stark

Assaraf

2006

Blood

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“…After its entry into cells, MTX is rapidly converted to γ -glutamyl polyglutamates through the action of folylpolyglutamate synthetase, which sequentially adds up to six glutamyl residues to MTX (Goldman et al 1968;Shane 1989;Zhao and Goldman 2003). This γ -linked sequential addition of glutamic acid residues enhances the intracellular retention of MTX.…”

Section: Extraction Of Mtx and Mtx-pgs From Rbcmentioning

confidence: 99%

Application of Fluorescence Polarization Immunoassay for Determination of Methotrexate-Polyglutamates in Rheumatoid Arthritis Patients

Hayashi

Fujimaki

Tsuboi

et al. 2008

Tohoku J. Exp. Med.

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Rheumatoid arthritis (RA) is a chronic disease characterized by the painful joints, inflammation, uncontrolled proliferation of synovial tissue and multisystem comorbidities. Weekly low-dose methotrexate (MTX) has been established as effective treatment in RA patients. MTX is converted to γ -glutamyl polyglutamates, an active form of MTX, through the action of folylpolyglutamate synthetase in the cells. MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) may be useful as a therapeutic marker of RA. However, the previously reported methods for the quantification of MTX and MTX-PGs in RBCs are impractical for clinical use due to time-consuming, laborious and high cost. We attempted to apply a method with the commercially available fluorescence polarization immunoassay (FPIA) kit. We found that anti-MTX monoclonal antibody showed the reactivity to 4-amino-10-methylpteroylheptaglutamic acid (MTX-PG 7 ) as equal to MTX. Good agreement was observed in the concentration-response curves between MTX and MTX-PG 7 spiked samples. Accordingly, the anti-MTX monoclonal antibody for FPIA appeared to show the equal reactivity to MTX and MTX-PGs. The recoveries of MTX and MTX-PG 7 from RBCs were 99.0% and 94.1%, respectively. Furthermore, we determined total MTX-PGs concentrations in RBCs of 71 patients with RA treated with weekly pulse MTX. Total MTX-PGs concentrations in 70% of the patients were found to be more than 50 nM that is the lower limit of MTX-PGs concentration in RBCs for expected therapeutic outcome. The routine measurement of total MTX-PGs concentration in RBCs might be useful for prediction about therapeutic outcome of MTX in RA patients.methotrexate; methotrexate-polyglutamate; rheumatoid arthritis; therapeutic drug monitoring; fluorescence polarization immunoassay.Tohoku

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Resistance to antifolates

Cited by 237 publications

References 281 publications

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

Loss of Sp1 function via inhibitory phosphorylation in antifolate-resistant human leukemia cells with down-regulation of the reduced folate carrier

Application of Fluorescence Polarization Immunoassay for Determination of Methotrexate-Polyglutamates in Rheumatoid Arthritis Patients

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