Abstract
We here explore the soluble Human Leukocyte Antigen-G (sHLA-G) expression level as clinical biomarker in metastatic colorectal cancer (mCRC). To this aim the sHLA-G protein was measured in plasma samples of 40 patients with mCRC treated with the FOLFIRI (irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and leucovorin (LV)) regimen. The results suggest a link between HLA-G levels and irinotecan (CPT-11) pharmacokinetic, leading to hypothesize a molecular interaction between sHLA-G and CPT-11. This interaction was confirmed experimentally by fluorescence spectroscopy. HLA-G is known to exist in a number of polymorphs that affect both the protein expression levels and its peptide-binding cleft. The interaction between HLA-G polymorphs and CPT-11 was explored by means of computational modelling, confirming the hypothesis that CPT-11 could actually target the peptide binding cleft of the most common HLA-G polymorphs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / secondary*
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Aged
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Antigens, Neoplasm / blood*
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Antigens, Neoplasm / chemistry
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Binding Sites
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Colorectal Neoplasms / drug therapy*
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Female
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Fluorouracil / administration & dosage
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HLA-G Antigens / blood*
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HLA-G Antigens / chemistry
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Humans
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Irinotecan / administration & dosage
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Irinotecan / blood*
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Irinotecan / pharmacokinetics
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Leucovorin / administration & dosage
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Male
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Middle Aged
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Models, Molecular
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Protein Binding
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Protein Conformation
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Protein Isoforms / blood
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Protein Isoforms / chemistry
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Solubility
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Spectrometry, Fluorescence
Substances
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Antigens, Neoplasm
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HLA-G Antigens
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Protein Isoforms
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Irinotecan
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Leucovorin
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Fluorouracil
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Camptothecin