Genetic variations of orosomucoid genes associated with serum alpha‐1‐acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer

Katori, Noriko; Sai, Kimie; Saito, Yoshiro; Fukushima-Uesaka, Hiromi; Kurose, Kouichi; Yomota, Chikako; Kawanishi, Toru; Nishimaki-Mogami, Tomoko; Naito, Mikihiko; Sawada, Jun Ichi; Kunitoh, Hideo; Nokihara, Hiroshi; Sekine, Ikuo; Ohe, Yuichiro; Yoshida, Teruhiko; Matsumura, Yasuhiro; Saijo, Nagahiro; Yamamoto, Noboru; Okuda, Haruhiro; Tamura, Tomohide

doi:10.1002/jps.22648

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…In addition, ORM1 has been shown to enhance endothelial cell migration and capillary tube formation in vitro (40). Moreover, several reports suggested that the serum levels of α-1-acid glycoprotein influenced the pharmacokinetics (PK)/pharmacodynamics (PD) of chemotherapy drugs such as docetaxel, PTX and imatinib (41)(42)(43)(44). As these reports remarked, α-1-acid glycoprotein may function as a carrier of PTX from the serum into the liver via the α-1-acid glycoprotein receptors, and this might result in the enhancement of the PTX metabolism.…”

Section: Discussionmentioning

confidence: 99%

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Wang

Yin

et al. 2016

International Journal of Oncology

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Abstract. Emerging drug resistance in epithelial ovarian cancer (EOC) thwarted progress in platinum-based chemotherapy, resulting in increased mortality, morbidity and healthcare costs. The aim of this study was to detect the responses induced by chemotherapy at protein and metabolite levels, and to search for new plasma markers that can predict resistance to platinum-based chemotherapy in EOC patients, leading to improved clinical response rates. Serum samples were collected and subjected to proteomic relative quantitation analysis and metabolomic analysis. Differentially expressed proteins and metabolites were subjected to bioinformatics and statistical analysis. Proteins that played a key role in platinum resistance were validated by western blotting and enzyme-linked immunosorbent assay (ELISA). Metabolites that were the main contributors to the groups and closely with clinical characteristics were identified based on the database using nuclear magnetic resonance (NMR). In total, 248 proteins from two independent experiments were identified using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach. Among them, FN1, SERPINA1, GPX3 and ORM1 were chosen for western blotting and ELISA validation. Platinum resistance likely associated with differentially expressed proteins and FN1, SERPINA1 and ORM1 may play a positive role in chemotherapy. HPLC-MS analysis of four groups revealed a total of 25,800 metabolic features, of which six compounds were chosen for candidate biomarkers and identified based on the database using NMR. The metabolic signatures of normal control (NC), platinum-sensitive (PTS) and platinum-resistant (PTR) groups were clearly separated from each other.Those findings may provide theoretical clues for the prediction of chemotherapeutic response and reverse of drug resistance, even lead to novel targets for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Wang

Yin

et al. 2016

International Journal of Oncology

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“…The AGP molecule consists of a single polypeptide chain of 183 amino acids with up to five asparaginyl linked glycans 107 . In addition to the high heterogeneity of glycans, polymorphisms have also been identified in the protein portion or AGP 108 .…”

Section: Stereoselectivity Of Plasma Protein Binding To Chiral Drugsmentioning

confidence: 99%

Stereoselective binding of chiral drugs to plasma proteins

et al. 2013

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Chiral drugs show distinct biochemical and pharmacological behaviors in the human body. The binding of chiral drugs to plasma proteins usually exhibits stereoselectivity, which has a far-reaching influence on their pharmacological activities and pharmacokinetic profiles. In this review, the stereoselective binding of chiral drugs to human serum albumin (HSA), α1-acid glycoprotein (AGP) and lipoprotein, three most important proteins in human plasma, are detailed. Furthermore, the application of AGP variants and recombinant fragments of HSA for studying enantiomer binding properties is also discussed. Apart from the stereoselectivity of enantiomer-protein binding, enantiomer-enantiomer interactions that may induce allosteric effects are also described. Additionally, the techniques and methods used to determine drug-protein binding parameters are briefly reviewed.

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“…The ORM 5′-flanking regions between −1097, −777 and +63, for ORM1, and −1092, −772 and +57, for ORM2, were amplified by polymerase chain reaction (PCR) from genomic DNA with wild type genotypes at the ORM1/2 promoter regions 17) using PrimeSTAR Max DNA polymerase (TaKaRa Bio Inc., Shiga, Japan) and primer sets that included EcoRV sites for cloning (Supplementary Table 1A). Amplified fragments were cloned into the firefly luciferase reporter vector, pGL4.12 (Promega, Madison, WI, U.S.A.) using an In-Fusion Dry-Down PCR Cloning Kit (Clontech, Mountain View, CA, U.S.A.), to obtain each full-length construct (FULL).…”

Section: Construction Of Orm-reporter Gene Plasmidsmentioning

confidence: 99%

Distal Promoter Regions Are Responsible for Differential Regulation of Human Orosomucoid-1 and -2 Gene Expression and Acute Phase Responses

Sai¹,

Kurose²,

Koizumi³

et al. 2014

Biological & Pharmaceutical Bulletin

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Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes, ORM1 and ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each ORM in HeLa cells. Luciferasereporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of ORM1 and ORM2 were compared under both basal and inducer-treated conditions. For ORM1 and ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for ORM1 after IL-1β treatment, while those for ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for ORM1, and at basal level and after inducer-treatments for ORM2. Higher transcription-induction activity in the distal promoter region was evident for ORM1 in the absence of C/EBPβ overexpression, and for ORM2 under C/EBPβ overexpression conditions. These findings suggest that the ORM distal promoter region differentially regulates expression of ORM genes at basal level and in acute phase responses.Key words orosomucoid; alpha 1 acid glycoprotein; distal promoter region; acute phase response; gene regulation Human orosomucoid (ORM), also known as alpha-1-acid glycoprotein, is an approximately 40-kDa acute-phase plasma protein. It has anti-inflammatory and immunomodulatory properties, and has effects on drug responses due to its drugbinding properties. 1-3)Human ORM is encoded by 2 genes, ORM1 and ORM2, with sequence homology across the coding region and the proximal promoter region (approximately 800-bp upstream from the transcription initiation site) of 94% and 98%, respectively.1-4) Despite this high homology, gene expressions of ORM1 and ORM2 are known to be differentially regulated. ORM1 is preferentially transcribed in human liver, a human hepatoma cell line and in transgenic mice carrying human ORM genes, 4,5) which may related to higher plasma concentration of ORM1 in human subjects.6-10) Both ORMs are increased in the patients with cancers, burnt injury or surgical operation, but their induction pattern varies according to pathophysiological conditions. [6][7][8][9][10] This may indicate that gene expression of ORM1 and ORM2 is differentially regulated; however, this possibility has not yet been evaluated. In the proximal promoter region of rodent orm, it is identified a glucocorticoid (GC) responsive element (GRE) and ...

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Genetic variations of orosomucoid genes associated with serum alpha‐1‐acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer

Cited by 10 publications

References 29 publications

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Stereoselective binding of chiral drugs to plasma proteins

Distal Promoter Regions Are Responsible for Differential Regulation of Human Orosomucoid-1 and -2 Gene Expression and Acute Phase Responses

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