関連する実験動画

Updated: Apr 29, 2026

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

音的ヘッジホッグ因子GLI1は,誘導性グルキュロニデーションによって薬剤耐性を授与する

Hiba Ahmad Zahreddine¹, Biljana Culjkovic-Kraljacic¹, Sarit Assouline²

¹Institute for Research in Immunology and Cancer and Department of Pathology and Cell Biology, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, Québec H3C 3J7, Canada.

|May 30, 2014

まとめ

サイトラビンとリバビリンに対する急性骨髄性白血病 (AML) の薬剤耐性は,GLI1.1をターゲットにすることで克服されました. 転写因子であるGLI1を阻害することで,薬剤の無活性化が防止され,AML治療の新たな戦略が提供されます.

科学分野:

腫瘍学腫瘍学
分子生物学は分子生物学である.
薬理学薬理学とは

背景:

薬剤耐性は,急性骨髄性白血病 (AML) 治療における重要な課題です.
サイトラビン (Ara-C) ベースの治療法では,AML患者の長期的な生存率は限られています.
eIF4E阻害剤であるリバビリンは,AMLにおいて初期的には有望であったが,耐性が発達した.

研究の目的:

AMLにおけるリバビリンとAra-Cに対する薬剤耐性のメカニズムを特定する.
この抵抗を媒介するGLI1とUGT1Aの役割を調査する.
AMLにおける薬剤耐性を克服するための戦略を探求する.

主な方法:

耐性AML細胞における遺伝子発現の分析.
薬物の代謝におけるGLI1の機能的役割を調査する.
臨床前モデルのGLI1阻害の有効性を評価する.

主要な成果:

グリオマ関連タンパク質1 (GLI1) とUDPグルキュロノシルトランスフェラーゼ (UGT1A) 酵素のレベルが上昇したのが,耐性細胞で観察されました.
GLI1は,リバビリンとAra-CのUGT1A依存型グルキュロニデーションを誘発するのに十分であることが判明し,薬剤耐性につながる.
GLI1の抑制は,遺伝的または薬理的に,リバビリンとAra-C.に対する感受性を回復させた.

結論:

AMLにおけるGLI1とUGT1Aを含む新薬耐性のメカニズムが特定されました.
GLI1は,グルクロン化によるリバビリンとAra-Cの不活性化において重要な役割を果たします.
GLI1をターゲットにすることは,AML患者の薬剤耐性を克服するための潜在的な治療戦略です.

さらに関連する動画

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

関連する概念動画

Phase II Reactions: Glucuronidation

Phase II Reactions: Glucuronidation

Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...

Drug Metabolism: Phase II Reactions

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...

Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...