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通过新型DNA微阵列快速灵敏检测与伊立替康毒性相关的UGT1A1基因多态性

Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray.

作者信息

Tsunedomi Ryouichi, Hazama Shoichi, Okayama Naoko, Oka Masaaki, Nagano Hiroaki

机构信息

Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Faculty of Medicine, Ube, Japan.

出版信息

Cancer Sci. 2017 Jul;108(7):1504-1509. doi: 10.1111/cas.13272. Epub 2017 Jun 5.


DOI:10.1111/cas.13272
PMID:28474802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5497725/
Abstract

Recent developments in the field of human genomics have greatly enhanced the potential for precision and personalized medicine. We have developed a novel DNA microarray, using a 3-mm square chip coated with diamond-like carbon to enhance the signal-to-background ratio, for use as an in vitro diagnostic tool in precision medicine. To verify the genotyping effectiveness of this newly developed DNA microarray we examined UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in DNA extracted from patients with metastatic colorectal cancer. It is established that the polymorphisms of UGT1A128 and UGT1A16 are significantly associated with severe toxicity induced by the anti-cancer drug irinotecan. For each sample, the results obtained with the novel microarray platform were compared with those obtained using other, more established, methods, including direct sequencing and the Invader assay. The polymorphisms tested included a single nucleotide substitution (UGT1A16) and a TA-repeat polymorphism (UGT1A128), both of which were detected simultaneously and accurately using our method. Moreover, our method required 1.5-fold less time to assay and 20-fold less sample than those required by the Invader assay. In summary, our newly developed DNA microarray is more practical than established methods, and is at least as accurate; this will increase the efficiency of polymorphism detection prior to diagnosis and the commencement of treatment, and can feasibly be applied in precision medicine.

摘要

人类基因组学领域的最新进展极大地提升了精准医学和个性化医疗的潜力。我们开发了一种新型DNA微阵列,它采用涂有类金刚石碳的3平方毫米芯片来提高信号背景比,用作精准医学中的体外诊断工具。为了验证这种新开发的DNA微阵列的基因分型有效性,我们检测了转移性结直肠癌患者提取的DNA中的尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT1A1)多态性。已确定UGT1A128和UGT1A16的多态性与抗癌药物伊立替康诱导的严重毒性显著相关。对于每个样本,将使用新型微阵列平台获得的结果与使用其他更成熟方法(包括直接测序和入侵检测法)获得的结果进行比较。所检测的多态性包括一个单核苷酸取代(UGT1A16)和一个TA重复多态性(UGT1A128),使用我们的方法能够同时且准确地检测到这两种多态性。此外,与入侵检测法相比,我们的方法检测所需时间减少了1.5倍,样本量减少了20倍。总之,我们新开发的DNA微阵列比现有方法更实用,且至少具有相同的准确性;这将提高诊断和治疗开始前多态性检测的效率,并可切实应用于精准医学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26cf/5497725/318807711552/CAS-108-1504-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26cf/5497725/318807711552/CAS-108-1504-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26cf/5497725/318807711552/CAS-108-1504-g001.jpg

相似文献

[1]
Rapid and sensitive detection of UGT1A1 polymorphisms associated with irinotecan toxicity by a novel DNA microarray.

Cancer Sci. 2017-7

[2]
Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study.

Cancer Biol Ther. 2011-11-1

[3]
Screening for adverse reactions to irinotecan treatment using the Invader UGT1A1 Molecular Assay.

Expert Rev Mol Diagn. 2006-7

[4]
UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma.

Cancer. 2008-5-1

[5]
UGT1A1 6/28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients.

Med Oncol. 2013-5-18

[6]
Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review.

Genet Med. 2009-1

[7]
Increased frequency of uridine diphosphate glucuronosyltransferase 1A1 7/7 in patients experiencing severe irinotecan-induced toxicities.

Clin Colorectal Cancer. 2007-7

[8]
Invader UGT1A1 molecular assay for irinotecan toxicity. A genetic test for an increased risk of toxicity from the cancer chemotherapy drug irinotecan (Camptosar).

Med Lett Drugs Ther. 2006-5-8

[9]
Rapid detection of UGT1A1 gene polymorphisms by newly developed Invader assay.

Clin Chem. 2004-8

[10]
Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients.

Drug Metab Pharmacokinet. 2016-2

引用本文的文献

[1]
C-Mannosyl tryptophan is a novel biomarker for thrombocytosis of myeloproliferative neoplasms.

Sci Rep. 2024-8-14

[2]
Development of a clinical microarray system for genetic analysis screening.

Pract Lab Med. 2022-12-23

[3]
Human variability in isoform-specific UDP-glucuronosyltransferases: markers of acute and chronic exposure, polymorphisms and uncertainty factors.

Arch Toxicol. 2020-8

[4]
Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in five Mouse Genotypes with a Background of FVB.

Pharm Res. 2018-4-10

本文引用的文献

[1]
Next-generation sequencing and empowering personalised cancer medicine.

Drug Discov Today. 2015-12

[2]
Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution.

Cancer Discov. 2014-10-7

[3]
A novel system for predicting the toxicity of irinotecan based on statistical pattern recognition with UGT1A genotypes.

Int J Oncol. 2014-10

[4]
Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and Japanese populations.

Mol Diagn Ther. 2014-6

[5]
Prospective phase II trial of second-line FOLFIRI in patients with advanced colorectal cancer including analysis of UGT1A1 polymorphisms: FLIGHT 2 study.

Anticancer Res. 2014-1

[6]
The quest to overcome resistance to EGFR-targeted therapies in cancer.

Nat Med. 2013-11-7

[7]
UGT1A1*6, 1A7*3, and 1A9*22 genotypes predict severe neutropenia in FOLFIRI-treated metastatic colorectal cancer in two prospective studies in Japan.

Cancer Sci. 2013-10-27

[8]
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.

N Engl J Med. 2013-9-12

[9]
UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism-directed phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer.

Anticancer Res. 2013-8

[10]
Genomics-driven oncology: framework for an emerging paradigm.

J Clin Oncol. 2013-4-15

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