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Terbinafine prevent...
Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression
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- Hu, Li-Peng (author)
- Shanghai Jiao Tong University
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- Huang, Wuqing (author)
- Fujian Medical University
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- Wang, Xu (author)
- Jiangsu University of Science and Technology
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- Xu, Chunjie (author)
- Shanghai Jiao Tong University
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- Qin, Wei-Ting (author)
- Shanghai Jiao Tong University
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- Li, Dongxue (author)
- Shanghai Jiao Tong University
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- Tian, Guangang (author)
- Shanghai Jiao Tong University
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- Li, Qing (author)
- Shanghai Jiao Tong University
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- Zhou, Yaoqi (author)
- Shanghai Jiao Tong University
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- Chen, Suyuan (author)
- Shanghai Jiao Tong University
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- Nie, Hui-Zhen (author)
- Shanghai Jiao Tong University
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- Hao, Yujun (author)
- Shanghai Jiao Tong University
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- Song, Jian (author)
- Shanghai Jiao Tong University
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- Zhang, Xue-Li (author)
- Shanghai Jiao Tong University
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- Sundquist, Jan (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Center for Primary Health Care Research,Icahn School of Medicine at Mount Sinai
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- Sundquist, Kristina (author)
- Lund University,Lunds universitet,Allmänmedicin, kardiovaskulär epidemiologi och levnadsvanor,Forskargrupper vid Lunds universitet,Allmänmedicin och klinisk epidemiologi,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine, Cardiovascular Epidemiology and Lifestyle,Lund University Research Groups,Family Medicine and Clinical Epidemiology,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Icahn School of Medicine at Mount Sinai,Center for Primary Health Care Research
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- Li, Jun (author)
- Shanghai Jiao Tong University
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- Jiang, Shu-Heng (author)
- Shanghai Jiao Tong University
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- Zhang, Zhi-Gang (author)
- Shanghai Jiao Tong University
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- Ji, Jianguang (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Family Medicine and Clinical Epidemiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Center for Primary Health Care Research
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 30:10, s. 3284-3299
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Hu, Li-Peng
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Huang, Wuqing
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Wang, Xu
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Xu, Chunjie
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Qin, Wei-Ting
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Li, Dongxue
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show more...
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Tian, Guangang
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Li, Qing
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Zhou, Yaoqi
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Chen, Suyuan
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Nie, Hui-Zhen
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Hao, Yujun
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Song, Jian
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Zhang, Xue-Li
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Sundquist, Jan
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Sundquist, Krist ...
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Li, Jun
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Jiang, Shu-Heng
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Zhang, Zhi-Gang
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Ji, Jianguang
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Molecular Therap ...
- By the university
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Lund University