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An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs

Development of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressin...

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Published in:Scientific reports 2022-02, Vol.12 (1), p.3093-3093, Article 3093
Main Authors: Tian, Tian, Miyazaki, Kanako, Chiba, Yuta, Funada, Keita, Yuta, Tomomi, Mizuta, Kanji, Fu, Yao, Kawahara, Jumpei, Han, Xue, Ando, Yuna, Funada, Ami, Yamada, Aya, Iwamoto, Tsutomu, Nakamura, Seiji, Takahashi, Ichiro, Fukumoto, Satoshi, Yoshizaki, Keigo
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creator Tian, Tian
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Chiba, Yuta
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Fu, Yao
Kawahara, Jumpei
Han, Xue
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Funada, Ami
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Nakamura, Seiji
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Fukumoto, Satoshi
Yoshizaki, Keigo
description Development of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressing side effects. Cyclophosphamide (CPA) is a commonly used anticancer drug and causes severe side effects in developing organs with intensive proliferation, including the teeth and hair. Using the organ culture model, we found that treatment with CPA disturbed the growth of tooth germs by inducing DNA damage, apoptosis and suppressing cellular proliferation and differentiation. Furthermore, low temperature suppressed CPA-mediated inhibition of organ development. Our ex vivo and in vitro analysis revealed that low temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase during CPA treatment. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our findings suggest that the side effects of anticancer drugs on organ development can be avoided by maintaining the internal environment under low temperature.
doi_str_mv 10.1038/s41598-022-06945-7
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subjects 631/136/2060
692/308/1426
Antineoplastic Agents - adverse effects
Antineoplastic drugs
Antitumor agents
Apoptosis
Cancer
Cell culture
Cell cycle
Cell Cycle Checkpoints - drug effects
Cell Proliferation - drug effects
Chemotherapy
Cyclophosphamide
Cyclophosphamide - adverse effects
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA Damage - drug effects
DNA Replication - drug effects
Drug development
Drugs
G1 phase
G1 Phase - drug effects
Humanities and Social Sciences
Humans
Hypoplasia
Low temperature
Models, Biological
multidisciplinary
Organ culture
Organ Culture Techniques
Phosphorylation
Science
Science (multidisciplinary)
Side effects
Temperature
title An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs
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