TY - JOUR
T1 - How chemotherapy and radiotherapy damage the tissue
T2 - Comparative biology lessons from feather and hair models
AU - Gao, Qing Xiang
AU - Zhou, Gui Xuan
AU - Lin, Sung Jan
AU - Paus, Ralf
AU - Yue, Zhi Cao
N1 - Funding Information:
The authors have declared no conflicting interest. For the record, RP consults for various industry-sponsored research project that target CIA. This work is supported in part by funds from the Department of Science and Technology, Fujian Province 2017J01630 and NSFC 81673094, 31871468 to ZY, and by departmental start-up funds from the University of Miami to RP.
Funding Information:
We thank Dr Feng Shao (NIBS, Beijing, China) for providing the GasderminE?/? mice, and Dr Benhua Xu (The Union Hospital affiliated with Fujian Medical University, Fujian, China) for technical assistance to irradiate the mice.
Funding Information:
Fujian Province, Grant/Award Number: 2017J01630; National Natural Science Foundation of China, Grant/Award Number: 31871468 and 81673094
Publisher Copyright:
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2019/4
Y1 - 2019/4
N2 - Chemotherapy and radiotherapy are common modalities for cancer treatment. While targeting rapidly growing cancer cells, they also damage normal tissues and cause adverse effects. From the initial insult such as DNA double-strand break, production of reactive oxygen species (ROS) and a general stress response, there are complex regulatory mechanisms that control the actual tissue damage process. Besides apoptosis, a range of outcomes for the damaged cells are possible including cell cycle arrest, senescence, mitotic catastrophe, and inflammatory responses and fibrosis at the tissue level. Feather and hair are among the most actively proliferating (mini-)organs and are highly susceptible to both chemotherapy and radiotherapy damage, thus provide excellent, experimentally tractable model systems for dissecting how normal tissues respond to such injuries. Taking a comparative biology approach to investigate this has turned out to be particularly productive. Started in chicken feather and then extended to murine hair follicles, it was revealed that in addition to p53-mediated apoptosis, several other previously overlooked mechanisms are involved. Specifically, Shh, Wnt, mTOR, cytokine signalling and ROS-mediated degradation of adherens junctions have been implicated in the damage and/or reparative regeneration process. Moreover, we show here that inflammatory responses, which can be prominent upon histological examination of chemo- or radiotherapy-damaged hair follicle, may not be essential for the hair loss phenotype. These studies point to fundamental, evolutionarily conserved mechanisms in controlling tissue responses in vivo, and suggest novel strategies for the prevention and management of adverse effects that arise from chemo- or radiotherapy.
AB - Chemotherapy and radiotherapy are common modalities for cancer treatment. While targeting rapidly growing cancer cells, they also damage normal tissues and cause adverse effects. From the initial insult such as DNA double-strand break, production of reactive oxygen species (ROS) and a general stress response, there are complex regulatory mechanisms that control the actual tissue damage process. Besides apoptosis, a range of outcomes for the damaged cells are possible including cell cycle arrest, senescence, mitotic catastrophe, and inflammatory responses and fibrosis at the tissue level. Feather and hair are among the most actively proliferating (mini-)organs and are highly susceptible to both chemotherapy and radiotherapy damage, thus provide excellent, experimentally tractable model systems for dissecting how normal tissues respond to such injuries. Taking a comparative biology approach to investigate this has turned out to be particularly productive. Started in chicken feather and then extended to murine hair follicles, it was revealed that in addition to p53-mediated apoptosis, several other previously overlooked mechanisms are involved. Specifically, Shh, Wnt, mTOR, cytokine signalling and ROS-mediated degradation of adherens junctions have been implicated in the damage and/or reparative regeneration process. Moreover, we show here that inflammatory responses, which can be prominent upon histological examination of chemo- or radiotherapy-damaged hair follicle, may not be essential for the hair loss phenotype. These studies point to fundamental, evolutionarily conserved mechanisms in controlling tissue responses in vivo, and suggest novel strategies for the prevention and management of adverse effects that arise from chemo- or radiotherapy.
KW - adverse effect
KW - chemotherapy
KW - feather
KW - hair
KW - radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=85058946577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058946577&partnerID=8YFLogxK
U2 - 10.1111/exd.13846
DO - 10.1111/exd.13846
M3 - Article
C2 - 30457678
AN - SCOPUS:85058946577
VL - 28
SP - 413
EP - 418
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 4
ER -