PMID- 30292832
OWN - NLM
STAT- MEDLINE
DCOM- 20190426
LR  - 20190426
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 360
DP  - 2018 Dec 1
TI  - FAK alleviates radiation-induced rectal injury by decreasing apoptosis.
PG  - 131-140
LID - S0041-008X(18)30465-4 [pii]
LID - 10.1016/j.taap.2018.10.007 [doi]
AB  - Radiation-induced rectal injury is closely related with radiotherapy efficiency. 
      Here, we investigated the effect of focal adhesion kinase (FAK) in 
      radiation-induced rectal injury. Peripheral blood samples of patients with rectal 
      cancer were collected prior to radiotherapy. Differentially expressed genes and 
      copy number variations (CNVs) were analyzed by microarray analysis. The CTCAE 
      v3.0 toxicity grades were used to assess acute rectal injury. The 
      radiosensitivity of human intestinal epithelial crypt (HIEC) cells were assayed 
      by colony formation, mitochondrial membrane potential, flow cytometry and western 
      blotting. The rectums of C57BL/6 mice were X-irradiated locally with a single 
      dose of 15 Gy. The effect of FAK on radiation-induced injury was investigated by 
      hematoxylin-eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL), immunohistochemistry (IHC) and quantitative 
      real-time PCR (qRT-PCR). FAK mRNA level was inversely correlated with rectal 
      injury severity in patient samples. A CNV amplification located on chromosome 8 
      was closely related with FAK. Further functional assays revealed increased levels 
      of gammaH2AX expression and apoptosis-related proteins in FAK-silenced HIEC cells. 
      The ratio of TUNEL, cl-caspase-3, cyto-c and bax/bcl-2 expression in the rectum 
      mucosa treated with a FAK inhibitor increased significantly. These results 
      demonstrated that FAK reduced radiation-induced rectal injury by decreasing 
      apoptosis.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Li, Jun-Jun
AU  - Li JJ
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Tu, Wen-Zhi
AU  - Tu WZ
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Chen, Xu-Ming
AU  - Chen XM
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Ying, Hou-Yu
AU  - Ying HY
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Chen, Ying
AU  - Chen Y
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Ge, Yu-Long
AU  - Ge YL
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Pathology, Cancer Hospital of Handan, Handan 056001, China.
FAU - Xu, Yi
AU  - Xu Y
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Chen, Ting-Feng
AU  - Chen TF
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China.
FAU - Zhang, Xiao-Wei
AU  - Zhang XW
AD  - Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, 
      China.
FAU - Ye, Jin-Jun
AU  - Ye JJ
AD  - Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing Medical 
      University, Nanjing 210009, China. Electronic address: jjye2004@163.com.
FAU - Liu, Yong
AU  - Liu Y
AD  - Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 201620, China. Electronic address: 
      liuyongrt@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181004
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Histones)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - DNA Copy Number Variations/physiology
MH  - Female
MH  - Focal Adhesion Kinase 1/*metabolism
MH  - Histones/metabolism
MH  - Humans
MH  - In Situ Nick-End Labeling/methods
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Radiation Injuries/*metabolism
MH  - Radiation Tolerance/physiology
MH  - Rectum/*metabolism
MH  - bcl-2-Associated X Protein/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - FAK
OT  - Radiosensitivity
OT  - Radiotherapy
OT  - Rectal injury
EDAT- 2018/10/08 06:00
MHDA- 2019/04/27 06:00
CRDT- 2018/10/08 06:00
PHST- 2018/07/22 00:00 [received]
PHST- 2018/10/01 00:00 [revised]
PHST- 2018/10/04 00:00 [accepted]
PHST- 2018/10/08 06:00 [pubmed]
PHST- 2019/04/27 06:00 [medline]
PHST- 2018/10/08 06:00 [entrez]
AID - S0041-008X(18)30465-4 [pii]
AID - 10.1016/j.taap.2018.10.007 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2018 Dec 1;360:131-140. doi: 10.1016/j.taap.2018.10.007. 
      Epub 2018 Oct 4.