PMID- 32195025
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 10
IP  - 2
DP  - 2020
TI  - Administration of trastuzumab with heart irradiation induced acute cardiotoxicity 
      in mice.
PG  - 536-544
AB  - Cardiac toxicity is one of the major advese effect associated with thoracic 
      irradiation. Breast cancer patients with human epidermal factor receptor-2 
      (Her-2) overexpression could be indicated for both radiation and anti-Her2 target 
      therapy. We aimed to investigate the early detection of radiation and Trastuzumab 
      (TRZ) induced acute cardiotoxicity in mice. In the present study, the heart of 
      animal was subjected to irradiation (IR, 14 Gy/1 Fx), TRZ was intraperitonealy 
      (i.p.) administrated to mice in 2 weeks (6 fractions). The IR plus TRZ group 
      received heart IR after TRZ. We found that body weight of mouse in treatment 
      groups reduced significantly as compared with that of mouse in control group 
      (P<0.05). At day 21, the diastolic function of mice decreased significantly in IR 
      plus TRZ group compared with control group measured by E/E' parameter using 
      echocardiography (57.72 vs 40.82, P<0.05). The left ventricular posterior wall 
      (LVPW) and interventricular septum (IVS) were also increased significantly in 
      diastolic phase at day 21 in the combined group compared with TRZ alone (LVPW: 
      0.95 mm vs 0.70 mm, P<0.05; IVS: 0.94 mm vs 0.65 mm P<0.05). Moreover, 
      hematoxylin and eosin (HE) staining of cardiac tissue showed that the arrangement 
      of myocardial cell was disordered in the combined group with vacuolar and 
      adipocyte changes, as well as the loose of structure of myocardial cells and the 
      pyknosis of the nucleus. Moderate damage was observed in irradiation-treated 
      group and TRZ-treated group. The expressions of gamma-H2AX, vascular cell adhesion 
      molecule-1 (VCAM-1) and von Willebrand Factor (vWF) were remarkedly appeared in 
      co-treatment group. Heart irradiation combined with TRZ treatment simultaneously 
      might cause acute cardiac toxicity in terms of the parameter of E/E', LVPW and 
      IVS. Our results suggest that the diastolic function could detect the early stage 
      of acute cardiotoxicity in heart exposed to irradiation and TRZ co-treatment in 
      mice. The DNA injury and microangiopathy might involve in cardiac injury that 
      aggravated by radiation and Trastuzumab treatments.
CI  - AJCR Copyright (c) 2020.
FAU - Yi, Peiqiang
AU  - Yi P
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Li, Huan
AU  - Li H
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Fang, Yuehua
AU  - Fang Y
AD  - Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine Shanghai, China.
FAU - Su, Jun
AU  - Su J
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Xu, Cheng
AU  - Xu C
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Cao, Lu
AU  - Cao L
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Li, Min
AU  - Li M
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
FAU - Chen, Jiayi
AU  - Chen J
AD  - Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20200201
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC7061744
OTO - NOTNLM
OT  - Trastuzumab
OT  - cardiotoxcity
OT  - echocardiography
OT  - radiation
COIS- None.
EDAT- 2020/03/21 06:00
MHDA- 2020/03/21 06:01
PMCR- 2020/02/01
CRDT- 2020/03/21 06:00
PHST- 2020/01/19 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/03/21 06:00 [entrez]
PHST- 2020/03/21 06:00 [pubmed]
PHST- 2020/03/21 06:01 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2020 Feb 1;10(2):536-544. eCollection 2020.