PMID- 29113154
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 14
IP  - 5
DP  - 2017 Nov
TI  - Synergistic inhibitory effects of an engineered antibody-like molecule ATF-Fc and 
      trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse 
      model.
PG  - 5189-5196
LID - 10.3892/ol.2017.6896 [doi]
AB  - The overexpression of the oncogene human epidermal growth factor receptor 2 
      (HER-2) has been associated with decreased disease-free survival and is a marker 
      of poor prognosis of invasive breast cancer. Although the high efficacy of 
      trastuzumab, a drug that targets the HER-2 oncogene, has been widely recognized, 
      the efficiency of the treatment remains at ~30%. Therefore, novel effective 
      treatments are required for patients with recurrent metastatic breast cancer. The 
      present study aimed to investigate the effects of an engineered antibody-like 
      molecule administered alone or in combination with trastuzumab on the tumor 
      growth and metastasis of HER-2-positive breast cancer. Another aim was to 
      investigate novel cancer therapies for HER-2-positive breast cancer. The 
      engineered antibody-like molecule consists of the amino-terminal fragment (ATF) 
      of human urokinase-type plasminogen (uPA) and is conjugated with the Fc fragment 
      of human immunoglobulin G1 (ATF-Fc). The anti-cancer effect of ATF-Fc (alone and 
      in combination with trastuzumab) on tumor cells and in a nude mouse tumor model 
      was evaluated by detecting the expression of uPA, urokinase plasminogen activator 
      receptor (uPAR) and HER-2. In vitro experiments demonstrated that specifically 
      blocking the uPA-uPAR and HER-2 signaling pathways may effectively promote the 
      apoptosis of breast cancer cells. Additionally, ATF-Fc-induced cell death in 
      HER-2-positive breast cancer cells was observed in vivo. When ATF-Fc was 
      administered in combination with trastuzumab, cell death was increased and breast 
      cancer metastasis was reduced. The novel engineered antibody-like molecule ATF-Fc 
      was able to inhibit HER-2-positive breast cancer cell growth and metastasis by 
      interfering with uPA and its receptor (uPA-uPAR) system. Additionally, the 
      antibody-like molecule exhibits a synergistic inhibitory effect when administered 
      in combination with trastuzumab.
FAU - Zhou, Hongwei
AU  - Zhou H
AD  - Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA 
      General Hospital, Beijing 100048, P.R. China.
FAU - Wang, Hongwei
AU  - Wang H
AD  - Department of Pathology, The First Affiliated Hospital of Chinese PLA General 
      Hospital, Beijing 100048, P.R. China.
FAU - Yu, Guangyuan
AU  - Yu G
AD  - Department of Medicine, The First Affiliated Hospital of Chinese PLA General 
      Hospital, Beijing 100048, P.R. China.
FAU - Wang, Zhihong
AU  - Wang Z
AD  - Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA 
      General Hospital, Beijing 100048, P.R. China.
FAU - Zheng, Xi
AU  - Zheng X
AD  - Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA 
      General Hospital, Beijing 100048, P.R. China.
FAU - Duan, Haifeng
AU  - Duan H
AD  - Beijing Institute of Radiation Medicine, Beijing 100039, P.R. China.
FAU - Sun, Junzhong
AU  - Sun J
AD  - Department of Geriatric Oncology, The First Affiliated Hospital of Chinese PLA 
      General Hospital, Beijing 100048, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170906
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5656026
OTO - NOTNLM
OT  - biological therapy
OT  - breast cancer
OT  - human epidermal growth factor receptor 2
OT  - therapeutic antibody
OT  - urokinase
EDAT- 2017/11/09 06:00
MHDA- 2017/11/09 06:01
PMCR- 2017/09/06
CRDT- 2017/11/09 06:00
PHST- 2016/02/10 00:00 [received]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/11/09 06:00 [entrez]
PHST- 2017/11/09 06:00 [pubmed]
PHST- 2017/11/09 06:01 [medline]
PHST- 2017/09/06 00:00 [pmc-release]
AID - OL-0-0-6896 [pii]
AID - 10.3892/ol.2017.6896 [doi]
PST - ppublish
SO  - Oncol Lett. 2017 Nov;14(5):5189-5196. doi: 10.3892/ol.2017.6896. Epub 2017 Sep 6.