PMID- 19417081
OWN - NLM
STAT- MEDLINE
DCOM- 20091023
LR  - 20220317
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 23
IP  - 9
DP  - 2009 Sep
TI  - Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents.
PG  - 3171-8
LID - 10.1096/fj.09-131383 [doi]
AB  - This study investigated potential cardiotoxicity as exerted by 
      Erbicin-derived-immunoagents (EDIAs), novel human anti-ErbB2 immunoagents 
      engineered by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human 
      RNase or the Fc region of a human IgG1. EDIAs are strongly cytotoxic on 
      ErbB2-positive cells in vitro and in vivo and bind to an epitope different from 
      that of Herceptin, a humanized anti-ErbB2 mAb effective in the therapy of breast 
      carcinoma, but cardiotoxic in a high percentage of cases. Toxicity and apoptosis 
      were tested in vitro by 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium 
      bromide (MTT), DNA fragmentation, and immunoblotting analyses. Echocardiography 
      was measured in mice after treatment with each immunoagent. Cardiac fibrosis and 
      detection of apoptosis were examined by Sirius red staining of collagen and TUNEL 
      assay, respectively. EDIAs were found in vitro to have no adverse effects on 
      cardiac cells for which Herceptin is severely toxic. In vivo studies on a mouse 
      model showed that the EDIAs did not alter cardiac function, whereas Herceptin and 
      doxorubicin, used as positive controls, significantly reduced the fractional 
      shortening parameter. Cardiac fibrosis and apoptosis were not significantly 
      affected in mice treated with EDIAs. Thus, EDIAs could fulfill the therapeutic 
      need of patients ineligible for Herceptin treatment due to cardiac dysfunction.
FAU - Riccio, Gennaro
AU  - Riccio G
AD  - Dipartimento di Biologia Strutturale e Funzionale, Universita di Napoli Federico 
      II, Napoli, Italy.
FAU - Esposito, Giovanni
AU  - Esposito G
FAU - Leoncini, Emanuela
AU  - Leoncini E
FAU - Contu, Riccardo
AU  - Contu R
FAU - Condorelli, Gianluigi
AU  - Condorelli G
FAU - Chiariello, Massimo
AU  - Chiariello M
FAU - Laccetti, Paolo
AU  - Laccetti P
FAU - Hrelia, Silvana
AU  - Hrelia S
FAU - D'Alessio, Giuseppe
AU  - D'Alessio G
FAU - De Lorenzo, Claudia
AU  - De Lorenzo C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090505
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cardiotoxins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use/toxicity
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/pharmacology/toxicity
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/complications/drug therapy
MH  - Cardiotoxins
MH  - DNA Fragmentation/drug effects
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Electrocardiography
MH  - Fibrosis/chemically induced
MH  - Humans
MH  - Mice
MH  - Protein Engineering/methods
MH  - Receptor, ErbB-2/*immunology
MH  - Trastuzumab
EDAT- 2009/05/07 09:00
MHDA- 2009/10/24 06:00
CRDT- 2009/05/07 09:00
PHST- 2009/05/07 09:00 [entrez]
PHST- 2009/05/07 09:00 [pubmed]
PHST- 2009/10/24 06:00 [medline]
AID - fj.09-131383 [pii]
AID - 10.1096/fj.09-131383 [doi]
PST - ppublish
SO  - FASEB J. 2009 Sep;23(9):3171-8. doi: 10.1096/fj.09-131383. Epub 2009 May 5.