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Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.

Elgström, Erika LU ; Ljungberg, Otto LU ; Eriksson, Sophie LU ; Örbom, Anders LU ; Strand, Sven-Erik LU ; Ohlsson, Tomas G LU ; Nilsson, Rune LU and Tennvall, Jan LU (2014) In Cancer Biotherapy & Radiopharmaceuticals 29(4). p.143-152
Abstract
Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors... (More)
Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Biotherapy & Radiopharmaceuticals
volume
29
issue
4
pages
143 - 152
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:24693940
  • wos:000336535800001
  • scopus:84900487931
ISSN
1557-8852
DOI
10.1089/cbr.2013.1576
language
English
LU publication?
yes
id
f6651499-9cf6-4234-834d-aca3197e1ea8 (old id 4431239)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24693940?dopt=Abstract
date added to LUP
2014-05-06 21:52:04
date last changed
2017-06-25 03:15:24
@article{f6651499-9cf6-4234-834d-aca3197e1ea8,
  abstract     = {Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.},
  author       = {Elgström, Erika and Ljungberg, Otto and Eriksson, Sophie and Örbom, Anders and Strand, Sven-Erik and Ohlsson, Tomas G and Nilsson, Rune and Tennvall, Jan},
  issn         = {1557-8852},
  language     = {eng},
  number       = {4},
  pages        = {143--152},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Cancer Biotherapy & Radiopharmaceuticals},
  title        = {Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.},
  url          = {http://dx.doi.org/10.1089/cbr.2013.1576},
  volume       = {29},
  year         = {2014},
}