PMID- 17303227
OWN - NLM
STAT- MEDLINE
DCOM- 20070531
LR  - 20070423
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 105
IP  - 2
DP  - 2007 May
TI  - Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human 
      ovarian carcinoma using a novel ex vivo tissue slice model.
PG  - 291-8
AB  - OBJECTIVES: The purpose of this study was to evaluate the cytotoxicity of a death 
      receptor 5 (DR5) targeting monoclonal antibody (TRA-8) in primary ovarian cancer 
      specimens utilizing a tissue slice technique that allows for assessment of 
      anti-tumor activity in a three-dimensional ex vivo model. METHODS: Nineteen 
      primary ovarian tumor specimens were obtained at the time of cytoreductive 
      surgery and tumor slices were prepared with the Krumdieck tissue slicer. Tumor 
      slices were incubated with TRA-8 for 24 h and a dose-response curve was 
      established for each specimen using non-linear modeling, with IC50 values used as 
      the parameter of TRA-8 sensitivity. In parallel with ATP viability assays, TRA-8 
      treated and untreated tumor slices were assessed by immunohistochemistry (IHC) 
      and western blot analysis to confirm apoptosis induction. RESULTS: Incubation 
      with 0-1000 ng/ml TRA-8 resulted in a dose response with maximum killing observed 
      at 1000 ng/ml compared to untreated control slices. IC50 values of 6.0 to >1000 
      ng/ml were calculated for individual tumor specimens. H&E, IHC, and western blot 
      specimens demonstrated TRA-8-induced cellular death in a dose-dependent fashion 
      via apoptosis and activation of caspases 3, 8, and 9. The apoptosis produced by 
      varying concentrations of TRA-8 was confirmed using the TUNEL technique. 
      Treatment with TRA-8 markedly reduced proliferation in the ovarian cancer cells 
      as measured by expression of Ki-67/SP6. CONCLUSIONS: This study demonstrates that 
      targeting DR5 with TRA-8 decreases cellular proliferation, increases caspase 
      activation, and induces apoptosis in this novel three-dimensional ex vivo model 
      of primary ovarian cancer.
FAU - Estes, Jacob M
AU  - Estes JM
AD  - Division of Gynecologic Oncology, The University of Alabama at Birmingham, 619 
      19th Street South, OHB 538, Birmingham, AL 35249, USA. jmestes21@mac.com
FAU - Oliver, Patsy G
AU  - Oliver PG
FAU - Straughn, J Michael Jr
AU  - Straughn JM Jr
FAU - Zhou, Tong
AU  - Zhou T
FAU - Wang, Wenquan
AU  - Wang W
FAU - Grizzle, William E
AU  - Grizzle WE
FAU - Alvarez, Ronald D
AU  - Alvarez RD
FAU - Stockard, Cecil R
AU  - Stockard CR
FAU - LoBuglio, Albert F
AU  - LoBuglio AF
FAU - Buchsbaum, Donald J
AU  - Buchsbaum DJ
LA  - eng
PT  - Journal Article
DEP - 20070215
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/immunology/*pharmacology
MH  - Blotting, Western
MH  - Drug Screening Assays, Antitumor
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Inhibitory Concentration 50
MH  - Middle Aged
MH  - Ovarian Neoplasms/immunology/pathology/*therapy
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*immunology
EDAT- 2007/02/17 09:00
MHDA- 2007/06/01 09:00
CRDT- 2007/02/17 09:00
PHST- 2006/07/29 00:00 [received]
PHST- 2006/12/17 00:00 [revised]
PHST- 2006/12/21 00:00 [accepted]
PHST- 2007/02/17 09:00 [pubmed]
PHST- 2007/06/01 09:00 [medline]
PHST- 2007/02/17 09:00 [entrez]
AID - S0090-8258(06)01035-3 [pii]
AID - 10.1016/j.ygyno.2006.12.033 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2007 May;105(2):291-8. doi: 10.1016/j.ygyno.2006.12.033. Epub 2007 
      Feb 15.