ArticleClinical cancer research : an official journal of the American Association for Cancer Research2007
Combination treatment with TRA-8 anti death receptor 5 antibody and CPT-11 induces tumor regression in an orthotopic model of pancreatic cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Basic and applied research progress of TRAIL in hematologic malignancies.Blood science (Baltimore, Md.) · 2025Review
- Novel Apoptosis-Inducing Agents for the Treatment of Cancer, a New Arsenal in the Toolbox.Cancers · 2019Review
- A Novel Imaging Biomarker Extracted from Fluorescence Microscopic Imaging of TRA-8/DR5 Oligomers Predicts TRA-8 Therapeutic Efficacy in Breast and Pancreatic Cancer Mouse Models.Molecular imaging and biology · 2016Article
- Targeting Acidity in Pancreatic Adenocarcinoma: Multispectral Optoacoustic Tomography Detects pH-Low Insertion Peptide Probes In Vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Dynamic contrast enhanced magnetic resonance imaging of an orthotopic pancreatic cancer mouse model.Journal of visualized experiments : JoVE · 2015Article
- Orthotopic pancreatic tumors detected by optoacoustic tomography using Syndecan-1.The Journal of surgical research · 2015Article
- Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine.Toxicology in vitro : an international journal published in association with BIBRA · 2014Article
- Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis.Cancer metastasis reviews · 2013Review
- Effect of anti-DR5 and chemotherapy on basal-like breast cancer.Breast cancer research and treatment · 2012Article
- Dual combination therapy targeting DR5 and EMMPRIN in pancreatic adenocarcinoma.Molecular cancer therapeutics · 2012Article
- Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer therapy.Anti-cancer drugs · 2011Article
- Micro-ultrasound for preclinical imaging.Interface focus · 2011Article
- Irinotecan synergistically enhances the antiproliferative and proapoptotic effects of axitinib in vitro and improves its anticancer activity in vivo.Neoplasia (New York, N.Y.) · 2011Article
- Combined modality therapy with TRAIL or agonistic death receptor antibodies.Cancer biology & therapy · 2011Review
- Targeting apoptosis signaling in pancreatic cancer.Cancers · 2011Article
- Molecular targeted approaches for treatment of pancreatic cancer.Current pharmaceutical design · 2011Review
- Homotypic gap junctional communication associated with metastasis suppression increases with PKA activity and is unaffected by PI3K inhibition.Cancer research · 2010Article
- KISS1 over-expression suppresses metastasis of pancreatic adenocarcinoma in a xenograft mouse model.Clinical & experimental metastasis · 2010Article
- Therapeutic antibodies for the treatment of pancreatic cancer.TheScientificWorldJournal · 2010Review
- Phase I trial of weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting death receptor 5 (DR5).Cancer biotherapy & radiopharmaceuticals · 2010Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeEvaluate the response of human pancreatic cancer cell lines and orthotopic tumors to TRA-8, an agonistic antibody to death receptor 5, in combination with irinotecan (CPT-11). EXPERIMENTAL
designMIA PaCa-2 and S2VP10 cells were treated with TRA-8 and/or CPT 11. Cell viability was determined by ATP assay. JC-1 mitochondrial depolarization and Annexin V assays confirmed cell death by apoptosis. Immunoblotting was used to evaluate protein changes. MIA PaCa-2 cells were injected into the pancreas of severe combined immunodeficient mice. Mice underwent abdominal ultrasound to quantitate tumor size before and after treatment with twice weekly injections of 200 microg TRA-8 and/or 25 mg/kg CPT-11 for one or two treatment cycles, each lasting 2 weeks.
resultsMIA PaCa-2 cells were more sensitive to TRA-8 and showed additive cytotoxicity, whereas S2VP10 cells showed synergistic cytotoxicity when treated with TRA-8 and CPT-11. Cell death occurred via apoptosis with increased cleavage of caspase-3, caspase-8, and caspase-9 and proapoptotic proteins Bid and poly(ADP)ribose polymerase after combination treatment compared with either agent alone. XIAP and Bcl-XL inhibitors of apoptosis were down-regulated. After a single cycle of in vivo combination therapy, tumor sizes had diminished significantly (P<0.001) at 8 days posttreatment compared with no treatment, CPT-11, and TRA-8; and there was a 50-day increase in survival with combination treatment over untreated controls (P=0.0002), 30 days over TRA-8, and a 36-day increase over CPT-11 monotherapy (P=0.0003). With two cycles of TRA-8/CPT-11 treatment, mean survival time increased significantly (P<0.001) to 169 days versus untreated controls, TRA-8 or CPT-11 (76, 121, or 108 days, respectively).
conclusionsCombination TRA-8 and CPT-11 therapy produced enhanced cytotoxicity and survival in the MIA PaCa-2 orthotopic model of pancreatic cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.