Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody.

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Abstract Text:

Background Resistance of tumors to cell death signals poses a complex clinical problem. We explored the therapeutic potential and in vivo toxicity of a combination of bortezomib, a proteasome inhibitor, and MD5-1, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (DR5) agonist monoclonal antibody, in mouse carcinomas. Methods Mice bearing Renca-FLAG (renal) or 4T1 (mammary) tumors were treated with bortezomib and/or MD5-1 and examined for lung metastases (Renca-FLAG: n = 93; 4T1: n = 40) or monitored for survival (Renca-FLAG: n = 143). Toxicity was assessed by histopathology and hematology. Viability and apoptotic signaling in Renca-FLAG and 4T1 cells treated with bortezomib alone or in combination with TRAIL were analyzed using 3-[4,5-dimethyiazol-2-yl-5]-[3-carboxymethyloxyphenyl]-2-[4-sulfophenyl]-2H tetrazolium assay and by measuring mitochondrial membrane depolarization and caspase-8 and caspase-3 activation. All statistical tests were two-sided. Results Bortezomib (20 nM) sensitized Renca-FLAG and 4T1 cells to TRAIL-mediated apoptosis (mean percent decrease in numbers of viable cells, bortezomib + TRAIL vs TRAIL: Renca-FLAG, 95% vs 34%, difference = 61%, 95% confidence interval [CI] = 52% to 69%, P < .001; 4T1, 85% vs 20%, difference = 65%, 95% CI = 62% to 69%, P < .001). Sensitization involved activation of caspase-8 and caspase-3 but not mitochondrial membrane depolarization, suggesting an amplified signaling of the extrinsic cell death pathway. Treatment with bortezomib and MD5-1 reduced lung metastases in mice carrying Renca and 4T1 tumors (mean number of metastases, bortezomib + MD5-1 vs MD5-1: Renca-FLAG, 1 vs 8, difference = 7, 95% CI = 5 to 9, P < .001; 4T1, 1 vs 12, difference = 11, 95% CI = 9 to 12, P < .001) and increased median survival of mice bearing Renca-FLAG tumors (bortezomib + MD5-1 vs bortezomib + control isotype antibody: 22 of 30 [73%] were still alive at day 180 vs median survival of 42 days [95% CI = 41 to 44 days, P < .001]) in the absence of obvious toxicity. Conclusion Bortezomib combined with DR5 agonist monoclonal antibody may be a useful treatment for metastatic solid tumors.

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of the National Cancer Institute

VOLUME: 100

Page Numbers: 649-62

Journal Abbreviation: J. Natl. Cancer Inst.

ISSN: 1460-2105

DAY: 29

MONTH: 04

YEAR: 2008

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503089

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody.

AFFILIATION: Laboratory of Experimental Immunology, Cancer and Inflammation Program, SAIC-Frederick, Inc, National Cancer Institute-Frederick, Frederick, MD 21702. sayerst@mail.nih.gov.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Natl Cancer Inst

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody Related Publications

• Accuracy and precision of two methods of blood lead estimation.
• Comparative studies in vector and linear electrocardiography.
• Continuous affinity-based selection: rapid screening and simultaneous amplification of bacterial surface-display libraries.
• Control of the water content of the body.
• Detection of genes with moderate effects on disease resistance using ovine mhc and resistance to nematodes as an example.
• Determination of lead in capillary blood using a paper punched disc atomic absorption technique. Application to the supervision of lead workers.
• Discharge of adrenocorticotrophic hormone in the absence of neural connections between the pituitary and hypothalamus.
• Effect of Dust on the Lungs.
• High Velocity Resistance Training In Older Men And Women: 2311: Board #224 June 1 9:00 AM -10:30 AM.
• High-speed power training: a novel approach to resistance training in older men and women. A brief review and pilot study.
• Hypothalamus and adenohypophysis: with special reference to corticotrophin release.
• Insulin hypersensitivity following the administration of desoxycorticosterone acetate.
• International Committee on Military Medicine and Pharmacy.
• Meta-analysis of genome-wide linkage studies of asthma and related traits.
• Non-voluntary passive euthanasia: the social consequences of euphemisms.
• Primary aldosteronism. The value of spironolactone in diagnosis.
• Promazine as a preanesthetic agent in horses.
• Research in industrial health problems.
• Salmeterol and cytokines modulate inositol-phosphate signalling in human airway smooth muscle cells via regulation at the receptor locus.
• Sensitizing tumor cells to immune-mediated cytotoxicity.
• Serial - Tips and tricks in performing a systematic review.
• Surgery and chemotherapy of brain tumors in children.
• Syphilis Control in Industry.
• THE EFFECTS OF SILICA DUST UPON THE LUNGS : PART II.
• THE EFFECTS OF SILICA DUST UPON THE LUNGS: PART I.
• The pituitary-adrenal system.
• The pituitary-adrenal system.
• Tips and tricks in performing a systematic review - chapter 4.
• Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody.
• Unsuccessful fluorouracil treatment of recalcitrant pustular psoriasis.