Search

Your search keyword '"Briere, D."' showing total 2 results
Start Over Author "Briere, D." Publisher american association for cancer research, inc
2 results on '"Briere, D."'

1. A novel antiandrogen, Compound 30, suppresses castration-resistant and MDV3100-resistant prostate cancer growth in vitro and in vivo.

Author

Kuruma H, Matsumoto H, Shiota M, Bishop J, Lamoureux F, Thomas C, Briere D, Los G, Gleave M, Fanjul A, and Zoubeidi A

Subjects
Animals, Apoptosis drug effects, Benzamides, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Disease Models, Animal, Gene Expression Regulation, Neoplastic drug effects, Humans, Male, Mice, Nitriles, Phenylthiohydantoin pharmacology, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Receptors, Androgen genetics, Receptors, Androgen metabolism, Transcription, Genetic, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Androgen Antagonists pharmacology, Antineoplastic Agents pharmacology, Drug Resistance, Neoplasm, Orchiectomy, Phenylthiohydantoin analogs & derivatives, Prostatic Neoplasms metabolism, Pyridinium Compounds pharmacology
Abstract

Resistance to antiandrogen drugs, like MDV3100, occurs in patients with castration-resistant prostate cancer (CRPC). Thus, preventing or treating antiandrogen resistance is a major clinical challenge. We identified a novel antiandrogen, Compound 30, and compared its efficacy with MDV3100. We found that Compound 30 inhibits androgen receptor (AR) activity in LNCaP cells, C4-2 cells, as well as MDV3100-resistant cell lines. Compared with MDV3100, Compound 30 treatment induces greater reduction in AR, prostate-specific antigen (PSA), and AR transcriptional activity, and prevents AR nuclear translocation in AR-sensitive LNCaP cells. Compound 30 has antiproliferative effects in LNCaP cells, in castrate-resistant C4-2 cells, and those resistant to MDV3100. Compound 30 was equally as effective as MDV3100 in reducing tumor volume and PSA in vivo. More importantly, Compound 30 is effective at inhibiting AR activity in MDV3100-resistant cell lines and significantly prevented tumor growth and PSA increases in mice bearing MDV3100-resistant xenografts. Together, our data show that Compound 30 strongly inhibited AR activity and suppressed castration-resistant LNCaP growth as well as MDV3100-resistant cell growth in vitro and in vivo. These data provide a preclinical proof-of-principle that Compound 30 could be a promising next generation anti-AR agent, especially in the context of antiandrogen-resistant tumors., (©2013 AACR)

Published
2013
Full Text
View/download PDF

2. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy.

Author

Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, and Jakubczak JL

Subjects
Administration, Oral, Animals, Aurora Kinases, Biological Availability, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Female, Heterocyclic Compounds, 3-Ring administration & dosage, Heterocyclic Compounds, 3-Ring pharmacology, Histones metabolism, Humans, Mice, Mice, Nude, Neoplasms pathology, Phosphorylation drug effects, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology, Protein Serine-Threonine Kinases metabolism, Pyrimidines administration & dosage, Pyrimidines pharmacology, Substrate Specificity drug effects, Xenograft Model Antitumor Assays, Heterocyclic Compounds, 3-Ring pharmacokinetics, Heterocyclic Compounds, 3-Ring therapeutic use, Neoplasms drug therapy, Neoplasms enzymology, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrimidines pharmacokinetics, Pyrimidines therapeutic use
Abstract

The Aurora family of highly related serine/threonine kinases plays a key role in the regulation of mitosis. Aurora1 and Aurora2 play important but distinct roles in the G(2) and M phases of the cell cycle and are essential for proper chromosome segregation and cell division. Overexpression and amplification of Aurora2 have been reported in different tumor types, including breast, colon, pancreatic, ovarian, and gastric cancer. PF-03814735 is a novel, potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases that is currently in phase I clinical trials for the treatment of advanced solid tumors. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. Although PF-03814735 produces significant inhibition of several other protein kinases, the predominant biochemical effects in cellular assays are consistent with inhibition of Aurora kinases. Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. These results support the clinical evaluation of PF-03814735 in cancer patients. Mol Cancer Ther; 9(4); 883-94. (c)2010 AACR.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results