Search

Your search keyword '"Shao Ning Yang"' showing total 2 results
Start Over Author "Shao Ning Yang" Journal nature medicine
2 results on '"Shao Ning Yang"'

1. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6–dependent B cell lymphomas

Author

Shao Ning Yang, Kapil N. Bhalla, Jennifer Walling, Karen L. Bunting, Ana I. Robles, Gabriela Chiosis, Ari Melnick, Rita Shaknovich, Lucas Tsikitas, Leandro Cerchietti, Alka Mallik, Eloisi Caldas Lopes, Lyuba Varticovski, and Katerina Hatzi

Subjects
Programmed cell death, Lymphoma, B-Cell, Bcl6, Hsp90, Article, General Biochemistry, Genetics and Molecular Biology, Hsp90 inhibitor, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Heat shock protein, medicine, Humans, HSP90 Heat-Shock Proteins, B cell, 030304 developmental biology, 0303 health sciences, biology, B-cell lymphoma, Promoter, General Medicine, targeted therapy, medicine.disease, Molecular biology, 3. Good health, Lymphoma, DNA-Binding Proteins, medicine.anatomical_structure, Apoptosis, 030220 oncology & carcinogenesis, Proto-Oncogene Proteins c-bcl-6, biology.protein, Cancer research, Protein Binding
Abstract

We report that Heat shock protein 90 (Hsp90) inhibitors selectively kill Diffuse Large B-cell Lymphomas (DLBCL) that are biologically dependent on the Bcl6 transcriptional repressor. Endogenous Hsp90 was found to interact with Bcl6 in DLBCL cells and could stabilize both Bcl6 mRNA and protein. Hsp90 formed a complex with Bcl6 at its target promoters and Hsp90 inhibitors de-repressed Bcl6 target genes. A stable mutant of Bcl6 rescued DLBCL cells from Hsp90 inhibitor induced apoptosis. Bcl6 and Hsp90 were almost invariantly co-expressed in the nuclei of primary DLBCL cells, suggesting that their interaction is relevant in this disease. We examined the pharmacokinetics, toxicity and efficacy of PU-H71, a recently developed purine derived Hsp90 inhibitor. PU-H71 preferentially accumulated in lymphomas compared to normal tissues and selectively suppressed Bcl6-dependent DLBCLs in vivo, inducing reactivation of key Bcl6 target genes and apoptosis. PU-H71 also induced cell death in primary human DLBCL specimens.

Published
2009
Full Text
View/download PDF

2. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6–dependent B cell lymphomas.

Author

Cerchietti, Leandro C., Lopes, Eloisi C., Shao Ning Yang, Hatzi, Katerina, Bunting, Karen L., Tsikitas, Lucas A., Mallik, Alka, Robles, Ana I., Walling, Jennifer, Varticovski, Lyuba, Shaknovich, Rita, Bhalla, Kapil N., Chiosis, Gabriela, and Melnick, Ari

Subjects
HEAT shock proteins, B cells, LYMPHOMAS, MESSENGER RNA, APOPTOSIS, PURINES
Abstract

We report that heat shock protein 90 (Hsp90) inhibitors selectively kill diffuse large B cell lymphomas (DLBCLs) that depend on the BCL-6 transcriptional repressor. We found that endogenous Hsp90 interacts with BCL-6 in DLBCL cells and can stabilize BCL-6 mRNA and protein. Hsp90 formed a complex with BCL-6 at its target promoters, and Hsp90 inhibitors derepressed BCL-6 target genes. A stable mutant of BCL-6 rescued DLBCL cells from Hsp90 inhibitor–induced apoptosis. BCL-6 and Hsp90 were almost invariantly coexpressed in the nuclei of primary DLBCL cells, suggesting that their interaction is relevant in this disease. We examined the pharmacokinetics, toxicity and efficacy of PU-H71, a recently developed purine-derived Hsp90 inhibitor. PU-H71 preferentially accumulated in lymphomas compared to normal tissues and selectively suppressed BCL-6–dependent DLBCLs in vivo, inducing reactivation of key BCL-6 target genes and apoptosis. PU-H71 also induced cell death in primary human DLBCL specimens. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results