| PI3Kδ inhibitor, GS-1101(CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. | |
| | |
MedLine Citation:
|
PMID: 22210877 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
GS-1101(CAL-101) is an oral PI3Kδ-specific inhibitor which has shown preclinical and clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. To investigate the potential role of PI3Kδ in Hodgkin lymphoma (HL), we screened 5 HL cell lines and primary samples from patients with HL for PI3Kδ isoform expression and constitutive PI3K pathway activation. Inhibition of PI3Kδ by GS-1101 resulted in the inhibition of Akt phosphorylation. Co-cultures with stroma cells induced Akt activation in HL cells and this effect was blocked by GS-1101. Conversely, production of the stroma-stimulating chemokine, CCL5, by HL cells was reduced by GS-1101. GS-1101 also induced dose-dependent apoptosis of HL cells at 48 hours. Reductions in cell viability and apoptosis were enhanced when combining GS-1101 with the mTOR inhibitor, everolimus. Our findings suggest that excessive PI3Kδ activity is characteristic in HL and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL. |
| | |
Authors:
|
Sarah A Meadows; Francisco Vega; Adam Kashishian; Dave Johnson; Volker Diehl; Langdon L Miller; Anas Younes; Brian J Lannutti |
Related Documents
:
|
17384247 - Magnetic fields protect from apoptosis via redox alteration. 7897207 - Thiol-mediated redox regulation of apoptosis. possible roles of cellular thiols other t... 21542897 - Trapped in a vicious loop: toll-like receptors sustain the spontaneous cytokine product... 17564307 - Antioxidant and antiinflammatory activities of ventol, a phlorotannin-rich natural agen... 16769337 - Differential response of neuroblastoma cells to trail is independent of pi3k/akt. 2562947 - Aids: a syndrome of immune dysregulation, dysfunction, and deficiency. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-30 |
Journal Detail:
|
Title: Blood Volume: - ISSN: 1528-0020 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2012-1-2 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7603509 Medline TA: Blood Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Gilead Sciences, Inc., Seattle, WA, United States; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or ...
Next Document: Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma.