ArticleThe Journal of clinical investigation2013
Efficacious proteasome/HDAC inhibitor combination therapy for primary effusion lymphoma.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- Trial
- A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma.Clinical lymphoma, myeloma & leukemia · 2018Trial
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.Translational oncology · 2025Article
- Repression of varicella zoster virus gene expression during quiescent infection in the absence of detectable histone deposition.PLoS pathogens · 2025Article
- Review
- Article
- Oncogenic Viruses and the Epigenome: How Viruses Hijack Epigenetic Mechanisms to Drive Cancer.International journal of molecular sciences · 2023Review
- Oncolytic strategy using new bifunctional HDACs/BRD4 inhibitors against virus-associated lymphomas.PLoS pathogens · 2023Article
- SUMO Modification of Histone Demethylase KDM4A in Kaposi's Sarcoma-Associated Herpesvirus-Induced Primary Effusion Lymphoma.Journal of virology · 2022Article
- HIV-Associated Lymphomas: Progress and New Challenges.Journal of clinical medicine · 2022Review
- Article
- KSHV/HHV8-mediated hematologic diseases.Blood · 2022Review
- Review
- Suberoyl bis-hydroxamic acid reactivates Kaposi's sarcoma-associated herpesvirus through histone acetylation and induces apoptosis in lymphoma cells.Journal of virology · 2021Article
- A Non-Coding RNA Network Involved in KSHV Tumorigenesis.Frontiers in oncology · 2021Article
- Targeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections.Frontiers in cellular and infection microbiology · 2021Review
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.PLoS pathogens · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Primary effusion lymphoma (PEL) is a rare form of aggressive B cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Current chemotherapy approaches result in dismal outcomes, and there is an urgent need for new PEL therapies. Previously, we established, in a direct xenograft model of PEL-bearing immune-compromised mice, that treatment with the proteasome inhibitor, bortezomib (Btz), increased survival relative to that after treatment with doxorubicin. Herein, we demonstrate that the combination of Btz with the histone deacetylase (HDAC) inhibitor suberoylanilidehydroxamic acid (SAHA, also known as vorinostat) potently reactivates KSHV lytic replication and induces PEL cell death, resulting in significantly prolonged survival of PEL-bearing mice. Importantly, Btz blocked KSHV late lytic gene expression, terminally inhibiting the full lytic cascade and production of infectious virus in vivo. Btz treatment led to caspase activation and induced DNA damage, as evidenced by the accumulation of phosphorylated γH2AX and p53. The addition of SAHA to Btz treatment was synergistic, as SAHA induced early acetylation of p53 and reduced interaction with its negative regulator MDM2, augmenting the effects of Btz. The eradication of KSHV-infected PEL cells without increased viremia in mice provides a strong rationale for using the proteasome/HDAC inhibitor combination therapy in PEL.
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Registered trials
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.