Evidence map›Paper›PMID 22687754›Full record

ArticleExperimental hematology2012

Epigenetic modifiers enhance the synergistic cytotoxicity of combined nucleoside analog-DNA alkylating agents in lymphoma cell lines.

Benigno C Valdez, Yago Nieto, David Murray, Yang Li, Guiyun Wang, Richard E Champlin, Borje S Andersson

Abstract read
In one paragraph

Article in Experimental hematology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Phase II Trial of High-Dose Gemcitabine/Busulfan/Melphalan with Autologous Stem Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin Lymphoma.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018
    Trial
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  5. Autologous stem cell transplantation for refractory or poor-risk relapsed Hodgkin's lymphoma: effect of the specific high-dose chemotherapy regimen on outcome.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2013
    Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Benigno C ValdezDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. bvaldez@mdanderson.org
Yago Nieto
David Murray
Yang Li
Guiyun Wang
Richard E Champlin
Borje S Andersson
The University of Texas MD Anderson Cancer Center · USAlberta Cancer Foundation · CA

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
THE THERAPY OF AMLP01CA055164 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI THOMAS, MATTIE J · 1992 to 2011
$25.3M
NCI NIH HHS CA16672NCI NIH HHS P01 CA055164NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt to design an efficacious and safe prehematopoietic stem cell transplantation conditioning regimen, we investigated the cytotoxicity of the combination of busulfan (B), melphalan (M), and gemcitabine (G) in lymphoma cell lines in the absence or presence of drugs that induce epigenetic changes. Cells were exposed to drugs individually or in combination and analyzed by the MTT proliferation assay, flow cytometry, and Western blotting. We used ~IC(10) drug concentrations (57 μM B, 1 μM M and 0.02 μM G), which individually did not have major effects on cell proliferation. Their combination resulted in 50% inhibition of proliferation. Reduction to almost half concentration (20 μM B, 0.7 μM M and 0.01 μM G) did not have significant effects, but addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (0.6 μM) to this combination resulted in a marked (~65%) growth inhibition. The cytotoxicity of these combinations correlates with the activation of the ataxia telangiectasia mutated-CHK2 pathway, phosphorylation of KRAB-associated protein-1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. The relevance of epigenetic changes is further shown by the induction of DNA methyltransferases in tumor cells with low constitutive levels of DNMT3A and DNMT3B. The addition of 5-aza-2'-deoxycytidine to (BMG+suberoylanilide hydroxamic acid) further enhances cell killing. Overall, BMG combinations are synergistically cytotoxic to lymphoma cells. Epigenetic changes induced by suberoylanilide hydroxamic acid and 5-aza-2'-deoxycytidine further enhance the cytotoxicity. This study provides a rationale for an ongoing clinical trial in our institution using (BMG+suberoylanilide hydroxamic acid) as pre-hematopoietic stem cell transplantation conditioning for lymphoma.

Indexed as

Antineoplastic Agents, AlkylatingAtaxia Telangiectasia Mutated ProteinsAzacitidineBusulfanCell Cycle ProteinsCell Line, TumorCell ProliferationCheckpoint Kinase 2CytotoxinsDecitabineDeoxycytidineDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDose-Response Relationship, DrugAntineoplastic Agents, AlkylatingAtaxia Telangiectasia Mutated ProteinsATM protein, humanAzacitidineBusulfanCell Cycle ProteinsCheckpoint Kinase 2CHEK2 protein, humanCytotoxinsDecitabineDeoxycytidineDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDNMT3A protein, humanGemcitabineHydroxamic AcidsMelphalanProtein Serine-Threonine KinasesTumor Suppressor Proteins

Identifiers

PMID22687754
PMCPMC3447105
OpenAlexW2036723718

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.