Evidence map›Paper›PMID 27248664›Full record

ArticleOncotarget2016

BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models.

Srikanth R Ambati, Jae-Hung Shieh, Benet Pera, Eloisi Caldas Lopes, Anisha Chaudhry, Elissa W P Wong, Ashish Saxena, Tsann-Long Su, Malcolm A S Moore

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
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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

9 authors at 2 institutions in 2 countries.

Srikanth R AmbatiDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Jae-Hung ShiehDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Benet PeraDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Eloisi Caldas LopesDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Anisha ChaudhryDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Elissa W P WongDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Ashish SaxenaDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Tsann-Long SuInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Malcolm A S MooreDepartment of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Memorial Sloan Kettering Cancer Center · USInstitute of Biomedical Sciences, Academia Sinica · TW

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2-3μM) and very weak activity in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and γH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient-derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent.

Indexed as

DNA DamageXenograft Model Antitumor AssaysAnimalsAntineoplastic Agents, AlkylatingApoptosisCamptothecinCell Line, TumorCell ProliferationDrug SynergismHCT116 CellsHumansIrinotecanMCF-7 CellsMice, Inbred NODMice, KnockoutMice, SCID1-(3-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-3-(4-(bis(2-chloroethyl)amino)phenyl)ureaAntineoplastic Agents, AlkylatingCamptothecinIrinotecanNitrogen Mustard CompoundsPhenylurea CompoundsDNA damageDNA repairEwing sarcomaPDX modelssoft-tissue sarcomas

Identifiers

PMID27248664
PMCPMC5190008
OpenAlexW2484214926

What OpenQuestion holds

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LicenceCC BY
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.