Evidence map›Paper›PMID 11296271›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2001

Applied molecular evolution of O6-benzylguanine-resistant DNA alkyltransferases in human hematopoietic cells.

B M Davis, L P Encell, S P Zielske, F C Christians, L Liu, S E Friebert, L A Loeb, S L Gerson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

8 authors at 3 institutions in 1 country.

B M DavisDivision of Hematology/Oncology, Molecular Virology Training Program, and the Comprehensive Cancer Center at Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106-4937, USA.
L P Encell
S P Zielske
F C Christians
L Liu
S E Friebert
L A Loeb
S L Gerson
University Hospitals of Cleveland · USUniversity of Washington · USCase Western Reserve University · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
Environmetal Pathology/Toxicology Training ProgramT32ES007032 · NIEHS · UNIVERSITY OF WASHINGTON · PI FAUSTMAN, ELAINE M, ROSENFELD, MICHAEL E · 1985 to 2023
$10.7M
CREATING MUTANT ENZYMES FOR GENE THERAPY OF CANCERR01CA078885 · NCI · UNIVERSITY OF WASHINGTON · PI LOEB, LAWRENCE A · 1998 to 2007
$3.7M
GENE TRANSFER INTO HEMATOPOIETIC PROGENITORSR01CA073062 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI GERSON, STANTON L · 1997 to 2006
$1.8M
TRANSGENIC EXPRESSION OF ALKYLTRANSFERASER01ES006288 · NIEHS · CASE WESTERN RESERVE UNIVERSITY · PI GERSON, STANTON L · 1992 to 2002
$890k
PHENYLBUTYRATE BIOACTIVITY ASSESSMENT IN PROSTATE CANCERR01CA075525 · NCI · JOHNS HOPKINS UNIVERSITY · PI CARDUCCI, MICHAEL A. · 1997 to 2000
$172k
NCI NIH HHS CA78885NCI NIH HHS P30 CA043703NCI NIH HHS P30CA43703NCI NIH HHS R01 CA073062NCI NIH HHS R01 CA078885NCI NIH HHS R01CA73062NCI NIH HHS UO1CA75525NIEHS NIH HHS R01ES06288NIEHS NIH HHS T32 ES007032NIEHS NIH HHS T32 ES07032
6 · The paper itself

Abstract

Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the creation of highly drug-resistant enzymes for cancer gene therapy. Seventeen O(6)-alkylguanine-DNA alkyltransferase (AGT) mutants highly resistant to O(6)-benzylguanine (BG) were identified previously by screening 8 million variants, using genetic complementation in Escherichia coli. To examine the potential of these mutants for use in humans, the sublibrary of AGT clones was introduced to human hematopoietic cells and stringently selected for resistance to killing by the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. This competitive analysis between the mutants in human cells revealed three AGT mutants that conferred remarkable resistance to the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. Of these, one was recovered significantly more frequently than the others. Upon further analysis, this mutant displayed a level of BG resistance in human hematopoietic cells greater than that of any previously reported mutant.

Indexed as

Directed Molecular EvolutionAmino Acid SequenceAntineoplastic AgentsCarmustineCell DeathCell SurvivalDrug Resistance, NeoplasmEnzyme StabilityGene LibraryGenetic TherapyGuanineHumansK562 CellsMolecular Sequence DataMutationO(6)-Methylguanine-DNA MethyltransferaseAntineoplastic AgentsCarmustineGuanineO(6)-benzylguanineO(6)-Methylguanine-DNA Methyltransferase

Identifiers

PMID11296271
PMCPMC33144
OpenAlexW2130740265

What OpenQuestion holds

Textmetadata
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.