Evidence map›Paper›PMID 21264291›Full record

ArticlePloS one2011

Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine.

Christine L Clouser, Colleen M Holtz, Mary Mullett, Duane L Crankshaw, Jacquie E Briggs, Jay Chauhan, Ilze Matise VanHoutan, Steven E Patterson, Louis M Mansky

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

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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 3 institutions in 1 country.

Christine L ClouserInstitute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Colleen M Holtz
Mary Mullett
Duane L Crankshaw
Jacquie E Briggs
Jay Chauhan
Ilze Matise VanHoutan
Steven E Patterson
Louis M Mansky
University of Minnesota · USMinneapolis VA Medical Center · USUniversity of Minnesota Medical Center · US

Funding

TRAINING GRANT IN MICROBIOLOGY/CANCER RESEARCHT32CA009138 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Scott M. Dehm · 1985 to 2026
$11.3M
MINNESOTA PAIN RESEARCH TRAINING PROGRAMT32DE007288 · NIDCR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HERZBERG, MARK C · 1996 to 2011
$8.8M
Mechanisms of HIV-1 VariationR01GM056615 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MANSKY, LOUIS M. · 2003 to 2011
$2.6M
MECHANISMS OF HIV1 VARIATIONR29GM056615 · NIGMS · OHIO STATE UNIVERSITY · PI MANSKY, LOUIS M · 1997 to 2001
$215k
NCI NIH HHS T32 CA009138NIDCR NIH HHS T32 DE007288NIDCR NIH HHS T32 DE07288NIGMS NIH HHS GM56615NIGMS NIH HHS R01 GM056615NIGMS NIH HHS R29 GM056615
6 · The paper itself

Abstract

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1, suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy.

Indexed as

AnimalsAnti-Retroviral AgentsCells, CulturedDeoxycytidineDisease ProgressionGemcitabineImmunoglobulin MLeukemia Virus, MurineMiceMice, Inbred C57BLMurine Acquired Immunodeficiency SyndromeRibonucleotide ReductasesSpleenViral LoadAnti-Retroviral AgentsDeoxycytidineGemcitabineImmunoglobulin MRibonucleotide Reductases

Identifiers

PMID21264291
PMCPMC3021508
OpenAlexW2152881245

What OpenQuestion holds

Textmetadata
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.