Evidence map›Paper›PMID 25069038›Full record

ArticleCancer letters2014

Metronomic cyclophosphamide schedule-dependence of innate immune cell recruitment and tumor regression in an implanted glioma model.

Junjie Wu, David J Waxman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

41 citing papers in PubMed, 60 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Breast cancer : basic and clinical research · 2022
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

2 authors at 1 institution in 1 country.

Junjie WuDivision of Cell and Molecular Biology, Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA.
David J WaxmanDivision of Cell and Molecular Biology, Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA. Electronic address: djw@bu.edu.
Boston University · US

Funding

HEPATIC METABOLISM OF ANTICANCER DRUGSR01CA049248 · NCI · DANA-FARBER CANCER INSTITUTE · PI WAXMAN, DAVID J · 1991 to 2014
$4.3M
NCI NIH HHS CA49248NCI NIH HHS R01 CA049248
6 · The paper itself

Abstract

Metronomic cyclophosphamide (CPA) treatment activates robust innate anti-tumor immunity and induces major regression of large, implanted brain tumor xenografts when administered on an intermittent, every 6-day schedule, but not on a daily low-dose or a maximum-tolerated dose CPA schedule. Here, we used an implanted GL261 glioma model to compare five intermittent metronomic CPA schedules to elucidate the kinetics and schedule dependence of innate immune cell recruitment and tumor regression. Tumor-recruited natural killer cells induced by two every 6-day treatment cycles were significantly ablated 1 day after a third CPA treatment, but largely recovered several days later. Natural killer and other tumor-infiltrating innate immune cells peaked 12 days after the last CPA treatment on the every 6-day schedule, suggesting that drug-free intervals longer than 6 days may show increased efficacy. Metronomic CPA treatments spaced 9 or 12 days apart, or on an alternating 6 and 9 day schedule, induced extensive tumor regression, similar to the 6-day schedule; however, the tumor-infiltrating natural killer cell responses were not sustained, leading to rapid resumption of tumor growth after day 24, despite ongoing metronomic CPA treatment. Increasing the CPA dose prolonged the period of tumor regression on the every 9-day schedule, but natural killer cell activation was markedly decreased. Thus, while several intermittent metronomic CPA treatment schedules can activate innate immune cell recruitment leading to major tumor regression, sustained immune and anti-tumor responses are only achieved on the 6-day schedule. However, even with this schedule, some tumors eventually relapse, indicating a need for further improvements in this immunogenic metronomic therapy.

Indexed as

Administration, MetronomicAnimalsAntineoplastic Agents, AlkylatingBrain NeoplasmsCell Adhesion MoleculesCell Line, TumorCyclophosphamideCytokinesDendritic CellsGliomaHumansImmunity, InnateKiller Cells, NaturalMacrophagesMaleMiceAntineoplastic Agents, AlkylatingCell Adhesion MoleculesCyclophosphamideCytokinesChemotherapy scheduleGL261 gliomaInnate immune responseMetronomic chemotherapyNatural killer cells

Identifiers

PMID25069038
PMCPMC4162810
OpenAlexW2162875441

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.