Evidence map›Paper›PMID 34938177›Full record

ArticleFrontiers in pharmacology2021

Identification and Characterization of Key Differentially Expressed Genes Associated With Metronomic Dosing of Topotecan in Human Prostate Cancer.

Taraswi Mitra Ghosh, Jason White, Joshua Davis, Suman Mazumder, Teeratas Kansom, Elena Skarupa, Grafton S Barnett, Gary A Piazza, R Curtis Bird, Amit K Mitra and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. 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
1.3field-weighted citation impact, top 18% 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, 9 citations in OpenAlex.

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  2. Review
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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

13 authors at 4 institutions in 1 country.

Taraswi Mitra GhoshDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Jason WhiteDepartment of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, United States.
Joshua DavisDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Suman MazumderDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Teeratas KansomDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Elena SkarupaDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Grafton S BarnettDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Gary A PiazzaDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
R Curtis BirdDepartment of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States.
Amit K MitraDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Clayton YatesDepartment of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, United States.
Brian S CummingsDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, United States.
Robert D ArnoldDepartment of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.
Auburn University · USCenter for Cancer Research · USUniversity of Alabama at Birmingham · USWayne State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Repetitive, low-dose (metronomic; METRO) drug administration of some anticancer agents can overcome drug resistance and increase drug efficacy in many cancers, but the mechanisms are not understood fully. Previously, we showed that METRO dosing of topotecan (TOPO) is more effective than conventional (CONV) dosing in aggressive human prostate cancer (PCa) cell lines and in mouse tumor xenograft models. To gain mechanistic insights into METRO-TOPO activity, in this study we determined the effect of METRO- and CONV-TOPO treatment in a panel of human PCa cell lines representing castration-sensitive/resistant, androgen receptor (+/-), and those of different ethnicity on cell growth and gene expression. Differentially expressed genes (DEGs) were identified for METRO-TOPO therapy and compared to a PCa patient cohort and The Cancer Genome Atlas (TCGA) database. The top five DEGs were SERPINB5, CDKN1A, TNF, FOS, and ANGPT1. Ingenuity Pathway Analysis predicted several upstream regulators and identified top molecular networks associated with METRO dosing, including tumor suppression, anti-proliferation, angiogenesis, invasion, metastasis, and inflammation. Further, the top DEGs were associated with increase survival of PCa patients (TCGA database), as well as ethnic differences in gene expression patterns in patients and cell lines representing African Americans (AA) and European Americans (EA). Thus, we have identified candidate pharmacogenomic biomarkers and novel pathways associated with METRO-TOPO therapy that will serve as a foundation for further investigation and validation of METRO-TOPO as a novel treatment option for prostate cancers.

Indexed as

mCRPCmetronomicprostate cancerRNA sequencingTCGAtopotecantranscriptomics

Identifiers

PMID34938177
PMCPMC8685420
OpenAlexW4200090770

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.