Evidence map›Paper›PMID 31796785›Full record

ArticleScientific reports2019

Actinomycin D and Telmisartan Combination Targets Lung Cancer Stem Cells Through the Wnt/Beta Catenin Pathway.

Ryan Green, Mark Howell, Roukiah Khalil, Rajesh Nair, Jiyu Yan, Elspeth Foran, Sandhyabanu Katiri, Jit Banerjee, Mandip Singh, Srinivas Bharadwaj and 2 more

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.9field-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.

NCT06168487 phase1recruitingnot on this mapstarted 2024, after this paper: background citation

Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer

TypeinterventionalSponsorTyler J CurielRan2024 to 2027Enrolled36ConditionsProstate CancerArmsTelmisartan, Standard of Care Regimen
NCT06815497 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Phase II Non-Randomized, Unblinded, Single-Center Trial of Telmisartan in Combination With Cytotoxic Regimens in Platinum-Resistant Ovarian Cancer Versus Historical Best Supportive Care

TypeinterventionalSponsorTyler J CurielRan2026 to 2029Enrolled33ConditionsOvarian CancerArmsTelmisartan
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 34 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

12 authors at 3 institutions in 1 country.

Ryan GreenDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.
Mark HowellDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.
Roukiah KhalilDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.
Rajesh NairTransgenex Nanobiotech Inc., Tampa, FL, 33613, USA.
Jiyu YanTransgenex Nanobiotech Inc., Tampa, FL, 33613, USA.
Elspeth ForanDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.ORCID http://orcid.org/0000-0002-7152-4683
Sandhyabanu KatiriDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.
Jit BanerjeeDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA.
Mandip SinghCollege of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA.
Srinivas BharadwajDepartment of Internal Medicine, University of South Florida, Tampa, FL, 33612, USA.
Shyam S MohapatraDepartment of Internal Medicine, University of South Florida, Tampa, FL, 33612, USA.
Subhra MohapatraDepartment of Molecular Medicine, University of South Florida, Tampa, FL, 33612, USA. smohapa2@usf.edu.
University of South Florida · USTransGenex Nanobiotech (United States) · USFlorida Agricultural and Mechanical University · US

Funding

An Integrated Nano-Cell Delivery Platform of Theranostics for Lung CancersR01CA152005 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI MOHAPATRA, SHYAM S, MOHAPATRA, SUBHRA · 2010 to 2014
$1.4M
BLRD VA I01 BX003413BLRD VA IK6 BX003778BLRD VA IK6 BX004212NCI NIH HHS R01 CA152005
6 · The paper itself

Abstract

The failure of lung cancer treatments has been attributed mostly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. Cancer initiating stem cells (CSCs), present in tumors in a small percentage, play critical roles in the development of drug resistance, metastasis, and cancer relapse. Hence, novel treatments targeting both bulk cancer cells and CSCs are under intense investigation. Herein, we report that lung cancer cells grown on a 3D fibrous scaffold form tumoroids that resemble in vivo tumors, expand CSCs, and provide a platform to identify anti-CSC drugs. The screening of an NCI library of FDA-approved drugs using tumoroid cultures led to identification of Actinomycin D (AD) as a top CSC inhibitor. Since CSCs are mostly resident in the tumor's inner core, AD was combined with an angiotensin receptor antagonist, Telmisartan (TS), which is known to increase drug permeability in tumors and was shown to have anti-CSC activity. Our results showed that AD + TS administered intra-tumorally was significantly more effective than either drug alone in both syngeneic and xenograft mouse models. The results of mechanistic studies revealed that CSC expansion in tumoroids was associated with activation of β catenin signaling and that AD + TS treatment reduced active β catenin levels in tumors. Together, these results establish the utility of the tumoroid culture system to expand CSCs ex vivo for targeted drug screening, to identify promising novel treatments with both anti-CSC and anti-cancer effects, and to individualize treatments for metastatic drug resistant lung cancer patients.

Indexed as

AnimalsApoptosisbeta CateninCell Line, TumorCell ProliferationDactinomycinHumansLung NeoplasmsMiceMice, Inbred C57BLMice, Inbred NODNeoplasm Recurrence, LocalNeoplastic Stem CellsSignal TransductionTelmisartanWnt Signaling Pathwaybeta CateninCTNNB1 protein, humanDactinomycinTelmisartan

Identifiers

PMID31796785
PMCPMC6890794
OpenAlexW2993608316

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.