Evidence map›Paper›PMID 31470802›Full record

ArticleBMC cancer2019

Human bronchial carcinoid tumor initiating cells are targeted by the combination of acetazolamide and sulforaphane.

Reza Bayat Mokhtari, Narges Baluch, Evgeniya Morgatskaya, Sushil Kumar, Angelo Sparaneo, Lucia Anna Muscarella, Sheyun Zhao, Hai-Ling Cheng, Bikul Das, Herman Yeger

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

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-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

13 citing papers in PubMed, 17 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

10 authors at 6 institutions in 4 countries.

Reza Bayat MokhtariDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada. oncoplasia@gmail.com.
Narges BaluchDepartment of Pediatrics, Queen's University, 76 Stuart St, Kingston, ON, K7L 2V7, Canada.
Evgeniya MorgatskayaDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Sushil KumarDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Williams Science Hall 3035, Department of Pharmaceutical Sciences 601 S. Saddle Creek Rd, Omaha, NE, 68106, USA.
Angelo SparaneoLaboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, FG, Italy.
Lucia Anna MuscarellaLaboratory of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013, San Giovanni Rotondo, FG, Italy.
Sheyun ZhaoDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Hai-Ling ChengInstitute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Rosebrugh Building, Room 407, Toronto, ON, M5S 3G9, Canada.
Bikul DasThoreau Laboratory for Global Health, M2D2, University of Massachusetts-Lowell, Innovation Hub, 110 Canal St, Lowell, MA, 01852, USA.
Herman YegerDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Hospital for Sick Children · CACasa Sollievo della Sofferenza · ITUniversity of Toronto · CANebraska Medical Center · USQueen's University · CAUniversity of Massachusetts Lowell · US

Funding

AIRC/MGAF 12983
6 · The paper itself

Abstract

backgroundBronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell (TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior.

methodsBronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids.

resultsData demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice.

conclusionsHuman bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.

Indexed as

AcetazolamideAnimalsAnticarcinogenic AgentsAntineoplastic Combined Chemotherapy ProtocolsBronchial NeoplasmsCarcinoid TumorCell Culture TechniquesCell Line, TumorCell ProliferationCell SurvivalFemaleGene Expression Regulation, NeoplasticHumansIsothiocyanatesMiceNanog Homeobox ProteinAcetazolamideAnticarcinogenic AgentsIsothiocyanatesNanog Homeobox ProteinNANOG protein, humanOctamer Transcription Factor-3POU5F1 protein, humanSOX2 protein, humanSOXB1 Transcription FactorssulforaphaneSulfoxides3D spheroidsAcetazolamideBronchial carcinoidCombination therapyOrthotopic lung modelSulforaphane

Identifiers

PMID31470802
PMCPMC6716820
OpenAlexW2971334346

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.