Evidence map›Paper›PMID 26121939›Full record

ArticleOral oncology2015

BH3-mimetic small molecule inhibits the growth and recurrence of adenoid cystic carcinoma.

Gerson A Acasigua, Kristy A Warner, Felipe Nör, Joseph Helman, Alexander T Pearson, Anna C Fossati, Shaomeng Wang, Jacques E Nör

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

Article in Oral oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Systemic therapies for salivary gland adenoid cystic carcinoma.American journal of cancer research · 2021
    Review
  6. Trends in Surgical Research in Head and Neck Cancer.Current treatment options in oncology · 2017
    Review
  7. Article
  8. Therapeutic Inhibition of the MDM2-p53 Interaction Prevents Recurrence of Adenoid Cystic Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Article
  9. 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

8 authors at 2 institutions in 2 countries.

Gerson A AcasiguaDepartment of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, United States; Department of Morphological Sciences, Federal University of Rio Grande do Sul, Brazil.
Kristy A WarnerDepartment of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, United States.
Felipe NörDepartment of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, United States; Department of Morphological Sciences, Federal University of Rio Grande do Sul, Brazil.
Joseph HelmanDepartment of Oral and Maxillofacial Surgery, University of Michigan School of Dentistry, United States; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States.
Alexander T PearsonDepartment of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, United States; Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, United States.
Anna C FossatiDepartment of Morphological Sciences, Federal University of Rio Grande do Sul, Brazil.
Shaomeng WangDepartment of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, United States; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States.
Jacques E NörDepartment of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, United States; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States; Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI, United States; Department of Otolaryngology, University of Michigan School of Medicine, Ann Arbor, MI, United States. Electronic address: jenor@umich.edu.
University of Michigan · USUniversidade Federal do Rio Grande do Sul · BR

Funding

Therapeutic Potential and Mechanism of Action of Potent Small Molecule InhibitorsP50CA097248 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WOLF, GREGORY T · 2002 to 2013
$25.3M
Salivary gland cancer stem cellsR01DE021139 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jacques Eduardo Nor · 2011 to 2026
$5.8M
Therapeutic Inhibition of MDM2/Bcl-2 in Pre-clinical Models of Adenoid Cystic CarR01DE023220 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NOR, JACQUES EDUARDO · 2012 to 2015
$1.5M
NCI NIH HHS P50 CA097248NCI NIH HHS P50-CA-97248NIDCR NIH HHS R01 DE021139NIDCR NIH HHS R01 DE023220NIDCR NIH HHS R01-DE21139NIDCR NIH HHS R01-DE23220
6 · The paper itself

Abstract

objectivesTo evaluate the anti-tumor effect of BM-1197, a new potent and highly specific small molecule inhibitor of Bcl-2/Bcl-xL, in preclinical models of human adenoid cystic carcinoma (ACC).

methodsLow passage primary human adenoid cystic carcinoma cells (UM-HACC-2A,-2B,-5,-6) and patient-derived xenograft (PDX) models (UM-PDX-HACC) were developed from surgical specimens obtained from 4 patients. The effect of BM-1197 on cell viability and cell cycle were evaluated in vitro using this panel of low passage ACC cells. The effect of BM-1197 on tumor growth, recurrence and tumor cell apoptosis in vivo was evaluated with the PDX model of ACC (UM-PDX-HACC-5).

resultsExposure of low passage primary human ACC cells to BM-1197 mediated an IC50 of 0.92-2.82 μM. This correlated with an increase in the fraction of apoptotic cells (p<0.0001) and an increase in caspase-3 activity (p<0.0001), but no noticeable differences in cell cycle (p>0.05). In vivo, BM-1197 inhibited tumor growth (p=0.0256) and induced tumor cell apoptosis (p=0.0165) without causing significant systemic toxicities, as determined by mouse weight over time. Surprisingly, weekly BM-1197 decreased the incidence of tumor recurrence (p=0.0297), as determined by Kaplan-Meier analysis.

conclusionThese data demonstrated that single agent BM-1197 induces apoptosis and inhibits tumor growth in preclinical models of adenoid cystic carcinoma. Notably, single agent BM-1197 inhibited tumor recurrence, which is considered a major clinical challenge in the clinical management of adenoid cystic carcinoma. Collectively, these results suggest that patients with adenoid cystic carcinoma might benefit from therapy with a BH3-mimetic small molecule.

Indexed as

Aniline CompoundsAnimalsApoptosisCarcinoma, Adenoid CysticCaspase 3Cell CycleFemaleHumansKaplan-Meier EstimateMaleMiceMiddle AgedNeoplasm Recurrence, LocalNeoplasms, ExperimentalSalivary Gland NeoplasmsSulfonamidesAniline CompoundsBM-1197Caspase 3SulfonamidesApoptosisBcl-2Bcl-x(L)Resistance to therapySalivary gland cancerTargeted therapyTumor recurrence

Identifiers

PMID26121939
PMCPMC4532618
OpenAlexW1959740745

What OpenQuestion holds

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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.