Evidence map›Paper›PMID 26902080›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2016

Tumor-specific promoter-driven adenoviral therapy for insulinoma.

Alan Wei-Shun Tseng, Chiachen Chen, Mary B Breslin, Michael S Lan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-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

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. International journal of molecular sciences · 2023
    Article
  5. Review
  6. Review
  7. Oncolytic viruses-immunotherapeutics on the rise.Journal of molecular medicine (Berlin, Germany) · 2016
    Review
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

4 authors at 3 institutions in 2 countries.

Alan Wei-Shun TsengThe Research Institute for Children, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA, 70118, USA.
Chiachen ChenThe Research Institute for Children, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA, 70118, USA.
Mary B BreslinThe Research Institute for Children, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA, 70118, USA.
Michael S LanThe Research Institute for Children, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA, 70118, USA. mlan@chnola-research.org.
Children's Hospital of New Orleans · USLouisiana State University Health Sciences Center New Orleans · USMedical Research Foundation · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInsulinomas are the most common type of neuroendocrine (NE) pancreatic islet tumors. Patients with insulinomas may develop complications associated with hyperinsulinemia. To increase the treatment options for insulinoma patients, we have tested a conditionally replicating adenovirus that has been engineered in such a way that it can specifically express therapeutic genes in NE tumors.

methodsWe used a promoter-specific adenoviral vector delivery system that is regulated by an INSM1 (insulinoma-associated-1) promoter, which is silent in normal adult tissues but active in developing NE cells and tumors. Through a series of modifications, using an insulator (HS4) and neuron-restrictive silencer elements (NRSEs), an oncolytic adenoviral vector was generated that retains tumor specificity and drives the expression of a mutated adenovirus E1A gene (Δ24E1A) and the herpes simplex virus thymidine kinase (HSV-tk) gene. The efficacy of this vector was tested in insulinoma-derived MIN, RIN, βTC-1 and pancreatic (Panc-1) cells using in vitro cell survival and in vivo tumor growth assays.

resultsUsing in vitro insulinoma-derived cell lines and an in vivo subcutaneous mouse tumor model we found that the INSM1 promoter-driven viruses were able to replicate specifically in INSM1-positive cells. INSM1-specific HSV-tk expression in combination with ganciclovir treatment resulted in dose-dependent tumor cell killing, leaving INSM1-negative cells unharmed. When we combined the INSM1-promoter driven HSV-tk with Δ24E1A and INSM1p-HSV-tk (K5) viruses, we found that the co-infected insulinoma-derived cells expressed higher levels of HSV-tk and exhibited more efficient tumor suppression than cells infected with INSM1p-HSV-tk virus alone.

conclusionsINSM1 promoter-driven conditionally replicating adenoviruses may serve as a new tool for the treatment of insulinoma and may provide clinicians with additional options to combat this disease.

Indexed as

InsulinomaPancreatic NeoplasmsPromoter Regions, GeneticAdenoviridaeAnimalsAntineoplastic AgentsBlotting, WesternCell Line, TumorGanciclovirGenetic TherapyGenetic VectorsHumansMiceOncolytic VirotherapyRepressor ProteinsThymidine KinaseAntineoplastic AgentsGanciclovirINSM1 protein, humanRepressor ProteinsThymidine KinaseEndocrine tumorGene therapyINSM1InsulinomaOncolytic

Identifiers

PMID26902080
PMCPMC13001840
OpenAlexW2277720811

What OpenQuestion holds

Textmetadata
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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.