Evidence map›Paper›PMID 26177970›Full record

ArticleGene therapy2015

Persistence of hAQP1 expression in human salivary gland cells following AdhAQP1 transduction is associated with a lack of methylation of hCMV promoter.

C Zheng, B J Baum, X Liu, C M Goldsmith, P Perez, S-I Jang, A P Cotrim, L McCullagh, I S Ambudkar, I Alevizos

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00372320 (Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of AdhAQP1, an Adenoviral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-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.

NCT00372320 phase1completednot on this map

Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of AdhAQP1, an Adenoviral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction

TypeinterventionalSponsorNational Institute of Dental and Craniofacial Research (NIDCR)Ran2006 to 2018Enrolled17ConditionsParotid Salivary DysfunctionArmsGene Transfer, AdhAQP1
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023
    Article
  3. Review
  4. Review
  5. Advances on mechanism and treatment of salivary gland in radiation injury.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021
    Article
  6. Article
  7. Article
  8. Article
  9. Aquaporins in Salivary Glands: From Basic Research to Clinical Applications.International journal of molecular sciences · 2016
    Review
  10. Article
  11. 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

10 authors at 2 institutions in 1 country.

C ZhengMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
B J BaumMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
X LiuMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
C M GoldsmithMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
P PerezMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
S-I JangMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
A P CotrimMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
L McCullaghMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
I S AmbudkarMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
I AlevizosMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
National Institute of Dental and Craniofacial Research · USNational Institutes of Health · US

Funding

Molecular Mechanisms Regulating Calcium Flux In Salivary GlandsZIADE000438 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI AMBUDKAR, INDU S. · 2009 to 2025
$42.5M
Clinical Investigations of Sjogren's SyndromeZIADE000704 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI WARNER, BLAKE · 2009 to 2025
$22.3M
Intramural NIH HHS ZIA DE000438
6 · The paper itself

Abstract

In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector encoding human aquaporin-1 (hAQP1). This vector uses the human cytomegalovirus enhancer/promoter (hCMVp). As subject peak responses were at times much longer (7-42 days) than expected, we hypothesized that the hCMVp may not be methylated in human salivary gland cells to the extent previously observed in rodent salivary gland cells. This hypothesis was supported in human salivary gland primary cultures and human salivary gland cell lines after transduction with AdhAQP1. Importantly, hAQP1 maintained its function in those cells. Conversely, when we transduced mouse and rat cell lines in vitro and submandibular glands in vivo with AdhAQP1, the hCMVp was gradually methylated over time and associated with decreased hAQP1 expression and function in vitro and decreased hAQP1 expression in vivo. These data suggest that the hCMVp in AdhAQP1was probably not methylated in transduced human salivary gland cells of responding subjects, resulting in an unexpectedly longer functional expression of hAQP1.

Indexed as

Gene ExpressionPromoter Regions, GeneticTransduction, GeneticAnimalsAquaporin 1Cell LineCytomegalovirusHumansMethylationMiceRatsSalivary GlandsAQP1 protein, humanAquaporin 1

Identifiers

PMID26177970
PMCPMC5798873
OpenAlexW1574505648

What OpenQuestion holds

Textmetadata
LicenceTDM
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.