Evidence map›Paper›PMID 37649964›Full record

ArticleMolecular & cellular oncology2023

Silencing Glypican-1 enhances the antitumor effects of Pictilisib via downregulating PI3K/Akt/ERK signaling in chemo-resistant esophageal adenocarcinoma.

Akshay Pratap, Andrea Qualman, Hedlund Garrett, Lindsey Westbrook, Erlinda The, Sanchayita Mitra, Mila Cordero, Kenneth Meza Monge, Juan-Pablo Idrovo, Argudit Chauhan and 7 more

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

Article in Molecular & cellular oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 24% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

17 authors at 3 institutions in 1 country.

Akshay PratapDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.ORCID https://orcid.org/0000-0002-9247-1840
Andrea QualmanDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.
Hedlund GarrettDepartment of Allergy and Clinical Immunology Flow Core, University of Colorado, Aurora, CO, USA.
Lindsey WestbrookDepartment of Pathology, University of Colorado, Aurora, CO, USA.
Erlinda TheDivision of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA.
Sanchayita MitraDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.
Mila CorderoSchool of Science, Engineering, & Technology, St. Mary's University, San Antonio, TX, USA.
Kenneth Meza MongeDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.
Juan-Pablo IdrovoDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.
Argudit ChauhanDepartment of Biomedical Engineering, University of Colorado, Boulder, USA.
Linling ChengDivision of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA.
Mitchell Jay CohenDivision of Gastrointestinal Tumor and Endocrine Surgery, University of Colorado, Aurora, CO, USA.
Benedetto MungoDivision of Surgical Oncology, University of Colorado, Aurora, CO, USA.
Sachin WaniDivision of Gastroenterology and Hepatology, University of Colorado, Aurora, CO, USA.
Robert Alexander MeguidDivision of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA.
Martin D McCarterDivision of Surgical Oncology, University of Colorado, Aurora, CO, USA.
Xianzhong MengDivision of Cardiothoracic Surgery, University of Colorado, Aurora, CO, USA.
University of Colorado Anschutz Medical Campus · USSt. Mary's University, Texas · USUniversity of Colorado Boulder · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Poorly differentiated esophageal adenocarcinoma (PDEAC) has a dismal prognosis. Glypican-1(GPC-1) is known to be upregulated in several cancer types in contrast to healthy tissues, rendering it as a biomarker. Nevertheless, the potential therapeutic targeting of GPC-1 has not been explored in PDEAC. There is accumulating evidence that GPC-1, via upregulation of PI3K/Akt/ERK signaling, plays a crucial role in the progression and chemoresistance in cancer. Pictilisib, a class I pan PI3K inhibitor, has shown promising antitumor results in clinical trials, however, has not gained widespread success due to acquired drug resistance. This study investigated the role of GPC-1 in chemo-resistant PDEAC and appraises the impact of targeted silencing of GPC-1 on the antitumor effects of Pictilisib in PDEAC cell lines. Immunohistochemistry assays in PDEAC tissue specimens demonstrated a pronounced intensity of staining with GPC-1. Upregulation of GPC-1 was found to be correlated with advanced stage and poor prognosis. In-vitro studies examined the influence of GPC-1 knockdown and Pictilisib, both as individual agents and in combination, on cytotoxicity, cell cycle distribution, apoptosis, and gene expression profiles. Silencing GPC-1 alone showed significantly reduced cell viability, migration, colony formation, epithelial-mesenchymal transition, and stemness in PDEAC cells. Significantly, knockdown of GPC-1 combined with low-dose Pictilisib led to enhancement of cytotoxicity, cell cycle arrest, and apoptosis in ESO-26 and OE-33 cells. In the xenograft mouse model, the combination of Pictilisib and GPC-1 knockdown exhibited synergy. These findings suggest that GPC-1 represents a promising target to augment chemosensitivity in esophageal adenocarcinoma.

Indexed as

chemoresistanceGlypican-1PI3K/Akt pathwaypictilisibPoorly differentiated esophageal adenocarcinoma (PDEAC)

Identifiers

PMID37649964
PMCPMC10464651
OpenAlexW4385875842

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

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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 Socratic graph.