Evidence map›Paper›PMID 33915939›Full record

ArticleBiomolecules2021

Inhibition of the Receptor for Advanced Glycation End Products Enhances the Cytotoxic Effect of Gemcitabine in Murine Pancreatic Tumors.

Priyanka Swami, Kelly A O'Connell, Swetha Thiyagarajan, Ayrianne Crawford, Prathamesh Patil, Prakash Radhakrishnan, Simon Shin, Thomas C Caffrey, James Grunkemeyer, Tammi Neville and 3 more

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

Article in Biomolecules, 2021. 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
1.1field-weighted citation impact, top 26% 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, 13 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

13 authors at 2 institutions in 1 country.

Priyanka SwamiDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.
Kelly A O'ConnellEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Swetha ThiyagarajanDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.ORCID 0000-0002-7782-0117
Ayrianne CrawfordEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Prathamesh PatilEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Prakash RadhakrishnanEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.ORCID 0000-0001-5314-1630
Simon ShinEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Thomas C CaffreyEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
James GrunkemeyerEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Tammi NevilleDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.ORCID 0000-0001-6642-9449
Stefan W VetterDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.
Michael A HollingsworthEppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Estelle LeclercDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.
University of Nebraska Medical Center · USNorth Dakota State University · US

Funding

Targeting CLEC-2/podoplanin as a therapeutic strategy for pancreatic cancerP20GM109024 · NIGMS · NORTH DAKOTA STATE UNIVERSITY · PI Megan Orr · 2016 to 2026
$20.5M
Tracking and Evaluation CoreU54GM128729 · NIGMS · UNIVERSITY OF NORTH DAKOTA · PI BASSON, MARC D. · 2018 to 2022
$20.3M
Pilot Projects: Core DP30GM103332 · NIGMS · NORTH DAKOTA STATE UNIVERSITY · PI SIBI, MUKUND P. · 2012 to 2016
$4.9M
NIGMS NIH HHS P20 GM109024NIGMS NIH HHS P30 GM103332NIGMS NIH HHS U54 GM128729
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a very difficult cancer to treat. Recent in vitro and in vivo studies suggest that the activation of the receptor for advanced glycation end products (RAGE) by its ligands stimulates pancreatic cancer cell proliferation and tumor growth. Additional studies show that, in the RAGE ligand, the high mobility group box 1 (HMGB1) protein plays an important role in chemoresistance against the cytotoxic agent gemcitabine by promoting cell survival through increased autophagy. We hypothesized that blocking the RAGE/HMGB1 interaction would enhance the cytotoxic effect of gemcitabine by reducing cell survival and autophagy. Using a preclinical mouse model of PDAC and a monoclonal antibody (IgG 2A11) as a RAGE inhibitor, we demonstrate that RAGE inhibition concurrent with gemcitabine treatment enhanced the cytotoxic effect of gemcitabine. The combination of IgG 2A11 and gemcitabine resulted in decreased autophagy compared to treatment with gemcitabine combined with control antibodies. Notably, we also observed that RAGE inhibition protected against excessive weight loss during treatment with gemcitabine. Our data suggest that the combination of gemcitabine with a RAGE inhibitor could be a promising therapeutic approach for the treatment of pancreatic cancer and needs to be further investigated.

Indexed as

AnimalsAntibodies, MonoclonalApoptosisAutophagyCell Line, TumorCell SurvivalDeoxycytidineGemcitabineHMGB1 ProteinMiceMicrotubule-Associated ProteinsPancreatic NeoplasmsPoly(ADP-ribose) PolymerasesReceptor for Advanced Glycation End ProductsTransplantation, HomologousAntibodies, MonoclonalDeoxycytidineGemcitabineHMGB1 ProteinMicrotubule-Associated ProteinsPoly(ADP-ribose) PolymerasesReceptor for Advanced Glycation End Productscachexiagemcitabinepancreatic cancerRAGE

Identifiers

PMID33915939
PMCPMC8067004
OpenAlexW3149403635

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.