Evidence mapPaperPMID 39000545Full record

ArticleInternational journal of molecular sciences2024

Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.

Reetobrata Basu, Prateek Kulkarni, Deborah Swegan, Silvana Duran-Ortiz, Arshad Ahmad, Lydia J Caggiano, Emily Davis, Christopher Walsh, Edward Brenya, Adeel Koshal and 4 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Growth Hormone, Not Simply Just a Hormone for Growth.Endocrinology and metabolism (Seoul, Korea) · 2026
    Review
  3. Article
  4. Article
  5. 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

14 authors.

Reetobrata BasuEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.ORCID 0000-0001-8415-1356
Prateek KulkarniEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.ORCID 0000-0002-4557-6535
Deborah SweganEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Silvana Duran-OrtizEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Arshad AhmadEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.ORCID 0009-0000-8427-8082
Lydia J CaggianoEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Emily DavisEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Christopher WalshEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
Edward BrenyaEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.ORCID 0009-0004-1161-6262
Adeel KoshalDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Rich BrodyInfinixBio LLC, Columbus, OH 43212, USA.
Uday SandbhorInfinixBio LLC, Columbus, OH 43212, USA.ORCID 0009-0003-8700-234X
Sebastian J C M M NeggersDepartment of Medicine, Endocrinology, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands.
John J KopchickEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.

Funding

Modulating Growth Hormone Action as a Target for Improved Health and LongevityR01AG059779 · NIA · OHIO UNIVERSITY ATHENS · PI John Joseph Kopchick · 2018 to 2026
$4.7M
NIA NIH HHS R01 AG059779
6 · The paper itself

Abstract

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)-GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor promotion and immune evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept toward considering GHR antagonists to improve chemotherapeutic outcomes in the highly chemoresistant PDAC.

Indexed as

Carcinoma, Pancreatic DuctalDeoxycytidineGemcitabinePancreatic NeoplasmsReceptors, SomatotropinXenograft Model Antitumor AssaysAnimalsCell Line, TumorDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudeDeoxycytidineGemcitabineReceptors, SomatotropinadjuvantchemoresistancechemotherapygemcitabineGHR antagonistGH receptor (GHR)growth hormone (GH)insulin-like growth factor 1 (IGF1)pancreatic cancerpancreatic ductal adenocarcinoma

Identifiers

PMID39000545
PMCPMC11242728

What Socratic 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 Socratic graph.