Evidence map›Paper›PMID 33753538›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2021

Synergistic Pharmacodynamic Effects of Gemcitabine and Fibroblast Growth Factor Receptor Inhibitors on Pancreatic Cancer Cell Cycle Kinetics and Proliferation.

Qingxiang Lin, Zhicheng Qian, William J Jusko, Donald E Mager, Wen Wee Ma, Robert M Straubinger

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Article
  4. Biochemistry and biophysics reports · 2022
    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

6 authors at 1 institution in 1 country.

Qingxiang LinDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.).
Zhicheng QianDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.).
William J JuskoDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.).
Donald E MagerDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.).
Wen Wee MaDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.).
Robert M StraubingerDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.M.S.; Z.Q., W.J.J., D.E.M.); Departments of Cell Stress Biology (Q.L., R.M.S.) and Pharmacology and Therapeutics (R.M.S.), Roswell Park Comprehensive Cancer Center, Buffalo, New York; and Department of Medicine, Mayo Clinic, Rochester, Minnesota (W.W.M.) rms@Buffalo.edu.ORCID 0000-0003-0870-9236
Roswell Park Comprehensive Cancer Center · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI CANDACE S JOHNSON · 1985 to 2026
$116.6M
YAP1 and RB1 cooperate to regulate lung cancer lineage plasticity and therapeutic resistanceU24CA274159 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI DAVID W. GOODRICH, Alan David Hutson · 2022 to 2026
$8.5M
Mechanistic Pharmacokinetics and PharmacodynamicsR35GM131800 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 2019 to 2023
$2.9M
Tumor priming sequences combined with novel nanoparticle drug carriers for enhanced therapeutic efficacy in pancreatic cancer: a tripartite USA/Northern Ireland/Republic of Ireland consortiumR01CA198096 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CLYNES, MARTIN, MA, WEN WEE · 2015 to 2019
$2.2M
Large-scale proteome-wide analysis with high accuracy/precision to guide pancreatic cancer therapy developmentR21CA234775 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MAGER, DONALD E, QU, JUN · 2019 to 2020
$399k
Pancreas cancer combination therapy based on stromal modulators and nano-carriersR21CA168454 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MA, WEN WEE, STRAUBINGER, ROBERT M · 2012 to 2013
$396k
NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA198096NCI NIH HHS R21 CA168454NCI NIH HHS R21 CA234775NCI NIH HHS U24 CA274159NIGMS NIH HHS R35 GM131800
6 · The paper itself

Abstract

Median survival of pancreatic ductal adenocarcinoma cancer (PDAC) is 6 months, with 9% 5-year survival. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and combination therapies integrating novel targeted agents could improve outcomes. Fibroblast growth factor (FGF) receptors (FGFRs) play important roles in PDAC growth and invasion. Therefore, FGFR inhibitors (FGFRi) merit further investigation. Efficacy of Gem combined with NVP-BGJ398, a pan-FGFRi, was investigated in multiple PDAC cell lines exposed to the drugs alone and combined. Cell cycle distribution and cell numbers were quantified over time. Two pharmacodynamic models were developed to investigate Gem/BGJ398 interactions quantitatively: a drug-mediated cell proliferation/death model, and a drug-perturbed cell cycle progression model. The models captured temporal changes in cell numbers, cell cycle progression, and cell death during drug exposure. Simultaneous fitting of all data provided reasonable parameter estimates. Therapeutic efficacy was then evaluated in a PDAC mouse model. Compared with Gem alone, combined Gem + FGFRi significantly downregulated ribonucleotide-diphosphate reductase large subunit 1 (RRM1), a gemcitabine resistance (GemR) biomarker, suggesting the FGFRi inhibited GemR emergence. The cell proliferation/death pharmacodynamic model estimated the drug interaction coefficient

Indexed as

Cell CycleCell ProliferationDeoxycytidineDrug SynergismGemcitabinePancreatic NeoplasmsReceptors, Fibroblast Growth FactorAnimalsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Pancreatic DuctalCell Line, TumorFemaleHumansKineticsMiceMice, NudeDeoxycytidineGemcitabineinfigratinibPhenylurea CompoundsPyrimidinesReceptors, Fibroblast Growth Factor

Identifiers

PMID33753538
PMCPMC9885358
OpenAlexW3139240374

What Socratic holds

Textmetadata
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.