Evidence map›Paper›PMID 41015572›Full record

ArticleCancer gene therapy2025

Paricalcitol and hydroxychloroquine modulates extracellular matrix and enhance chemotherapy efficacy in pancreatic cancer.

Dhana Sekhar Reddy Bandi, Sujith Sarvesh, Jeremy Foote, Doug Welsch, Changde Cheng, Mehmet Akce, Ganji Purnachandra Nagaraju, Bassel F El-Rayes

Abstract read
In one paragraph

Article in Cancer gene therapy, 2025. 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
–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

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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.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Dhana Sekhar Reddy BandiDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Sujith SarveshDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Jeremy FooteDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Doug WelschDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Changde ChengDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Mehmet AkceDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Ganji Purnachandra NagarajuDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID 0000-0002-4989-5234
Bassel F El-RayesDepartment of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA. belrayes@uabmc.edu.ORCID 0000-0003-0405-5503

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
ProAgio in Pancreatic CancerR01CA294647 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Bassel El-Rayes, Zhi-Ren Liu · 2024 to 2026
$1.7M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01CA294647NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA294647UAB | Comprehensive Cancer Center, University of Alabama at Birmingham (UAB Comprehensive Cancer Center) 5P30CAO13148-47
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis and limited therapeutic options. In a previous publication, our group defined some of the mechanisms that vitamin D analogue paricalcitol (P) and hydroxychloroquine (H) potentiated the effects of gemcitabine-based chemotherapy in PDAC. Based on this, we hypothesized that PH may potentiate 5-fluorouracil (5FU) and Oxaliplatin-based chemotherapy, and this may involve a novel mechanism of extracellular matrix (ECM) modulation. The combination of PH with 5FU+Oxaliplatin significantly increased the cell death, apoptosis, and S-phase cell cycle arrest as compared to untreated or 5FU + Oxaliplatin-treated MIA PaCa-2, HPAC and KPC cell lines. In vivo, the combination therapy inhibited PDAC growth and altered the immune landscape by activating T and NK cells. Proteomic analysis revealed significant reduction in ECM proteins, specifically integrin beta-4 (ITGB4). Confirmation of the role of ITGB4 was performed through genetic knockdown of ITGB4, which led ECM inhibition. In conclusion, the combination of PH significantly enhances the efficacy of Oxaliplatin and 5FU. We identified a new mechanism of action of PH through inhibiting ITGB4, leading to ECM modulation. These results suggest that the combination of PH with cytotoxic chemotherapy should be tested in PDAC clinical trials.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Pancreatic DuctalErgocalciferolsExtracellular MatrixHydroxychloroquinePancreatic NeoplasmsAnimalsCell Line, TumorFluorouracilHumansMiceOxaliplatinXenograft Model Antitumor AssaysErgocalciferolsFluorouracilHydroxychloroquineOxaliplatinparicalcitol

Identifiers

PMID41015572
PMCPMC12702779

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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.