Evidence map›Paper›PMID 32004588›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2020

Ultrasound-mediated delivery of miRNA-122 and anti-miRNA-21 therapeutically immunomodulates murine hepatocellular carcinoma in vivo.

Jennifer C Wischhusen, Sayan Mullick Chowdhury, Taehwa Lee, Huaijun Wang, Sunitha Bachawal, Rammohan Devulapally, Rayhaneh Afjei, Uday Kumar Sukumar, Ramasamy Paulmurugan

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

30 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
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  6. Review
  7. Article
  8. Review
  9. miRNAs in HCC, pathogenesis, and targets.Hepatology (Baltimore, Md.) · 2024
    Article
  10. Review
  11. Engineering Versatile Nanomedicines for Ultrasonic Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
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  18. Article
  19. Review
  20. Expression Analysis ofInternational journal of molecular sciences · 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

9 authors at 3 institutions in 2 countries.

Jennifer C WischhusenApoptosis, Cancer and Development Laboratory, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, 69008 Lyon, France; Department of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Sayan Mullick ChowdhuryDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Taehwa LeeDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Huaijun WangDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: whjwang@stanford.edu.
Sunitha BachawalDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: bachawal@stanford.edu.
Rammohan DevulapallyDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA.
Rayhaneh AfjeiDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: rafjei@stanford.edu.
Uday Kumar SukumarDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: udkr8817@stanford.edu.
Ramasamy PaulmuruganDepartment of Radiology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: paulmur8@stanford.edu.
Stanford Medicine · USStanford University · USUniversité Claude Bernard Lyon 1 · FR

Funding

Therapeutic miRNA Modulation of Hepatocellular Carcinoma Using Ultrasound Guided Drug DeliveryR01CA209888 · NCI · STANFORD UNIVERSITY · PI DAHL, JEREMY, PAULMURUGAN, RAMASAMY · 2017 to 2021
$3.1M
Molecular Ultrasound for Early Breast Cancer DetectionR01CA155289 · NCI · STANFORD UNIVERSITY · PI WILLMANN, JUERGEN KARL · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA155289NCI NIH HHS R01 CA209888
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the most common cause of cancer-related mortality, and patients with HCC show poor response to currently available treatments, which demands new therapies. We recently developed a synthetic microRNA-based molecularly targeted therapy for improving HCC response to chemotherapy by eliminating drug resistance. We used ultrasound-targeted microbubble destruction (UTMD) to locally deliver microRNA-loaded nanoparticles to HCC. Since the immune microenvironment plays a crucial role in HCC disease development and response to treatment, and UTMD and microRNAs have the potential to interfere with the immune system, in this study we analyzed the immunomodulatory effects of UTMD and miRNAs in HCC. We used an immunocompetent syngeneic HCC mouse model for the study. We conducted cytokine profiling in tumor, lymph nodes, and serum of animals within the first 24 h of treatment to analyze changes in the level of pro- and antitumoral cytokines. The results showed: (1) Hepa1-6 syngeneic tumors expressed HCC-related cytokines, (2) UTMD-microRNA combination therapy triggered transient cytokine storms, and (3) delivery of microRNA-122 and anti-microRNA-21 affected the immune microenvironment by decreasing the level of GM-CSF in tumors while modulating protumoral IL-1α, IL-1β, IL-5, IL-6 and IL-17 and antitumoral IL-2 and IL-12 in tumor-proximal lymph nodes, and increasing IL-2 in the serum of tumor-bearing mice. Local delivery of targeted therapy by UTMD significantly reduced the concentration of IL-12 and IL-17 in lymph nodes of treated and contralateral tumors suggesting a systemic response.

conclusionUTMD-mediated delivery of microRNA-122 and anti-microRNA-21 modulated the immune microenvironment of Hepa1-6 tumors at the level of cytokine expressions. Exploiting antitumoral immune effects could enhance the therapeutic efficacy of the proposed combination therapy for HCC.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsMicroRNAsAnimalsHumansMiceMicrobubblesTumor MicroenvironmentUltrasonographyMicroRNAsMIRN122 microRNA, humanMIRN21 microRNA, humanCytokine screeningLocal drug deliveryPoly (lactic-co-glycolic acid) nanoparticlesTumor immune responseUltrasound-targeted microbubble destruction

Identifiers

PMID32004588
PMCPMC7170770
OpenAlexW3003991562

What OpenQuestion holds

Textmetadata
LicenceTDM
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.