Evidence map›Paper›PMID 26518752›Full record

ArticleBiochemical pharmacology2015

Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth.

Yong Zhao, Mei-Juan Tu, Yi-Feng Yu, Wei-Peng Wang, Qiu-Xia Chen, Jing-Xin Qiu, Ai-Xi Yu, Ai-Ming Yu

Abstract read
In one paragraph

Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 3 pooled it
–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

52 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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  20. Osteosarcoma and Metastasis.Frontiers in oncology · 2021
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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

8 authors.

Yong ZhaoDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430070, China; Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Mei-Juan TuDepartment of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Yi-Feng YuDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430070, China.
Wei-Peng WangDepartment of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Qiu-Xia ChenDepartment of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Jing-Xin QiuDepartment of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Ai-Xi YuDepartment of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430070, China. Electronic address: yuaixi@whu.edu.cn.
Ai-Ming YuDepartment of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA. Electronic address: aimyu@ucdavis.edu.

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
MicroRNA-1291 in Regulation of Xenobiotic Disposition and Cell DifferentiationU01CA175315 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI YU, AIMING · 2014 to 2018
$1.6M
A New MicroRNA-1291 Replacement Therapy for Pancreatic Cancer DiseaseR41AA024029 · NIAAA · MIRNA THERAPEUTICS, INC. · PI BADER, ANDREAS G, YU, AIMING · 2014 to 2014
$225k
NCI NIH HHS P30 CA093373NCI NIH HHS P30CA093373NCI NIH HHS U01 CA175315NCI NIH HHS U01CA175315NIAAA NIH HHS R41 AA024029NIAAA NIH HHS R41AA024029
6 · The paper itself

Abstract

Osteosarcoma (OS) is the most common form of primary malignant bone tumor and prevalent among children and young adults. Recently we have established a novel approach to bioengineering large quantity of microRNA-34a (miR-34a) prodrug for miRNA replacement therapy. This study is to evaluate combination treatment with miR-34a prodrug and doxorubicin, which may synergistically suppress human OS cell growth via RNA interference and DNA intercalation. Synergistic effects were indeed obvious between miR-34a prodrug and doxorubicin for the suppression of OS cell proliferation, as defined by Chou-Talalay method. The strongest antiproliferative synergism was achieved when both agents were administered simultaneously to the cells at early stage, which was associated with much greater degrees of late apoptosis, necrosis, and G2 cell cycle arrest. Alteration of OS cellular processes and invasion capacity was linked to the reduction of protein levels of miR-34a targeted (proto-)oncogenes including SIRT1, c-MET, and CDK6. Moreover, orthotopic OS xenograft tumor growth was repressed to a significantly greater degree in mouse models when miR-34a prodrug and doxorubicin were co-administered intravenously. In addition, multiple doses of miR-34a prodrug and doxorubicin had no or minimal effects on mouse blood chemistry profiles. The results demonstrate that combination of doxorubicin chemotherapy and miR-34a replacement therapy produces synergistic antiproliferative effects and it is more effective than monotherapy in suppressing OS xenograft tumor growth. These findings support the development of mechanism-based combination therapy to combat OS and bioengineered miR-34a prodrug represents a new natural miRNA agent.

Indexed as

AnimalsBioengineeringBone NeoplasmsCell Line, TumorDose-Response Relationship, DrugDoxorubicinDrug Therapy, CombinationGrowth InhibitorsHumansMaleMiceMice, NudeMicroRNAsNeoplasm InvasivenessOsteosarcomaProdrugsDoxorubicinGrowth InhibitorsMicroRNAsMIRN34 microRNA, humanProdrugsChemotherapyDoxorubicinmiR-34aOrthotopic tumorOsteosarcoma

Identifiers

PMID26518752
PMCPMC4725324

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Registered trials

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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.