Evidence map›Paper›PMID 30863015›Full record

ArticleDrug design, development and therapy2019

siRNA-based breast cancer therapy by suppressing 17β-hydroxysteroid dehydrogenase type 1 in an optimized xenograft cell and molecular biology model in vivo.

Fang Li, ZhiHan Zhu, Man Xue, WanHong He, Ting Zhang, LingLin Feng, ShengXiang Lin

Open access · goldAbstract read
In one paragraph

Article in Drug design, development and therapy, 2019. 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 39% 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, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
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

7 authors at 2 institutions in 2 countries.

Fang LiNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
ZhiHan ZhuNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
Man XueNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
WanHong HeNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
Ting ZhangNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
LingLin FengNHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, and Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai 200032, China, fenglinglinxin@163.com.
ShengXiang LinAxe Molecular Endocrinology and Nephrology, CHU Research Center and Department of Molecular Medicine, Laval University, Québec, G1V 4G2, QC, Canada, sxlin@crchul.ulaval.ca.
Fudan University · CNUniversité Laval · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeHormone-dependent breast cancer is the most common form of breast cancer, and inhibiting 17β-HSD1 can play an attractive role in decreasing estrogen and cancer cell proliferation. However, the majority of existing inhibitors have been developed from estrogens and inevitably possess residual estrogenicity. siRNA knockdown provides a highly specific way to block a targeted enzyme, being especially useful to avoid estrogenicity. Application of 17β-HSD1-siRNA in vivo is limited by the establishment of an animal model, as well as the potential nuclease activity in vivo. We tried to reveal the in vivo potential of 17β-HSD1-siRNA-based breast cancer therapy. MATERIALS AND

methodsTo establish a competent animal model, daily subcutaneous injection of an estrone micellar aqueous solution was adopted to provide the substrate for estradiol biosynthesis. The effects of three different doses of estrone (0.1, 0.5, and 2.5 µg/kg/day) on tumor growth in T47D-17β-HSD1-inoculated group were investigated and compared with the animals inoculated with wild type T47D cells. To solve in vivo delivery problem of siRNA, "17β-HSD1-siRNA/LPD", a PEGylated and modified liposome-polycation-DNA nanoparticle containing 17β-HSD1-siRNA was prepared by the thin film hydration method and postinsertion technology. Finally, "17β-HSD1-siRNA/LPD" was tested in the optimized model. Tumor growth and 17β-HSD1 expression were assessed.

resultsComparison with the untreated group revealed significant suppression of tumor growth in "17β-HSD1-siRNA/LPD"-treated group when HSD17B1 gene expression was knocked down.

conclusionThese findings showed promising in vivo assessments of 17β-HSD1-siRNA candidates. This is the first report of an in vivo application of siRNA for steroid-converting enzymes in a nude mouse model.

Indexed as

Disease Models, AnimalAnimalsAntineoplastic AgentsBreast NeoplasmsCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorEnzyme InhibitorsEstradiol DehydrogenasesFemaleHumansMiceMice, Inbred BALB CMice, NudeRNA, Small InterferingStructure-Activity RelationshipAntineoplastic AgentsEnzyme InhibitorsEstradiol DehydrogenasesHSD17B1 protein, humanRNA, Small Interferinganimal modelbreast cancerestrogengene silencingHSD17B1

Identifiers

PMID30863015
PMCPMC6391152
OpenAlexW2917800338

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.