Evidence map›Paper›PMID 31609087›Full record

ArticleCancer medicine2019

A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in a peritoneally disseminated xenograft model.

Hidenori Ando, Masakazu Fukushima, Kiyoshi Eshima, Taichi Hasui, Taro Shimizu, Yu Ishima, Cheng-Long Huang, Hiromi Wada, Tatsuhiro Ishida

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

Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Hidenori AndoDepartment of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Masakazu FukushimaDepartment of Cancer Metabolism and Therapy, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Kiyoshi EshimaDelta-Fly Pharma Inc, Tokushima, Japan.
Taichi HasuiDepartment of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Taro ShimizuDepartment of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Yu IshimaDepartment of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Cheng-Long HuangDepartment of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Hiromi WadaDepartment of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Tatsuhiro IshidaDepartment of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.ORCID 0000-0002-1333-6465
Tokushima University · JPKyoto University · JPTokushima Bunri University · JP

Funding

Tokushima University
6 · The paper itself

Abstract

purposeIn advanced gastric cancer, peritoneal dissemination is a life-threatening mode of metastasis. Since the treatment options with conventional chemotherapy remain limited, any novel therapeutic strategy that could control such metastasis would improve the outcome of treatment. We recently developed a unique RNA interference therapeutic regimen (DFP-10825) consisting of short hairpin RNA against thymidylate synthase (TS shRNA) and cationic liposomes. The treatment with DFP-10825 has shown remarkable antitumor activity in peritoneally disseminated human ovarian cancer-bearing mice via intraperitoneal administration. In this study, we expanded DFP-10825 to the treatment of peritoneally disseminated gastric cancer.

methodsDFP-10825 was administered intraperitoneally into mice with intraperitoneally implanted human gastric cancer cells (MKN45 or NCI-N87). Antitumor activity and host survival benefits were monitored. Intraperitoneal distribution of fluorescence-labeled DFP-10825 was monitored in this MKN45 peritoneally disseminated mouse model.

resultsIntraperitoneal injection of DFP-10825 suppressed tumor growth in two peritoneally disseminated cancer models (MKN45 and NCI-N87) and increased the survival time of the MKN45 model without severe side effects. Throughout the treatment regimen, no significant body weight loss was associated with the administration of DFP-10825. Interestingly, after intraperitoneal injection, fluorescence-labeled DFP-10825 retained for more than 72 hours in the peritoneal cavity and selectively accumulated in disseminated tumors.

conclusionsIntraperitoneal injection of DFP-10825 demonstrated effective antitumor activity without systemic severe adverse effects via the selective delivery of RNAi molecules into disseminated tumors in the peritoneal cavity. Our current study indicates that DFP-10825 could become an alternative option to improve the outcomes of patients with peritoneally disseminated gastric cancer.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorHumansInjections, IntraperitonealLiposomesMaleMicePeritoneal NeoplasmsRNA, Small InterferingStomach NeoplasmsThymidylate SynthaseXenograft Model Antitumor AssaysAntineoplastic AgentsDFP-10825LiposomesRNA, Small InterferingThymidylate SynthaseDFP-10825gastric cancerperitoneal disseminationRNAi therapeuticS-1thymidylate synthase (TS)

Identifiers

PMID31609087
PMCPMC6885878
OpenAlexW2980947278

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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.