“Lack of experience and understanding” forces duplication retractions of liver cancer paper

dovelogoA group of researchers in China has lost their paper on liver cancer after the first author admitted to duplication, also known, inelegantly, as self-plagiarism.

The paper, “Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells,” appeared in the July 2013 issue of the Journal of Drug Design, Development and Therapy, a Dove Press title.

According to the abstract:

Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma.

Here’s the notice:

It has come to the notice of this journal that the published paper: Cheng M, Xu H, Wang Y, et al. Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells. Drug Des Devel Ther. 2013;7:1287–1299. Plagiarised the work of: Cheng M, Gao X, Wang Y, et al. Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo. Marine Drugs. 2013;11(9):3517–3536.
The first author, Mingrong Cheng, brought this to our attention, has admitted the fault was his own, due to lack of experience and understanding, and apologized.

Somewhat confusing, however, is that the Marine Drugs paper was submitted in August 2013. So why wouldn’t that one have been retracted?

Speaking of Marine Drugs, here’s the abstract from that paper:

Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR) and 1H-nuclear magnetic resonance (1H-NMR). By combining GA-CTS and 5-FU (5-fluorouracil), we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.

We think the folks at Dove might want to compare that text to the abstract for another 2013 paper by Cheng, “Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics,” in the International Journal of Nanomedicine. Consider:

The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model.

And this one, also from the International Journal of Nanomedicine, in 2013:

Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival.

One thought on ““Lack of experience and understanding” forces duplication retractions of liver cancer paper”

  1. Essential information on the first page of the journal (http://www.dovepress.com/drug-design-development-and-therapy-journal) that would also lend clues about the failure of the publisher and the editors/peers in detecting this duplication during submission and peer review:
    a) the EIC is Chinese, Professor Shufeng Zhou;
    b) there is an IF of 3.486;
    c) 15 days from submission to first editorial decision;
    d) 42 days from editorial acceptance to publication.

    Actually, what is the journal name? The journal page lists it as “Drug Design, Development and Therapy” but RW has it listed as “Journal of Drug Design, Development and Therapy”. Is “Journal of” correct, or not?

    Dove Press authorship responsibilities (http://www.dovepress.com/author_guidelines.php) state (sounds an awful lot like the ICMJE guidelines):
    “Authorship credit should be based on:
    1) Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data;
    2) Drafting the article or revising it critically for important intellectual content;
    3) Final approval of the version to be published; and
    4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
    Authors should meet conditions 1, 2, 3, and 4.”

    So even though Mingrong Cheng was thrown under the bus (or threw himself under the bus), let’s be abundantly clear: all co-authors share communal responsibility.

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