Evidence map›Paper›PMID 30465822›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2019

Drug-free albumin-triggered sensitization of cancer cells to anticancer drugs.

Lian Li, Jiyuan Yang, Sirima Soodvilai, Jiawei Wang, Praneet Opanasopit, Jindřich Kopeček

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 24 citations in OpenAlex.

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  8. Multi-targeted immunotherapeutics to treat B cell malignancies.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  9. Article
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  12. Article
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  15. Polymer nanomedicines.Advanced drug delivery reviews · 2020
    Review
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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

6 authors at 2 institutions in 2 countries.

Lian LiDepartment of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
Jiyuan YangDepartment of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
Sirima SoodvilaiDepartment of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA; Faculty of Pharmacy, Silpakorn University,Nakhon Pathom, Thailand.
Jiawei WangDepartment of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
Praneet OpanasopitFaculty of Pharmacy, Silpakorn University,Nakhon Pathom, Thailand.
Jindřich KopečekDepartment of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jindrich.kopecek@utah.edu.
University of Utah · USSilpakorn University · TH

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI KATHARINE S ULLMAN · 1986 to 2026
$72.6M
Drug-Free Macromolecular TherapeuticsR01GM095606 · NIGMS · UNIVERSITY OF UTAH · PI KOPECEK, JINDRICH H. · 2011 to 2018
$2.3M
NIGMS NIH HHS R01 GM095606
6 · The paper itself

Abstract

Chemosensitization strategies have been used to sensitize cancer cells to conventional drugs, but their utility is often obstructed by additional off-target toxicity, limited access to intracellular targets and heterogeneous tumor pathogenesis. To address these challenges, we rationally developed a drug-free human serum albumin (HSA)-based therapeutic (KH-1) that functions extracellularly and exhibits pleiotropic effect on multiple intracellular signaling pathways. It is a two-step touch-trigger system that consists of a pretargeting anchor on surface receptor CD20 (anti-CD20 Fab' conjugated with a morpholino oligonucleotide 1) and a CD20 clustering actuator (HSA grafted with multiple copies of complementary morpholino oligonucleotide 2). The extracellular actuation by surface CD20 crosslinking boosts robust activations of numerous intracellular responses, and promotes cancer cell susceptibility to various anticancer drugs, including docetaxel (microtubule stabilizer), gemcitabine (nucleoside analogue) and GDC-0980 (PI3K/mTOR inhibitor). The broad applicability of KH-1 is demonstrated to result from simultaneous inhibition of survival pathways and augmentation of apoptotic pathways. In addition, KH-1 covalently conjugated with anthracycline anticancer agent, epirubicin, integrates the advantages of both chemosensitization function and improved intracellular drug delivery in a single system and takes effect on the same cell. Therefore, in the present study, we have provided mechanistic demonstration that crosslinking of surface receptors can be leveraged to elicit chemosensitization.

Indexed as

Antigens, CD20Antineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCell SurvivalDeoxycytidineDocetaxelDrug Resistance, NeoplasmEpirubicinGemcitabineHumansPyrimidinesSerum Albumin, Human1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-oneAntigens, CD20Antineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicDeoxycytidineDocetaxelEpirubicinGemcitabinePyrimidinesSerum Albumin, HumanChemosensitizationDrug-free macromolecular therapeuticsHuman serum albuminReceptor crosslinkingSignal transduction

Identifiers

PMID30465822
PMCPMC6317733
OpenAlexW2901034718

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.