Evidence map›Paper›PMID 26088171›Full record

ArticleScientific reports2015

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform.

Qi Liu, Cheng Zhang, Xianting Ding, Hui Deng, Daming Zhang, Wei Cui, Hongwei Xu, Yingwei Wang, Wanhai Xu, Lei Lv and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2015. 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
–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

7 citing papers in PubMed.

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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

16 authors.

Qi LiuSchool of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China, and Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Cheng ZhangDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Xianting DingMed-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
Hui DengCancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
Daming ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Wei CuiSchool of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China, and Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Hongwei XuDepartment of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Yingwei WangDepartment of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Wanhai XuDepartment of Urology, The Forth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Lei LvCancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China.
Hongyu ZhangCancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China.
Yinghua HeCancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China.
Qiong WuSchool of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China, and Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Moshe SzyfDepartment of Pharmacology and Therapeutics McGill University Medical School 3655 Sir William Osler Promenade #1309, Montreal, Quebec Canada.
Chih-Ming HoMechanical and Aerospace Engineering Department, Biomedical Engineering Department, University of California, Los Angeles, CA 90095-1597, USA.
Jingde Zhu1] Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui 230031, China [2] Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai 200032, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holds promise for optimization of anti-cancer combination chemotherapy.

Indexed as

Drug Evaluation, PreclinicalModels, TheoreticalAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCell SurvivalDisease Models, AnimalDrug Resistance, NeoplasmDrug Therapy, CombinationHumansMiceSignal TransductionTumor BurdenUrinary Bladder NeoplasmsXenograft Model Antitumor AssaysAntineoplastic Agents

Identifiers

PMID26088171
PMCPMC5155572

What OpenQuestion holds

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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.