Evidence map›Paper›PMID 27440271›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017

Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer.

Rafael Duran, Sahar Mirpour, Vasily Pekurovsky, Shanmugasundaram Ganapathy-Kanniappan, Cory F Brayton, Toby C Cornish, Boris Gorodetski, Juvenal Reyes, Julius Chapiro, Rüdiger E Schernthaner and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

15 authors.

Rafael DuranRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Sahar MirpourRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Vasily PekurovskyRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Shanmugasundaram Ganapathy-KanniappanRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Cory F BraytonDepartment of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Toby C CornishDepartment of Pathology, Division of Gastrointestinal and Liver Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Boris GorodetskiRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Juvenal ReyesDepartment of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins Hospital, Baltimore, Maryland.
Julius ChapiroRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Rüdiger E SchernthanerRussell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland.
Constantine FrangakisDepartment of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
MingDe LinDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut.
Jessica D SunThreshold Pharmaceuticals, South San Francisco, California.
Charles P HartThreshold Pharmaceuticals, South San Francisco, California.
Jean-François GeschwindDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut. jeff.geschwind@yale.edu.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
See, Reach, Treat Tumor-Optimized Transarterial Chemoembolization DrugDeliveryR01CA160771 · NCI · YALE UNIVERSITY · PI GESCHWIND, JEAN-FRANCOIS H, LIN, MINGDE · 2011 to 2015
$2.6M
NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA160771
6 · The paper itself

Abstract

purposeTo evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intra-arterial therapy (HAIAT) with evofosfamide in a rabbit model. EXPERIMENTAL

designVX2-tumor-bearing rabbits were assigned to 4 intra-arterial therapy (IAT) groups (n = 7/group): (i) saline (control); (ii) evofosfamide (Evo); (iii) doxorubicin-lipiodol emulsion followed by embolization with 100-300 μm beads (conventional, cTACE); or (iv) cTACE and evofosfamide (cTACE + Evo). Blood samples were collected pre-IAT and 1, 2, 7, and 14 days post-IAT. A semiquantitative scoring system assessed hepatocellular damage. Tumor volumes were segmented on multidetector CT (baseline, 7/14 days post-IAT). Pathologic tumor necrosis was quantified using manual segmentation on whole-slide images. Hypoxic fraction (HF) and compartment (HC) were determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia, and metabolism were quantified (γ-H2AX, Annexin V, caspase-3, Ki-67, HIF1α, VEGF, GAPDH, MCT4, and LDH).

resultscTACE + Evo showed a similar profile of liver enzymes elevation and pathologic scores compared with cTACE. Neither hematologic nor renal toxicity were observed. Animals treated with cTACE + Evo demonstrated smaller tumor volumes, lower tumor growth rates, and higher necrotic fractions compared with cTACE. cTACE + Evo resulted in a marked reduction in the HF and HC. Correlation was observed between decreases in HF or HC and tumor necrosis. cTACE + Evo promoted antitumor effects as evidenced by increased expression of γ-H2AX, apoptotic biomarkers, and decreased cell proliferation. Increased HIF1α/VEGF expression and tumor glycolysis supported HAIAT.

conclusionsHAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and enhanced anticancer effects of evofosfamide in combination with cTACE pave the way towards clinical trials in patients with liver cancer. Clin Cancer Res; 23(2); 536-48. ©2016 AACR.

Indexed as

Tumor HypoxiaAnimalsApoptosisBiomarkers, TumorCell ProliferationCirculating Tumor DNACombined Modality TherapyDisease Models, AnimalDoxorubicinEthiodized OilHumansLiver NeoplasmsNitroimidazolesPhosphoramide MustardsRabbitsBiomarkers, TumorCirculating Tumor DNADoxorubicinEthiodized OilNitroimidazolesPhosphoramide MustardsTH 302

Identifiers

PMID27440271
PMCPMC5241187

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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.