Evidence map›Paper›PMID 34032307›Full record

ArticleThe Prostate2021

Longitudinal measurement of subcutaneous and intratibial human prostate cancer xenograft growth and response to ionizing radiation by plasma Alu and LINE-1 ctDNA: A comparison to standard methods.

Alok Mishra, Kenji Zennami, Esteban Velarde, Daniel L J Thorek, Srinivasan Yegnasubramanian, Theodore L DeWeese, Shawn E Lupold

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Prostate, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 50% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
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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

7 authors at 1 institution in 1 country.

Alok MishraDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kenji ZennamiDepartment of Urology, The James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Esteban VelardeDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Daniel L J ThorekDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-2437-1239
Srinivasan YegnasubramanianDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Theodore L DeWeeseDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Shawn E LupoldDepartment of Urology, The James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0002-5449-0362
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
Kallikrein-Targeted Alpha-Particle Therapy of Late-Stage Prostate CancerR01CA201035 · NCI · WASHINGTON UNIVERSITY · PI THOREK, DANIEL LYNDON JAFFE · 2017 to 2020
$1.4M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236
6 · The paper itself

Abstract

backgroundCurrent preclinical models of metastatic prostate cancer (PCa) require sophisticated technologies and/or genetically engineered cells for the noninvasive monitoring of tumors in remote sites, such as bone. Recent developments in circulating tumor DNA (ctDNA) analysis provide an alternative method for noninvasive tumor monitoring at a low cost. Here, we sought to evaluate human Alu and LINE-1 ctDNA for the longitudinal measurement of subcutaneous and intratibial human PCa xenograft growth and response to ionizing radiation (IR) through comparison with standard slide caliper and bioluminescence measurements. MATERIAL AND

methodsIntratibial and subcutaneous xenografts were established in male athymic nude mice using LNCaP cells that stably express firefly luciferase. A subset of tumors was treated with a single dose of IR (CT-guided focal IR, 6 Gy). Tumor measurements were simultaneously taken by slide caliper (subcutaneous only), in vivo bioluminescence imaging, and quantitative real-time PCR (qPCR) of human-specific Alu and LINE-1 ctDNA for several weeks.

resultsLevels of ctDNA and bioluminescence increased concordantly with subcutaneous and intratibial tumor growth. A statistically significant correlation (Spearman) was observed between ctDNA and subcutaneous tumor volume (LINE-1, r = .94 and Alu, r = .95, p < .0001), ctDNA and bioluminescence (LINE-1, r = .66 and Alu, r = .60, p < .002), and bioluminescence and tumor volume (r = .66, p = .0003). Bioluminescence and ctDNA were also significantly correlated in intratibial tumors (LINE-1, r = .82 and Alu, r = .81, p < .0001). Following external beam IR, the tumor responses varied briefly by method of measurement, but followed a similar trend. Statistically significant correlations were maintained between ctDNA and slide caliper measurement in irradiated subcutaneous tumors (LINE-1, r = .64 and Alu, r = .44, p < .02), and ctDNA and bioluminescence in intratibial tumors (LINE-1, r = .55, p = .018).

conclusionsReal-time qPCR of circulating human Alu and LINE-1 DNA provides an accurate measurement of subcutaneous and intratibial xenograft burden that is comparable with conventional bioluminescence imaging and slide caliper measurement. Transient differences in measurements were observed following tumor-targeted IR, but overall all measurements mirrored tumor growth and response.

Indexed as

Xenograft Model Antitumor AssaysAlu ElementsAnimalsCirculating Tumor DNAHumansLong Interspersed Nucleotide ElementsLuminescent MeasurementsMaleMiceMice, NudeProstatic NeoplasmsSubcutaneous FatTibiaTumor BurdenCirculating Tumor DNAbioluminescent imagingbone metastasesctDNAionizing radiationmouse modelsprostate cancer

Identifiers

PMID34032307
PMCPMC13579567
OpenAlexW3164570425

What OpenQuestion holds

Textmetadata
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.