Dataset Information

Quantitative assessment of human uterine fibroid xenograft using sequential in vivo bioluminescence imaging.

ABSTRACT: Uterine fibroid is one of the most common solid tumors occurring in reproductive age women. Lack of accurate methods for In vivo quantitative assessment of uterine fibroid progression severely impedes the basic research and drug screen of this disease. To solve this problem, the correlation between bioluminescence imaging (BLI) and initial cell number used to form xenograft was investigated in this study. The results showed that both subcutaneous (SC) and intraperitoneal (IP) D-luciferin administration led to fast increase of bioluminescence signal (BLS) intensity and caused large variation of peak signal intensity of xenografts through the analysis of BLI kinetic curves. We found that a distinct linear stage appeared in xenograft BLI curve for each mouse subjected to IP-injection of D-luciferin. Moreover, a high positive correlation was found between linear slope and the initial number of human uterine fibroid smooth muscle cells (fSMCs) used for xenograft formation. Our research indicates that the slope of linear stage in BLI curve is more appropriate for in vivo quantitative assessment of human uterine fibroid xenograft.

SUBMITTER: Pan Y

PROVIDER: S-EPMC6511785 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Quantitative assessment of human uterine fibroid xenograft using sequential in vivo bioluminescence imaging.

Pan Yihong Y Xiao Tongqian T Zhou Yuanshuai Y Chai Zhihong Z Xu Zhongjuan Z Dai Meizhen M Chen Xuejiao X Suo Guangli G Tao Deyou D

American journal of translational research 20190415 4

Uterine fibroid is one of the most common solid tumors occurring in reproductive age women. Lack of accurate methods for <i>In vivo</i> quantitative assessment of uterine fibroid progression severely impedes the basic research and drug screen of this disease. To solve this problem, the correlation between bioluminescence imaging (BLI) and initial cell number used to form xenograft was investigated in this study. The results showed that both subcutaneous (SC) and intraperitoneal (IP) D-luciferin ...[more]

PMID: 31105842

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Project description:Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010-2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov.

Project description:BackgroundHeritability estimates (including twin and single nucleotide polymorphism [SNP]-based heritability studies) for fibroids have been inconsistent across prior studies ranging between 9 and 69%. These inconsistencies are due to variations in study design and included populations. A major design issue has been lack of imaging confirmation to identify controls, where asymptomatic women without imaging confirmation may be misclassified as controls leading to an attenuation of heritability estimates. To reconcile the differences in prior heritability estimates and the impact of misclassification of controls on heritability, we determined SNP-based heritability and characterized the genetic architecture of pelvic image-confirmed fibroid cases and controls.MethodsAnalyses were performed among women of European American descent using genome-wide SNP data from BioVU, a clinical database composed of DNA linked to de-identified electronic health records. We estimated the genetic variance explained by all SNPs using Genome-Wide Complex Trait Analysis on imputed data. Fibroid cases and controls were identified using a previously reported phenotyping algorithm that required pelvic imaging confirmation.ResultsIn total, we used 1,067 image-confirmed fibroid cases and 1,042 image-confirmed fibroid controls. The SNP-based heritability estimate for fibroid risk was h2 = 0.33 ± 0.18 (p = 0.040). We investigated the relationship between heritability per chromosome and chromosome length (r2 < 1%), with chromosome 8 explaining the highest proportion of variance for fibroid risk. There was no enrichment for intergenic or genic SNPs for the fibroid SNP-based heritability. Excluding loci previously associated with fibroid risk from genome-wide association study did not attenuate fibroid heritability suggesting that loci associating with fibroid risk are yet to be discovered.ConclusionsWe observed that fibroid SNP-based heritability was higher than the previous estimate using genome-wide SNP data that relied on self-reported outcomes, but within the range of prior twin pair studies. Furthermore, these data support that imprecise phenotyping can significantly affect the ability to estimate heritability using genotype data.

Dataset Information

Quantitative assessment of human uterine fibroid xenograft using sequential in vivo bioluminescence imaging.

Publications

Quantitative assessment of human uterine fibroid xenograft using sequential in vivo bioluminescence imaging.

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