Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease

Abstract

Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies.

In Vivo Observation of Endothelial Cell-Assisted Vascularization in Pancreatic Cancer Xenograft Engineering

“…Patient-derived xenograft models are typically investigated using immunodeficient rodents implanted with tumorous biopsies or cultured cancer cells [17,27,28]. For different tumor types, particularly the brain and hormone-dependent tumors, the variability in the PDX success rate is an issue that remains to be resolved [29][30][31]. Pancreatic cancer xenografts generated with MIA PaCa-2 and MS1 cells can be a potent model system for effective pancreatic ductal adenocarcinoma PDX formation [32,33].…”

Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer

“…PDX models are established by direct engraftment of the patient's tumor into immunodeficient mice. These models recapitulate the principal histologic and genetic properties of corresponding patients' tumor, and retain more tumor heterogeneity than other preclinical models [5,6]. Therefore, we can anticipate patient's clinical outcome by referring to PDXs, and thus are useful for clinical translational research, drug screening, and biomarker discovery and validation.…”

EC313-a tissue selective SPRM reduces the growth and proliferation of uterine fibroids in a human uterine fibroid tissue xenograft model

“…Various SPRMs are found to be very effective in range of biological activity including contraception, preoperative treatment of uterine leiomyomas 1 . UFs are the most common benign tumors in reproductive age women, are asymptomatic in at least 50% of afflicted women, in others, they cause significant morbidity and affect quality of life 2 . Women with UFs have abnormal uterine bleeding, dysmenorrhea, pelvic pain unrelated to menstruation, as well as pressure symptoms such as bloating, urinary frequency and bowel disturbances 3 .…”