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DICER governs characteristics of glioma stem cells and the resulting tumors in xenograft mouse models of glioblastoma. Those models that do exist have questionable clinical relevance. We explored intratumoral heterogeneity produced by AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry.
Single cell cloning revealed the phenotypic plasticity of AA3, consistent with the intratumoral heterogeneity observed in xenografts. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development. The zebrafish is a widely accepted model to study leukemia. This chapter highlights using transgenic- and xenograft -based models in zebrafish to study a specific leukemogenic mutation and analyze therapeutic responses in vivo.
In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived- xenograft Medulloblastoma models. Medulloblastoma is a cerebellar neoplasia of the central nervous system. Among these, MBgroup are highly metastatic with the worst prognosis.
The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models , together with the non-invasive in vivo biolumiscence imaging BLI technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment.
Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3. Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice.
We describe a method to use the in vivo bioluminescent imaging BLI showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment.
There is a need to develop patient's derived- xenograft PDX model systems to test novel drugs for medulloblastoma treatment within each molecular sub. A human lung xenograft mouse model of Nipah virus infection. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells.
Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV.
Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI.
This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.
Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis. Identifying effective treatment for papillomatosis is limited by a lack of animal models , and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. The xenograft began growing after 5 weeks and was serially passaged over multiple generations.
Each generation showed a consistent log-growth pattern, and in all xenografts , the presence of the human papillomavirus HPV genome was confirmed by polymerase chain reaction PCR. Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation.
We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing.
In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.
Next generation patient-derived prostate cancer xenograft models. PubMed Central. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease.
This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues.
The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease.
These xenograft models could therefore be viewed as next-generation models of prostate cancer. Combest, Austin J. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic PK , toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound.
A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models , OSTs, GEMMs, and human patients has not been performed. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models one GEMM, one human cell line xenograft , and two OSTs.
Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors. The ideal substitute for the diseased aortic valve is yet to be found.
Jude Medical, Inc. Paul, Minn. The first two xenografts require inflow and outflow suturelines; the third xenograft needs a single-sutureline implantation. At follow-up, reintervention on the xenograft was necessary in one patient endocarditis in group 1, none in group 2, and six in group 3 technical cause, group 3; valve tear, group 2. Maturation of the developing human fetal prostate in a rodent xenograft model.
Saffarini, Camelia M. The etiology of prostate cancer is unknown, although both animal and epidemiologic data suggest that early life exposures to various toxicants, may impact DNA methylation status during development, playing an important role. Methods We have developed a xenograft model to characterize the growth and differentiation of human fetal prostate implants gestational age weeks that can provide new data on the potential role of early life stressors on prostate cancer.
DNA methylation profiles of laser capture micro-dissected tissue demonstrated tissue-specific markers clustered by their location in either the epithelium or stroma of human prostate tissue. Functional classification analysis identified CpG-related gene clusters in methylated epithelial and stromal human xenografts. Conclusion This study of human fetal prostate tissue establishes a xenograft model that demonstrates dynamic growth and maturation, allowing for future mechanistic studies of the developmental origins of later life proliferative prostate disease.
Patient-derived xenografts as preclinical neuroblastoma models. The prognosis for children with high-risk neuroblastoma is often poor and survivors can suffer from severe side effects. Predictive preclinical models and novel therapeutic strategies for high-risk disease are therefore a clinical imperative.
However, conventional cancer cell line-derived xenografts can deviate substantially from patient tumors in terms of their molecular and phenotypic features.
Patient-derived xenografts PDXs recapitulate many biologically and clinically relevant features of human cancers. Importantly, PDXs can closely parallel clinical features and outcome and serve as excellent models for biomarker and preclinical drug development.
Here, we review progress in and applications of neuroblastoma PDX models. Neuroblastoma orthotopic PDXs share the molecular characteristics, neuroblastoma markers, invasive properties and tumor stroma of aggressive patient tumors and retain spontaneous metastatic capacity to distant organs including bone marrow. The recent identification of genomic changes in relapsed neuroblastomas opens up opportunities to target treatment-resistant tumors in well-characterized neuroblastoma PDXs.
We highlight and discuss the features and various sources of neuroblastoma PDXs, methodological considerations when establishing neuroblastoma PDXs, in vitro 3D models , current limitations of PDX models and their application to preclinical drug testing. Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts PDOX for preclinical drug studies by implanting cancer stem cells CSC cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice.
Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features.
Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines.
In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and -negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress.
Our findings document the importance of optimization of the implantation site for. Zebrafish xenograft models of cancer and metastasis for drug discovery. The zebrafish is increasingly used for cancer modelling , particularly xenografting of human cancer cell lines, and drug discovery, and may provide novel scientific and therapeutic insights. However, this model system remains underexploited. They summarise previous work investigating the metastatic cascade, such as tumour-induced angiogenesis, intravasation, extravasation, dissemination and homing, invasion at secondary sites, assessing metastatic potential and evaluation of cancer stem cells in zebrafish.
However, their ability to sufficiently reproduce and predict the behaviour of human cancer and metastasis remains unproven. For this to be resolved, novel mechanisms must to be discovered in zebrafish that are subsequently validated in humans, and for therapeutic interventions that modulate cancer favourably in zebrafish to successfully translate to human clinical studies. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.
Does halofuginone HF inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas.
Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF.
Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0. HF treatment did not change the expression level of ovarian steroid hormone receptors.
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