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In JoVE (1)
Other Publications (7)
- Expert Reviews in Molecular Medicine
- Investigative Ophthalmology & Visual Science
- Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
- Archives of Pathology & Laboratory Medicine
- Molecular Therapy : the Journal of the American Society of Gene Therapy
- Cancer Research
- Molecular Therapy : the Journal of the American Society of Gene Therapy
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Articles by Mary Y. Hurwitz in JoVE
JoVE Clinical and Translational Medicine
Estabelecimento e propagação de Tumores Humanos em Retinoblastoma Imune camundongos deficientes
1Interdepartmental Program in Translational Biology & Molecular Medicine, Baylor College of Medicine, 2Texas Children's Cancer Center, Baylor College of Medicine, 3Department of Pediatrics, Baylor College of Medicine, 4Department of Pathology, The Methodist Hospital Research Institute, 5Department of Ophthalmology, Retinoblastoma Center of Houston, 6Baylor College of Medicine, Center for Cell and Gene Therapy, 7Center for Cell and Gene Therapy, Baylor College of Medicine
Um método é descrito para propagar tumores retinoblastoma humano em camundongos. Células tumorais são diretamente injetadas nos olhos de ratos imune deficiente. Tumores secundários foram estabelecidas com sucesso usando as duas células diretamente colhidas a partir de tumores humanos e tumorspheres cultivadas.
Other articles by Mary Y. Hurwitz on PubMed
Retinoblastoma: from Bench to Bedside
Retinoblastoma (Rb) is the most common primary ocular malignancy of children and is caused by a mutation in the gene RB1. Approximately 40% of cases are associated with one or more constitutional mutations, and are therefore heritable, whereas the other 60% are sporadic. Rb is exclusively found in young children. In some cases, Rb tumours metastasise to extraocular organs including bone, lung and brain. Although there is no effective treatment for metastatic disease, non-metastatic cases can be cured by removal of the eye(enucleation). Newer treatment strategies emphasise salvaging the affected eye whenever possible. Animal models of Rb have been developed with xenograft and transgenic techniques. Each model has both strengths and weaknesses for exploring the mechanisms of disease development and progression and the efficacy of new treatment strategies.
Efficient Gene Transfer into Retinal Cells Using Adenoviral Vectors: Dependence on Receptor Expression
A number of ocular diseases are potentially amenable to gene therapy interventions if appropriate vectors for the targeted administration of therapeutic genes can be identified. In vitro and in vivo transduction efficiency of a Group C serotype 5 adenoviral vector containing the fiber domain derived from a Group B serotype 35 adenovirus and the gene encoding green fluorescent protein (AdV5/F35-GFP) was compared to an AdV5-GFP vector for transgene delivery to human retinoblastoma and to human and murine retinas.
Response of Retinoblastoma with Vitreous Tumor Seeding to Adenovirus-mediated Delivery of Thymidine Kinase Followed by Ganciclovir
To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma.
Extensively Necrotic Retinoblastoma is Associated with High-risk Prognostic Factors
Retinoblastoma is the most common malignant intraocular tumor in children. It has been shown that adjuvant therapy following enucleation in patients with high-risk histopathologic features significantly decreases the mortality. We describe the association of extensive necrosis of tumor and intraocular structures with 2 of the major risk factors: optic nerve invasion and choroidal invasion. This may alert the pathologist who makes the observation of extensive necrosis to carefully search for histologic features associated with adverse outcome.
Modulation of Adenoviral Transduction in Vitro and in Vivo by Hyaluronan and Its Receptor CD44
Adenovirus infection is a significant cause of ocular, respiratory, and gastrointestinal illness and can spread rapidly. Morbidity is considerable in immune-suppressed individuals and there is significant mortality. There are no effective therapies. During preclinical studies of adenoviral-mediated gene therapy for ocular disorders, we noticed a significant increase in transduction when the target cells were exposed to adenovirus in the presence of ocular vitreous. The vitreous is mainly comprised of water, collagen, and the large polysaccharide hyaluronan. In this paper, we report data that implicate hyaluronan in the adenoviral infectious process and show that interference with the interaction between hyaluronan and its cellular receptor CD44 can block adenovirus transduction in vitro and in vivo.
Treatment of Invasive Retinoblastoma in a Murine Model Using an Oncolytic Picornavirus
Retinoblastoma, the most common intraocular malignancy of childhood, metastasizes by initial invasion of the choroid and the optic nerve. There is no effective treatment for metastatic retinoblastoma, especially when the central nervous system (CNS) is involved, and prevention of this complication is a treatment priority. Seneca Valley Virus (SVV-001) is a conditionally replication-competent picornavirus that is not pathogenic to normal human cells but can kill human retinoblastoma cells in vitro with an IC(50) of <1 viral particle (vp) per cell. A xenograft murine model of metastatic retinoblastoma was used to examine the therapeutic potential of SVV-001. Histopathologic analysis of ocular and brain tissues after a single tail vein injection of SVV-001 (1 x 10(13) vp/kg) showed effective treatment of choroid and ocular nerve tumor invasion (1 of 20 animals with invasive disease in the treated group versus 7 of 20 animals with invasive disease in the control group; P = 0.017) and prevention of CNS metastasis (0 of 20 animals with CNS metastatic disease in the treated group versus 4 of 20 animals with CNS disease in the control group; P = 0.036). There were no observed adverse events due to the virus in any of the treated animals. SVV-001 may be effective as a treatment of locally invasive and metastatic retinoblastoma.
Absence of Systemic Immune Response to Adenovectors After Intraocular Administration to Children with Retinoblastoma
The ocular environment has been shown to induce tolerance to locally administered antigens. We therefore investigated whether there was a systemic immune response against adenoviral vectors injected into the vitreous of retinoblastoma patients enrolled in a phase 1 clinical trial of adenoviral-mediated thymidine kinase gene transfer. Sections of enucleated eyes were immunostained with antibodies against inflammatory cells. A trend toward increasing numbers of plasma cells, T cells, macrophages, and antigen-presenting cells was observed in the injected subjects' eyes, but systemically, there was no significant increase in the number of adenovirus-specific cytotoxic T lymphocytes (CTLs) or in adenovirus neutralizing antibodies. Therefore, in contrast to studies showing significant immunogenicity of Ad-RSVtk following injection into extraocular tumors, injection into the eye produces only a mild local inflammatory response without evidence of systemic cellular or humoral immune responses to adenovirus.
