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Find video protocols related to scientific articles indexed in Pubmed.
Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy.
J. Clin. Oncol.
PUBLISHED: 09-02-2014
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Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks.
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Rb suppresses human cone-precursor-derived retinoblastoma tumours.
Nature
PUBLISHED: 09-01-2014
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Retinoblastoma is a childhood retinal tumour that initiates in response to biallelic RB1 inactivation and loss of functional retinoblastoma (Rb) protein. Although Rb has diverse tumour-suppressor functions and is inactivated in many cancers, germline RB1 mutations predispose to retinoblastoma far more strongly than to other malignancies. This tropism suggests that retinal cell-type-specific circuitry sensitizes to Rb loss, yet the nature of the circuitry and the cell type in which it operates have been unclear. Here we show that post-mitotic human cone precursors are uniquely sensitive to Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN and MDM2. Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation. Moreover, Rb-depleted cone precursors formed tumours in orthotopic xenografts with histological features and protein expression typical of human retinoblastoma. These findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. More generally, they demonstrate that cell-type-specific circuitry can collaborate with an initiating oncogenic mutation to enable tumorigenesis.
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Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.
Radiat Environ Biophys
PUBLISHED: 08-26-2014
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Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.
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Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment.
Cancer Res.
PUBLISHED: 08-16-2014
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Eph receptor tyrosine kinases are critical for cell-cell communication during normal and oncogenic tissue patterning and tumor growth. Somatic mutation profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its oncogenic expression pattern and role in tumorigenesis remain largely undefined. Here, we report unexpected EphA3 overexpression within the microenvironment of a range of human cancers and mouse tumor xenografts where its activation inhibits tumor growth. EphA3 is found on mouse bone marrow-derived cells with mesenchymal and myeloid phenotypes, and activation of EphA3(+)/CD90(+)/Sca1(+) mesenchymal/stromal cells with an EphA3 agonist leads to cell contraction, cell-cell segregation, and apoptosis. Treatment of mice with an agonistic ?-EphA3 antibody inhibits tumor growth by severely disrupting the integrity and function of newly formed tumor stroma and microvasculature. Our data define EphA3 as a novel target for selective ablation of the tumor microenvironment and demonstrate the potential of EphA3 agonists for anticancer therapy.
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Retinal toxicities of cancer therapy drugs: biologics, small molecule inhibitors, and chemotherapies.
Retina (Philadelphia, Pa.)
PUBLISHED: 06-21-2014
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To review reported retinal side effects from current cancer therapy drugs.
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The Resilience Activation Framework: a Conceptual Model of How Access to Social Resources Promotes Adaptation and Rapid Recovery in Post-disaster Settings.
J Behav Health Serv Res
PUBLISHED: 05-30-2014
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A number of governmental agencies have called for enhancing citizens' resilience as a means of preparing populations in advance of disasters, and as a counterbalance to social and individual vulnerabilities. This increasing scholarly, policy, and programmatic interest in promoting individual and communal resilience presents a challenge to the research and practice communities: to develop a translational framework that can accommodate multidisciplinary scientific perspectives into a single, applied model. The Resilience Activation Framework provides a basis for testing how access to social resources, such as formal and informal social support and help, promotes positive adaptation or reduced psychopathology among individuals and communities exposed to the acute collective stressors associated with disasters, whether human-made, natural, or technological in origin. Articulating the mechanisms by which access to social resources activate and sustain resilience capacities for optimal mental health outcomes post-disaster can lead to the development of effective preventive and early intervention programs.
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Exenteration and Custom Implant Brachytherapy as a Treatment for Recurrent Primary Extraskeletal Orbital Ewing Sarcoma.
Ophthal Plast Reconstr Surg
PUBLISHED: 05-13-2014
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A 6-year-old boy initially presented to an outside hospital with a right orbital mass with biopsy positive for translocation involving EWS RNA-binding protein 1 gene and imaging consistent with primary extraskeletal Ewing sarcoma (ES). There was no evidence of metastatic disease. Patient underwent gross tumor resection and adjuvant chemotherapy (VAdriaC/IE) followed by postoperative 45-Gy proton beam radiation. After 19 months, a solitary in-field local recurrence occurred, which was unsuccessfully surgically resected. Thereafter, treatment commenced with irinotecan and temozolomide, and the patient presented to the center of the authors. MRI showed locally recurrent disease without evidence of metastatic disease. Right orbital exenteration was performed, and an orbital mold was fashioned to deliver brachytherapy. There were no complications. The patient had no evidence of recurrent disease at 37-month follow up. This is the first report of orbital implant brachytherapy for recurrent primary ES of the orbit, and an additional report of primary extraskeletal ES of the orbit, which is a rare primary orbital tumor.
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Fire in Australian savannas: from leaf to landscape.
Glob Chang Biol
PUBLISHED: 04-16-2014
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Savanna ecosystems comprise 22% of the global terrestrial surface and 25% of Australia (almost 1.9 million km(2) ) and provide significant ecosystem services through carbon and water cycles and the maintenance of biodiversity. The current structure, composition and distribution of Australian savannas have coevolved with fire, yet remain driven by the dynamic constraints of their bioclimatic niche. Fire in Australian savannas influences both the biophysical and biogeochemical processes at multiple scales from leaf to landscape. Here, we present the latest emission estimates from Australian savanna biomass burning and their contribution to global greenhouse gas budgets. We then review our understanding of the impacts of fire on ecosystem function and local surface water and heat balances, which in turn influence regional climate. We show how savanna fires are coupled to the global climate through the carbon cycle and fire regimes. We present new research that climate change is likely to alter the structure and function of savannas through shifts in moisture availability and increases in atmospheric carbon dioxide, in turn altering fire regimes with further feedbacks to climate. We explore opportunities to reduce net greenhouse gas emissions from savanna ecosystems through changes in savanna fire management.
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School interventions after the Joplin tornado.
Prehosp Disaster Med
PUBLISHED: 03-21-2014
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To qualitatively describe interventions by schools to meet children's needs after the May 2011 Joplin, Missouri tornado.
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Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.
Ophthalmology
PUBLISHED: 03-19-2014
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Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model.
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New insights into the analysis of the electrode kinetics of flavin adenine dinucleotide redox center of glucose oxidase immobilized on carbon electrodes.
Langmuir
PUBLISHED: 03-13-2014
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New insights into electrochemical kinetics of the flavin adenine dinucleotide (FAD) redox center of glucose-oxidase (GlcOx) immobilized on reduced graphene oxide (rGO), single- and multiwalled carbon nanotubes (SW and MWCNT), and combinations of rGO and CNTs have been gained by application of Fourier transformed AC voltammetry (FTACV) and simulations based on a range of models. A satisfactory level of agreement between experiment and theory, and hence establishment of the best model to describe the redox chemistry of FAD, was achieved with the aid of automated e-science tools. Although still not perfect, use of Marcus theory with a very low reorganization energy (?0.3 eV) best mimics the experimental FTACV data, which suggests that the process is gated as also deduced from analysis of FTACV data obtained at different frequencies. Failure of the simplest models to fully describe the electrode kinetics of the redox center of GlcOx, including those based on the widely employed Laviron theory is demonstrated, as is substantial kinetic heterogeneity of FAD species. Use of a SWCNT support amplifies the kinetic heterogeneity, while a combination of rGO and MWCNT provides a more favorable environment for fast communication between FAD and the electrode.
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(106)Ru plaque brachytherapy for uveal melanoma: Factors associated with local tumor recurrence.
Brachytherapy
PUBLISHED: 02-28-2014
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Plaque brachytherapy is a common form of treatment for uveal melanoma, and the Collaborative Ocular Melanoma Study (COMS) used (125)I. Recently, (106)Ru has been reintroduced for plaque brachytherapy in the United States. We reviewed our experience treating uveal melanoma with (106)Ru plaque brachytherapy using COMS planning techniques, hypothesizing that we would observe similar outcomes to those in the COMS.
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How precise are reported protein coordinate data?
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 02-27-2014
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Atomic coordinates in the Worldwide Protein Data Bank (wwPDB) are generally reported to greater precision than the experimental structure determinations have actually achieved. By using information theory and data compression to study the compressibility of protein atomic coordinates, it is possible to quantify the amount of randomness in the coordinate data and thereby to determine the realistic precision of the reported coordinates. On average, the value of each C(?) coordinate in a set of selected protein structures solved at a variety of resolutions is good to about 0.1?Å.
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Retinoblastoma: saving life with vision.
Annu. Rev. Med.
PUBLISHED: 01-16-2014
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Retinoblastoma has gone from >95% mortality to >95% survival in the past 100 years. Once enucleation techniques were perfected, the majority of children survived, but without the eye (or vision in that eye). Over the past 100 years, progressively better techniques have been developed for salvaging vision without sacrificing patient survival. Presently, 99% of children treated at our center survive their cancer, >99% retain at least one eye, and >90% retain normal vision in at least one eye. The introduction of ophthalmic artery chemosurgery has been the most dramatic, non-radiation-based mode to maximally preserve vision.
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Whole-body magnetic resonance imaging (WB-MRI) as surveillance for subsequent malignancies in survivors of hereditary retinoblastoma: a pilot study.
Pediatr Blood Cancer
PUBLISHED: 01-10-2014
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Individuals with hereditary retinoblastoma (RB) are at very high risk of developing subsequent malignant neoplasms (SMNs) of which osteosarcoma (OS) is one of the most common. We hypothesized that annual surveillance using whole-body magnetic resonance imaging (WB-MRI) in asymptomatic survivors of hereditary RB would detect SMN of the bone and soft tissues at an early stage.
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Risk Factors for Severe Neutropenia following Intra-Arterial Chemotherapy for Intra-Ocular Retinoblastoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (?grade 3) neutropenia.
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Death by water: precautionary water submersion for intravitreal injection of retinoblastoma eyes.
Open Ophthalmol J
PUBLISHED: 01-01-2014
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There is growing interest in intravitreal injections of chemotherapy for retinoblastoma. However, concerns for potential tumor seeding through the needle track has prompted the use of risk-reducing precautionary methods. Presented here is a novel technique, which can be easily replicated, requires minimal sophisticated equipment and with laboratory data supporting its concept. Sterile distilled water submersion for 3 minutes renders retinoblastoma cells nonviable and can be employed as a precautionary method following intravitreal injection in the technique described here.
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Electroretinogram monitoring of dose-dependent toxicity after ophthalmic artery chemosurgery in retinoblastoma eyes: six year review.
PLoS ONE
PUBLISHED: 01-01-2014
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To report electroretinogram responses of retinoblastoma children under anesthesia before and after treatment with chemotherapeutic drugs (melphalan, topotecan, carboplatin) delivery by ophthalmic artery chemosurgery (OAC).
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Extraocular extension of uveal melanoma after fine-needle aspiration, vitrectomy, and open biopsy.
JAMA Ophthalmol
PUBLISHED: 09-14-2013
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The most potentially devastating complication of fine-needle aspiration biopsy (FNAB) or open biopsy is extraocular extension of the tumor. In this collaborative case series, we report 4 cases of orbital recurrence of malignant melanoma as a late complication of biopsy and/or vitrectomy performed at referring institutions and then sent to us for evaluation.
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Non-selectivity of ERG reductions in eyes treated for retinoblastoma.
Doc Ophthalmol
PUBLISHED: 06-17-2013
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We have monitored retinal function in patients treated for retinoblastoma (primarily, but not exclusively by intra-arterial chemotherapy infusion) by electroretinography (ERG) recordings for the past 7 years. We here present data from 599 ERG studies of 108 patients, in which a complete ERG protocol including both photopic and scotopic recordings was performed, in justification of our frequent practice of reporting primarily 30-Hz photopic flicker amplitude data.
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Salvage/adjuvant brachytherapy after ophthalmic artery chemosurgery for intraocular retinoblastoma.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-20-2013
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To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma.
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Ocular manipulation reduces both ipsilateral and contralateral electroretinograms.
Doc Ophthalmol
PUBLISHED: 05-17-2013
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To determine the electroretinogram (ERG) changes in eyes manipulated in the course of local ablative therapy (transpupil thermotherapy (TTT), cryotherapy or both) or scleral depression and in un-manipulated fellow, healthy eyes.
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Sensitivity of rabbit ventricular action potential and Ca²? dynamics to small variations in membrane currents and ion diffusion coefficients.
Biomed Res Int
PUBLISHED: 04-28-2013
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Little is known about how small variations in ionic currents and Ca²? and Na? diffusion coefficients impact action potential and Ca²? dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%-10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca²? peaks are highly sensitive to 10% increase in L-type Ca²? current; moderately influenced by 10% increase in Na?-Ca²? exchanger, Na?-K? pump, rapid delayed and slow transient outward K? currents, and Cl? background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca²? fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca²? channels and Na?-Ca²? exchanger in between junctional and submembrane spaces while Ca²?-activated Cl?-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca²?, but not in Na? transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca²? signaling.
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A synergetic screening approach with companion effector for combination therapy: application to retinoblastoma.
PLoS ONE
PUBLISHED: 02-12-2013
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For many cancers, the lack of potency and the toxicity of current drugs limits the dose achievable in patients and the efficacy of treatment. Among them, retinoblastoma is a rare cancer of the eye for which better chemotherapeutic options are needed. Combination therapy is a compelling approach to enhance the efficacy of current treatment, however clinical trials to test rationally designed combinations of approved drugs are slow and expensive, and limited by our lack of in-depth knowledge of drug specificity. Since many patients already turn to nutraceuticals in hopes of improving their condition, we hypothesized that certain approved drugs could potentially synergize with widely consumed supplements. Following this hypothesis, we devised an alternative screening strategy aimed at taking advantage of a bait compound such as a nutraceutical with potential therapeutic benefits but low potency, by screening chemical libraries for approved drugs that synergize with this companion effector. As a proof of concept, we sought to identify approved drugs with synergetic therapeutic effects toward retinoblastoma cells in combination with the antioxidant resveratrol, popular as a supplement. We systematically tested FDA-approved drugs and known bioactives seeking to identify such pairs, which led to uncovering only a few additive combinations; but to our surprise, we identified a class of anticancer drugs widely used in the clinic whose therapeutic effect is antagonized with resveratrol. Our observations could explain in part why some patients do not respond well to treatment. Our results validate this alternative approach, and we expect that our companion effector strategy could significantly impact both drug discovery and the nutraceutical industry.
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SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries.
Pediatr Blood Cancer
PUBLISHED: 01-17-2013
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Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence-based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP-PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue.
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Carboplatin +/- topotecan ophthalmic artery chemosurgery for intraocular retinoblastoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/- topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery.
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Characterization of computed tomography scan abnormalities in patients with biopsy-proven hepatic metastases from uveal melanoma.
Arch. Ophthalmol.
PUBLISHED: 12-14-2011
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To describe the computed tomography (CT) features in patients with biopsy-proven hepatic metastases of uveal melanoma and correlate these findings with survival.
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Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results.
Br J Ophthalmol
PUBLISHED: 11-03-2011
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To review the effectiveness of intra-arterial chemotherapy for advanced intra-ocular retinoblastoma with vitreous and/or subretinal seeds in naive (untreated) and previously treated eyes.
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Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma.
Gynecol. Oncol.
PUBLISHED: 08-30-2011
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In the US, second non-ocular malignancies are the primary cause of death in retinoblastoma survivors with the germline RB1 mutation. Soft tissue sarcomas are one of the most likely malignancies to pose a risk to these patients, with leiomyosarcoma (LMS) being the most common subtype. As our cohort is followed for a longer period, we discover new second malignancy risks for these patients.
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Persistence of mental health needs among children affected by Hurricane Katrina in New Orleans.
Prehosp Disaster Med
PUBLISHED: 08-16-2011
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Hurricane Katrina made landfall in August 2005 and destroyed the infrastructure ofNew Orleans. Mass evacuation ensued. The immediate and long-lasting impact of these events on the mental health of children have been reported in survey research. This study was done to describe the nature of mental health need of children during the four years after Hurricane Katrina using clinical data from a comprehensive healthcare program. Medical and mental health services were delivered on mobile clinics that traveled to medically underserved communities on a regular schedule beginning immediately after the hurricane. Patients were self-selected residents of New Orleans. Most had incomes below the federal poverty level and were severely affected by the hurricane.
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Primary melanoma of the optic nerve in a patient with 16-year follow up.
Ophthal Plast Reconstr Surg
PUBLISHED: 08-11-2011
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Primary melanoma of the optic nerve is rare. Limited reports in the literature have been the subject of considerable controversy, as many of these melanomas have later been found to be metastatic disease or local extensions of a juxtapapillary choroidal melanoma. Moreover, these have often been reported in patients with a history of ocular or oculocutaneous pigmentary disorders. The authors present a case of primary melanoma of the optic nerve in a patient with no history of pigmentary disorder and 16 years of follow up.
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Leveraging e-Science infrastructure for electrochemical research.
Philos Trans A Math Phys Eng Sci
PUBLISHED: 07-20-2011
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As in many scientific disciplines, modern chemistry involves a mix of experimentation and computer-supported theory. Historically, these skills have been provided by different groups, and range from traditional wet laboratory science to advanced numerical simulation. Increasingly, progress is made by global collaborations, in which new theory may be developed in one part of the world and applied and tested in the laboratory elsewhere. e-Science, or cyber-infrastructure, underpins such collaborations by providing a unified platform for accessing scientific instruments, computers and data archives, and collaboration tools. In this paper we discuss the application of advanced e-Science software tools to electrochemistry research performed in three different laboratories--two at Monash University in Australia and one at the University of Oxford in the UK. We show that software tools that were originally developed for a range of application domains can be applied to electrochemical problems, in particular Fourier voltammetry. Moreover, we show that, by replacing ad-hoc manual processes with e-Science tools, we obtain more accurate solutions automatically.
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Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors.
Hum. Genet.
PUBLISHED: 06-07-2011
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Autosomal dominant conditions are known to be associated with advanced paternal age, and it has been suggested that retinoblastoma (Rb) also exhibits a paternal age effect due to the paternal origin of most new germline RB1 mutations. To further our understanding of the association of parental age and risk of de novo germline RB1 mutations, we evaluated the effect of parental age in a cohort of Rb survivors in the United States. A cohort of 262 Rb patients was retrospectively identified at one institution, and telephone interviews were conducted with parents of 160 survivors (65.3%). We classified Rb survivors into three groups: those with unilateral Rb were classified as sporadic if they had no or unknown family history of Rb, those with bilateral Rb were classified as having a de novo germline mutation if they had no or unknown family history of Rb, and those with unilateral or bilateral Rb, who had a family history of Rb, were classified as familial. We built two sets of nested logistic regression models to detect an increased odds of the de novo germline mutation classification related to older parental age compared to sporadic and familial Rb classifications. The modeling strategy evaluated effects of continuous increasing maternal and paternal age and 5-year age increases adjusted for the age of the other parent. Mean maternal ages for survivors classified as having de novo germline mutations and sporadic Rb were similar (28.3 and 28.5, respectively) as were mean paternal ages (31.9 and 31.2, respectively), and all were significantly higher than the weighted general US population means. In contrast, maternal and paternal ages for familial Rb did not differ significantly from the weighted US general population means. Although we noted no significant differences between mean maternal and paternal ages between each of the three Rb classification groups, we found increased odds of a survivor being in the de novo germline mutation group for each 5-year increase in paternal age, but these findings were not statistically significant (de novo vs. sporadic ORs 30-34 = 1.7 [0.7-4], ? 35 = 1.3 [0.5-3.3]; de novo vs. familial ORs 30-34 = 2.8 [1.0-8.4], ? 35 = 1.6 [0.6-4.6]). Our study suggests a weak paternal age effect for Rb resulting from de novo germline mutations consistent with the paternal origin of most of these mutations.
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Retinoblastoma presenting in a child with hypomelanosis of Ito.
Open Ophthalmol J
PUBLISHED: 05-24-2011
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To describe a case of a child with a known history of pigmentary mosaicism suggestive of Hypomelanosis of Ito presenting with unilateral leukocoria, who was ultimately diagnosed with retinoblastoma.
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Interactive financial decision support for clinical research trials.
J Health Care Finance
PUBLISHED: 05-03-2011
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The purpose of this article is to describe a decision support approach useful for evaluating proposals to conduct clinical research trials. Physicians often do not have the time or background to account for all the expenses of a clinical trial. Their evaluation process may be limited and driven by factors that do not indicate the potential for financial losses that a trial may impose. We analyzed clinical trial budget templates used by hospitals, health science centers, research universities, departments of medicine, and medical schools. We compiled a databank of costs and reviewed recent research trials conducted by the Department of Cardiothoracic Surgery in a major academic health science center. We then developed an interactive spreadsheet-based budgetary decision support approach that accounts for clinical trial income and costs. It can be tailored to provide quick and understandable data entry, accurate cost rates per subject, and clear go/no-go signals for the physician.
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Secondary skull base malignancies in survivors of retinoblastoma: the memorial sloan kettering cancer center experience.
Skull Base
PUBLISHED: 04-27-2011
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We report the pathology and outcome of secondary skull base tumors in patients previously treated with external beam radiation for retinoblastoma (Rb). Rb patients are at increased risk of second head and neck primary malignancies due to early radiation exposure during treatment and loss of RB1 protein in genetic carriers. An institutional database was reviewed for patients with retinoblastoma who had previously received radiation therapy and subsequently developed skull base tumors. Seventeen patients met the selection criteria. The median age of Rb diagnosis was 12 months. Thirteen cases underwent enucleation in addition to radiation therapy as part of initial Rb treatment. A median of 19 years elapsed between the diagnosis of Rb and diagnosis of skull base malignancy. The most common tumors were osteogenic sarcoma (39%) and leiomyosarcoma (22%). Eleven (71%) patients received postoperative chemotherapy, and 7 (41%) received postoperative radiotherapy. Three (24%) patients underwent salvage surgery for recurrent disease. Five-year survival was 68%, and 10-year survival was 51% by Kaplan-Meier analysis. Secondary malignancy in Rb patients is a well-defined event. The use of surgery with appropriate adjuvant therapy was associated with a 51% 10-year survival in this study population.
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Intra-arterial and oral digoxin therapy for retinoblastoma.
Ophthalmic Genet.
PUBLISHED: 03-29-2011
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Preclinical studies demonstrate that cardiac glycosides such as ouabain and digoxin have antitumor effects on retinoblastoma cells in vitro and in a xenograft murine model of retinoblastoma.
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Therapeutic implications of the emerging molecular biology of uveal melanoma.
Clin. Cancer Res.
PUBLISHED: 03-28-2011
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Uveal melanoma represents the most common primary intraocular malignancy in adults. Although uveal and cutaneous melanomas both arise from melanocytes, uveal melanoma is clinically and biologically distinct from its more common cutaneous counterpart. Metastasis occurs frequently in this disease, and once distant spread occurs, outcomes are poor. No effective systemic therapies are currently available; however, recent advances in our understanding of the biology of this rare and devastating disease, combined with the growing availability of targeted agents, which can be used to rationally exploit these findings, hold the promise for novel and effective therapies in the foreseeable future. Herein, we review our rapidly growing understanding of the molecular biology of uveal melanoma, including the pathogenic roles of GNAQ (guanine nucleotide binding protein q polypeptide)/11, PTEN (phosphatase and tensin homolog), IGF (insulin-like growth factor)/IGF-1 receptor, MET (hepatocyte growth factor), BAP1 [breast cancer 1, early onset (BRCA1)-associated protein-1], and other key molecules, potential therapeutic strategies derived from this emerging biology, and the next generation of recently initiated clinical trials for the treatment of advanced uveal melanoma.
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Sinonasal adenocarcinoma: a rare second malignancy in long term retinoblastoma survivors.
Pediatr Blood Cancer
PUBLISHED: 03-23-2011
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Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.
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Rural and suburban population surge following detonation of an improvised nuclear device: a new model to estimate impact.
Disaster Med Public Health Prep
PUBLISHED: 03-16-2011
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The objective of the study was to model urban evacuation into surrounding communities after the detonation of an improvised nuclear device (IND) to assist rural and suburban planners in understanding and effectively planning to address the effects of population surges.
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Germline mutations in BAP1 predispose to melanocytic tumors.
Nat. Genet.
PUBLISHED: 02-16-2011
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Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.
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Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience.
Arch. Ophthalmol.
PUBLISHED: 02-14-2011
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To determine whether intra-arterial chemotherapy is safe and effective in advanced intraocular retinoblastoma. Retinoblastoma often presents with advanced intraocular disease and, despite conventional treatment with intravenous chemotherapy and external beam radiation therapy, may still require enucleation.
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Histopathologic findings of eyes enucleated after treatment with chemosurgery for retinoblastoma.
Open Ophthalmol J
PUBLISHED: 01-18-2011
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Intra-arterial chemotherapy (chemosurgery) for the treatment of retinoblastoma has been performed more than 1600 times (more than 1400 times in Japan and 200 times in New York) over the past 20 years.Despite this treatments success some eyes cannot be saved and require enucleation. Here we report the histopathologic findings of the remaining intraocular tumor of eyes that were enucleated following treatment that included chemosurgery in New York City.
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Intraocular teratoma in association with sacrococcygeal teratoma: a clinicopathologic report.
J Pediatr Ophthalmol Strabismus
PUBLISHED: 12-06-2010
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A benign sacrococcygeal teratoma was resected from an infant at birth. Four weeks later, intraocular tumors were identified in the right eye. The eye expanded in size and was removed at 16 weeks. A benign cystic intraocular teratoma was identified.
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A global sensitivity tool for cardiac cell modeling: Application to ionic current balance and hypertrophic signaling.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 11-25-2010
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Cardiovascular diseases are the major cause of death in the developed countries. Identifying key cellular processes involved in generation of the electrical signal and in regulation of signal transduction pathways is essential for unraveling the underlying mechanisms of heart rhythm behavior. Computational cardiac models provide important insights into cardiovascular function and disease. Sensitivity analysis presents a key tool for exploring the large parameter space of such models, in order to determine the key factors determining and controlling the underlying physiological processes. We developed a new global sensitivity analysis tool which implements the Morris method, a global sensitivity screening algorithm, onto a Nimrod platform, which is a distributed resources software toolkit. The newly developed tool has been validated using the model of IP3-calcineurin signal transduction pathway model which has 30 parameters. The key driving factors of the IP3 transient behaviour have been calculated and confirmed to agree with previously published data. We next demonstrated the use of this method as an assessment tool for characterizing the structure of cardiac ionic models. In three latest human ventricular myocyte models, we examined the contribution of transmembrane currents to the shape of the electrical signal (i.e. on the action potential duration). The resulting profiles of the ionic current balance demonstrated the highly nonlinear nature of cardiac ionic models and identified key players in different models. Such profiling suggests new avenues for development of methodologies to predict drug action effects in cardiac cells.
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Emergency response and public health in Hurricane Katrina: what does it mean to be a public health emergency responder?
J Public Health Manag Pract
PUBLISHED: 10-02-2010
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Since 9/11, federal funds directed toward public health departments for training in disaster preparedness have dramatically increased, resulting in changing expectations of public health workers roles in emergency response. This article explores the public health emergency responder role through data collected as part of an oral history conducted with the 3 health departments that responded to Hurricane Katrina in Mississippi and Louisiana. The data reveals a significant change in public health emergency response capacity as a result of federal funding. The role is still evolving, and many challenges remain, in particular, a clear articulation of the public health role in emergency response, the integration of the public health and emergency responder cultures, identification of the scope of training needs and strategies to maintain new public health emergency response skills, and closer collaboration with emergency response agencies.
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Spontaneously Resolving Periocular Erythema and Ciliary Madarosis Following Intra-arterial Chemotherapy for Retinoblastoma.
Middle East Afr J Ophthalmol
PUBLISHED: 09-17-2010
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To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma.
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Measuring individual disaster recovery: a socioecological framework.
Disaster Med Public Health Prep
PUBLISHED: 09-01-2010
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Disaster recovery is a complex phenomenon. Too often, recovery is measured in singular fashion, such as quantifying rebuilt infrastructure or lifelines, without taking in to account the affected populations individual and community recovery. A comprehensive framework is needed that encompasses a much broader and far-reaching construct with multiple underlying dimensions and numerous causal pathways; without the consideration of a comprehensive framework that investigates relationships between these factors, an accurate measurement of recovery may not be valid. This study proposes a model that encapsulates these ideas into a single framework, the Socio-Ecological Model of Recovery.
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Children as bellwethers of recovery: dysfunctional systems and the effects of parents, households, and neighborhoods on serious emotional disturbance in children after Hurricane Katrina.
Disaster Med Public Health Prep
PUBLISHED: 08-23-2010
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Over 160,000 children were displaced from their homes after Hurricane Katrina. Tens of thousands of these children experienced the ongoing chaos and uncertainty of displacement and transiency, as well as significant social disruptions in their lives. The objectives of this study were to estimate the long-term mental health effects of such exposure among children, and to elucidate the systemic pathways through which the disaster effect operates.
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High-throughput cardiac science on the Grid.
Philos Trans A Math Phys Eng Sci
PUBLISHED: 07-21-2010
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Cardiac electrophysiology is a mature discipline, with the first model of a cardiac cell action potential having been developed in 1962. Current models range from single ion channels, through very complex models of individual cardiac cells, to geometrically and anatomically detailed models of the electrical activity in whole ventricles. A critical issue for model developers is how to choose parameters that allow the model to faithfully reproduce observed physiological effects without over-fitting. In this paper, we discuss the use of a parametric modelling toolkit, called Nimrod, that makes it possible both to explore model behaviour as parameters are changed and also to tune parameters by optimizing model output. Importantly, Nimrod leverages computers on the Grid, accelerating experiments by using available high-performance platforms. We illustrate the use of Nimrod with two case studies, one at the cardiac tissue level and one at the cellular level.
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Strategies to manage retinoblastoma in developing countries.
Pediatr Blood Cancer
PUBLISHED: 07-05-2010
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Survival of retinoblastoma is >90% in developed countries but there are significant differences with developing countries in stage at presentation, available treatment options, family compliance, and survival. In low-income countries (LICs), children present with advanced disease, and the reasons are socioeconomic and cultural. In middle-income countries (MICs), survival rates are better (>70%), but there is a high prevalence of microscopically disseminated extraocular disease. Programs for eye preservation have been developed, but toxicity-related mortality is higher. Although effective treatment of microscopically extraocular disease improved the outcome, worldwide survival will be increased only by earlier diagnosis and better treatment adherence.
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Tumor-associated retinal astrocytes promote retinoblastoma cell proliferation through production of IGFBP-5.
Am. J. Pathol.
PUBLISHED: 05-27-2010
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Retinoblastomas consist of cone-like neoplastic cells and diverse non-neoplastic cells whose roles in tumorigenesis have not been defined. Here, we investigated the glial cells that constitute 2% to 3% of the cells in retinoblastoma tumors, including their origin, their relationship to a potential retinoblastoma stem cell population, and their effects on tumor cell proliferation. Retinoblastoma glia consistently expressed the retinal astrocyte marker Pax2 but inconsistently expressed the Müller cell and occasional astrocyte marker CRALBP. Many of the glia expressed the stem cell-associated Sox2 but nevertheless were non-neoplastic as they coexpressed Rb and/or retained two RB1 alleles. Conversely, the glia were distinct from the non-neoplastic cells that strongly expressed the stem cell-associated ABCG2. Adherent Pax2(+),Sox2(+),Rb(+) glia readily grew from explanted retinoblastomas and produced soluble factors that enhanced the proliferation of cocultured retinoblastoma cells. This effect was emulated by normal retinal glia and appeared to be mediated by insulin-like growth factor binding protein-5 (IGFBP-5), as it was mimicked by recombinant IGFBP-5 and mitigated by neutralizing IGFBP-5 antibody. As glia-derived IGFBP-5 was earlier found to promote photoreceptor survival, our findings indicate that retinal astrocytes enhance the proliferation of cone-like retinoblastoma cells by deploying a factor that also provides trophic support to the tumor cells non-neoplastic counterparts. These observations suggest that a tissue-specific microenvironmental feature cooperates with oncogenic mutations in a cancer cell of origin to promote retinoblastoma tumorigenesis.
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High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma.
Pediatr Blood Cancer
PUBLISHED: 05-21-2010
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Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include high-dose chemotherapy with autologous hematopoietic stem cell rescue.
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Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma.
Pediatr Blood Cancer
PUBLISHED: 05-21-2010
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We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series.
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Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery).
Ophthalmology
PUBLISHED: 04-09-2010
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To report on our 3-year experience with the use of superselective ophthalmic artery infusion of chemotherapy as initial, primary treatment for intraocular retinoblastoma.
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MrGrid: a portable grid based molecular replacement pipeline.
PLoS ONE
PUBLISHED: 03-18-2010
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The crystallographic determination of protein structures can be computationally demanding and for difficult cases can benefit from user-friendly interfaces to high-performance computing resources. Molecular replacement (MR) is a popular protein crystallographic technique that exploits the structural similarity between proteins that share some sequence similarity. But the need to trial permutations of search models, space group symmetries and other parameters makes MR time- and labour-intensive. However, MR calculations are embarrassingly parallel and thus ideally suited to distributed computing. In order to address this problem we have developed MrGrid, web-based software that allows multiple MR calculations to be executed across a grid of networked computers, allowing high-throughput MR.
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Hepatic abnormalities identified on abdominal computed tomography at diagnosis of uveal melanoma.
Arch. Ophthalmol.
PUBLISHED: 03-10-2010
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To determine the prevalence of hepatic abnormalities identified during abdominal computed tomography (CT) performed within 1 month of the diagnosis of primary uveal melanoma.
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Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization.
J. Cutan. Pathol.
PUBLISHED: 01-27-2010
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A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work-up of conjunctival melanocytic proliferations.
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Effect of weight loss after bariatric surgery on skin and the extracellular matrix.
Plast. Reconstr. Surg.
PUBLISHED: 01-06-2010
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Obese patients experience dramatic physical and metabolic changes in the skin and its collagen. Bariatric surgery is known to result in significant improvement in obesity-associated comorbid conditions and metabolic disturbances. The aim of this study was to evaluate skin quality following weight loss surgery and its suitability to produce an extracellular matrix for use in reconstructive procedures.
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Pharmacokinetic analysis of topotecan after intra-vitreal injection. Implications for retinoblastoma treatment.
Exp. Eye Res.
PUBLISHED: 01-02-2010
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Topotecan is a promising drug with activity against retinoblastoma, however, attaining therapeutic concentrations in the vitreous humor is still a challenge for the treatment of vitreous seeds in retinoblastoma. Our aim was to characterize topotecan pharmacokinetics in vitreous and aqueous humor, and to assess the systemic exposure after intra-vitreal injection in rabbits as an alternative route for maximizing local drug exposure. Anesthetized rabbits were administered intra-vitreal injections of 5 microg of topotecan. Vitreous, aqueous, and blood samples were collected at pre-defined time points. A validated high-performance liquid chromatography assay was used to quantitate topotecan (lactone and carboxylate) concentrations. Topotecan pharmacokinetic parameters were determined in vitreous, aqueous and plasma using a compartmental analysis. Topotecan lactone concentrations in the vitreous of the injected eye were about 8 ng/mL 48 h after drug administration. The median maximum vitreous, aqueous and plasma total topotecan concentrations (C(max)) were 5.3, 0.68 and 0.21 microg/mL, respectively. The C(max) vitreous/aqueous of treated eyes and the C(max) vitreous/plasma were approximately 8 and 254, respectively. Total topotecan exposure (AUC) in the vitreous of the injected eye was 50 times greater than the total systemic exposure. These findings suggest that intra-vitreal administration of only 5 microg of topotecan reaches significant local levels over an extended period of time while minimizing systemic exposure in the rabbit. Intra-vitreal topotecan administration offers a promising alternative route for enhanced drug exposure in the vitreous humor with potential application for treatment of vitreal seeds in retinoblastoma while avoiding systemic toxicities.
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Risk of cataract extraction among adult retinoblastoma survivors.
Arch. Ophthalmol.
PUBLISHED: 11-11-2009
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To investigate the risk of cataract extraction among adult retinoblastoma survivors.
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Diagnosis of retinoblastoma: how good are referring physicians?
Ophthalmic Genet.
PUBLISHED: 10-27-2009
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To evaluate accuracy of the referring diagnoses of retinoblastoma to a tertiary cancer referral center.
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Episcleral implants for topotecan delivery to the posterior segment of the eye.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-15-2009
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Purpose. Intravenous or periocular topotecan has been proposed as new treatment modality for patients with advanced intraocular retinoblastoma, but systemic topotecan lactone exposure induced by both approaches may cause toxicity. The purpose of this study was to develop a topotecan-loaded ocular delivery system to minimize systemic exposure and achieve selective transscleral penetration. Methods. Biocompatible polymer implants containing low (0.3 mg) or high (2.3 mg) topotecan load were manufactured and characterized in vitro. Adrenaline (500 mug) was coloaded to induce local vasoconstriction in vivo in 2 of 4 animal groups. Implants were inserted into the episclera of rabbits, and topotecan (lactone and total) concentrations in ocular tissues and plasma were determined over a period of 48 hours. Results. In vitro, implants released 30% to 50% of the loaded drug within 48 hours and 45% to 70% by day 10. In vivo, topotecan lactone was highly accumulated in locally exposed ocular tissues (ranging from 10(5) to 10(6) ng/g in sclera and choroid and 10(2) to10(3) ng/g in retina) over 48 hours with all the formulations studied. Low vitreous topotecan lactone levels (approximately 5 ng/mL) were found in animals receiving concomitant local vasoconstriction and high load implants. Topotecan lactone concentrations in plasma and in contralateral eyes were minimal or undetectable as a marker of tissue selectivity of the proposed strategy. Conclusions. These studies may contribute to improving the efficacy and safety of chemotherapy treatments for retinoblastoma and may support the role of the local vasculature and tissues promoting drug clearance and local accumulation during transscleral drug delivery.
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Familial retinoblastoma in developing countries.
Pediatr Blood Cancer
PUBLISHED: 05-13-2009
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Although screening for familial retinoblastoma has been shown to be beneficial we suspected that such screening programs may be less than optimal in developing countries (DC).
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Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 05-06-2009
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To identify clinical features at presentation to help in detecting patients with retinoblastoma and pathology risk factors (PRFs) preoperatively, and therefore selecting a high-risk population that could benefit from preoperative treatment.
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A phase I study of periocular topotecan in children with intraocular retinoblastoma.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 04-11-2009
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To identify the maximum tolerated dose and dose-limiting toxicity of periocular topotecan in patients with relapsed or resistant intraocular retinoblastoma who are facing imminent enucleation.
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Cause-specific mortality in long-term survivors of retinoblastoma.
J. Natl. Cancer Inst.
PUBLISHED: 04-07-2009
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Subsequent malignant neoplasms are a major cause of premature death in survivors of hereditary retinoblastoma. Radiotherapy further increases the risk of death. Mortality information is limited among long-term survivors who were irradiated for hereditary retinoblastoma.
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Published international classification of retinoblastoma (ICRB) definitions contain inconsistencies--an analysis of impact.
Ophthalmic Genet.
PUBLISHED: 01-28-2009
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To determine the impact of subtle differences (most notably in their classification of group E eyes) in two published versions of the ICRB (Philadelphia and the Childrens Hospital Los Angeles).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.