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Sample records for retinoblastoma protein-mediated terminal

  1. Retinoblastoma

    International Nuclear Information System (INIS)

    Desjardins, L.; Doz, F.; Schlienger, P.; Validire, P.; Quintana, E.; Zucker, J.M.

    1996-01-01

    Early symptoms of retinoblastoma (leukocoria, strabismus) and the various steps of the diagnosis and differential diagnosis are reviewed. Retrolental fibroplasia, larva migrans, Coats disease, and above all uveitis are the main differential diagnoses. Pathologic features that allow the diagnosis and have a bearing on the prognosis are described. Genetic factors involved in the genesis of retinoblastoma are reviewed, including recent data provides by molecular biology studies of chromosome 13. Currently available treatments include enucleation, external beam radiation, iodine-125 disks, xenon photo-coagulation, cryo-application, chemotherapy, and carbo-platinum combined with diode laser hyperthermia. The indications of each of these methods in intra- and extra-ocular retinoblastomas are discussed, as well as results and complications. Emphasis is put on the high risk of a second cancer. 47 refs., 4 figs

  2. Retinoblastoma

    International Nuclear Information System (INIS)

    Schipper, J.

    1980-01-01

    Retinoblastoma is a rare, highly malignant tumour of the retina which predominantly affects young children. The growth originates from single or multiple foci in the retina of one or both eyes. The tumour may occur either sporadically or may be inherited. Retinoblastoma is extra-ordinary in its medical, genetic and therapeutic significance. The irradiation method which has been used for the conservative treatment of retinoblastoma at Utrecht since 1971 is described. Treatment is carried out on a 6 MeV or 8 MeV linear accelerator using a lateral D-shaped field of 26x32 mm 2 . This D-shaped field is especially contoured to irradiate the entire retina with sparing of the radiosensitive lens as much as possible. Between 1971 and 1980, 30 children with retinoblastoma have received irradiation to at least one eye using the accurate irradiation technique. The results of treatment of these patients are presented. In the treatment it is not always possible to entirely exclude the lens from the treatment field. As a consequence, cataract may be induced. (Auth.)

  3. Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family

    Energy Technology Data Exchange (ETDEWEB)

    Liban, Tyler J.; Medina, Edgar M.; Tripathi, Sarvind; Sengupta, Satyaki; Henry, R. William; Buchler, Nicolas E.; Rubin, Seth M. (UCSC); (Duke); (MSU)

    2017-04-24

    The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD–CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein–E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.

  4. Neonatal retinoblastoma

    Directory of Open Access Journals (Sweden)

    Tero T Kivelä

    2017-01-01

    Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support

  5. The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

    Science.gov (United States)

    May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

    2010-08-01

    The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

  6. IVF and retinoblastoma revisited

    NARCIS (Netherlands)

    Dommering, Charlotte J.; van der Hout, Annemarie H.; Meijers-Heijboer, Hanne; Marees, Tamara; Moll, Annette C.

    2012-01-01

    Objective: To evaluate the suggested association between IVF, retinoblastoma, and tumor methylation characteristics. Design: Laboratory analysis. Setting: National Retinoblastoma Center in the Netherlands. Patient(s): Retinoblastoma tumors from seven children conceived by IVF or intracytoplasmic

  7. IVF and retinoblastoma revisited

    NARCIS (Netherlands)

    Dommering, Charlotte J.; van der Hout, Annemarie H.; Meijers-Heijboer, Hanne; Marees, Tamara; Moll, Annette C.

    Objective: To evaluate the suggested association between IVF, retinoblastoma, and tumor methylation characteristics. Design: Laboratory analysis. Setting: National Retinoblastoma Center in the Netherlands. Patient(s): Retinoblastoma tumors from seven children conceived by IVF or intracytoplasmic

  8. Current treatment of retinoblastoma

    International Nuclear Information System (INIS)

    Shields, J.A.

    1985-01-01

    Retinoblastoma is a highly malignant intraocular tumor of childhood which requires prompt treatment once the diagnosis has been established. The traditionally accepted methods include enucleation, external irradiation, scleral plaque irradiation, photocoagulation, cryotherapy, chemotherapy. This article will provide an update on the modern methods of treatment which are available for retinoblastoma. It is based largely on personal experience with approximately 200 new patients with retinoblastoma who were evaluated and treated between 1974 and 1984 in the Oncology Service of Wills Eye Hospital with an overall survival of 97%. This article will be an overall review which will not go into statistical detail. (Auth.)

  9. Computed tomography of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Lindahl, S.

    Retinoblastoma is the most common primary malignant intraocular tumor in children. The clinical features are leucocoria and/or strabismus. The ophthalmic diagnosis is straight forward in clear eye media with a white gray mass in the fundus. With opaque ocular media, other diagnostic procedures such as CT and ultrasonography are important. In the present study the results of CT examinations of 23 patients with histologically proven retinoblastomas are presented. The mean age of the patients was two years. The characteristic CT finding is a partly calcified intravitreous mass lesion mostly confined within the eyeball. Two cases showed retrobulbar extension and two intracranical tumor extension. No metastasis was found in the brain, liver, spleen, long bones, chest or skull. The radiologic screening procedures for retinoblastoma metastasis are discussed. In patients suspected to have a retinoblastoma, it is recommended to perform CT of the orbits and brain in order to detect the tumor and its possible retrobulbar and intracranial extension.

  10. Computed tomography of retinoblastoma

    International Nuclear Information System (INIS)

    Lindahl, S.

    1986-01-01

    Retinoblastoma is the most common primary malignant intraocular tumor in children. The clinical features are leucocoria and/or strabismus. The ophthalmic diagnosis is straight forward in clear eye media with a white gray mass in the fundus. With opaque ocular media, other diagnostic procedures such as CT and ultrasonography are important. In the present study the results of CT examinations of 23 patients with histologically proven retinoblastomas are presented. The mean age of the patients was two years. The characteristic CT finding is a partly calcified intravitreous mass lesion mostly confined within the eyeball. Two cases showed retrobulbar extension and two intracranical tumor extension. No metastasis was found in the brain, liver, spleen, long bones, chest or skull. The radiologic screening procedures for retinoblastoma metastasis are discussed. In patients suspected to have a retinoblastoma, it is recommended to perform CT of the orbits and brain in order to detect the tumor and its possible retrobulbar and intracranial extension. (orig.)

  11. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  12. Rabbit Model of Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Shin Jeong Kang

    2011-01-01

    Full Text Available We created a rabbit model of retinoblastoma and confirmed the tumor clinically and histopathologically. Seventeen New Zealand rabbits were immunosuppressed with cyclosporin A at doses of 10–15 mg/kg. At day 3, the animals received a 30 μl subretinal injection of 1×106 cultured WERI retinoblastoma cells. Digital fundus images were captured before euthanasia, and the eyes were submitted for histopathology. Retinoblastoma cells grew in all the inoculated eyes and established a tumor under the retina and/or in the vitreous. New blood vessels in the tumor were observed starting at week 5. Cuffs of viable tumor cells surrounded the blood vessels with regions of necrosis present at 70–80 μm from nutrient vessels. Occasional tumor seeds in the vitreous histologically exhibited central necrosis. This rabbit model demonstrated similar fundus appearance and pathologic features to human retinoblastoma and may be used as a model to test various routes of drug delivery for retinoblastoma.

  13. Naturally death-resistant precursor cells revealed as the origin of retinoblastoma

    DEFF Research Database (Denmark)

    Trinh, Emmanuelle; Lazzerini Denchi, Eros; Helin, Kristian

    2004-01-01

    The molecular mechanisms and the cell-of-origin leading to retinoblastoma are not well defined. In this issue of Cancer Cell, Bremner and colleagues describe the first inheritable model of retinoblastoma, revealing that loss of the pocket proteins pRb and p107 deregulates cell cycle exit in retinal...... precursors. The authors show that a subset of these precursors contain an inherent resistance to apoptosis, and that while most terminally differentiate, some are likely to acquire additional mutations, leading to tumor formation. Thus, this work defines the cell-of-origin of retinoblastoma and suggests...... that mutations giving increased proliferative capacity are required for retinoblastoma development....

  14. Irradiation sequels of retinoblastomas

    International Nuclear Information System (INIS)

    Benk, V.; Habrand, J.L.; Bloch Michel, E.; Soussaline, M.; Sarrazin, D.

    1993-01-01

    From 1975 to 1985, 34 children with a non-metastatic retinoblastoma were irradiated at the Institut Gustave-Roussy. After enucleation, 19 bilateral tumors were irradiated by two lateral opposed fields and 15 unilateral tumors by one lateral and anterior field, in the case of optic nerve being histologically positive. Dose was 45 Gy, 1.8 Gy per fraction. The 10-year-survival rate for unilateral and bilateral retinoblastomas was 79%. Long term sequels were available for 25 patients: 88% retained one functional eye. Three children with bilateral retinoblastomas developed a cataract in the residual eye between 2 and 5 years after irradiation, none with unilateral tumor. Nine patients (36%), seven with unilateral and two with bilateral tumor developed a cosmetical problem that required multiple surgical rehabilitation between 3 and 14 years after irradiation. Nine children (36%), five with unilateral and four with bilateral tumors developed growth hormone deficit between 2 and 8 years after irradiation that required hormone replacement. Their pituitary gland received 22 to 40 Gy. No osteosarcoma occurred in this population. Among long-term sequels, following irradiation for retinoblastoma, cosmetical deformities represent disabling sequels that could justify new approaches in radiotherapy, as protontherapy combined with 3-D-treatment planning

  15. Genetics Home Reference: retinoblastoma

    Science.gov (United States)

    ... Some studies suggest that additional genetic changes can influence the development of retinoblastoma ; these changes may help explain variations ... usually occurs in childhood, typically leading to the development of ... and there is no family history of the disease. Affected individuals are born ...

  16. Radiation management of retinoblastoma

    International Nuclear Information System (INIS)

    Takemasa, Kazuhiko; Ito, Hisao; Nishiguchi, Iku; Hashimoto, Shozo; Tanaka, Yasuhiko; Oguchi, Yoshihisa

    1992-01-01

    Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated. (author)

  17. Radiation management of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Takemasa, Kazuhiko; Ito, Hisao; Nishiguchi, Iku; Hashimoto, Shozo; Tanaka, Yasuhiko; Oguchi, Yoshihisa (Keio Univ., Tokyo (Japan). School of Medicine)

    1992-06-01

    Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated. (author).

  18. Radiation management of retinoblastoma

    International Nuclear Information System (INIS)

    Takemasa, Kazuhiko; Ito, Hisao; Hashimoto, Shozo; Tanaka, Yasuhiko; Oguchi, Yoshihisa

    1991-01-01

    An analysis has been conducted of 45 patients treated for retinoblastoma at Keio University Hospital between 1970 and 1990. Of these patients, 32 had unilateral lesion and 13 had bilateral lesion. Further, since their disease was far advanced, 29 patients with unilateral lesion and 12 patients with bilateral lesion underwent enucleation. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral manifestation of the disease were treated with radiotherapy (45-50 Gy) with or without cryotherapy and photocoagulation. One patient with unilateral lesion, who had received both radiotherapy and chemotherapy, showed metastases at the first presentation at our clinic and thus was excluded from this analysis. Among 16 eyes of 15 patients who were given radiotherapy, 6 eyes developed recurrence and needed to have further treatment. In 6 eyes out of 12, cataract developed, and out of 10 eyes in which eye function was evaluable, good vision was able to be preserved in 5 eyes. (author)

  19. Retinoblastoma: a most unusual presentation

    African Journals Online (AJOL)

    Dr. C. Pedro-Egbe

    Although leukocoria and strabismus are the most common presenting signs of retinoblastoma, a retrospective study by Abramson et al. identified 32 distinct presenting signs of retinoblastoma.6-8. A few other studies have also noted some distinct characteristics exhibited by children whose conditions were diagnosed in the ...

  20. Ultrasonographic findings of retinoblastoma

    International Nuclear Information System (INIS)

    Chung, Sung Hoo; Kang, Ik Won; Park, Yang Hee; Kim, Chu Wan; Chi, Je Geun

    1982-01-01

    Retinoblastoma is the most common intraocular tumor in infants and young children which has relatively favorable prognosis with early diagnosis and adequate treatment, however, it can be lethal if the treatment is delayed or inadequate. Clinically, early diagnosis is often difficult because of minimal subjective and objective signs and symptoms, and the patients are usually too young to complain visual disturbance. When ophthalmoscopicexamination is impossible due to presence of opaue media in front of tumor mass as associated inflammatory reaction, hemorrhage, corneal opacity, retinal detachment, etc, ultrasonography is necessary for diagnosis of retinoblastoma. Authors analyzed ultrasonographic al findings with pathological correlation on 10 cases of confirmed retinoblastoma during the period of March 1981 to September1982 at the Seoul National University Hospital. In all cases, ultrasonography demonstrates intraocular masses and all of which are cystic type.Reflectivity of masses are higher than retroorbital fat tissue in 8 cases, and 7 cases show irregular internal echogenic texture. There is no correlation between reflexivity and internal echogenic texture with microscopic findings as rosette, pseudo rosette and micro cysts. Calcifications are demonstrated by ultrasonography as strong reflectiveness with posterior sonic shadowing in 9 cases and 9 of 10 cases are well correlated with calcifications in pathologic specimens. Anechoic cystic areas are shown in 9 cases, and 6 of 10 cases are well correlated with necrosis in pathologic specimen. In all cases, there is no attenuation of sound within tumor masses, and no demonstrable choroidal excavation. Associated retinal detachment is hardly identifiable in irregular contour and internal texture of cystic tumor masses

  1. Radiotherapy for retinoblastoma

    International Nuclear Information System (INIS)

    Murayama, Shigeyuki; Kagami, Yoshikazu; Tokuue, Koichi; Sumi, Minako; Ikeda, Hiroshi; Kaneko; Akihiro

    1999-01-01

    A retrospective chart review was made of the patients with retinoblastoma received eye conservative therapy between 1980 and 1992. Of 112, 77 had bilateral disease and 35 had unilateral disease. A definitive external radiation therapy (ERT) was used in 106 eyes and ERT combined with concurrent or adjuvant therapy in 29 eyes. Five-year cumulative eye-ball conservation rate for Reese-Ellsworth classification group I to V were 95%, 95.5%, 93.3%, 100% and 58.5%, respectively. Useful vision (>0.01) was maintained in 90.2% of 61 eyes which were treated by definitive ERT initially and experienced no local recurrence. (author)

  2. The N Terminus of the Retinoblastoma Protein Inhibits DNA Replication via a Bipartite Mechanism Disrupted in Partially Penetrant Retinoblastomas

    Science.gov (United States)

    Borysov, Sergiy I.; Nepon-Sixt, Brook S.

    2015-01-01

    The N-terminal domain of the retinoblastoma (Rb) tumor suppressor protein (RbN) harbors in-frame exon deletions in partially penetrant hereditary retinoblastomas and is known to impair cell growth and tumorigenesis. However, how such RbN deletions contribute to Rb tumor- and growth-suppressive functions is unknown. Here we establish that RbN directly inhibits DNA replication initiation and elongation using a bipartite mechanism involving N-terminal exons lost in cancer. Specifically, Rb exon 7 is necessary and sufficient to target and inhibit the replicative CMG helicase, resulting in the accumulation of inactive CMGs on chromatin. An independent N-terminal loop domain, which forms a projection, specifically blocks DNA polymerase α (Pol-α) and Ctf4 recruitment without affecting DNA polymerases ε and δ or the CMG helicase. Individual disruption of exon 7 or the projection in RbN or Rb, as occurs in inherited cancers, partially impairs the ability of Rb/RbN to inhibit DNA replication and block G1-to-S cell cycle transit. However, their combined loss abolishes these functions of Rb. Thus, Rb growth-suppressive functions include its ability to block replicative complexes via bipartite, independent, and additive N-terminal domains. The partial loss of replication, CMG, or Pol-α control provides a potential molecular explanation for how N-terminal Rb loss-of-function deletions contribute to the etiology of partially penetrant retinoblastomas. PMID:26711265

  3. Tumours following retinoblastoma radiotherapy

    International Nuclear Information System (INIS)

    Mollot, J.-P.

    1978-01-01

    Radioinduced tumours in young patients irradiated in childhood for retinoblastoma take on a particularly deadly aspect. The onset of this true clinical entity characterized by a long post-irradiation latency period induced by a dose above 6000 rads is a real tragedy. The vast majority of patients then enter into a long martyrdom ending in death. The only cure is surgical, but seldom possible. Treatment is limited to palliative radiotherapy, effective for a while, and chemiotherapy as a last resort but often difficult to prescribe. Prevention alone is the answer. The quality and reliability of the radiotherapeutic treatment depend not only on the personal talent of the radiotherapist but above all on the standard of the equipment. A strong reduction in the doses employed as well as recent technological progress improving the material, its precision and reproducibility appear already to have lowered the frequency curve of these fatal radioinduced tumours [fr

  4. A transgenic mouse model for trilateral retinoblastoma

    NARCIS (Netherlands)

    O'Brien, J.M.; Marcus, D.M.; Bernards, R.A.; Carpenter, J.L.; Windle, J.J.; Mellon, P.; Albert, D.M.

    1990-01-01

    We present a murine model of trilateral retinoblastoma. Ocular retinoblastoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically

  5. Retinoblastoma – to expand awareness

    African Journals Online (AJOL)

    lead to delay in diagnosis, possibly loss of vision or even loss of life. Both the public and ... These retinoblastomas show altered gene copy number ... and an examination under anaesthesia, in which the number, size and location ... effects than external beam radiotherapy but is not ... attention to arrival at the unit. Advanced.

  6. modes of presentation, management and outcome of retinoblastoma

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    and short-term outcomes of retinoblastoma treatment at ... incidence of retinoblastoma during the HIV period. Apart .... differentiated retinoblastoma. .... The Zambian health delivery ... the guardian from home and the extra cost of hospital stay.

  7. Inhibition of Retinoblastoma Protein Inactivation

    Science.gov (United States)

    2017-11-01

    CONTRACT NUMBER Inhibition of Retinoblastoma Protein Inactivation 5b. GRANT NUMBER W81XWH-14-1-0329 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Seth M...confirmed 108 compounds as giving a dose-response curve with at least 30% inhibition at 10 µM. The flowchart of hit progression is shown on the...Cancer Research Program under Award No. W81XWH-14-1-0329 to S.M.R. Opinions, interpretations, conclusions, and recommendations are those of the author

  8. Late onset retinoblastoma presenting with vitreous haemorrhage

    DEFF Research Database (Denmark)

    Bagger, Mette; Prause, Jan Ulrik; Heegard, Steffen

    2012-01-01

    in the retina. A vascularized gelatinous mass was revealed after vitrectomy. Later the patient developed white cysts in the anterior chamber and histological findings were indicative of a retinoblastoma. The patient was enucleated and the diagnosis of retinoblastoma was confirmed. Intraocular surgery in young...... people with unknown retinoblastoma enhances the risk of metastasis development, orbital recurrence and death. Unexplained vitreous haemorrhage can obscure the view of a tumour but ultrasonic findings of a retinal mass calls for further imaging e.g. through MRI. The case illustrates the importance...

  9. [Familial retinoblastoma: cytogenetic study of the tumor].

    Science.gov (United States)

    Robledo Batanero, M; Manzanal Martínez, A; Ayuso García, C; Benítez Ortiz, J

    1990-05-01

    We report a case of familiar retinoblastoma, in which both mother and daughter show bilateral retinoblastoma. The cytogenetic study, in both peripheral blood lymphocytes and tumoral tissue did not show alterations on the 13 chromosome, although we found a complex kariotype in tumoral tissue defined by three celular lines. In all of them appears a marker in which the 6 chromosome is involved (der 6). The derivated of 6 chromosome are markers highly characteristic of the retinoblastoma cases, and can be related with the aggressivity of tumor and the appearance of the second tumors.

  10. Clinicopathological pattern and management of retinoblastoma in ...

    African Journals Online (AJOL)

    shobha

    leucocoria, proptosis, hyphaema without history of trauma, unexplained ... Conclusion: Retinoblastoma, a treatable tumor is characterized by late presentation as illustrated in our ..... Great Britain 1969-80: Incidence, treatment and survival.

  11. Immunohistochemical demonstration of glial markers in retinoblastomas

    DEFF Research Database (Denmark)

    Schrøder, H D

    1987-01-01

    Twenty retinoblastomas were studied immunohistochemically in order to visualize glial cells. In the retina, the glial cells in the ganglion cell layer and the Müller cells were GFAP positive, while only the glial cells of the ganglion cell layer expressed S-100 reactivity. In the tumours S-100/GFAP...... cells reactive for both S-100 and GFAP were demonstrated. The latter findings may represent differentiation in a glial direction in the more mature parts of retinoblastoma....

  12. BTG interacts with retinoblastoma to control cell fate in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Daniele Conte

    Full Text Available BACKGROUND: In the genesis of many tissues, a phase of cell proliferation is followed by cell cycle exit and terminal differentiation. The latter two processes overlap: genes involved in the cessation of growth may also be important in triggering differentiation. Though conceptually distinct, they are often causally related and functional interactions between the cell cycle machinery and cell fate control networks are fundamental to coordinate growth and differentiation. A switch from proliferation to differentiation may also be important in the life cycle of single-celled organisms, and genes which arose as regulators of microbial differentiation may be conserved in higher organisms. Studies in microorganisms may thus contribute to understanding the molecular links between cell cycle machinery and the determination of cell fate choice networks. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that in the amoebozoan D. discoideum, an ortholog of the metazoan antiproliferative gene btg controls cell fate, and that this function is dependent on the presence of a second tumor suppressor ortholog, the retinoblastoma-like gene product. Specifically, we find that btg-overexpressing cells preferentially adopt a stalk cell (and, more particularly, an Anterior-Like Cell fate. No btg-dependent preference for ALC fate is observed in cells in which the retinoblastoma-like gene has been genetically inactivated. Dictyostelium btg is the only example of non-metazoan member of the BTG family characterized so far, suggesting that a genetic interaction between btg and Rb predated the divergence between dictyostelids and metazoa. CONCLUSIONS/SIGNIFICANCE: While the requirement for retinoblastoma function for BTG antiproliferative activity in metazoans is known, an interaction of these genes in the control of cell fate has not been previously documented. Involvement of a single pathway in the control of mutually exclusive processes may have relevant implication in the

  13. Retinoblastoma

    Science.gov (United States)

    ... Feb 20, 2018 Gene Therapy May Be a Game-Changer for People With Inherited Retinal Disease Dec 19, 2017 ... the Academy Jobs at the Academy Financial Relationships with Industry Medical Disclaimer Privacy Policy Terms of Service For ...

  14. Retinoblastoma

    Science.gov (United States)

    ... NEI Intranet (Employees Only) *PDF files require the free Adobe® Reader® software for viewing. This website is maintained by the NEI Office of Science Communications, Public Liaison, and Education. Technical questions about this website can be addressed ...

  15. Retinoblastoma: genetic considerations and report of a new animal model

    NARCIS (Netherlands)

    Albert, D.M.; O'Brien, J.M.; Marcus, D.M.; Bernards, R.A.

    1990-01-01

    Retinoblastoma is the most common primary, intraocular neoplasm of childhood. Histologically, retinoblastoma resembles, in many respects, other pediatric malignancies such as medulloblastoma and neuroblastoma. These tumors are composed of small, basophilic cells with scanty cytoplasm and often

  16. Transcriptional inhibition by the retinoblastoma protein

    DEFF Research Database (Denmark)

    Fattaey, A; Helin, K; Harlow, E

    1993-01-01

    The retinoblastoma protein, pRB, appears to play a key role in coordinating the regulation of cell cycle position and transcriptional events. pRB undergoes specific cell-cycle-dependent phosphorylation, being underphosphorylated in G1 and heavily phosphorylated in S, G2, and M. The underphosphory......The retinoblastoma protein, pRB, appears to play a key role in coordinating the regulation of cell cycle position and transcriptional events. pRB undergoes specific cell-cycle-dependent phosphorylation, being underphosphorylated in G1 and heavily phosphorylated in S, G2, and M......-mediated transcription would be lost by mutation in the retinoblastoma gene in human tumours, by pRB's interaction with DNA tumour virus oncoproteins, or by phosphorylation during the cell cycle....

  17. Intensity modulated radiotherapy (IMRT) in bilateral retinoblastoma

    International Nuclear Information System (INIS)

    Atalar, Banu; Ozyar, Enis; Gunduz, Kaan; Gungor, Gorkem

    2010-01-01

    External beam radiotherapy (EBRT) for retinoblastoma has traditionally been done with conventional radiotherapy techniques which resulted high doses to the surrounding normal tissues. A 20 month-old girl with group D bilateral retinoblastoma underwent intensity modulated radiotherapy (IMRT) to both eyes after failing chemoreduction and focal therapies including cryotherapy and transpupillary thermotherapy. In this report, we discuss the use of IMRT as a method for reducing doses to adjacent normal tissues while delivering therapeutic doses to the tumour tissues compared with 3-dimensional conformal radiotherapy (3DCRT). At one year follow-up, the patient remained free of any obvious radiation complications. Image guided IMRT provides better dose distribution than 3DCRT in retinoblastoma eyes, delivering the therapeutic dose to the tumours and minimizing adjacent tissue damage

  18. Herramienta para la Deteccion de Retinoblastoma

    OpenAIRE

    Vargas-Cuentas , Natalia Indira; Roman-Gonzalez , Avid

    2015-01-01

    International audience; El retinoblastoma, es un tumor que se presenta en la retina de las personas, especialmente en los niños. Una detección temprana del mismo, podría ser muy útil y salvar la vida del niño. Es en ese sentido, que el presente trabajo propone una herramienta sencilla para la detección de retinoblastoma analizando fotografías tomadas con flash en las cuales, en el ojo del niño se puede detectar la presencia de leucoria. Esta detección se realiza utilizando las funciones de de...

  19. Tumor regression patterns in retinoblastoma

    International Nuclear Information System (INIS)

    Zafar, S.N.; Siddique, S.N.; Zaheer, N.

    2016-01-01

    To observe the types of tumor regression after treatment, and identify the common pattern of regression in our patients. Study Design: Descriptive study. Place and Duration of Study: Department of Pediatric Ophthalmology and Strabismus, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from October 2011 to October 2014. Methodology: Children with unilateral and bilateral retinoblastoma were included in the study. Patients were referred to Pakistan Institute of Medical Sciences, Islamabad, for chemotherapy. After every cycle of chemotherapy, dilated funds examination under anesthesia was performed to record response of the treatment. Regression patterns were recorded on RetCam II. Results: Seventy-four tumors were included in the study. Out of 74 tumors, 3 were ICRB group A tumors, 43 were ICRB group B tumors, 14 tumors belonged to ICRB group C, and remaining 14 were ICRB group D tumors. Type IV regression was seen in 39.1% (n=29) tumors, type II in 29.7% (n=22), type III in 25.6% (n=19), and type I in 5.4% (n=4). All group A tumors (100%) showed type IV regression. Seventeen (39.5%) group B tumors showed type IV regression. In group C, 5 tumors (35.7%) showed type II regression and 5 tumors (35.7%) showed type IV regression. In group D, 6 tumors (42.9%) regressed to type II non-calcified remnants. Conclusion: The response and success of the focal and systemic treatment, as judged by the appearance of different patterns of tumor regression, varies with the ICRB grouping of the tumor. (author)

  20. The retinoblastoma protein as a transcriptional repressor

    DEFF Research Database (Denmark)

    Helin, K; Ed, H

    1993-01-01

    The retinoblastoma protein (pRB) is one of the best-studied tumour suppressor gene products. Its loss during the genesis of many human tumours, its inactivation by several DNA tumour virus oncoproteins, and its ability to inhibit cell growth when introduced into dividing cells all suggest that p...

  1. Expression of multidrug resistance proteins in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Swati Shukla

    2017-11-01

    Full Text Available AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS: Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS: Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1 expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

  2. Expression of multidrug resistance proteins in retinoblastoma.

    Science.gov (United States)

    Shukla, Swati; Srivastava, Arpna; Kumar, Sunil; Singh, Usha; Goswami, Sandeep; Chawla, Bhavna; Bajaj, Mandeep Singh; Kashyap, Seema; Kaur, Jasbir

    2017-01-01

    To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

  3. Expression of multidrug resistance proteins in retinoblastoma

    Science.gov (United States)

    Shukla, Swati; Srivastava, Arpna; Kumar, Sunil; Singh, Usha; Goswami, Sandeep; Chawla, Bhavna; Bajaj, Mandeep Singh; Kashyap, Seema; Kaur, Jasbir

    2017-01-01

    AIM To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy. PMID:29181307

  4. Retinoblastoma: genetics, diagnosis, treatment and sequelae

    International Nuclear Information System (INIS)

    Halperin, Edward C.

    1995-01-01

    There has been a conceptual breakthrough in our understanding of the molecular and genetic basis of the origins of human neoplasia. Mutations in three broad categories of genes have been shown to contribute to the origins and progression of neoplasia in humans: the oncogenes, the tumor suppressor genes, and the mutator genes. The retinoblastoma gene (RB1) is the best characterized tumor suppressor gene. It was first localized by Knudson and coworkers who observed an association between a deletion on the long arm of chromosome 13 and an inherited predisposition to retinoblastoma. The RB1 gene is composed of 27 exons encompassing more than 200 kilobases of genomic DNA. The product of the RB1 gene is a 105-107 kDa nuclear phosphoprotein which plays a part in regulating cellular DNA synthesis. Tumors arise, as predicted by Knudson's 'two-hit' hypothesis, as a result of bi-allelic mutation of the RB1 gene. Inactivating mutations of the RB1 gene have been identified in various tumors, showing the RB1 gene product has an important role in regulating cell proliferation beyond its effect on retinoblasts. The RB1 gene was cloned and identified in 1986. Returning the RB1 gene to a retinoblastoma cell in culture reduces its tumorgenic potential. Retinoblastoma is the most common malignant intraocular tumor of childhood. The tumor consists of undifferentiated small anaplastic cells which may be round or polygonal. Both Flexner and Wintersteiner described the arrangement of the more differentiated malignant retinoblastoma cells in neuroepithelial rosettes which appear to represent an attempt to differentiate into photoreceptor cells. The tumor commonly presents with a white pupillary light reflex. The diagnosis is generally made based on physical examination, confirmatory photographs and diagnostic imaging studies and, in many cases, a supportive family history. The most widely used grouping system was proposed by Algernon Reese and Robert Ellsworth. The primary goal of

  5. Retinoblastoma: Genetics, diagnosis, treatment and sequelae

    International Nuclear Information System (INIS)

    Halperin, Edward C.

    1996-01-01

    There has been a conceptual breakthrough in our understanding of the molecular and genetic basis of the origins of human neoplasia. Mutations in three broad categories of genes have been shown to contribute to the origins and progression of neoplasia in humans: the oncogenes, the tumor suppressor genes, and the mutator genes. The retinoblastoma gene (RB1) is the best characterized tumor suppressor gene. It was first localized by Knudson and coworkers who observed an association between a deletion on the long arm of chromosome 13 and an inherited predisposition to retinoblastoma. The RB1 gene is composed of 27 exons encompassing more than 200 kilobases of genomic DNA. The product of the RB1 gene is a 105-107 kDa nuclear phosphoprotein which plays a part in regulating cellular DNA synthesis. Tumors arise, as predicted by Knudson's 'two-hit' hypothesis, as a result of biallelic mutation of the RB1 gene. Inactivating mutations of the RB1 gene have been identified in various tumors, showing the RB1 gene product has an important role in regulating cell proliferation beyond its effect on retinoblasts. The RB1 gene was cloned and identified in 1986. Returning the RB1 gene to a retinoblastoma cell in culture reduces its tumorgenic potential. Retinoblastoma is the most common malignant intraocular tumor of childhood. The tumor consists of undifferentiated small anaplastic cells which may be round or polygonal. Both Flexner and Wintersteiner described the arrangement of the more differentiated malignant retinoblastoma cells in neuroepithelial rosettes which appear to represent an attempt to differentiate into photoreceptor cells. The tumor commonly presents with a white pupillary light reflex. The diagnosis is generally made based on physical examination, confirmatory photographs and diagnostic imaging studies and, in many cases, a supportive family history. The most widely used grouping system was proposed by Algernon Reese and Robert Ellsworth. The primary goal of

  6. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization

    Energy Technology Data Exchange (ETDEWEB)

    Graaf, Pim de; Rodjan, Firazia; Castelijns, Jonas A. [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Goericke, Sophia [University Hospital, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Galluzzi, Paolo [Azienda Ospedaliera e Universitaria Senese, Policlinico ' ' Le Scotte' ' , Unit of Diagnostic and Therapeutic Neuroradiology, Siena (Italy); Maeder, Philippe [CHUV, Service de Radiodiagnostic et Radiologie Interventionelle, Lausanne (Switzerland); Brisse, Herve J. [Institut Curie, Departement d' Imagerie, Paris (France)

    2012-01-15

    Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation. (orig.)

  7. Atraso diagnóstico do retinoblastoma

    OpenAIRE

    Rodrigues,Karla E. S.; Latorre,Maria do Rosário D. O.; Camargo,Beatriz de

    2004-01-01

    OBJETIVOS: Identificar os principais sinais e sintomas do retinoblastoma e determinar o tempo médio entre o início dos sintomas e o diagnóstico. MÉTODOS: Estudo retrospectivo, com revisão dos prontuários das crianças diagnosticadas com retinoblastoma entre janeiro de 1991 e junho de 2000 no Departamento de Pediatria do Hospital do Câncer de São Paulo. Análise estatística: teste t de Student, análise e variância, teste de Tukey-HSD (honest significant differences), teste de Levene, análise de ...

  8. Postirradiation sarcoma in retinoblastoma. Induction or predisposition

    International Nuclear Information System (INIS)

    Schwarz, M.B.; Burgess, L.P.; Fee, W.E. Jr.; Donaldson, S.S.

    1988-01-01

    An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.13 references

  9. Imaging in the trilateral retinoblastoma syndrome

    International Nuclear Information System (INIS)

    Bagley, L.J.; Hurst, R.W.; Zimmerman, R.A.; Shields, J.A.; Shields, C.L.; De Potter, P.

    1996-01-01

    The medical records, CT, and MRI of ten children with trilateral retinoblastoma were reviewed. The intracranial pathology consisted of eight pineal neoplasms and two parasellar lesions, at least seven of the which were calcified. Two lesions demonstrated calcification only (no soft tissue mass) at initial presentation. Hydrocephalus was seen in eight cases, and concurrent or subsequent subarachnoid dissemination was documented in seven. Only one patient is known to be alive at the present time. The imaging features of the midline intracranial tumors mirror those of the ocular neoplasm. As calcification may be the only clue to the presence of the intracranial malignancy, close surveillance of high-risk patients with retinoblastoma with initial CT and follow-up MRI is suggested. (orig.). With 3 figs., 1 tab

  10. Imaging in the trilateral retinoblastoma syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Bagley, L.J. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104 (United States); Hurst, R.W. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104 (United States); Zimmerman, R.A. [Department of Radiology, Children`s Hospital of Philadelphia, 34 th St. and Civic Center Blvd., Philadelphia, PA 19104 (United States); Shields, J.A. [Ocular Oncology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107 (United States); Shields, C.L. [Ocular Oncology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107 (United States); De Potter, P. [Ocular Oncology Service, Wills Eye Hospital, 900 Walnut St., Philadelphia, PA 19107 (United States)

    1996-02-01

    The medical records, CT, and MRI of ten children with trilateral retinoblastoma were reviewed. The intracranial pathology consisted of eight pineal neoplasms and two parasellar lesions, at least seven of the which were calcified. Two lesions demonstrated calcification only (no soft tissue mass) at initial presentation. Hydrocephalus was seen in eight cases, and concurrent or subsequent subarachnoid dissemination was documented in seven. Only one patient is known to be alive at the present time. The imaging features of the midline intracranial tumors mirror those of the ocular neoplasm. As calcification may be the only clue to the presence of the intracranial malignancy, close surveillance of high-risk patients with retinoblastoma with initial CT and follow-up MRI is suggested. (orig.). With 3 figs., 1 tab.

  11. Radiation management of retinoblastoma; An analysis

    Energy Technology Data Exchange (ETDEWEB)

    Takemasa, Kazuhiko; Ito, Hisao; Hashimoto, Shozo; Tanaka, Yasuhiko; Oguchi, Yoshihisa (Keio Univ., Tokyo (Japan). School of Medicine)

    1991-12-01

    An analysis has been conducted of 45 patients treated for retinoblastoma at Keio University Hospital between 1970 and 1990. Of these patients, 32 had unilateral lesion and 13 had bilateral lesion. Further, since their disease was far advanced, 29 patients with unilateral lesion and 12 patients with bilateral lesion underwent enucleation. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral manifestation of the disease were treated with radiotherapy (45-50 Gy) with or without cryotherapy and photocoagulation. One patient with unilateral lesion, who had received both radiotherapy and chemotherapy, showed metastases at the first presentation at our clinic and thus was excluded from this analysis. Among 16 eyes of 15 patients who were given radiotherapy, 6 eyes developed recurrence and needed to have further treatment. In 6 eyes out of 12, cataract developed, and out of 10 eyes in which eye function was evaluable, good vision was able to be preserved in 5 eyes. (author).

  12. Diffuse infiltrating retinoblastoma invading subarachnoid space

    Directory of Open Access Journals (Sweden)

    Kase S

    2011-06-01

    Full Text Available Satoru Kase1, Kazuhiko Yoshida1, Shigenobu Suzuki2, Koh-ichi Ohshima3, Shigeaki Ohno4, Susumu Ishida11Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo; 2Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo; 3Section of Ophthalmology, Okayama Medical Center, Okayama; 4Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, JapanAbstract: We report herein an unusual case of diffuse infiltrating retinoblastoma involving the brain, which caused a patient’s death 27 months after enucleation. An eight-year-old boy complained of blurred vision in his right eye (OD in October 2006. Funduscopic examination showed optic disc swelling, dense whitish vitreous opacity, and an orange-colored subretinal elevated lesion adjacent to the optic disc. Fluorescein angiography revealed hyperfluorescence in the peripapillary region at an early-phase OD. Because the size of the subretinal lesion and vitreous opacity gradually increased, he was referred to us. His visual acuity was 20/1000 OD on June 20, 2007. Slit-lamp biomicroscopy showed a dense anterior vitreous opacity. Ophthalmoscopically, the subretinal orange-colored area spread out until reaching the mid peripheral region. A B-mode sonogram and computed tomography showed a thick homogeneous lesion without calcification. Gadolinium-enhanced magnetic resonance imaging showed a markedly enhanced appearance of the underlying posterior retina. Enucleation of the right eye was performed nine months after the initial presentation. Histopathology demonstrated retinal detachment and a huge choroidal mass invading the optic nerve head. The tumor was consistent with diffuse infiltrating retinoblastoma. The patient died due to brain involvement 27 months after enucleation. Ophthalmologists should be aware that diffuse infiltrating retinoblastoma may show an unfavorable course if its diagnosis is delayed

  13. MicroRNAs horizon in retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Mojgan Mirakholi

    2013-12-01

    Full Text Available In the retinoblastoma research, it is of great interest to identify molecular markers associated with the genetics of tumorigenesis. microRNAs (miRNAs are small non-coding RNA molecules that play a regulatory role in many crucial cellular pathways such as differentiation, cell cycle progression, and apoptosis. A body of evidences showed dysregulation of miRNAs in tumor biology and many diseases. They potentially play a significant role in tumorigenesis processes and have been the subject of research in many types of cancers including retinal tumorigenesis. miRNA expression profiling was found to be associated with tumor development, progression and treatment. These associations demonstrate the putative applications of miRNAs in monitoring of different aspect of tumors consisting diagnostic, prognostic and therapeutic. Herein, we review the current literature concerning to the study of miRNA target recognition, function to tumorigenesis and treatment in retinoblastoma. Identification the specific miRNA biomarkers associated with retinoblastoma cancer may help to establish new therapeutic approaches for salvage affected eyes in patients.

  14. Genetics and Molecular Diagnostics in Retinoblastoma--An Update.

    Science.gov (United States)

    Soliman, Sameh E; Racher, Hilary; Zhang, Chengyue; MacDonald, Heather; Gallie, Brenda L

    2017-01-01

    Retinoblastoma is the prototype genetic cancer: in one or both eyes of young children, most retinoblastomas are initiated by biallelic mutation of the retinoblastoma tumor suppressor gene, RB1, in a developing retinal cell. All those with bilateral retinoblastoma have heritable cancer, although 95% have not inherited the RB1 mutation. Non-heritable retinoblastoma is always unilateral, with 98% caused by loss of both RB1 alleles from the tumor, whereas 2% have normal RB1 in tumors initiated by amplification of the MYCN oncogene. Good understanding of retinoblastoma genetics supports optimal care for retinoblastoma children and their families. Retinoblastoma is the first cancer to officially acknowledge the seminal role of genetics in cancer, by incorporating "H" into the eighth edition of cancer staging (2017): those who carry the RB1 cancer-predisposing gene are H1; those proven to not carry the familial RB1 mutation are H0; and those at unknown risk are HX. We suggest H0* be used for those with residual <1% risk to carry a RB1 mutation due to undetectable mosaicism. Loss of RB1 from a susceptible developing retinal cell initiates the benign precursor, retinoma. Progressive genomic changes result in retinoblastoma, and cancer progression ensues with increasing genomic disarray. Looking forward, novel therapies are anticipated from studies of retinoblastoma and metastatic tumor cells and the second primary cancers that the carriers of RB1 mutations are at high risk to develop. Here, we summarize the concepts of retinoblastoma genetics for ophthalmologists in a question/answer format to assist in the care of patients and their families. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  15. Tratamiento conservador en pacientes con retinoblastoma bilateral

    Directory of Open Access Journals (Sweden)

    Juan C. Suárez

    2008-11-01

    Full Text Available OBJETIVO: comparar el tratamiento convencional del retinoblastoma bilateral, usado hasta hace algunos años, consistente en radioterapia o enucleación bilateral, con el tratamiento conservador actual que incluye termoterapia transpupilar (TTT o TTT/quimioterapia al menos en un ojo, en niños con diagnóstico de retinoblastoma bilateral. DISEÑO: estudio retrospectivo descriptivo. MUESTRA: 20 pacientes con diagnóstico de retinoblastoma bilateral que consultaron al Hospital Universitario San Vicente de Paúl, de Medellín, Colombia, entre 1997 y 2007. MÉTODO: se hizo enucleación del ojo con el tumor de mayor tamaño. En el otro ojo se hizo tratamiento con TTT, con el láser diodo (810 nm, spot amplio, solo o combinado con otras terapias. RESULTADOS: se dividió a los pacientes en dos grupos: 16 pacientes (32 ojos en el grupo 1 tratados conservadoramente y 4 pacientes (8 ojos en el grupo 2 con tratamiento convencional. El rango de edad fue de 1-72 meses en el grupo 1 y de 1-12 meses en el grupo 2. El tiempo de seguimiento fue de 7-67 meses para el grupo 1 y de 13-73 meses para el grupo 2. En el grupo 1 se hizo enucleación de 16 ojos (50%, radioterapia externa de uno (3,1%, quimioterapia más termoterapia de 5 (15,6% y quimioterapia más termoterapia más crioterapia de 10 (31,3%. En todos los pacientes se logró preservar al menos un ojo. En el grupo 2, se enuclearon 7 ojos (87,5% y se hizo radioterapia externa más enucleación en un paciente (12.5%. Además, todos los pacientes recibieron quimioterapia. CONCLUSIÓN: la terapia conservadora actual consistente en tratamiento local (termoterapia, crioterapia o braquiterapia y quimiorreducción permite preservar al menos un ojo y en algunos casos de los dos, muchas veces con buena agudeza visual, en niños con retinoblastoma bilateral; se evitan así la enucleación bilateral y la radioterapia externa usada en el tratamiento convencional con todos sus efectos secundarios. La enucleación contin

  16. Retinoblastoma: Assessing the Level of Knowledge of Tumour By ...

    African Journals Online (AJOL)

    For 60% leucocoria was the only sign suspect of retinoblastoma, for 80% strabismus was the only sign of retinoblastoma, only 10% had associated leucocoria and strabismus as two early signs of this cancer. Twelve percent had a score equal to 3/3, eight (8%) had a score equal to 2/3, and 80% had a score of less than or ...

  17. Cancer incidence after retinoblastoma - Radiation dose and sarcoma risk

    NARCIS (Netherlands)

    Wong, FL; Boice, JD; Abramson, DH; Tarone, RE; Kleinerman, RA; Stovall, M; Goldman, MB; Seddon, JM; Tarbell, N; Fraumeni, JF; Li, FP

    1997-01-01

    Context.-There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. Objective.-To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.

  18. Inhibitory effect of puerarin on proliferation of retinoblastoma cells ...

    African Journals Online (AJOL)

    ... 71.4 ± 4.5 % for control and Bmi-1 siRNA-treated groups, respectively. Conclusions: The results show that puerarin exert suppressive effects on human retinoblastoma Y79 cells and therefore may find application in the treatment of intraocular tumor. Keywords: Cancer, Puerarin, Retinoblastoma Y79 cells, mTOR inhibition, ...

  19. Retinoblastoma bilateral de aparecimento tardio: relato de caso Late presentation of bilateral retinoblastoma: case report

    Directory of Open Access Journals (Sweden)

    Maria Cecília Santos Cavalcanti Melo

    2008-06-01

    Full Text Available É relatado um caso de retinoblastoma de aparecimento tardio, com características pouco freqüentes, com o objetivo de melhorar o controle da afecção. Em 1993, SJMMF, nove meses, masculino, leucodermo, apresentou tumor na retina esquerda. O paciente tinha história familiar de retinoblastoma. A enucleação foi realizada, comprovando-se retinoblastoma. Os exames para estadiamento sistêmico foram normais. O olho direito evoluiu normal por dez anos. Em exame de rotina, foram constatadas três lesões de retinoblastoma na retina nasal. Foi feita termoterapia transpupilar, com laser de diodo de 810 nm. Após 30 dias, as lesões regrediram. Após 60 dias houve recidiva na borda da lesão, onde foi realizada crioterapia transescleral, com regressão do tumor por seis meses. Durante o controle, observaram-se condensações próximas à lesão tumoral atrófica (sementes vítreas. Foi feito braquiterapia com Iodo125, havendo desaparecimento das mesmas após 30 dias. Novas sementes surgiram três meses pós-braquiterapia, depositadas na superfície retiniana, sendo tratadas com crioterapia transescleral e termoterapia transpupilar, havendo regressão. O paciente evoluiu com nova semente vítrea após seis meses, a qual, após depositar-se na superfície da retina, foi tratada com termoterapia transpupilar. Está em seguimento há 38 meses desde o aparecimento do tumor bilateral, mantendo acuidade visual de 20/20 e exames clínicos normais. Considera-se importante este caso pela pouca freqüência de aparecimento da doença nesta idade. Julga-se necessário o alerta para os casos de retinoblastoma já considerados curados.A case of retinoblastoma with uncommon features is reported, aiming at improving follow-up. In 1993, SJMMF, 9-month-old white boy, presented a squint in the left eye. A retinal tumor was detected. The patient had a family history of retinoblastoma. Enucleation was performed and retinoblastoma was proved. The patient underwent

  20. The effects of BSO on GSH contents and radiosensitivity of retinoblastoma cells

    International Nuclear Information System (INIS)

    Yi Xanjin; Ding Li; Jin Yizun; Ni Chuo; Wang Wenji; Yi Yuzhen

    1995-01-01

    The radiobiological effects of thiol modifier BSO on retinoblastoma were studied using cultured retinoblastoma cell lines Y-79 and So-Rb 50 and retinoblastoma bearing nude mouse. The preliminary results showed that BSO can deplete intracellular GSH contents of retinoblastoma cells in vitro and vivo. In vitro data demonstrated that low and nontoxic concentration BSO increased the retinoblastoma cells radiosensitivity especially under the hypoxic condition

  1. Histopathologic grading of anaplasia in retinoblastoma.

    Science.gov (United States)

    Mendoza, Pia R; Specht, Charles S; Hubbard, G Baker; Wells, Jill R; Lynn, Michael J; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E

    2015-04-01

    To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P = .003) and increased risk of metastasis (P = .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P = .01 for metastasis, P = .03 for death) but anaplasia was not (P = .63 for metastasis, P = .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P = .0004) and death (P = .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Trilateral retinoblastoma with unilateral eye involvement

    Directory of Open Access Journals (Sweden)

    Gabriel Costa de Andrade

    2015-08-01

    Full Text Available SummaryRetinoblastomas (RB are the main forms of intraocular tumor in childhood, with a worldwide incidence of 1 case per 15,000 to 20,000 live births. Trilateral RB (RBT is a rare combination of unilateral or bilateral RB with a midline intracranial neoplasm of neuroblastic origin, usually found in the pineal region or the suprasellar region, presenting variable incidence of 0.5% up to 6% among patients with RB. The article reports a case of unilateral RBT in a patient treated at Hospital A.C.Camargo.

  3. Structure and expression of the Xenopus retinoblastoma gene.

    Science.gov (United States)

    Destrée, O H; Lam, K T; Peterson-Maduro, L J; Eizema, K; Diller, L; Gryka, M A; Frebourg, T; Shibuya, E; Friend, S H

    1992-09-01

    We have cloned a Xenopus homology (XRb1) of the human retinoblastoma susceptibility gene. DNA sequence analysis shows that the XRb1 gene product is highly conserved in many regions. The leucine repeat motif and many of the potential cdc2 phosphorylation sites, as well as potential sites for other kinases, are retained. The region of the protein homologous to the SV40 T antigen binding site and the basic region directly C-terminal to the E1A binding site are all conserved. XRb1 gene expression at the RNA level was studied by Northern blot analysis. Transcripts of 4.2 and 10-kb are present as maternal RNA stores in the oocyte. While the 4.2-kb product is stable until at least the mid-blastula stage, the 10-kb transcript is selectively degraded. Between stages 11 and 13 the 10-kb transcript reappears and also a minor product of approximately 11 kb becomes apparent. Both the 4.2- and the 10-kb transcripts remain present until later stages of development and are also present in all adult tissues examined, although at differing levels. Antibodies raised against human p105Rb which recognize the protein product of the XRb1 gene, pXRb1, detect the Xenopus 99-kDa protein prior to the mid-blastula stage, but at lower levels than at later stages in development.

  4. Human Papilloma Virus in Retinoblastoma Tissues from Korean Patients

    Science.gov (United States)

    Ryoo, Na-Kyung; Kim, Ji-Eun; Kim, Namju; Lee, Min-Jeong; Khwarg, Sang-In

    2013-01-01

    Purpose Recent reports suggest the association of human papilloma virus (HPV) with retinoblastoma. This study was performed to elucidate whether HPV infection is related to retinoblastoma among Koreans. Methods A total of 54 cases diagnosed with retinoblastoma were enrolled from Seoul National University Children's Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Presence of human papilloma viral DNA was detected by in situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues using both probes against high- and low risk HPV types. Results The mean age at diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients with retinoblastoma. HPV was not detected in any of the retinoblastoma samples using either high risk or low risk HPV probes. Conclusions Our study, being the first study in the Korean population, proposes that HPV infection may have no causal relationship with retinoblastoma in Koreans. PMID:24082775

  5. Clinical Value of CD24 Expression in Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Jia Li

    2012-01-01

    Full Text Available Background. The expression of CD24 has been detected in a wide variety of human malignancies. Downregulation of CD24 inhibits proliferation and induces apoptosis in tumor cells, whereas its upregulation increases tumor growth and metastasis. However, no data on CD24 protein levels in retinoblastoma are available, and the mechanism of CD24 involvement in retinoblastoma progress has not been elucidated. The aim of this study was to explore the expression profile of CD24 in the retinoblastoma tumor samples and to correlate with clinicopathological parameters. Methods. Immunohistochemistry was performed for CD24 on the archival paraffin sections of retinoblastoma and correlated with clinicopathological features. Western blotting was performed to confirm immunoreactivity results. Results. CD24 immunoreactivity was observed in 72.0% (36/50 of the retinoblastoma specimens. Among the 35 low-risk tumors, CD24 was expressed in 62.9% (22/35 tumors and among the 15 high-risk tumors, CD24 was expressed in 93.3% (14/15 tumors. High-risk tumors showed significantly increased expression of CD24 compared to tumors with low-risk (<0.05. Conclusions. This is the first correlation between CD24 expression and histopathology in human retinoblastoma. Our study showed increased expression of CD24 in high risk tumors compared to low risk tumors. Further functional studies are required to explore the role of CD24 in retinoblastoma.

  6. Diffuse Anterior Retinoblastoma with Sarcoidosis-Like Nodule

    Directory of Open Access Journals (Sweden)

    Koji Kitazawa

    2015-12-01

    Full Text Available Background: Retinoblastomas account for 4% of malignancies in children, 1-2% of which are diffuse infiltrating retinoblastomas. Diffuse anterior retinoblastoma is rare and does not involve the retina. Here, we report on a diffuse anterior retinoblastoma with large sarcoidosis-like nodules on the iris that were responsive to anti-inflammatory therapy. Case: We present a 6-year-old girl who had anterior uveitis with white nodules on the iris and posterior surface of the cornea in her right eye. The nodules initially responded well to anti-inflammatory treatment. However, anterior segment optical coherence tomography (AS-OCT showed that the nodules gradually grew, shrinking the iris. We then collected the aqueous humor for diagnosis. A biopsy revealed clusters of small cells with a high nuclear-to-cytoplasm ratio with partial rosette formation. Therefore, we diagnosed diffuse anterior retinoblastoma without retinal involvement and performed enucleation of the right eye. The histopathology demonstrated undifferentiated cells similar to those seen on the biopsy, and tumor cells invaded the iris stroma, posterior surface of the cornea, ciliary body, and sclera. After the enucleation, she underwent chemotherapy and remains alive. Conclusion: A differential diagnosis of retinoblastoma should be considered when white nodules refractory to anti-inflammatory therapy occur in the eye, even in the absence of obvious retinal masses. AS-OCT findings are useful in assessing retinoblastoma.

  7. Global issues and opportunities for optimized retinoblastoma care.

    Science.gov (United States)

    Gallie, Brenda L; Zhao, Junyang; Vandezande, Kirk; White, Abigail; Chan, Helen S L

    2007-12-01

    The RB1 gene is important in all human cancers. Studies of human retinoblastoma point to a rare retinal cell with extreme dependency on RB1 for initiation but not progression to full malignancy. In developed countries, genetic testing within affected families can predict children at high risk of retinoblastoma before birth; chemotherapy with local therapy often saves eyes and vision; and mortality is 4%. In less developed countries where 92% of children with retinoblastoma are born, mortality reaches 90%. Global collaboration is building for the dramatic change in mortality that awareness, simple expertise and therapies could achieve in less developed countries. Copyright 2007 Wiley-Liss, Inc.

  8. Multifocal osteosarcoma as second tumor after childhood retinoblastoma

    International Nuclear Information System (INIS)

    Potepan, P.; Laffranchi, A.; Danesini, G.M.; Spagnoli, I.; Luksch, R.; Sozzi, G.; Testi, A.; Parafioriti, A.; Giardini, R.

    1999-01-01

    We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases. (orig.)

  9. Distant metastatic retinoblastoma without central nervous system involvement

    Directory of Open Access Journals (Sweden)

    Mohammad Javed Ali

    2013-01-01

    Full Text Available Retinoblastoma is the most common intraocular malignancy in children, with a reported incidence ranging from 1 in 15,000 to 1 in 18,000 live births. Metastatic retinoblastoma is rare in developed countries, with a reported range from 4.8% in the United States to 5.8% in the United Kingdom. However, the frequency reported from developing countries varies from 9 to 11% at presentation. The mortality is very high owing to late presentations, delayed diagnosis compounded by socio-economic factors. The management of metastatic retinoblastoma is evolving, but it is still a challenge in pediatric oncology. We present a case of an extensive skeletal metastasis that initially presented as a massive orbital retinoblastoma.

  10. Molecular-genetic analysis of two cases with retinoblastoma ...

    Indian Academy of Sciences (India)

    Unknown

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of ... to chromosomal deletion, single-nucleotide alteration, microdeletion, loss ... informed consent of the parent.

  11. Craniospinal Irradiation for Trilateral Retinoblastoma Following Ocular Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Lawrence B.; Bentel, Gunilla; Sherouse, George W.; Spencer, David P.; Light, Kim

    2015-01-15

    A case study is presented. Craniospinal radiotherapy and a three-field pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

  12. Scleral buckling for retinal detachment in patients with retinoblastoma

    International Nuclear Information System (INIS)

    Buzney, S.M.; Pruett, R.C.; Regan, C.D.; Walton, D.S.; Smith, T.R.

    1984-01-01

    Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years

  13. Scleral buckling for retinal detachment in patients with retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Buzney, S.M.; Pruett, R.C.; Regan, C.D.; Walton, D.S.; Smith, T.R.

    1984-10-15

    Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years.

  14. Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

    Science.gov (United States)

    Pritchard, Eleanor M; Dyer, Michael A; Guy, R Kiplin

    2016-01-01

    While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

  15. Retinoblastoma: concerning its initiation and treatment

    Directory of Open Access Journals (Sweden)

    Ying-Ping Deng

    2013-06-01

    Full Text Available Retinoblastoma (RB is the most common intraocular cancer of infancy and childhood. This cancer is initiated by mutation on RB1, the tumor suppressor gene that is responsible for the regulation of both cell cycle and gnome stability in retinal cells. Patients with a constitutional mutation on RB1 can be inherited. RB occurs approximately 1 in every 15 000-20 000 live births. The worldwide mortality for this cancer is about 5%-11%. However, this rate rises to about 40%-70% in developing countries due to a delay in diagnosis. A wide variety of options are available for the treatment, but often a combination of therapies is adopted to optimize individualized care.

  16. Cobalt60 plaques in recurrent retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fass, D.; McCormick, B.; Abramson, D.; Ellsworth, R. (Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, NY, NY (USA))

    1991-08-01

    Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 {times} 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, the authors are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications.

  17. Cobalt60 plaques in recurrent retinoblastoma

    International Nuclear Information System (INIS)

    Fass, D.; McCormick, B.; Abramson, D.; Ellsworth, R.

    1991-01-01

    Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 x 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, the authors are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications

  18. ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection.

    Science.gov (United States)

    Sharkey, Liam K R; Edwards, Thomas A; O'Neill, Alex J

    2016-03-22

    Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition. Copyright © 2016 Sharkey et al.

  19. A study on the toxicity of three radiosensitizers on retinoblastoma cells by MTT assay

    International Nuclear Information System (INIS)

    Yi Xianjin; Jin Yizun; Ding Li; Ni Zhou; Wang Wenji

    1994-01-01

    The toxicity of three radiosensitizers BSO, CM and RSU-1069 on retinoblastoma cells was determined and the efficiency of in vitro MTT assay on drug-screening for retinoblastoma was also evaluated. The results showed that the MTT assay is very useful. The toxicity of radiosensitizers on retinoblastoma cells is dependent on cell line characteristics, drug concentration and time of exposure to it

  20. Design and Implementation of the Retinoblastoma Collaborative Laboratory.

    Science.gov (United States)

    Qaiser, Seemi; Limo, Alice; Gichana, Josiah; Kimani, Kahaki; Githanga, Jessie; Waweru, Wairimu; Dimba, Elizabeth A O; Dimaras, Helen

    2017-01-01

    The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. The RbCoLab is a central lab in Nairobi that receives retinoblastoma specimens from all over Kenya. Specimens were processed using evidence-based standard operating procedures. Images were produced by a digital scanner, and pathology reports were disseminated online. The lab implemented standard operating procedures aimed at improving the accuracy, completeness, and timeliness of pathology reports, enhancing the care of Kenyan retinoblastoma patients. Integration of digital technology to support pathology services supported knowledge transfer and skills transfer. A bidirectional educational network of local pathologists and other clinicians in the circle of care of the patients emerged and served to emphasize the clinical importance of cancer pathology at multiple levels of care. A 'Robin Hood' business model of health care service delivery was developed to support sustainability and scale-up of cancer pathology services. The application of evidence-based protocols, comprehensive training, and collaboration were essential to bring improvements to the care of retinoblastoma patients in Kenya. When embraced as an integrated component of retinoblastoma care, digital pathology offers the opportunity for frequent connection and consultation for development of expertise over time.

  1. Socioeconomic and psychological impact of treatment for unilateral intraocular retinoblastoma.

    Science.gov (United States)

    Soliman, S E; Dimaras, H; Souka, A A; Ashry, M H; Gallie, B L

    2015-06-01

    To identify the socioeconomic and psychosocial impacts of clinical treatment decisions for advanced unilateral intraocular retinoblastoma. Retrospective observational case series. institutional study at Alexandria Main University Hospital. records of 66 unilateral retinoblastoma cases treated from May 2005 to May 2013 were retrospectively reviewed. Sixty cases were eligible (International Intraocular Retinoblastoma Classification [IIRC] group C, D or E). two treatment groups were compared: enucleation vs. salvage treatment. Salvage treatment eyes were further subdivided based on IIRC group. Six socioeconomic parameters (financial burden, financial impact, psychological, social, medical and tumor impacts) were scored. Parameter scores ranged from 0 to 3, for overall score range 0 (no adverse impact) to 18 (severe adverse impact). derived Socioeconomic scores were correlated with treatment and outcomes. The enucleation group (28 eyes) had a median overall Socioeconomic score of 4/18, significantly lower than the salvage treatment group (32 eyes), median score 11/18 (PSocioeconomic score varied with IIRC group. Attempted eye salvage failed in 25 children, due to uncontrolled tumor (44%) and socioeconomic impact of cumulative therapies (56%). Treatment duration and Socioeconomic score were higher for the 5 children in the salvage treatment group who developed metastatic disease compared to those without metastasis (Psocioeconomic and psychosocial impacts of attempted ocular salvage for unilateral intraocular retinoblastoma are severe, in comparison to primary enucleation. Primary enucleation is a good treatment for unilateral retinoblastoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Current Trends in the Management of Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Hayyam Kıratlı

    2014-09-01

    Full Text Available Retinoblastoma is the most common primary intraocular malignant tumor of early childhood, and 95% of all cases are diagnosed before the age of 5 years. Tumors are evaluated and classified based on laterality, genetic features, the number, location and size of foci. Currently, systemic and intaarterial chemotherapy are the most commonly used management options worldwide. Group A tumors are treated with focal techniques including transpupillary thermotherapy, cryotherapy, or laser photocoagulation. Groups B and C tumors are managed with systemic chemotherapy and focal consolidation techniques. Group D lesions are best treated with systemic chemotherapy, subtenon carboplatin injection or external beam radiotherapy. Alternatively, groups B, C and D tumors can be primarily treated with intraarterial chemotherapy. Intravitreal melphalan injection can be an alternative treatment for eyes with recurrent or persistent vitreous seeding. Group E eyes are often enucleated, however, depending on the fellow eye, systemic or intraarterial chemotherapy may be administered. Systemic chemotherapy is also mandatory if high-risk histopathological features are found after enucleation. (Turk J Ophthalmol 2014; 44: Supplement 22-8

  3. Atraso diagnóstico do retinoblastoma Delayed diagnosis in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Karla E. S. Rodrigues

    2004-12-01

    Full Text Available OBJETIVOS: Identificar os principais sinais e sintomas do retinoblastoma e determinar o tempo médio entre o início dos sintomas e o diagnóstico. MÉTODOS: Estudo retrospectivo, com revisão dos prontuários das crianças diagnosticadas com retinoblastoma entre janeiro de 1991 e junho de 2000 no Departamento de Pediatria do Hospital do Câncer de São Paulo. Análise estatística: teste t de Student, análise e variância, teste de Tukey-HSD (honest significant differences, teste de Levene, análise de regressão linear, curva ROC, regressão logística e análise de sobrevida pelo método de Kaplan-Meier. RESULTADOS: Foram revisados 327 prontuários, sendo 171 pacientes do sexo masculino. A idade média foi de 25 meses. Doença localizada foi verificada em 269 pacientes. Os sintomas mais freqüentes foram leucocoria (79%, estrabismo (10,7% e tumoração (3,4%. O tempo médio de queixa foi de 5,8 meses. Pacientes maiores de 2 anos de idade apresentaram maior tempo de queixa em relação aos lactentes (7,2 meses versus 4,7 meses; p = 0,001. Pacientes com estrabismo tiveram maior tempo de queixa (8,8 meses em comparação com pacientes com tumoração (2,3 meses ou leucocoria (5,6 meses (p = 0,014. Pacientes com doença metastática apresentaram maior tempo de queixa (10,6 meses; p OBJECTIVES: To identify the main symptoms of retinoblastoma and to determine the mean time between symptom onset and diagnosis (lag time. PATIENTS AND METHODS: We carried out a retrospective analysis of the patients diagnosed with retinoblastoma between January 1991 and June 2000, at the Pediatric Department of the Hospital do Câncer, São Paulo, Brazil. Statistical analyses performed were: Student's t test, ANOVA, Tukey-HSD test (honest significant differences, Levene's test, multiple regression, ROC curve, logistic regression, Kaplan-Meier, and log rank. RESULTS: 327 medical records (171 males were reviewed. The mean age was 25 months. Localized disease was

  4. Adenocarcinoma of the ethmoid following radiotherapy for bilateral retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Rowe, L.D.; Lane, R.; Snow, J.B. Jr.

    1980-01-01

    Adenocarcinoma of the ethmoid sinus is rare, representing only 4 to 8% of malignancies of the paranasal sinuses. An extraordinary case of papillary adenocarcinoma of the ethmoid sinus arising 30 years following high-dose radiotherapy for bilateral retinoblastoma is presented. Second fatal mesenchymal and epithelial primaries have been described in 8.5% of patients with bilateral retinoblastomas previously treated with radiotherapy; however, papillary adenocarcinoma arising within the paranasal sinuses has not been reported. Aggressive treatment including partial maxillectomy, radical pansinusectomy, radical neck dissection followed by regional radiotherapy and systemic chemotherapy failed to prevent the development of fatal hepatic metastases. The high incidence of second fatal primary neoplasms in patients with bilateral retinoblastomas receiving radiation suggests an innate susceptibility that may add to the risk of radiotherapy.

  5. Adenocarcinoma of the ethmoid following radiotherapy for bilateral retinoblastoma

    International Nuclear Information System (INIS)

    Rowe, L.D.; Lane, R.; Snow, J.B. Jr.

    1980-01-01

    Adenocarcinoma of the ethmoid sinus is rare, representing only 4 to 8% of malignancies of the paranasal sinuses. An extraordinary case of papillary adenocarcinoma of the ethmoid sinus arising 30 years following high-dose radiotherapy for bilateral retinoblastoma is presented. Second fatal mesenchymal and epithelial primaries have been described in 8.5% of patients with bilateral retinoblastomas previously treated with radiotherapy; however, papillary adenocarcinoma arising within the paranasal sinuses has not been reported. Aggressive treatment including partial maxillectomy, radical pansinusectomy, radical neck dissection followed by regional radiotherapy and systemic chemotherapy failed to prevent the development of fatal hepatic metastases. The high incidence of second fatal primary neoplasms in patients with bilateral retinoblastomas receiving radiation suggests an innate susceptibility that may add to the risk of radiotherapy

  6. A retinoblastoma orthologue is a major regulator of S-phase, mitotic, and developmental gene expression in Dictyostelium.

    Directory of Open Access Journals (Sweden)

    Kimchi Strasser

    Full Text Available The retinoblastoma tumour suppressor, Rb, has two major functions. First, it represses genes whose products are required for S-phase entry and progression thus stabilizing cells in G1. Second, Rb interacts with factors that induce cell-cycle exit and terminal differentiation. Dictyostelium lacks a G1 phase in its cell cycle but it has a retinoblastoma orthologue, rblA.Using microarray analysis and mRNA-Seq transcriptional profiling, we show that RblA strongly represses genes whose products are involved in S phase and mitosis. Both S-phase and mitotic genes are upregulated at a single point in late G2 and again in mid-development, near the time when cell cycling is reactivated. RblA also activates a set of genes unique to slime moulds that function in terminal differentiation.Like its mammalian counterpart Dictyostelium, RblA plays a dual role, regulating cell-cycle progression and transcriptional events leading to terminal differentiation. In the absence of a G1 phase, however, RblA functions in late G2 controlling the expression of both S-phase and mitotic genes.

  7. [Pathological profiles of retinoblastoma in Senegal].

    Science.gov (United States)

    Dial, C; Doh, K; Thiam, I; Ndoye Roth, P; Moreira, C; Woto-Gaye, G

    2016-11-01

    Describe the macroscopic and microscopic profiles of retinoblastoma (RB) in Senegal and correlate histological criteria with progression to establish severity factors. We realized a retrospective study over 10 years (January 2005-December 2014). Only patients (n=67) who underwent histological analysis of the enucleation specimen (n=68) were followed until the end of the study. The tumor measured an average of 3.8cm (2/4.5). Endophytic tumor development was observed in 55 cases (80.8%), exophytic in 6 cases (8.9%) and mixed in 7 cases (10.3%). Retinal detachment was present in 13 cases (19.2%). The RB was well differentiated in 11 cases (16.2%), moderately differentiated in 31 cases (45.6%) and undifferentiated in 26 cases. Optic nerve (ON) invasion was present in 18 cases (26.5%). The tumor was extraretinal in 37 cases (54.4%). The anterior chamber was invaded in 6 cases (8.8%). The global survival at 2 years was 84% and 70% at 5 years. On multivariate analysis, well differentiated tumors and stage pT1 were associated with remission. Retrolaminar ON invasion, massive choroidal invasion and stage pT3 were risk factors for recurrence. Poor tumor differentiation, invasion of the ON resection margin, tumor invasion through the sclera, and stage pT4 were predictive of death. The pathologist is a principal actor in the management of RB because his account guide the post-surgical management strategy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Presenting signs of retinoblastoma at a tertiary level teaching ...

    African Journals Online (AJOL)

    The commonest presenting sign was proptosis 22(53.7%) followed by leucocorea nine (22%),ocular inflammation four (9.0 %), strabismus three (7.3%), glaucoma one (2.4%), loss of vision one (2.4%)and hyphemaone (2.4%). Conclusion: The commonest presenting signs of retinoblastoma in our set up were Proptosis ...

  9. Discharge and infection in retinoblastoma post-enucleation sockets

    NARCIS (Netherlands)

    Mourits, Daphne L.; Hartong, Dyonne T.; Budding, Andries E.; Bosscha, Machteld I.; Tan, H. Stevie; Moll, Annette C.

    2017-01-01

    To investigate the causes and treatment options for socket discharge and infection in patients enucleated for retinoblastoma (Rb). A questionnaire was filled out by (parents of) ocular prosthesis-wearing patients with a history of enucleation as treatment for Rb. We collected data on patients'

  10. Multiple malignancies in a patient with bilateral retinoblastoma

    NARCIS (Netherlands)

    Ceha, H. M.; Balm, A. J.; de Jong, D.; van 't Veer, L. J.

    1998-01-01

    A case is presented of a patient with bilateral retinoblastoma, treated at infancy with surgery, chemotherapy and radiotherapy, who subsequently developed at least four additional histologically distinct malignancies: a Ewing sarcoma of the left fibula, two extraskeletal osteosarcomas of the left

  11. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  12. Retinoblastoma in Adolescence: Report of an Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Khalili

    2010-04-01

    Full Text Available Herein, we report the clinical, pathologic and photographic findings of a 16year-old girl who presented with gradual enlargement of a vascularized, hemorrhagicperipapillary mass that eventually led to vitreous hemorrhage and rubeosis iridis.Histopathological findings after enucleation were positive for retinoblastoma. Thepatient did not have any metastasis during her 20 months of follow up.

  13. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  14. Optimized lens-sparing treatment of retinoblastoma with electron beams

    NARCIS (Netherlands)

    Steenbakkers, RJHM; Altschuler, MD; DAngio, GJ; Goldwein, JW; Kassaee, A

    1997-01-01

    Purpose: The ideal lens-sparing radiotherapy technique for retinoblastoma calls for 100% dose to the entire retina including the ora serrata and zero dose to the lens, Published techniques, most of which use photons, have not accomplished this ideal treatment. We describe here a technique that

  15. Presentation of retinoblastoma at a paediatric eye clinic in Ghana ...

    African Journals Online (AJOL)

    Background: Retinobalstoma, the commonest childhood malignant intraocular tumour, is usually diagnosed early with over 90% survival rate in developed countries. In developing countries, the diagnosis is late resulting in less than 50% survival. Objective: To determine retinoblastoma stages at presentation and patients¡¦ ...

  16. Proton Radiation Therapy for the Treatment of Retinoblastoma

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    Mouw, Kent W. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Sethi, Roshan V.; Yeap, Beow Y.; MacDonald, Shannon M.; Chen, Yen-Lin E.; Tarbell, Nancy J.; Yock, Torunn I.; Munzenrider, John E.; Adams, Judith [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Grabowski, Eric [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Mukai, Shizuo [Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-11-15

    Purpose: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT). Methods and Materials: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012. Results: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy. At a median follow-up of 8 years (range, 1-24 years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18%), especially in patients with early-stage disease (11% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61% of the preserved eyes (30 of 49): 14 of 30 eyes (47%) had 20/40 visual acuity or better, 7 of 30 (23%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy. Conclusions: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed.

  17. Can preoperative MR imaging predict optic nerve invasion of retinoblastoma?

    International Nuclear Information System (INIS)

    Song, Kyoung Doo; Eo, Hong; Kim, Ji Hye; Yoo, So-Young; Jeon, Tae Yeon

    2012-01-01

    Purpose: To evaluate the accuracy of pre-operative MRI for the detection of optic nerve invasion in retinoblastoma. Materials and methods: Institutional review board approval and informed consent were waived for this retrospective study. A total of 41 patients were included. Inclusion criteria were histologically proven retinoblastoma, availability of diagnostic-quality preoperative MR images acquired during the 4 weeks before surgery, unilateral retinoblastoma, and normal-sized optic nerve. Two radiologists retrospectively reviewed the MR images independently. Five imaging findings (diffuse mild optic nerve enhancement, focal strong optic nerve enhancement, optic sheath enhancement, tumor location, and tumor size) were evaluated against optic nerve invasion of retinoblastoma. The predictive performance of all MR imaging findings for optic nerve invasion was also evaluated by the receiver operating characteristic curve analysis. Results: Optic nerve invasion was histopathologically confirmed in 24% of study population (10/41). The differences in diffuse mild enhancement, focal strong enhancement, optic sheath enhancement, and tumor location between patients with optic nerve invasion and patients without optic nerve invasion were not significant. Tumor sizes were 16.1 mm (SD: 2.2 mm) and 14.9 mm (SD: 3.6 mm) in patients with and without optic nerve involvement, respectively (P = 0.444). P-Values from binary logistic regression indicated that all five imaging findings were not significant predictors of tumor invasion of optic nerve. The AUC values of all MR imaging findings for the prediction of optic nerve invasion were 0.689 (95% confidence interval: 0.499–0.879) and 0.653 (95% confidence interval: 0.445–0.861) for observer 1 and observer 2, respectively. Conclusion: Findings of MRI in patients with normal-sized optic nerves have limited usefulness in preoperatively predicting the presence of optic nerve invasion in retinoblastoma.

  18. Can preoperative MR imaging predict optic nerve invasion of retinoblastoma?

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    Song, Kyoung Doo, E-mail: kdsong0308@gmail.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Eo, Hong, E-mail: rtombow@gmail.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Kim, Ji Hye, E-mail: jhkate.kim@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Yoo, So-Young, E-mail: sy1131.yoo@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Jeon, Tae Yeon, E-mail: hathor97.jeon@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2012-12-15

    Purpose: To evaluate the accuracy of pre-operative MRI for the detection of optic nerve invasion in retinoblastoma. Materials and methods: Institutional review board approval and informed consent were waived for this retrospective study. A total of 41 patients were included. Inclusion criteria were histologically proven retinoblastoma, availability of diagnostic-quality preoperative MR images acquired during the 4 weeks before surgery, unilateral retinoblastoma, and normal-sized optic nerve. Two radiologists retrospectively reviewed the MR images independently. Five imaging findings (diffuse mild optic nerve enhancement, focal strong optic nerve enhancement, optic sheath enhancement, tumor location, and tumor size) were evaluated against optic nerve invasion of retinoblastoma. The predictive performance of all MR imaging findings for optic nerve invasion was also evaluated by the receiver operating characteristic curve analysis. Results: Optic nerve invasion was histopathologically confirmed in 24% of study population (10/41). The differences in diffuse mild enhancement, focal strong enhancement, optic sheath enhancement, and tumor location between patients with optic nerve invasion and patients without optic nerve invasion were not significant. Tumor sizes were 16.1 mm (SD: 2.2 mm) and 14.9 mm (SD: 3.6 mm) in patients with and without optic nerve involvement, respectively (P = 0.444). P-Values from binary logistic regression indicated that all five imaging findings were not significant predictors of tumor invasion of optic nerve. The AUC values of all MR imaging findings for the prediction of optic nerve invasion were 0.689 (95% confidence interval: 0.499–0.879) and 0.653 (95% confidence interval: 0.445–0.861) for observer 1 and observer 2, respectively. Conclusion: Findings of MRI in patients with normal-sized optic nerves have limited usefulness in preoperatively predicting the presence of optic nerve invasion in retinoblastoma.

  19. Retinoblastoma atípico: a propósito de un caso Atypic retinoblastoma: apropos of a case

    Directory of Open Access Journals (Sweden)

    Beatriz N. Rodríguez Rodríguez

    2003-06-01

    Full Text Available En una niña de 11 años de edad se presentó un caso atípico de retinoblastoma unilateral y se consultó inicialmente por una hemorragia vítrea. El ultrasonido no orientó diagnóstico. Posteriormente apareció un hifema total espontáneo con hipertensión ocular incontrolable que decidió la enucleación. El estudio anátomo-patológico concluyó un retinoblastoma poco diferenciado con extensa área de necrosis y hemorragia intratumoral.An atypic case of unilateral retinoblastoma was reported in an 11-year-old girl that was seen due to a vitreal hemorrhage at first. The ultrasound did not help to make a diagnosis. Later on, a total spontaneous hyphema with uncontrollable ocular hypertension appeared that led surgeons to perform enucleation. By the anatomopathological study, it was concluded that it was a little differentiated retinoblastoma with an extensive area of necrosis and intratumoral hemorrhage.

  20. Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre.

    Science.gov (United States)

    Künkele, Annette; Wilm, Josephine; Holdt, Markus; Lohmann, Dietmar; Bornfeld, Norbert; Eggert, Angelika; Temming, Petra; Schulte, Johannes H

    2015-07-01

    Retinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk factors are used worldwide. Between 1997 and 2009, 420 children were diagnosed with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors were assessed. Patients with post-laminar optic nerve infiltration or choroid or minor scleral invasion received six courses of adjuvant chemotherapy using vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with microscopic extension beyond the sclera to the resection margin of the optic nerve or potential spread due to vitrectomy received chemotherapy plus orbital radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with local extraocular invasion detected on MRI. Following this protocol, 42 of the 420 patients and 21 referred from other centres showed high-risk histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment. During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in group 2 developed metastases and died. No patients died from toxicity. The 5-year overall survival was 100% for group 1 and 80% for group 2. This retrospective single-site study reveals a 10% incidence of high-risk features in children with retinoblastoma diagnosed at the German Retinoblastoma Referral Centre. Overall survival rates of 98.3% underline the safety of this adjuvant chemotherapy protocol and its efficiency in preventing metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma

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    Martin, Alissa [Division of Hematology, Oncology, and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Jones, Aunica [Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Bryar, Paul J. [Departments of Ophthalmology and Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Mets, Marilyn [Division of Ophthalmology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States); Weinstein, Joanna [Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States); Division of Hematology, Oncology, and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Zhang, Gang [Biostatistics Research Core, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Laurie, Nikia A., E-mail: n-laurie@northwestern.edu [Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States)

    2013-11-01

    Highlights: •We validate miR-449a/b expression in primary human retinoblastomas and cell lines. •Exogenous miRs-449a/b inhibited proliferation in retinoblastoma cell lines. •Exogenous miRs-449a/b increased apoptosis in retinoblastoma cell lines. •miRs-449a/b could serve as viable therapeutic targets for retinoblastoma treatment. -- Abstract: Retinoblastoma is the most common pediatric cancer of the eye. Currently, the chemotherapeutic treatments for retinoblastoma are broad-based drugs such as vincristine, carboplatin, or etoposide. However, therapies targeted directly to aberrant signaling pathways may provide more effective therapy for this disease. The purpose of our study is to illustrate the relationship between the expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis. We are the first to confirm an inhibitory effect of miR-449a and -449b in retinoblastoma by demonstrating significantly impaired proliferation and increased apoptosis of tumor cells when these miRNAs are overexpressed. This study suggests that these miRNAs could serve as viable therapeutic targets for retinoblastoma treatment.

  2. Radiation management of bilateral retinoblastoma: the need to preserve vision

    International Nuclear Information System (INIS)

    Gagnon, J.D.; Ware, C.M.; Moss, W.T.; Stevens, K.R.

    1980-01-01

    Thirty-four patients with retinoblastoma were treated in the Radiation Therapy Department of the University of Oregon Health Sciences Center from 1944 to 1978. Twenty-five of these patients had bilateral disease. Most patients were treated with megavoltage equipment and received doses of 5000 rad in 5 weeks. According to the lifetable method, five year survival was 67.6%; it increased to 85.7% if patients who were treated with orthovoltage equipment were excluded. Seventy-one percent of evaluable patients had useful vision at 5 years; an additional two patients had useful vision for two years after radiation therapy. The value of even limited vision during this critical time of sensorimotor and psychological development is discussed. Orthovoltage equipment should not be used to irradiate patients with retinoblastoma

  3. Aspiration of radiation cataract in children of retinoblastoma

    International Nuclear Information System (INIS)

    Kawashima, Hidetoshi; Minoda, Kensei.

    1985-01-01

    We operated on the radiation cataracts of 12 retinoblastoma patients who had been treated by conservative therapeutic means including radiation, cryoapplication, photocoagulation, and cytostatic agents. Before the surgery, we checked that the tumor had disappeared or scarred by means of CT-scan, Ultrasonography, X-ray, and so on. Visual acuity of 1.0 or more was retained in two eyes (17 %). Four eyes (33 %) retained visual acuity of 0.6-0.4, one eye (8 %) retained 0.1 and the remaining five eyes (42 %) had visual acuity of less than 0.1. We experienced no serious complications during or after the surgeries. The reason for poorer visual acuity was either macular involvement of the tumor or radiation retinopathy due to larger dosis of radiation. Therefore, we conclude that aspiration of radiation cataract is an effective treatment of retinoblastoma patients after the tumor has disappeared or scarred. (author)

  4. Causes, outcome and prevention of abandonment in retinoblastoma in India.

    Science.gov (United States)

    Kumar, Archana; Moulik, Nirmalya Roy; Mishra, Ravi Krishna; Kumar, Dipak

    2013-05-01

    The high-cure rates of 90% in retinoblastoma are not replicated in developing countries due to late presentation and poor compliance to treatment. The present study takes a closer look at causes of abandonment of therapy and effectiveness of counselling in reducing abandonment. A retrospective study of children with retinoblastoma registered at our centre from March 2008 through August 2011. Fifty (49.50%) of 101 children registered for treatment abandoned therapy. Abandonment rates were significantly higher in rural as compared to urban children (P = 0.02). There was no significant difference in rate of abandonment between stages or laterality of disease and other socio-demographic factors. Telephone calls were more effective than letters in tracing patients (31.2% vs. 2.4%). Major reasons cited behind abandonment were financial problems (30%) and unwillingness to enucleate (20%). Of the 12 children who returned and were retreated 6 (50%) died of progressive disease. Nineteen (73%) of those who did not return died at home. Abandonment rates steadily declined from 71.42% in 2008 to 16.66% in 2011 (P = 0.01) due to effective pre-abandonment counselling by a support team under the National Retinoblastoma Registry of India from 2009. Abandonment rates for children with retinoblastoma continue to be unacceptably high. Rural background, financial constraints and hesitancy to enucleate were important causes behind abandonment. Outcome of patients who abandoned treatment was uniformly dismal. Inclusion of support team and intensified initial counselling helped in improving compliance. Copyright © 2013 Wiley Periodicals, Inc.

  5. {sup 106}Ruthenium Plaque Therapy (RPT) for Retinoblastoma

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    Murakami, Naoya, E-mail: namuraka@ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Suzuki, Shigenobu [Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yoshimura, Ryoichi [Department of Diagnostic Radiology and Oncology, Head and Neck Reconstruction Division, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Inaba, Koji; Kuroda, Yuki; Morota, Madoka; Mayahara, Hiroshi; Sakudo, Mototake; Wakita, Akihisa; Okamoto, Hiroyuki; Sumi, Minako; Kagami, Yoshikazu [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Nakagawa, Keiichi; Ohtomo, Kuni [Department of Radiology, University of Tokyo Hospital, Tokyo (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2012-09-01

    Purpose: To evaluate the effectiveness of episcleral {sup 106}ruthenium plaque therapy (RPT) in the management of retinoblastoma. Methods and Materials: One hundred one RPTs were retrospectively analyzed that were performed in 90 eyes of 85 patients with retinoblastoma at National Cancer Center Hospital between 1998 and 2008. Each RPT had a corresponding tumor and 101 tumors were considered in the analysis of local control. Median follow-up length was 72.8 months. Median patient age at the RPT was 28 months. Median prescribed doses at reference depth and outer surface of the sclera were 47.4 Gy and 162.3 Gy, respectively. Results: Local control rate (LCR) and ocular retention rate (ORR) at 2 years were 33.7% and 58.7%, respectively. Unilateral disease, International Classification of Retinoblastoma group C or more advanced at the first presentation or at the time of RPT, vitreous and/or subretinal seeding, tumor size greater than 5 disc diameter (DD), reference depth greater than 5 mm, dose rate at reference depth lower than 0.7 Gy/hour, dose at the reference depth lower than 35 Gy, and (biologically effective dose with an {alpha}/{beta} ratio of 10 Gy) at the reference depth lower than 40 Gy{sub 10} were associated with unfavorable LCR. Two patients died of metastatic disease. Radiation complications included retinal detachment in 12 eyes (13.3%), proliferative retinopathy in 6 (6.7%), rubeosis iris in 2 (2.2%), and posterior subcapsular cataract in 23 (25.6%). Conclusion: RPT is an effective eye-preserving treatment for retinoblastoma.

  6. Thermography in the diagnosis of retinoblastoma in children

    International Nuclear Information System (INIS)

    Bogdasarov, Yu.B.; Lenskaya, O.P.; Belkina, B.M.

    1985-01-01

    The authors presented the results of thermographic examination in combination with echography and computerized tomography were presented in children with suspected retinoblastoma (30 primary examined patients and 30 patients examined to assess therapeutic efficacy). The results of the examination showed the relationship of the hyperthermia zone with tumor stage. All the patients recieved remote gamma-therapy and polychemotherapy. The usefulness of the thermographic method for efficacy assessment was shown

  7. Postradiation leiomyosarcoma of the orbit complicating bilateral retinoblastoma

    International Nuclear Information System (INIS)

    Font, R.L.; Jurco, S.; Brechner, R.J.

    1983-01-01

    A 31-year-old woman had bilateral retinoblastoma diagnosed in early childhood. The right eye was enucleated at the age of 1 year, and the left eye was treated with radiation therapy (a total dose of 16,000 rad). Twenty-three years later, in 1975, a subcutaneous mass was noted in the left periorbital region. A biopsy specimen of the mass was taken and a diagnosis of pleomorphic postradiation sarcoma was made. Electron microscopic studies of the periorbital mass confirmed the diagnosis of leiomyosarcoma. After additional radiation therapy, the residual mass was surgically excised. Five years later, a right renal mass, which histologically proved to be a renal cell carcinoma, was discovered. She was treated with nephrectomy, radiation, and chemotherapy. A recent follow-up examination disclosed that the patient is alive and apparently without any evidence of metastatic disease, 30 years after the diagnosis of bilateral retinoblastoma was made. The literature is reviewed regarding postradiation sarcomas and the occurrence of second malignant neoplasms in patients with retinoblastoma

  8. Postradiation leiomyosarcoma of the orbit complicating bilateral retinoblastoma.

    Science.gov (United States)

    Font, R L; Jurco, S; Brechner, R J

    1983-10-01

    A 31-year-old woman had bilateral retinoblastoma diagnosed in early childhood. The right eye was enucleated at the age of 1 year, and the left eye was treated with radiation therapy (a total dose of 16,000 rad). Twenty-three years later, in 1975, a subcutaneous mass was noted in the left periorbital region. A biopsy specimen of the mass was taken and a diagnosis of pleomorphic postradiation sarcoma was made. Electron microscopic studies of the periorbital mass confirmed the diagnosis of leiomyosarcoma. After additional radiation therapy, the residual mass was surgically excised. Five years later, a right renal mass, which histologically proved to be a renal cell carcinoma, was discovered. She was treated with nephrectomy, radiation, and chemotherapy. A recent follow-up examination disclosed that the patient is alive and apparently without any evidence of metastatic disease, 30 years after the diagnosis of bilateral retinoblastoma was made. The literature is reviewed regarding postradiation sarcomas and the occurrence of second malignant neoplasms in patients with retinoblastoma.

  9. CT and MR findings in retinoblastoma : correlation with histopathologic examination

    International Nuclear Information System (INIS)

    Park, Son Won; Han, Moon Hee; Chi, Je G.; Yu, Young Suk; Kim, Yeon Mee; Chung, Jin Haeng; Yu, In Kyu; Chang, Kee Hyun; Yeon, Kyung Mo

    1997-01-01

    To evaluate histopathologic correlation of the component of the lesion on CT and MR of retinoblastomas. Gross pathologic findings of 24 enucleated eyeballs in 24 patients with retinoblastomas were compared with preoperative CT (n=19) and MR (n=5) findings. In eight eyeballs, in which there were findings other than mass, histopathologic findings were reviewed and correlated with image findings. Retinal detachment and subretinal hemorrhage which were not detected on CT were demonstrated in two of eight eyeballs on histopathologic examination. In one eyeball, retinal detachment and subretinal effusion were detected on both CT and in a pathologic specimen. In two eyeballs with peripheral heterogeneous MR enhancement of the masses, tumor necrosis and calcification were demonstrated in the central non-emhancing portion of the mass, In two eveballs, linear soft tissue along the retina apart from the main mass were revealed as tumor spread along the retinal surface. In one patient, retinal thickening on MR was presumed to be an MR artifact and no lesion was found in the gross specimen. On CT, retinal detachment and subretinal hemorrhage associated with retinoblastoma can mimic mass, and tumor spread along the retinal surface can be seen as a linear retinal lesion. On MR, tumor necrosis and calcification can be a cause of heterogeneous enhancement

  10. Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway.

    Science.gov (United States)

    Gao, Yali; Lu, Xiaohe

    2016-02-01

    The aberrant expression of MEG3 has been found in some types of cancers; however, little is known concerning the function of MEG3 in retinoblastoma. To elucidate the roles of MEG3 in retinoblastoma, MEG3 expression was quantified in 63 retinoblastoma samples and corresponding nontumor tissues in this work. Moreover, retinoblastoma cell lines were transfected with pcDNA3.1-MEG3 or si-MEG3, after which proliferation, apoptosis, and expression of β-catenin were assayed. TOP-Flash reporter assay was also used to investigate the activity of the Wnt/β-catenin pathway. The results showed that MEG3 was downregulated in retinoblastoma tissues, and the level of MEG3 was negatively associated with IIRC stages and nodal or distant metastasis. More importantly, Kaplan-Meier survival analysis demonstrated that patients with low MEG3 expression had poorer survival and multivariate Cox regression analysis revealed that MEG3 was an independent prognostic factor in retinoblastoma patients. We also observed that MEG3 expression can be modulated by DNA methylation by using 5-aza-CdR treatment. In addition, overexpression of MEG3 suppressed proliferation, promoted apoptosis, and influences the activity of the Wnt/β-catenin pathway in retinoblastoma cell lines. Furthermore, we found that Wnt/β-catenin pathway activator rescued the anticancer effect of MEG3 in retinoblastoma. In conclusion, our study for the first time demonstrated that MEG3 was a tumor suppressor by negatively regulating the activity of the Wnt/β-catenin pathway in the progression of retinoblastoma and might serve as a prognostic biomarker and molecular therapeutic target.

  11. World disparities in risk definition and management of retinoblastoma: a report from the International Retinoblastoma Staging Working Group.

    Science.gov (United States)

    Chantada, Guillermo L; Doz, François; Orjuela, Manuela; Qaddoumi, Ibrahim; Sitorus, Rita S; Kepak, Tomas; Furmanchuk, Anna; Castellanos, Mauricio; Sharma, Tarun; Chevez-Barrios, Patricia; Rodriguez-Galindo, Carlos

    2008-03-01

    Following from the publication of the International Retinoblastoma Staging System, an open internet discussion group was created at the www.cure4kids.org resource. The results of a survey distributed among participants are discussed. Although most patients with retinoblastoma were treated under prospective protocols, there was a wide variation in the definition of risk criteria and in the criteria for giving adjuvant chemotherapy following enucleation. Definition of high-risk histological features and the criteria for use of adjuvant therapy will be standardized in future studies. Internet meetings are a valuable mechanism for enabling participation from under-resourced countries in the development of cooperative studies. (c) 2007 Wiley-Liss, Inc.

  12. Optical Coherence Tomography-Guided Decisions in Retinoblastoma Management.

    Science.gov (United States)

    Soliman, Sameh E; VandenHoven, Cynthia; MacKeen, Leslie D; Héon, Elise; Gallie, Brenda L

    2017-06-01

    Assess the role of handheld optical coherence tomography (OCT) in guiding management decisions during diagnosis, treatment, and follow-up of eyes affected by retinoblastoma. Retrospective, noncomparative, single-institution case series. All children newly diagnosed with retinoblastoma from January 2011 to December 2015 who had an OCT session during their active treatment at The Hospital for Sick Children (SickKids) in Toronto, Canada. The OCT sessions for fellow eyes of unilateral retinoblastoma without any suspicious lesion and those performed more than 6 months after the last treatment were excluded. Data collected included age at presentation, sex, family history, RB1 mutation status, 8th edition TNMH cancer staging and International Intraocular Retinoblastoma Classification (IIRC), and number of OCT sessions per eye. Details of each session were scored for indication-related details (informative or not) and assessed for guidance (directive or not), diagnosis (staging changed, new tumors found or excluded), treatment (modified, stopped, or modality shifted), or follow-up modified. Frequency of OCT-guided management decisions, stratified by indication and type of guidance (confirmatory vs. influential). Sixty-three eyes of 44 children had 339 OCT sessions over the course of clinical management (median number of OCT scans per eye, 5; range, 1-15). The age at presentation and presence of a heritable RB1 mutation significantly correlated with an increased number of OCT sessions. Indications included evaluation of post-treatment scar (55%) or fovea (16%), and posterior pole scanning for new tumors (11%). Of all sessions, 92% (312/339) were informative; 19 of 27 noninformative sessions had large, elevated lesions; of these, 14 of 19 were T2a or T2b (IIRC group C or D) eyes. In 94% (293/312) of the informative sessions, OCT directed treatment decisions (58%), diagnosis (16%), and follow-up (26%). Optical coherence tomography influenced and changed management from pre

  13. Peso y talla en niños con retinoblastoma

    Directory of Open Access Journals (Sweden)

    Cecilia Ridaura-Sanz

    2015-03-01

    Full Text Available Introducción: la talla baja se ha descrito como característica clínica de niños con retinoblastoma. Esta particularidad puede estar relacionada directamente con la enfermedad de base o con factores externos.  Objetivo: el propósito de esta investigación fue conocer la frecuencia de talla y peso bajos en niños mexicanos con retinoblastoma y correlacionar los valores antropométricos con variables de la enfermedad y ambientales. Materiales y métodos: se analizaron expedientes clínicos de 346 pacientes con retinoblastoma. Se obtuvieron los datos de peso y talla referidos al ingreso; antes del tratamiento. Se comparó el valor de Z con las referencias de la distribución normal de la población mexicana. La asociación de las medidas antropométricas con las variables clínicas, sociales y genéticas se estableció con la prueba de c2. Resultados: la talla y el peso promedio de los niños con retinoblastoma fueron significativamente más bajos que los de la población general (p < 0.001 y p = 0.013, respectivamente. La talla y peso bajos fueron más frecuentes en niños con enfermedad avanzada, provenientes de medio rural y de bajo nivel socioeconómico. Conclusiones: los déficits en peso y talla en niños con retinoblastoma se deben a factores relacionados con enfermedad avanzada al momento del diagnóstico, lo cual a su vez es consecuencia de la situación de marginación de la población rural mexicana. Dado que la mayoría de las variables sociales y ambientales están muy relacionadas y que no podemos descartar posibles factores genéticos, las conclusiones de este estudio deben verificarse analizando las medidas de los padres y hermanos y establecer grupos comparativos para controlar las variables confusas.

  14. Radiation therapy for retinoblastoma: a retrospective review of 120 patients

    International Nuclear Information System (INIS)

    Pradhan, Deepak G.; Sandridge, Amy L.; Mullaney, Paul; Abboud, Emad; Karcioglu, Zeynel A.; Kandil, Alaa; Mustafa, Mahmoud M.; Gray, Alan J.

    1997-01-01

    Purpose: To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist Hospital and Research Centre (KFSH and RC), Riyadh, Saudi Arabia from 1976 to 1993. Methods and Materials: A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the α/β ratio for early effects and tumor control at 10, Tk = 21 days, T pot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy 10 for early effects, and 101 Gy 3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months. Results: Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had

  15. Conserved retinoblastoma protein-binding motif in human cytomegalovirus UL97 kinase minimally impacts viral replication but affects susceptibility to maribavir

    Directory of Open Access Journals (Sweden)

    Chou Sunwen

    2009-01-01

    Full Text Available Abstract The UL97 kinase has been shown to phosphorylate and inactivate the retinoblastoma protein (Rb and has three consensus Rb-binding motifs that might contribute to this activity. Recombinant viruses containing mutations in the Rb-binding motifs generally replicated well in human foreskin fibroblasts with only a slight delay in replication kinetics. Their susceptibility to the specific UL97 kinase inhibitor, maribavir, was also examined. Mutation of the amino terminal motif, which is involved in the inactivation of Rb, also renders the virus hypersensitive to the drug and suggests that the motif may play a role in its mechanism of action.

  16. Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

    NARCIS (Netherlands)

    Neumann, S.

    2008-01-01

    Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

  17. Intravitreal chemotherapy in retinoblastoma: expanded use beyond intravitreal seeds.

    Science.gov (United States)

    Abramson, David H; Ji, Xunda; Francis, Jasmine H; Catalanotti, Federica; Brodie, Scott E; Habib, Larissa

    2018-06-06

    Ophthalmic artery chemosurgery (OAC) has changed the face of retinoblastoma treatment and led to a higher rate of globe salvage. The introduction of intravitreal chemotherapy (IVitC) has further enhanced globe salvage with increased success in treatment of intravitreal seeds. Our group has seen success at treating non-vitreous disease that is refractory to OAC using IVitC. This study was undertaken to quantify and report on this success. A retrospective review was used to identify patients treated with IVitC for indications other than vitreous seeds from two centres. The indication, prior and concurrent treatment, response time and duration of treatment were documented. Kaplan-Meier estimates were used to evaluate ocular and recurrence-free survival. Ocular toxicity was evaluated using the 30 Hz flicker electroretinogram (ERG). Continuous and categorical variables were compared with Student's t-test and χ 2 test, respectively. Fifty-six eyes from 52 retinoblastoma patients were identified. There were no disease-related or treatment-related deaths. One patient developed a second primary malignancy (pinealoblastoma) and subsequent leptomeningeal spread. Ninety-eight per cent of the eyes showed clinical regression. Recurrence was seen in 14.3%. Of the recurrences, five occurred in retinal tumours and three in subretinal seeds. The Kaplan-Meier estimated risk of recurrence in all patients treated was 83.5% (95% CI 7.9 to 14.1) at 10 months. The mean change in ERG over treatment course was -17.7 μV. Intravitreal chemotherapy is successful for the treatment of subretinal seeds and recurrent retinal tumours and could be considered as adjunctive therapy in globe-sparing treatment of retinoblastoma. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Update on Intra-Arterial Chemotherapy for Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Mario Zanaty

    2014-01-01

    Full Text Available The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

  19. In vitro Rb-1 gene transfer to retinoblastoma cell lines

    International Nuclear Information System (INIS)

    Choi, Sang Wook; Ham, Yong Hoh; Kim, Mee Heui

    1994-04-01

    After transfection of Rb-vector to packaging cell line (CRIP) by Ca-P precipitation method, we could select nineteen colonies of G-418 resistant clone by ring cloning. Each colony was transduced to NIH3T3 cells to select the one which produces high titer virus. After NIH3T3 cells transduction, we could get 28 colony counts for the high, 127 for the middle, and 6 for the low viral titer. With the supernatant of the high viral titer colony (CRIPRb 2-5). We transduct retinoblastoma cell lines. 5 figs, 11 refs. (Author)

  20. New research progress of microRNAs in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Jing Zeng

    2014-11-01

    Full Text Available Retinoblastoma(RBis the most common intraocular malignancy of children with extremely poor prognosis. MicroRNAs are small non-coding single-stranded RNAs in eukaryotic cells, which regulate the expression of gene by mRNA degradation or translation inhibition. MicroRNAs, acting as oncogenes or tumor suppressor genes, are associated with the occurrence and development of RB directly, which is vital for the early diagnosis and clinical targeted therapy of RB. This review summarized the expression of microRNAs in RB and the related mechanism.

  1. Direct Involvement of Retinoblastoma Family Proteins in DNA Repair by Non-homologous End-Joining

    Directory of Open Access Journals (Sweden)

    Rebecca Cook

    2015-03-01

    Full Text Available Deficiencies in DNA double-strand break (DSB repair lead to genetic instability, a recognized cause of cancer initiation and evolution. We report that the retinoblastoma tumor suppressor protein (RB1 is required for DNA DSB repair by canonical non-homologous end-joining (cNHEJ. Support of cNHEJ involves a mechanism independent of RB1’s cell-cycle function and depends on its amino terminal domain with which it binds to NHEJ components XRCC5 and XRCC6. Cells with engineered loss of RB family function as well as cancer-derived cells with mutational RB1 loss show substantially reduced levels of cNHEJ. RB1 variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support cNHEJ despite being able to confer cell-cycle control. Our data identify RB1 loss as a candidate driver of structural genomic instability and a causative factor for cancer somatic heterogeneity and evolution.

  2. Retinoblastoma in the Democratic Republic of Congo: 20-Year Review from a Tertiary Hospital in Kinshasa

    Directory of Open Access Journals (Sweden)

    Aimé Kazadi Lukusa

    2012-01-01

    Full Text Available Background. To determine clinical profile and management of retinoblastoma among children at Kinshasa in Democratic Republic of Congo. Patients and methods. The medical records of patients with a diagnosis of retinoblastoma seen at the University Hospital of Kinshasa from January 1985 till December 2005 were retrospectively reviewed. Demographic profile, clinical data, modes of treatment and outcome were analysed. Results. A total of 49 children, of whom 40 had adequate data on record were identified as retinoblastoma (28 males and 12 females. Nine cases had bilateral disease. The median age at the first symptoms was 9 months (range, 1 month to 6 years for unilateral retinoblastoma and 18 months (range, 1 month to 3.5 years for bilateral retinoblastoma. The median age at the first oncology consultation was 2.4 years (range, 6 months to 6 years for unilateral retinoblastoma and 2.4years (range, 9 months to 4 years for bilateral disease. Leukokoria was present in 67.5% of subjects. Seventy-five percent abandoned the treatment. The mortality was 92.5%. Conclusion. In Democratic Republic of Congo, retinoblastoma remains a life threatening disease characterized by late referral to a specialized unit and affordability of chemotherapy; all leading to an extension of the disease and high mortality.

  3. The toxic effects, GSH depletion and radiosensitivity by BSO on retinoblastoma

    International Nuclear Information System (INIS)

    Xianjin Yi; Li Ding; Yizun Jin; Chuo Ni; Wenji Wang

    1994-01-01

    Retinoblastoma is the most common intraocular malignant tumor in children. Previous investigations have reported that buthionine sulfoximine (BSO) can deplete intracellular glutathione (GSH) by specific inhibition and increase cellular radiosensitivity. The toxic effects, GSH depletion and radiosensitivity effects of BSO on retinoblastoma cells are reported in this paper. GSH content of retinoblastoma cell lines Y-79, So-Rb50 and retinoblastoma xenograft is 2.7 ± 1.3 X 1.0 -12 mmol/cell, 1.4 ± 0.2 X 1.0 -12 mmol/cell, and 2.8 ± 1.2 μmol/g, respectively. The ID 50 of BSO on Y-79 and So-Rb50 in air for 3 h exposure is 2.5 mM and 0.2 mM, respectively. GSH depletion by 0.1 mM BSO for 24 h on Y-79 cells and 0.01 mM BSO for 24 h on So-Rb50 cells is 16.35%, and 4.7% of control. GSH depletion in tumor and other organ tissues in retinoblastoma-bearing nude mice after BSO administration is differential. GSH depletion after BSO exposure in Y-79 cells in vitro decreases the Do value of retinoblastoma cells. The SER of 0.01 mM and 0.05 mM BSO for 24 h under hypoxic conditions is 1.21 and 1.36, respectively. Based on these observations, the authors conclude that BSO toxicity on retinoblastoma cells depends on the characteristics of the cell line and that BSO can increase hypoxic retinoblastoma cells' radiosensitivity in vitro. Further study of BSO radiosensitization on retinoblastoma in vivo using nude mouse xenografts is needed. 25 refs., 3 figs., 3 tabs

  4. The toxic effects, GSH depletion and radiosensitivity by BSO on retinoblastoma

    International Nuclear Information System (INIS)

    Yi Xianjin; Ni Chuo; Wang Wengi; Li Ding; Jin Yizun

    1993-01-01

    Retinoblastoma is the most common intraocular malignant tumor in children. Previous investigations have reported that buthionine sulfoximine (BSO) can deplete intracellular glutathione (GSH) by the specific inhibition and increase cellular radiosensitivity. The toxic effects, GSH depletion and radiosensitivity of BSO on retinoblastoma were reported. GSH content of retinoblastoma cell lines Y-79, So-Rb50 and retinoblastoma xenograft is (2.7 +- 1.3) x 10 -12 mmol/cell, (1.4 +- 0.2) x 10 -12 mmol/cell, and 2.8 +- 1.2 μmol/g respectively. The ID50 of BSO on Y-79 and So-Rb50 in air for 3h exposure is 2.5 mM and 0.2 mM respectively. GSH depletion by 0.1 mM BSO for 24h on Y-79 cells and 0.01 mM BSO for 24 h on So-Rb50 cells is 16.35%, and 4.7% of control. GSH depletion in tumor and other organ tissues in retinoblastoma bearing nude mice after BSO administration is differential. BSH depletion after BSO exposure in Y-79 cells in vitro decrease the D 0 value of retinoblastoma cells. The SER of 0.01 mM and 0.05 mM BSO for 24 h under the hypoxic condition is 1.21 and 1.36 respectively. Based on these observations, the authors conclude that BSO toxicity on retinoblastoma cells depends on the characteristics of cell line and BSO can increase hypoxic retinoblastoma cells radiosensitivity in vitro. Further study of BSO radiosensitization on retinoblastoma in vivo using nude mouse xenograft is needed

  5. Retinoblastoma incidence patterns in the US Surveillance, Epidemiology, and End Results program.

    Science.gov (United States)

    Wong, Jeannette R; Tucker, Margaret A; Kleinerman, Ruth A; Devesa, Susan S

    2014-04-01

    IMPORTANCE Several studies have found no temporal or demographic differences in the incidence of retinoblastoma except for age at diagnosis, whereas other studies have reported variations in incidence by sex and race/ethnicity. OBJECTIVE To examine updated US retinoblastoma incidence patterns by sex, age at diagnosis, laterality, race/ethnicity, and year of diagnosis. DESIGN, SETTING, AND PARTICIPANTS The Surveillance, Epidemiology, and End Results (SEER) databases were examined for retinoblastoma incidence patterns by demographic and tumor characteristics. We studied 721 children in SEER 18 registries, 659 in SEER 13 registries, and 675 in SEER 9 registries. MAIN OUTCOMES AND MEASURES Incidence rates, incidence rate ratios (IRRs), and annual percent changes in rates. RESULTS During 2000-2009 in SEER 18, there was a significant excess of total retinoblastoma among boys compared with girls (IRR, 1.18; 95% CI, 1.02 to 1.36), in contrast to earlier reports of a female predominance. Bilateral retinoblastoma among white Hispanic boys was significantly elevated relative to white non-Hispanic boys (IRR, 1.81; 95% CI, 1.22 to 2.79) and white Hispanic girls (IRR, 1.75; 95% CI, 1.11 to 2.91) because of less rapid decreases in bilateral rates since the 1990s among white Hispanic boys than among the other groups. Retinoblastoma rates among white non-Hispanics decreased significantly since 1992 among those younger than 1 year and since 1998 among those with bilateral disease. CONCLUSIONS AND RELEVANCE Although changes in the availability of prenatal screening practices for retinoblastoma may have contributed to these incidence patterns, further research is necessary to determine their actual effect on the changing incidence of retinoblastoma in the US population. In addition, consistent with other cancers, an excess of retinoblastoma diagnosed in boys suggests a potential effect of sex on cancer origin.

  6. Dosimetric Study of Current Treatment Options for Radiotherapy in Retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Eldebawy, Eman [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Department of Radiation Oncology, Children' s Cancer Hospital, Cairo (Egypt); Parker, William, E-mail: william.parker@mcgill.ca [Department of Medical Physics, McGill University Health Centre, Montreal, Quebec (Canada); Abdel Rahman, Wamied [Department of Medical Physics, McGill University Health Centre, Montreal, Quebec (Canada); Freeman, Carolyn R. [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada)

    2012-03-01

    Purpose: To determine the best treatment technique for patients with retinoblastoma requiring radiotherapy to the whole eye. Methods and Materials: Treatment plans for 3 patients with retinoblastoma were developed using 10 radiotherapy techniques including electron beams, photon beam wedge pair (WP), photon beam three-dimensional conformal radiotherapy (3D-CRT), fixed gantry intensity-modulated radiotherapy (IMRT), photon volumetric arc therapy (VMAT), fractionated stereotactic radiotherapy, and helical tomotherapy (HT). Dose-volume analyses were carried out for each technique. Results: All techniques provided similar target coverage; conformity was highest for VMAT, nine-field (9F) IMRT, and HT (conformity index [CI] = 1.3) and lowest for the WP and two electron techniques (CI = 1.8). The electron techniques had the highest planning target volume dose gradient (131% of maximum dose received [D{sub max}]), and the CRT techniques had the lowest (103% D{sub max}) gradient. The volume receiving at least 20 Gy (V{sub 20Gy}) for the ipsilateral bony orbit was lowest for the VMAT and HT techniques (56%) and highest for the CRT techniques (90%). Generally, the electron beam techniques were superior in terms of brain sparing and delivered approximately one-third of the integral dose of the photon techniques. Conclusions: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques.

  7. The success of primary chemotherapy for group D heritable retinoblastoma.

    Science.gov (United States)

    Cohen, V M L; Kingston, J; Hungerford, J L

    2009-07-01

    To report the ocular survival and event-free survival following primary multiagent chemotherapy for group D, heritable bilateral retinoblastoma (RB). The RB database was used to identify children with heritable, bilateral RB treated with primary chemotherapy (six cycles of vincristine, etoposide and carboplatin). Only Group D eyes with more than 12 months' follow-up were analysed. The timing, number and type of salvage treatments were recorded. Kaplan-Meier estimates for the ocular survival and event-free survival (percentage of eyes that avoided external beam radiotherapy and/or enucleation) were performed as a function of time. Of 18 group D eyes, two (11%) were treated successfully with chemotherapy alone, nine (50%) underwent successful salvage treatment, and seven (39%) were enucleated. The median time from completing chemotherapy to enucleation was 9 months (range 4 to 25 months). Ocular survival was 67% at 2 years. External beam radiotherapy proved successful salvage treatment in five of nine eyes, so the event-free survival was 34% at 2 years. Multiagent chemotherapy alone is rarely sufficient for the preservation of group D eyes. External beam radiotherapy and plaque radiotherapy remain important salvage treatments for advanced, heritable retinoblastoma.

  8. Chemotherapy as an adjuvant to Radiotherapy in treatment of Retinoblastoma

    International Nuclear Information System (INIS)

    Ahmed, A.H.M.

    2015-01-01

    Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. Various studies show that while enucleation remains the standard of care for advanced intraocular tumours, conservative modalities that can result in globe salvage and preservation of useful vision are being increasingly employed. Such modalities include systemic chemotherapy, focal consolidation with transpupillary thermo therapy, laser photocoagulation and cryotherapy, plaque brachytherapy, and delivery of local chemotherapy using subconjunctival, sub-tenon, or intra-arterial routes. When used alone or in combination, these treatment modalities can help in avoidance of external beam radiotherapy or enucleation, thus reducing the potential for long-term side effects, while salvaging useful vision. Radioactive plaque brachytherapy has an established role in selected patients with intraocular retinoblastoma. Local injections of chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been used with varying degrees of success, usually as an adjunct to systemic chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown promising results.

  9. The modality and results of complex treatment of extended retinoblastoma in children

    International Nuclear Information System (INIS)

    Belkina, B.M.; Durnov, L.A.; Polyakov, V.G.; Goldobenko, G.V.; Glekov, I.V.; Ushakova, T.L.

    1997-01-01

    Analysis of the results of combined treatment of retinoblastoma in children according to the program developed in the Scientific and Research Institute of Pediatric Oncology and Hematology is performed. The treatment program permits to avoid in many cases the unjustified removal of eye. Combination of treatment methods (surgery, radiotherapy and chemotherapy) and their sequence depends on the classification by stages of retinoblastoma development according to the TNM system. Five year survival in case of monoretinoblastoma with surgical operation at the first stage and without is 92% and 82% corresponding while in case of double retinoblastoma - 83% and 84%

  10. Novel function of the retinoblastoma protein in fat: regulation of white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; te Riele, Hein; Kristiansen, Karsten

    2004-01-01

    the major energy store and brown adipocytes being potent energy-dissipaters through thermogenesis. Yet, little is known about factors differentially regulating the formation of white and brown fat cells. Members of the retinoblastoma protein family (pRB, p107, p130) have been implicated in the regulation...... of adipocyte differentiation, and expression and phosphorylation of the three retinoblastoma family proteins oscillate in a characteristic manner during differentiation of the white preadipocyte cell line 3T3-L1. We have recently demonstrated a surprising function of the retinoblastoma protein...... in the regulation of white versus brown adipocyte differentiation in vitro and possibly in vivo. Here we summarize the current knowledge on the retinoblastoma protein in fat cells, with particular emphasis on its potential role in adipocyte lineage commitment and differentiation....

  11. Tratamento conservador em retinoblastoma intra-ocular Conservative treatment for intraocular retinoblastoma

    Directory of Open Access Journals (Sweden)

    Clélia Maria Erwenne

    2003-12-01

    bilaterais foram conservados 48,9% dos olhos tratados. Entre os unilaterais, para os mesmos estádios obteve-se: I 0/0; II 2/2 (100,0%; III 1/3 (33,3%; IV 1/3 (33,3%; V 0/7 (0%. Considerando-se o total de unilaterais foram conservados 26,6% dos olhos. Não se observou nefro ou ototoxicidade às drogas neste grupo.PURPOSE: To report the results of conservation of the ocular globe after treatment with carboplatin and laser; with or without the use of other forms of local treatment or radiotherapy, if necessary. METHODS: All eyes, initially untreated, were evaluated using indirect ophthalmology under inhalation anesthesia in an outpatient clinic treatment setting. They were categorized according to the Reese-Ellsworth system; thereafter, the patients were evaluated clinically by a pediatric oncologist. The patients received the first cycle of chemotherapy consisting of intravenous carboplatin 200 mg/m², vincristine 1.5 mg/m² and etoposide 150 mg/m², for three days. This was followed by other cycles with intervals of between 21 and 28 days. From 7 to 15 days after the end of the chemotherapy cycle, another indirect ophthalmoscopy under inhalation anesthesia was performed, with documentation of the findings and laser hyperthermia application, using a Diode laser, 810 nm, continuous pulse with a large spot size. The procedure (chemotherapy and laser was repeated until complete cicatrization of all lesions was observed, or until the need for another treatment modality such as radiotherapy or enucleation became apparent. Follow-up examinations every two months during the first year and three months thereafter were done for review and for treatment of recurrent or new lesions. Pediatric oncology follow-up was also done throughout the entire initial assessment and follow-up period. RESULTS: We treated a total of 62 patients with retinoblastoma, of whom 32 were male and 30 female. Fifteen were unilateral and 47 were bilateral with a total of 107 eyes. The mean age was 16.9 months (2

  12. Breaking down barriers to communicating complex retinoblastoma information: can graphics be the solution?

    Science.gov (United States)

    Chiu, Hannah H; Dimaras, Helen; Downie, Rob; Gallie, Brenda

    2015-06-01

    To investigate the impact of a graphical timeline summarizing bilateral retinoblastoma disease and treatment outcomes on parents' understanding of complex medical information. Cross-sectional survey. Parents of children with retinoblastoma who were being actively managed at The Hospital for Sick Children were recruited. Forty-five parents from 42 families participated. After a standardized presentation on retinoblastoma and visual tool named Disease-Specific electronic Patient Illustrated Clinical Timeline (DePICT), parents completed a 19-item questionnaire designed to assess their understanding of treatment choices for 2 eyes in bilateral retinoblastoma as communicated using DePICT. SPSS was used to perform statistical analysis. Forty-five parents from 42 families participated (65% female). Median age of participants was 34 years. Median level of participant education was completion of college/trade school. The median level of annual income was $40,000 to $70,000 CDN. Median time since diagnosis of retinoblastoma in their child was 13.5 months. Twenty-three (51%) participants were parents of children with unilateral retinoblastoma, and 22 (49%) were parents of children with bilateral retinoblastoma. Median number of correct answers was 15 of 19, and mean score was 77%. Normal distribution of scores was noted. English as a first language was significantly associated with score (p = 0.01). No significant association was observed between other variables and score in all analyses. This study builds on the validation of DePICT by demonstrating that parents can achieve good comprehension even when considering choices for treatment for 2 eyes with bilateral retinoblastoma. Clinical application of this tool can enhance the consent process. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  13. Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes

    International Nuclear Information System (INIS)

    Abramovsky-Kaplan, I.; Jones, I.S.

    1984-01-01

    Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit increased spontaneous fragility. X-irradiation (25-200 rad) did not significantly increase SCE in unilateral retinoblastoma lymphocytes when compared with controls (P greater than 0.50). However, bilaterally affected subjects and three unaffected relatives demonstrated a statistically significant increase in SCE (P less than 0.01). In conclusion, hereditary retinoblastoma lymphocytes appear more radiosensitive than sporadic retinoblastoma, perhaps, reflecting the increased second malignancies in germinal mutation retinoblastoma. In addition, the analysis of radiation-induced SCE in peripheral blood lymphocytes of RB patients and family members may provide a valuable tool increasing the accuracy of genetic counseling for this disorder. Additional studies of RB patients and families are needed to assess the relevance of this approach to genetic counseling

  14. Radiation regression patterns after cobalt plaque insertion for retinoblastoma

    International Nuclear Information System (INIS)

    Buys, R.J.; Abramson, D.H.; Ellsworth, R.M.; Haik, B.

    1983-01-01

    An analysis of 31 eyes of 30 patients who had been treated with cobalt plaques for retinoblastoma disclosed that a type I radiation regression pattern developed in 15 patients; type II, in one patient, and type III, in five patients. Nine patients had a regression pattern characterized by complete destruction of the tumor, the surrounding choroid, and all of the vessels in the area into which the plaque was inserted. This resulting white scar, corresponding to the sclerae only, was classified as a type IV radiation regression pattern. There was no evidence of tumor recurrence in patients with type IV regression patterns, with an average follow-up of 6.5 years, after receiving cobalt plaque therapy. Twenty-nine of these 30 patients had been unsuccessfully treated with at least one other modality (ie, light coagulation, cryotherapy, external beam radiation, or chemotherapy)

  15. Radiation regression patterns after cobalt plaque insertion for retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Buys, R.J.; Abramson, D.H.; Ellsworth, R.M.; Haik, B.

    1983-08-01

    An analysis of 31 eyes of 30 patients who had been treated with cobalt plaques for retinoblastoma disclosed that a type I radiation regression pattern developed in 15 patients; type II, in one patient, and type III, in five patients. Nine patients had a regression pattern characterized by complete destruction of the tumor, the surrounding choroid, and all of the vessels in the area into which the plaque was inserted. This resulting white scar, corresponding to the sclerae only, was classified as a type IV radiation regression pattern. There was no evidence of tumor recurrence in patients with type IV regression patterns, with an average follow-up of 6.5 years, after receiving cobalt plaque therapy. Twenty-nine of these 30 patients had been unsuccessfully treated with at least one other modality (ie, light coagulation, cryotherapy, external beam radiation, or chemotherapy).

  16. A pilot study of hyperfractionated radiotherapy for infants with retinoblastoma

    International Nuclear Information System (INIS)

    Harris, Eleanor E.R.; Meadows, Anna T.; Shields, Jerry; D'Angio, Giulio J.; Goldwein, Joel W.

    1996-01-01

    Purpose: This study was undertaken to assess the use of twice daily fractionated radiotherapy using low doses per fraction in the treatment of intraocular retinoblastoma in infants in terms of local control, ocular complications and bony growth disturbances. Methods: Children were irradiated using standard techniques including en face electrons (3 patients) or opposed lateral photon fields to one or both orbits (7 patients). Patients were treated with 100 cGy twice daily with an inter fraction interval of 4 or more hours to total doses of 43 to 45 Gy. No patients received chemotherapy. Results: Ten children under the age of 13 months were entered onto the twice daily radiation protocol from 4/87 through 6/90. Nine patients presented with nonfamilial bilateral retinoblastoma; one later failed in the pineal region representing trilateral retinoblastoma. The tenth patient had advanced unilateral disease. Of 19 eyes involved with tumor, 13 were group V and all patients had at least one eye with advanced disease (group III-V). Two patients underwent enucleation of the more advanced eye up front and received radiation to the intact eye only. Overall survival was 8 of 10 patients with a median follow-up of 28 months (range 12-47 months). Two patients died of distant metastases, one with local recurrence and one with trilateral disease but local control. Local recurrence after initial external beam radiation therapy only was seen in 8 of 19 eyes (42%). Failures occurred in 6 of 13 group V eyes, 1 of 2 group IV eyes and 1 of 2 group III eyes. Further local therapy included plaque therapy in 3 eyes, cryotherapy in 3 eyes and enucleation in one eye. Surgery was refused for one patient with bilateral recurrences. Ultimate local control after external beam irradiation plus additional local therapies was 16 of 19 eyes (84%). Post-irradiation ocular loss occurred in 5 of 19 eyes. Therefore, overall local control with ocular preservation was achieved in 14 of 19 eyes (74%). Vision

  17. Treatment of retinoblastoma by precision megavoltage radiation therapy

    International Nuclear Information System (INIS)

    Schipper, J.; Peperzeel, H.A. van; Tan, K.E.W.P.

    1985-01-01

    The principal treatment concept in the Utrecht Retinoblastoma Centre is megavoltage irradiation, followed by light coagulation and/or cryotherapy if there is any doubt as to whether the residual tumour is still active. Radiation therapy is administered by means of a simple but highly accurate temporal beam technique. A standardized dose of 45 Gy is given in 15 fractions of 3 Gy at 3 fractions per week. From 1971 to 1982, 39 children with retinoblastoma have been irradiated in at least one eye. Of the 73 affected eyes, 18 were primarily enucleated, one received light coagulation only, and 54 received radiation therapy. Of the 54 irradiated eyes, 32 were additionally treated by light coagulation and/or cryotherapy for suspicious residual tumour (in 29 eyes), recurrent tumour (in 1 eye), and/or new tumour (in 3 eyes) and 10 were ultimately enucleated. Two eyes also received hyperthermia. The percentages of cure of the irradiated eyes with a minimum follow-up of 2 years were 100% (14/14), 100% (9/9,) 83% (10/12), 79% (11/14) and 0% (0/5) in the Reese-Ellsworth groups I to V-A, respectively. Of the saved eyes 95% achieved useful vision. Eighteen eyes developed a clinically detectable radiation cataract; in five of these the lens was aspirated. Cataracts developed exclusively in those lenses of which a posterior portion of more than 1 mm had to be included in the treatment field. The likelihood and the degree of cataract formation was found to be directly related to the dose of radiation to the germinative zone of the lens epithelium. The minimum cataractogenic dose found in this series was 8 Gy. (Auth.)

  18. Treatment of retinoblastoma by precision megavoltage radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schipper, J.; Peperzeel, H.A. van (Rijksuniversiteit Utrecht (Netherlands). Academisch Ziekenhuis); Tan, K.E.W.P. (Royal Dutch Eye Hospital, Utrecht, Netherlands)

    1985-02-01

    The principal treatment concept in the Utrecht Retinoblastoma Centre is megavoltage irradiation, followed by light coagulation and/or cryotherapy if there is any doubt as to whether the residual tumour is still active. Radiation therapy is administered by means of a simple but highly accurate temporal beam technique. A standardized dose of 45 Gy is given in 15 fractions of 3 Gy at 3 fractions per week. From 1971 to 1982, 39 children with retinoblastoma have been irradiated in at least one eye. Of the 73 affected eyes, 18 were primarily enucleated, one received light coagulation only, and 54 received radiation therapy. Of the 54 irradiated eyes, 32 were additionally treated by light coagulation and/or cryotherapy for suspicious residual tumour (in 29 eyes), recurrent tumour (in 1 eye), and/or new tumour (in 3 eyes) and 10 were ultimately enucleated. Two eyes also received hyperthermia. The percentages of cure of the irradiated eyes with a minimum follow-up of 2 years were 100% (14/14), 100% (9/9), 83% (10/12), 79% (11/14) and 0% (0/5) in the Reese-Ellsworth groups I to V-A, respectively. Of the saved eyes 95% achieved useful vision. Eighteen eyes developed a clinically detectable radiation cataract; in five of these the lens was aspirated. Cataracts developed exclusively in those lenses of which a posterior portion of more than 1 mm had to be included in the treatment field. The likelihood and the degree of cataract formation was found to be directly related to the dose of radiation to the germinative zone of the lens epithelium. The minimum cataractogenic dose found in this series was 8 Gy.

  19. Optimized lens-sparing treatment of retinoblastoma with electron beams

    International Nuclear Information System (INIS)

    Steenbakkers, Roel J.H.M.; Altschuler, Martin D.; D'Angio, Giulio J.; Goldwein, Joel W.; Kassaee, Alireza

    1997-01-01

    Purpose: The ideal lens-sparing radiotherapy technique for retinoblastoma calls for 100% dose to the entire retina including the ora serrata and zero dose to the lens. Published techniques, most of which use photons, have not accomplished this ideal treatment. We describe here a technique that approaches this ideal configuration using electron beam therapy. Methods and Materials: Dose-modeling calculations were made using a computer program built around a proprietary algorithm. This program calculates 3D dose distribution for electrons and photons and uses the Cimmino feasibility method for the inverse problem of beam weighting to achieve the prescribed dose. The algorithm has been verified in the ocular region by measurements in a RANDO phantom. To search for an ideal lens-sparing beam setup, a stylized phantom of an 8-month-old infant was generated with built-in inhomogeneities, and a phantom of a 5-year-old child was generated from a patient CT series. Results: Of more than 100 different beam setups tested, two 9 MeV electron beams at gantry angles plus and minus 26 degrees from the optic nerve axis achieved the best distribution. Both fields have a lens block and an isocenter between the globe and origin of the optic nerve. When equal doses are given to both fields, the entire extent of the retina (including ora serrata) received 100%, while the lens received 10% or less. Conclusion: The two-oblique-electron-beam technique here described appears to meet most of the stringent dosimetry needed to treat retinoblastoma. It is suitable for a range of ages, from infancy to early childhood years

  20. Protein mediated synthesis of fluorescent Au-nanoclusters for metal sensory coatings

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Manja; Raff, Johannes [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biogeochemistry

    2017-06-01

    Fluorescent Au-nanocluster were successfully synthesized and used for the selective detection of Cu{sup 2} {sup +}. The synthesized Au-BSA-nanoclusters remain functional also after immobilization and show high thermal stability. Additionally, the transfer of the protein mediated Au-nanocluster synthesis route to S-layer proteins was achieved. (The presented work is part of the project BIONEWS dealing with long-term stable cells for the set-up and regeneration of sensor and actor materials for strategic relevant metals, in particular rare earth elements).

  1. Clinical presentation of retinoblastoma in Alexandria: A step toward earlier diagnosis.

    Science.gov (United States)

    Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad

    2017-01-01

    To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.

  2. Colorimetric and longitudinal analysis of leukocoria in recreational photographs of children with retinoblastoma.

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    Alireza Abdolvahabi

    Full Text Available Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., "white eye" in recreational photographs. A quantitative definition or scale of leukocoria--as it appears during recreational photography--has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop® and standard color space conversion algorithms (operable in Microsoft Excel® to quantify leukocoria in actual "baby pictures" of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings. One particular patient with bilateral retinoblastoma ("Patient Zero" was photographed >7, 000 times by his parents (who are authors of this study over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patient's life. This study establishes: (i that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii that Hue, Saturation and Value (i.e., HSV color space are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography.

  3. Información sobre las secuelas y futuros riesgos para los sobrevivientes de retinoblastoma Information on late effects and future risks for retinoblastoma survivors

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    Laura Schwartz

    2005-04-01

    Full Text Available Los índices de sobrevida de los pacientes con cáncer en la infancia han aumentado en las últimas décadas. Se observan secuelas como consecuencia de esta enfermedad y su tratamiento. Los sobrevivientes de retinoblastoma presentan efectos adversos como consecuencia de la cirugía, la radioterapia y la quimioterapia. Las formas bilaterales irradiadas presentan un riesgo aumentado de desarrollar un segundo cáncer. Tanto los casos que presentaron retinoblastoma unilateral o bilateral pueden transmitir esta enfermedad a su descendencia. El diagnóstico de este tumor es excepcional después de los 4 años de edad y no se sabe claramente qué conocimiento tienen estos sobrevivientes del diagnóstico, del tratamiento y de los futuros riesgos. El consentimiento informado y el posterior resumen de historia clínica no aclaran demasiado a los padres. Los pacientes curados de retinoblastoma se verían beneficiados con un seguimiento prolongado en las instituciones en que fueron tratados, ya que les permitiría recibir información acerca de lo padecido, del tratamiento, de los riesgos y se podrían identificar las consecuencias posteriores de la enfermedad y su tratamiento.The survival rates of childhood cancer have increased in the past few decades. Late consequences related to the cancer and the treatment are observed. The late effects in retinoblastoma survivors are related to the surgery, the radiotherapy and the chemotherapy. Patients with irradiated bilateral retinoblastoma are at high risk to develop a second cancer. Survivors of bilateral or unilateral forms could transmit this disease to their offspring. The diagnosis of retinoblastoma is exceptional after 4 years of age, and it is not clear whether these survivors have knowledge of their diagnosis, treatment and future risks. The informed consent and the summary of the clinical histories do not help to clarify the situation. It will be of great benefit for the patients cured of retinoblastoma

  4. Epidemiologic Study of Retinoblastoma in Recife, Pernambuco - Brazil: January 1985 - July 1997 Estudo Epidemiológico do Retinoblastoma no Recife - Pernambuco - Brasil: janeiro 1985 - julho 1997

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    Armando Anderson Abreu

    1999-10-01

    Full Text Available Background: Retinoblastoma is by far the most frequent malignant intraocular tumor of childhood. This study was performed to characterize the clinical, diagnostic, treatment and prognostic aspects in patients with retinoblastoma in three reference centers for this pathology in the city of Recife, Pernambuco - Brazil. Methods: A consecutive series of 85 patients with retinoblastoma was reviewed. The authors selected 66 patients (77.6% that fulfilled the inclusion criteria for these study. Results: Of a total of 66 patients with retinoblastoma, 4.5% had a previous history of the disease in the family. Males were more affected than females at a ratio (male/female of 1.12. The mean age of appearance of the first symptoms was 23.8 months, with leukocoria and ocular hyperemia being the most frequent. The mean age at time of diagnosis was 31.7 months and for surgical treatment 32.8 months. The right eye was affected in 42.4% of the cases and the left was involved in 37.9% of cases. The tumor was unilateral in 80.3% and bilateral in 19.7% of the cases. There was extraocular involvement in 62.1%, and it was intraocular in 37.9% of the patients. Treatment was surgery combined with chemotherapy in 47.0% of the patients. 27.3% of the patients died and 19.7% abandoned the treatment. Conclusions: The data on the epidemiology of retinoblastoma found in our city resembles that of other developing countries, concerning the epidemioloy of retinoblastoma.Objetivo: O retinoblastoma é o tumor maligno intraocular mais freqüente da infância. O objetivo deste estudo foi avaliar aspectos clínicos, de diagnóstico, tratamento e prognóstico em pacientes portadores de retinoblastoma atendidos em três centros de referência para esta patologia na cidade do Recife - PE. Métodos: Revisamos 85 prontuários de portadores de retinoblastoma e apresentamos o resultado da análise de 66 destes pacientes, atendidos durante o período de janeiro de 1985 a julho de 1997

  5. Postenucleation orbits in retinoblastoma: treatment with 125I brachytherapy

    International Nuclear Information System (INIS)

    Stannard, Clare; Sealy, Ross; Hering, Egbert; Hough, Jan; Knowles, Ruth; Lecuona, Karin; Reddi, V. Bala

    2002-01-01

    Purpose: Children with retinoblastoma that extends into or through the choroid, sclera, or optic nerve are at risk of developing orbital disease, as well as metastases. Previously, these enucleated orbits were treated with external beam radiotherapy in addition to chemotherapy. 125 I brachytherapy for tumors in and around the eye was pioneered by Sealy in Cape Town, South Africa, in 1974. In 1983, he developed a technique to irradiate the contents of the orbit while limiting the dose to the bony orbit and eyelids. Methods and Materials: Six nylon tubes containing 125 I seeds were implanted through the eyelids around the periphery of the orbit. Each contained a metal gutter that screens the outer part of the seeds from the bony orbit. A seventh unscreened tube was placed in the center, and a metal disc with 125 I seeds on its posterior surface was secured beneath the eyelids. Between 1983 and 2000, 57 orbits were treated in 56 children with retinoblastoma. Thirty-six were treated prophylactically and 21, with tumor at the resection line of the nerve, extrascleral tumor, or metastases, were treated therapeutically. They received a median dose of 34 Gy in 70 h; 30 also received chemotherapy. Children with tumor at the resection line of the nerve also received treatment to the craniospinal axis. Results: The median follow-up of the 35 patients treated prophylactically was 35 months (range 0-187). Seven patients died, 6 of metastases, at a median of 10 months (range 4-29) after the implant. Eight of the 13 patients with microscopic extraocular tumor survived a median of 29 months (range 5-156). None of the 8 patients presenting with orbital tumor or metastases survived. No orbital recurrences developed in any of the patients. Cosmesis was considerably improved compared with previous forms of irradiation. Conclusion: Orbital brachytherapy is an effective method of irradiating the orbit to prevent recurrent tumor, the treatment time is short, and the cosmesis is much more

  6. Psychosocial factors influencing parental decision to allow or refuse potentially lifesaving enucleation in children with retinoblastoma

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    Rolando Enrique D. Domingo

    2017-01-01

    Full Text Available Objective: Retinoblastoma is the most common malignancy of the eye and ocular adnexa in the Philippines. It is curable when treated early, but delay in enucleation is common due to the parental refusal of surgery for varied reasons. The aim of this study is to identify the psychosocial barriers and facilitating factors for accepting versus refusing enucleation as treatment for retinoblastoma. Methods: This is a cross-sectional descriptive study utilizing structured interviews and a questionnaire. It was conducted at the Retinoblastoma Clinic of the Philippine General Hospital. A questionnaire using the Likert scale was constructed after performing key informant interviews and focus group discussions. It was pretested and revised before parents of patients with retinoblastoma were invited to participate in the study. Descriptive statistics, quantitative item analyses using inter-item correlations and item-total correlations was performed. Results: Factors that correlate with refusal to enucleate are the beliefs that cancer is a fatal illness, the fear of unacceptable esthetic outcome of the surgery, and the cost of treatment. Favorable factors include value of life, high regard for the opinion of medical practitioners, and appreciation of the efficacy of treatment. Conclusions: There are several favorable factors and barriers that health practitioners must consider in facilitating parental decision-making toward enucleation for retinoblastoma.

  7. The genetic alteration of retinoblastoma gene in esophageal cancer

    International Nuclear Information System (INIS)

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it's alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author)

  8. [Eyeball salvage treatment or enucleation for advanced retinoblastoma].

    Science.gov (United States)

    Qian, J; Xue, K

    2016-10-11

    The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732) .

  9. Retinoblastoma: Achieving new standards with methods of chemotherapy

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available The management of retinoblastoma (RB has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  10. Expression and clinical significance of Pax6 gene in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Hai-Dong Huang

    2013-07-01

    Full Text Available AIM: To discuss the expression and clinical significance of Pax6 gene in retinoblastoma(Rb. METHODS: Totally 15 cases of fresh Rb organizations were selected as observation group and 15 normal retinal organizations as control group. Western-Blot and reverse transcriptase polymerase chain reaction(RT-PCRmethods were used to detect Pax6 protein and Pax6 mRNA expressions of the normal retina organizations and Rb organizations. At the same time, Western Blot method was used to detect the Pax6 gene downstream MATH5 and BRN3b differentiation gene protein level expression. After the comparison between two groups, the expression and clinical significance of Pax6 gene in Rb were discussed. RESULTS: In the observation group, average value of mRNA expression of Pax6 gene was 0.99±0.03; average value of Pax6 gene protein expression was 2.07±0.15; average value of BRN3b protein expression was 0.195±0.016; average value of MATH5 protein expression was 0.190±0.031. They were significantly higher than the control group, and the differences were statistically significant(PCONCLUSION: Abnormal expression of Pax6 gene is likely to accelerate the occurrence of Rb.

  11. The genetic alteration of retinoblastoma gene in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).

  12. Dosimetric intercomparison between protons and electrons therapies applied to retinoblastoma

    International Nuclear Information System (INIS)

    Braga, Flavia Vieira

    2008-01-01

    In this work we propose a construction of a simple human eye model in order to simulate the dosimetric response for a treatment with protons and electrons in a retinoblastoma cancer. The computational tool used in this simulation was the Geant4 code, in the version 4.9.1, all these package are free and permit simulate the interaction of radiation with matter. In our simulation we use a box with 4 cm side, with water, for represent the human eye. The simulation was performed considering mono energetics beams of protons and electrons with energy range between 50 and 70 MeV for protons and 2 and 10 MeV for electrons. The simulation was based on the advanced hadron therapy example of the Geant 4 code. In these example the phantom is divided in voxels with 0.2 mm side and it is generated the energy deposited in each voxel. The simulation results show the energy deliver in each voxel, with these energie we can calculate the dose deposited in that region. We can see the dose profile of, proton and electron, and we can see in both cases that for protons the position of delivered dose is well know, that happen in the position where the proton stop, for electrons the energies is delivered along the way and pass the desired position for high dose deposition. (author)

  13. Retinoblastoma loss modulates DNA damage response favoring tumor progression.

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    Marcos Seoane

    Full Text Available Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS, crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRas(V12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies.

  14. Autologous fat graft in irradiated orbit postenucleation for retinoblastoma.

    Science.gov (United States)

    Klinger, Francesco; Maione, Luca; Vinci, Valeriano; Lisa, Andrea; Barbera, Federico; Balia, Laura; Caviggioli, Fabio; Di Maria, Alessandra

    2018-01-05

    Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.

  15. Analysis of MDM2 and MDM4 single nucleotide polymorphisms, mRNA splicing and protein expression in retinoblastoma.

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    Justina McEvoy

    Full Text Available Retinoblastoma is a childhood cancer of the developing retina that begins in utero and is diagnosed in the first years of life. Biallelic RB1 gene inactivation is the initiating genetic lesion in retinoblastoma. The p53 gene is intact in human retinoblastoma but the pathway is believed to be suppressed by increased expression of MDM4 (MDMX and MDM2. Here we quantify the expression of MDM4 and MDM2 mRNA and protein in human fetal retinae, primary retinoblastomas, retinoblastoma cell lines and several independent orthotopic retinoblastoma xenografts. We found that MDM4 is the major p53 antagonist expressed in retinoblastoma and in the developing human retina. We also discovered that MDM4 protein steady state levels are much higher in retinoblastoma than in human fetal retinae. This increase would not have been predicted based on the mRNA levels. We explored several possible post-transcriptional mechanisms that may contribute to the elevated levels of MDM4 protein. A proportion of MDM4 transcripts are alternatively spliced to produce protein products that are reported to be more stable and oncogenic. We also discovered that a microRNA predicted to target MDM4 (miR191 was downregulated in retinoblastoma relative to human fetal retinae and a subset of samples had somatic mutations that eliminated the miR-191 binding site in the MDM4 mRNA. Taken together, these data suggest that post-transcriptional mechanisms may contribute to stabilization of the MDM4 protein in retinoblastoma.

  16. Repair and replication of DNA in hereditary (bilateral) retinoblastoma cells after X-irradiation

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Char, D.; Charles, W.C.; Rand, N.

    1982-01-01

    Fibroblasts from patients with hereditary retinoblastoma reportedly exhibit increased sensitivity to killing by X-rays. Although some human syndromes with similar or greater hypersensitivity to DNA-damaging agents (e.g., X-rays, ultraviolet light, and chemical carcinogens), such as xeroderma pigmentosum, are deficient in DNA repair, most do not have such clearly demonstrable defects in repair. Retinoblastoma cells appear to be normal in repairing single-strand breaks and performing repair replication after X-irradiation and also in synthesizing poly(adenosine diphosphoribose). Semiconservative DNA replication in these cells, however, is slightly more resistant than normal after X-irradiation, suggesting that continued replication of damaged parental DNA could contribute to the pathogenesis of the disease. This effect is small, however, and may be a consequence rather than a cause of the fundamental enzymatic abnormality in retinoblastoma that causes the tumorigenesis

  17. Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.

    Science.gov (United States)

    Houston, Samuel K; Pina, Yolanda; Clarke, Jennifer; Koru-Sengul, Tulay; Scott, William K; Nathanson, Lubov; Schefler, Amy C; Murray, Timothy G

    2011-07-23

    The purpose of this study was to evaluate by microarray the hypothesis that LH(BETA)T(AG) retinoblastoma tumors exhibit regional and temporal variations in gene expression. LH(BETA)T(AG) mice aged 12, 16, and 20 weeks were euthanatized (n = 9). Specimens were taken from five tumor areas (apex, anterior lateral, center, base, and posterior lateral). Samples were hybridized to gene microarrays. The data were preprocessed and analyzed, and genes with a P 2.5 were considered to be differentially expressed. Differentially expressed genes were analyzed for overlap with known networks by using pathway analysis tools. There were significant temporal (P regional differences in gene expression for LH(BETA)T(AG) retinoblastoma tumors. At P 2.5, there were significant changes in gene expression of 190 genes apically, 84 genes anterolaterally, 126 genes posteriorly, 56 genes centrally, and 134 genes at the base. Differentially expressed genes overlapped with known networks, with significant involvement in regulation of cellular proliferation and growth, response to oxygen levels and hypoxia, regulation of cellular processes, cellular signaling cascades, and angiogenesis. There are significant temporal and regional variations in the LH(BETA)T(AG) retinoblastoma model. Differentially expressed genes overlap with key pathways that may play pivotal roles in murine retinoblastoma development. These findings suggest the mechanisms involved in tumor growth and progression in murine retinoblastoma tumors and identify pathways for analysis at a functional level, to determine significance in human retinoblastoma. Microarray analysis of LH(BETA)T(AG) retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.

  18. Rhegmatogenous retinal detachment in an eye of retinoblastoma treated by radiation and cryocoagulation

    International Nuclear Information System (INIS)

    Inoue, Makoto; Tanaka, Yasuhiko; Kawai, Masataka; Nii, Seiji; Katsura, Hiroshi; Kaneko, Akihiro

    1999-01-01

    A 4-month-old female infant was diagnosed as bilateral retinoblastoma. The left eye was treated by enucleation and the right by radiation. The right eye received repeated thermochemotherapy, cryocoagulation and photocoagulation for recurrence. Total retinal detachment was detected after surgery for complicated cataract at the age of 2 years 9 months. Vitreous surgery led to the detection of posterior vitreous detachment and retinal breaks in the coagulated scar areas with vitreoretinal adhesion around the calcified tumor. During the following one year, the retina has been attached with no reoccurrence of the tumor. This case illustrates that rhegmatogenous retinal detachment is a possibility in retinoblastoma treated by radiation or retinal coagulations. (author)

  19. Retinoblastoma: experience of a referral center in the North Region of Portugal

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    Rocha-Bastos R

    2014-05-01

    Full Text Available RA da Rocha-Bastos,1 JR Araújo,1 RS Silva,2 MJ Gil-da-Costa,2 E Brandão,1 NJ Farinha,2,3 F Falcão-Reis,1,4 T Dinah-Bragança1 1Department of Ophthalmology, Hospital São João, 2Hematology and Oncology Unit, Pediatric Hospital, Hospital São João, 3Pediatrics Department, Faculty of Medicine, University of Porto, 4Department of Sense Organs, Faculty of Medicine, University of Porto, Porto, Portugal Purpose: To describe the experience of the Ophthalmology Department of Hospital São João (HSJ, a tertiary health care center in North Region, Portugal, in terms of the diagnosis, treatment, and follow-up of retinoblastoma. Methods: This was a retrospective study of patients diagnosed with retinoblastoma in Hospital São João, between 1978 and 2012. Results: Fifty patients with retinoblastoma were evaluated in our institution between 1978 and 2012. Four patients were excluded due to loss of follow-up. Among the 46 retinoblastoma cases, 33 (71.7% were unilateral and 13 (28.3% bilateral, with a mean age at diagnosis of 22.19 months and 6.92 months, respectively (P<0.001. Leukocoria was the most common presenting sign (36.9%, followed by strabismus (19.6%, a combination of leukocoria and strabismus (8.7%, and buphthalmia (2.2%. Between 1978 and 1992, nine retinoblastoma cases were referred to our hospital, all of them unilateral, and, in each case, enucleation was performed, with or without salvage therapy. Between 1993 and 2012, 18 eyes with retinoblastoma were successfully managed with conservative treatment. Conclusion: Demographic results were generally coincident with previous reports. It is crucial to screen leukocoria in pediatric practice, even in asymptomatic children. The outcome of retinoblastoma treatment in our hospital is similar to other series in developed countries. Keywords: retinoblastoma, leukocoria, strabismus, enucleation, pediatric cancer

  20. Retinoblastoma pathway defects show differential ability to activate the constitutive DNA damage response in human tumorigenesis

    DEFF Research Database (Denmark)

    Tort, F.; Bartkova, J.; Sehested, M.

    2006-01-01

    culture models with differential defects of retinoblastoma pathway components, as overexpression of cyclin D1 or lack of p16(Ink4a), either alone or combined, did not elicit detectable DDR. In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse...... with their hierarchical positions along the retinoblastoma pathway. Our data provide new insights into oncogene-evoked DDR in human tumorigenesis, with potential implications for individualized management of tumors with elevated cyclin D1 versus cyclin E, due to their distinct clinical variables and biological behavior....

  1. Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Jørgensen, Claus; Petersen, Rasmus K

    2004-01-01

    Adipocyte precursor cells give raise to two major cell populations with different physiological roles: white and brown adipocytes. Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation. Functional inactivation of pRB in wild-type mouse embryo...... fibroblasts (MEFs) and white preadipocytes by expression of simian virus 40 large T antigen results in the expression of the brown fat-specific uncoupling protein 1 (UCP-1) in the adipose state. Retinoblastoma gene-deficient (Rb-/-) MEFs and stem cells, but not the corresponding wild-type cells, differentiate...

  2. Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Ursula Winter

    Full Text Available Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure or metronomic (7-day continuous exposure treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50 was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks and metronomic (5 days a week for 2 weeks topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3-23 was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p0.05. In mice, continuous topotecan lead to significantly lower tumor volumes compared to conventional treatment after 14 days of treatment (p<0.05. Continuous exposure to melphalan or topotecan increased the chemosensitivity of retinoblastoma and endothelial cells to both chemotherapy agents with lower IC50 values compared to short-term treatment. These findings were validated in an in vivo model. None of the dosing modalities induced

  3. [Treatment modalities and results of comprehensive therapy for extended retinoblastoma in children].

    Science.gov (United States)

    Belkina, B M; Durnov, L A; Poliakov, V G; Goldobenko, G V; Glekov, I V; Ushakova, T L

    1997-01-01

    New procedures of laser therapy and chemotherapy have extended the scope of application of organ-saving treatment at advanced stages of retinoblastoma in childhood, thus making it possible to preserve the eye fully functional or cosmetic. Not having to perform such mutilating procedures as ophthalmectomy or eye socket exenteration contributes to psychological and physical rehabilitation. At the same time, as a comparison of the results of surgery carried out at initial stages and surgery-free treatment showed that palliative therapy is characterized by impressive rates of 5-year survival. New vistas have opened of in the management of pediatric retinoblastoma, particularly in cases of stage III tumor and bilateral involvement.

  4. HaloTag protein-mediated specific labeling of living cells with quantum dots

    International Nuclear Information System (INIS)

    So, Min-kyung; Yao Hequan; Rao Jianghong

    2008-01-01

    Quantum dots emerge as an attractive alternative to small molecule fluorophores as fluorescent tags for in vivo cell labeling and imaging. This communication presents a method for specific labeling of live cells using quantum dots. The labeling is mediated by HaloTag protein expressed at the cell surface which forms a stable covalent adduct with its ligand (HaloTag ligand). The labeling can be performed in one single step with quantum dot conjugates that are functionalized with HaloTag ligand, or in two steps with biotinylated HaloTag ligand first and followed by streptavidin coated quantum dots. Live cell fluorescence imaging indicates that the labeling is specific and takes place at the cell surface. This HaloTag protein-mediated cell labeling method should facilitate the application of quantum dots for live cell imaging

  5. Discharge and infection in retinoblastoma post-enucleation sockets.

    Science.gov (United States)

    Mourits, Daphne L; Hartong, Dyonne T; Budding, Andries E; Bosscha, Machteld I; Tan, H Stevie; Moll, Annette C

    2017-01-01

    To investigate the causes and treatment options for socket discharge and infection in patients enucleated for retinoblastoma (Rb). A questionnaire was filled out by (parents of) ocular prosthesis-wearing patients with a history of enucleation as treatment for Rb. We collected data on patients' characteristics, cleaning habits of the prosthesis, frequency of socket irritation, discharge, and infection, and use of antibiotics. With ordinal logistic regression analysis, factors related to the outcome parameters (frequency of irritation, mucoid and purulent discharge) were identified. In a subset of young asymptomatic and symptomatic patients, a swab culture of the socket was performed to determine the presence of microorganisms. A total of 186 patients or their parents (mean age of the patients: 17.3 years, ranging from 0.8 to 88.3 years) filled out the questionnaire. Irritation, mucoid discharge, and purulent discharge were frequently (once a month or more often) experienced in 75 (39.5%), 127 (66.8%), and 15 (13.2%) sockets, respectively. Younger age was associated with a higher frequency of mucoid and purulent discharge. Radiation therapy, chemotherapy, gender, age at surgery, cleaning frequency, and nocturnal wear were not associated with the outcome parameters. In a subgroup of 26 patients, the sockets were swabbed and cultured. All symptomatic patients had a positive bacterial culture versus 15% (2/13) of the asymptomatic patients ( P socket infection. These complaints were found to decrease with increasing age, but did not seem to be influenced by cleaning or wearing habits. Symptomatic sockets, with and without discharge, were correlated with the presence of pathogenic bacteria for which local antibiotic treatment seemed effective in most cases.

  6. Cell size checkpoint control by the retinoblastoma tumor suppressor pathway.

    Science.gov (United States)

    Fang, Su-Chiung; de los Reyes, Chris; Umen, James G

    2006-10-13

    Size control is essential for all proliferating cells, and is thought to be regulated by checkpoints that couple cell size to cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressor pathway are consistent with a role in size checkpoint control, but indirect effects on size caused by altered cell cycle kinetics are difficult to rule out. The multiple fission cell cycle of the unicellular alga Chlamydomonas reinhardtii uncouples growth from division, allowing direct assessment of the relationship between size phenotypes and checkpoint function. Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous cell divisions and small cells, suggesting a role for MAT3 in size control. We identified suppressors of an mat3 null allele that had recessive mutations in DP1 or dominant mutations in E2F1, loci encoding homologs of a heterodimeric transcription factor that is targeted by RB-related proteins. Significantly, we determined that the dp1 and e2f1 phenotypes were caused by defects in size checkpoint control and were not due to a lengthened cell cycle. Despite their cell division defects, mat3, dp1, and e2f1 mutants showed almost no changes in periodic transcription of genes induced during S phase and mitosis, many of which are conserved targets of the RB pathway. Conversely, we found that regulation of cell size was unaffected when S phase and mitotic transcription were inhibited. Our data provide direct evidence that the RB pathway mediates cell size checkpoint control and suggest that such control is not directly coupled to the magnitude of periodic cell cycle transcription.

  7. Quality of life of adult retinoblastoma survivors in the Netherlands

    Directory of Open Access Journals (Sweden)

    Cohen-Kettenis Peggy T

    2007-06-01

    Full Text Available Abstract Background To assess the quality of life (QoL and predictors thereof in Dutch adult hereditary and non-hereditary retinoblastoma (RB survivors. Methods In this population-based cross-sectional study, a generic QoL questionnaire (SF-36 and a disease-specific interview were administered to 87 adult RB survivors aged 18 to 35 years. Their QoL data were compared with those of a Dutch healthy reference group. Among the RB hereditary/non-hereditary survivors, the QoL was compared and predictors for QoL were identified by linear multiple regression analyses. Results As a group, RB survivors scored significantly lower than the reference group on the SF-36 subscale 'mental health' (t = -27, df = 86, p Conclusion In this exploratory study, it appears that the group of adult RB survivors experience a relatively good overall but slightly decreased QoL compared with the reference group. However, they report more problems with regard to their mental health (anxiety, feelings of depression, and loss of control. Hereditary RB survivors differ significantly from non-hereditary RB survivors only in 'general health'. Bullying in childhood and subjective experience of impairment are the main predictors of a worse QoL. In order to prevent worsening of QoL, or perhaps to improve it, clinicians should make an inventory of these issues at an early stage. We recommend further research to assess the specific psychological factors that may lead to mental health problems in this population.

  8. Intra-arterial chemotherapy for retinoblastoma: First Indian report

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available Aim: To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC for retinoblastoma (RB in Indian eyes. Materials and Methods: Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg and topetecan (1 mg (n = 4 or melphalan (3 mg/5 mg/7.5 mg alone (n = 2 between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates. Results: IAC was employed as primary (n = 1 or secondary (n = 5 modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions. Eyes were classified according to international classification of RB as Group B (n = 1, C (n = 1, D (n = 2 and E (n = 2. Following IAC, complete regression of the main tumor was seen in 3 cases (50%, partial regression in 2 (33%, while 1 case (15% showed no response. Of 4 eyes with subretinal seeds, 1 (25% eye had complete regression while 3 (75% eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40% eyes had complete regression while 3 (60% eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%. Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17% eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months. Conclusion: IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

  9. A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery

    International Nuclear Information System (INIS)

    Adegbola, Onikepe; Pasternack, Gary R.

    2005-01-01

    We have previously shown pp32 and the retinoblastoma protein interact. pp32 and the retinoblastoma protein are nuclear receptor transcriptional coregulators: the retinoblastoma protein is a coactivator for androgen receptor, the major regulator of prostate cancer growth, while pp32, which is highly expressed in prostate cancer, is a corepressor of the estrogen receptor. We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. Using affinity purification and mass spectrometry, we identify members of the pp32-retinoblastoma protein complex as PSF and nonO/p54nrb, proteins implicated in coordinate regulation of nuclear receptor-mediated transcription and splicing. We show that the pp32-retinoblastoma protein complex is modulated during TPA-induced K562 differentiation. Present evidence suggests that nuclear receptors assemble multiprotein complexes to coordinately regulate transcription and mRNA processing. Our results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing

  10. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yiting; Wu, Dan; Xia, Fengjie; Xian, Hongyu; Zhu, Xinyue [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, 400716 (China); Huang, Zhenping, E-mail: huangzhenping19633@163.com [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China)

    2016-04-29

    Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma. - Highlights: • High expression of HDAC9 correlates with poor patient prognosis. • Downregulation of HDAC9 inhibits cell proliferation in retinoblastoma cells. • Downregulation of HDAC9 induces cell cycle arrest at G1 phase in retinoblastoma cells. • Downregulation of HDAC9 suppresses tumor growth in nude mice.

  11. Skin fibroblasts from a D-deletion type retinoblastoma patient are abnormally X-ray sensitive

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1977-01-01

    Retinoblastoma is a rare malignant eye tumour that appears either spontaneously or in genetically predisposed persons. The latter group is composed of persons who inherit the tumour with a dominant mode of transmission (the familial type) and those who have a deletion in the long arm of chromosome 13 referred to as the D-deletion type. When this deletion is present it is observed in many somatic cells and is often associated with structural defects. Survivors of the genetic forms of retinoblastoma have an increased risk of the development of cancers at other sites. A single genetic locus is unlikely to predispose many somatic cells to tumour formation unless a fundamental molecular defect, possibly related to DNA repair, is present. In order to investigate this hypothesis a study was made of the in vitro X-ray sensitivity of skin fibroblasts derived from three retinoblastoma patients, comprising a pair of twins with the familial type accompanied by no gross chromosome abnormalities, and a patient with the D-deletion type. It was found that fibroblasts derived from the D-deletion patient were significantly more radiosensitive than those from the other two patients. X-ray survival curves are shown. It is concluded that skin fibroblasts derived from a patient with the D-deletion variant of retinoblastoma are abnormally radiosensitive. Future investigations may indicate a specific defect in molecular repair of DNA that will explain the predisposition of these patients to the development of other tumours. (U.K.)

  12. A longitudinal investigation of parenting stress in caregivers of children with retinoblastoma.

    Science.gov (United States)

    Willard, Victoria W; Qaddoumi, Ibrahim; Zhang, Hui; Huang, Lu; Russell, Kathryn M; Brennan, Rachel; Wilson, Matthew W; Rodriguez-Galindo, Carlos; Phipps, Sean

    2017-04-01

    Retinoblastoma is typically diagnosed in young children and may present unique parenting challenges. Qualitative research suggests that parents experience distress related to the initial diagnosis and treatment that subsequently resolves. The objectives were to systematically assess parenting stress over time in parents of young children with retinoblastoma and to examine associations between parenting stress and child outcomes. Parents of children with retinoblastoma completed the Parenting Stress Index (PSI) during serial psychological assessments scheduled based on the child's age (6 months to 5 years). Caregivers of 92 patients (85.9% mothers) completed the assessments. Child outcomes included developmental functioning and parent-reported adaptive functioning. At baseline and age 5, all subscales on the PSI were within normal limits, and most were significantly below normative means (i.e., demonstrating low levels of stress). All domains remained relatively stable over time. Associations between parenting stress and child outcomes were much stronger at age 5 than at baseline. Child-directed parenting stress was a small but significant contributor to declines in child functioning over time. Parents of children with retinoblastoma report normal levels of parenting stress while their children are young. However, baseline parenting stress appears to contribute to changes in child functioning over time. Future studies should assess illness-related aspects of adjustment to further understand the parenting experience of young children with cancer and/or having a visually impaired child. © 2016 Wiley Periodicals, Inc.

  13. The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation

    DEFF Research Database (Denmark)

    Fajas, Lluis; Egler, Viviane; Reiter, Raphael

    2002-01-01

    The retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP). We show here that the peroxisome proliferator-activated receptor gamma...

  14. Characterization of the retinoblastoma binding proteins RBP1 and RBP2

    DEFF Research Database (Denmark)

    Fattaey, A R; Helin, K; Dembski, M S

    1993-01-01

    The retinoblastoma gene product, pRB, regulates cell proliferation by binding to and inhibiting the activity of key growth promoting proteins. Several cellular proteins have been shown to bind directly to pRB and the genes encoding a number of them have been isolated. The protein product of one...

  15. Total retinal detachments due to retinoblastoma: Outcomes following intra-arterial chemotherapy/ophthalmic artery chemosurgery.

    Directory of Open Access Journals (Sweden)

    Megan A Rowlands

    Full Text Available To report on the rate and timing of retinal reattachment and outcomes for retinoblastoma children who have total retinal detachments at presentation to our center and were treated with intra-arterial chemotherapy (ophthalmic artery chemosurgery, OAC.Single-center retrospective review of retinoblastoma patients who presented with total retinal detachments and were subsequently treated with OAC at MSKCC between May 2006 and July 2016. Endpoints were retinal detachment resolution, visual function, ERG amplitude, ocular survival, and patient survival from metastases.87 eyes of 84 retinoblastoma patients were included. Using a survival multistate model, by 36 months of follow-up, there was a 54% cumulative probability of complete retinal reattachment and a 76% probability of partial reattachment. 24% of eyes that completely reattached received only OAC without any prior or adjuvant treatments. Eyes that completely reattached were significantly more likely to have been diagnosed at a younger age (p<0.0001 and to have greater initial ERG values (p = 0.006. At final follow-up, 14% of eyes had gained at least 25 μV of ERG activity, and 8.0% had achieved hand motion vision or better, including one to 20/60. 13% of eyes were enucleated. No patient died from metastatic disease, and only one developed metastases.OAC can successfully treat previously considered "non-salvageable" retinoblastoma eyes with total retinal detachments, promote retinal reattachment in the majority of eyes, and preserve ocular and patient survival.

  16. Retinoblastoma - MR appearance using a surface coil in comparison with histopathological results

    Energy Technology Data Exchange (ETDEWEB)

    Lemke, Arne-Joern; Kazi, Iris; Mergner, Ulrike; Senfft von Pilsach, Marie-Isabell; Felix, Roland [Campus Virchow-Klinikum, Charite, Universitaetsmedizin Berlin, Berlin (Germany); Foerster, Paul I. [Universitaetsaugenklinik, Klinikum der Universitaet Muenchen-Innenstadt, Muenchen (Germany); Heimann, Heinrich; Bechrakis, Nikolaos; Foerster, Michael [Campus Benjamin-Franklin, Charite, Universitaetsmedizin Berlin, Berlin (Germany); Schueler, Andreas [Universitaetsaugenklinik Essen, Essen (Germany); Hosten, Norbert [Institut fuer Diagnostische Radiologie und Neuroradiologie, Klinikum der Ernst-Moritz-Arndt-Universitaets Greifswald, Greifswald (Germany)

    2007-01-15

    The purpose of this work was to evaluate the characteristic appearance of untreated retinoblastoma on a large sample in comparison to the histological findings after therapeutical enucleation. In a prospective clinical trial 46 children with retinoblastoma in 63 affected untreated eyes were examined under general anesthesia on MRI using a 1.5-T system. The examinations were performed with a special surface coil applying an examination protocol including fast T2- and T1-weighted spin echo sequences and additional fast T1-WI after intravenous injection of Gd-DTPA in different planes. The imaging results were compared to the histopathological findings in 29 patients with 30 affected eyes. Comparing MRI findings and histopathological results, optic nerve infiltration was detected with a sensitivity of 53.8% and a specificity of 82.3% on MRI, infiltration of the choroid with a sensitivity of 75.0% and a specificity of 100.0%, and the degree of tumor calcification with a sensitivity of 91.7% and a specificity of 88.9%. In this study the characteristic MR appearance of untreated retinoblastoma was evaluated. MRI was helpful in relevant aspects of pretherapeutical retinoblastoma staging, deficits remain regarding optic nerve infiltration. (orig.)

  17. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Helin, K; Harlow, E; Fattaey, A

    1993-01-01

    Loss of a functional retinoblastoma tumor suppressor gene product, pRB, is a key step in the development of many human tumors. pRB is a negative regulator of cell proliferation and appears to participate in control of entry into the S phase of the cell cycle. The recent demonstration that pRB binds...

  18. Deregulated MAPK activity prevents adipocyte differentiation of fibroblasts lacking the retinoblastoma protein

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Petersen, Rasmus K; Jørgensen, Claus

    2002-01-01

    A functional retinoblastoma protein (pRB) is required for adipose conversion of preadipocyte cell lines and primary mouse embryo fibroblasts (MEFs) in response to treatment with standard adipogenic inducers. Interestingly, lack of functional pRB in MEFs was recently linked to elevated Ras activity...

  19. Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice

    NARCIS (Netherlands)

    Boesten, L.S.M.; Zadelaar, A.S.M.; Nieuwkoop, A. van; Hu, L.; Jonkers, J.; Water, B. van de; Gijbels, M.J.J.; Made, I. van der; Winther, M.P.J. de; Havekes, L.M.; Vlijmen, B.J.M. van

    2006-01-01

    The cellular composition of an atherosclerotic lesion is determined by cell infiltration, proliferation, and apoptosis. The tumor suppressor gene retinoblastoma (Rb) has been shown to regulate both cell proliferation and cell death in many cell types. To study the role of macrophage Rb in the

  20. Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience.

    Science.gov (United States)

    Gobin, Y Pierre; Dunkel, Ira J; Marr, Brian P; Brodie, Scott E; Abramson, David H

    2011-06-01

    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. Single-arm, prospective registry from May 30, 2006, to May 30, 2010, at an ophthalmic oncology referral center with ambulatory care. A total of 95 eyes of 78 patients with unilateral or bilateral retinoblastoma were treated. The intervention was selective catheterization of the ophthalmic artery and injection of chemotherapy, usually melphalan with or without topotecan. Drug dosage was determined by age and angioanatomy. The main outcome measures were procedural success, event-free (enucleation or radiotherapy) ocular survival, and ocular and extraocular complications. Catheterization succeeded in 98.5% of procedures. There were 289 chemotherapy injections (median, 3 per eye). The Kaplan-Meier estimates of ocular event-free survival rates at 2 years were 70.0% (95% confidence interval, 57.9%-82.2%) for all eyes, 81.7% (95% confidence interval, 66.8%-96.6%) for eyes that received intra-arterial chemotherapy as primary treatment, and 58.4% (95% confidence interval, 39.5%-77.2%) for eyes that had previous treatment failure with intravenous chemotherapy and/or external beam radiation therapy. There were no permanent extraocular complications. Our experience suggests that intra-arterial chemotherapy is safe and effective in the treatment of advanced intraocular retinoblastoma.

  1. Restrictions in daily life after retinoblastoma from the perspective of the survivors

    NARCIS (Netherlands)

    van Dijk, J.; Oostrom, K.J.; Huisman, J.; Moll, A.C.; Cohen-Kettenis, P.T.; Ringens, P.J.; Imhof, S.M.

    2010-01-01

    Background. Little is known about the impact of retinoblastoma (RB) on the health status of survivors in terms of disabilities and worries, both of which may restrict participation in activities of daily life. Methods. In this population-based cross-sectional study, content analysis was used to

  2. RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Mol, Berber M.; Moll, Annette C.; Burton, Margaret; Cloos, Jacqueline; Dorsman, Josephine C.; Meijers-Heijboer, Hanne; van der Hout, Annemarie H.

    Background Retinoblastoma (Rb) is a childhood cancer of the retina, commonly initiated by biallelic inactivation of the RB1 gene. Knowledge of the presence of a heritable RB1 mutation can help in risk management and reproductive decision making. We report here on RB1 mutation scanning in a unique

  3. Radiation-induced fibrosarcoma of the mandible following treatment for bilateral retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Ferlito, A; Recher, G [Padua Univ. (Italy); Tomazzoli, L

    1979-10-01

    A case of fibrosarcoma of the mandible following radiotherapy for bilateral retinoblastoma and occurring in an 11-year-old female child is described. After a clinical description of the case, reported with histological documentation, problems connected with the pathogenesis of the malignancies are dealt with. Besides irradiation, genetic mutation as a carcinogenetic co-factor is taken into consideration. (author).

  4. 3D diagnostic imaging of retinoblastoma with a novel optical coherence tomography clinical system

    NARCIS (Netherlands)

    Nadyarnykh, O.; Moll, Annette C; De Boer, Johannes F.

    Purpose : Reliable in-vivo differentiation between the vital tumor / benign masses, and side effects is the main challenge for retinoblastoma, a retinal malignancy occurring in infancy. We have started an observational clinical study using our novel swept source OCT imaging system operating at

  5. Alteration of plant meristem function by manipulation of the Retinoblastoma-like plant RRB gene

    Science.gov (United States)

    Durfee, Tim [Madison, WI; Feiler, Heidi [Albany, CA; Gruissem, Wilhelm [Forch, CH; Jenkins, Susan [Martinez, CA; Roe, Judith [Manhattan, KS; Zambryski, Patricia [Berkeley, CA

    2007-01-16

    This invention provides methods and compositions for altering the growth, organization, and differentiation of plant tissues. The invention is based on the discovery that, in plants, genetically altering the levels of Retinoblastoma-related gene (RRB) activity produces dramatic effects on the growth, proliferation, organization, and differentiation of plant meristem.

  6. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Carlée, L.; Kerkhoven, R.M.; Bernards, R.A.

    1995-01-01

    The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes. These kinases phosphorylate a number of cellular substrates, among which is the product of the retinoblastoma gene, pRb. Phosphorylation of pRb in late

  7. Irradiation sequels of retinoblastomas. Sequelles de l'irradiation externe des retinoblastomes

    Energy Technology Data Exchange (ETDEWEB)

    Benk, V; Habrand, J L; Bloch Michel, E; Soussaline, M; Sarrazin, D [Centre de Lutte Contre le Cancer Gustave-Roussy, 94 - Villejuif (France)

    1993-01-01

    From 1975 to 1985, 34 children with a non-metastatic retinoblastoma were irradiated at the Institut Gustave-Roussy. After enucleation, 19 bilateral tumors were irradiated by two lateral opposed fields and 15 unilateral tumors by one lateral and anterior field, in the case of optic nerve being histologically positive. Dose was 45 Gy, 1.8 Gy per fraction. The 10-year-survival rate for unilateral and bilateral retinoblastomas was 79%. Long term sequels were available for 25 patients: 88% retained one functional eye. Three children with bilateral retinoblastomas developed a cataract in the residual eye between 2 and 5 years after irradiation, none with unilateral tumor. Nine patients (36%), seven with unilateral and two with bilateral tumor developed a cosmetical problem that required multiple surgical rehabilitation between 3 and 14 years after irradiation. Nine children (36%), five with unilateral and four with bilateral tumors developed growth hormone deficit between 2 and 8 years after irradiation that required hormone replacement. Their pituitary gland received 22 to 40 Gy. No osteosarcoma occurred in this population. Among long-term sequels, following irradiation for retinoblastoma, cosmetical deformities represent disabling sequels that could justify new approaches in radiotherapy, as protontherapy combined with 3-D-treatment planning.

  8. The murine retinoblastoma homolog maps to chromosome 14 near Es-10

    NARCIS (Netherlands)

    Stone, J.C.; Crosby, J.J.; Kozak, C.A.; Schievella, A.R.; Bernards, R.A.; Nadeau, J.H.

    1989-01-01

    Restriction fragment length variants have been exploited to map genetically Rb-1, the murine homolog of the human retinoblastoma gene. Rb-1 localized to mouse chromosome 14 on the basis of results from analysis of somatic cell hybrids. In an interspecific backcross involving Mus spretus, Rb-1 and

  9. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

    Directory of Open Access Journals (Sweden)

    Sailaja V. Elchuri

    2018-05-01

    Full Text Available Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1. Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  10. Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Hashem Alsaab

    2017-04-01

    Full Text Available The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF, loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid-conjugated-folic acid (SMA-FA was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS and transmission electron microscopy (TEM. Cytotoxicity studies were conducted on (Y-79 and WERI-RB retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19, indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies.

  11. Characterization, treatment and prognosis of retinoblastoma with central nervous system metastasis.

    Science.gov (United States)

    Hu, Huimin; Zhang, Weiling; Wang, Yizhuo; Huang, Dongsheng; Shi, Jitong; Li, Bin; Zhang, Yi; Zhou, Yan

    2018-04-23

    Retinoblastoma is the most common primary intraocular tumor and more and more attention has been paid to the developing countries. This study was aimed to evaluate the clinical features, treatment, and prognosis of retinoblastoma patients with central nervous system (CNS) metastasis in Beijing Tongren Hospital, one of the largest tertiary eye centers in China. Clinical data of 31 consecutive retinoblastoma patients with CNS metastases, who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between September 2005 and December 2015, were retrospective analyzed. The median age at presentation was 29 months (range from 5 to 108 months). Magnetic resonance imaging (MRI) results indicated that 16 patients (56.6%, 16/31) presented with meningeal involvement, 12 (38.7%, 12/31) presented with intracranial mass, 11 (35.5%, 11/31) presented with thickened optic nerve, and 5 (16.1%, 5/31) presented with concurrent meningeal and spinal cord membrane involvement. Retinoblastoma cells were detected in the cerebrospinal fluid (CSF) of 12 patients (44.4%, 12/27). Laboratory examinations on the blood and CSF were performed for 11 patients who had received six cycles of systemic chemotherapy, indicated that the serum level of neurone-specific enolase (NSE) after chemotherapy was significantly lower than that before chemotherapy (P < 0.05). At the end of the follow-up, 25 patients were dead with a median survival time of 6 months (1 d - 21 months), and 6 cases were alive and continued to receive treatment. Our results were basically consistent with previous reports in the developing countries, and it could be guidance for clinical treatment, prognosis and prevention of CNS metastases in retinoblastoma.

  12. A 10-year experience of outcome in chemotherapy-treated hereditary retinoblastoma.

    Science.gov (United States)

    Bartuma, Katarina; Pal, Niklas; Kosek, Sonja; Holm, Stefan; All-Ericsson, Charlotta

    2014-08-01

    The aim is to report the 10-year retrospective experience of systemic chemotherapy for a population-based group of patients with hereditary retinoblastoma at a national referral centre. The outcomes include control rates, treatment side-effects, adjuvant therapy, failure rate, survival, secondary cancers and visual acuity. All patients (n = 24, 46 eyes) diagnosed with retinoblastoma and treated with systemic chemotherapy at a national referral centre during 2001-2011 were included. Data were extracted from medical records. The patients were followed for a mean of 60 months (range 13-144). Four-six cycles of VEC was administered to all newly diagnosed group B/C/D/E eyes with bilateral disease and 83% (38 of 46) responded to the treatment. None of the patients discontinued chemotherapy because of adverse reactions. Altogether 26% (12 of 46) of the eyes received second-line therapy (other than thermotherapy, cryotherapy and chemotherapy). The failure rate was 35% (16 of 46) and mortality rate 0%. None of the patients developed CNS manifestations (metastases or trilateral retinoblastoma). One of the patients developed a second primary tumour (osteosarcoma) 4 years following retinoblastoma diagnosis. Altogether 17% (4 of 24) patients received radiation therapy, 28% (13 of 46) of the eyes had to be enucleated, and one patient underwent bilateral enucleation. The age-correlated visual acuity was mean of 73% of expected visual acuity. Group A/B retinoblastomas have a distinct chemotherapy response, while group C/D/E tumours do not respond as well. The success rate was 65%; while patients have a good prognosis for life, approximately one-third of all hereditary cases received radiation therapy or underwent enucleation. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Discharge and infection in retinoblastoma post-enucleation sockets

    Directory of Open Access Journals (Sweden)

    Mourits DL

    2017-03-01

    Full Text Available Daphne L Mourits,1 Dyonne T Hartong,1 Andries E Budding,2 Machteld I Bosscha,1 H Stevie Tan,1 Annette C Moll1 1Department of Ophthalmology, VU University Medical Center, 2Department of Microbiology, Academic Medical Center, Amsterdam, the Netherlands Purpose: To investigate the causes and treatment options for socket discharge and infection in patients enucleated for retinoblastoma (Rb. Methods: A questionnaire was filled out by (parents of ocular prosthesis-wearing patients with a history of enucleation as treatment for Rb. We collected data on patients’ characteristics, cleaning habits of the prosthesis, frequency of socket irritation, discharge, and infection, and use of antibiotics. With ordinal logistic regression analysis, factors related to the outcome parameters (frequency of irritation, mucoid and purulent discharge were identified. In a subset of young asymptomatic and symptomatic patients, a swab culture of the socket was performed to determine the presence of microorganisms. Results: A total of 186 patients or their parents (mean age of the patients: 17.3 years, ranging from 0.8 to 88.3 years filled out the questionnaire. Irritation, mucoid discharge, and purulent discharge were frequently (once a month or more often experienced in 75 (39.5%, 127 (66.8%, and 15 (13.2% sockets, respectively. Younger age was associated with a higher frequency of mucoid and purulent discharge. Radiation therapy, chemotherapy, gender, age at surgery, cleaning frequency, and nocturnal wear were not associated with the outcome parameters. In a subgroup of 26 patients, the sockets were swabbed and cultured. All symptomatic patients had a positive bacterial culture versus 15% (2/13 of the asymptomatic patients (P<0.001. Common cold was correlated with both symptoms and presence of bacteria. Haemophilus influenzae and Staphylococcus aureus were the species most frequently cultured. Conclusion: Ocular prosthesis-wearing patients often experienced mucoid

  14. Arrestin-related proteins mediate pH signaling in fungi

    OpenAIRE

    Herranz, Silvia; Rodríguez, José M.; Bussink, Henk-Jan; Sánchez-Ferrero, Juan C.; Arst, Herbert N.; Peñalva, Miguel A.; Vincent, Olivier

    2005-01-01

    Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-depe...

  15. Protein-mediated efficient synergistic "antenna effect" in a ternary system in D₂O medium.

    Science.gov (United States)

    Ghorai, Shyamal Kr; Samanta, Swarna Kamal; Mukherjee, Manini; Ghosh, Sanjib

    2012-08-16

    A ternary system consisting of a protein, catechin (either + or - epimer), and Tb(III) in suitable aqueous buffer medium at physiological pH (= 6.8) has been shown to exhibit highly efficient "antenna effect". Steady state and time-resolved emission studies of each component in the binary complexes (protein with Tb(III) and (+)- or (-)-catechin with Tb(III)) and the ternary systems along with the molecular docking studies reveal that the efficient sensitization could be ascribed to the effective shielding of microenvironment of Tb(III) from O-H oscillator and increased Tb-C (+/-) interaction in the ternary systems in aqueous medium. The ternary system exhibits protein-mediated efficient antenna effect in D(2)O medium due to synergistic ET from both the lowest ππ* triplet state of Trp residue in protein and that of catechin apart from protection of the Tb(III) environment from matrix vibration. The simple system consisting of (+)- or (-)-catechin and Tb(III) in D(2)O buffer at pH 6.8 has been prescribed to be a useful biosensor.

  16. Refractive-index-based screening of membrane-protein-mediated transfer across biological membranes.

    Science.gov (United States)

    Brändén, Magnus; Tabaei, Seyed R; Fischer, Gerhard; Neutze, Richard; Höök, Fredrik

    2010-07-07

    Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediated transport across lipid bilayer membranes. This method is based on a direct recording of the temporal variations in the refractive index that occur upon a transfer-dependent change in the solute concentration inside liposomes associated to a surface plasmon resonance (SPR) active sensor surface. The applicability of the method is demonstrated by a functional study of the aquaglyceroporin PfAQP from the malaria parasite Plasmodium falciparum. Assays of the temperature dependence of facilitated diffusion of sugar alcohols on a single set of PfAQP-reconstituted liposomes reveal that the activation energies for facilitated diffusion of xylitol and sorbitol are the same as that previously measured for glycerol transport in the aquaglyceroporin of Escherichia coli (5 kcal/mole). These findings indicate that the aquaglyceroporin selectivity filter does not discriminate sugar alcohols based on their length, and that the extra energy cost of dehydration of larger sugar alcohols, upon entering the pore, is compensated for by additional hydrogen-bond interactions within the aquaglyceroporin pore. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors.

    Directory of Open Access Journals (Sweden)

    Patrick Vancura

    Full Text Available The mammalian retina harbors a circadian clockwork that regulates vision and promotes healthiness of retinal neurons, mainly through directing the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors. The gene Gnaz-a unique Gi/o subfamily member-was seen in the present study to be expressed in photoreceptors where its protein product Gαz shows a daily rhythm in its subcellular localization. Apart from subcellular localization, Gnaz displays a daily rhythm in expression-with peak values at night-in preparations of the whole retina, microdissected photoreceptors and photoreceptor-related pinealocytes. In retina, Gnaz rhythmicity was observed to persist under constant darkness and to be abolished in retina deficient for Clock or dopamine D4 receptors. Furthermore, circadian regulation of Gnaz was disturbed in the db/db mouse, a model of diabetic retinopathy. The data of the present study suggest that Gnaz links the circadian clockwork-via dopamine acting on D4 receptors-to G protein-mediated signaling in intact but not diabetic retina.

  18. The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

    Science.gov (United States)

    Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

    2016-01-01

    The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

  19. Cooxidation of styrene by horseradish peroxidase and phenols. A biochemical model for protein-mediated cooxidation

    International Nuclear Information System (INIS)

    Ortiz de Montellano, P.R.; Grab, L.A.

    1987-01-01

    Styrene is oxidized to styrene oxide and benzaldehyde when incubated with horseradish peroxidase, H 2 O 2 , and 4-methylphenol. Styrene oxide is not formed in the absence of any of these reaction components or of molecular oxygen. The coupling products 2-(4-methylphenoxy)-1-phenylethane, 2-(4-methylphenoxy)-1-phenylethan-1-ol, and 2-(4-methylphenoxy)-2-phenylethan-1-ol are not formed, but the ortho-linked dimer of 4-methylphenol is a major product. The epoxide oxygen is labeled in the presence of 18 O 2 but not H 2 18 O 2 . Styrene oxide formation is not inhibited by mannitol or superoxide dismutase. The stereochemistry of trans-[1- 2 H]styrene is partially scrambled in the epoxide product. EPR signals attributable to the 2,4-dihydroxyl-5-methylphenoxy radical, a product of the oxidation of 4-methylcatechol, are observed if Zn 2+ is added to stabilize the radical. This radical is only detected in the presence of styrene. The results imply that styrene is epoxidized by the hydroperoxy radical generated by addition of molecular oxygen to the 4-methylphenoxy radical. The epoxidation mimics the chemistry proposed to occur in the protein-mediated cooxidation of styrene by hemoglobin and myoglobin

  20. Dissecting functions of the retinoblastoma tumor suppressor and the related pocket proteins by integrating genetic, cell biology, and electrophoretic techniques

    DEFF Research Database (Denmark)

    Hansen, Klaus; Lukas, J; Holm, K

    1999-01-01

    The members of the 'pocket protein' family, comprising the retinoblastoma tumor suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell proliferation and modulate fundamental biological processes including embryonic development, differentiation, homeostatic tissue renewal...

  1. Control of cell proliferation, endoreduplication, cell size, and cell death by the retinoblastoma-related pathway in maize endosperm

    KAUST Repository

    Sabelli, Paolo A.; Liu, Yan; Dante, Ricardo Augusto; Lizarraga, Lucina E.; Nguyen, Hong N.; Brown, Sara W.; Klingler, John; Yu, Jingjuan; LaBrant, Evan; Layton, Tracy M.; Feldman, Max; Larkins, Brian A.

    2013-01-01

    , and programmed cell death. Although manipulation of these processes could maximize grain yield, how they are regulated and integrated is poorly understood. We show that the Retinoblastoma-related (RBR) pathway controls key aspects of endosperm development

  2. Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children's Oncology Group.

    Directory of Open Access Journals (Sweden)

    Saeedeh Azary

    Full Text Available Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception contribute to the two phenotypes (bilateral or unilateral of sporadic retinoblastoma.Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424 were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma.Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR, 8.9; 95% confidence interval (CI 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption.The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.

  3. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ginkel, Paul R. van; Yan, Michael B. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Bhattacharya, Saswati [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Pediatrics, University of Wisconsin, Madison, WI 53792 (United States); Polans, Arthur S., E-mail: aspolans@wisc.edu [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Kenealey, Jason D. [UW Carbone Cancer Center, University of Wisconsin, Madison, WI 53792 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792 (United States); Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT 84602 (United States)

    2015-11-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP{sub 3} pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca{sup 2+}-dependent pro-apoptotic pathways inhibit cancer cell growth.

  4. Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells

    International Nuclear Information System (INIS)

    Ginkel, Paul R. van; Yan, Michael B.; Bhattacharya, Saswati; Polans, Arthur S.; Kenealey, Jason D.

    2015-01-01

    Paclitaxel, etoposide, vincristine and doxorubicin are examples of natural products being used as chemotherapeutics but with adverse side effects that limit their therapeutic window. Natural products derived from plants and having low toxicity, such as quercetin, resveratrol, epigallocatechin gallate and piceatannol, have been shown to inhibit tumor cell growth both in vitro and in pre-clinical models of cancer, but their mechanisms of action have not been fully elucidated, thus restricting their use as prototypes for developing synthetic analogs with improved anti-cancer properties. We and others have demonstrated that one of the earliest and consistent events upon exposure of tumor cells to these less toxic natural products is a rise in cytoplasmic calcium, activating several pro-apoptotic pathways. We describe here a G protein/inositol 1,4,5-trisphosphate pathway (InsP3) in MDA-MB-231 human breast cancer cells that mediates between these less toxic natural products and the release of calcium from the endoplasmic reticulum. Further, we demonstrate that this elevation of intracellular calcium modulates p53 activity and the subsequent transcription of several pro-apoptotic genes encoding PIG8, CD95, PIDD, TP53INP, RRM2B, Noxa, p21 and PUMA. We conclude from our findings that less toxic natural products likely bind to a G protein coupled receptor that activates a G protein-mediated and calcium-dependent pathway resulting selectively in tumor cell death. - Highlights: • Natural products having low toxicity increase cytoplasmic calcium in cancer cells. • A G-protein/IP 3 pathway mediates the release of calcium from the ER. • The elevation of intracellular calcium modulates p53 activity. • p53 and other Ca 2+ -dependent pro-apoptotic pathways inhibit cancer cell growth.

  5. Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP.

    Science.gov (United States)

    Zheng, Xunhai; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

    2013-06-18

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. Light-induced, GTP-binding protein mediated membrane currents of Xenopus oocytes injected with rhodopsin of cephalopods.

    Science.gov (United States)

    Ando, H; Seidou, M; Kito, Y

    1991-01-01

    Xenopus oocytes that were injected with rhabdomeric membranes of squid and octopus photoreceptors acquired light sensitivity. The injected oocytes showed a light-induced current having characteristics similar to other G-protein-mediated Cl- currents induced by the activation of other membrane receptors. Pretreatment of the oocytes with pertussis toxin before the injection suppressed the generation of the light-induced current, indicating an ability of cephalopod rhodopsin to cross-react with an endogenous G-protein of Xenopus oocytes.

  7. Post-radiation retinal infiltrates simulating recurrent retinoblastoma: a clinical and pathologic case report

    International Nuclear Information System (INIS)

    Judisch, G.F.; Folberg, R.

    1987-01-01

    An 8-month-old boy was found to have a sporadic unilateral stage IIa retinoblastoma, extending inferiorly and temporally from the right fovea. Within 5 weeks of diagnosis the tumor was treated with 4500 rads fractionated over 20 treatments. Examination under anesthesia (EUA) 1 month later revealed unequivocal clinical and echographic evidence of tumor regression. EUA 3 months after completion of radiation therapy revealed continued tumor regression with no evidence of new tumor formation. The third EUA, performed 6 months after radiation treatment, showed that multiple discreet gray-white retinal infiltrates had developed, predominantly in the area immediately below the regressed tumor. Because of concern that these lesions represented viable retinoblastoma, the eye was enucleated. Pathologic examination of these lesions revealed them to be collections of foamy cells containing melanin granules suggestive of pigment epithelial origin

  8. A TaqI RFLP identified at the retinoblastoma locus on chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Shiang, R; Murray, J C [Univ. of Iowa, Iowa City (USA); Wiggs, J; Dryja, T [Massachusetts Eye and Ear Infirmary, Boston (USA)

    1988-09-26

    Probe D95HS0.5 is a 0.6 kb fragment subcloned into Bluescribe a pUC19 derivative from a bacterio phage library isolated by a cDNA probe of the retinoblastoma gene. The fragment is released with the enzymes HindIII and SaII. TaqI identifies a 2 allele polymorphism with a band at 2.1 kb and 1.8 kb with a frequency of 0.97 and 0.03 respectively. There are no constant bands. The probe was assigned to chromosome 13 using a linkage analysis with retinoblastoma. Co-dominant inheritance was shown in 3 CEPH pedigrees.

  9. Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala

    Science.gov (United States)

    Bendfeldt, Giovana; Lou, Hong; Giron, Veronica; Garrido, Claudia; Valverde, Patricia; Barnoya, Margarita; Castellanos, Mauricio

    2014-01-01

    Analysis of 327 consecutive cases at a pediatric referral hospital of Guatemala reveals that retinoblastoma accounts for 9.4% of all cancers and the estimated incidence is 7.0 cases/million children, higher than the United States or Europe. The number of familial cases is low, and there is a striking disparity in indigenous children due to late diagnosis, advanced disease, rapid progression and elevated mortality. Nine germline mutations in 18 patients were found; two known and five new mutations. Hypermethylation of RB1 was identified in 13% of the tumors. An early diagnosis program could identify cases at an earlier age and improve outcome of retinoblastoma in this diverse population. PMID:24814393

  10. A palliative approach for rehabilitation of a pediatric patient with retinoblastoma

    Directory of Open Access Journals (Sweden)

    Himanshi Aggarwal

    2013-01-01

    Full Text Available Retinoblastoma is a highly malignant neoplasm. Most of the cases are usually far advanced at the time of detection, requiring enucleation to salvage the child′s life. However, the cosmetic rehabilitation of these patients should always be an integral part of their treatment, which helps in their re-integration in the society. This paper presents a case of 5-year-old patient who had undergone enucleation of her left eye due to retinoblastoma. A multidisciplinary approach, including ophthalmologist, psychotherapist, and a prosthodontist, was adopted to meet her physical, psychological, functional, emotional, social, and cosmetic demands. The patient was rehabilitated cosmetically with precisely fabricated ocular prosthesis. An ocular prosthesis is a highly positive and non-invasive approach to improve the cosmetic appearance and psychological well-being of patient.

  11. Isolated lower extremity metastases, 9 years after initial diagnosis of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mulligan, M.E.; Smith, S.E. [University of Maryland, Department of Radiology, Medical School, Baltimore, MD (United States); McCarthy, E.F. [Johns Hopkins Hospital, Department of Pathology, Baltimore, MD (United States)

    2006-10-15

    We report the development of isolated lower extremity metastases, in a child, 9 years after her initial diagnosis and treatment of bilateral infantile retinoblastomas. The radiographic, scintigraphic, computed tomographic, and magnetic resonance imaging findings are discussed. The dominant metastatic focus was blastic, involving the medial cuneiform. Additional occult lesions were found in the base of the second metatarsal, middle cuneiform, navicular and tibial diaphysis. An open biopsy confirmed the diagnosis. The occurrence of late distant metastases is rare in the USA. (orig.)

  12. Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein

    DEFF Research Database (Denmark)

    Zhu, L; van den Heuvel, S; Helin, K

    1993-01-01

    The cellular protein p107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human p107 and have used this clone to study the function of p107. We show that, like pRB, p107 is a potent inhibitor of E2F-mediated trans...

  13. Terminal Ballistics

    CERN Document Server

    Rosenberg, Zvi

    2012-01-01

    This book covers the important issues of terminal ballistics in a comprehensive way combining experimental data, numerical simulations and analytical modeling. The first chapter reviews the experimental equipment which are used for ballistic tests and the diagnostics for material characterization under impulsive loading conditions. The second chapter covers essential features of the codes which are used for terminal ballistics such as the Euler vs. Lagrange schemes and meshing techniques, as well as the most popular material models. The third chapter, devoted to the penetration mechanics of rigid penetrators, brings the update of modeling in this field. The fourth chapter deals with plate perforation and the fifth chapter deals with the penetration mechanics of shaped charge jets and eroding long rods. The last two chapters discuss several techniques for the disruption and defeating of the main threats in armor design. Throughout the book the authors demonstrate the advantages of numerical simulations in unde...

  14. Terminal structure

    Science.gov (United States)

    Schmidt, Frank [Langenhagen, DE; Allais, Arnaud [Hannover, DE; Mirebeau, Pierre [Villebon sur Yvette, FR; Ganhungu, Francois [Vieux-Reng, FR; Lallouet, Nicolas [Saint Martin Boulogne, FR

    2009-10-20

    A terminal structure (2) for a superconducting cable (1) is described. It consists of a conductor (2a) and an insulator (2b) that surrounds the conductor (2a), wherein the superconducting cable (1) has a core with a superconducting conductor (5) and a layer of insulation that surrounds the conductor (5), and wherein the core is arranged in such a way that it can move longitudinally in a cryostat. The conductor (2a) of the terminal structure (2) is electrically connected with the superconducting conductor (5) or with a normal conductor (6) that is connected with the superconducting conductor (5) by means of a tubular part (7) made of an electrically conductive material, wherein the superconducting conductor (5) or the normal conductor (6) can slide in the part (7) in the direction of the superconductor.

  15. Termination unit

    Energy Technology Data Exchange (ETDEWEB)

    Traeholt, Chresten; Willen, Dag; Roden, Mark; Tolbert, Jerry C.; Lindsay, David; Fisher, Paul W.; Nielsen, Carsten Thidemann

    2016-05-03

    Cable end section comprises end-parts of N electrical phases/neutral, and a thermally-insulation envelope comprising cooling fluid. The end-parts each comprises a conductor and are arranged with phase 1 innermost, N outermost surrounded by the neutral, electrical insulation being between phases and N and neutral. The end-parts comprise contacting surfaces located sequentially along the longitudinal extension of the end-section. A termination unit has an insulating envelope connected to a cryostat, special parts at both ends comprising an adapter piece at the cable interface and a closing end-piece terminating the envelope in the end-section. The special parts houses an inlet and/or outlet for cooling fluid. The space between an inner wall of the envelope and a central opening of the cable is filled with cooling fluid. The special part at the end connecting to the cryostat houses an inlet or outlet, splitting cooling flow into cable annular flow and termination annular flow.

  16. Clinical presentation of intraocular retinoblastoma; 5-year hospital-based registry in Egypt

    International Nuclear Information System (INIS)

    El Zomor, H.; Nour, R.; Alieldin, A.; Taha, H.; Montasr, M.M.; Moussa, E.; El Nadi, E.; Alfaar, A.S.; Alfaar, A.S.; El Zomor, H.; Taha, H.; Alieldin, A.; Montasr, M.M.; Moussa, E.; El Nadi, E.; Ezzat, S.

    2015-01-01

    Purpose: To study the presenting signs of Retinoblastoma in Egypt at Egypt’s main pediatric oncology referral center. Methods: This is a prospective descriptive study (hospital-based registry) conducted at Children’s Cancer Hospital Egypt between July 2007 and December 2012. Results: Out of 262 patients diagnosed with retinoblastoma, 244 were suffering from intra-ocular disease at presentation. One hundred thirty-nine (57%) patients presented with unilateral disease, while 105 (43%) suffered bilateral disease. The mean age at presentation was 20.6 ± 17 months, averaging 18.87 ± 11.76 months for bilateral and 25.72 ± 18.78 months for unilateral disease. The most common clinical presentation was leukocoria in 180 (73.8%) patients, strabismus in 32 (13.1%) patients and decreased visual acuity in 12 (4.9%) patients. Group D and E disease represented 62% of all affected eyes. Patients with advanced disease (Group C–E) had longer duration of symptoms.Conclusion: In Egypt, retinoblastoma patients present more frequently with advanced disease. There is an ever-increasing need to develop a national team dedicated to studying disease significance and formulating a national awareness program.

  17. Quantification of lacrimal function after D-shaped field irradiation for retinoblastoma

    International Nuclear Information System (INIS)

    Imhof, S.M.; Tan, K.E.W.P.; Hofman, P.

    1993-01-01

    To study the quantitative effects of mega-voltage external beam irradiation in a D-shaped field in patients with retinoblastoma, biomicroscopy was performed in 61 patients and tear function tests (Schirmer-lactoferrin and lysozyme tests) on 45 eyes in 34 irradiated patients. The results were compared with those obtained in 25 non-irradiated control eyes. The Schirmer test was significantly diminished in irradiated eyes, as were the lactoferrin and lysozyme values. A mild to severe keratitis was found in 17 of the 61 patients (28%). A significant correlation (p<0.005) was found between the severe keratitis and the mean Schirmer values; the mean lactoferrin and lysozyme values were diminished in all patients but did not correlate significantly with the corneal abnormalities. These quantitative data, obtained in patients treated for retinoblastoma, affirm the qualitative data found in patients irradiated for other reasons such as orbital or sinus tumours. Irradiation for retinoblastoma is not a harmless treatment and serious late side effects have to be considered. (Author)

  18. Insights on ornithine decarboxylase silencing as a potential strategy for targeting retinoblastoma.

    Science.gov (United States)

    Muthukumaran, Sivashanmugam; Bhuvanasundar, Renganathan; Umashankar, Vetrivel; Sulochana, K N

    2018-02-01

    Ornithine Decarboxylase (ODC) is a key enzyme involved in polyamine synthesis and is reported to be up regulated in several cancers. However, the effect of ODC gene silencing in retinoblastoma is to be understood for utilization in therapeutic applications. Hence, in this study, a novel siRNA (small interference RNA) targeting ODC was designed and validated in Human Y79 retinoblastoma cells for its effects on intracellular polyamine levels, Matrix Metalloproteinase 2 & 9 activity and Cell cycle. The designed siRNA showed efficient silencing of ODC mRNA expression and protein levels in Y79 cells. It also showed significant reduction of intracellular polyamine levels and altered levels of oncogenic LIN28b expression. By this study, a regulatory loop is proposed, wherein, ODC silencing in Y79 cells to result in decreased polyamine levels, thereby, leading to altered protein levels of Lin28b, MMP-2 and MMP-9, which falls in line with earlier studies in neuroblastoma. Thus, by this study, we propose ODC silencing as a prospective strategy for targeting retinoblastoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Long non-coding RNA H19 suppresses retinoblastoma progression via counteracting miR-17-92 cluster.

    Science.gov (United States)

    Zhang, Aihui; Shang, Weiwei; Nie, Qiaoli; Li, Ting; Li, Suhui

    2018-04-01

    Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis. Mechanistically, we identified seven miR-17-92 cluster binding sites on H19, and found that H19 directly bound to miR-17-92 cluster via these seven binding sites. Through binding to miR-17-92 cluster, H19 relieves the suppressing roles of miR-17-92 cluster on p21. Furthermore, H19 represses STAT3 activation induced by miR-17-92 cluster. Hence, our results revealed that H19 upregulates p21 expression, inhibits STAT3 phosphorylation, and downregulates the expression of STAT3 target genes BCL2, BCL2L1, and BIRC5. In addition, functional assays demonstrated that the mutation of miR-17-92 cluster binding sites on H19 abolished the proliferation inhibiting, cell cycle arrest and cell apoptosis inducing roles of H19 in retinoblastoma. In conclusion, our data suggested that H19 inhibits retinoblastoma progression via counteracting the roles of miR-17-92 cluster, and implied that enhancing the action of H19 may be a promising therapeutic strategy for retinoblastoma. © 2017 Wiley Periodicals, Inc.

  20. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.

    Science.gov (United States)

    Munier, Francis L; Soliman, Sameh; Moulin, Alexandre P; Gaillard, Marie-Claire; Balmer, Aubin; Beck-Popovic, Maja

    2012-08-01

    The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

  1. Outcome of Retinoblastoma Following Limited Sessions of Intra-Arterial Chemotherapy in Iran

    International Nuclear Information System (INIS)

    Ghassemi, Fariba; Ghanaati, Hossein; Karkhaneh, Reza; Boujabadi, Leila; Tabatabaie, Seied Zia; Rajabi, Mohammad Taher

    2014-01-01

    The management of retinoblastoma remains a challenge to the multidisciplinary team, particularly as treatment affects not only visual outcomes, but also ocular retention and morbidity. Management of retinoblastoma has evolved over the past two decades. To report the result of intra-ophthalmic artery chemotherapy (IAC) for the treatment of refractory and advanced retinoblastoma tumors. All patients who had failed to respond adequately to previous treatments and six naive patients with advanced retinoblastoma, receiving IAC between 2009 and 2012, were included in this institutional interventional case series. The patients received 1-2 treatments of IAC given 4-8 weeks apart. Complete response was defined as regressed tumor and complete disappearance of seeding clinically and partial response was defined as partial regression of the tumor with live parts of the tumor and/or lessening of seeds, but not complete disappearance of them clinically. A total of 24 eyes of 24 patients were treated with IAC during the study period. The mean age at the time of IAC was 38.9 months (14-120 months), and the mean follow-up was 16.8 months (3-36 months) after IAC. Tumor control was achieved in 14 eyes (58.3%). Type 3 (combined fleshy and calcified remnants) was the most common type of regression (37.5%). Complications included vitreous hemorrhage in nine eyes (37.5%), arterial occlusion in two (8.3%), cyclitic membrane possibly secondary to ischemia and tractional retinal detachment in one patient (4.2%), chorioretinal atrophy in three (12.5%) patients, and neovascular glaucoma in one eye (4.2%). In eight (33.3%) patients, no complication happened. Globe salvage was achieved in 62.5% of the cases. The success rate for naive patients was 84%. Sixty-seven percent of the cases received transpupillary thermotherapy and cryotherapy before IAC. Intra-ophthalmic artery melphalan is an effective treatment for advanced cases of retinoblastoma, with a reasonable level of success. In the short

  2. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  3. Abnormalities in structure and expression of the retinoblastoma gene in small cell lung cancer cell lines and xenografts in nude mice

    DEFF Research Database (Denmark)

    Rygaard, K; Sorenson, G D; Pettengill, O S

    1990-01-01

    The putative retinoblastoma gene (Rb) is a tumor suppressor gene which is believed to cause retinoblastomas when both alleles are inactivated, leading to lack of the encoded Mr 110,000-116,000 phosphoprotein. Inactivation of the Rb gene has also been found in several other tumor types, including...

  4. Leiomyosarcoma of the bladder in a 16-year-old girl with a history of cyclophosphamide therapy for bilateral retinoblastoma during infancy

    International Nuclear Information System (INIS)

    Al-Zahrani, Ali A.; Kamal, Baher A.; Eldarawani, Hamed M.; Hashim, Tariq M.

    2006-01-01

    A 16-year-old female with bladder leiomyosarcoma had a history of bilateral retinoblastoma at 6 months of life. She received cyclophosphamide chemotherapy after surgical enucleation. In this report, we discussed the possible role of retinoblastoma or cyclophosphamide as a target for development of bladder leiomyosarcoma. (author)

  5. Novel retinoblastoma treatment avoids chemotherapy: the effect of optimally timed combination therapy with angiogenic and glycolytic inhibitors on LHBETATAG retinoblastoma tumors

    Directory of Open Access Journals (Sweden)

    Samuel K Houston

    2011-01-01

    Full Text Available Samuel K Houston1, Yolanda Piña1, Timothy G Murray1, Hinda Boutrid1, Colleen Cebulla2, Amy C Schefler1, Wei Shi1, Magda Celdran1, William Feuer1, Jaime Merchan3, Ted J Lampidis41Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, The Ohio State University, Columbus, OH, USA; 3Division of Hematology/Oncology, Department of Medicine, 4Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of optimally timed combination treatment with angiogenic and glycolytic inhibitors on tumor burden, hypoxia, and angiogenesis in advanced retinoblastoma tumors.Methods: LHBETATAG mice (n = 30 were evaluated. Mice were divided into 5 groups (n = 6 and received injections at 16 weeks of age (advanced tumors with a saline, b anecortave acetate (AA, c 2-deoxyglucose (2-DG, d AA + 2-DG (1 day post-AA treatment, or e AA + 2-DG (1 week post-AA treatment. Eyes were enucleated at 21 weeks and tumor sections were analyzed for hypoxia, angiogenesis, and tumor burden.Results: Eyes treated with 2-DG 1 day post-AA injection showed a 23% (P = 0.03 reduction in tumor burden compared with 2-DG alone and a 61% (P < 0.001 reduction compared with saline-treated eyes. Eyes treated with 2-DG 1 week post-AA injection showed no significant decrease in tumor burden compared with 2-DG alone (P = 0.21 and a 56% (P < 0.001 decrease in comparison with saline-treated eyes. 2-DG significantly reduced the total density of new blood vessels in tumors by 44% compared to saline controls (P < 0.001, but did not affect the density of mature vasculature.Conclusions: Combination therapy with angiogenic and glycolytic inhibitors significantly enhanced tumor control. Synergistic effects were shown to be dependent on the temporal course of treatment

  6. Terminal ballistics

    CERN Document Server

    Rosenberg, Zvi

    2016-01-01

    This book comprehensively discusses essential aspects of terminal ballistics, combining experimental data, numerical simulations and analytical modeling. Employing a unique approach to numerical simulations as a measure of sensitivity for the major physical parameters, the new edition also includes the following features: new figures to better illustrate the problems discussed; improved explanations for the equation of state of a solid and for the cavity expansion process; new data concerning the Kolsky bar test; and a discussion of analytical modeling for the hole diameter in a thin metallic plate impacted by a shaped charge jet. The section on thick concrete targets penetrated by rigid projectiles has now been expanded to include the latest findings, and two new sections have been added: one on a novel approach to the perforation of thin concrete slabs, and one on testing the failure of thin metallic plates using a hydrodynamic ram.

  7. Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

    DEFF Research Database (Denmark)

    Hakim-Weber, Robab; Krogsdam, Anne-M; Jørgensen, Claus

    2011-01-01

    Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate...... this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs...... of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis...

  8. Estudo do raspado de conjuntiva de pacientes tratados de retinoblastoma: Etapa II -- citologia Study of conjunctival scrape smears in patients treated for retinoblastoma: Phase II - cytology

    Directory of Open Access Journals (Sweden)

    Maria Carmen Menezes Santos

    2002-06-01

    Full Text Available Objetivo: A citologia da conjuntiva humana tem sido amplamente estu-dada. A falta de dados sobre as características do raspado ocular em pacientes tratados de retinoblastoma submetidos à enucleação e radioterapia foi o que motivou este estudo. Métodos: Foram examinadas 114 órbitas de 58 pacientes. Este trabalho apresenta os resultados da citologia conjuntival, em 4 condições, com e sem enucleação, com e sem radioterapia. Resultados: No infiltrado leucocitário das órbitas com bulbo ocular predominaram os linfócitos e nas demais, os polimorfonucleares neutrófilos. De maneira geral, as alterações das células epiteliais mais encontradas nas lâminas dos esfregaços conjuntivais de órbitas irradiadas foram: células com núcleo aumentado e nucléolo proeminente e com hialinização do citoplasma. Conclusão: Os achados citológicos do raspado conjuntival não indicaram perfil característico e distinto para cada grupo.Purpose: Human conjunctival cytology has been extensively studied. Lack of data about the characteristics of conjunctival smears in patients treated for retinoblastoma who underwent enucleation and radiotherapy motivated this study. Methods: A previously studied group of 114 orbits of 58 patients was examined. The authors present the results of conjunctival cytology in 4 different situations, with and without enucleation, with and without radiotherapy. Results: In the leukocytic infiltrate in orbits with ocular bulbi predominated the lymphocyte, while in the others predominated the polymorphonuclear neutrophil. In general, the majority of epithelial cell alterations seen in the conjunctival smears of irradiated orbits were: cell with large nuclei, prominent nucleoli, and cytoplasmatic hyalinization. Conclusion: The cytological findings of the conjunctival smears do not indicate a characteristic and distinct pattern for each group.

  9. Worldwide enucleation techniques and materials for treatment of retinoblastoma: an international survey.

    Directory of Open Access Journals (Sweden)

    Daphne L Mourits

    Full Text Available To investigate the current practice of enucleation with or without orbital implant for retinoblastoma in countries across the world.A digital survey identifying operation techniques and material used for orbital implants after enucleation in patients with retinoblastoma.We received a response of 58 surgeons in 32 different countries. A primary artificial implant is routinely inserted by 42 (72.4% surgeons. Ten (17.2% surgeons leave the socket empty, three (5.2% decide per case. Other surgeons insert a dermis fat graft as a standard primary implant (n=1, or fill the socket in a standard secondary procedure (n=2; one uses dermis fat grafts and one artificial implants. The choice for porous implants was more frequent than for non-porous implants: 27 (58.7% and 15 (32.6%, respectively. Both porous and non-porous implant types are used by 4 (8.7% surgeons. Twenty-five surgeons (54.3% insert bare implants, 11 (23.9% use separate wrappings, eight (17.4% use implants with prefab wrapping and two insert implants with and without wrapping depending on type of implant. Attachment of the muscles to the wrapping or implant (at various locations is done by 31 (53.4% surgeons. Eleven (19.0% use a myoconjunctival technique, nine (15.5% suture the muscles to each other and seven (12.1% do not reattach the muscles. Measures to improve volume are implant exchange at an older age (n=4, the use of Restylane SQ (n=1 and osmotic expanders (n=1. Pegging is done by two surgeons.No (worldwide consensus exists about the use of material and techniques for enucleation for the treatment of retinoblastoma. Considerations for the use of different techniques are discussed.

  10. A retinoblastoma orthologue is required for the sensing of a chalone in Dictyostelium discoideum.

    Science.gov (United States)

    Bakthavatsalam, Deenadayalan; White, Michael J V; Herlihy, Sarah E; Phillips, Jonathan E; Gomer, Richard H

    2014-03-01

    Retinoblastoma-like proteins regulate cell differentiation and inhibit cell proliferation. The Dictyostelium discoideum retinoblastoma orthologue RblA affects the differentiation of cells during multicellular development, but it is unclear whether RblA has a significant effect on Dictyostelium cell proliferation, which is inhibited by the secreted proteins AprA and CfaD. We found that rblA⁻ cells in shaking culture proliferate to a higher density, die faster after reaching stationary density, and, after starvation, have a lower spore viability than wild-type cells, possibly because in shaking culture, rblA⁻ cells have both increased cytokinesis and lower extracellular accumulation of CfaD. However, rblA⁻ cells have abnormally slow proliferation on bacterial lawns. Recombinant AprA inhibits the proliferation of wild-type cells but not that of rblA⁻ cells, whereas CfaD inhibits the proliferation of both wild-type cells and rblA⁻ cells. Similar to aprA⁻ cells, rblA⁻ cells have a normal mass and protein accumulation rate on a per-nucleus basis, indicating that RblA affects cell proliferation but not cell growth. AprA also functions as a chemorepellent, and RblA is required for proper AprA chemorepellent activity despite the fact that RblA does not affect cell speed. Together, our data indicate that an autocrine proliferation-inhibiting factor acts through RblA to regulate cell density in Dictyostelium, suggesting that such factors may signal through retinoblastoma-like proteins to control the sizes of structures such as developing organs or tumors.

  11. A retrospective review of visual outcome and complications in the treatment of retinoblastoma.

    LENUS (Irish Health Repository)

    O'Doherty, M

    2005-01-01

    The aim of this study was to look at the visual outcome and treatment complications of children diagnosed with Retinoblastoma during the years 1985-2003 inclusive. A retrospective review of all patients records was performed. Patient characteristics, treatment methods and complications were recorded. Twenty eight children presented to Temple street Hospital between 1985-2003. Six of these infants had bilateral tumours. The mean age at presentation was 23.7 months. Sixty-nine percent presented with Leucocoria, of these 33% also had a squint. The mean duration of symptoms was only known in 58% and this figure was approximately 19.8 months. Enucleation was performed in 24 eyes of 24 patients. Three patients required adjuvant chemotherapy post enucleation. Two eyes was treated with external beam radiation and one eye with plaque radiotherapy. One eye (second eye) was treated with systemic chemotherapy and radiation. Five eyes of three patients were treated with systemic chemotherapy followed by adjuvant Argon laser, cryotherapy and diode laser to each eye.The complications of each treatment group was recorded. The visual outcome in the salvaged eyes was favourable. There were no deaths recorded. Though chemotherapy with adjuvant local treatments provide adequate treatment for early tumours, enucleation still plays a major role in the treatment of Retinoblastoma. The total eye salvage rate in this study was 29% with an enucleation rate of 90% in unilateral cases and 33% in bilateral cases. Sixty-six percent of bilateral eyes affected were salvaged. Seventy-one percent of tumours were diagnosed after a parent noticed a gross abnormality of the eye. This highlights the possible need for screening for retinoblastoma in the infant population.

  12. Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes.

    Directory of Open Access Journals (Sweden)

    Xiaoyun Wu

    Full Text Available The retinoblastoma (Rb tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.

  13. O uso da quimioterapia no tratamento do retinoblastoma: avaliação retrospectiva The use of chemotherapy in the treatment of retinoblastoma: retrospective analysis

    Directory of Open Access Journals (Sweden)

    Fernando Leite Kronbauer

    2000-12-01

    Full Text Available Objetivo:Análise retrospectiva de pacientes com retinoblastoma considerando: 1 - estadiamento e apresentação tumoral à tomografia, 2 - proporção de pacientes com margens comprometidas (nervo óptico no exame anatomopatológico dos olhos enucleados e 3-tratamento com quimioterapia. Métodos: Revisados os prontuários de 11 pacientes consecutivos com diagnóstico de retinoblastoma entre fevereiro/98 e setembro/99, tratados conjuntamente no setor de Oncologia Pediátrica e Serviço de Oftalmologia. Foram selecionados aqueles submetidos à quimioterapia com vincristina, etoposida e carboplatina (VEC num total de 7 pacientes. Foram avaliados: apresentação tumoral (estadiamento, resposta à quimioterapia e sobrevida destes pacientes. Resultados: Os 7 pacientes estudados foram diagnosticados entre 15 e 38 meses de idade (média=25,7 meses, sendo 3 unilaterais, 3 bilaterais e 1 trilateral (pinealoblastoma. Todos pacientes foram tratados com quimioterapia (VEC administrados em 2 a 5 ciclos e divididos em 2 grupos: Grupo 1 - Pacientes tratados com quimioterapia primária visando redução tumoral e preservação de 1 dos olhos (5 pacientes; Grupo 2 - Pacientes tratados com quimioterapia agressiva para doença extra-ocular (2 pacientes. Dos 5 pacientes tratados com quimioterapia primária (4 submetidos a enucleação devido ao grande volume tumoral, 4 obtiveram redução tumoral, 2 responderam apenas inicialmente indo à óbito em 10 meses de média e 1 apresentou-se quimiorresistente. Pacientes com tumor bilateral foram submetidos a radioterapia (EBTR no olho menos acometido. O tempo médio de seguimento após quimioterapia primária foi 12,4 meses. Os dois pacientes submetidos à enucleação e quimioterapia adjuvante, apresentavam metástase cerebral e foram a óbito em média 4/5 meses após início do tratamento. Conclusão: Esse estudo revelou que: 1-os casos de retinoblastoma são diagnosticados tardiamente em nosso meio. 2 - A porcentagem

  14. Induction of growth stimulation in skin fibroblasts from retinoblastoma donors after ionizing radiation

    International Nuclear Information System (INIS)

    Diatloff-Zito, C.; Macieira-Coelho, A.; Turleau, C.; Cabanis, M.O.; Grouchy, J. de

    1983-01-01

    Skin fibroblasts from normal children and two children with a 13q14 deletion retinoblastoma (Rb) were submitted to fractionated doses of γ radiations. Irradiation reduced the population doublings in normal fibroblasts and the decline was inversely related to the dose. An increase in population doublings was obtained with one of the Rb cell lines. Foci appeared in the irradiated culture of the other Rb donor. It is suggested that fibroblasts from patients with Rb are able to express some phenotypical properties of transformed cells, perhaps related to factors rendering them more susceptible to carcinogens [fr

  15. Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma

    DEFF Research Database (Denmark)

    Helin, K; Holm, K; Niebuhr, A

    1997-01-01

    107, or p130 leads to growth arrest in the G1 phase of the cell cycle, and this arrest is abolished by complex formation with the adenovirus E1A, human papilloma virus E7, or simian virus 40 T oncoproteins. Inactivation of pRB by gross structural alterations or point mutations in the RB-1 gene has...... been described in a variety of human tumors, including retinoblastomas, osteosarcomas, and small cell lung carcinomas. Despite the structural and functional similarity between pRB, p107, and p130, alterations in the latter two proteins have not been identified in human tumors. We have screened a panel...

  16. A delayed diagnosis of unsuspected retinoblastoma in an in vitro fertilisation infant with retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Tian Tian; Xun-Da Ji; Qi Zhang; Jie Peng; Pei-Quan Zhao

    2016-01-01

    Dear Editor,Iam Dr.Tian Tian,from the Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China.I write to present a rare case report of a delayed diagnosis of unsuspected retinoblastoma(RB)in an in vitro fertilisation(IVF)infant with retinopathy of prematurity.The simultaneous presentation of RB and prematurity of retinopathy(ROP)in an IVF infant is very rare.The relationship between RB and IVF is still indeterminate and mechanisms that lead to ocular or systemic abnormalities

  17. Danish retinoblastoma patients 1943-2013 - genetic testing and clinical implications

    DEFF Research Database (Denmark)

    Gregersen, Pernille A; Urbak, Steen F; Funding, Mikkel

    2015-01-01

    , the rate has been stable around 1 per 14 000 live births with 95% of the patients surviving their retinoblastoma. Stratifying data on the time of diagnosis and status of genetic testing, the number of screened patients gradually increased from 5% in the beginning of the period to 96% in the last five...... to offspring and elevated risk of second primary cancers, we recommend information and access to genetic counseling and RB1 screening. This has ethical, psychological and possible economic consequences, and should be handled with caution...

  18. Long-term visual results in eyes cured for retinoblastoma by radiation

    International Nuclear Information System (INIS)

    Holbek, S.; Ehlers, N.

    1989-01-01

    Twenty-four eyes from 18 patients cured for retinoblastoma by radiation on an average 12 years previously, were re-examined with respect to visual performance. The macular functions, i.e. visual acuity, colour vision and contrast sensitivity demonstrated performances predictable from tumour localization and radiation dose to the macula. The rod functions, i.e. visual field and dark adaptation were found to be relatively resistant to the radiation treatment. A special problem encountered in two-eyed patients was the unavoidable amblyopia dut to unequal handicaps in the two eyes at the vulnerable age. (author)

  19. Long-term visual results in eyes cured for retinoblastoma by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Holbek, S.; Ehlers, N. (Department of Ophthalmology, Aarhus University Hospital, Aarhus (Denmark))

    1989-01-01

    Twenty-four eyes from 18 patients cured for retinoblastoma by radiation on an average 12 years previously, were re-examined with respect to visual performance. The macular functions, i.e. visual acuity, colour vision and contrast sensitivity demonstrated performances predictable from tumour localization and radiation dose to the macula. The rod functions, i.e. visual field and dark adaptation were found to be relatively resistant to the radiation treatment. A special problem encountered in two-eyed patients was the unavoidable amblyopia dut to unequal handicaps in the two eyes at the vulnerable age. (author).

  20. Recent decreasing frequency of enucleation for intraocular retinoblastoma in Upper Egypt

    International Nuclear Information System (INIS)

    Abdallh, A.M.

    2006-01-01

    To evaluate the efficacy of combined systematic chemotherapy (chemoreduction) and local ophthalmic therapy (LT) is preventing or delaying external beam radiotherapy (EBRT) and enucleation in patients with intraocular retinoblastoma. This was a prospective, nonrandomized, single-institution, clinical study. Twenty-eight patients (37 eyes) with newly diagnosed intraocular retinoblastoma were included in this study. Primary enucleation was performed for 7 eyes with advanced intraocular retinoblastoma at presentation before starting chemoreduction. Using Reese-Ellsworth (RE) staging for RB, the remaining 30 eyes were as follows: Two in group I, 3 in group II, 8 in group III, 7 in group IV, and 9 in group V. All the 30 eyes were initially treated with 6 cycles of chemoredution using vincristine, etoposide and carboplatin, repeated every three weeks. After total of 6 cycles, each tumor was re-evaluated decide on the next mode of therapy. In cases where the tumor was reduced enough, LT (Thermotherapy, or cryotherapy, but plaque radiotherapy was unavailable) was applied. In cases where the tumor was reduced but insufficient for LT, we added another 3 cycles of same regimen in some patients; or we performed chemotherapy (CTT) for others, according to size of the residual tumor. Eyes failed to respond to tochemorduction and LT, received EBRT or were enucleated. Following 6 cycles of chemoreduction, all tumors showed an initial regression, and all vitreous and subretinal seeds showed calcification or disappearance of most of them. Among the 30 eyes, 12 eyes achieved complete response (CR), and 18 eyes achieved partial response (PR). Only 7 eyes (stage I to III) showed sufficient reduction of tumor size for the LT to be applied for, for which, TTT (4 eyes), and cryotherapy (3 eyes) were performed. Chemotherapy (CTT) was performed for 9 patients (13 eyes, 15 tumors). At the end of follow-up period, 14 of the total 30 eyes (46.7%) could not be salvaged with chemoreduction and LT

  1. X-ray sensitivity of fibroblasts from patients with hereditary retinoblastoma and their families.

    OpenAIRE

    Pledger, J. V.; Craft, A. W.; Bartlett, K.; Long, D. R.

    1987-01-01

    The in vitro response to X-irradiation of cultured human fibroblasts was studied using a colony forming assay. A comprehensive reference range was established, giving a median D0 value of 98.5 cGy with an interquartile range of 86.5-110.5 cGy. Cells from 3 retinoblastoma family pedigrees were studied and the cell survival after exposure to X-rays was compared between affected (11 samples) and unaffected (26 samples) family members. No significant differences in response to ionising radiation ...

  2. Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Dong Yoon Kim

    2016-11-01

    Full Text Available Abstract Background To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. Methods Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers. Results In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm3 vs. 747.87 ± 118.83 mm3, respectively, P < 0.001. Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05 and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05. In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05. And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation. Conclusions Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that

  3. Termination unit

    Science.gov (United States)

    Traeholt, Chresten [Frederiksberg, DK; Willen, Dag [Klagshamn, SE; Roden, Mark [Newnan, GA; Tolbert, Jerry C [Carrollton, GA; Lindsay, David [Carrollton, GA; Fisher, Paul W [Heiskell, TN; Nielsen, Carsten Thidemann [Jaegerspris, DK

    2014-01-07

    This invention relates to a termination unit comprising an end-section of a cable. The end section of the cable defines a central longitudinal axis and comprising end-parts of N electrical phases, an end-part of a neutral conductor and a surrounding thermally insulation envelope adapted to comprising a cooling fluid. The end-parts of the N electrical phases and the end-part of the neutral conductor each comprising at least one electrical conductor and being arranged in the cable concentrically around a core former with a phase 1 located relatively innermost, and phase N relatively outermost in the cable, phase N being surrounded by the neutral conductor, electrical insulation being arrange between neighboring electrical phases and between phase N and the neutral conductor, and wherein the end-parts of the neutral conductor and the electrical phases each comprise a contacting surface electrically connected to at least one branch current lead to provide an electrical connection: The contacting surfaces each having a longitudinal extension, and being located sequentially along the longitudinal extension of the end-section of the cable. The branch current leads being individually insulated from said thermally insulation envelope by individual electrical insulators.

  4. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Na [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Chen, Yan [Central Laboratory, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Wang, Zhengmin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Chen, Guoling [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Lin, Qin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology, First Affiliated Hospital of Fujian Medical University, Otolaryngology Institute of Fujian Province, Fuzhou (China); Chen, Zheng-Yi, E-mail: Zheng-yi_chen@meei.harvard.edu [Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Li, Huawei, E-mail: hwli@shmu.edu.cn [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  5. Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Francis, Jasmine H., E-mail: francij1@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gobin, Y. Pierre; Marr, Brian P. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States); Brodie, Scott E. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mount Sinai School of Medicine, New York, New York (United States); Dunkel, Ira J.; Abramson, David H. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States)

    2013-11-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.

  6. Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the staging of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Khurana, Aman; Wan, Wenshuai; Yeom, Kristen [Stanford University, Department of Radiology, Stanford, CA (United States); Eisenhut, Christina A. [Technical University of Munich, Department of Radiology, Munich (Germany); Ebrahimi, Katayoon B. [Johns Hopkins University, Department of Ocular Oncology, Baltimore, MD (United States); Patel, Chirag [University of California Davis, Department of Radiology, Davis, CA (United States); O' Brien, Joan M. [University of Pennsylvania, Department of Ophthalmology, Philadelphia, PA (United States); Daldrup-Link, Heike E. [Stanford University, Department of Radiology, Stanford, CA (United States); Stanford University, Department of Radiology, Pediatric Radiology Section, Lucile Packard Children' s Hospital, Stanford, CA (United States)

    2013-05-15

    To compare the diagnostic value of magnetic resonance (MR) imaging and ophthalmoscopy for staging of retinoblastoma. MR and ophthalmoscopic images of 36 patients who underwent enucleation were evaluated retrospectively following institutional review board approval. Histopathology being the standard of reference, the sensitivity and specificity of both diagnostic modalities were compared regarding growth pattern, iris neoangiogenesis, retinal detachment, vitreous seeds and optic nerve invasion. Data were analysed via McNemar's test. Both investigations showed no significant difference in accuracy for the detection of different tumour growth patterns (P = 0.80). Vitreous seeding detection was superior by ophthalmoscopy (P < 0.001). For prelaminar optic nerve invasion, MR imaging showed similar sensitivity as ophthalmoscopy but increased specificity of 40 % (CI 0.12-0.74) vs. 20 % (0.03-0.56). MR detected optic nerve involvement past the lamina cribrosa with a sensitivity of 80 % (0.28-0.99) and a specificity of 74 % (0.55-0.88). The absence of optic nerve enhancement excluded histopathological infiltration, but the presence of optic nerve enhancement included a high number of false positives (22-24 %). Ophthalmoscopy remains the method of choice for determining extent within the globe while MR imaging is useful for evaluating extraocular tumour extension. Thus, both have their own strengths and contribute uniquely to the staging of retinoblastoma. (orig.)

  7. Managing the consequences of aggressive conservative treatment for refractory retinoblastoma with vitreous seeding

    Directory of Open Access Journals (Sweden)

    Aubrey Brink

    2014-08-01

    Full Text Available A 4 year-old girl with bilateral, non-familial retinoblastoma (RB was referred to our care after primary enucleation OS and active tumor OD refractory to multiple therapies (intravenous chemotherapy, laser/cryotherapy, and I-125 plaque radiotherapy. Vitreous seeding OD, initially controlled by several sessions of Ophthalmic Artery Infusion Chemotherapy (OAIC and periocular chemotherapy, recurred shortly thereafter. The patient underwent intravitreal (IVit Melphalan injections achieving tumor control despite the concurrent development of keratopathy, pupillary synechiae, cataract, and necrosis of the inferior fornix and the adjacent orbital fat, all secondary to the treatments administered. Repeated amniotic membrane implants and tarsorrhaphy were performed to alleviate the symptoms. Despite being tumor free for 6 months, a poor fundus view and treatment-related complications prompted us to consider enucleation, but parents declined. Following recent negative magnetic resonance imaging (MRI, her cataract was removed. She was then found to have tumor recurrence. Her eye was enucleated 12 months ago and she recovered well from the surgery. As ocular oncology embarks in eye-preserving treatments for retinoblastoma, it is important to address the cumulative effects and associated impact of such treatments and the possibility of failure.

  8. Success of intra-arterial chemotherapy (chemosurgery) for retinoblastoma: effect of orbitovascular anatomy.

    Science.gov (United States)

    Marr, Brian P; Hung, Crystal; Gobin, Yves P; Dunkel, Ira J; Brodie, Scott E; Abramson, David H

    2012-02-01

    To review results of orbital angiography performed during intra-arterial chemotherapy (chemosurgery) for treatment of retinoblastoma to assess the association of angiographic variability in orbitovascular anatomy with tumor response and outcomes. Medical records and 64 orbital angiograms were reviewed for 56 pediatric patients with retinoblastoma undergoing chemosurgery using a combination of melphalan hydrochloride, topotecan hydrochloride, or carboplatin. The major orbital arteries and capillary blush patterns were graded, and tumor response and recurrence were compared using the log-rank and Fisher exact tests. Statistically significant variables for tumor response were lacrimal artery prominence (P = .001), previous treatment (P = .003), and lacrimal blush (P = .004). The only statistically significant variable for vitreous seed response was ciliary body blush (P = .03). Statistically significant variables influencing time to recurrence and time to enucleation were choroidal blush absence (P = .01) and lacrimal artery presence (P = .03), respectively. The success of intra-arterial chemotherapy is dependent on delivery of drug to the target tumor within the eye via the ophthalmic artery. Because of the small volume of drug used (0.50-1.25 mL per treatment) and the selectivity of catheterization, variables affecting orbital blood flow greatly influence drug delivery and the success of chemosurgery.

  9. X-ray sensitivity of fibroblasts from patients with hereditary retinoblastoma and their families

    International Nuclear Information System (INIS)

    Pledger, J.V.; Craft, A.W.; Bartlett, K.; Long, D.R.

    1987-01-01

    The in vitro response to X-irradiation of cultured human fibroblasts was studied using a colony forming assay. A comprehensive reference range was established, giving a median Dsub(0) value of 98.5 cGy with an interquartile range of 86.5-110.5 cGy. Cells from 3 retinoblastoma family pedigrees were studied and the cell survival after exposure to X-rays was compared between affected (11 samples) and unaffected (26 samples) family members. No significant differences in response to ionising radiation were found between the controls, the affected and the unaffected members of the 3 families. The affected members had a median Dsub(0) of 97.5 cGy (interquartile range 87.5-107.5 cGy) and the unaffected members had a median Dsub(0) of 102 cGy (interquartile range 93-111 cGy). Thus radiosensitivity is not a useful marker for the detection of the retinoblastoma gene. (author)

  10. Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

    Science.gov (United States)

    Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

    2013-01-01

    Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. PMID:23211596

  11. Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    International Nuclear Information System (INIS)

    Francis, Jasmine H.; Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil; Gobin, Y. Pierre; Marr, Brian P.; Brodie, Scott E.; Dunkel, Ira J.; Abramson, David H.

    2013-01-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG

  12. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    International Nuclear Information System (INIS)

    Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

    2013-01-01

    Highlights: ► Shh activation in neonatal cochleae enhances sensory cell proliferation. ► Proliferating supporting cells can transdifferentiate into hair cells. ► Shh promotes proliferation by transiently modulating pRb activity. ► Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  13. Mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence

    Directory of Open Access Journals (Sweden)

    André Alves Dias

    2012-12-01

    Full Text Available When grown in the presence of exogenous collagen I, Mycobacterium bovis BCG was shown to form clumps. Scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. Since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed BCG cytoadherence in the presence of exogenous collagen I. Collagen increased the interaction of the bacilli with A549 type II pneumocytes or U937 macrophages, suggesting that BCG is able to recruit collagen to facilitate its attachment to host cells. Using an affinity chromatography approach, we have isolated a BCG collagen-binding protein corresponding to the previously described mycobacterial laminin-binding histone-like protein (LBP/Hlp, a highly conserved protein associated with the mycobacterial cell wall. Moreover, Mycobacterium leprae LBP/Hlp, a well-characterized adhesin, was also able to bind collagen I. Finally, using recombinant fragments of M. leprae LBP/Hlp, we mapped the collagen-binding activity within the C-terminal domain of the adhesin. Since this protein was already shown to be involved in the recognition of laminin and heparan sulphate-containing proteoglycans, the present observations reinforce the adhesive activities of LBP/Hlp, which can be therefore considered as a multifaceted mycobacterial adhesin, playing an important role in both leprosy and tuberculosis pathogenesis.

  14. An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss.

    Directory of Open Access Journals (Sweden)

    Franco Lombino

    Full Text Available Mutations in Amyloid-ß Precursor Protein (APP and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD, respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr(668 of ß-CTF because phosphorylation of Thr(668 is increased in AD cases. We created a knock-in mouse bearing a Thr(668Ala mutation (APP(TA mice that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr(668 is a viable therapeutic strategy for human dementias.

  15. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbæk, Mads; Alsner, Jan; Marcussen, Niels

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective...

  16. Analysis of the RB1 gene in children with retinoblastoma having residential connections to West Cumbria, England

    Energy Technology Data Exchange (ETDEWEB)

    Cowell, J K [Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Morris, J A [Department of Pathology, Royal Lancaster Infirmary, Lancaster LA1 4RP (United Kingdom); Tawn, E J [Westlakes Research Institute, Moor Row, Cumbria CA24 3JY (United Kingdom)

    2005-03-01

    Six of eight cases of retinoblastoma previously identified as having a residential association with West Cumbria, England, in which the Sellafield nuclear installation is situated, were examined for the presence of a constitutional RB1 mutation. No mutations were detected, thus providing strong evidence against an environmental or occupational genotoxic effect causing germline mutations in the parents of these children. (note)

  17. Stage of presentation and visual outcome of patients screened for familial retinoblastoma: nationwide registration in the Netherlands

    NARCIS (Netherlands)

    Imhof, S. M.; Moll, A. C.; Schouten-van Meeteren, A. Y. N.

    2006-01-01

    In the Netherlands a comprehensive programme for screening just after birth for familial retinoblastoma is taking place. In this report the stage of the disease at the time of detection, by way of screening, and the long term visual outcome in these patients was evaluated. A nationwide,

  18. Activation of peroxisome proliferator-activated receptor gamma bypasses the function of the retinoblastoma protein in adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B.; Petersen, R K; Larsen, B M

    1999-01-01

    The retinoblastoma protein (pRB) is an important regulator of development, proliferation, and cellular differentiation. pRB was recently shown to play a pivotal role in adipocyte differentiation, to interact physically with adipogenic CCAAT/enhancer-binding proteins (C/EBPs), and to positively...

  19. External beam radiation for retinoblastoma: Results, patterns of failure, and a proposal for treatment guidelines

    International Nuclear Information System (INIS)

    Hernandez, J. Carlos; Brady, Luther W.; Shields, Jerry A.; Shields, Carol L.; Potter, Patrick de; Karlsson, Ulf L.; Markoe, Arnold M.; Amendola, Beatriz E.; Singh, Arun

    1996-01-01

    Purpose: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. Methods and Materials: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. Results: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). Conclusions: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control

  20. Olfactory proteins mediating chemical communication in the navel orangeworm moth, Amyelois transitella.

    Directory of Open Access Journals (Sweden)

    Walter S Leal

    2009-09-01

    Full Text Available The navel orangeworm, Amyelois transitella Walker (Lepidoptera: Pyralidae, is the most serious insect pest of almonds and pistachios in California for which environmentally friendly alternative methods of control--like pheromone-based approaches--are highly desirable. Some constituents of the sex pheromone are unstable and could be replaced with parapheromones, which may be designed on the basis of molecular interaction of pheromones and pheromone-detecting olfactory proteins.By analyzing extracts from olfactory and non-olfactory tissues, we identified putative olfactory proteins, obtained their N-terminal amino acid sequences by Edman degradation, and used degenerate primers to clone the corresponding cDNAs by SMART RACE. Additionally, we used degenerate primers based on conserved sequences of known proteins to fish out other candidate olfactory genes. We expressed the gene encoding a newly identified pheromone-binding protein, which was analyzed by circular dichroism, fluorescence, and nuclear magnetic resonance, and used in a binding assay to assess affinity to pheromone components.We have cloned nine cDNAs encoding olfactory proteins from the navel orangeworm, including two pheromone-binding proteins, two general odorant-binding proteins, one chemosensory protein, one glutathione S-transferase, one antennal binding protein X, one sensory neuron membrane protein, and one odorant receptor. Of these, AtraPBP1 is highly enriched in male antennae. Fluorescence, CD and NMR studies suggest a dramatic pH-dependent conformational change, with high affinity to pheromone constituents at neutral pH and no binding at low pH.

  1. Growth patterns of survivors of retinoblastoma treated with ophthalmic artery chemosurgery.

    Directory of Open Access Journals (Sweden)

    Sruti S Akella

    Full Text Available Although studies from pediatric cancers (largely acute lymphoblastic leukemia have shown that patients undergoing systemic chemotherapy may experience decreased growth velocity during the treatment phase, no such data exist for retinoblastoma patients treated with systemic chemotherapy or ophthalmic artery chemosurgery (OAC. The purpose of this study is to report growth patterns of our retinoblastoma (Rb population who were treated with OAC in a retrospective, single center (Memorial Sloan Kettering Cancer Center review of 341 patients treated between 2006 and 2016. Children who only received OAC were classified as naive; those who were treated initially with systemic chemotherapy and subsequently presented to our center for OAC were termed secondary; and a small group of patients who received single-agent systemic chemotherapy prior to OAC were labeled bridge. For all patients, height and weight were recorded at monthly intervals during OAC (short-term and then annually during a follow-up period (long-term up to 3 years after treatment. Excluded from this study were children who received external radiation therapy and those with genetic syndromes, which are independently associated with growth derangements. During OAC, there was no significant difference in growth velocity between the naïve and secondary groups. In either group, number of treatments also did not affect growth rate. Three years after the end of OAC, naïve patients were in the 68th percentile by height (95% CI 61.30, 74.63 compared to secondary patients in the 61st percentile (95% CI 51.1, 71.47. Both groups were in the same weight percentiles during the first two years of follow-up but at the three-year follow-up period, naïve patients were in the 63rd percentile (95% CI 57.4, 69.4 and secondary patients were in the 60th percentile (95% CI 50.4, 69.7. OAC for retinoblastoma does not appear to impact short-term growth velocity, weight gain during the treatment period or after

  2. Dosimetric intercomparison between protons and electrons therapies applied to retinoblastoma; Intercomparacao dosimetrica entre terapias de protons e eletrons aplicada ao retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Flavia Vieira

    2008-07-01

    In this work we propose a construction of a simple human eye model in order to simulate the dosimetric response for a treatment with protons and electrons in a retinoblastoma cancer. The computational tool used in this simulation was the Geant4 code, in the version 4.9.1, all these package are free and permit simulate the interaction of radiation with matter. In our simulation we use a box with 4 cm side, with water, for represent the human eye. The simulation was performed considering mono energetics beams of protons and electrons with energy range between 50 and 70 MeV for protons and 2 and 10 MeV for electrons. The simulation was based on the advanced hadron therapy example of the Geant 4 code. In these example the phantom is divided in voxels with 0.2 mm side and it is generated the energy deposited in each voxel. The simulation results show the energy deliver in each voxel, with these energie we can calculate the dose deposited in that region. We can see the dose profile of, proton and electron, and we can see in both cases that for protons the position of delivered dose is well know, that happen in the position where the proton stop, for electrons the energies is delivered along the way and pass the desired position for high dose deposition. (author)

  3. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    International Nuclear Information System (INIS)

    Kim, Dong Hun; Kim, Il Joong; Yang, Jae Han; Byun, Joo Nam; Lee, Bong Jae; Kim, Jeong Hun; Yu, Young Suk

    2007-01-01

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo

  4. Various ocular MR imaging in a mouse implanted with a new cell line of retinoblastoma and the correlation with the pathology: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hun; Kim, Il Joong; Yang, Jae Han; Byun, Joo Nam; Lee, Bong Jae [Chosun University, College of Medicine, Gwangju (Korea, Republic of); Kim, Jeong Hun; Yu, Young Suk [Seoul National University, College of Medicine, Seoul (Korea, Republic of)

    2007-05-15

    We wanted to show various MR and correlated pathologic images of retinoblastoma in nude mouse with a new human retinoblastoma cell line (SNUOT-Rb1), which was inoculated into the intravitreous cavity. The established cell line was inoculated into the intravitreous cavity of 36 eyeballs of 18 mice and the transplanted retinoblastoma was examined for 3 months. The T1-weighted (T1WI), T2-weighted (T2WI), and contrast enhanced (Gd-DTPA) T1-weighted images were obtained with using a small loop coil. After scanning, the mice's eyeballs were extracted and the hematoxylin and eosin stained specimens were examined with a microscope. We compared the MR imagings with pathologic findings and evaluated the character of the tumors. The innoculated cells in the eyeballs of the mice grew into retinoblastoma (23/36, 64%). The eyeballs with retinoblastoma protruded externally and showed focal hemorrhage. Most tumors showed iso-signal intensity on TIWI (13/23, 57%), high signal intensity on T2WI (17/23, 74%), and good enhancement (21/23, 91%) with contrast. Almost all of the tumors (n = 21) were located in the retina and three extraretinal tumors were confirmed by pathology. Involvement of the optic nerve was suspected on MRI and this was confirmed by pathology in 6 cases and 5 cases, respectively. We could demonstrate various MR imagings of transplanted retinoblastoma by using the new tumor cell line in vivo.

  5. Retinoblastoma protein co-purifies with proteasomal insulin-degrading enzyme: Implications for cell proliferation control

    Energy Technology Data Exchange (ETDEWEB)

    Radulescu, Razvan T., E-mail: ratura@gmx.net [Molecular Concepts Research (MCR), Muenster (Germany); Duckworth, William C. [Department of Medicine, Phoenix VA Health Care System, Phoenix, AZ (United States); Levy, Jennifer L. [Research Service, Phoenix VA Health Care System, Phoenix, AZ (United States); Fawcett, Janet, E-mail: janet.fawcett@va.gov [Research Service, Phoenix VA Health Care System, Phoenix, AZ (United States)

    2010-04-30

    Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110 kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.

  6. External radiotherapy for circumscribed choroidal haemangiomas using a modified retinoblastoma technique

    International Nuclear Information System (INIS)

    Eide, N.; Syrdalen, P.; Tausjoe, J.; Tveraa, K.

    1995-01-01

    This report describes two cases of circumscribed choroidal haemangiomas involving the fovea, complicated by serous retinal detachment. Laser photocoagulation, generally accepted as the treatment of choice for choroidal haemangioma, was considered either to be of no visual benefit or a risk for jeopardizing vision further due to the subfoveolar lesions. Fractionated radiotherapy using a lens-sparing, modified retinoblastoma technique, was given, using circular fields of 15 mm diameter. The dose was 24 Gy in 8 fractions. In both eyes the retina reattached completely. The visual acuity improved markedly in the first, and was restored to the prior level in the second. Normalization of a high intraocular pressure was also achieved in the second case. We believe this method to be a reasonable and effective therapy for some choroidal haemangiomas after careful individual consideration. (au) 17 refs

  7. Retinoblastoma and the Genetic Theory of Cancer: An Old Paradigm Trying to Survive to the Evidence

    International Nuclear Information System (INIS)

    Mastrangelo, D.; Lore, C.; Hadjistilianou, T.; De Francesco, S.

    2009-01-01

    Retinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called “tumor suppressor gene”, the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account.

  8. Characterization and Expression Analysis of a Retinoblastoma-Related Gene from Chinese Wild Vitis pseudoreticulata.

    Science.gov (United States)

    Wen, Zhifeng; Gao, Min; Jiao, Chen; Wang, Qian; Xu, Hui; Walter, Monika; Xu, Weirong; Bassett, Carole; Wang, Xiping

    2012-01-01

    Retinoblastoma-related (RBR) genes, a conserved gene family in higher eukaryotes, play important roles in cell differentiation, development, and mammalian cell death; however, little is known of their function in plants. In this study, a RBR gene was isolated from the Chinese wild grape, Vitis pseudoreticulata W. T. Wang clone "Baihe-35-1", and designated as VpRBR . The cDNA sequence of VpRBR was 3,030 bp and contained an open reading frame of 3,024 bp. Conceptual translation of this gene indicated a composition of 1,007 amino acids with a predicted molecular mass of 117.3 kDa. The predicted protein showed a retinoblastoma-associated protein domain A from amino acid residues 416 to 579, and domain B from residues 726 to 855. The result of expression analysis indicated that VpRBR was expressed in tissues, leaves, stem, tendrils, flower, and grape skin at different expression levels. Further quantitative reverse transcription-PCR (qRT-PCR) data indicated that VpRBR levels were higher in Erysiphe necator-treated "Baihe-35-1" and "Baihe-13-1", two resistant clones of Chinese wild V. pseudoreticulata , than in E. necator-treated "Hunan-1", a susceptible clone of V. pseudoreticulata . Furthermore, the expression of VpRBR in response to salicylic acid (SA), methyl jasmonate (MeJA), and ethylene (Eth) in grape leaves was also investigated. Taken together, these data indicate that VpRBR may contribute to some aspect of powdery mildew resistance in grape.

  9. Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein.

    Science.gov (United States)

    Gray, Steven G; Iglesias, Antonio H; Lizcano, Fernando; Villanueva, Raul; Camelo, Sandra; Jingu, Hisaka; Teh, Bin T; Koibuchi, Noriyuki; Chin, William W; Kokkotou, Efi; Dangond, Fernando

    2005-08-05

    To effectively direct targeted repression, the class I histone deacetylases (HDACs) associate with many important regulatory proteins. In this paper we describe the molecular characterization of a member of the Jumonji domain 2 (JMJD2) family of proteins, and demonstrate its binding to both class I HDACs and the retinoblastoma protein (pRb). JMJD2 proteins are characterized by the presence of two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers, one JmjN, one JmjC (containing an internal retinoblastoma-binding protein 2 (RBBP2)-like sequence), and two Tudor domains. The first member of this group, JMJD2A, is widely expressed in human tissues and cell lines, and high endogenous expression of JMJD2A mRNA was found in several cell types, including human T-cell lymphotropic virus 1 (HTLV-1)-infected cell lines. JMJD2A and JMJD2B exhibit cell type-specific responses to the HDAC inhibitor trichostatin A. We show that the JMJD2A protein associates in vivo with pRb and class I HDACs, and mediates repression of E2F-regulated promoters. In HTLV-1 virus-infected cells, we find that JMJD2A binds to the viral Tax protein. Antibodies to JMJD2A recognize the native protein but also a half-sized protein fragment, the latter up-regulated in THP-1 cells during the G(2)/M phase of the cell cycle. The ability of JMJD2A to associate with pRb and HDACs and potentiate pRb-mediated repression of E2F-regulated promoters implies an important role for this protein in cell proliferation and oncogenesis.

  10. An international survey of classification and treatment choices for group D retinoblastoma

    Directory of Open Access Journals (Sweden)

    Jasmine H Francis

    2017-06-01

    Full Text Available AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children’s Hospital of Los Angeles (CHLA version, 33% used the Children’s Oncology Group (COG version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001. CONCLUSION: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version

  11. Glycodendrimeric phenylporphyrins as new candidates for retinoblastoma PDT: blood carriers and photodynamic activity in cells.

    Science.gov (United States)

    Wang, Ze-Jian; Chauvin, Benoît; Maillard, Philippe; Hammerer, Fabien; Carez, Danièle; Croisy, Alain; Sandré, Catherine; Chollet-Martin, Sylvie; Prognon, Patrice; Paul, Jean-Louis; Blais, Jocelyne; Kasselouri, Athena

    2012-10-03

    Photodynamic therapy (PDT) has recently been proposed as a possible indication in the conservative treatment of hereditary retinoblastoma. In order to create photosensitizers with enhanced targeting ability toward retinoblastoma cells, meso-tetraphenylporphyrins bearing one glycodendrimeric moiety have been synthesized. The binding properties to plasma proteins and photodynamic activity of two monodendrimeric porphyrins bearing three mannose units via monoethylene glycol (1) or diethylene glycol (2) linkers have been compared to that of the non-dendrimeric tri-substituted derivative [TPP(p-Deg-O-α-ManOH)(3)]. The dendrimeric structure was found to highly increase the binding affinity to plasma proteins and to modify to some extent plasma distribution. HDL and to a lesser extent LDL have been shown to be the main carriers of dendrimeric and non-dendrimeric compounds. The phototoxicity observed for the two glycodendrimers (1) and (2) (LD(50)=0.5 μM) in Y79 cells is of the same order of magnitude that for TPP(p-Deg-O-α-ManOH)(3) (LD(50)=0.7 μM), with a similar cellular uptake level for (1) and a lower for (2). A serum content increase from 2% to 20% (v/v) in the incubation medium was found to inhibit both cellular uptake and photoactivity of dendrimeric derivatives, whereas those of TPP(p-Deg-O-α-ManOH)(3) remained little affected. Specificities of glycodendrimeric porphyrins, combining a lower cellular uptake together with a higher affinity toward plasma proteins, make these derivatives possible candidates for a vascular targeting PDT. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosome relocalization, and spindle pole body morphogenesis.

    Science.gov (United States)

    Espagne, Eric; Vasnier, Christelle; Storlazzi, Aurora; Kleckner, Nancy E; Silar, Philippe; Zickler, Denise; Malagnac, Fabienne

    2011-06-28

    We identify a large coiled-coil protein, Sme4/PaMe4, that is highly conserved among the large group of Sordariales and plays central roles in two temporally and functionally distinct aspects of the fungal sexual cycle: first as a component of the meiotic synaptonemal complex (SC) and then, after disappearing and reappearing, as a component of the spindle pole body (SPB). In both cases, the protein mediates spatial juxtaposition of two major structures: linkage of homolog axes through the SC and a change in the SPB from a planar to a bent conformation. Corresponding mutants exhibit defects, respectively, in SC and SPB morphogenesis, with downstream consequences for recombination and astral-microtubule nucleation plus postmeiotic nuclear migration. Sme4 is also required for reorganization of recombination complexes in which Rad51, Mer3, and Msh4 foci relocalize from an on-axis position to a between-axis (on-SC) position concomitant with SC installation. Because involved recombinosome foci represent total recombinational interactions, these dynamics are irrespective of their designation for maturation into cross-overs or noncross-overs. The defined dual roles for Sme4 in two different structures that function at distinct phases of the sexual cycle also provide more functional links and evolutionary dynamics among the nuclear envelope, SPB, and SC.

  13. Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

    Science.gov (United States)

    Chao, An- Ning; Kao, Ling-Yuh; Liu, Laura; Wang, Nan-Kai

    2016-03-15

    Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the

  14. Experimental Model to Study the Role of Retinoblastoma Gene Product (pRb) for Determination of Adipocyte Differentiation.

    Science.gov (United States)

    Popov, B V; Shilo, P S; Zhidkova, O V; Zaichik, A M; Petrov, N S

    2015-06-01

    Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines hyperexpressing functionally active or inactive mutant pRb. The cells producing active exogenous pRb demonstrated high sensitivity to adipocyte differentiation inductors, whereas production of inactive form of the exogenous protein suppressed adipocyte differentiation. The obtained lines can serve as the experimental model for studying the role of pRb in determination of adipocyte differentiation.

  15. Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death

    Science.gov (United States)

    Marchong, Mellone N.; Yurkowski, Christine; Ma, Clement; Spencer, Clarellen; Pajovic, Sanja; Gallie, Brenda L.

    2010-01-01

    CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01). Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8) (p = 0.01) and had fewer multifocal tumors at PND28 (p = 0.016), compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003). In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers), while proliferation in vivo remained unaffected (p = 0.121). Activated caspase-3 was significantly decreased and β-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death. PMID:20421947

  16. Cdh11 acts as a tumor suppressor in a murine retinoblastoma model by facilitating tumor cell death.

    Directory of Open Access Journals (Sweden)

    Mellone N Marchong

    2010-04-01

    Full Text Available CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01. Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8 (p = 0.01 and had fewer multifocal tumors at PND28 (p = 0.016, compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003. In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers, while proliferation in vivo remained unaffected (p = 0.121. Activated caspase-3 was significantly decreased and beta-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death.

  17. kosh Terminal Aerodrome Forecast

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    Data.gov (United States)

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  19. koaj Terminal Aerodrome Forecast

    Data.gov (United States)

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  20. krhi Terminal Aerodrome Forecast

    Data.gov (United States)

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  1. kbpk Terminal Aerodrome Forecast

    Data.gov (United States)

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  2. khuf Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  3. kbpi Terminal Aerodrome Forecast

    Data.gov (United States)

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  4. ktrk Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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  6. katy Terminal Aerodrome Forecast

    Data.gov (United States)

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  7. tjmz Terminal Aerodrome Forecast

    Data.gov (United States)

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  8. kdet Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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  13. kloz Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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  15. kdec Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  16. paor Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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  18. kdrt Terminal Aerodrome Forecast

    Data.gov (United States)

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  19. kstl Terminal Aerodrome Forecast

    Data.gov (United States)

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  20. kbfi Terminal Aerodrome Forecast

    Data.gov (United States)

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  1. khsv Terminal Aerodrome Forecast

    Data.gov (United States)

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  2. pafa Terminal Aerodrome Forecast

    Data.gov (United States)

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  3. kekn Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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  10. kmgm Terminal Aerodrome Forecast

    Data.gov (United States)

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  11. khib Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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  13. kfar Terminal Aerodrome Forecast

    Data.gov (United States)

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  16. klse Terminal Aerodrome Forecast

    Data.gov (United States)

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  17. ksts Terminal Aerodrome Forecast

    Data.gov (United States)

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  18. koth Terminal Aerodrome Forecast

    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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  16. Organizational Relationship Termination Competence

    DEFF Research Database (Denmark)

    Ritter, Thomas; Geersbro, Jens

    2011-01-01

    termination are found to significantly affect a firm's relationship termination competence. The findings suggest that managers should regard termination as a legitimate option in customer relationship management. In order to decrease the number of unwanted customers, managers must accept termination......Most firms are involved in a number of customer relationships that drain the firm's resources. However, many firms are hesitant to address this problem. This paper investigates customer relationship termination at the organizational level. We develop and analyze the organizational dimensions...... of organizational termination in order to improve our understanding of the management of termination. The impact of these termination dimensions on the percentage of unwanted customers is developed and tested using PLS on data gathered from a cross-sectional survey of more than 800 sales representatives. We find...

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    Data.gov (United States)

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  8. kcre Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  9. klws Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  10. kotm Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  11. khqm Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  12. kabr Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  13. klal Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  14. kelp Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  15. kecg Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  16. khbg Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  17. kpbf Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  18. konp Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  19. pkwa Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  20. ktvf Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  1. paga Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  2. khks Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  3. kdsm Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  4. kpsm Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  5. kgrb Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  6. kgmu Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  7. papg Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  8. kbgm Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  9. pamc Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  10. klrd Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  11. ksan Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  12. patk Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  13. kowb Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  14. klru Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  15. kfxe Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  16. kjct Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  17. kcrg Terminal Aerodrome Forecast

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    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  18. paaq Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  19. kaex Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  20. klbx Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  1. kmia Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  2. kpit Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  3. kcrw Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  4. paen Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  5. kast Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  6. kuin Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  7. kmht Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  8. kcys Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  9. kflo Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  10. pakn Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  11. pabt Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  12. krdg Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  13. khdn Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  14. kjac Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  15. kphx Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  16. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  17. Proton and electron deep dose profiles for retinoblastoma based on GEANT 4 code

    International Nuclear Information System (INIS)

    Braga, Flavia V.; Campos, Tarcisio P.R. de; Ribeiro, Kilder L.

    2009-01-01

    Herein, the dosimetry responses to a retinoblastoma proton and electron radiation therapy were investigated. The computational tool applied to this simulation was the Geant4 code, version 4.9.1. The code allows simulating the charge particle interaction with eyeball tissue. In the present simulation, a box of 4 cm side water filled had represented the human eye. The simulation was performed considering mono energetic beams of protons and electrons with spectra of 57 to 70 MeV for protons and 2 to 8 MeV for electrons. The simulation was guide by the advanced hadron therapy example distributed with the Geant4 code. The phantom was divided in voxels with 0.2 mm side. The energy deposited in each voxel was evaluated taken the direct beam at one face. The simulation results show the delivery energy and therefore the dose deposited in each voxel. The deep dose profiles to proton and electron were plotted. The well known Bragg peak was reproduced for protons. The maximum delivered dose defined the position at the proton stopped. However, to electrons, the absorbed energies were delivered along its path producing a more continuous distribution following the water depth, but also being stopped in the end of its path. (author)

  18. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-01-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  19. MiR-200c suppresses the migration of retinoblastoma cells by reversing epithelial mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xiao-Lei Shao

    2017-08-01

    Full Text Available AIM: To analyze the relationship between clinical features and epithelial mesenchymal transition (EMT in retinoblastoma (RB, further to investigate whether miR-200c regulates the EMT and migration of RB cells. METHODS: Expression of EMT-related markers and tumor-related factors were detected by immuno-histochemistry analysis in RB tissue from 29 cases. Correlations between their expression and clinical characteristics were analyzed. The regulation effects of miR-200c on EMT-related markers, tumor-related factors were observed in mRNA level and protein level by real-time polymerase chain reaction (PCR and Western blot, respectively, in Y79 and Weri-rb1 cells. Its effects on migration force of these RB cell lines were also detected with Transwell test. RESULTS: Lower expression of E-cadherin was present in the cases with malignant prognosis. MiR-200c promoted the expression of E-cadherin and decreased the expression of Vimentin and N-cadherin in Y79 and Weri-rb1 cells. Migration force of RB cells could be inhibited by miR-200c. CONCLUSION: EMT might be associated with bad prognosis in RB. MiR-200c suppresses the migration of retinoblastomatous cells by reverse EMT.

  20. RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients (2,074 Eyes).

    Science.gov (United States)

    Kaliki, Swathi; Patel, Anamika; Iram, Sadiya; Ramappa, George; Mohamed, Ashik; Palkonda, Vijay A R

    2017-11-23

    To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India. Retrospective study of 1,457 patients with RB (2,074 eyes). The mean age at presentation of RB was 29 months (median, 24 months; range, presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment-included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively. The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.

  1. Interaction of fish aryl hydrocarbon receptor paralogs (AHR1 and AHR2) with the retinoblastoma protein

    Energy Technology Data Exchange (ETDEWEB)

    Merson, Rebeka R., E-mail: rmerson@ric.edu [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Biology Department, Rhode Island College, 500 Mt. Pleasant Ave., Providence, RI 02908 (United States); Karchner, Sibel I.; Hahn, Mark E. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2009-08-13

    The aryl hydrocarbon receptor (AHR) mediates the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. In some mammalian cell lines, TCDD induces G1 cell cycle arrest, which depends on an interaction between the AHR and the retinoblastoma tumor suppressor (RB). Mammals possess one AHR, whereas fishes possess two or more AHR paralogs that differ in the domains important for AHR-RB interactions in mammals. To test the hypothesis that fish AHR paralogs differ in their ability to interact with RB, we cloned RB cDNA from Atlantic killifish, Fundulus heteroclitus, and studied the interactions of killifish RB protein with killifish AHR1 and AHR2. In coimmunoprecipitation experiments, in vitro-expressed killifish RB coprecipitated with both AHR1 and AHR2. Consistent with these results, both killifish AHR1 and AHR2 interacted with RB in mammalian two-hybrid assays. These results suggest that both fish AHR1 and AHR2 paralogs may have the potential to influence cell proliferation through interactions with RB.

  2. Expressions of matrix metalloproteinase-2 and extracellular matrix metalloproteinase inducer in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Yu-Hong Cheng

    2015-07-01

    Full Text Available AIM: To investigate expressions of matrix metalloproteinase-2(MMP-2and extracellular matrix metalloproteinase inducer(EMMPRINin retinoblastoma(Rband the relationships between MMP-2, EMMPRIN and tumor development.METHODS:Immunohistochemical technique was used to detect expressions of MMP-2 and EMMPRIN in 39 cases of paraffin embedded Rb samples. Quantitative analysis of expressions of MMP-2 and EMMPRIN were assessed by measuring the mean gray scale of Rb tissue with LEICA IM50 Color Pathologic Analysis System. The differences of expressions of MMP-2 and EMMPRIN in each clinical and pathological stage were statistically analyzed, and the same step was also undertaken to study the relationship between Rb with MMP-2 positive expression and that with EMMPRIN positive expression.RESULTS: The positive expression rate of MMP-2 was 90%(Gray value: 109.64±14.52; 35/39, and that of EMMPRIN was 85%(Gray value: 108.01±13.60; 33/39. The expressions of MMP-2 and EMMPRIN were significantly higher in tumors of glaucomatous stage(Gray value: 108.21±11.47 and 107.56±14.32than those in intraocular stage(Gray value: 121.13±11.32 and 119.34±12.66; PPPPPPCONCLUSION: The positive expression levels of MMP-2 and EMMPRIN may correlate with tumor infiltration and metastasis.

  3. Proton and electron deep dose profiles for retinoblastoma based on GEANT 4 code

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Flavia V., E-mail: flaviafisica@gmail.co [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pos-graduacao em Ciencias e Tecnicas Nucleares; Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Campos, Tarcisio P.R. de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pos-graduacao em Ciencias e Tecnicas Nucleares; Ribeiro, Kilder L., E-mail: kilderlr@gmail.co [Universidade Estadual de Feira de Santana (UEFS), BA (Brazil). Dept. de Fisica

    2009-07-01

    Herein, the dosimetry responses to a retinoblastoma proton and electron radiation therapy were investigated. The computational tool applied to this simulation was the Geant4 code, version 4.9.1. The code allows simulating the charge particle interaction with eyeball tissue. In the present simulation, a box of 4 cm side water filled had represented the human eye. The simulation was performed considering mono energetic beams of protons and electrons with spectra of 57 to 70 MeV for protons and 2 to 8 MeV for electrons. The simulation was guide by the advanced hadron therapy example distributed with the Geant4 code. The phantom was divided in voxels with 0.2 mm side. The energy deposited in each voxel was evaluated taken the direct beam at one face. The simulation results show the delivery energy and therefore the dose deposited in each voxel. The deep dose profiles to proton and electron were plotted. The well known Bragg peak was reproduced for protons. The maximum delivered dose defined the position at the proton stopped. However, to electrons, the absorbed energies were delivered along its path producing a more continuous distribution following the water depth, but also being stopped in the end of its path. (author)

  4. The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

    Science.gov (United States)

    Varley, J M; Armour, J; Swallow, J E; Jeffreys, A J; Ponder, B A; T'Ang, A; Fung, Y K; Brammar, W J; Walker, R A

    1989-06-01

    We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

  5. Polymerase chain reaction detection of retinoblastoma gene deletions in paraffin-embedded mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1991-01-01

    A Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene using microtomed sections from paraffin-embedded radiation-induced and spontaneous tumors as the DNA source. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments relative to control PCR products on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons) were analyzed. Tumors in six neutron-irradiated mice also had no mRb deletions. However, one of six tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  6. The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis.

    Science.gov (United States)

    Goupille, Olivier; Penglong, Tipparat; Kadri, Zahra; Granger-Locatelli, Marine; Denis, Raphaël; Luquet, Serge; Badoual, Cécile; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

    2017-12-19

    GATA transcription factors and their FOG cofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOG factors. We recently demonstrated that interactions between retinoblastoma protein (pRb) and GATA-1 are crucial for erythroid proliferation and differentiation. We show here that the LXCXE pRb-binding site of FOG-2 is involved in adipogenesis. Unlike GATA-1, which inhibits cell division, FOG-2 promotes proliferation. Mice with a knockin of a Fog2 gene bearing a mutated LXCXE pRb-binding site are resistant to obesity and display higher rates of white-to-brown fat conversion. Thus, each component of the GATA/FOG complex (GATA-1 and FOG-2) is involved in pRb/E2F regulation, but these molecules have markedly different roles in the control of tissue homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Restrictions in daily life after retinoblastoma from the perspective of the survivors.

    Science.gov (United States)

    van Dijk, Jennifer; Oostrom, Kim J; Huisman, Jaap; Moll, Annette C; Cohen-Kettenis, Peggy T; Ringens, Peter J; Imhof, Saskia M

    2010-01-01

    Little is known about the impact of retinoblastoma (RB) on the health status of survivors in terms of disabilities and worries, both of which may restrict participation in activities of daily life. In this population-based cross-sectional study, content analysis was used to extract data on perceived restrictions and worries, from semi-structured interviews held with 156 RB survivors aged 8-35 years. The International Classification of Functioning Disabilities and Health (ICF) was used as a framework. Of all survivors, 55% perceive RB-related restrictions in daily life activities (school, professional career, mobility, self-care, intimate relationships). Young/adolescent survivors (6%) and adult survivors (15%) frequently report anxiety about developing a second primary tumor (SPT). Compared with the general population, RB survivors did not differ in rates of employment or marital status. However, special educational services were more frequently offered, and the level of completed education was lower. RB has influenced the lives of most survivors and, even though their prognosis was good, illness-related restrictions are common. Especially fear of developing SPT and of further loss of vision are important life-long problems, and many survivors had special education needs. The ICF might serve as a bridge between families and professionals, because this classification may facilitate early detection of problems. Copyright 2009 Wiley-Liss, Inc.

  8. A Bistable Circuit Involving SCARECROW-RETINOBLASTOMA Integrates Cues to Inform Asymmetric Stem Cell Division

    Science.gov (United States)

    Cruz-Ramírez, Alfredo; Díaz-Triviño, Sara; Blilou, Ikram; Grieneisen, Verônica A.; Sozzani, Rosangela; Zamioudis, Christos; Miskolczi, Pál; Nieuwland, Jeroen; Benjamins, René; Dhonukshe, Pankaj; Caballero-Pérez, Juan; Horvath, Beatrix; Long, Yuchen; Mähönen, Ari Pekka; Zhang, Hongtao; Xu, Jian; Murray, James A.H.; Benfey, Philip N.; Bako, Laszlo; Marée, Athanasius F.M.; Scheres, Ben

    2012-01-01

    SUMMARY In plants, where cells cannot migrate, asymmetric cell divisions (ACDs) must be confined to the appropriate spatial context. We investigate tissue-generating asymmetric divisions in a stem cell daughter within the Arabidopsis root. Spatial restriction of these divisions requires physical binding of the stem cell regulator SCARECROW (SCR) by the RETINOBLASTOMA-RELATED (RBR) protein. In the stem cell niche, SCR activity is counteracted by phosphorylation of RBR through a cyclinD6;1-CDK complex. This cyclin is itself under transcriptional control of SCR and its partner SHORT ROOT (SHR), creating a robust bistable circuit with either high or low SHR-SCR complex activity. Auxin biases this circuit by promoting CYCD6;1 transcription. Mathematical modeling shows that ACDs are only switched on after integration of radial and longitudinal information, determined by SHR and auxin distribution, respectively. Coupling of cell-cycle progression to protein degradation resets the circuit, resulting in a “flip flop” that constrains asymmetric cell division to the stem cell region. PMID:22921914

  9. Dosimetric evaluation in heterogeneous tissue of anterior electron beam irradiation for treatment of retinoblastoma

    International Nuclear Information System (INIS)

    Kirsner, S.M.; Hogstrom, K.R.; Kurup, R.G.; Moyers, M.F.

    1987-01-01

    A dosimetric study of anterior electron beam irradiation for treatment of retinoblastoma was performed to evaluate the influence of tissue heterogeneities on the dose distribution within the eye and the accuracy of the dose calculated by a pencil beam algorithm. Film measurements were made in a variety of polystyrene phantoms and in a removable polystyrene eye incorporated into a tissue substitute phantom constructed from a human skull. Measurements in polystyrene phantoms were used to demonstrate the algorithm's ability to predict the effect of a lens block placed in the beam, as well as the eye's irregular surface shape. The eye phantom was used to measure dose distributions within the eye in both the sagittal and transverse planes in order to test the algorithm's ability to predict the dose distribution when bony heterogeneities are present. Results show (1) that previous treatment planning conclusions based on flat, uniform phantoms for central-axis depth dose are adequate; (2) that a three-dimensional heterogeneity correction is required for accurate dose calculations; and (3) that if only a two-dimensional heterogeneity correction is used in calculating the dose, it is more accurate for the sagittal than the transverse plane

  10. Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing

    Science.gov (United States)

    García-Chequer, A.J.; Méndez-Tenorio, A.; Olguín-Ruiz, G.; Sánchez-Vallejo, C.; Isa, P.; Arias, C.F.; Torres, J.; Hernández-Angeles, A.; Ramírez-Ortiz, M.A.; Lara, C.; Cabrera-Muñoz, M.L.; Sadowinski-Pine, S.; Bravo-Ortiz, J.C.; Ramón-García, G.; Diegopérez-Ramírez, J.; Ramírez-Reyes, G.; Casarrubias-Islas, R.; Ramírez, J.; Orjuela, M.A.; Ponce-Castañeda, M.V.

    2016-01-01

    Genes are frequently lost or gained in malignant tumors and the analysis of these changes can be informative about the underlying tumor biology. Retinoblastoma is a pediatric intraocular malignancy, and since deletions in chromosome 13 have been described in this tumor, we performed genome wide sequencing with the Illumina platform to test whether recurrent losses could be detected in low coverage data from DNA pools of Rb cases. An in silico reference profile for each pool was created from the human genome sequence GRCh37p5; a chromosome integrity score and a graphics 40 Kb window analysis approach, allowed us to identify with high resolution previously reported non random recurrent losses in all chromosomes of these tumors. We also found a pattern of gains and losses associated to clear and dark cytogenetic bands respectively. We further analyze a pool of medulloblastoma and found a more stable genomic profile and previously reported losses in this tumor. This approach facilitates identification of recurrent deletions from many patients that may be biological relevant for tumor development. PMID:26883451

  11. Alteration of the retinoblastoma gene locus in radium-exposed individuals

    International Nuclear Information System (INIS)

    Hardwick, J.P.; Schlenker, R.; Huberman, E.

    1991-01-01

    This study was performed to determine if the retinoblastoma suppressor gene was altered in individuals exposed to radium. We analyzed the Rb gene in 30 individuals, 17 of whom were exposed to radium either occupationally or iatrogenically. In the kidney DNA from four of nine radium-exposed individuals, the Rb gene was deleted. Three of these alterations in the Rb gene were internal deletions, which resulted in the absence of Rb mRNA accumulation. These results imply that the Rb gene is susceptible to radium-induced damage and confirm previous showing that radiation preferentially causes genomic deletions. The pronounced alterations in the non-tumorigenic femurs from radium-exposed individuals suggests that in the many years of exposure there was a selection of cells with alterations, presumably because of their growth advantage. Also it implies that deletions of one of the Rb alleles can be one of the events (perhaps an initial one) in the progression of radium-induced sarcomas. 11 refs., 2 figs

  12. Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Erica M. [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Niu, MengMeng; Bergholz, Johann [Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China); Jim Xiao, Zhi-Xiong, E-mail: jxiao@bu.edu [Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 (United States); Center of Growth, Metabolism and Aging, College of Life Sciences, Sichuan University, Chengdu, 610014 China (China)

    2015-05-29

    The p53 tumor suppressor gene plays a critical role in regulation of proliferation, cell death and differentiation. The MDM2 oncoprotein is a major negative regulator for p53 by binding to and targeting p53 for proteasome-mediated degradation. The small molecule inhibitor, nutlin-3, disrupts MDM2-p53 interaction resulting in stabilization and activation of p53 protein. We have previously shown that nutlin-3 activates p53, leading to MDM2 accumulation as concomitant of reduced retinoblastoma (Rb) protein stability. It is well known that Rb is important in muscle development and myoblast differentiation and that rhabdomyosarcoma (RMS), or cancer of the skeletal muscle, typically harbors MDM2 amplification. In this study, we show that nutlin-3 inhibited myoblast proliferation and effectively prevented myoblast differentiation, as evidenced by lack of expression of muscle differentiation markers including myogenin and myosin heavy chain (MyHC), as well as a failure to form multinucleated myotubes, which were associated with dramatic increases in MDM2 expression and decrease in Rb protein levels. These results indicate that nutlin-3 can effectively inhibit muscle cell differentiation. - Highlights: • Nutlin-3 inhibits myoblast proliferation and prevents differentiation into myotubes. • Nutlin-3 increases MDM2 expression and down-regulates Rb protein levels. • This study has implication in nutlin-3 treatment of rhabdomyosarcomas.

  13. CONTAINER TERMINALS IN EUROPE

    Directory of Open Access Journals (Sweden)

    Bart W. WIEGMANS

    2001-01-01

    Full Text Available This paper aims to address the linkage between logistics (in particular, the management of marketing channel flows and transport markets, while also the interaction between these two markets and intermodal container terminals is analysed. The marketing channel theory is used to describe all relevant actors and flows that run through marketing channels, starting with customer needs and ending with customer satisfaction. Porter's theory of competitive advantages is used to review competitive forces in both markets. Finally, a competitor analysis is performed for the logistics and transport market. These theories are applied so as to be able to determine the competitive position of intermodal container terminals with a view to the management of marketing channel flows and the physical transport of freight flows. Hence, the central question of this paper is: Which markets are served by intermodal container terminals and with whom are they competing? At present, neither the maritime container terminals nor the continental container terminals appear to have a significant influence in the logistics service market; they concentrate mainly on the physical movement of containers (transshipment. Furthermore, maritime container terminals and continental container terminals are not dominant players in the transport service market. Our conclusion is that continental terminals are predominantly competing with unimodal road transport, with neighbouring continental terminals and with barge transport companies.

  14. Intra-Arterial Chemotherapy as Primary Therapy for Retinoblastoma in Infants Less than 3 Months of Age: A Series of 10 Case-Studies.

    Directory of Open Access Journals (Sweden)

    Miaojuan Chen

    Full Text Available Retinoblastoma is the most common primary malignant intra-ocular tumor in children. Although intra-arterial chemotherapy (IAC by selectively infusing chemotherapy through the ophthalmic artery has become an essential technique in the treatment of advanced intra-ocular retinoblastoma in children, the outcome of IAC as primary therapy for infants less than 3 months of age remains unknown. In this retrospective study, we reviewed the outcome of IAC as primary therapy for retinoblastoma in infants less than 3 months of age.We retrospectively reviewed ten retinoblastoma patients attending our center from January 2009 to September 2015 and beginning primary IAC before the age of 3 months. The patient characteristics, overall outcomes and therapy-related complications were assessed.The mean patient age at the first IAC treatment was 10.4 weeks (range 4.9-12.9 weeks. These eyes were classified according to the International Classification of Retinoblastoma (ICRB as group A (n = 0, B (n = 2, C (n = 0, D (n = 9, or E (n = 2. A total of 28 catheterizations were performed, and the procedure was stopped in one patient because of internal carotid artery spasm. Each eye received a mean of 2.6 cycles of IAC (range 2-4 cycles. After IAC with a mean follow-up of 28.3 months (range 9-65 months, tumor regression was observed in 12 of 13 eyes. One eye was enucleated due to tumor progression. All patients are alive and no patient has developed metastatic disease or other malignancies.Our experience suggests IAC as primary therapy is a feasible and promising treatment for retinoblastoma in infants less than 3 months of age.

  15. [The efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in retinoblastoma therapy].

    Science.gov (United States)

    Liang, J H; Cheng, Y; Deng, X; Yu, Y Y; Li, X X

    2016-10-11

    Objective: To evaluate the efficacy of large spot indirect ophthalmoscopy laser alone or combined with systemic chemotherapy in the treatment of early and middle stage retinoblastoma. Methods: Retrospective series case study. Clinical data of 21 patients (22 eyes) who were diagnosed as retinoblastoma (RB) in Peking University People's Hospital from March 2009 to August 2014 were collected. Medical and family history, ocular ultrasound, orbital and cranial MRI or CT examination of RB Children were detailed recorded. Ocular examination and laser treatment were performed under general anesthesia, once every 3-4 weeks until the tumor was under control. The observation period was at least 3 months after the last treatment. The ocular examination included intraocular pressure measurement, anterior segment and fundus examination and the fundus photography with Retcam. Laser therapeutic instrument was large spot indirect ophthalmoscopy laser of 810nm wavelength. Results: Of the 21 children, 16 were male and 5 were female. The range of age was 3 to 82 months averaged 17.3 months. Among 22 eyes, four with small tumor, eight with medium tumor, and ten with large tumor. Two eyes underwent laser treatment only and 20 eyes underwent laser treatment combined with systemic chemotherapy. During the average observation period of 33.9 months, 15 tumors were treated successfully, but 7 failed. The total success rate was 68.2%. The number and success rate of small, medium and large tumor eyes were 4 (100%), 5 (62.5%) and 5 (50%), respectively. There was one case of tumor brain metastases, and the classification of contralateral eye of the child was E phase. Iris burns happened in one eye, obvious vitreous proliferation in one eye and mild vitreous hemorrhage occurred in two eyes, which did not affect the treatment of laser. However, obvious tumor hemorrhage happened in two eyes and affected laser therapy. There was no complicated cataract, iatrogenic retinal hole and tumor intravitreal

  16. Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Chi-Tuan; Blanc, Raphael; Pistocchi, Silvia; Bartolini, Bruno; Piotin, Michel [Fondation Rothschild Hospital, Department of Interventional Neuroradiology, Paris (France); Lumbroso-Le Rouic, Livia [Institut Curie, Department of Ocular Oncology, Paris (France)

    2012-08-15

    Intra-arterial infusion of chemotherapy into the ophthalmic artery for treatment of retinoblastoma has been realized after catheterization of the internal carotid and temporary balloon occlusion beyond the orifice of the ophthalmic artery, or more recently after superselective canulation of the ophthalmic artery by a microcatheter. The superselective catheterization of the ophthalmic artery could be cumbersome because of the implantation of the ostium on the carotid siphon or because of the tortuosity of the carotid siphon. We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery. (orig.)

  17. Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

    DEFF Research Database (Denmark)

    Mercader, Josep; Ribot, Joan; Murano, Incoronata

    2009-01-01

    Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ-line haploinsufficiency of the pRb gene (Rb) on the...... first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances. Key words: brown adipose tissue, white adipose tissue, energy metabolism, genetic animal model....

  18. Lazy Productivity via Termination

    NARCIS (Netherlands)

    Endrullis, J.; Hendriks, R.D.A.

    2011-01-01

    We present a procedure for transforming strongly sequential constructor-based term rewriting systems (TRSs) into context-sensitive TRSs in such a way that productivity of the input system is equivalent to termination of the output system. Thereby automated termination provers become available for

  19. Termination of cycle rewriting

    NARCIS (Netherlands)

    Zantema, H.; König, B.; Bruggink, H.J.S.; Dowek, G.

    2014-01-01

    String rewriting can not only be applied on strings, but also on cycles and even on general graphs. In this paper we investigate termination of string rewriting applied on cycles, shortly denoted as cycle rewriting, which is a strictly stronger requirement than termination on strings. Most

  20. Radiotherapy and genetic susceptibility to cancer in a cohort of retinoblastoma patients

    International Nuclear Information System (INIS)

    Kleinerman, R. A.; Abranson, D. H.; Seddon, J. M.; Stovall, M.; Tucker, M. A.

    2004-01-01

    High-dose radiotherapy for retinoblastoma, a rare childhood cancer of the eye caused by a germline mutation in the RB-1 gene, has been associated with an increased risk of sarcomas, predominantly in the head and neck region, in childhood and adolescence. Many RB patients are cured and survive into adulthood. It is important to quantify their risk of adult-onset cancers, because somatic mutations in the RB-1 gene are common in the pathways of several epithelial cancers that typically occur in adults. We have been studying a large cohort of 1601 RB survivors, who were diagnosed 1914-84 at two medical centers, to identify the risk of second cancers and evaluate the interaction between radiation and genetic factors that may modify these risks. Most of the RB patients were diagnosed at one year of age or younger, 80% of the hereditary patients and 20% of the sporadic patients received radiotherapy for RB. A typical radiation treatment in the 1970s consisted of 45 Gy to the entire retina delivered in 15 fractions over several weeks. At last follow up, 20% of the cohort was 40 years of age and older, an age at which cancer rates begin to rise in the general population. We ascertained the incidence of new cancers through 2001 and compared the observed number of cancers in the cohort to the expected number of cancers estimated from age, sex and calendar year-specific cancer incidence rates from the U. S. We calculated the excess risk (ER) of cancer per 1,000 person years (observed minus expected number of cancers/person years at risk time 1000). The excess risk of second cancers in 963 hereditary patients (ER=9.3) exceeded the risk in the 638 sporadic patients (Excess risk=0.06). Substantially higher risks of second cancers were noted for irradiated (ER=10.1) compared to non-irradiated, hereditary patients (ER=4.5). Increased risks likely related to radiation were observed for cancers of the bone, soft tissue, brain, nasal cavities, and eye and orbit. Newly identified

  1. Kitimat LNG terminal

    International Nuclear Information System (INIS)

    Schmaltz, I.; Boulton, R.

    2007-01-01

    Kitimat Liquefied Natural Gas (LNG) terminal is a terminal development company owned by Galveston LNG, a privately owned Canadian energy development company. This presentation provided information on Kitimat LNG with particular reference to its terminal located in Bish Cove on the Douglas Channel in British Columbia. This LNG terminal is reported to be the only fully permitted regasification terminal on the west coast of Canada and the United States. The presentation addressed market fundamentals including several graphs, such as world natural gas proved reserves in 2006; LNG supplements to Canadian gas supplies; global LNG demand for 2005-2020; average annual United States LNG imports; and global LNG liquefaction projects. Other market fundamentals were described, including that Kitimat is the only other approved terminal aside from the Costa Azul terminal in Mexico; Kitimat is the only west coast LNG import terminal that connects to midwest and eastern North American markets through existing gas pipelines; LNG producers are looking for destination diversification; and markets and marketers are looking for supply diversification. The authors noted that by 2010, western Canadian gas demand will exceed Californian demand. Other topics that were discussed in the presentation included Canadian natural gas field receipts; unadjusted bitumen production outlook; oil sands gas demand; forward basis fundamentals; and the commercial drivers of the Kitimat LNG terminal. The presentation also discussed the pacific trail pipelines, a partnership between Galveston LNG and Pacific Northern Gas to develop the natural gas transmission line from Kitimat to Summit. The presentation concluded with a discussion of the benefits of Kitimat LNG terminal such as providing access to the largest natural gas markets in the world via major gas transmission lines with spare capacity. figs

  2. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    International Nuclear Information System (INIS)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-01-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF 1 mice irradiated with 60 Co γ rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of 60 Co γ rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from γ-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5' region of the mRb gene

  3. External beam irradiation for retinoblastoma: patterns of failure and dose-response analysis

    International Nuclear Information System (INIS)

    Foote, R.L.; Garretson, B.R.; Schomberg, P.J.; Buskirk, S.J.; Robertson, D.M.; Earle, J.D.

    1989-01-01

    Eighteen children with retinoblastoma (25 eyes) were treated with external beam radiation at the Mayo Clinic between January 1977 and January 1987; 15 eyes were in groups I to III and 10 were in groups IV and V. The median number of tumors per eye was 3. Radiation therapy consisted of 4- or 6-MV photons. Doses varied from 39 to 51 Gy in 1.8- to 3.0-Gy fractions. Fourteen eyes were treated through lateral fields by anterior segment-sparing techniques, and 11 eyes were treated by an anterior approach with no attempt at anterior segment sparing. All patients survived (median follow-up, 31.5 months). Cataracts developed in five eyes at a median of 23 months, four in eyes treated with anterior segment-sparing techniques. Of the 15 group I to III eyes, 6 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation and 2 were enucleated. Of the 10 group IV and V eyes, 8 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation, 1 with persistent disease is being followed closely, and 3 were enucleated. Ten (71%) of the 14 eyes treated with anterior segment-sparing techniques required additional treatment. Four (36%) of the 11 eyes treated with an anterior approach required additional treatment. Ninety percent of the tumors 10 disc diameters or smaller (1 disc diameter = 1.6 mm) were controlled independently of dose and fractionation used when they were not in the low-dose area of the anterior retina of an eye treated with an anterior segment-sparing technique. We find that use of lateral, anterior segment-sparing techniques has a high risk of anterior retinal tumor development and cataract formation and should be abandoned in favor of techniques that treat the entire retina

  4. External beam irradiation for retinoblastoma: patterns of failure and dose-response analysis

    Energy Technology Data Exchange (ETDEWEB)

    Foote, R.L.; Garretson, B.R.; Schomberg, P.J.; Buskirk, S.J.; Robertson, D.M.; Earle, J.D.

    1989-03-01

    Eighteen children with retinoblastoma (25 eyes) were treated with external beam radiation at the Mayo Clinic between January 1977 and January 1987; 15 eyes were in groups I to III and 10 were in groups IV and V. The median number of tumors per eye was 3. Radiation therapy consisted of 4- or 6-MV photons. Doses varied from 39 to 51 Gy in 1.8- to 3.0-Gy fractions. Fourteen eyes were treated through lateral fields by anterior segment-sparing techniques, and 11 eyes were treated by an anterior approach with no attempt at anterior segment sparing. All patients survived (median follow-up, 31.5 months). Cataracts developed in five eyes at a median of 23 months, four in eyes treated with anterior segment-sparing techniques. Of the 15 group I to III eyes, 6 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation and 2 were enucleated. Of the 10 group IV and V eyes, 8 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation, 1 with persistent disease is being followed closely, and 3 were enucleated. Ten (71%) of the 14 eyes treated with anterior segment-sparing techniques required additional treatment. Four (36%) of the 11 eyes treated with an anterior approach required additional treatment. Ninety percent of the tumors 10 disc diameters or smaller (1 disc diameter = 1.6 mm) were controlled independently of dose and fractionation used when they were not in the low-dose area of the anterior retina of an eye treated with an anterior segment-sparing technique. We find that use of lateral, anterior segment-sparing techniques has a high risk of anterior retinal tumor development and cataract formation and should be abandoned in favor of techniques that treat the entire retina.

  5. Localized whole eye radiotherapy for retinoblastoma using a 125I applicator, 'claws'

    International Nuclear Information System (INIS)

    Stannard, Clare; Sealy, Rossall; Hering, Egbert; Korrubel, Jan; Hill, John; Barron, Adrian; Knowles, Ruth

    2001-01-01

    Purpose: To treat children with retinoblastoma, who require whole eye radiotherapy, with a specially designed 125 I applicator that irradiates the eye while sparing the surrounding tissues. Methods and Materials: Under general anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4 appendages, each loaded with 125 I seeds, are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and 11 received 40 Gy during 122 hours, when the relative biologic effectiveness was taken as 1 instead of 1.5. Six had received prior chemotherapy. Results: Twenty-four eyes were followed up for 2-157 months (median 29). Although 22 eyes responded, local control was achieved in 13 patients, 3 of whom required additional treatment for new tumors; a further 3 required additional treatment for tumor recurrence as well as new tumors. One of these eyes was enucleated for neovascular glaucoma. All 6 Group I-III eyes and 6 of 18 Group V eyes were retained for 2-157 months (median 39), with good vision in 10 eyes. Three developed cataracts 7, 8, and 12 years later, 1 of which has been removed. Conclusions: This is a new way of irradiating the whole eye with a minimal dose to the surrounding tissues. The treatment time is only 5 days. It is effective in Groups I-III, but only 33% of Group V eyes retained vision. No late cosmetic defects occurred

  6. Radiation therapy for retinoblastoma: comparison of results with lens-sparing versus lateral beam techniques

    International Nuclear Information System (INIS)

    McCormick, B.; Ellsworth, R.; Abramson, D.; Haik, B.; Tome, M.; Grabowski, E.; LoSasso, T.

    1988-01-01

    From 1979 through 1986, 170 children were seen at our institution diagnosed with retinoblastoma. Sixty-six of the children with involvement of 121 eyes, were referred for definitive external beam radiation to one or both eyes. During the study period, two distinct radiation techniques were used. From 1980 through mid-1984, a lens-sparing technique included an anterior electron beam with a contact lens mounted lead shield, combined with a lateral field, was used. Since mid-1984, a modified lateral beam technique has been used, mixing lateral electrons and superior and inferior lateral oblique split beam wedged photons. Doses prescribed were similar for both techniques, ranging from 3,850 to 5,000 cGy in 4 to 5 weeks. The lens-sparing and the modified lateral techniques are compared for local control. For eyes with Group I through III disease, the lens-sparing technique resulted in local control in 33% of the eyes treated, where the modified lateral technique controlled 83% of the eyes treated (p = .006). Mean time to relapse was identical in both groups, that is 24 and 26 months respectively. Most relapses were successfully treated with further local therapy, including laser or cryosurgery, or 60Co plaques. Five eyes required enucleation following initial treatment with the lens-sparing technique, but none thus far with the lateral beam technique. For eyes with Group IV and V disease, no significant differences were found between the two techniques in terms of local control or eventual need for enucleation. With a mean follow-up time of 33 months for the entire group, the 4-year survival is 93%. Two of the 4 deaths are due to second primary tumor, and all 4 have occurred in the lens-sparing group. Because follow-up time is more limited in the lateral beam group, this is not statistically significant and direct survival comparisons are premature

  7. Hepatitis C virus induces E6AP-dependent degradation of the retinoblastoma protein.

    Directory of Open Access Journals (Sweden)

    Tsubasa Munakata

    2007-09-01

    Full Text Available Hepatitis C virus (HCV is a positive-strand RNA virus that frequently causes persistent infections and is uniquely associated with the development of hepatocellular carcinoma. While the mechanism(s by which the virus promotes cancer are poorly defined, previous studies indicate that the HCV RNA-dependent RNA polymerase, nonstructural protein 5B (NS5B, forms a complex with the retinoblastoma tumor suppressor protein (pRb, targeting it for degradation, activating E2F-responsive promoters, and stimulating cellular proliferation. Here, we describe the mechanism underlying pRb regulation by HCV and its relevance to HCV infection. We show that the abundance of pRb is strongly downregulated, and its normal nuclear localization altered to include a major cytoplasmic component, following infection of cultured hepatoma cells with either genotype 1a or 2a HCV. We further demonstrate that this is due to NS5B-dependent ubiquitination of pRb and its subsequent degradation via the proteasome. The NS5B-dependent ubiquitination of pRb requires the ubiquitin ligase activity of E6-associated protein (E6AP, as pRb abundance was restored by siRNA knockdown of E6AP or overexpression of a dominant-negative E6AP mutant in cells containing HCV RNA replicons. E6AP also forms a complex with pRb in an NS5B-dependent manner. These findings suggest a novel mechanism for the regulation of pRb in which the HCV NS5B protein traps pRb in the cytoplasm, and subsequently recruits E6AP to this complex in a process that leads to the ubiquitination of pRb. The disruption of pRb/E2F regulatory pathways in cells infected with HCV is likely to promote hepatocellular proliferation and chromosomal instability, factors important for the development of liver cancer.

  8. A tool for planning retinoblastoma services in sub-Saharan Africa.

    Science.gov (United States)

    Hampejsková, Lindsay; Bascaran, Covadonga; Zondervan, Marcia

    2017-04-01

    Cancer care remains inadequate in low-middle income countries (LMICs). Children with cancer have 80% chance of surviving in high-income countries compared to 20% in LMICs. Retinoblastoma (RB), an aggressive eye cancer of childhood and top childhood cancer in sub-Saharan Africa (SSA), has a low survival rate, due to a delay in diagnosis and abandonment of treatment. The purpose of this study is to provide a tool for planning human resources required to manage RB in SSA. Online tool was developed with 19 modifiable fields and 23 estimates. Routine data were used to populate modifiable fields: population, birthrate, infant mortality rate, and total fertility rate. Values were held constant: frequency, 1:17,000; familial cases, 8%; unilateral RB, 74%; extraocular disease, 70%; and survival postextraocular treatment, 10%. One thousand twenty-three RB incident and familial cases are estimated each year across Ethiopia, Ghana, Malawi, Nigeria, Tanzania, Uganda, Zambia, and Zimbabwe: 75 familial, 700 unilateral, 717 extraocular disease, and 645 palliative. Nigeria represents 431 cases and Zimbabwe 33 cases. Over the eight countries, a total of 41,558 patient visits are estimated each year consisting of unilateral enucleation, follow-up visits, intensive treatment, and familial screening, with a total of 2,802 prosthetic eyes being required each year. In the absence of data, estimates are essential for planning countrywide medical services. More attention is needed around planning for services from the Ministry level including emphasis on building multidisciplinary teams for diseases such as RB, including countrywide database and integrated clinical practice guidelines among all levels of care. © 2016 Wiley Periodicals, Inc.

  9. Nonleaking battery terminals.

    Science.gov (United States)

    Snider, W. E.; Nagle, W. J.

    1972-01-01

    Three different terminals were designed for usage in a 40 ampere/hour silver zinc battery which has a 45% KOH by weight electrolyte in a plastic battery case. Life tests, including thermal cycling, electrical charge and discharge for up to three years duration, were conducted on these three different terminal designs. Tests for creep rate and tensile strength were conducted on the polyphenylene oxide plastic battery cases. Some cases were unused and others containing KOH electrolyte were placed on life tests. The design and testing of nonleaking battery terminals for use with a KOH electrolyte in a plastic case are considered.

  10. Fractionated stereotaxic radiotherapy in the treatment of the retinoblastoma: preliminary results; Radiotherapie stereotaxique fractionnee dans le traitement du retinoblastome: resultats preliminaires

    Energy Technology Data Exchange (ETDEWEB)

    Pica, A. [Centre Hospitalier Universitaire Vaudois (CHUV), Service de Radiotherapie, Lausanne (Switzerland); Moeckli, R.; Do, H. [Institut de Radiophysique Appliquee, Lausanne (Switzerland); Balmer, A.; Munier, F. [Hopital ophtalmique Jules-Gonin, Lausanne (Switzerland); Chollet Rivier, M. [Centre Hospitalier Universitaire Vaudois (CHUV), Service d' Anesthesie, Lausanne (Switzerland)

    2006-11-15

    The objective of this study is to evaluate the impact in term of morbidity at short and long term and the response to the fractionated stereotaxic radiotherapy with a micro multi slides collimator in the treatment of the retinoblastoma. (N.C.)

  11. High-resolution MRI using orbit surface coils for the evaluation of metastatic risk factors in 143 children with retinoblastoma. Part 1: MRI vs. histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Sirin, Selma; Schlamann, Marc; Schweiger, Bernd; Goericke, Sophia L. [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Metz, Klaus A. [University Hospital Essen, Department of Pathology and Neuropathology, Essen (Germany); Bornfeld, Norbert; Holdt, Markus [University Hospital Essen, Department of Ophthalmology, Essen (Germany); Temming, Petra; Schuendeln, Michael M. [University Hospital Essen, Department of Pediatric Hematology and Oncology, Essen (Germany)

    2015-08-15

    A reliable detection of metastatic risk factors is important for children with retinoblastoma to choose the right therapeutic regimen. First studies using high-resolution magnetic resonance imaging (MRI) with orbit surface coils were promising. The aim of this study was therefore to evaluate the ability of high-resolution MRI to detect metastatic and especially advanced metastatic risk factors in a large group of children with retinoblastoma. One hundred forty-three consecutive children with retinoblastoma (148 enucleated eyes, 64 girls, 79 boys, mean age 19.7 ± 15.3) who received pretherapeutical high-resolution MRI with orbit surface coils on 1.5 T MR scanner systems between 2007 and 2012 and subsequent primary enucleation within 14 days were included in this retrospective study. Image analysis was performed by two neuroradiologists experienced in ocular imaging in consensus. Histopathology served as gold standard. Sensitivity/specificity for the detection of metastatic risk factors using high-resolution MRI with orbit surface coils were 60 %/88.7 % for postlaminar optic nerve infiltration, 65.5 %/95.6 % for choroidal invasion, 100 %/99.3 % for scleral invasion, and 100 %/100 % for peribulbar fat invasion, respectively. The results increased for the detection of advanced metastatic risk factors, 81.8 %/89.1 % for deep postlaminar optic nerve infiltration, 70.6 %/97.6 % for massive choroidal invasion. High-resolution MRI is clinically valuable for the detection of metastatic, especially of advanced metastatic risk factors in children with retinoblastoma. (orig.)

  12. Nontraumatic terminal ileal perforation

    Directory of Open Access Journals (Sweden)

    Wani Rauf A

    2006-03-01

    Full Text Available Abstract Background There is still confusion and controversy over the diagnosis and optimal surgical treatment of non traumatic terminal ileal perforation-a cause of obscure peritonitis. Methods This study was a prospective study aimed at evaluating the clinical profile, etiology and optimal surgical management of patients with nontraumatic terminal ileal perforation. Results There were 79 cases of nontraumatic terminal ileal perforation; the causes for perforation were enteric fever(62%, nonspecific inflammation(26%, obstruction(6%, tuberculosis(4% and radiation enteritis (1%. Simple closure of the perforation (49% and end to side ileotransverse anastomosis(42% were the mainstay of the surgical management. Conclusion Terminal ileal perforation should be suspected in all cases of peritonitis especially in developing countries and surgical treatment should be optimized taking various accounts like etiology, delay in surgery and operative findings into consideration to reduce the incidence of deadly complications like fecal fistula.

  13. Terminated Multifamily Mortgages Database

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes all terminated HUD Multifamily mortgages except those from the Hospital Mortgage Insurance Program. It includes the Holder and Servicer at the...

  14. Coal terminal directory

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-06-15

    The directory gives a comprehensive listing of the world's coal terminals, in a total of 50 countries including information on throughput, facilities, storage capacity, and vessel size limitation.

  15. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-07-08

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection*

    Science.gov (United States)

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-01-01

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. PMID:27226547

  17. Visual communication and terminal equipment

    International Nuclear Information System (INIS)

    Kang, Cheol Hui

    1988-06-01

    This book is divided two parts about visual communication and terminal equipment. The first part introduces visual communication, which deals with foundation of visual communication, technique of visual communication, equipment of visual communication, a facsimile and pictorial image system. The second part contains terminal equipment such as telephone, terminal equipment for data transmission on constitution and constituent of terminal equipment for data transmission, input device and output device, terminal device and up-to-date terminal device.

  18. Visual communication and terminal equipment

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Cheol Hui

    1988-06-15

    This book is divided two parts about visual communication and terminal equipment. The first part introduces visual communication, which deals with foundation of visual communication, technique of visual communication, equipment of visual communication, a facsimile and pictorial image system. The second part contains terminal equipment such as telephone, terminal equipment for data transmission on constitution and constituent of terminal equipment for data transmission, input device and output device, terminal device and up-to-date terminal device.

  19. Long-term medical outcomes in survivors of extra-ocular retinoblastoma: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience.

    Science.gov (United States)

    Friedman, Danielle Novetsky; Sklar, Charles A; Oeffinger, Kevin C; Kernan, Nancy A; Khakoo, Yasmin; Marr, Brian P; Wolden, Suzanne L; Abramson, David H; Dunkel, Ira J

    2013-04-01

    Data on long-term outcomes of survivors of extra-ocular retinoblastoma are lacking. The authors sought to provide the first report characterizing long-term outcomes among survivors of extra-ocular retinoblastoma. Retrospective analysis of long-term medical outcomes in 19 survivors of extra-ocular retinoblastoma treated between 1992 and 2009. Severity of outcomes was graded using Common Terminology Criteria for Adverse Events. All patients received intensive multimodality therapy for their extra-ocular disease after management of their primary intra-ocular disease, including conventional chemotherapy (n = 19, 100%), radiotherapy (n = 15, 69%), and/or high-dose chemotherapy with autologous stem cell transplant (n = 17, 89%). The median follow-up was 7.8 years from diagnosis of extra-ocular retinoblastoma (range 2-17.8 years). The most common long-term non-visual outcomes were hearing loss (n = 15, 79%), short stature (n = 7, 37%), and secondary malignancies [SMN] (n = 6, 31%). Sixty-eight percent of survivors exhibited ≥2 non-visual long-term outcomes of any grade. Except short stature, which was not graded for severity, Grade 3-4 outcomes were limited to: ototoxicity (n = 8; n = 4 require hearing aids), SMNs (n = 6), and unequal limb length (n = 1). Five patients who developed SMNs carried a known RB1 mutation. SMNs developed at a median of 11.1 years after initial diagnosis; two patients died of their SMN. Long-term cardiac, pulmonary, hepatobiliary, or renal conditions were not identified in any survivors. Long-term outcomes are commonly seen in extra-ocular retinoblastoma survivors but the majority are mild-moderate in their severity. Longer comprehensive follow-up is needed to fully assess treatment-related outcomes but the information collected to date may affect management decisions for children with extra-ocular disease. Copyright © 2012 Wiley Periodicals, Inc.

  20. Modification of the Campylobacter jejuni N-linked glycan by EptC protein-mediated addition of phosphoethanolamine

    DEFF Research Database (Denmark)

    Scott, Nichollas E; Nothaft, Harald; Edwards, Alistair V G

    2012-01-01

    . Interrogation of these data allowed the identification of a phosphoethanolamine (pEtN)-modified variant of the N-glycan that was attached to multiple proteins. The pEtN moiety was attached to the terminal GalNAc of the canonical N-glycan. Deletion of the pEtN transferase eptC removed all evidence of the p......, yet above background levels of pEtN-glycan were also observed in E. coli not expressing eptC, suggesting that endogenous E. coli pEtN transferases can mediate the addition of pEtN to N-glycans. The addition of pEtN must be considered in the context of glycoengineering and may alter C. jejuni glycan...