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Sample records for lymphoma neuroblastoma retinoblastoma

  1. Neuroblastoma in Children: Just Diagnosed Information

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  2. Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Aerts Isabelle

    2006-08-01

    Full Text Available Abstract Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of 1/15,000–20,000 live births. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulites and exophthalmia may also be observed. Sixty per cent of retinoblastomas are unilateral and most of these forms are not hereditary (median age at diagnosis two years. Retinoblastoma is bilateral in 40% of cases (median age at diagnosis one year. All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject constitutionally carrying an RB1 gene mutation has a greater than 90% risk of developing retinoblastoma but is also at increased risk of developing other types of cancers. Diagnosis is made by fundoscopy. Ultrasound, magnetic resonance imaging (MRI and computed tomography (CT scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. Conservative treatment for at least one eye is possible in most of the bilateral cases. It includes laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Vital prognosis, related to retinoblastoma alone, is now excellent in patients with unilateral or bilateral forms of retinoblastoma. Long term follow-up and early counseling regarding the risk of second primary

  3. Identification of alpha 2-adrenergic receptor sites in human retinoblastoma (Y-79) and neuroblastoma (SH-SY5Y) cells

    Energy Technology Data Exchange (ETDEWEB)

    Kazmi, S.M.; Mishra, R.K.

    1989-02-15

    The existence of specific alpha 2-adrenergic receptor sites has been shown in human retinoblastoma (Y-79) and neuroblastoma (SH-SH5Y) cells using direct radioligand binding. (/sup 3/H)Rauwolscine, a selective alpha 2-adrenergic receptor antagonist, exhibited high affinity, saturable binding to both Y-79 and SH-SY5Y cell membranes. The binding of alpha 1 specific antagonist, (/sup 3/H)Prazocine, was not detectable in either cell type. Competition studies with antagonists yielded pharmacological characteristics typical of alpha 2-adrenergic receptors: rauwolscine greater than yohimbine greater than phentolamine greater than prazocine. Based on the affinity constants of prazocine and oxymetazoline, it appears that Y-79 cells contain alpha 2A receptor, whereas SH-SY5Y cells probably represent a mixture of alpha 2A and alpha 2B receptors. alpha 2-agonists clonidine and (-)epinephrine inhibition curves yielded high and low affinity states of the receptor in SH-SY5Y cells. Gpp(NH)p and sodium ions reduced the proportion of high affinity sites of alpha 2 receptors. These two neuronal cell lines of human origin would prove useful in elucidating the action and regulation of human alpha 2-adrenergic receptors and their interaction with other receptor systems.

  4. Neuroblastoma

    Science.gov (United States)

    Davidoff, Andrew M.

    2011-01-01

    Neuroblastoma is a heterogeneous disease; tumors can spontaneously regress or mature, or display an aggressive, therapy-resistant phenotype. Increasing evidence indicates that the biologic and molecular features of neuroblastoma significantly influence and are highly predictive of clinical behavior. Because of this, neuroblastoma has served as a paradigm for biological risk assessment and treatment assignment. Most current clinical studies of neuroblastoma base therapy and its intensity on a risk stratification that takes into account both clinical and biologic variables predictive of relapse. For example, surgery alone offers definitive therapy with excellent outcome for patients with low-risk disease, while patients at high-risk for disease relapse are treated with intensive multimodality therapy. In this review recent advances in the understanding of the molecular genetic events involved in neuroblastoma pathogenesis are discussed, and how they are impacting the current risk stratification and providing potential targets for new therapeutic approaches for children with neuroblastoma. In addition, the results of significant recent clinical trials for the treatment of neuroblastoma are reviewed. PMID:22248965

  5. Neuroblastoma

    Science.gov (United States)

    ... also may be at higher risk for other cancers. Caring for Your Child Being told your child has neuroblastoma can be ... Cancer Center Use Finn's Story to Talk About Cancer Preparing Your Child for Surgery Late Effects of Cancer and Cancer ...

  6. 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 form

  7. Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-07-01

    Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  8. Expression of retinoblastoma protein and P16 proteins in classic Hodgkin lymphoma : relationship with expression of p53 and presence of Epstein-Barr virus in the regulation of cell growth and death

    NARCIS (Netherlands)

    Kim, LH; Peh, SC; Poppema, S

    2006-01-01

    Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins INK4A (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of H

  9. IVF and retinoblastoma revisited.

    NARCIS (Netherlands)

    Dommering, C.J.; Hout, A.H. van der; Meijers-Heijboer, H.; Marees, T.; Moll, A.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 spe

  10. 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 spe

  11. [Retinoblastoma update].

    Science.gov (United States)

    Aerts, I; Lumbroso-Le Rouic, L; Gauthier-Villars, M; Brisse, H; Doz, F

    2016-01-01

    Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of 2 years, and in most cases they are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of 1 year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10-15% of children with a unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms at diagnosis are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, location), the risks for vision, and the possible hereditary nature of the disease. The main prognostic aspects are still early detection and adapted coverage by a multidisciplinary, highly specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is made according to the histological risk factors. The most important recent therapeutic advances concern conservative treatment, which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy, or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion and intravitreal injections, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblastoma is now excellent in industrialized countries, but long-term survival is still related to the

  12. Treatment Options for Retinoblastoma

    Science.gov (United States)

    ... an increased risk of trilateral retinoblastoma and other cancers. A child with heritable retinoblastoma has an increased risk of ... talk with your child's doctors about the effects cancer treatment can have on your child. Regular follow-up by health professionals who are ...

  13. Treatment Option Overview (Retinoblastoma)

    Science.gov (United States)

    ... an increased risk of trilateral retinoblastoma and other cancers. A child with heritable retinoblastoma has an increased risk of ... talk with your child's doctors about the effects cancer treatment can have on your child. Regular follow-up by health professionals who are ...

  14. Stages of Retinoblastoma

    Science.gov (United States)

    ... an increased risk of trilateral retinoblastoma and other cancers. A child with heritable retinoblastoma has an increased risk of ... talk with your child's doctors about the effects cancer treatment can have on your child. Regular follow-up by health professionals who are ...

  15. General Information about Retinoblastoma

    Science.gov (United States)

    ... an increased risk of trilateral retinoblastoma and other cancers. A child with heritable retinoblastoma has an increased risk of ... talk with your child's doctors about the effects cancer treatment can have on your child. Regular follow-up by health professionals who are ...

  16. Retinoblastoma in transgenic mice

    NARCIS (Netherlands)

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

    1990-01-01

    Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, pl0

  17. Genetics Home Reference: retinoblastoma

    Science.gov (United States)

    ... dim light or in photographs taken with a flash. Other signs and symptoms of retinoblastoma include crossed ... Childhood Cancer Foundation) National Organization for Rare Disorders (NORD) Resource list from the University of Kansas Medical ...

  18. What is Retinoblastoma?

    Science.gov (United States)

    ... cortex , allowing us to see. How does retinoblastoma develop? The eyes develop very early as babies grow in the womb. ... a certain point, these cells stop dividing and develop into mature retinal cells. Rarely, something goes wrong ...

  19. Retinoblastoma, an inside job.

    Science.gov (United States)

    Bremner, Rod

    2009-06-12

    Why are some cell types more prone to transformation than others? In this issue, Xu et al. (2009) show that retinoblastoma cells co-opt several intrinsic features of cone photoreceptors for their survival and growth.

  20. 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.

  1. Epstein-Barr virus infection is inversely correlated with the expression of retinoblastoma protein in Reed-Sternberg cells in classic Hodgkin lymphoma.

    Science.gov (United States)

    Al-Salam, Suhail; Awwad, Aktham; Alashari, Mouied

    2014-01-01

    Classic Hodgkin lymphoma (cHL) is characterized by few neoplastic Hodgkin/Reed-Sternberg (H/RS) cells in a background of intense inflammatory infiltrate. Epstein-Barr virus (EBV) has been shown to affect cell cycle and regulation of apoptosis. In total, 82 cases of cHL were studied. Five- micrometer sections were prepared and stained with haematoxylin and eosin and immunohistochemical streptavidin-biotin methods for EBV-LMP-1, pRb, ki-67 and cleaved caspase-3. In-situ hybridization for EBV encoded RNA was used to confirm the detection of EBV in H/RS cells. There were 45 nodular sclerosis, 28 mixed cellularity, 4 lymphocyte-rich, and 5 lymphocyte depletion subtypes in this series of cases. EBV and pRb were detected in 55% (46/82) and 64% (50/82) of the cases respectively. EBV was detected in 78% (25/32) of pRb-negative cases and 81% (29/36) of EBV-negative cases are pRb-positive. A statistically significant inverse relationship was observed between the presence of EBV and expression of pRb (P = 0.001). In conclusion, EBV infection is inversely correlated with pRb in H/RS cells in cHL.

  2. Retinoblastoma; Le retinoblastome

    Energy Technology Data Exchange (ETDEWEB)

    Desjardins, L.; Doz, F.; Schlienger, P.; Validire, P.; Quintana, E.; Zucker, J.M. [Institut Curie, 75 - Paris (France)

    1996-05-01

    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.

  3. Genetics and management of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Bakhshi Sameer

    2007-01-01

    Full Text Available Retinoblastoma is the most common intraocular tumor in childhood. In majority of early stage retinoblastoma, the eyeballs as well as vision can be preserved with chemotherapy and local intraocular therapy with laser or photocoagulation. However, more than half the patients in India and other developing nations present in advanced stage of the disease. This article reviews the genetics, clinical approach, and treatment options for retinoblastoma focussing on advances in chemotherapy for intraocular retinoblastoma (chemoreduction, as well as improvement in survival in advanced retinoblastoma with surgery, chemotherapy, radiotherapy, and bone marrow transplantation.

  4. Neuroblastoma and Its Zebrafish Model.

    Science.gov (United States)

    Zhu, Shizhen; Thomas Look, A

    2016-01-01

    Neuroblastoma, an important developmental tumor arising in the peripheral sympathetic nervous system (PSNS), accounts for approximately 10 % of all cancer-related deaths in children. Recent genomic analyses have identified a spectrum of genetic alterations in this tumor. Amplification of the MYCN oncogene is found in 20 % of cases and is often accompanied by mutational activation of the ALK (anaplastic lymphoma kinase) gene, suggesting their cooperation in tumor initiation and spread. Understanding how complex genetic changes function together in oncogenesis has been a continuing and daunting task in cancer research. This challenge was addressed in neuroblastoma by generating a transgenic zebrafish model that overexpresses human MYCN and activated ALK in the PSNS, leading to tumors that closely resemble human neuroblastoma and new opportunities to probe the mechanisms that underlie the pathogenesis of this tumor. For example, coexpression of activated ALK with MYCN in this model triples the penetrance of neuroblastoma and markedly accelerates tumor onset, demonstrating the interaction of these modified genes in tumor development. Further, MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. In the context of MYCN overexpression, activated ALK provides prosurvival signals that block this apoptotic response, allowing continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma. This application of the zebrafish model illustrates its value in rational assessment of the multigenic changes that define neuroblastoma pathogenesis and points the way to future studies to identify novel targets for therapeutic intervention.

  5. Neuroblastoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian; Ley-Zaporozhan, J.; Schenk, J.P. [Univ. Hospital Heidelberg (Germany). Div. of Pediatric Radiology; Guenther, P. [Univ. Heidelberg (Germany). Division of Pediatric Surgery; Deubzer, H.E.; Witt, O. [Children' s Hospital Heidelberg (Germany). Dept. of Pediatric Oncology; German Cancer Research Center Heidelberg (Germany). Clinical Cooperation Unit Pediatric Oncology

    2011-03-15

    Neuroblastoma is an embryonic tumor of the sympathetic nervous system which represents one of the most common malignancies in early childhood. Its clinical and biological behavior show a remarkable heterogeneity, ranging from spontaneous regression to inexorable progression with a fatal outcome. This review summarizes the clinical risk stratification and treatment options. An extensive overview of the role of imaging during the course of the disease and typical imaging findings in all imaging modalities are demonstrated. (orig.)

  6. [Retinoblastoma: recent advances].

    Science.gov (United States)

    Jehanne, Mathilde; Brisse, Hervé; Gauthier-Villars, Marion; Lumbroso-le Rouic, Livia; Freneaux, Paul; Aerts, Isabelle

    2014-04-01

    Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 to 1/20,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of two years, and in most cases are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of one year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10 to 15% of children with an unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, localization…), the risk to vision and the possible hereditary nature of the disease. The main prognostic aspects are still premature detection and adapted coverage by a multi-disciplinary specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. The most important recent therapeutic advances concern the conservative treatment which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblatoma is now excellent in industrialized countries, but long-term survival is still

  7. 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).

  8. Retinoblastoma , our experience

    OpenAIRE

    2013-01-01

    Introduction: The retinoblastoma is the most common malignant ocular tumor of childhood with an incidence of 1: 15000 – 20000 births and it is due to a mutation on RB1 gene, a tumoral supressor gene. The average age of diagnosis is 12 months in bilateral and 24 months in unilateral cases. Late diagnosis usually means lost of eye function or even death, that’s why the early screening in every child is so critical. Goals: Review and approach the diagnosis and current treatment o...

  9. New insights into the genetics of neuroblastoma.

    Science.gov (United States)

    Sridhar, Srishma; Al-Moallem, Batool; Kamal, Hawra; Terrile, Marta; Stallings, Raymond L

    2013-04-01

    Neuroblastoma is a genetically and clinically heterogeneous tumor of childhood, arising from precursor cells of the sympathetic nervous system. It is still a challenging cancer for pediatric oncology, as some tumors will spontaneously regress, while others will become refractory to all forms of therapy. The clinical course of this disease is greatly influenced by both patient age and the genetic abnormalities that occur within the tumors. MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) amplification and loss of chromosome 11q heterozygosity have been known to be indicative of poor prognosis. In this article, we review how mutations and structural alterations in specific genes contribute to inheritable predisposition to neuroblastoma and/or to aggressive disease pathogenesis, as well as implications for diagnosis and therapy. These genes include PHOX2B (paired-like homeobox 2b), ALK (anaplastic lymphoma receptor tyrosine kinase), and ATRX (alpha thalassemia/mental retardation syndrome X-linked).

  10. Genetics Home Reference: neuroblastoma

    Science.gov (United States)

    ... the neck can cause nerve damage known as Horner syndrome , which leads to drooping eyelids, small pupils, ... named? Additional Information & Resources MedlinePlus (3 links) Encyclopedia: Horner Syndrome Encyclopedia: Neuroblastoma Health Topic: Neuroblastoma Genetic and ...

  11. Diffuse anterior retinoblastoma: current concepts

    Directory of Open Access Journals (Sweden)

    Yang J

    2015-07-01

    Full Text Available Jing Yang,1–3 Yalong Dang,1–3 Yu Zhu,1 Chun Zhang2,3 1Department of Ophthalmology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou City, Henan Province, 2Department of Ophthalmology, Peking University Third Hospital, 3Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: Diffuse anterior retinoblastoma is a rare variant of retinoblastoma seeding in the area of the vitreous base and anterior chamber. Patients with diffuse anterior retinoblastoma are older than those with the classical types, with the mean age being 6.1 years. The original cells of diffuse anterior retinoblastoma are supposed to be cone precursor. Patients most commonly present with pseudouveitis, pseudohypopyon, and increased intraocular pressure. The retina under fundus examination is likely to be normal, and the clinical features mimic the inflammation progress, which can often lead to misdiagnosis. The published diffuse anterior retinoblastoma cases were diagnosed after fine-needle aspiration biopsy running the potential risk of inducing metastasis. The most common treatment for diffuse anterior retinoblastoma is enucleation followed by systematic chemotherapy according to the patient’s presentation and clinical course. This review summarizes the recent advances in etiology (including tumorigenesis and cell origin, pathology, diagnosis, differential diagnosis, and new treatment. The challenges of early diagnosis and prospects are also discussed. Keywords: pathology, microenvironment, treatment, diagnosis 

  12. Molecular pathology of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Kandalam Mallikarjuna

    2010-01-01

    Full Text Available Retinoblastoma (RB is an embryonic neoplasm of retinal origin. For many years, scientists have sought the fundamental origins of tumorigenesis, with the ultimate hope of discovering a cure. Indeed, these efforts have led to a significant understanding that multiple molecular and genetic aberrations, such as uncontrolled proliferation and the inhibition of apoptosis that contribute to the canonical characteristics of tumor biology. Despite these advances, a thorough understanding, such as the precise cells, which are the targets of neoplastic transformation, especially in solid tumors, is currently lacking. The focus of this review is to emphasize the molecular defects involved in the RB tumor progression and mechanisms associated with inhibition of tumor cell apoptotic processes. This review also discusses the importance of target molecules characterization and their potential therapeutic or prognostic use in RB disease.

  13. Genetic and Epigenetic Discoveries in Human Retinoblastoma.

    Science.gov (United States)

    McEvoy, Justina D; Dyer, Michael A

    2015-01-01

    Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary genetic lesions following RB1 inactivation. One of the major discoveries from retinoblastoma sequencing studies is that some retinoblastoma tumors have stable genomes. Subsequent epigenetic studies showed that changes in the epigenome contribute to the rapid progression of retinoblastoma following RB1 gene inactivation. In addition, gene amplification and elevated expression of p53 antagonists, MDM2 and MDM4, may also play an important role in retinoblastoma tumorigenesis. The knowledge gained from these recent molecular, cellular, genomic, and epigenomic analyses are now being integrated to identify new therapeutic approaches that can help save lives and vision in children with retinoblastoma, with fewer long-term side effects.

  14. Hodgkin's Lymphoma

    Science.gov (United States)

    ... behavior. Your type determines your treatment options. Classical Hodgkin's lymphoma Classical Hodgkin's lymphoma is the more common ... Hodgkin's lymphoma Lymphocyte-rich Hodgkin's lymphoma Lymphocyte-predominant Hodgkin's lymphoma This much rarer type of Hodgkin's lymphoma ...

  15. 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 expres

  16. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-10-18

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

  17. Olfactory Neuroblastoma: Diagnostic Difficulty

    Directory of Open Access Journals (Sweden)

    Vidya MN,

    2011-01-01

    Full Text Available Olfactory neuroblastoma is an uncommon malignant tumor of sinonasal tract arising from the olfactory neuro epithelium. The olfactory neuroblastomas presenting with divergent histomorphologies like, epithelial appearance of cells, lacking a neuro fibrillary background and absence of rosettes are difficult to diagnose. Such cases require immunohistochemistry to establish the diagnosis. We describe the clinical features, pathological and immunohistochemical findings of grade IV Olfactory neuroblastoma in a 57 year old man

  18. Neuroblastoma: computed tomographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Choon Sik; Ahn, Chang Su; Kim, Myung Jun; Oh, Ki Keun [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    1994-01-15

    To evaluate the characteristic CT findings of neuroblastoma, we studied neuroblastomas. We analysed CT findings of available 25 cases among pathologically proved 51 neuroblastomas from Jan. 1983 to Sept. 1990. The most frequent site of origin is adrenal gland (40%) and the second is retroperitoneum (32%) and the third ismediastinum (16%). Characteristic CT findings are as follows: Calcifications within the tumor is detected in 86% of abdominal neuroblastomas and 50% of mediastinal origin. Hemorrhagic and necrotic changes within the tumor is noted at 86% in the tumor of abdominal origin and 25% in mediastinal neuroblastomas. Contrast enhanced study showed frequently seperated enhanced appearance with/without solid contrast enhancement. Encasements of major great vessels such as aorta and IVC with/without displacement by metastatic lymph nodes or tumor are frequently seen in 90% of abdominal neuroblastomas. Multiple lymphadenopathy are detected in 95% of abdominal neuroblastomas and 25% of mediastinal neuroblastomas. The most common organ or contiguous direct invasion is kidney in 6 cases and the next one is liver but intraspinal canal invasion is also noted in 2 cases. We concluded that diagnosis of neuroblastoma would be easily obtained in masses of pediatric group from recognition of above characteristic findings.

  19. Trilateral retinoblastoma in transgenic mice

    NARCIS (Netherlands)

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

    1989-01-01

    Retinoblastoma, a heritable malignancy, occurs in the eyes of children at a median age of 2 years. It is a malignancy which has been widely studied as a model for genetic predisposition to cancer. The disease occurs in both heritable and nonheritable forms. Thirty to 40% of children with retinoblas

  20. Suprasellar retinoblastoma in a 5-month-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun Woo; Yoon, Hye-Kyung; Han, Bokyung Kim [Department of Radiology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710 (Korea); Shin, Hyung-Jin [Department of Neurosurgery, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul (Korea)

    2002-12-01

    Trilateral retinoblastoma is the association of bilateral retinoblastomas and an intracranial primitive neuroectodermal tumour. Bilateral retinoblastomas with a pineal tumour are typical manifestations of this association. However, there may be variants, including unilateral retinoblastoma with intracranial tumour. The intracranial tumour can occur in the suprasellar or parasellar regions even before presentation of the retinal mass. We report a female infant with a suprasellar retinoblastoma and unilateral intraocular retinoblastoma. (orig.)

  1. Lactate dehydrogenase (LDH activity in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Maurya OPS

    1987-01-01

    Full Text Available LDH estimation in aqueous and serum was carried out in 10 cases of retinoblastoma and 10 control cases (normal. LDH estimation was done by calorimetric method devised by King-Wooten (1964 (1. LDH levels were quite high in serum and aqueous in retinoblastoma, as compared to control cases LDH aqueous/serum ratio was significantly higher in retinoblastoma as compared to control

  2. Inhibition of Retinoblastoma Protein Inactivation

    Science.gov (United States)

    2016-09-01

    phosphorylation, which dissociates the E2F transcription factor from Rb. Our goal is to find and characterize molecules that stabilize the complex...between phosphorylated Rb and E2F. In this second year of the project period, we further tested our proposed mechanism for how molecules enhance the...Retinoblastoma protein, E2F transcription factor, high throughput screen, drug discovery, x-ray crystallography 16. SECURITY CLASSIFICATION OF: 17

  3. Conservative treatment modalities in retinoblastoma

    Directory of Open Access Journals (Sweden)

    Bhavna Chawla

    2013-01-01

    Full Text Available Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. The purpose of this article is to review the literature on various conservative treatment modalities available for the treatment of retinoblastoma and their effectiveness, when used alone or in combination. Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for published peer reviewed data on conservative treatment modalities for retinoblastoma. Various studies show that while enucleation remains the standard of care for advanced intraocular tumors, 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 thermotherapy, 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. It is important to recognize that today, several treatment options are available that can obviate the need for enucleation, and cure the cancer with preservation of functional vision. A thorough knowledge and understanding of these conservative treatment modalities is essential for appropriate management.

  4. A clinical study of retinoblastoma

    Directory of Open Access Journals (Sweden)

    L Subha

    2015-01-01

    Full Text Available Aim: The aim was to analyze general incidence, age incidence, laterality, common mode of presentation, staging of the tumor, radiological evidence, histopathological confirmation, management and follow-up of cases, which were diagnosed as retinoblastoma. Design: Interventional case series study from April 1997 to March 2000. Materials and Methods: Detailed history regarding the symptoms such as white reflex, watering, pain, redness, protrusion of eyeball, squint, hyphema, and defective vision were obtained. Family history regarding consanguinity between parents, health of the siblings and other relatives were recorded. Ocular examination included vision, pupillary reaction, detailed fundus examination, ocular tension, and corneal diameter. Investigations included X-ray orbit and skull, computed tomography scan orbit and brain, B-scan orbit, serum and aqueous lactate dehydrogenase; enucleated eyes were subjected to holoprosencephaly (HPE. Enucleation, radiotherapy, cryotherapy and chemotherapy were modalities of treatment. The empty socket and the other apparently normal eye were examined carefully at each visit. Results: The incidence of retinoblastoma is less when compared to other diseases of the eye. There was no sex predilection. Most of the cases diagnosed were sporadic and unilateral. Age of onset is earlier for bilateral cases than unilateral cases. Consanguinity bears close relationship with bilateral involvement. Predominant clinical sign is white reflex in the pupillary area. Majority of cases presented in the second stage of the disease. Enucleation plays a greater role in the management of retinoblastoma. HPE should include several sections of the optic nerve to find out skip lesions.

  5. Drugs Approved for Neuroblastoma

    Science.gov (United States)

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

  6. Late onset retinoblastoma presenting with vitreous haemorrhage

    DEFF Research Database (Denmark)

    Bagger, Mette; Prause, Jan Ulrik; Heegaard, 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...

  7. Recent Trends in the Management of Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Samuray Tuncer

    2015-04-01

    Full Text Available Retinoblastoma is the most common intraocular malignancy of childhood. Significant progress has been made in the past few years in the management of retinoblastoma. Thus, the patients’ survival and ocular salvage rates have shown marked improvement. The current treatment strategies for retinoblastoma include enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Enucleation is generally reserved for eyes with extensive retinoblastoma, in which there is no hope for useful vision. From mid-1990s, intravenous chemoreduction has been used efficiently in the management of group A, B, or C, and some D eyes according to the International Classification of Retinoblastoma. Intravenous chemoreduction combined with focal treatments (cryotherapy, transpupillary thermotherapy, and brachytherapy have provided favorable tumor control for most of these eyes. In 2008, superselective intra-arterial chemotherapy has been popularized. This treatment involves injection of a chemotherapeutic agent (mostly melphalan after selective catheterization of the ophthalmic artery under neuroradiologic intervention. This provides higher success in advanced group D and Group E eyes that have relatively lower rate of tumor control with conventional intravenous chemoreduction. In conclusion, significant advances that have emerged recently in the management of retinoblastoma led to an increase in ocular salvage rates. Recently, popularized modality of intra-arterial chemotherapy offers hope in the control of eyes with advanced retinoblastoma. (Turk J Ophthalmol 2015; 45: 71-6

  8. Long noncoding RNAs and neuroblastoma.

    Science.gov (United States)

    Pandey, Gaurav Kumar; Kanduri, Chandrasekhar

    2015-07-30

    Neuroblastoma is a disease that affects infants and despite intense multimodal therapy, high-risk patients have low survival rates (neuroblastoma have just begun to be elucidated. This review summarises where we are with regards to lncRNAs in neuroblastoma. The known mechanistic roles of lncRNAs during neuroblastoma pathogenesis are discussed, as well as the relationship between lncRNA expression and the differentiation capacity of neuroblastoma cells. We speculate about the use of some of these lncRNAs, such as those mapping to the 6p22 hotspot, as biomarkers for neuroblastoma prognosis and treatment. This novel way of thinking about both neuroblastoma and lncRNAs brings a new perspective to the prognosis and treatment of high-risk patients.

  9. Heritable retinoblastoma and accelerated aortic valve disease

    Science.gov (United States)

    Abeyratne, L R; Kingston, J E; Onadim, Z; Dubrey, S W

    2013-01-01

    Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI. The Rb protein (pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans. 1 Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. 2 3 We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of ‘cancer susceptibility genes’; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect. PMID:23595191

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

    African Journals Online (AJOL)

    shobha

    The goal is to increase number of children successfully cured of this disease in our environment. Keywords: ..... avoiding direct treatment as this can lead to vitreous seeding. .... Shields CL, Shields JA, Shah P. Retinoblastoma in older children.

  11. 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......-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....

  12. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  13. Retinoblastoma

    Science.gov (United States)

    ... Uveitis Focus On Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center ... Uveitis Focus On Pediatric Ophthalmology Education Center Oculofacial Plastic Surgery Center Laser Surgery Education Center Redmond Ethics Center ...

  14. Genomic differences between retinoma and retinoblastoma.

    Science.gov (United States)

    Sampieri, Katia; Mencarelli, Maria Antonietta; Epistolato, Maria Carmela; Toti, Paolo; Lazzi, Stefano; Bruttini, Mirella; De Francesco, Sonia; Longo, Ilaria; Meloni, Ilaria; Mari, Francesca; Acquaviva, Antonio; Hadjistilianou, Theodora; Renieri, Alessandra; Ariani, Francesca

    2008-01-01

    Genomic copy number changes are involved in the multi-step process transforming normal retina in retinoblastoma after RB1 mutational events. Previous studies on retinoblastoma samples led to a multi-step model in which after two successive RB1 mutations, further genomic changes accompany malignancy: 1q32.1 gain is followed by 6p22 gain, that in turn is followed by 16q22 loss and 2p24.1 gain. Retinoma is a benign variant of retinoblastoma that was initially considered a tumor regression, but recent evidences suggest that it rather represents a pre-malignant lesion. Genetic studies on retinoma tissue have rarely been performed. We investigated by Real-Time qPCR, copy number changes of candidate genes located within the 4 hot-spot regions (MDM4 at 1q32.1, MYCN at 2p24.1, E2F3 at 6p22 and CDH11 at 16q22) in retina, retinoma and retinoblastoma tissues from two different patients. Our results demonstrated that some copy number changes thought to belong to early (MDM4 gain) or late stage (MYCN and E2F3 gain) of retinoblastoma are already present in retinoma at the same (for MDM4) or at lower (for MYCN and E2F3) copy number variation respect to retinoblastoma. CDH11 copy number is not altered in the two retinoma samples, but gain is present in one of the two retinoblastomas. Our results suggest that MDM4 gain may be involved in the early transition from normal retina to retinoma, while MYCN and E2F3 progressive gain may represent driving factors of tumor progression. These results also confirm the pre-malignant nature of retinoma.

  15. Preliminary Report of Molecular Detection of Retinoblastoma Gene Mutations

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    To develop gene diagnosis for retinoblastoma predisposition, it is necessary to disclose the retinoblastoma gene mutations or deletions in detail. Genomic DNA from tumor and peripheral white blood cells in 33 patients with retinoblastoma was detected with 3.8kb probe derived from 3' end of retinoblastoma gene cDNA. The gene abnormalities, including deletion, partial deletion and rearrangement, were found in 18 patients. Further research will be aimed at microdeletions or mutations for those patients wti...

  16. Retinoblastoma Registry report--Hospital Kuala Lumpur experience.

    Science.gov (United States)

    Jamalia, R; Sunder, R; Alagaratnam, J; Goh, P P

    2010-06-01

    Retinoblastoma is a childhood ocular cancer. The aim of this paper is to describe the clinical and epidemiological characteristics of patients with retinoblastoma in a major paediatric ophthalmology center in the country. Retrospective information was collected through the retinoblastoma registry. Late presentation with advanced staging is a major problem.

  17. Anti-tumor activity of arginine deiminase via arginine deprivation in retinoblastoma.

    Science.gov (United States)

    Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Kim, Dong Hun; Min, Bon-Hong; Kim, Kyu-Won

    2007-12-01

    In spite of recent advances in the treatment of retinoblastoma, chemotherapy is still challenging in high-stage intraocular retinoblastoma or metastatic retinoblastoma. Here, we investigated whether arginine deprivation via arginine deiminase (ADI) could be a new anti-tumor therapy in retinoblastoma cells. Expression of argininosuccinate synthetase (ASS) was detected in human retinoblastoma tissues. Even with a high expression of ASS, ADI effectively inhibited the proliferation of retinoblastoma cells and induced retinoblastoma cell death in a dose-dependent manner. These results indicate that arginine deprivation via ADI could be another treatment option for retinoblastoma due to low ASS activity in retinoblastoma cells.

  18. Non-Hodgkin lymphoma

    Science.gov (United States)

    Lymphoma - non-Hodgkin; Lymphocytic lymphoma; Histiocytic lymphoma; Lymphoblastic lymphoma; Cancer - non-Hodgkin lymphoma ... National Cancer Institute: PDQ adult non-Hodgkin lymphoma treatment. Bethesda, MD: National Cancer Institute. Updated ... . Accessed ...

  19. PPARγ in Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Alessandro Peri

    2008-01-01

    Full Text Available Neuroblastoma (NB is the most common extracranial tumor in children and accounts for around 15% of all paediatric oncology deaths. The treatment of NB includes surgery, chemotherapy, and radiotherapy. Unfortunately, most children with NB present with advanced disease, and more than 60% of patients with high-risk features will have a poor prognosis despite intensive therapy. Agonists of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ have been shown to have pleiotropic effects, including antineoplastic effects. The studies that addressed the role and the possible mechanism(s of action of PPARγ in NB cells are reviewed.

  20. Review of Retinoblastoma and Report of Three Cases of Bilateral Retinoblastoma

    Directory of Open Access Journals (Sweden)

    M Kheirandish

    2009-01-01

    Full Text Available Retinoblastoma is a retinal malignant tumor that occurs in early childhood. The annual incidence of retinoblastoma is approximately one per 14 000 live births. 250 to 300 new cases are reported in the United States each year. It develops due to inactivation of both alleles of the retinoblastoma susceptibility (RB1 gene. All hereditary cases (55% are with bilateral and multifocal lesions, but in non hereditary cases (45%, retinoblastoma is always unilateral and unifocal. Leukocoria (white reflection of pupil and strabismus are the most frequent clinical manifestations of retinoblastoma. In funduscopy under general anesthesia, the lesion appears as a white tumor with angiomatous dilatation of the vessels. Treatment approaches include chemotherapy, focal laser, enucleation and radiotherapy. The goals of treatment are eye preservation and improvement in patient survival rate; reduction of local tumor relapse and recurrence and development of new tumors. Follow up is by general and complete eye examination in order to diagnose related malignancies, especially in cases of radiotherapy. We report three bilateral retinoblastoma cases (10 months, 5 and6 years old with strabismus and visual loss. Imaging showed involvement of both globes without CNS involvement. The tumor was controlled by providing adequate treatment for the cases

  1. Functional analysis of Burkitt's lymphoma mutant c-Myc proteins

    OpenAIRE

    1996-01-01

    The c-myc gene encodes a sequence-specific DNA binding protein that activates transcription of cellular genes. Transcription activation by Myc proteins is regulated by phosphorylation of serine and threonine residues within the transactivation domain and by complex formation with the retinoblastoma-related protein p107. In Burkitt’s lymphoma, missense mutations within the c-Myc transactivation domain have been found with high frequency. It has been reported that mutant c-Myc proteins derived ...

  2. LGR5 regulates pro-survival MEK/ERK and proliferative Wnt/β-catenin signalling in neuroblastoma.

    Science.gov (United States)

    Vieira, Gabriella Cunha; Chockalingam, S; Melegh, Zsombor; Greenhough, Alexander; Malik, Sally; Szemes, Marianna; Park, Ji Hyun; Kaidi, Abderrahmane; Zhou, Li; Catchpoole, Daniel; Morgan, Rhys; Bates, David O; Gabb, Peter David; Malik, Karim

    2015-11-24

    LGR5 is a marker of normal and cancer stem cells in various tissues where it functions as a receptor for R-spondins and increases canonical Wnt signalling amplitude. Here we report that LGR5 is also highly expressed in a subset of high grade neuroblastomas. Neuroblastoma is a clinically heterogenous paediatric cancer comprising a high proportion of poor prognosis cases (~40%) which are frequently lethal. Unlike many cancers, Wnt pathway mutations are not apparent in neuroblastoma, although previous microarray analyses have implicated deregulated Wnt signalling in high-risk neuroblastoma. We demonstrate that LGR5 facilitates high Wnt signalling in neuroblastoma cell lines treated with Wnt3a and R-spondins, with SK-N-BE(2)-C, SK-N-NAS and SH-SY5Y cell-lines all displaying strong Wnt induction. These lines represent MYCN-amplified, NRAS and ALK mutant neuroblastoma subtypes respectively. Wnt3a/R-Spondin treatment also promoted nuclear translocation of β-catenin, increased proliferation and activation of Wnt target genes. Strikingly, short-interfering RNA mediated knockdown of LGR5 induces dramatic Wnt-independent apoptosis in all three cell-lines, accompanied by greatly diminished phosphorylation of mitogen/extracellular signal-regulated kinases (MEK1/2) and extracellular signal-regulated kinases (ERK1/2), and an increase of BimEL, an apoptosis facilitator downstream of ERK. Akt signalling is also decreased by a Rictor dependent, PDK1-independent mechanism. LGR5 expression is cell cycle regulated and LGR5 depletion triggers G1 cell-cycle arrest, increased p27 and decreased phosphorylated retinoblastoma protein. Our study therefore characterises new cancer-associated pathways regulated by LGR5, and suggest that targeting of LGR5 may be of therapeutic benefit for neuroblastomas with diverse etiologies, as well as other cancers expressing high LGR5.

  3. RFC-1 80G>A polymorphism in case-mother/control-mother dyads is associated with risk of nephroblastoma and neuroblastoma.

    Science.gov (United States)

    Montalvão-de-Azevedo, Rafaela; Vasconcelos, Gisele M; Vargas, Fernando R; Thuler, Luiz Claudio; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

    2015-02-01

    Embryonic tumors are associated with an interruption during normal organ development; they may be related to disturbances in the folate pathway involved in DNA synthesis, methylation, and repair. Prenatal supplementation with folic acid is associated with a decreased risk of neuroblastoma, brain tumors, retinoblastoma, and nephroblastoma. The aim of this study was to investigate the association between MTHFR rs1801133 (C677T) and RFC-1 rs1051266 (G80A) genotypes with the risk of developing nephroblastoma and neuroblastoma. Case-mother/control-mother dyad study. Samples from Brazilian children with nephroblastoma (n=80), neuroblastoma (n=66), healthy controls (n=453), and their mothers (case n=93; control n=75) were analyzed. Genomic DNA was isolated from peripheral blood cells and/or buccal cells and genotyped to identify MTHFR C677T and RFC-1 G80A polymorphisms. Differences in genotype distribution between patients and controls were tested by multiple logistic regression analysis. Risk for nephroblastoma and neuroblastoma was two- to fourfold increased among children with RFC-1 polymorphisms. An increased four- to eightfold risk for neuroblastoma and nephroblastoma was seen when the child and maternal genotypes were combined. Our results suggest that mother and child RFC-1 G80A genotypes play a role on the risk of neuroblastoma and nephroblastoma since this polymorphism may impair the intracellular levels of folate, through carrying fewer folate molecules to the cell interior, and thus, the intracellular concentration is not enough to maintain regular DNA synthesis and methylation pathways.

  4. 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.)

  5. Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer

    Science.gov (United States)

    2017-03-28

    Childhood Choroid Plexus Tumor; Childhood Medulloblastoma; Childhood Pineoblastoma; Childhood Soft Tissue Sarcoma; Childhood Supratentorial Primitive Neuroectodermal Tumor; Neuroblastoma; Osteosarcoma; Retinoblastoma; Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  6. Childhood Cancer Statistics

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  7. Tests and Procedures

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  8. What Is Cancer?

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  9. Avascular Necrosis

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  10. Relapse or Recurrence

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  11. Childhood Soft Tissue Sarcoma: Treatment Information

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  12. Anxiety Around Medical Procedures

    Science.gov (United States)

    ... Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Cancer Resources Childhood Cancer Statistics Coping With Cancer CureSearch CancerCare App Late Effects ...

  13. Adolescent Neuroblastoma of Lower Limb

    Directory of Open Access Journals (Sweden)

    Rajeshwari K

    2013-04-01

    Full Text Available Neuroblastoma is an embryonic tumour of neural crest origin, commonly seen in children with upper abdomen involvement. Rarely neuroblastomas present in adolescents and adults involving lower limb. Histopathologically neuroblastoma of lower limb can be confused with other small round cell tumour especially with Ewing's sarcoma and rhabdomyosarcoma. A 16 year old male presented with 15x11cm swelling, pain and multiple discharging sinuses of right leg since 4 months. Routine haematological and biochemical analysis were within normal limits. Radiology of right leg showed large soft tissue swelling encompassing the pathological fracture of tibia and bowing of fibula. Fine needle aspiration of the swelling revealed malignant small round cell tumour. Histopathology revealed poorly differentiated neuroblastoma of lower limb. The immunohistochemistry of Synaptophysin and Chromogranin were positive and CD 99 was negative. Neuroblastoma diagnosed at unusual site with uncommon age has poor prognosis. Hence, one must keep in mind the differential diagnosis of neuroblastoma as one of the differential diagnosis in evaluating the soft tissue tumours of lower limb.

  14. Hodgkin Lymphoma (For Teens)

    Science.gov (United States)

    ... Can I Help Someone Who's Being Bullied? Volunteering Hodgkin Lymphoma KidsHealth > For Teens > Hodgkin Lymphoma Print A ... to check for disease, including lymphoma. What Is Hodgkin Lymphoma? Hodgkin lymphoma is a type of cancer ...

  15. 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).

  16. 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.

  17. Atraso diagnóstico do retinoblastoma

    OpenAIRE

    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 ...

  18. 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...... positive glial cells were found in areas near the retina and along many tumour vessels. Some S-100 reactive cells previously interpreted as tumour cells were refound in a few tumours. In areas with Flexner-Winterstein rosettes and in areas with light cells showing photoreceptor-like differentiation, glial...... 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....

  19. Neonatal intrathoracic neuroblastoma: unusual presentation with haemothorax

    Directory of Open Access Journals (Sweden)

    Joana Jardim

    2015-03-01

    Full Text Available Thoracic neuroblastomas are rare in the neonatal period. They may be asymptomatic or cause respiratory distress. Congenital haemothorax present at birth, as the result of intravascular disseminated coagulopathy, is an uncommon initial presentation of intrathoracic neuroblastomas.

  20. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  1. 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

  2. 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.

  3. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children.

    Science.gov (United States)

    Schiavon, Jose Luiz de Oliveira; Caran, Eliana Maria Monteiro; Odone Filho, Vicente; Lederman, Henrique Manoel

    2016-01-01

    To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%.

  4. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children*

    Science.gov (United States)

    Schiavon, Jose Luiz de Oliveira; Caran, Eliana Maria Monteiro; Odone Filho, Vicente; Lederman, Henrique Manoel

    2016-01-01

    Objective To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%. PMID:28100931

  5. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children

    Directory of Open Access Journals (Sweden)

    Jose Luiz de Oliveira Schiavon

    Full Text Available Abstract Objective: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results: We found anterior abdominal aorta displacement in 26 (39.39% of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%, nephroblastoma in 3 (11.54%, and Burkitt lymphoma in 1 (3.85%. The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%.

  6. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children

    Energy Technology Data Exchange (ETDEWEB)

    Schiavon, Jose Luiz de Oliveira; Caran, Eliana Maria Monteiro; Lederman, Henrique Manoel, E-mail: schiavon00@gmail.com [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Odone Filho, Vicente [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Faculdade de Medicina

    2016-11-15

    Objective: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results: We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%. (author)

  7. 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

  8. 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. De

  9. Locoregional MYCN-amplified neuroblastoma.

    Science.gov (United States)

    Morales La Madrid, Andres; Volchenboum, Samuel; Gastier-Foster, Julie M; Pyatt, Robert; Liu, Don; Pytel, Peter; Lavarino, Cinzia; Rodriguez, Eva; Cohn, Susan L

    2012-10-01

    MYCN-amplification is strongly associated with other high-risk prognostic factors and poor outcome in neuroblastoma. Infrequently, amplification of MYCN has been identified in localized tumors with favorable biologic features. Outcome for these children is difficult to predict and optimal treatment strategies remain unclear. We report a 5-month-old who presented with an MYCN-amplified INSS stage 3, pelvic neuroblastoma. The tumor had favorable histology, hyperdiploidy, and lacked 1p36 and 11q23 aberrations. Although the patient met the criteria for high-risk neuroblastoma, because of the discordant prognostic markers we elected to treat her according to an intermediate-risk protocol. She remains event-free more than 18 months.

  10. Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-06-04

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  11. 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

  12. 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 pRB...... negatively regulates some aspect of normal cell growth. The discovery that pRB associates with transcription factors such as E2F has provided the first model for pRB function. In this review, we discuss how pRB may regulate cell growth by repressing transcription of genes essential for cell proliferation....

  13. 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.

  14. Gastric lymphoma

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    Sravani Padala

    2016-06-01

    Full Text Available Gastrointestinal lymphomas represent 5-20% of extra nodal lymphomas and mainly occur in the stomach and small intestine. Clinical findings are not specific, thus often determining a delay in the diagnosis. Imaging features at conventional and cross-sectional imaging must be known by the radiologist since he/she plays a pivotal role in the diagnosis and disease assessment, thus assisting in the choice of the optimal treatment to patients. This review focuses on the wide variety of imaging presentation of esophageal, gastric, and small and large bowel lymphoma presenting their main imaging appearances at conventional and cross-sectional imaging, mainly focusing on computed tomography and magnetic resonance, helping in the choice of the best imaging technique for the disease characterization and assessment and the recognition of potential complications. Gastrointestinal tract is the most common extra nodal site involved by lymphoma. Although lymphoma can involve any part of the gastrointestinal tract .The most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. [Int J Res Med Sci 2016; 4(6.000: 2481-2486

  15. How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells?*

    Institute of Scientific and Technical Information of China (English)

    Yong Moon; Yongil Kwon; Shun Yu

    2013-01-01

    A body of evidence suggests that ethanol can lead to damage of neuronal cel s. However, the me-chanism underlying the ethanol-induced damage of neuronal cel s remains unclear. The role of mi-togen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neurob-lastoma cel s. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cel viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cel death and cel cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G 1 arrest of cel cycle of the SK-N-SH neuroblastoma cel s. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cel s. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cel death. Ethanol also increased p53 phosphorylation, fol owed by an increase in p21 tumor sup-pressor protein and a decrease in phospho-Rb (retinoblastoma) protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol me-diates apoptosis of SK-N-SH neuroblastoma cel s by activating p53-related cel cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cel death pathway.

  16. Nuclear medicine therapy of neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Amsterdam The Netherlands Cancer Institute, Amsterdam (Netherlands). Dept. of Nuclear Medicine

    1999-12-01

    Specific targeting of radionuclides to neuroblastoma, a neural crest tumor occurring predominantly in young children and associated with a relatively poor prognosis, may be achieved via the metabolic route (Mibg), receptor binding (peptides) or immunological approach (antibodies). The clinical role of {sup 1}31{sup I}-Mibg therapy and radioimmunotherapy in neuroblastoma is discussed. In recurrent or progressive metastatic disease after conventional treatment modalities have failed, {sup 1}31{sup I}-Mibg therapy, with an overall objective response rate of 35%, is probably the best palliative treatment, as the invasiveness and toxicity of this therapy compare favourably with that of chemotherapy, immunotherapy and external beam radiotherapy. In patients presenting with inoperable stage III and IV neuroblastoma, {sup 1}31{sup I}-Mibg therapy at diagnosis is at least as effective as combination chemotherapy but is associated with much less toxicity. In patients with recurrent disease {sup 1}31{sup I}-Mibg therapy in combination with hyperbaric oxygen therapy proved feasible and encouraging effects on survival have ben observed. Attempts to intensify the treatment in relapsed patients by combination of {sup 1}31{sup I}-Mibg therapy with high dose chemotherapy and/or total body irradiation have met with considerable toxicity. Developments in Mibg therapy aiming at improving the therapeutic index are mentioned. Early results of radioimmunotherapy using {sup 1}31{sup I}-UJ13A or {sup 1}31{sup I}-3F8 monoclonal antibodies have shown moderate objective response and considerable side effects in patients with stage IV neuroblastoma, who had relapsed or failed conventional therapy. New developments in radioimmunotherapy of neuroblastoma include the use of chimeric antibodies, the enhancement of tumor uptake by modulation of antigen expression or by increasing the tumor perfusion/vascularity/permeability, the use of other labels and multistep targeting techniques, e.g. using

  17. 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.

  18. 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.

  19. Hodgkin lymphoma - children

    Science.gov (United States)

    Lymphoma - Hodgkin - children; Hodgkin disease - children; Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... In children, Hodgkin lymphoma is more likely to occur between ages 15 to 19 years. The cause of this type of ...

  20. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... Too Tall or Too Short All About Puberty Hodgkin Lymphoma KidsHealth > For Kids > Hodgkin Lymphoma Print A ... of the cool things he's missed. What Is Hodgkin Lymphoma? Lymphoma (say: lim-FOH-mah) is cancer ...

  1. Breast lymphoma

    African Journals Online (AJOL)

    Expression of oestrogen receptor protein as determined by ... lymphomas. While this classification has been fairly widely accepted, a ... minimum a full history and physical examination, chest radiographs ... and hepatic function. A number ...

  2. Hodgkin's Lymphoma

    Science.gov (United States)

    ... for information in your local library and on the Internet. Start your information search with the National Cancer ... www.mayoclinic.org/diseases-conditions/hodgkins-lymphoma/basics/definition/CON-20030667 . Mayo Clinic Footer Legal Conditions and ...

  3. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  4. T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). T-cell lymphomas account for ...

  5. Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    C. Hoyoux

    2012-01-01

    Full Text Available Paravertebral malignant tumors constitute 4.8% of cancer cases in pediatric oncology and are mostly composed of neuroblastoma (46.4% and soft tissue sarcomas (35.7%. We describe the case of a Caucasian 6-year-old boy who was admitted for middle back pain radiated to limbs and progressively increasing weakness of the legs, suggesting a spinal cord disease. The exploration revealed two paravertebral masses extending through the neural foraminae into the epidural space. The association with elevated serum neuron specific enolase suggested at first the diagnosis of neuroblastoma, but the pathological examination revealed a Burkitt's lymphoma. This is a rare location of sporadic Burkitt's lymphoma with neurologic syndrome as first symptoms.

  6. Primary orbital neuroblastoma with intraocular extension

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Vallinayagam

    2015-01-01

    Full Text Available Neuroblastoma is an undifferentiated malignancy of primitive neuroblasts. Neuroblastoma is among the most common solid tumors of childhood. Orbital neuroblastoma is typically a metastatic tumor. In this case report, we describe a 2-year-old child with a rapidly progressing orbital tumor. Computed tomography revealed an orbital mass lesion with extraocular and intraocular components. An incisional biopsy was done, and a histopathological examination showed features suggestive of neuroblastoma. Systemic workup including ultrasonography of the abdomen, chest roentgenogram, whole body computed tomography, and bone scintigraphy showed no evidence of systemic involvement. The diagnosis of primary orbital neuroblastoma was made, and the child was subjected to chemotherapy followed by rapid melting of the tumor. Neuroblastoma should be considered in the differential diagnosis of childhood orbital tumors.

  7. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  8. Primary orbital neuroblastoma in a neonate

    Directory of Open Access Journals (Sweden)

    Mirzai Hasan

    2006-01-01

    Full Text Available Neuroblastoma is an undifferentiated malignant tumor of the primitive neuroblasts. Orbital neuroblastoma is typically a metastatic tumor. We describe a two-days-old girl, who presented with a large tumor in her left orbit. Magnetic resonance imaging revealed that the tumor originated from the retrobulbar area, extending into the upper and lateral orbit. She was operated on the fifth day of life. A histopathologic diagnosis of neuroblastoma was made. Medical evaluation including chest roentgenogram, ultrasonography of the abdomen, whole body computerized tomogram and bone scintigraphy showed no evidence of systemic involvement or metastasis. Neuroblastoma should be considered in the differential diagnosis of neonatal orbital tumors.

  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. modes of presentation, management and outcome of retinoblastoma ...

    African Journals Online (AJOL)

    SITWALA COMPUTERS

    modes of presentation, management of retinoblastoma and. UTH from January ... only whilst 3.4% had exenteration, chemotherapy and ... surgery, chemotherapy and radiotherapy. .... 57.6% of the patients had Examination Under Anesthesia.

  11. 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.

  12. Array comparative genomic hybridization in retinoma and retinoblastoma tissues.

    Science.gov (United States)

    Sampieri, Katia; Amenduni, Mariangela; Papa, Filomena Tiziana; Katzaki, Eleni; Mencarelli, Maria Antonietta; Marozza, Annabella; Epistolato, Maria Carmela; Toti, Paolo; Lazzi, Stefano; Bruttini, Mirella; De Filippis, Roberta; De Francesco, Sonia; Longo, Ilaria; Meloni, Ilaria; Mari, Francesca; Acquaviva, Antonio; Hadjistilianou, Theodora; Renieri, Alessandra; Ariani, Francesca

    2009-03-01

    In retinoblastoma, two RB1 mutations are necessary for tumor development. Recurrent genomic rearrangements may represent subsequent events required for retinoblastoma progression. Array-comparative genomic hybridization was carried out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma patients. Two unilateral cases also showed areas of retinoma. The most frequent imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3, 2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and 16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral cases (P = 0.002). Unilateral cases were divided into low-level ( or = 7) chromosomal instability groups. The first group presented with younger age at diagnosis (mean 511 days) compared with the second group (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign lesion no rearrangements were detected, whereas the adjacent retinoblastoma displayed seven aberrations. The other retinoma case identified by retrospective histopathological examination shared three rearrangements with the adjacent retinoblastoma. Two other gene-free rearrangements were retinoma specific. One rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene. Genomic profiling indicated that the first retinoma was a pretumoral lesion, whereas the other represents a subclone of cells bearing 'benign' rearrangements overwhelmed by another subclone presenting aberrations with higher 'oncogenic' potential. In summary, the present study shows that bilateral and unilateral retinoblastoma have different chromosomal instability that correlates with the age of tumor onset in unilateral cases. This is the first report of genomic profiling in retinoma tissue, shedding light on the different nature of lesions named 'retinoma'.

  13. Retinoblastoma protein: a central processing unit

    Indian Academy of Sciences (India)

    M Poznic

    2009-06-01

    The retinoblastoma protein (pRb) is one of the key cell-cycle regulating proteins and its inactivation leads to neoplastic transformation and carcinogenesis. This protein regulates critical G1-to-S phase transition through interaction with the E2F family of cell-cycle transcription factors repressing transcription of genes required for this cell-cycle check-point transition. Its activity is regulated through network sensing intracellular and extracellular signals which block or permit phosphorylation (inactivation) of the Rb protein. Mechanisms of Rb-dependent cell-cycle control have been widely studied over the past couple of decades. However, recently it was found that pRb also regulates apoptosis through the same interaction with E2F transcription factors and that Rb–E2F complexes play a role in regulating the transcription of genes involved in differentiation and development.

  14. Retinoblastoma protein: a central processing unit.

    Science.gov (United States)

    Poznic, M

    2009-06-01

    The retinoblastoma protein (pRb) is one of the key cell-cycle regulating proteins and its inactivation leads to neoplastic transformation and carcinogenesis. This protein regulates critical G1 -to-S phase transition through interaction with the E2F family of cell-cycle transcription factors repressing transcription of genes required for this cell-cycle check-point transition. Its activity is regulated through network sensing intracellular and extracellular signals which block or permit phosphorylation (inactivation) of the Rb protein. Mechanisms of Rb-dependent cell-cycle control have been widely studied over the past couple of decades. However, recently it was found that pRb also regulates apoptosis through the same interaction with E2F transcription factors and that Rb-E2F complexes play a role in regulating the transcription of genes involved in differentiation and development.

  15. CT diagnosis of retinoblastoma with histopathologic correlations

    Energy Technology Data Exchange (ETDEWEB)

    Olivecrona, H. [Dept. of Radiology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Agerberg, P.A. [Dept. of Radiology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Huaman, A. [Dept. of Pathology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    1994-08-01

    The authors correlated the radiologic and histopathologic characteristics of 108 retinoblastomas in 98 patients. Calcifications were demonstrable by CT scans in 92.6% of the cases, whereas only 82% were evident upon routine histologic study. Cases of severe invasion of the optic nerve beyond the lamina cribrosa and up to the surgical margin of the nerve were detected by CT scans. Lesser degrees of invasion could not be determined by the same method. Orbital extension was also demonstrable, whereas invasion limited to the sclera was rarely accessible to CT diagnosis. Choroidal invasion was not detectable. Computerized tomography detected enlargement of the ipsilateral lacrimal gland in 17.5% of patients. This phenomenon correlates with invasion of the choroid and the optic nerve. (orig.)

  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. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  18. Nuclear medicine imaging of pheochromocytoma and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Sisson, J.C.; Shulkin, B.L. [Michigan Health Systems Univ., Ann Arbor, MI (United States). Div. of Nuclear Medicine, Dept. of Internal Medicine

    1999-09-01

    Both pheochromocytomas and neuroblastomas can now be identified and located with a high level of accuracy. Scintigraphy with MIBG has become an indispensable diagnostic method for defining the extent and location of many if not most pheochromocytomas. To define the stage, to document the course and to evaluate the response to therapies in patients with neuroblastoma, imaging with MIBG is now essential.

  19. Retinoma and Phthisis Bulbi of Retinoblastoma 1.Clinical and Genetic Analysis

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    Retinoma and phthisis bulbi of retinoblastoma are rare entitiesfound in retinoblastoma patients and their relatives.Eleven cases of phthisisbulbi of retinoblastoma and 9 cases of retinoma were identified from 1966 to1991 in our center.The clinic data show that retinoma and phthisis bulbi areclosely related to the retinoblastoma gene.Enucleation should be carried outas soon as possible without hesitation for the phthisis of eyes with retinoblas-toma.Genetic counseling and frequent observation should be p...

  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

    Purpose The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. Method 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. Results 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. Discussion 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. PMID:28275608

  1. Outcomes of Cataract Surgery Following Treatment for Retinoblastoma

    Science.gov (United States)

    Kim, Hyeong Min; Lee, Byung Joo; Kim, Jeong Hun

    2017-01-01

    Purpose To evaluate the long-term visual outcomes and complications of cataract surgery in eyes previously treated for retinoblastoma. Methods We reviewed the medical records of patients who underwent cataract extraction and intraocular lens implantation at Seoul National University Children's Hospital for a secondary cataract that developed after retinoblastoma treatment. Results During the period between 1990 and 2014, 208 eyes of 147 patients received eye-salvaging treatment (radiotherapy, chemotherapy, and local therapy) for retinoblastoma at Seoul National University Children's Hospital. Among these eyes, a secondary cataract was detected in 17 eyes of 14 patients, and five eyes of five patients underwent cataract surgery. The median age of cataract formation was 97 months (range, 38 to 153 months). The medial interval between the diagnosis of retinoblastoma and cataract formation was 79 months (range, 29 to 140 months). All patients received posterior chamber intraocular lens insertion after irrigation and aspiration of the lens through a scleral tunnel incision. Anterior vitrectomy and posterior capsulotomy were performed in two eyes and a laser capsulotomy was subsequently performed in one eye. No intraoperative and postoperative complications occurred. The median follow-up after surgery was 36 months (range, 14 to 47 months). The final best corrected visual acuities were improved in all five eyes. No intraocular tumor recurrences or metastases occurred. Conclusions After retinoblastoma regression, cataract extraction in our series was not associated with tumor recurrence or metastasis. Visual improvement was noted in every patient. PMID:28243024

  2. 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.

  3. Cell death, chromosome damage and mitotic delay in normal human, ataxia telangiectasia and retinoblastoma fibroblasts after x-irradiation.

    Science.gov (United States)

    Zampetti-Bosseler, F; Scott, D

    1981-05-01

    We recently showed (Scott and Zampetti-Bosseler 1980) that X-ray sensitive mouse lymphoma cells sustain more chromosome damage, mitotic delay and spindle defects than X-ray resistant cells. We proposed that (a) chromosome aberrations contribute much more to lethality than spindle defects, and (b) that DNA lesions are less effectively repaired in the sensitive cells and give rise to more G2 mitotic delay and chromosome aberrations. Our present results on human fibroblasts with reported differential sensitivity to ionizing radiation (i.e. normal donors and patients with ataxia telangiectasia and retinoblastoma) support the first hypothesis since we observed a positive correlation between chromosome aberration frequencies and cell killing and no induced spindle defects. Our second hypothesis is however not substantiated since X-ray sensitive fibroblasts from the ataxia patient suffered less mitotic delay than cells from normal donors. A common lesion for mitotic delay and chromosome aberrations can still be assumed by adopting the hypothesis of Painter and Young (1981) that the defect in ataxia cells is not in repair but in a failure of DNA damage to initiate mitotic delay. In contrast to other reports, we found the retinoblastoma cells to be of normal radiation sensitivity (cell killing and aberration).

  4. The role of intravitreal chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  5. 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

  6. 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

  7. Masquerade syndrome:Retinoblastoma presenting as phacolytic glaucoma

    Institute of Scientific and Technical Information of China (English)

    Li-Jing Peng; Syed Shoeb Ahmad; Nor Haizura Bt Abd Rani; May May Choo; Shuaibah Abdul Ghani

    2016-01-01

    We aim to report an uncommon presentation of retinoblastoma and its management. A 4-year-old boy presented with left eye pain for 1 week with eye redness after being hit by a ball. On examination, the visual acuity in his right eye was 6/6 and left eye was no perception to light. The conjunctiva in his left eye was injected and cornea was edematous. There was pseudohypopyon inferiorly. Lens was opaque and there was no fundus view. Intraocular pressure was 50 mmHg. Patient was initially treated as phacolytic glaucoma with severe inflammation. B scan showed intralesional calcification with retinal detachment. CT orbit showed left intraocular mass with calcification and optic nerve involvement. Thus, our final diagnosis was left eye retinoblastoma. Patient was performed a enucleation with chemotherapy in left eye. One year after the treatment, there was no local and distant invasion of the tumor. Anterior inflammation is a rare form of masquerade syndrome associated with retinoblastoma.

  8. [Plasmablastic lymphoma].

    Science.gov (United States)

    Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

    2016-11-04

    Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  9. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik H; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B-cell lymph......Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B...... chemotherapy with or without adjuvant treatment is the treatment of choice for high-grade or disseminated lymphomas. The majority of subtypes, especially low-grade subtypes, have a good prognosis with few recurrences or progression. Some subtypes, including mycosis fungoides, have a poorer prognosis...

  10. Narcolepsy/Cataplexy and Occult Neuroblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-11-01

    Full Text Available Investigators at the University of Chicago and Northwestern University, Chicago, IL; University Hospital Southampton, UK; and Kiev Paediatric Hospital, Ukraine, report three children with narcolepsy and cataplexy subsequently diagnosed with neuroblastoma.

  11. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  12. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  13. Childhood neuroblastoma masquerading as pheochromocytoma: case report

    OpenAIRE

    Moon SB

    2016-01-01

    Suk-Bae MoonDepartment of Surgery, Kangwon National University Hospital, Kangwon National School of Medicine, Kangwon National University, Chuncheon, South KoreaAbstract: Neuroblastoma is the most common extracranial solid tumor in children. Mild hypertension is a frequent symptom, presumably an effect of catecholamines that tumors release. Reported herein is the rare occurrence of severe hypertension and subsequent heart failure attributable to adrenal gland neuroblastoma. A 3-year-old boy p...

  14. Olfactory neuroblastoma: A case report

    Science.gov (United States)

    USLU, GONCA HANEDAN; CANYILMAZ, EMINE; ZENGIN, AHMET YASAR; MUNGAN, SEVDEGUL; YONEY, ADNAN; BAHADIR, OSMAN; GOCMEZ, HUSEYIN

    2015-01-01

    Olfactory neuroblastoma (ON) is a rare type of malignant neoplasm originating from the olfactory neuroepithelial cells of the nasal cavity. ON is also known as esthesioneuroblastoma or neuroendocrine carcinoma. The malignancy accounts for <3% of tumors originating in the nasal cavity. Through the nasal cavity, ON may infiltrate the sinuses, the orbit and the cranium. The tumor is characterized by a pattern of slow growth and local recurrences. Treatment options are surgical excision or surgery combined with a radiotherapy (RT) and/or chemotherapy combination treatment. The present study reports the case of a 69-year-old patient with a mass in the nasal cavity who was treated by combined surgical excision and RT. The literature for ON and the treatment of the tumor are also discussed. PMID:26788185

  15. Neuroblastoma

    Science.gov (United States)

    ... and feet movements (called opsoclonus-myoclonus syndrome, or "dancing eyes and dancing feet") Exams and Tests The health care provider ... cases, surgery alone is enough. Often, though, other therapies are needed as well. Anticancer medicines ( chemotherapy ) may ...

  16. Testicular lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

    1994-01-01

    In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...... were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens...

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

    African Journals Online (AJOL)

    Methods: The effect of puerarin was examined on human retinoblastoma Y79 cells ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, ..... Hou SZ, Su ZR, Chen SX, Ye MR, Huang S, Liu L, Lai. XP.

  18. Carboplatin-associated ototoxicity in children with retinoblastoma.

    Science.gov (United States)

    Qaddoumi, Ibrahim; Bass, Johnnie K; Wu, Jianrong; Billups, Catherine A; Wozniak, Amy W; Merchant, Thomas E; Haik, Barrett G; Wilson, Matthew W; Rodriguez-Galindo, Carlos

    2012-04-01

    Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence of ototoxicity and its risk factors in children with retinoblastoma who were treated with carboplatin. We reviewed the audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine according to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37). Ototoxicity was evaluated by three different grading systems. Twelve patients (20%) developed ototoxicity at some time after treatment initiation; however, ototoxicity resolved in two patients, and thus,10 patients (17%) had sustained hearing loss as documented at their most recent audiologic evaluation. Nine of these 10 patients had grade 3 or 4 ototoxicity, and nine patients were less than 6 months of age at the start of chemotherapy. Age at the start of chemotherapy was the only risk factor identified as a significant predictor of sustained hearing loss. Younger age was associated with an increased incidence of hearing loss. The different ototoxicity grading systems showed good overall agreement in the identification of patients with ototoxicity. Agreement was greatest between the Brock and Children's Cancer Group systems. We found that young patients with retinoblastoma who were treated with systemic carboplatin had a higher incidence of ototoxicity than previously reported. Younger patients (ototoxicity than were older patients. Children treated with carboplatin should routinely undergo thorough, long-term audiologic monitoring.

  19. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism.

    Science.gov (United States)

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-11-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care.

  20. Photoacoustic imaging features of intraocular tumors: Retinoblastoma and uveal melanoma

    Science.gov (United States)

    Xu, Guan; Xue, Yafang; Özkurt, Zeynep Gürsel; Slimani, Naziha; Hu, Zizhong; Wang, Xueding; Xia, Kewen; Ma, Teng; Zhou, Qifa; Demirci, Hakan

    2017-01-01

    The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images. The optical absorption spectrum of each tumor was quantified by fitting to a polynomial model. The microscopic architectures of the tumors were quantified by frequency domain analysis of the PA signals. Both the optical spectral and architectural features agree with the histological findings of the tumors. The mouse and human retinoblastoma showed comparable total optical absorption spectra at a correlation of 0.95 (p<0.005). The quantitative PAI features of human retinoblastoma and uveal melanoma have shown statistically significant difference in two tailed t-tests (p<0.05). Fully compatible with the concurrent procedures, PAI could be a potential tool complementary to other diagnostic modalities for characterizing intraocular tumors. PMID:28231293

  1. Retinoblastoma-like RRB gene of arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Durfee, Tim; Feiler, Heidi; Gruissem, Wilhelm; Jenkins, Susan; Roe, Judith; Zambryski, Patricia

    2004-02-24

    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.

  2. 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.

  3. Proton Radiation Therapy for the Treatment of Retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Cholinergic regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Kristensen, Bo; Georg, Birgitte; Fahrenkrug, Jan

    1997-01-01

    Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing......Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing...

  6. Catecholamines influence myocardial 123I MIBG uptake in neuroblastoma patients

    NARCIS (Netherlands)

    Palen, R.L.F. van der; Bulten, B.F.; Mavinkurve-Groothuis, A.M.C.; Bellersen, L.; Laarhoven, H.W.M. van; Kapusta, L.; Geus-Oei, L.F. de

    2013-01-01

    Aim: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. Patients, methods:30 neuroblastoma patients were retrospectively assessed on cardiac

  7. 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.

  8. Stages of Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  9. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  10. FNA diagnosis of CD99 positive neuroblastoma: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Gagandeep Kaur

    2012-01-01

    Full Text Available Tissue diagnosis of small round cell tumors relies heavily on immunohistochemical staining. Two of the small round cell tumors, namely neuroblastoma and primitive neuroectodermal tumor, have considerable morphologic overlap. Many studies suggest that CD99 positivity virtually excludes the diagnosis of neuroblastoma. We report a case of poorly differentiated neuroblastoma in which aberrant CD99 positivity led to diagnostic dilemma.

  11. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  12. Stages of Adult Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  13. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts Peripheral T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma and ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Peripheral T-cell lymphoma (PTCL) ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Primary Intrarenal Neuroblastoma with Hypertension and Disseminated Intravascular Coagulation

    Directory of Open Access Journals (Sweden)

    Bibi Shahin Shamsian

    2013-01-01

    Full Text Available The primary intrarenal neuroblastoma (IRNB is a rare condition. Intrarenal neuroblastoma typically results from direct renal invasion from an adrenal neuroblastoma, but true intrarenal neuroblastoma originates either sequestered adrenal rests during the fetal life or intrarenal sympathetic ganglia. Clinical, radiological, and pathological correlation is very essential for diagnosis and appropriate management of this type of unusual cases. The distinction of this rare tumor from Wilms’ tumor is an important challenge since both tumors have major differences in prognostic and therapeutic response. We present a 3-year-old boy of primary intrarenal neuroblastoma with extensive abdominal and mediastinal mass, persistent hypertension, and disseminated intravascular coagulation (DIC.

  16. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma; Radioterapia do segmento cefalico em pacientes portadores de neuroblastoma avancado

    Energy Technology Data Exchange (ETDEWEB)

    Weltman, Eduardo

    1995-07-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  17. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  18. Non-Hodgkin's Lymphoma

    Science.gov (United States)

    ... These include the lymphatic vessels, tonsils, adenoids, spleen, thymus and bone marrow. Occasionally, non-Hodgkin's lymphoma involves ... understand the possible link between pesticides and the development of non-Hodgkin's lymphoma. Older age. Non-Hodgkin's ...

  19. Achados histopatológicos em retinoblastoma Histopathologic findings in retinoblastoma

    Directory of Open Access Journals (Sweden)

    João Pessoa de Souza Filho

    2005-06-01

    Full Text Available OBJETIVO: Descrever e analisar os principais achados histopatológicos no retinoblastoma com ênfase na invasão de nervo óptico e túnicas oculares, correlacionando-os ao tratamento realizado. MÉTODOS: Vinte e oito olhos com diagnóstico de retinoblastoma tratados por enucleação na Universidade Federal de São Paulo entre dezembro de 2000 e outubro de 2002 foram submetidos à revisão histopatológica. Os dados clínicos incluiram idade, sexo, raça, lateralidade e tratamento realizado. Na revisão histopatológica foram avaliados neovascularização da íris e seio camerular, grau de diferenciação do tumor e invasão do nervo óptico e coróide de acordo com a classificação de Khelfaoui. RESULTADOS: De 27 pacientes, 13 (48,1% eram do sexo masculino e 14 (51,9% eram do sexo feminino, 16 (59,3% eram da raça branca, 5 (18,5% eram da raça amarela, 4 (14,8% eram pardos e 2 (7,4% eram negros. A média da idade dos pacientes foi de 22,7 meses, sendo 13 casos bilaterais e 14 casos unilaterais. Com relação ao tratamento utilizado, 13 (46,4% olhos foram submetidos a enucleação primária e 15 (53,6% tiveram tratamento prévio. Na avaliação histopatológica, 15 (53,6% tumores eram bem diferenciados. Neovascularização da íris e/ou seio camerular foram observados em 60,6% e necrose e calcificação em 89,2% dos casos. O envolvimento da coróide foi observado em 18 (64,2% dos casos (grau II e III e a invasão de nervo óptico em 8 (28,5% (graus II, III e IV. Dos casos submetidos ao tratamento prévio 40% tinham algum grau de invasão das túnicas oculares e apenas 6,67% apresentavam simultaneamente invasão do nervo óptico e das túnicas oculares. Entretanto nos olhos que foram submetidos à enucleação primária 30,7% apresentavam invasão das túnicas oculares e 53,8% apresentavam simultaneamente invasão do nervo óptico e das túnicas oculares. CONCLUSÃO: Neovascularização, necrose e calcificação foram achados mais comumente

  20. On Analytical Methods in Neuroblastoma Detection

    Directory of Open Access Journals (Sweden)

    R. Martínez-Díaz

    2013-01-01

    quantitative and consistent methods of evaluation are needed to assess reponse to patient therapy. Whole-body I123-metaiodobenzylguanidine (mIBG scintigraphy is used as primary medical image modality to detect neuroblastoma tumours due to its high specificity and sensitivity. However, current oncological guidelines are based on qualitative observer-dependent analysis. This fact makes it difficult to compare results of scintigraphies taken at different moments during therapy or at different institutions. In this paper, we review analytical methods used in neuroblastoma detection and propose an observer-independent method to quantitatively analyse a I123-mIBG scintigraphy.

  1. Efficient photodynamic therapy on human retinoblastoma cell lines.

    Directory of Open Access Journals (Sweden)

    Jan Walther

    Full Text Available Photodynamic therapy (PDT has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma.

  2. Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines

    Science.gov (United States)

    Walther, Jan; Schastak, Stanislas; Dukic-Stefanovic, Sladjana; Wiedemann, Peter; Neuhaus, Jochen; Claudepierre, Thomas

    2014-01-01

    Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma. PMID:24498108

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Genetic perspective of retinoblastoma: From present to future

    OpenAIRE

    2016-01-01

    Retinoblastoma (RB) is the most common malignant intraocular tumor in children. In the last decade, basic research has led to a better understanding of events after two hits in RB susceptibility gene (RB1), molecular mechanism of tumor growth, the cell of origin of RB, etc. This would pave way to identify biomarkers and molecular targeted therapy for better treatment option in the future. Furthermore, improvement in molecular techniques has led to enhanced diagnostic methods for early diagnos...

  5. Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake

    Science.gov (United States)

    The incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring. The authors used a ca...

  6. Ocular Adnexal Follicular Lymphoma

    DEFF Research Database (Denmark)

    Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

    2014-01-01

    , and 31 (45%) had stage IIE lymphoma. Patients with disseminated lymphoma had stage IIIE (9 of 19 [47%]) and stage IV (10 of 19 [53%]) disease, whereas patients with a relapse of systemic lymphoma presented with stage IE (8 of 10 [80%]), stage IIE (1 of 10 [10%]), and stage IIIE (1 of 10 [10%]) disease...

  7. Intraarterial chemotherapy for kissing macula tumors in retinoblastoma.

    Science.gov (United States)

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

    2012-01-01

    To describe the management of kissing macula retinoblastoma tumors treated with intraarterial chemotherapy. Superselective infusion of chemotherapy (combinations of melphalan, topotecan, and carboplatin) into the ophthalmic artery of children with retinoblastoma who had kissing macula tumors was administered on an outpatient basis. Results were assessed with indirect ophthalmoscopy, RetCam digital photography, B-scan ultrasonography, and electroretinograms. Three children with bilateral retinoblastoma (aged 6.1, 7, and 16 months) and kissing macula tumors in an eye were treated. All children are alive without the need for removal of the eye, systemic chemotherapy, or external beam irradiation. In each case, the kissing tumors retracted, leaving an anatomically normal fovea. Final 30-Hz flicker electroretinograms were 93.9, 65, and 63.9 μV (under anesthesia). There were no significant systemic toxicities. Superselective infusion of chemotherapy by means of the ophthalmic artery of young children with kissing macula tumors resulted in prompt shrinkage of tumors away from the fovea. There were no systemic side effects.

  8. Plasmablastic lymphoma

    Science.gov (United States)

    Han, Xiao; Duan, Minghui; Hu, Lixing; Zhou, Daobin; Zhang, Wei

    2017-01-01

    Abstract Background: Plasmablastic lymphoma (PBL) is a B-cell malignancy associated with human immunodeficiency virus (HIV). PBL could also influence the HIV-negative patients. The study aimed to identify prognostic factors for survival among Chinese PBL patients. Materials and methods: Eligible patients from literature and Peking Union Medical College Hospital (PUMCH) were included in this study. Clinical characteristics and immunophenotypic data were extracted. Kaplan–Meier curve was used to describe the survival status. Cox regression was used for multivariate analysis. Results: A total of 60 Chinese PBL patients were included, including 54 patients from 36 published articles and 6 new patients that have not been reported. The median overall survival was 7 months (95% confidence interval 3.853–10.147 months). An overwhelming majority (79.31%) of the included cases were Ann Arbor stage IV patients. All the Chinese PBL patients were HIV-negative; 46.81% were Epstein-Barr virus-positive. CD38, CD138, or MUM1 was positively expressed in more than 80% of patients; CD20 expression was also found in 22.03% of cases. Kaplan–Meier curve revealed obvious differences in patient survival between patients in primary stages and advanced stages, as well as between patients with kidney involvement and those without kidney involvement. Cox regression analysis indicated that stage and age were 2 prognostic factors for patient survival. Conclusions: Advanced stage might be associated with poor prognosis among PBL HIV-negative patients in Chinese. PMID:28248855

  9. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  10. 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.

  11. p53 Cellular Localization and Function in Neuroblastoma

    Science.gov (United States)

    Tweddle, Deborah A.; Malcolm, Archie J.; Cole, Michael; Pearson, Andrew D.J.; Lunec, John

    2001-01-01

    This study investigated the hypothesis that p53 accumulation in neuroblastoma, in the absence of mutation, is associated with functional inactivation, which interferes with downstream mediators of p53 function. To test this hypothesis, p53 expression, location, and functional integrity was examined in neuroblastoma by irradiating 6 neuroblastoma cell lines and studying the effects on p53 transcriptional function, cell cycle arrest, and induction of apoptosis, together with the transcriptional function of p53 after irradiation in three ex vivo primary, untreated neuroblastoma tumors. p53 sequencing showed five neuroblastoma cell lines, two of which were MYCN-amplified, and that all of the tumors were wild-type for p53. p53 was found to be predominantly nuclear before and after irradiation and to up-regulate the p53 responsive genes WAF1 and MDM2 in wild-type p53 cell lines and a poorly-differentiated neuroblastoma, but not a differentiating neuroblastoma or the ganglioneuroblastoma part of a nodular ganglioneuroblastoma in short term culture. This suggests intact p53 transcriptional activity in proliferating neuroblastoma. Irradiation of wild-type p53 neuroblastoma cell lines led to G1 cell cycle arrest in cell lines without MYCN amplification, but not in those with MYCN amplification, despite induction of WAF1. This suggests MYCN amplification may alter downstream mediators of p53 function in neuroblastoma. PMID:11395384

  12. 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 retin...

  13. Incidence of retinoblastoma in Dutch children conceived by IVF: an expanded study.

    NARCIS (Netherlands)

    Marees, T.; Dommering, C.J.; Imhof, S.M.; Kors, W.A.; Ringens, P.J.; Leeuwen, F.E. van; Moll, A.C.

    2009-01-01

    BACKGROUND: In 2003, we reported an increased risk of retinoblastoma in children conceived by IVF between 1995 and 2002. However, population-based studies among children conceived by IVF did not find an elevated risk of retinoblastoma. METHODS: From nationwide estimates of numbers of live births con

  14. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M; Coupland, Sarah E; Prause, Jan U;

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed b...

  15. Molecular-genetic analysis of two cases with retinoblastoma: benefits for disease management

    Indian Academy of Sciences (India)

    Govindasamy Kumaramanickavel; Biju Joseph; Komaravelly Narayana; Sribhargava Natesh; Gandra Mamatha; Mahesh P. Shanmugam; Anuradha Elamparathi; Jyotirmay Biswas

    2003-04-01

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma patients from India. The two patients, one with bilateral and the other with unilateral retinoblastoma, underwent complete ophthalmic examination, cytogenetic study, retinoblastoma gene (RB1) mutational analysis and RB1 promoter region methylation screening. In the bilateral retinoblastoma patient deletion of chromosome region 13q14 in peripheral blood lymphocytes and a hemizygous novel 8-bp deletion in exon 4 of RB1 in tumour sample were observed. In the unilaterally affected patient CGA to TGA transition protein truncation mutations were observed in exons 8 and 14 of RB1.

  16. The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    Wanli Liu; Zhongyao Wu

    2005-01-01

    Purpose: To study cyclosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs.Methods: To study the growth curve of cyclosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyclosporine A combined with seven antineoplastic drugs.Results: The average IC50 of cyclosporine A on the 27 retinoblastoma cells is 67.81μg/ml and the average inhibitive rate of these samples is 26.1% when cyclosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyclosporine A and the increasing average inhibitive rate is more than 5.Conclusion: Cyclosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells.

  17. Evolução da terapêutica do retinoblastoma Development in the treatment of retinoblastoma

    Directory of Open Access Journals (Sweden)

    Célia Beatriz Gianotti Antoneli

    2003-08-01

    Full Text Available OBJETIVO: Mostrar a evolução do tratamento do retinoblastoma ao longo de uma década e suas implicações na sobrevida global e na preservação da visão. MÉTODOS: Trezentos e dezenove pacientes foram avaliados no estudo. Analisamos 257 pacientes portadores de retinoblastoma admitidos no Hospital do Câncer, entre janeiro de 1986 a dezembro de 1996, divididos em dois grupos de acordo com tratamento a que foram submetidos (1986 a 1990 e 1991 a 1996. Analisamos ainda 62 pacientes portadores de retinoblastoma intra-ocular entre janeiro de 1996 e maio de 2000 que foram submetidos a quimiorredução, aliada a medidas oftalmológicas, sem enucleação ou radioterapia externa. RESULTADOS: Em pacientes com doença intra-ocular, nos dois períodos, não houve significância estatística com relação à sobrevida. Analisamos 59 pacientes com retinoblastoma extra-ocular, de acordo com a classificação do CCG (Children´s Cancer Group, e a sobrevida global em 5 anos foi maior no 2º período, (63,7% vs. 41%; p= 0,059. Entre 1996 e 2000 analisamos 62 pacientes com retinoblastoma intra-ocular com visão preservada, sendo 47 (75,8% com doença bilateral e 15 (24,2% com tumor unilateral. Os portadores de tumor bilateral tiveram uma taxa de preservação de visão de 49,8%, versus 26,7% para os pacientes com tumor unilateral. CONCLUSÕES: Tumores intra-oculares mantêm altas taxas de cura e preservação da visão. Novas combinações de drogas poderão melhorar a sobrevida dos extra-oculares. Quanto às perspectivas futuras, há pesquisas envolvendo terapia gênica/molecular e terapêutica anti-angiogênese. Apesar de toda a evolução, o diagnóstico precoce é a arma mais poderosa, na cura dos portadores deste tumor.PURPOSE: The management of retinoblastoma (Rb has gradually changed over the past years achieving a satisfactory result (increasing overall survival and avoiding enucleations. METHODS: Three hundred and nineteen patients with retinoblastoma

  18. MMSET is highly expressed and associated with aggressiveness in neuroblastoma

    DEFF Research Database (Denmark)

    Hudlebusch, Heidi Rye; Skotte, Julie; Santoni-Rugiu, Eric;

    2011-01-01

    tumor types as well. We have performed immunohistochemical staining of tissue microarrays and found that MMSET protein is frequently and highly expressed in neuroblastoma (MMSET positive in 75% of neuroblastomas, n=164). The expression level of MMSET in neuroblastomas was significantly associated...... with poor survival, negative prognostic factors, and metastatic disease. Moreover, a subset of neuroblastomas for which pre- and post-chemotherapy biopsies were available displayed a strong decrease in MMSET protein levels after chemotherapy. In agreement with neuroblastomas becoming more differentiated...... after treatment, we show that retinoic acid-induced differentiation of human neuroblastoma cells in vitro also leads to a strong decrease in MMSET levels. Furthermore, we demonstrate that the high levels of MMSET in normal neural progenitor cells are strongly downregulated during differentiation...

  19. Solitary calvarial metastases : An unusual presentation of thoracic neuroblastoma

    Directory of Open Access Journals (Sweden)

    Grover S

    2003-01-01

    Full Text Available A primary thoracic origin occurs only in 20% of neuroblastomas, and their classical presentation is mediastinal or cord compression. Skeletal metastases of neuroblastomas are characteristically multiple, and calvarial deposits usually show simultaneous involvement of orbit. Solitary metastases in neuroblastoma, is an unusual entity and its presentation as a large calvarial mass, especially from a thoracic primary, is rare. Furthermore, calvarial metastases are relatively uncommon in children compared to adults. We discuss the clinical, radiographic, CT features, and differential diagnosis of a large calvarial mass with sunray spiculation in a child, which was due to a solitary metastases from an occult thoracic neuroblastoma. The possibility of neuroblastoma presenting in this unique fashion and the importance of considering a chemosensitive tumor such as neuroblastoma in the differential diagnosis of a solitary calvarial mass in a child is highlighted by our report.

  20. Lymphoma in acquired generalized lipodystrophy.

    Science.gov (United States)

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  1. Stage 4S Bilateral Adrenal Neuroblastoma in a Newborn

    Directory of Open Access Journals (Sweden)

    Rahul Gupta

    2014-02-01

    Full Text Available Stage 4S bilateral adrenal neuroblastoma presenting in the neonatal period is extremely rare. A 1-day-old male with 4S bilateral adrenal neuroblastoma complicated by marked hepatomegaly managed by chemotherapy is being reported. The provisional diagnosis of neuroblastoma was made in the fetal life during the last trimester of pregnancy. Cardiomyopathy due to doxorubicin cytotoxicity developed over ensuing years, which is being treated.

  2. Common and unusual craniofacial manifestations of metastatic neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    D' Ambrosio, Nicholas [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Crouse Hospital, Department of Radiology, Syracuse, NY (United States); Lyo, John; Young, Robert; Haque, Sophia; Karimi, Sasan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2010-06-15

    Although neuroblastoma is a common childhood malignancy, which frequently metastasizes, involvement of the facial bones and paranasal sinuses are uncommonly reported in the literature. However, over the last several years, we have encountered an increasing number of cases of metastatic neuroblastoma to the central nervous system and head and neck. This article will review the common and uncommon imaging manifestations of metastatic neuroblastoma, with emphasis on the orbits, maxillofacial bones, and paranasal sinuses. (orig.)

  3. Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage.

    Science.gov (United States)

    Zhang, Jing-Xing; Wang, Rui; Xi, Jin; Shen, Lin; Zhu, An-You; Qi, Qi; Wang, Qi-Yi; Zhang, Lun-Jun; Wang, Feng-Chao; Lü, He-Zuo; Hu, Jian-Guo

    2017-03-01

    Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM. The increase in intracellular reactive oxygen species (ROS) generation and lipid peroxidation induced by H2O2 was also abrogated by morroniside. H2O2 induced a reduction in mitochondrial membrane potential, increased caspase-3 activity, and caused downregulation of B cell lymphoma-2 (Bcl-2) and upregulation of Bcl-2-associated X protein (Bax) expression. These effects were blocked by morroniside pretreatment. Thus, morroniside protects human neuroblastoma cells against oxidative damage by inhibiting ROS production while suppressing Bax and stimulating Bcl-2 expression, thereby blocking mitochondrial-mediated apoptosis. These results indicate that morroniside has therapeutic potential for the prevention and treatment of neurodegenerative diseases.

  4. 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

  5. Diagnóstico y tratamiento de retinoblastoma

    OpenAIRE

    Nie Meiting

    2012-01-01

    El retinoblastoma es el tumor maligno más frecuente en la infancia, sin embargo sigue siendo un tumor raro en niños. Se asocia a una inactivación de ambos alelos del gen supresor tumoral. Pueden aparecer esporádicamente o pueden ser familiares y existen varios patrones de diseminación tumoral que pueden variar el pronóstico tanto visual como del globo ocular. El signo más frecuente es la leucocoria seguido por estrabismo, con una edad promedio de presentación a los 2 años en casos unilaterale...

  6. 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.

  7. A Very Rare Adult Case with Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Fatih Selcukbiricik

    2011-09-01

    Full Text Available We report a 53-year-old male patient who underwent paravertebral mass excision at the D10–11–12 vertebral levels in 2007. The histopathological evaluation of the mass showed the presence of neuroblastoma. The patient was diagnosed with stage IV neuroblastoma. He received 6 courses of chemotherapy and exhibited a stable course until March 2010. When he was reevaluated in March 2010, progression in the metastatic lesion as well as local recurrence was detected. The patient, who was restarted on chemotherapy, developed progressive weakness and loss of sensation of the lower extremity. The neurosurgical investigation revealed an irreversible loss in motor functions. The patient is currently on symptomatic treatment.

  8. Pediatric lymphomas in Brazil

    Directory of Open Access Journals (Sweden)

    Gabriela Gualco

    2010-01-01

    Full Text Available OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36% and mature (64% cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%, followed by diffuse large B-cell lymphomas (24%. In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%, followed by peripheral T-cell lymphoma, then not otherwise specified (25%. In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%. Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.

  9. Lymphomas of large cells.

    Science.gov (United States)

    Staples, W G; Gétaz, E P

    1977-09-03

    Historial aspects of the classification of large-cell lymphomas are described. Immunological characterization of the lymphomas has been made possible by identification of T and B lymphocytes according to their cell membrane surface characteristics. The pathogenesis of lymphomas has been clarified by the germinal (follicular) centre cell concepts of Lennert and Lukes and Collins. The various classifications are presented and compared. Whether these subdivisions will have any relevance in the clinical context remains to be seen.

  10. Lymphoma Microenvironment and Immunotherapy.

    Science.gov (United States)

    Xu, Mina L; Fedoriw, Yuri

    2016-03-01

    Understanding of the lymphoma tumor microenvironment is poised to expand in the era of next-generation sequencing studies of the tumor cells themselves. Successful therapies of the future will rely on deeper appreciation of the interactions between elements of the microenvironment. Although the phenotypic, cytogenetic, and molecular characterization of tumor cells in lymphomas has progressed faster than most other solid organ tumors, concrete advancements in understanding the lymphoma microenvironment have been fewer. This article explores the composition of the lymphoma tumor microenvironment; its role in immune surveillance, evasion, and drug resistance; and its potential role in the development of targeted therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Bilateral primary breast lymphoma

    Institute of Scientific and Technical Information of China (English)

    Jung Im Yi; Byung Joo Chae; Ja Seong Bae; Bong Joo Kang; Ahwon Lee; Byung Joo Song; Sang Seol Jung

    2010-01-01

    @@ Primary breast lymphoma (PBL) is rare, accounting for 0.04%-0.50% of breast malignancies and 1.7% of extranodal lymphoma.1,2 The originally described diagnostic criteria for PBL2 remains the standard definition for this disease. These criteria are breast location as the clinical site of presentation, absence of history of previous lymphoma or evidence of widespread disease at diagnosis, close association of lymphoma with breast tissue in pathologic specimens, and involvement of ipsilateral lymph nodes if they develop simultaneously with PBL.

  12. Primary gastrointestinal lymphoma

    Institute of Scientific and Technical Information of China (English)

    Prasanna Ghimire; Guang-Yao Wu; Ling Zhu

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific,thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways.

  13. Bilateral Primary Intraocular Lymphoma

    Directory of Open Access Journals (Sweden)

    Mehrdad Karimi

    2011-01-01

    Full Text Available Purpose: To report a case of bilateral primary intraocular lymphoma. Case report: A 33-year-old man presented with bilateral blurred vision since two years ago. Examination revealed large keratic precipitates, anterior chamber reaction, posterior subcapsular cataracts, and vitreous infiltration. After a short trial of topical and periocular steroids, diagnostic 25-gauge pars plana vitrectomy was performed and cytologic evaluation of the aspirate confirmed a diagnosis of intraocular lymphoma. The patient was subsequently managed with intravitreal methotrexate in both eyes and responded favorably. Central nervous system workup for lymphoma was negative. Conclusion: Primary intraocular lymphoma should be considered in young adults suffering from chronic recalcitrant panuveitis.

  14. Whole-body MRI of neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo, E-mail: hwgoo@amc.seoul.k [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul 138-736 (Korea, Republic of)

    2010-09-15

    Whole-body MRI (WBMRI) is an emerging imaging method that has a great potential in pediatric oncologic imaging. It appears useful in staging and monitoring neuroblastoma although its clinical impact has not been thoroughly evaluated. Among various imaging techniques currently available for WBMRI, coronal and sagittal STIR imaging with a quadrature body coil at 1.5T MR system is recommended for a standard protocol. Nevertheless, further technical improvements are anticipated at 3.0T MR system and multi-channel surface coil system. Scan time of WBMRI is reasonably short ranging from 20 min to 60 min. In localized neuroblatoma, WBMRI may help in predicting surgical risks by evaluating image-defined risk factors accurately. In addition, WBMRI is quite useful in detecting distant metastasis, assessing initial treatment responses, and identifying tumor recurrence of neuroblastoma. We should understand limitations of WBMRI in the evaluation of lymph node involvement, in the differentiation between viable tumor and non-viable residual lesion, and in the detection of calcified lesion. Diffusion-weighted imaging may improve diagnostic accuracy of WBMRI. Complementary use of WBMRI and other metabolic imaging method such as MIBG scintigraphy or PET probably increases diagnostic accuracy and, subsequently, improves clinical outcome of children with neuroblastoma.

  15. Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells.

    Science.gov (United States)

    Liu, Mengling; Xia, Yingfeng; Ding, Jane; Ye, Bingwei; Zhao, Erhu; Choi, Jeong-Hyeon; Alptekin, Ahmet; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Yang, Liqun; Cui, Hongjuan; Zha, Yunhong; Ding, Han-Fei

    2016-10-04

    High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Genetic Profile of Retinoblastoma Patients from a Referral Hospital in Gujarat

    Directory of Open Access Journals (Sweden)

    Sunil G Oza

    2012-06-01

    Full Text Available Background & objectives: Retinoblastoma is the most common intraocular malignancy of infant and childhood. It is the first disease for which a genetic etiology of cancer has been described and the first suppressor gene identified. The chromosomal abnormality found in retinoblastoma cases is deletion of 13q14. The aim of this study was to carry out karyotypic study in Retinoblastoma cases and identifying nature of chromosomal abnormalities in these patients to determine recurrence risks to assist genetic counseling. Materials and Methods: Karyotypic study was perform by Trypsin- Giemsa Banding for 17 unilateral and 8 bilateral retinoblastoma patients (total 25 for that their blood samples were taken. A prior written consent was taken from the parents of these patients. Results: Out of 25 cases of Retinoblastoma, one female (4% had 13q14 deletion and 24 (96% showed normal chromosomal constitution and not a single case of translocation and mosaicism were found. Conclusion: Karyotyping is the simplest and affordable genetic test for most of the retinoblastoma families especially in a developing country like India. Genetic testing is crucial for accurate risk prediction for retinoblastoma in close relatives of probands and provides a basis for genetic counseling. [National J of Med Res 2012; 2(3.000: 322-324

  17. Association of Electroencephalography (EEG) Power Spectra with Corneal Nerve Fiber Injury in Retinoblastoma Patients.

    Science.gov (United States)

    Liu, Jianliang; Sun, Juanjuan; Diao, Yumei; Deng, Aijun

    2016-09-04

    BACKGROUND In our clinical experience we discovered that EEG band power may be correlated with corneal nerve injury in retinoblastoma patients. This study aimed to investigate biomarkers obtained from electroencephalography (EEG) recordings to reflect corneal nerve injury in retinoblastoma patients. MATERIAL AND METHODS Our study included 20 retinoblastoma patients treated at the Department of Ophthalmology, Affiliated Hospital of Weifang Medical University between 2010 and 2014. Twenty normal individuals were included in the control group. EEG activity was recorded continuously with 32 electrodes using standard EEG electrode placement for detecting EEG power. A cornea confocal microscope was used to examine corneal nerve injury in retinoblastoma patients and normal individuals. Spearman rank correlation analysis was used to analyze the correlation between corneal nerve injury and EEG power changes. The sensitivity and specificity of changed EEG power in diagnosis of corneal nerve injury were also analyzed. RESULTS The predominantly slow EEG oscillations changed gradually into faster waves in retinoblastoma patients. The EEG pattern in retinoblastoma patients was characterized by a distinct increase of delta (PEEG spectra power and negatively correlated with theta EEG spectra power. The diagnostic sensitivity and specificity by compounding in the series were 60% and 67%, respectively. CONCLUSIONS Changes in delta and theta of EEG appear to be associated with occurrence of corneal nerve injury. Useful information can be provided for evaluating corneal nerve damage in retinoblastoma patients through analyzing EEG power bands.

  18. 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.

  19. Ultrastructural changes of mitochondria in human retinoblastoma: correlation with tumor differentiation and invasiveness.

    Science.gov (United States)

    Singh, Lata; Nag, Tapas C; Kashyap, Seema

    2016-05-01

    Retinoblastoma still represents a challenge for pediatric tumors. Mitochondria have been implicated in tumor progression, cell differentiation, and apoptotic pathways. Electron microscopy allows the study of mitochondrial morphology and it is still debated in human retinoblastoma. Demographic, clinical, and histopathological parameters were recorded in 17 enucleated retinoblastoma specimens. Hematoxylin and eosin staining was performed to study tumor characteristics and the extent of invasion in ocular structures. The aim of this study was to describe and analyze the mitochondrial morphology in human retinoblastoma by transmission electron microscopy (TEM). There was a male preponderance in our study. Ages ranged from 2 to 78 months. Histopathological analysis revealed that 15 (88.2 %) tumors were poorly differentiated retinoblastomas. Massive choroidal invasion was the most frequent histopathological high-risk factor among the others. Histopathological high-risk factors were found in 7/17 (41.1 %) cases. Tumor samples of all patients were examined by means of TEM. All cases showed tumor cells with high nucleocytoplasmic ratio. Poorly differentiated retinoblastoma cases showed fewer mitochondria, scant cytoplasm, disorganized organelles (mitochondria), and necrosis, whereas well-differentiated retinoblastomas had larger number of mitochondria and more organized organelles. However, there was no significant difference in mitochondrial changes between invasive and noninvasive tumors. Our study observed that cristolysis and swollen mitochondria were more frequent in retinoblastoma tumors. Understanding the structural and functional characteristics of mitochondria in retinoblastoma might be essential for the design of future therapeutic strategies. The authors have no proprietary or commercial interest in any materials discussed in this article.

  20. Expression and methylation pattern of p16 in neuroblastoma tumorigenesis.

    Science.gov (United States)

    Aktas, Safiye; Celebiler, Aydan Cavusoglu; Zadeoğlulari, Zeynep; Diniz, Gulden; Kargi, Aydanur; Olgun, Nur

    2010-03-01

    Understanding migration, population and differentiation of primordial neural crest cells will help in evolving biology of neuroblastoma. P16 is a tumour suppressor gene contributing in cell cycle arrest as cyclin dependent kinase inhibitor. Methylation is an important mechanism for silencing tumor suppressor genes. The aim of this study was to evaluate the role of p16 and its methylation pattern in neuroblastoma tumorigenesis. This study included 23 cases (11 male; 12 female) and 31 samples from archival paraffin embedded tissues. P16 was studied in 5 samples of normal adrenal medullar tissue, 5 samples of adrenal tissue including blastic rests, 5 samples of neuroblastoma in situ tissue and in 8 samples of neuroblastoma tissues primary and after chemotherapy in each group. The adrenal gland tissues were obtained from paediatric autopsy cases. Expression of p16 was searched by immunohistochemistry. Methylation specific PCR was used to detect the methylation rate of p16. The age range of autopsy cases was between 20 weeks of foetal age and 36 months of infant age. The mean age of neuroblastoma cases was 45 months. P16 expression was positive in normal adrenal tissues, in one of 5 samples of adrenal blastic rest tissue and in all of samples of after chemotherapy; while no expression was observed in neuroblastoma and neuroblastoma in situ tissues. P16 methylation was observed in samples of neuroblastoma in situ and primary neuroblastoma tissues. Our results suggest that p16 and its methylation seems to play role in neuroblastoma tumorigenesis and in the migration, population and differentiation of primordial neural crest cells. Inhibitors of DNA methylation may provide a useful tool for restoring p16 activity in neuroblastoma treatment.

  1. 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.

  2. [Molecular abnormalities in lymphomas].

    Science.gov (United States)

    Delsol, G

    2010-11-01

    Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities

  3. Sarcoidosis Occurring After Lymphoma

    Science.gov (United States)

    London, Jonathan; Grados, Aurélie; Fermé, Christophe; Charmillon, Alexandre; Maurier, François; Deau, Bénédicte; Crickx, Etienne; Brice, Pauline; Chapelon-Abric, Catherine; Haioun, Corinne; Burroni, Barbara; Alifano, Marco; Le Jeunne, Claire; Guillevin, Loïc; Costedoat-Chalumeau, Nathalie; Schleinitz, Nicolas; Mouthon, Luc; Terrier, Benjamin

    2014-01-01

    Abstract Sarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or 18fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or 18FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse. PMID:25380084

  4. δ-OPIOID RECEPTOR ADAPTATION IN NEUROBLASTOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    D-M,Chuang; M.Belchers; J.Barg; J.Rowinski; G.Clark; C.A.Gloeckner; A.Ho; X-M.Gao; C.J.Coscia

    1993-01-01

    The mechanisms underlying tolerance and dependence arising from chronic opioid exposure are poorly understood. However, the development of neuroblastoma and neurohybrid cell culturea, has provided a simplified model for the atudy of opioid receptor adaptation. Using neuroblastoma NG108-15 cells,

  5. Inhibition of hemopoiesis in vitro by neuroblastoma-derived gangliosides

    NARCIS (Netherlands)

    Sietsma, H; Nijhof, W; Dontje, B; Vellenga, E; Kamps, WA; Kok, JW

    1998-01-01

    Hemopoiesis is disturbed in bone marrow-involving cancers like leukemia and neuroblastoma. Shedding of gangliosides by tumor cells may contribute to this tumor-induced bone marrow suppression, We studied in vitro the inhibitory effects of murine neuroblastoma cells (Neuro-2a and C1300) and their

  6. A Neuroblastoma × Glioma Hybrid Cell Line with Morphine Receptors

    Science.gov (United States)

    Klee, Werner A.; Nirenberg, Marshall

    1974-01-01

    A neuroblastoma × glioma hybrid cell line with well-developed neural properties was found that has high-affinity morphine receptors. The average cell contains approximately 3 × 106 receptors. In contrast, parent cells and other neuroblastoma or hybrid cell lines tested had few or no morphine receptors. PMID:4530316

  7. Biomarkers for lymphoma

    Science.gov (United States)

    Zangar, Richard C.; Varnum, Susan M.

    2014-09-02

    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  8. [Secondary orbital lymphoma].

    Science.gov (United States)

    Basanta, I; Sevillano, C; Álvarez, M D

    2015-09-01

    A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    Angioimmunoblastic T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Cancerous lymphocytes can travel to ...

  10. Dye-mediated photosensitization of murine neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Sieber, F.; Sieber-Blum, M.

    1986-04-01

    The purpose of this study was to determine if photosensitization mediated by the fluorescent dye, merocyanine 540, could be used to preferentially kill murine neuroblastoma cells in simulated autologous remission marrow grafts. Simultaneous exposure of Neuro 2a or NB41A3 neuroblastoma cells to merocyanine 540 and white light reduced the concentration of in vitro-clonogenic tumor cells 50,000-fold. By contrast, the same treatment had little effect on the graft's ability to rescue lethally irradiated syngeneic hosts. Lethally irradiated C57BL/6J X A/J F1 mice transplanted with photosensitized mixtures of neuroblastoma cells and normal marrow cells (1:100 or 1:10) survived without developing neuroblastomas. It is conceivable that merocyanine 540-mediated photosensitization will prove useful for the extracorporeal purging of residual neuroblastoma cells from human autologous remission marrow grafts.

  11. Globe salvage using chemoreduction for advanced retinoblastoma in a glaucomatous eye with buphthalmos.

    Science.gov (United States)

    Parvus, Britt J; Salazar, Pedro F; Shields, Carol L; Shields, Jerry A

    2009-01-01

    To report globe salvage using chemoreduction (CRD) for advanced retinoblastoma in a glaucomatous eye with buphthalmos. Case report. A 7-month-old girl presented with epiphora and buphthalmos in the right eye. She was found to have bilateral retinoblastoma. Classified as group E, the right eye exhibited a total retinal detachment and buphthalmos from secondary glaucoma. The left eye was classified as group B. Systemic workup revealed no metastatic disease. CRD was employed with future planned enucleation of the right eye. After six cycles of CRD and focal consolidating treatments, complete regression of retinoblastoma in both eyes was achieved. The right eye showed complete resolution of the retinal detachment and no active tumor or seeds at 18 months follow-up, allowing for salvage of the eye. In this child with secondary glaucoma and buphthalmos from retinoblastoma, CRD provided complete tumor control and globe salvage.

  12. Subtenon Carboplatin in the Management of Intraocular Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Reza Karkhaneh

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the efficacy of adjuvant subtenon carboplatin in the management of intraocular retinoblastoma. METHODS: This study was conducted as a randomized, double-masked clinical trial. A diagnosis of intraocular retinoblastoma was made based on clinical examination, ultrasonography and orbital CT-scanning. The greatest basal dimension of the tumors was estimated in disc diameter (DD by indirect ophthalmoscopy. Tumor thickness was determined by ultrasonography. Each eye was assigned to one of 10 blocks based on tumor stage (Reese-Ellsworth classification and randomly received systemic chemotherapy alone (control group or systemic chemotherapy plus 20mg subtenon carboplatin (case group. Indirect laser photocoagulation or cryotherapy was performed as additional treatment. RESULTS: The study included 35 tumors in 17 eyes of 14 patients (19 tumors in 8 eyes in the control group and 16 tumors in 9 eyes in the case group. There was 57.22% and 61.73% decrease in tumor thickness in the control and case groups, respectively. This difference was not statistically significant (P=0.12. The decrease in greatest basal tumor dimension in the control group (47.32% was not significantly different from that in the case group (38.80%. One eye (12.5% in the control group and 3 eyes (33.3% in the case group were enucleated. CONCLUSION

  13. 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

  14. Management of Neuroblastoma: ICMR Consensus Document.

    Science.gov (United States)

    Bansal, Deepak; Totadri, Sidharth; Chinnaswamy, Girish; Agarwala, Sandeep; Vora, Tushar; Arora, Brijesh; Prasad, Maya; Kapoor, Gauri; Radhakrishnan, Venkatraman; Laskar, Siddharth; Kaur, Tanvir; Rath, G K; Bakhshi, Sameer

    2017-06-01

    Neuroblastoma (NBL) is the most common extra-cranial solid tumor in childhood. High-risk NBL is considered challenging and has one of the least favourable outcomes amongst pediatric cancers. Primary tumor can arise anywhere along the sympathetic chain. Advanced disease at presentation is common. Diagnosis is established by tumor biopsy and elevated urinary catecholamines. Staging is performed using bone marrow and mIBG scan (FDG-PET/bone scan if mIBG unavailable or non-avid). Age, stage, histopathological grading, MYCN amplification and 11q aberration are important prognostic factors utilized in risk stratification. Low-risk disease including Stage 1 and asymptomatic Stage 2 disease has an excellent prognosis with non-mutilating surgery alone. Perinatal adrenal neuroblastoma may be managed with close observation alone. Intermediate-risk disease consisting largely of unresectable/symptomatic Stage 2/3 disease and infants with Stage 4 disease has good outcome with few cycles of chemotherapy followed by surgical resection. Paraspinal neuroblastomas with cord compression are treated emergently, typically with upfront chemotherapy. Asymptomatic Stage 4S disease may be followed closely without treatment. Organ dysfunction and age below 3 mo would warrant chemotherapy in 4S. High-risk disease includes older children with Stage 4 disease and MYCN amplified tumors. High-risk disease has a suboptimal outcome, though the survival is improving with multimodality therapy including autologous stem cell transplant and immunotherapy. Relapse after multimodality therapy is difficult to salvage. Late presentation, lack of transplant facility, malnutrition and treatment abandonment are additional hurdles for survival in India. The review provides a consensus document on management of NBL for developing countries, including India.

  15. Primary pediatric gastrointestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2011-01-01

    Full Text Available Background: Primary non-Hodgkin′s lymphoma (NHL of the gastrointestinal (GI tract is the most common extranodal lymphoma in pediatric age group. Yet, the overall incidence is very low. The rarity of the disease as well as variable clinical presentation prevents early detection when the possibility of cure exists. Materials and Methods: We studied six cases of primary GI NHL in pediatric age group with reference to their clinical presentation, anatomic distribution and histopathologic characteristics. Results: All were males except one. Intestinal obstruction was the presenting feature in 50%. Half the cases showed ileocaecal involvement, while large bowel was involved in 16%. Histology showed four cases of diffuse large B-cell lymphoma (DLBCL, one case of Burkitt lymphoma, and one Burkitt-like lymphoma. Immunohistochemistry for Tdt, CD20, CD3, CD30, bcl2, bcl6 confirmed the morphological diagnosis. Conclusion: Pediatric GI lymphoma commonly involves the ileocaecal region and presents with intestinal obstruction. A higher prevalence of DLBCL is found compared to other series. A high proliferative index is useful in differentiating Burkitt-like lymphoma from DLBCL.

  16. Establishment of Retinoblastoma Model in NOD-SCID Mice and Study of Metastasis

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Yongping Li; Xiufeng Zhong; Wenge Huang; Li Nie; Wenxin Zhang

    2005-01-01

    Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis.Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneously in NOD-SCID mice. Animal acts and tumor formation, growth and metastasis in NOD-SCID mice were observed. Primary and metastatic tumors were studied pathohistologically by HE and immunohistochemical staining.Results: The latent periods of tumor growth were 12~19 days and the taken rate of tumor was 100%. 32 days later, 5 NOD-SCID mice were found with tumors that had metastasized to areas mainly located in the abdominal cavity and the side of the kidney; the metastatic time of tumors in the mice also differed. The tumor cells of the primary nodules and the metastasis were similar with human retinoblastoma cells and positive in immunohistochemical staining of NSE.Conclusion: The subcutaneous model of retinoblastoma in NOD-SCID mice showed a high taken rate and a short latent period of tumor, which had a high metastatic rate and was the best model in research of behaviors of retinoblastoma at present.

  17. A Study of Immunoactivity of Retinal S—Antigen in Retinoblastoma

    Institute of Scientific and Technical Information of China (English)

    YueSong; GuangdaYao

    1995-01-01

    Purposese:To study retinal S-antigen expression in human retinoblastoma and as-sess if there is a correlation between S-antigen immunoactivity and degree of retinoblastoma cell differentiations.Methods:Ten cases of Chinese retinoblastoma parafin-embedded tissues were ap-plied for this thudy.A strain of monoclonal antibody,MabA9C6,Which defines an epitope in S-antigen retained in fixed-tissue sections,was used to study S-antigen expression in 10 cases of retinoblastomas.S-antigen was localized by the biotina-vidin indirect immunoperoxidase technique and purified MabA9C6 ascites fluid was used with1100dilution.The whole procedure could be finished within a few hours.Results:The S-antigen immunosctivity was observed in different pattterns:the“normal”photorecepto elements incorporated in 3cases of growing tumors;3of 4Fleurettes and E-W rosettes;and scattered tumor cells in50%of the cases.Conclusions:The result suggests that the expression of S-antigen in retinoblas-toma may be used to assess the degree of tumor differentiation as anothe tumor marker in retinoblastoma.

  18. Primary leptomeningeal lymphoma

    Science.gov (United States)

    Taylor, Jennie W.; Flanagan, Eoin P.; O'Neill, Brian P.; Siegal, Tali; Omuro, Antonio; DeAngelis, Lisa; Baehring, Joachim; Nishikawa, Ryo; Pinto, Fernando; Chamberlain, Marc; Hoang-Xuan, Khe; Gonzalez-Aguilar, Alberto; Batchelor, Tracy; Blay, Jean-Yves; Korfel, Agnieszka; Betensky, Rebecca A.; Lopes, Maria-Beatriz S.

    2013-01-01

    Objective: To evaluate clinical presentation, optimal diagnostic evaluation and treatment, and outcome in primary leptomeningeal lymphoma, a rare form of primary CNS lymphoma without parenchymal or systemic involvement. Methods: The International Primary CNS Lymphoma Collaborative Group, a multidisciplinary group of physicians with a particular interest in primary CNS lymphoma, retrospectively identified cases of lymphoma isolated to the leptomeninges as diagnosed by CSF cytology, flow cytometry, or biopsy, without systemic or parenchymal brain/spinal cord lymphoma or immunodeficiency. Results: Forty-eight patients were identified, with median age at diagnosis of 51 years and median Eastern Cooperative Oncology Group performance status of 2. Presenting symptoms were multifocal in 68%. Leptomeningeal enhancement was seen in 74% and CSF profile was abnormal in all cases. CSF cytology detected malignant lymphocytes in 67%. Flow cytometry identified monoclonal population in 80%, as did receptor gene rearrangement studies in 71%. Sixty-two percent had B-cell lymphoma, 19% T-cell, and 19% unclassified. Treatment varied and included fractionated radiotherapy (36%), systemic chemotherapy (78%), and intra-CSF chemotherapy (66%), with 66% receiving ≥2 modalities. Seventy-one percent had a favorable clinical response; ultimately, 44% received salvage treatment. Median overall survival was 24 months, with 11 patients still alive at 50 months follow-up. Conclusion: Primary leptomeningeal lymphoma is a rare form of primary CNS lymphoma. Patients usually present with multifocal symptoms, with evidence of leptomeningeal enhancement and diagnostic CSF analysis. Although treatment is highly variable, patients have a better prognosis than previously reported and a subset may be cured. PMID:24107866

  19. 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).

  20. RETINOBLASTOMA RELATED1 mediates germline entry in Arabidopsis.

    Science.gov (United States)

    Zhao, Xin'Ai; Bramsiepe, Jonathan; Van Durme, Matthias; Komaki, Shinichiro; Prusicki, Maria Ada; Maruyama, Daisuke; Forner, Joachim; Medzihradszky, Anna; Wijnker, Erik; Harashima, Hirofumi; Lu, You; Schmidt, Anja; Guthörl, Daniela; Logroño, Rosa Sahún; Guan, Yonsheng; Pochon, Gaetan; Grossniklaus, Ueli; Laux, Thomas; Higashiyama, Tetsuya; Lohmann, Jan U; Nowack, Moritz K; Schnittger, Arp

    2017-04-28

    To produce seeds, flowering plants need to specify somatic cells to undergo meiosis. Here, we reveal a regulatory cascade that controls the entry into meiosis starting with a group of redundantly acting cyclin-dependent kinase (CDK) inhibitors of the KIP-RELATED PROTEIN (KRP) class. KRPs function by restricting CDKA;1-dependent inactivation of the Arabidopsis Retinoblastoma homolog RBR1. In rbr1 and krp triple mutants, designated meiocytes undergo several mitotic divisions, resulting in the formation of supernumerary meiocytes that give rise to multiple reproductive units per future seed. One function of RBR1 is the direct repression of the stem cell factor WUSCHEL (WUS), which ectopically accumulates in meiocytes of triple krp and rbr1 mutants. Depleting WUS in rbr1 mutants restored the formation of only a single meiocyte. Copyright © 2017, American Association for the Advancement of Science.

  1. Genetic perspective of retinoblastoma: From present to future

    Directory of Open Access Journals (Sweden)

    Madhavan Jagadeesan

    2016-01-01

    Full Text Available Retinoblastoma (RB is the most common malignant intraocular tumor in children. In the last decade, basic research has led to a better understanding of events after two hits in RB susceptibility gene (RB1, molecular mechanism of tumor growth, the cell of origin of RB, etc. This would pave way to identify biomarkers and molecular targeted therapy for better treatment option in the future. Furthermore, improvement in molecular techniques has led to enhanced diagnostic methods for early diagnosis, genetic counseling, and prevention of the disease. This review will help to understand the essence of basic research work conducted in recent times and its implication in the management of RB in the future.

  2. Unusually very late-onset new growth of intraocular retinoblastoma: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yeshigeta Gelaw

    2017-04-01

    Conclusions and importance: Despite initial satisfactory treatment and complete regression of the tumor, very late-onset new growth of intraocular retinoblastoma can occur. Hence, life-long follow-up in all patients with retinoblastoma is warranted, given the risk for new tumor formation even later in life. To our knowledge, this is the first report of new growth of intraocular retinoblastoma after regression for more than a decade.

  3. Radiotherapy for Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Lena [Rigshospitalet Copenhagen Univ. (Denmark). Depts. of Oncology and Haematology; Yahalom, Joachim (eds.) [Memorial Sloan-Kettering Cancer, New York, NY (United States). Dept. of Radiation Oncology

    2011-07-01

    This book deals in detail with all aspects of the best practice in modern radiotherapy for Hodgkin lymphoma. It provides the background and rationale for the inclusion of radiotherapy in today's combined-modality approach, including special clinical situations such as Hodgkin lymphoma in children, in the pregnant patient, and in the elderly. Radiotherapy planning using state-of-the-art imaging, target definition, planning software, and treatment equipment is expounded in detail. Acute and long-term side effects of radiotherapy are analyzed, and the implications for modern radiotherapy approaches in Hodgkin lymphomas are explained. (orig.)

  4. 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.

  5. Treatment of retinoblastoma: current status and future perspectives.

    Science.gov (United States)

    Rodriguez-Galindo, Carlos; Chantada, Guillermo L; Haik, Barrett G; Wilson, Matthew W

    2007-07-01

    Treatment of retinoblastoma must be individualized. Most patients with unilateral, non-metastatic retinoblastoma can be cured with enucleation alone. In patients with histologic risk factors, adjuvant chemotherapy is recommended, with the addition of orbital radiation for patients with trans-scleral involvement or tumor present at the level of the cut end of the optic nerve. Patients with metastases require intensive chemotherapy and consolidation with autologous hematopoietic stem cell rescue. Patients with bilateral or multifocal disease represent a major challenge. Cure of the disease is the first priority, but the therapeutic approach also has to consider eye and vision preservation. The approach is conservative, and only eyes with very advanced disease are enucleated upfront. Patients are treated with chemotherapy and intensive focal treatments, with the aim of delaying or avoiding radiation therapy and enucleation. For patients with early intraocular stage (Reese-Ellsworth groups I-III and International Groups A-B), the two-drug combination of vincristine and carboplatin is recommended. Patients with more advanced intraocular disease (Reese-Ellsworth groups IV-V and International Groups C-D) require more intensive chemotherapy. Standard of care for these patients incorporates etoposide into the regimen. Effective agents with good intraocular penetration, such as topotecan, are being investigated. Because most failures are secondary to progression of the vitreous seeds, subconjunctival carboplatin is added in cases with poor response of the vitreous tumors. Patients must be monitored very closely, with examinations under anesthesia every 4 to 6 weeks, and focal treatments are applied during the procedure. These include cryotherapy for small anterior tumors, thermotherapy and laser photocoagulation for small posterior tumors, and brachytherapy for larger tumors. New treatment approaches under development include the refinement of periocular chemotherapy

  6. A multicentre report from the Mexican Retinoblastoma Group

    Science.gov (United States)

    Leal-Leal, C; Flores-Rojo, M; Medina-Sansón, A; Cerecedo-Díaz, F; Sánchez-Félix, S; González-Ramella, O; Pérez-Pérez, F; Gómez-Martínez, R; Quero-Hernández, A; Altamirano-Álvarez, E; Alejo-González, F; Figueroa-Carbajal, J; Ellis-Irigoyen, A; Tejocote-Romero, I; Cervantes-Paz, R; Pantoja-Guillén, F; Vega-Vega, L; Carrete-Ramírez, F

    2004-01-01

    Background: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico. Methods: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained. Results: The authors analysed 500 cases; age range was 0–182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude’s staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up. Conclusions: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB. PMID:15258028

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

    OpenAIRE

    Laura Schwartz

    2005-01-01

    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 transmi...

  8. Treatment Options for Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  9. General Information about AIDS-Related Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  10. General Information about Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  11. Treatment Options for AIDS-Related Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  12. Treatment Option Overview (Childhood Hodgkin Lymphoma)

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  13. Treatment Option Overview (Adult Hodgkin Lymphoma)

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  14. Stages of Childhood Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  15. Treatment Options for Hodgkin Lymphoma during Pregnancy

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  16. Non-Hodgkin Lymphoma (For Parents)

    Science.gov (United States)

    ... Kids to Be Smart About Social Media Non-Hodgkin Lymphoma KidsHealth > For Parents > Non-Hodgkin Lymphoma Print ... harmful things out of the body. About Non-Hodgkin Lymphoma No n-Hodgkin lymphoma is a disease ...

  17. Lymphoma Research Foundation

    Science.gov (United States)

    ... the stem cell transplantation process. Read More LYMPHOMA RESEARCH Featured Researcher – David Scott, MBChB, PhD Dr. Scott ... and Advocacy News Action Center Advocacy Tool Kit Research LRF Research Portfolio Disease-Specific Focus Areas Grants ...

  18. General Information about Adult Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  19. Treatment Option Overview (Adult Non-Hodgkin Lymphoma)

    Science.gov (United States)

    ... Lymphoma Treatment AIDS-Related Lymphoma Treatment Chronic Lymphocytic Leukemia Treatment (small lymphocytic lymphoma) Mycosis Fungoides (Including Sézary Syndrome) Treatment (cutaneous T-cell lymphoma) Primary CNS Lymphoma Treatment Non-Hodgkin lymphoma ...

  20. Inhibition of Mahkota Dewa (Phaleria macrocarpa bioactive fraction on proliferation of human retinoblastoma tumor cells Y-79 through suppression of mRNA level of cyclin E

    Directory of Open Access Journals (Sweden)

    Nugroho Trilaksana

    2017-04-01

    Conclusions: Our results suggest that DLBS1425 is a potential anticancer agent which targets genes involved in cell proliferation in human retinoblastoma cells which make it pharmacologically ideal for the prevention and/or treatment of retinoblastoma cancer.

  1. Intrarenal neuroblastoma mimics Wilms' tumor; Neuroblastoma intrarenal mimetizando tumor de Wilms

    Energy Technology Data Exchange (ETDEWEB)

    Muniz, Maria T. Cartaxo; Soares, Andrezza B.; Freitas, Elizabete M. [Pernambuco Univ., Recife, PE (Brazil). Hospital Universitario Oswaldo Cruz. Inst. de Ciencias Biologicas]. E-mail: tcartaxo@icb.upe.br; Araujo, Marcela [Centro Infantil Boldrini, Campinas, SP (Brazil). Lab. de Biologia Molecular; Pureza, Leda M.M.; Morais, Adriana; Antunes, Consuelo; Salles, Terezinha de J. Marques; Borges, Josenilda C.; Morais, Vera L.L. de [Pernambuco Univ., Recife, PE (Brazil). Hospital Universitario Oswaldo Cruz; Romualdo Filho, Jose [Pernambuco Univ., Recife, PE (Brazil). Hospital Universitario Oswaldo Cruz. Centro Integrado de Anatomia Patologica; Magalhaes, Mario H. [Instituto Nacional de Cancer, Rio de Janeiro, RJ (Brazil). Dept. de Patologia

    2005-07-01

    This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor. The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the meso gastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcely of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparotomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified metastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographically resembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical and molecular analysis in the diagnosis of intrarenal neuroblastoma. (author)

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

    Directory of Open Access Journals (Sweden)

    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

  3. Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

    Directory of Open Access Journals (Sweden)

    A. M. Stroganova

    2016-01-01

    Full Text Available Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site, some histological, molecular biochemical (ploidy and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc. characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes and intrachromosomal (homogenically painted regions. Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the

  4. Immune response to racotumomab in a child with relapsed neuroblastoma

    Directory of Open Access Journals (Sweden)

    CLAUDIA VANESA SAMPOR

    2012-12-01

    Full Text Available Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside.

  5. Eicosanoids in cancer: new therapeutic targets in neuroblastoma

    OpenAIRE

    Rasmuson, Agnes

    2012-01-01

    Cancer is one of the most common causes of death for both children and adults in developed countries. Neuroblastoma is a cancer of the sympathetic nervous system that affects infants and young children. Neuroblastoma tumors are the most common solid extracranial tumors in children and are also the most deadly. About half of the patients diagnosed are classified as high-risk, and despite an intensive multimodal treatment, the survival rate for these patients is only 55%. The overall survival f...

  6. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Hodgkin Lymphoma This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Hodgkin Lymphoma Adcetris (Brentuximab Vedotin) Ambochlorin (Chlorambucil) Amboclorin (Chlorambucil) ...

  7. Mesenchymal change and drug resistance in neuroblastoma.

    Science.gov (United States)

    Naiditch, Jessica A; Jie, Chunfa; Lautz, Timothy B; Yu, Songtao; Clark, Sandra; Voronov, Dimitry; Chu, Fei; Madonna, Mary Beth

    2015-01-01

    Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P change via multiple pathways in the transition to a drug-resistant state. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Radiologic findings of olfactory neuroblastoma (Esthesioblastoma

    Directory of Open Access Journals (Sweden)

    Alpaslan Yavuz

    2013-12-01

    Full Text Available Olfactory neuroblastoma (ONB also known as esthesioblastoma is a rare malignant neoplasm originating from olfactive epitelium, usually locate in the olfactory region of the nasal cavity and anterior skull base. Few cases have been published in the literature yet. Detailed radiologic and histopathological examination is necessary for diagnosis and staging ONB. Prognosis is favorable especially for locally advanced tumors; regional and distant metastasis has been accepted as indicators of poor prognosis. Surgery and radiotherapy are the main therapeutic modalities in use today. We reported the x-ray graphic, B Mod-Doppler Ultrasound (US and Computed Tomography (CT findings of 64 years-old male with ONB in this presentation. J Clin Exp Invest 2013; 4 (4: 532-534

  9. Blasting neuroblastoma using optimal control of chemotherapy.

    Science.gov (United States)

    Collins, Craig; Fister, K Renee; Key, Bethany; Williams, Mary

    2009-07-01

    A mathematical model is used to investigate the effectiveness of the chemotherapy drug Topotecan against neuroblastoma. Optimal control theory is applied to minimize the tumor volume and the amount of drug utilized. The model incorporates a state constraint that requires the level of circulating neutrophils (white blood cells that form an integral part of the immune system) to remain above an acceptable value. The treatment schedule is designed to simultaneously satisfy this constraint and achieve the best results in fighting the tumor. Existence and uniqueness of the solution of the optimality system, which is the state system coupled with the adjoint system, is established. Numerical simulations are given to demonstrate the behavior of the tumor and the immune system components represented in the model.

  10. Crystal Structure of Human Retinoblastoma Binding Protein 9

    Energy Technology Data Exchange (ETDEWEB)

    Vorobiev, S.; Su, M; Seetharaman, J; Huang, Y; Chen, C; Maglaqui, M; Janjua, H; Montelione, G; Tong, L; et. al.

    2009-01-01

    As a step towards better integrating protein three-dimensional (3D) structural information in cancer systems biology, the Northeast Structural Genomics Consortium (NESG) (www.nesg.org) has constructed a Human Cancer Pathway Protein Interaction Network (HCPIN) by analysis of several classical cancer-associated signaling pathways and their physical protein-protein interactions. Many well-known cancer-associated proteins play central roles as hubs or bottlenecks in the HCPIN (http://nmr.cabm.rutgers.edu/hcpin). NESG has selected more than 1000 human proteins and protein domains from the HCPIN for sample production and 3D structure determination. The long-range goal of this effort is to provide a comprehensive 3D structure-function database for human cancer-associated proteins and protein complexes, in the context of their interaction networks. Human retinoblastoma binding protein 9 (RBBP9) is one of the HCPIN proteins targeted by NESG. RBBP9 was initially identified as the product of a new gene, Bog (for B5T over-expressed gene), in several transformed rat liver epithelial cell lines resistant to the growth-inhibitory effect of TGF-1 as well as in primary human liver tumors. RBBP9 contains the retinoblastoma (Rb) binding motif LxCxE in its sequence, and was shown to interact with Rb by yeast two-hybrid and coimmunoprecipitation experiments. Mutation of the Leu residue in this motif to Gln blocked the binding to Rb. RBBP9 can displace E2F1 from E2F1-Rb complexes, and over expression of RBBP9 overcomes TGF-1 induced growth arrest and results in transformation of rat liver epithelial cells leading to hepatoblastoma-like tumors in nude mice. RBBP9 may also play a role in cellular responses to chronic low dose radiation. A close homolog of RBBP9, sharing 93% amino acid sequence identity and also known as RBBP10, interacts with a protein with sua5-yciO-yrdC domains.

  11. Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model.

    Science.gov (United States)

    Li, Zhanrong; Wu, Xianghua; Li, Jingguo; Yao, Lin; Sun, Limei; Shi, Yingying; Zhang, Wenxin; Lin, Jianxian; Liang, Dan; Li, Yongping

    2012-01-01

    Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on retinoblastoma and to investigate the potential mechanisms involved. Celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4- nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma. CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC(50) of 17.733 μg/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65 proteins decreased after exposure to CNPs 54.4 μg/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice. CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be

  12. Intravascular large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Ricardo García-Muñoz

    2014-01-01

    Full Text Available Intravascular large B cell lymphoma (IVBCL is a rare type of extranodal large B cell lymphoma characterized by selective growth of lymphoma cells within the microvasculature. We present an illustrative case of intravascular B cell lymphoma suspected by the presence of a very small monoclonal B cell population identified by immunophenotype and polymerase chain reaction in bone marrow. The diagnosis was confirmed by skin biopsy.

  13. 506U78 in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or T-cell Lymphoma

    Science.gov (United States)

    2013-01-22

    Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  14. Characteristics of an Established Retinoblastoma Cell Line HXO—Rb44

    Institute of Scientific and Technical Information of China (English)

    HepingXu; HechengZhu

    1995-01-01

    Purpose:To study the retinoblastoma cell culture and to establish a new retinoblastoma cellline.Methods:22 retinoblastomes were cultured by using the method of single cellsus-pension.Characteristics of the cultured cells were studied in the following pro-grams:tumor cell morphology in vitro,electron microscopic,growth curve,cloning in soft agar,immunohistochemistry,karyotype and tumorigenicity.Results.22 retinoblastoas were cultured successfully in ivtro,only a cotinued cell line HXO-Rb44was established(more than3years).The characteristics of this cell line are that it grew as a suspension of round cell in graps like clusters in vitro,its population doubling time was 44hours,and it could be cloned in softa-gar.Histopathologic and ulatastructured pictures showed the characteristics of Rb.HXO-Rb44cell was positive to NSE and negative to GFAP in immunohis-tochemical staining.A subcutaneous injection of HXO-Rb44cells produced a retinoblastoma in BALB/C athumic nude mice.Conclusions:HXO-Rb44 has the characteristice of retinoblastoma and is a new retinoblastoma cell line.It is a useflu material for study this tumor both in basic and clinical fields.

  15. Treating retinoblastoma in the first year of life in a national tertiary paediatric hospital in Mexico.

    Science.gov (United States)

    Asencio-López, Laura; Torres-Ojeda, Alan A; Isaac-Otero, Gabriela; Leal-Leal, Carlos A

    2015-09-01

    Retinoblastoma is the most common primary ocular malignancy in childhood, but little has been documented on the clinical and biological differences in children diagnosed before one year of age. We observed patients in this age group and followed them for up to 19 years. This retrospective, descriptive, observational study reviewed the medical records of Mexican patients, who were diagnosed with retinoblastoma before one year of age at a national paediatric hospital from 1995 to 2014. The variables analysed were age at diagnosis, weight, presenting signs, the time from first symptoms to diagnosis, family history, laterality, ocular rescue and survival rate. The 108 patients had a mean age of 7.65 months and 15.7% had a family history of retinoblastoma. The majority (55.5%) had bilateral retinoblastoma, the most common presenting sign was leukocoria (86.1%), and the most common stage of diagnosis was Group V (84.1%). More than half were underweight for their age. The overall survival rate was 92% and the disease-free survival rate was 84%. Retinoblastoma is a malignancy that can be present at birth, especially if it is a bilateral hereditary form of the disease. Leukocoria was the main presenting sign. Early diagnosis dramatically improved the prognosis for ocular rescue. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  16. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines.

    Science.gov (United States)

    Große-Kreul, Jan; Busch, Maike; Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole

    2016-01-01

    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma.

  17. Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines

    Science.gov (United States)

    Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole

    2016-01-01

    Trefoil factor family (TFF) peptides have been shown to effect cell proliferation, apoptosis, migration and invasion of normal cells and various cancer cell lines. In the literature TFF peptides are controversially discussed as tumor suppressors and potential tumor progression factors. In the study presented, we investigated the effect of TFF3 overexpression on growth, viability, migration and tumorigenicity of the human retinoblastoma cell lines Y-79, WERI-Rb1, RBL-13 and RBL-15. As revealed by WST-1 and TUNEL assays as well as DAPI and BrdU cell counts, recombinant human TFF3 significantly lowers retinoblastoma cell viability and increases apoptosis levels. Transient TFF3 overexpression likewise significantly increases RB cell apoptosis. Stable, lentiviral TFF3 overexpression lowers retinoblastoma cell viability, proliferation and growth and significantly increases cell death in retinoblastoma cells. Blockage experiments using a broad-spectrum caspase inhibitor and capase-3 immunocytochemistry revealed the involvement of caspases in general and of caspase-3 in particular in TFF3 induced apoptosis in retinoblastoma cell lines. Soft agarose and in ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF3 overexpression influences anchorage independent growth and significantly decreases the size of tumors forming from retinoblastoma cells. Our study demonstrates that forced TFF3 expression exerts a significant pro-apoptotic, anti-proliferative, and tumor suppressive effect in retinoblastoma cells, setting a starting point for new additive chemotherapeutic approaches in the treatment of retinoblastoma. PMID:27626280

  18. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma.

    Science.gov (United States)

    Spel, Lotte; Boelens, Jaap-Jan; van der Steen, Dirk M; Blokland, Nina J G; van Noesel, Max M; Molenaar, Jan J; Heemskerk, Mirjam H M; Boes, Marianne; Nierkens, Stefan

    2015-11-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20-40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neuroblastoma treatment, these immune escape mechanisms restrain clinical results. Therefore, we aimed to improve neuroblastoma immunogenicity to further the development of antigen-specific immunotherapy against neuroblastoma. We found that neuroblastoma cells significantly increase surface expression of MHC I upon exposure to active NK cells which thereby readily sensitize neuroblastoma cells for recognition by CTLs. We show that oncoprotein PRAME serves as an immunodominant antigen for neuroblastoma as NK-modulated neuroblastoma cells are recognized by PRAMESLLQHLIGL/A2-specific CTL clones. Furthermore, NK cells induce MHC I upregulation in neuroblastoma through contact-dependent secretion of IFNγ. Our results demonstrate remarkable plasticity in the peptide/MHC I surface expression of neuroblastoma cells, which is reversed when neuroblastoma cells experience innate immune attack by sensitized NK cells. These findings support the exploration of NK cells as adjuvant therapy to enforce neuroblastoma-specific CTL responses.

  19. 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.

  20. Regulation of the retinoblastoma proteins by the human herpesviruses

    Directory of Open Access Journals (Sweden)

    Kalejta Robert F

    2009-01-01

    Full Text Available Abstract Viruses are obligate intracellular parasites that alter the environment of infected cells in order to replicate more efficiently. One way viruses achieve this is by modulating cell cycle progression. The main regulators of progression out of G0, through G1, and into S phase are the members of the retinoblastoma (Rb family of tumor suppressors. Rb proteins repress the transcription of genes controlled by the E2F transcription factors. Because the expression of E2F-responsive genes is required for cell cycle progression into the S phase, Rb arrests the cell cycle in G0/G1. A number of viral proteins directly target Rb family members for inactivation, presumably to create an environment more hospitable for viral replication. Such viral proteins include the extensively studied oncoproteins E7 (from human papillomavirus, E1A (from adenovirus, and the large T (tumor antigen (from simian virus 40. Elucidating how these three viral proteins target and inactivate Rb has proven to be an invaluable approach to augment our understanding of both normal cell cycle progression and carcinogenesis. In addition to these proteins, a number of other virally-encoded inactivators of the Rb family have subsequently been identified including a surprising number encoded by human herpesviruses. Here we review how the human herpesviruses modulate Rb function during infection, introduce the individual viral proteins that directly or indirectly target Rb, and speculate about what roles Rb modulation by these proteins may play in viral replication, pathogenesis, and oncogenesis.

  1. 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).

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2017-10-09

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  4. Mutations in PIK3CA are infrequent in neuroblastoma

    Directory of Open Access Journals (Sweden)

    Mazanek Pavel

    2006-07-01

    Full Text Available Abstract Background Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. Methods Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain "hot spots" where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. Results We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%. Neither mutation (R524M and E982D has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively. Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model

  5. Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; Josefsson, Pär; Jørgensen, Judit;

    2016-01-01

    AIM OF DATABASE: The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. STUDY POPULATION: The LYFO database was established in 1982 as a seminational database including...... all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. MAIN VARIABLES: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each...... patient: a primary registration form, a treatment form, a relapse form, and a follow-up form. Variables are used to calculate six result quality indicators (mortality 30 and 180 days after diagnosis, response to first-line treatment, and survival estimates 1, 3, and 5 years after the time of diagnosis...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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 differentiation of white and brown fat cells is controlled by a similar set of transcription factors, including PPARgamma and C/EBPalpha. However, despite many similarities between the two types of fat cells, they carry out essentially opposite functions in vivo, with white adipocytes being...... 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...

  8. 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

    of patients diagnosed before DNA testing was offered. Knowledge of heredity increases the chance of early diagnosis in offspring, leading to improved prognosis. We present data from the Danish retinoblastoma patients that emphasize the need for genetic counseling and RB1 screening in all untested......, 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......-year period. A cohort of 181 retinoblastoma survivors with sporadic disease (15% heritable) did not receive genetic testing. Since the introduction of routine testing, one of 14 sporadic unilateral patients tested (7%) has been identified with a germline mutation. Before routine testing, five additional...

  9. Ophthalmic lymphoma: epidemiology and pathogenesis.

    Science.gov (United States)

    Sjö, Lene Dissing

    2009-02-01

    With a lifetime risk of 1% and 700 new cases per year, Non-Hodgkin lymphoma (NHL) is the seventh most frequent type of cancer in Denmark. The incidence of NHL has increased considerably in Western countries over the last decades; consequently, NHL is an increasing clinical problem. Ophthalmic lymphoma, (lymphoma localized in the ocular region, i.e. eyelid, conjunctiva, lacrimal sac, lacrimal gland, orbit, or intraocularly) is relatively uncommon, accounting for 5%-10% of all extranodal lymphomas. It is, however, the most common orbital malignancy. The purpose of this thesis was to review specimens from all Danish patients with a diagnosis of ophthalmic lymphoma during the period 1980-2005, in order to determine the distribution of lymphoma subtypes, and the incidence- and time trends in incidence for ophthalmic lymphoma. Furthermore, an extended analysis of the most frequent subtype, extranodal marginal zone lymphoma (MALT lymphoma), was done to analyse clinical factors and cytogenetic changes with influence on prognosis. A total of 228 Danish patients with a biopsy-reviewed verified diagnosis of ocular adnexal-, orbital-, or intraocular lymphoma were identified. We found that more than 50% of orbital- and ocular adnexal lymphomas were of the MALT lymphoma subtype, whereas diffuse large B-cell lymphoma (DLBCL) predominated intraocularly (Sjo et al. 2008a). Furthermore, lymphoma arising in the lacrimal sac was surprisingly predominantly DLBCL (Sjo et al. 2006). Incidence rates were highly dependent on patient age. There was an increase in incidence rates for the whole population from 1980 to 2005, corresponding to an annual average increase of 3.4% (Sjo et al. 2008a). MALT lymphoma arising in the ocular region was found in 116 patients (Sjo et al. 2008b). One third of patients had a relapse or progression of disease after initial therapy and relapses were frequently found at extra-ocular sites. Overall survival, however, was not significantly poorer for patients

  10. Lymphoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Juanita Parnis

    2012-01-01

    Full Text Available Primary non-Hodgkins lymphoma of the uterine cervix is a very rare diagnosis. A 54-year-old woman presented with a 3-month history of postmenopausal bleeding per vaginum. On examination, a friable, fungating lesion was seen on the cervix. Histology revealed a CD 20 positive high-grade non-Hodgkin’s diffuse large B cell lymphoma from cervical biopsies and endometrial curettage. She was diagnosed as stage IE after workup and subsequently treated with six cycles of R-CHOP chemotherapy followed by radiotherapy of the involved field.

  11. Primary Pancreatic Lymphomas

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2006-05-01

    Full Text Available Extranodal non-Hodgkin’s lymphomas (NHLs represent up to 30-40% of all NHL cases. The gastrointestinal tract is the most commonly involved extranodal site; accounting for about half of such cases [1]. Stomach and the small intestine constitute the most common gastrointestinal sites. Secondary invasion of the pancreas from contiguous, retroperitoneal lymph node disease is the prevalent mode of involvement. Secondary involvement of the pancreas from the duodenum or adjacent peripancreatic lymphadenopathy is well-known. Primary pancreatic lymphoma (PPL is an extremely rare disease [2]. PPL can present as an isolated mass mimicking pancreatic carcinoma. However, unlike carcinomas, PPL are potentially treatable [3].

  12. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

  13. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

  14. Integrative analysis of neuroblastoma and pheochromocytoma genomics data

    Directory of Open Access Journals (Sweden)

    Szabó Peter M

    2012-10-01

    Full Text Available Abstract Background Pheochromocytoma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. We have performed a large-scale in silico analysis of altogether 1784 neuroblastoma and 531 pheochromocytoma samples to establish similarities and differences using analysis of mRNA and microRNA expression, chromosome aberrations and a novel bioinformatics analysis based on cooperative game theory. Methods Datasets obtained from Gene Expression Omnibus and ArrayExpress have been subjected to a complex bioinformatics analysis using GeneSpring, Gene Set Enrichment Analysis, Ingenuity Pathway Analysis and own software. Results Comparison of neuroblastoma and pheochromocytoma with other tumors revealed the overexpression of genes involved in development of noradrenergic cells. Among these, the significance of paired-like homeobox 2b in pheochromocytoma has not been reported previously. The analysis of similar expression patterns in neuroblastoma and pheochromocytoma revealed the same anti-apoptotic strategies in these tumors. Cancer regulation by stathmin turned out to be the major difference between pheochromocytoma and neuroblastoma. Underexpression of genes involved in neuronal cell-cell interactions was observed in unfavorable neuroblastoma. By the comparison of hypoxia- and Ras-associated pheochromocytoma, we have found that enhanced insulin like growth factor 1 signaling may be responsible for the activation of Src homology 2 domain containing transforming protein 1, the main co-factor of RET. Hypoxia induced factor 1α and vascular endothelial growth factor signaling included the most prominent gene expression changes between von Hippel-Lindau- and multiple endocrine neoplasia type 2A-associated pheochromocytoma. Conclusions These pathways include previously undescribed pathomechanisms of neuroblastoma and pheochromocytoma and associated gene products may serve as diagnostic markers and therapeutic

  15. Correlation between the International Neuroblastoma Pathology Classification and genomic signature in neuroblastoma.

    Science.gov (United States)

    Nakazawa, Atsuko; Haga, Chizuko; Ohira, Miki; Okita, Hajime; Kamijo, Takehiko; Nakagawara, Akira

    2015-06-01

    The International Neuroblastoma Pathology Classification (INPC) has a prognostic impact that distinguishes two categories of neuroblastoma: favorable histology (FH) and unfavorable histology (UH). We analyzed 92 cases of neuroblastoma with the INPC evaluation and genomic grouping to investigate the correlation between the INPC and genomic signature, together with their prognostic significance. The correlation of UH tumor and partial gains and/or losses (GGP), as well as the correlation of FH tumor and whole gains and/or losses (GGW), was statistically significant. Both UH and GGP were late-onset (median age at diagnosis was 36 and 48 months, respectively) and had poor prognosis (overall survival rate [OS], 43.1% and 42.4%, respectively). In contrast, both FH and GGW were early-onset (median age at diagnosis, 4 and 9.5 months, respectively) and had favorable prognosis (OS, 88.6% and 87.1%, respectively). Unfavorable histology and GGP had significantly inferior OS compared to FH and GGW. Overall survival was not significantly different among the genomic groups in FH; however, it was inferior in UH with GGP. In UH with a single copy MYCN, genomic subgroups GGP2s (both 1p and 11q losses) and GGP3s (partial 11q loss but not 1p loss) indicated significantly poor prognosis compared to GGP4s (no partial 1p and 11q loss). As INPC and MYCN amplification were found to be the most powerful prognostic biological factors, they should be included with genomic grouping as treatment stratification for patients with UH and single copy of MYCN.

  16. APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway

    Science.gov (United States)

    Ramanujan, Ajeena; Tiwari, Swati

    2016-01-01

    The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti-cancer and anti-viral drugs. PMID:27402801

  17. 神经母细胞瘤中间变性淋巴瘤激酶基因改变%Genetic aberration of ALK in neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    殷敏智; 陈洁枫; 沈萍; 马靖; 张忠德

    2014-01-01

    目的:观察国内儿童散发性神经母细胞瘤( neuroblastoma, NB)中间变性淋巴瘤激酶( anaplastic lymphoma kinase, ALK)的表达,探讨其在NB发生、发展中的作用。方法应用荧光原位杂交法( fluorescence in situ hybridization, FISH)检测56例ALK蛋白异常表达的NB中ALK基因的表达。结果 FISH检测显示56例NB中ALK基因46例为正常,10例为异常,其中9例为ALK增多(16%),1例为扩增(1.8%)。结论 ALK基因是NB一个主要的易感基因,国内儿童ALK基因异常的发生率与国外文献报道相近,其有可能成为治疗NB的主要靶点之一。%Purpose To investigate the genetic changes of ALK gene in sporadic neuroblastoma in China, and to explore its role in neuroblastoma. Methods Total 56 cases of NB with overexpressed ALK protein were studied by fluorescence in situ hybridization ( FISH) , using interphase Vysis LSI ALK dual-color and break apart rearrangement probes. Literature under the subject was searched through PubMed. Results Of the 56 cases, ALK gain was found in 9 (16%) cases, ALK amplification was found in 1 (1. 8%) case only. No alterations of ALK were detected in the remaining 46 cases. Conclusion As a major predisposition gene as well as a poten-tial therapeutic target for neuroblastoma, the frequency of aberrant copy numbers of ALK gene in Chinese NB patients is closely similar with previously published results.

  18. Terapia fotodinâmica combinada com oxigenoterapia: uma abordagem no retinoblastoma?

    OpenAIRE

    Neves, Ana Rita Marques

    2016-01-01

    O retinoblastoma é o tumor intraocular maligno mais comum nas crianças e apresenta uma incidência de 1 em cada 15 000 a 20 000 nascimentos. A terapia fotodinâmica (PDT) é um tratamento promissor no que diz respeito ao retinoblastoma e apresenta-se como uma abordagem terapêutica emergente no tratamento de outras neoplasias malignas, podendo induzir morte celular através de um mecanismo que envolve o stresse oxidativo, depois da ativação luminosa das moléculas fotossensibilizadoras. A oxigenote...

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

    Directory of Open Access Journals (Sweden)

    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. Meningioma 40 years after radiation therapy for retinoblastoma: genetic and phenotypic analysis, and minireview of literature.

    Science.gov (United States)

    Balik, V; Sarissky, M; Lohmann, D; Sulla, I

    2008-11-01

    The authors present a case of 44-year-old Caucasian female diagnosed with meningothelial meningioma 40 years after radiotherapy for sporadic unilateral retinoblastoma. The genetic analysis of DNA from the meningioma revealed no oncogenic mutation in the RB1 gene. The analysis of meningioma cells by flow cytometry revealed the following immunophenotype: vimentin++ CD56+ GFAP- EGFR-. Intermediate intensities of Her-2/neu and Pgp expression were detected in a small percentage of tumour cells. Data suggest that the tumour was most likely induced by radiotherapy and did not arise as a second tumour as there was no hereditary predisposition to retinoblastoma.

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

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Makoto; Tanaka, Yasuhiko; Kawai, Masataka; Nii, Seiji [Keio Univ., Tokyo (Japan). School of Medicine; Katsura, Hiroshi; Kaneko, Akihiro

    1999-08-01

    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)

  2. Microarray-based analysis: identification of hypoxia-regulated microRNAs in retinoblastoma cells.

    Science.gov (United States)

    Xu, Xiaofang; Jia, Renbing; Zhou, Yixiong; Song, Xin; Wang, Jing; Qian, Guanxiang; Ge, Shengfang; Fan, Xianqun

    2011-05-01

    Hypoxia is an essential feature of retinoblastoma and contributes to poor prognosis and resistance to conventional therapy. MicroRNAs (miRNAs) are small non-coding RNAs involved in a wide variety of biological processes, including cell differentiation, proliferation, death and metabolism. However, the relationship between hypoxia and the expression of miRNAs in retinoblastoma is not well understood. In this study, we aimed to analyze the pattern of miRNA expression in a retinoblastoma cell line under hypoxic conditions and to identify the miRNAs regulated by hypoxia, as well as their possible functions. miRNA expression profiling in retinoblastoma cells (HXO-RB44) under normal and hypoxic conditions was assessed by microarray techniques. The differentially expressed miRNAs were subjected to bioinformatic analyses to predict and categorise the key miRNAs and their target genes. A quantitative real-time RT-PCR approach was used to validate their expression. A Cell Counting kit was used to evaluate the functional significance of miR-181b in RB cell proliferation. There were 46 miRNAs that changed expression more than 2-fold in response to hypoxia (34 up-regulated and 12 down-regulated). We identified a cluster of miRNAs that includes miR-181b, miR-125a-3p, miR-30c-2, miR-497 and miR-491-3p as hypoxia-regulated miRNAs (HRMs) in retinoblastoma cells, of which miR-181b was the most typically differentially expressed miRNA under hypoxic conditions. Functionally, these HRMs are involved in apoptosis, cell adhesion, cell proliferation and mRNA processing, all processes that associate closely with the hypoxia response of cancer cells. Additionally, we found that administration of miR-181b inhibitor can suppress proliferation of retinoblastoma cells. These findings provide the first evidence that miRNAs play an important role in the hypoxia response of retinoblastoma cells. MiR-181b, the most typically up-regulated miRNA may aid in future clinical intervention of

  3. Right adrenal gland neuroblastoma infiltrating the liver and mimicking mesenchymal hamartoma: A case report

    Directory of Open Access Journals (Sweden)

    Ahmed Abo-Elenain

    2015-01-01

    Conclusion: We represent a rare case of neuroblastoma which arose from the right adrenal gland and infiltrated the adjacent liver substance mimicking mesenchymal hamartoma of the liver. Neuroblastoma is rarely presented with pyrexia of unknown origin. Neuroblastoma should be considered in differential diagnosis of abdominal mass in all infants and children.

  4. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours.

    Science.gov (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-03-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  5. N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma

    NARCIS (Netherlands)

    Bernards, R.A.

    1991-01-01

    In neuroblastoma, amplification of the N-myc gene is closely correlated with increased metastatic ability. The mechanism by which N-myc acts to increase neuroblastoma malignancy is poorly understood as yet. It is shown here that transfection of N-myc in a neuroblastoma cell line causes suppression o

  6. File list: His.Neu.20.AllAg.Neuroblastoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: ALL.Neu.05.AllAg.Neuroblastoma [Chip-atlas[Archive

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  16. File list: His.Neu.10.AllAg.Neuroblastoma [Chip-atlas[Archive

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  17. Primary Pulmonary Hodgkin Lymphoma

    OpenAIRE

    Shumaila Tanveer; Ahmed El Damati; Ayman El Baz; Ahmed Alsayyah; Tarek ElSharkawy; Mohamed Regal

    2015-01-01

    Primary pulmonary Hodgkin lymphoma (PPHL) is a rare disease. Herein, we report a case of PPHL with diagnostic concerns encountered during initial evaluation which is of paramount importance to keep the differential diagnosis in cases with high index of sus- picion for this rare entity.

  18. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  19. Lymphatic system and lymphoma

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009236 Clinical significance in detection of immunoglobulin heavy chain clonal rearrangement in bone marrow of patients with B cell lymphoma.CHEN Zhiyu(陈治宇),et al.Dept Med Oncol,Cancer Hosp,Fudan Univ;Dept Oncel,Shanghai Med Coll,Fudan Univ,Shanghai 200032,Chin J Oncol,2009;3193):183-188.

  20. Lymphatic system and lymphoma

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970385 The changes of cell immune function in ap-tients with non-Hodgkin’s lymphoma by flow cytome-try analysis. LU Ming(吕鸣), et al. Clin ImmunolCenter, Changzheng Hosp, 2nd Milit Med Univ, Shang-hai, 200003. Shanghai Med J 1997; 20(2): 73-75.

  1. Centrofacial angiocentric lymphoma.

    Science.gov (United States)

    Peral-Cagigal, Beatriz; Galdeano-Arenas, María; Crespo-Pinilla, Juan Ignacio; García-Cantera, José Miguel; Sánchez-Cuéllar, Luis Antonio; Verrier-Hernández, Alberto

    2005-01-01

    The centrofacial angiocentric lymphoma is a rare lymphoid neoplasm, with an often-difficult diagnosis due to the non-specific clinical picture. On many occasions it is necessary to perform various biopsies to reach the correct diagnosis. This lymphoma is an aggressive Non-Hodgkin's (NHL) type, which is normally found in the upper respiratory tract (predominantly in the nasal cavity), and has an ominous prognosis, as the average survival rate is between 12 and 18 months (1). It is predominantly found in subjects of oriental and South American extraction, who are between the ages of 50 and 60 years and with a slight tendency towards males (2:1). This is the case study of a female Ecuadorian patient who was referred to our department with a hemifacial edema, chocolate- like rhinorrhea and nasal respiratory obstruction, which had been treated with antibiotics and anti-inflammatories for a month without success. After performing a number of diagnostic tests, it was found histologically that the patient had an extranodal T-cell lymphoma of the nasal type (also known as T-cell angiocentric lymphoma).

  2. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    Science.gov (United States)

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations.

  3. Does I-131-MIBG underestimate skeletal disease burden in neuroblastoma?

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2004-10-01

    Full Text Available Background: Controversy persists as to the need for both MIBG and bone scanning in routine evaluation of neuroblastoma. Aim: To compare the efficacy of I-131- metaiodobenzylguanidine (MIBG scan against that of conventional Tc99m- methylene diphosphonate (MDP bone scan for the detection of skeletal deposition of neuroblastoma. Methods and Material: The study included 57 patients (36 boys, 21 girls: age range 1-14 years of neuroblastoma who underwent both bone scan with Tc99m-MDP and I-131-MIBG scan within 15 days of each other at presentation and during follow-up. Results: At presentation 11(19.2% patients had evidence of skeletal metastases on MDP scan against 7 patients who showed bony secondaries on MIBG scan. Of the 7 patients, with positive MIBG and MDP scans, MDP scan detected 11 sites whereas MIBG scan detected 7 sites. On follow-up study, 3 patients with initial abnormal MDP scan but normal MIBG scan, developed skeletal metastases detectable on MIBG scan, whereas 3 of the 46 patients who had normal MDP and MIBG scan at presentation; developed skeletal metastases detectable on MDP scan. MIBG scan was concordant in 2 of them but was normal in the third patient. Conclusion: I-131-MIBG underestimates skeletal disease burden in neuroblastoma. Therefore, Tc99m-MDP bone scan should remain a part of routine assessment of patients with neuroblastoma.

  4. Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology.

    Science.gov (United States)

    Salazar, Brittany M; Balczewski, Emily A; Ung, Choong Yong; Zhu, Shizhen

    2016-12-27

    Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring "big data" applications in pediatric oncology. Computational strategies derived from big data science-network- and machine learning-based modeling and drug repositioning-hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which "big data" and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.

  5. 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.

  6. The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians.

    Science.gov (United States)

    Zhu, Shu Jun; Pearson, Bret J

    2013-01-15

    Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are well known for their regenerative abilities, which rely on a large population of pluripotent adult stem cells. However, the mechanisms by which planarians maintain a precise population of adult stem cells while balancing proliferation and cell death, remain to be elucidated. Here we have identified, characterized, and functionally tested the core Retinoblastoma (Rb) pathway components in planarian adult stem cell biology. The Rb pathway is an ancient and conserved mechanism of proliferation control from plants to animals and is composed of three core components: an Rb protein, and a transcription factor heterodimer of E2F and DP proteins. Although the planarian genome contains all components of the Rb pathway, we found that they have undergone gene loss from the ancestral state, similar to other species in their phylum. The single Rb homolog (Smed-Rb) was highly expressed in planarian stem cells and was required for stem cell maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show that planarians and their phylum have undergone the most severe reduction in E2F genes observed thus far, and the single remaining E2F was predicted to be a repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper-proliferation. Finally, we showed that known Rb-interacting genes in other systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar to Rb in expression and phenotypes when knocked down by RNAi, suggesting that these established interactions with Rb may also be conserved in planarians. Together, these results showed that planarians use the conserved components of the Rb tumor suppressor pathway to control proliferation and cell survival.

  7. 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.

  8. 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

    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 (Pprosthesis-wearing patients often experienced mucoid discharge, and less often irritation and 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. PMID:28280296

  9. Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin Lymphoma Followed by Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Tennese, Alysa; Skrabek, Pamela J; Nasr, Michel R; Sekiguchi, Debora R; Morales, Carmen; Brown, Theresa C; Weisenburger, Dennis D; Perry, Anamarija M

    2017-05-01

    Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

  10. Cytopathogenicity of Naegleria for cultured neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Fulford, D.E.

    1985-01-01

    The cytopathic activity of live Naegleria amoebae and cell-free lysates of Naegleria for B-103 rat neuroblastoma cells was investigated using a /sup 51/Cr release assay. Live amoebae and cell-free lysates of N. fowleri, N. australiensis, N. lovaniensis, and N. gruberi all induced sufficient damage to radiolabeled B-103 cells to cause a significant release of chromium. The cytotoxic activity present in the cell-free lysates of N. fowleri can be recovered in the supernatant fluid following centrifugation at 100,000xg and precipitation of the 100,000xg supernatant fluid with ammonium sulfate. Initial characterization of the cytotoxic factor indicates that it is a heat labile, pH sensitive, soluble protein. The cytotoxic activity is abolished by either extraction, unaffected by repeated freeze-thawing, and is not sensitive to inhibitors of proteolytic enzymes. Phospholipase A activity was detected in the cytotoxic ammonium sulfate precipitable material, suggesting that this enzyme activity may have a role in the cytotoxic activity of the cell-free lysates.

  11. Refractory diarrhea: A paraneoplastic syndrome of neuroblastoma.

    Science.gov (United States)

    Han, Wei; Wang, Huan-Min

    2015-07-01

    Neuroblastoma (NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide (VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage I-II, and one was at stage III. Four patients survived (followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

  12. Management of intracranial invasive olfactory neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-wei; ZHANG Ming-shan; QI Ji; ZHANG Jun-ting; LI Gui-lin; LUO Lin; WANG Zhong-cheng

    2007-01-01

    Background Olfactory neuroblastoma (ONB) is a rare tumor that often arise from the nasal cavity. The aim of this study was to investigate the clinical characteristics and treatments of intracranial invasive ONB.Methods Between July 2001 and August 2005, 5 patients with intracranial invasive ONB were treated in our department. Their clinical features, radiological and pathological characteristics, and surgical treatments were analyzed.Among the 5 patients, 1 received transnasal biopsy, and 4 were operated through the transfrontal or extended bifrontal approaches to reconstruct the skull base. After the operation, all the patients received radiotherapy, and one received chemotherapy. They were followed up for 6 to 45 months.Results The ONB was resected totally in the 4 patients. In all the patients, nasal obstruction was alleviated without cerebrospinal fluid leakage. The visual acuity was improved in 3 patients, who had a decreased visual acuity before the operation. Two patients had metastasis into the lumbosacral spinal canal 6 and 8 months after the operation, one of them received a second operation and the other died.Concluslon ONB has no specific symptoms. Intracranial ONB should be resected as far as possible, and treated by radiotherapy afterthe operation.

  13. Development of autoimmunity in lymphoma.

    Science.gov (United States)

    Jardin, Fabrice

    2008-03-01

    Development of lymphoproliferative diseases during the course of autoimmune and chronic inflammatory conditions is well established. Conversely, development of clinical or biological signs of autoimmunity at the time of the diagnosis of lymphoma or during its course indicates that lymphoma and autoimmune manifestations may constitute two faces of the same process. The aim of this review is to describe autoimmune manifestations related to non-Hodgkin's lymphoma and Hodgkin's lymphoma, their specificity according to the lymphoma subtype and their physiopathological signification. Lymphoma-related autoimmune manifestations include mainly skin diseases, hematological manifestations, rheumatic diseases and renal lesions. Despite the lack of studies providing a systematic prospective assessment, autoimmune manifestations are observed in all lymphoma subtypes and seem particularly prevalent in marginal-zone lymphoma and T-cell lymphoma. Autoimmune manifestation's physiopathology may implicate production of autoantibodies by CD5-positive autoreactive B cells, a loss of immune tolerance, an alteration of the Fas/Fas-ligand pathway and/or a chronic antigenic stimulation. Monoclonal antibodies (including rituximab, Campath-1H or epratuzumab) constitute the most promising approach to treat lymphoma-related immune disorders.

  14. 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.

  15. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-07-24

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  16. ALK Gene Copy Number Gain and Immunohistochemical Expression Status Using Three Antibodies in Neuroblastoma.

    Science.gov (United States)

    Kim, Eun Kyung; Kim, Sewha

    2017-01-01

    Anaplastic lymphoma kinase ( ALK) gene aberrations-such as mutations, amplifications, and copy number gains-represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) of the cohort, respectively. There were positive correlations between ALK copy number and IHC-positive rate in ALK1 and 5A4 antibodies ( P copy number gain differed among the three antibodies, with 75% sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC positivity was frequently observed in INSS stage IV and high-risk group patients. In conclusion, this study identified that an increase in the ALK copy number is a frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed consistent ALK IHC positivity with all kinds of antibodies. In contrast, the detection performance of ALK copy number gain was antibody dependent, with the D5F3 antibody showing the best sensitivity.

  17. Treatment Options for Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Hodgkin lymphoma. Lymphocyte-depleted Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin lymphoma. ... about health care. Reviewers and Updates Editorial Boards write the PDQ cancer information summaries and keep them ...

  18. General Information about Primary CNS Lymphoma

    Science.gov (United States)

    ... Research Primary CNS Lymphoma Treatment (PDQ®)–Patient Version General Information About Primary CNS Lymphoma Go to Health ... start in the eye (called ocular lymphoma). Enlarge Anatomy of the lymph system, showing the lymph vessels ...

  19. Cell-nonautonomous function of the retinoblastoma tumour suppressor protein: new interpretations of old phenotypes.

    NARCIS (Netherlands)

    D. Whyatt (David); F.G. Grosveld (Frank)

    2002-01-01

    textabstractLoss of the retinoblastoma protein (pRb) induces a cell-nonautonomous defect in both erythroid and neuronal differentiation. It has previously been thought that this reflects a requirement for pRb function in cells that normally support erythropoiesis and neurogenesis, rather than in the

  20. 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...

  1. 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

    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...

  2. 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 th

  3. A cancer derived mutation in the Retinoblastoma gene with a distinct defect for LXCXE dependent interactions

    Directory of Open Access Journals (Sweden)

    Demone Jordan

    2010-03-01

    Full Text Available Abstract Background The interaction between viral oncoproteins such as Simian virus 40 TAg, adenovirus E1A, and human papilloma virus E7, and the retinoblastoma protein (pRB occurs through a well characterized peptide sequence, LXCXE, on the viral protein and a well conserved groove in the pocket domain of pRB. Cellular proteins, such as histone deacetylases, also use this mechanism to interact with the retinoblastoma protein to repress transcription at cell cycle regulated genes. For these reasons this region of the pRB pocket domain is thought to play a critical role in growth suppression. Results In this study, we identify and characterize a tumor derived allele of the retinoblastoma gene (RB1 that possesses a discrete defect in its ability to interact with LXCXE motif containing proteins that compromises proliferative control. To assess the frequency of similar mutations in the RB1 gene in human cancer, we screened blood and tumor samples for similar alleles. We screened almost 700 samples and did not detect additional mutations, indicating that this class of mutation is rare. Conclusions Our work provides proof of principal that alleles encoding distinct, partial loss of function mutations in the retinoblastoma gene that specifically lose LXCXE dependent interactions, are found in human cancer.

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

    Science.gov (United States)

    Durfee, Tim; Feiler, Heidi; Gruissem, Wilhelm; Jenkins, Susan; Roe, Judith; Zambryski, Patricia

    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.

  5. Growth suppression by p16ink4 requires functional retinoblastoma protein

    NARCIS (Netherlands)

    Medema, R.H.; Herrera, R.E.; Lam, F.; Weinberg, R.A.

    1995-01-01

    p16ink4 has been implicated as a tumor suppressor that is lost from a variety of human tumors and human cell lines. p16ink4 specifically binds and inhibits the cyclin-dependent kinases 4 and 6. In vitro, these kinases can phosphorylate the product of the retinoblastoma tumor suppressor gene. Thus, p

  6. Cell-nonautonomous function of the retinoblastoma tumour suppressor protein: new interpretations of old phenotypes.

    NARCIS (Netherlands)

    D. Whyatt (David); F.G. Grosveld (Frank)

    2002-01-01

    textabstractLoss of the retinoblastoma protein (pRb) induces a cell-nonautonomous defect in both erythroid and neuronal differentiation. It has previously been thought that this reflects a requirement for pRb function in cells that normally support erythropoiesis and neurogenesis, rather than in the

  7. 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 G

  8. 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...

  9. Expression of FasL in Proliferation of Retinoblastoma Cells: A Mechanism Fas Counterattack

    Directory of Open Access Journals (Sweden)

    Hendrian Dwikoloso Soebagjo

    2014-08-01

    Full Text Available Purpose: The aim of this study were to determine the association of increasing of FasL with increasing proliferation of retinoblastoma cells. Materials and Methods: The protein expression was analyzed in 30 retinoblastoma samples from paraffin block using immunohistochemical method for evaluation of FasL, CDK4, and Ki-67 expression. Results: Among 30 retinoblastoma samples, FasL expression majority was negative in 33.3 % (10 samples and strong in 36,8 % (11 samples. CDK4 majority 53,3% was weak expression and Ki-67 was high expression also in 53,3% (16 samples. The expression of FasL was significantly related to CDK4 (r: 0.363; p: 0.048. The CDK4 was also significantly related to Ki-67 expression (r: 0.601; p: 0.000. Conclusion: The increasing of FasL on the mechanism Fas counterattack induces proliferation of retinoblastoma cells. [Cukurova Med J 2014; 39(4.000: 788-794

  10. Effects of PPARγ agonistrosiglitazone on human retinoblastoma cell in vitro and in vivo.

    Science.gov (United States)

    Cao, Xianyong; He, Lin; Li, Yanhua

    2015-01-01

    The aim of the study was to evaluate the antitumor effects of the PPARγ agonist rosiglitazone on the human retinoblastoma. The cell biological behavior was detected, specifically, the effects of rosiglitazone on cell viability and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hochest 33258 staining and the migration assay showed that rosiglitazone blocked the invasion and migration of the carcinoma cells through the reconstituted extracellular matrix (Matrigel). The effect of rosiglitazone on NF-κB-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay. Then human retinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice, and the animals were treated with rosiglitazone (20 mg/kg, 40 mg/kg, and 80 mg/kg) to verify its anti-tumor effect in vivo. Rosiglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that rosiglitazone could modulate the proliferative and apoptosis related signal, reduce NF-κB-dependent reporter gene transcription induced by LPS. Rosiglitazone markedly reduced the growth of Y79 cells transplanted into the mice without causing significant side effects. Our results suggested that rosiglitazone demonstrated antitumor activity against the human retinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and inhibiting metastasis and invasion in vitro and delaying tumor growth in vivo.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Delayed mutation as a cause of retinoblastoma: application to genetic counseling.

    Science.gov (United States)

    Herrmann, J

    1976-01-01

    The genealogic and genetic data on retinoblastoma were reviewed and interpreted according to the model of delayed mutation; then applications of the model to specific situations in genetic counseling were considered. Patients with multiple congenital abnormalities and systemic chromosome aberrations are regarded as belonging to a different category of retinoblastoma cases than the more common patients without such abnormalities. The model of delayed mutation is considered for the latter group of patients. According to the model, mutation at the retinoblastoma locus can be delayed or complete and can occur during meiotic or mitotic cell division. Genotypically, three clases of individuals can be identified in retinoblastoma families: homozygous normal, heterozygous for the premutated allele, and heterozygous for the (fully) mutated allele; the other possible combinations of individuals have apparently not been observed. There is to date no evidence to suggest incomplete penetrance of the mutant allele, but 14% of individuals who have the mutant gene are "only" unilaterally affected. Carriers produce normal, affected and carrier offspring in the empiric proportion of, respectively, 54.5%, 36.4% and 9.1%. Most difficulties in genetic counseling arise because affected individuals may have inherited the premutated or the mutated allele and because unaffected individuals may have inherited the normal or the premutated allele. These aspects were considered for individuals presenting as sporadic-unilateral, sporadic-bilateral, familial-unilateral and familial-bilateral cases, and the empiric risk figures for various situations were quoted from the literature.

  13. 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

  14. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong; Li, Yang; Song, Gaojie; Zhang, David; Shaw, Neil; Liu, Zhi-Jie; (Chinese Aca. Sci.)

    2009-07-10

    Retinoblastoma (RB), a carcinoma of the retina, is caused by mutations in the long arm of chromosome 13, band 13q14. The esterase D (ESD) gene maps at a similar location as the RB gene locus and therefore serves as a potential marker for the prognosis of retinoblastoma. Because very little is known about the structure and function of ESD, we determined the 3-dimensional structure of the enzyme at 1.5 {angstrom} resolution using X-ray crystallography. ESD shows a single domain with an {alpha}/{beta}-hydrolase fold. A number of insertions are observed in the canonical {alpha}/{beta}-hydrolase fold. The active site is located in a positively charged, shallow cleft on the surface lined by a number of aromatic residues. Superimposition studies helped identify the typical catalytic triad residues -- Ser-153, His264, and Asp230 -- involved in catalysis. Mutagenesis of any of the catalytic triad residues to alanine abolished the enzyme activity. Backbone amides of Leu54 and Met150 are involved in the formation of the oxyanion hole. Interestingly, a M150A mutation increased the enzyme activity by 62%. The structure of human ESD determined in this study will aid the elucidation of the physiological role of the enzyme in the human body and will assist in the early diagnosis of retinoblastoma. Wu, D., Li, Y., Song, G., Zhang, D., Shaw, N., Liu, Z. J. Crystal structure of human esterase D: a potential genetic marker of retinoblastoma.

  15. 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.

    2014-01-01

    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 na

  16. Acetaminophen induces human neuroblastoma cell death through NFKB activation.

    Directory of Open Access Journals (Sweden)

    Inmaculada Posadas

    Full Text Available Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation into the mitochondria, cytochrome c release and caspase activation. AAP activates the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP metabolism is partially responsible for this activation, because blockade of the cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and its translocation to the nucleus, where NFkB p65 increased IL-1β production. This increase contributed to neuroblastoma cell death through a mechanism involving Bax accumulation into the mitochondria, cytochrome c release and caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide SN50 prevented AAP-mediated cell death and IL-1β production. Moreover, overexpression of the antiapoptotic protein Bcl-x(L did not decrease AAP-mediated IL-1β production, but prevented both AAP and IL-1β-mediated cell death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and U87MG glioblastoma cell lines. The results presented here suggest that AAP activates the intrinsic death pathway in neuroblastoma cells through a mechanism involving NFkB and IL-1β.

  17. Preclinical models for neuroblastoma: establishing a baseline for treatment.

    Directory of Open Access Journals (Sweden)

    Tal Teitz

    Full Text Available BACKGROUND: Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system. PRINCIPAL FINDINGS: Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. SIGNIFICANCE: The studies suggest that use of both the TH-NMYC model of neuroblastoma and the

  18. No evidence for involvement of SDHD in neuroblastoma pathogenesis

    Directory of Open Access Journals (Sweden)

    Roels Frank

    2004-08-01

    Full Text Available Abstract Background Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma. Methods SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria. Results Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype. Conclusions Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis.

  19. Multimodality imaging of cardiothoracic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Brett W., E-mail: bcarter2@mdanderson.org [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Wu, Carol C. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Khorashadi, Leila [Department of Radiology, Mount Auburn Hospital, Cambridge, MA 02138 (United States); Godoy, Myrna C.B.; Groot, Patricia M. de [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Abbott, Gerald F. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Lichtenberger III, John P. [Department of Radiology, David Grant Medical Center, Travis AFB, CA 94535 (United States)

    2014-08-15

    Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and {sup 18}F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

  20. Hypothermia & Hodgkin lymphoma in children

    OpenAIRE

    Köse, Doğan; Köksal, Yavuz; Çalışkan, Ümran

    2016-01-01

    Hypothermia associated with Hodgkin lymphoma is defined rarely. This may be caused by a dysfunction that shall occur in hypothalamus, central and peripheral vascular system, skin and muscles. In this study, two Hodgkin lymphoma cases with developed hypothermia are presented. Case 1: An “Hodgkin lymphoma, mixed cellular type” was diagnosed by a biopsy conducted due to lesions found in her spleen on a girl in 7 ages, who applied to the hospital with complaints such as fever, weight loss and nig...

  1. FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    2014-01-06

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell

  2. Correlation of CD24 expression with histological grading and TNM staging of retinoblastoma.

    Science.gov (United States)

    Ishaq, Syed Muhammad; Kehar, Shahnaz Imdad; Zafar, Shahid; Hasan, Syed Furqan Ul

    2016-01-01

    Correlation of CD24 expression with histological grading and TNM staging of retinoblastoma. This cross-sectional study was conducted in the Department of Pathology, BMSI, JPMC and NICH from 1(st) January 2009 to 31(st) December 2013. A total 68 diagnosed cases of retinoblastoma were selected for CD24 immuno staining. The data was analyzed by using SPSS version 22. Out of 68 cases 7.35% showed grade 1 followed by 11.76% in G2, 26.47% in G3 and 54.41% in G4. Majority of cases i.e. 60.29% in stage IV followed by 19.11% in stage I, 10.29% each in stage II and stage III. CD24 immuno staining positivity was seen in majority of grade 3 and grade 4. In grade 3, 38.88% showed moderate and 22.22% strong immuno reaction. Amongst grade 4, 40.54% showed moderate and 13.51% strong positive. Variable immuno pattern was observed according to TNM staging. In stage I, 46.15% showed moderate and 7.69% strong positivity, while in stage II, 57.14% were negative for saining. In stage III, 42.85% were negative while 28.57% each showed moderate and strong staining. Majority of cases in stage IV i.e. 48.78% were negative for staining while 34.14%, 17.07% showed moderate and severe CD24 immuno staining. Majority of grade I retinoblastoma were in TNM stage I & II and mostly were immuno negative. Lymph node and distant metastatic cases were 75% in G4 and 25% in G3, all of them showed moderate to strong immunoreactivity. These results showed that CD24 expression may be a marker of poor prognosis in retinoblastoma. Whereas TNM staging of retinoblastomas with CD24 expression had varying pattern and showed no significant correlation between them.

  3. Treatment outcome of osteosarcoma after bilateral retinoblastoma: a retrospective study of eight cases.

    Science.gov (United States)

    Lee, Jun Ah; Choi, Sang Yul; Kang, Hyoung Jin; Lee, Ji Won; Kim, Hyery; Kim, Jeong Hun; Sung, Ki Woong; Shin, Hee Young; Ahn, Hyo Seop; Park, Kyung Duk

    2014-10-01

    To analyse clinical characteristics and treatment outcomes of osteosarcoma that developed in survivors of bilateral retinoblastoma. Three institutions participated in this retrospective study. Among survivors of bilateral retinoblastoma who were diagnosed and treated between 1995 and 2012, 8 cases (4 male, 4 female) of osteosarcoma were identified. Medical records were thoroughly reviewed. Median age at diagnosis of bilateral retinoblastoma was 8.5 months (range 1.4-18.4 months). Treatment modalities for retinoblastoma were: enucleation+chemotherapy+radiotherapy (n=6); chemotherapy combined with focal therapy (n=1); and chemotherapy+radiotherapy (n=1). Median radiotherapy dose was 46.5 Gy (range 45-54 Gy). Median age at diagnosis of osteosarcoma was 8.9 years (range 5.4-20.3 years). Median interval between retinoblastoma and osteosarcoma was 8.2 years (range 5.0-20.0 years). Tumour locations were femur (n=5), tibia (n=1), mandible (n=1), and nasal cavity (n=1). Two patients presented with lung metastasis. Seven patients received multimodal treatment, and treatment was refused in 1 patient. After diagnosis of osteosarcoma, the patients were followed for a median of 17.3 months (range 4.4-56.4 months). The 2-year overall survival and event-free survival rates were 56.3 ± 19.9% and 33.3 ± 18.0%, respectively. At the time of analysis, 5 patients remained alive, and 2 of them were on therapy. Of the 3 surviving patients without evidence of disease, 2 received high dose chemotherapy with autologous peripheral blood stem cell support. Our data could be used as a basis for future studies aimed at reaching consensus about long term follow-up and treatment guidelines for this genetically susceptible group of patients. 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.

  4. Lymphoma-associated dysimmune polyneuropathies.

    Science.gov (United States)

    Stübgen, Joerg-Patrick

    2015-08-15

    Lymphoma consists of a variety of malignancies of lymphocyte origin. A spectrum of clinical peripheral neuropathy syndromes with different disease mechanisms occurs in about 5% of lymphoma patients. There exists a complex inter-relationship between lymphoproliferative malignancies and autoimmunity. An imbalance in the regulation of the immune system presumably underlies various immune-mediated neuropathies in patients with lymphoma. This article reviews lymphoma and more-or-less well-defined dysimmune neuropathy subgroups that are caused by humoral and/or cell-mediated immune disease mechanisms directed against known or undetermined peripheral nerve antigens.

  5. Simultaneous measurement of neural spike recordings and multi-photon calcium imaging in neuroblastoma cells.

    Science.gov (United States)

    Kim, Suhwan; Jung, Unsang; Baek, Juyeong; Kang, Shinwon; Kim, Jeehyun

    2012-11-08

    This paper proposes the design and implementation of a micro-electrode array (MEA) for neuroblastoma cell culturing. It also explains the implementation of a multi-photon microscope (MPM) customized for neuroblastoma cell excitation and imaging under ambient light. Electrical signal and fluorescence images were simultaneously acquired from the neuroblastoma cells on the MEA. MPM calcium images of the cultured neuroblastoma cell on the MEA are presented and also the neural activity was acquired through the MEA recording. A calcium green-1 (CG-1) dextran conjugate of 10,000 D molecular weight was used in this experiment for calcium imaging. This study also evaluated the calcium oscillations and neural spike recording of neuroblastoma cells in an epileptic condition. Based on our observation of neural spikes in neuroblastoma cells with our proposed imaging modality, we report that neuroblastoma cells can be an important model for epileptic activity studies.

  6. New miRNAs cloned from neuroblastoma

    Directory of Open Access Journals (Sweden)

    Glatting Karl-Heinz

    2008-01-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a novel class of gene expression regulators implicated in cancer biology. Neuroblastoma (NB is an embryonal tumour consisting of neural crest-derived undifferentiated cells and is characterised by variable clinical courses ranging from spontaneous regression to therapy-resistant progression. Recent advances identified a subset of miRNAs with putative function in NB biology. However, the full repertoire of miRNAs expressed in NBs is not available. Results We describe miRNA profiles of 13 NB specimens and 2 NB cell lines as determined by miRNA cloning. A total of 3153 sequences were sequenced and analysed by a miRNA prediction tool (miRpredict. Our library covered 27% miRNAs known to date. 39 reads corresponding to 25 individual sequences were classified as novel miRNAs, including miRNA* species of 10 known miRNAs. Expression of 5 new miRNA* forms and 8 individual sequences was supported by Northern blotting. Most of the novel miRNA genes are not related to each other and do not share homology with the annotated sequences in the public miRNA database, but they are conserved within mammals or have close homologues in primates genomes. Conclusion We provide evidence for 29 new miRNA and miRNA-like sequences (24 novel sequences and 5 miRNAs discovered initially in other species. Some of these newly identified sequences reside within frequently altered chromosomal regions in NB tumours and may play a role in NB biology.

  7. 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

  8. Pathobiology of Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Pier Paolo Piccaluga

    2011-01-01

    Full Text Available Despite its well-known histological and clinical features, Hodgkin's lymphoma (HL has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B-cell derivation of the tumor in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognizes a basic distinction between lymphocyte predominance HL (LP-HL and classic HL (cHL, reflecting the differences in clinical presentation and behavior, morphology, phenotype, and molecular features. cHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between cHL and anaplastic large-cell lymphoma have become sharper, whereas those between LP-HL and T-cell-rich B-cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumor in at-risk patients have been proposed and are on the way to being applied.

  9. Intravascular lymphoma mimicking vasculitis.

    Science.gov (United States)

    Prayson, Richard A

    2016-12-01

    Intravascular lymphoma is a rare malignancy which is characterized by a proliferation of atypical appearing B cells, generally confined to vascular lumina. A tissue biopsy demonstrating the pathology is required to make a diagnosis. The tumor is often disseminated at the time of diagnosis and prognosis is poor, even with aggressive chemotherapy. Neurologic presentations of this neoplasm can be quite varied. This report documents the presence of intravascular lymphoma diagnosed on a brain biopsy in a 60-year-old man. He initially presented 6months before brain biopsy with chest pain and hypotension, warranting coronary artery bypass graft surgery. Four months later, he presented with signs attributed to a stroke (diaphoresis, slumped over in a chair and left hand weakness). He subsequently developed a sudden onset wide-based gait, left leg numbness, word finding difficulties and worsening confusion. A MRI study showed multiple infarcts in the brain, including cerebellum. Invasive angiogram suggested vasculitis. He was started on a course of treatment for presumed central nervous system vasculitis. He continued to develop signs suggestive of ongoing infarct development and a biopsy from the right parietal was taken. The biopsy showed atypical intravascular CD20 positive staining B cells, consistent with intravascular lymphoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Comparison of kinetics of X-ray-induced cell killing in normal, ataxia telagiectasia and hereditary retinoblastoma fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, H.; Little, J.B. (Harvard School of Public Health, Boston, MA (USA). Lab. of Radiobiology)

    1983-05-01

    Survival, cumulative labeling indices and chromosomal aberrations were studied in normal, ataxia telangiectasia (AT) and hereditary retinoblastoma fibroblasts after X-irradiation during density-inhibition of growth and immediate release by subculture to low density. Th

  11. Danish National Lymphoma Registry

    Directory of Open Access Journals (Sweden)

    Arboe B

    2016-10-01

    Full Text Available Bente Arboe,1 Pär Josefsson,2 Judit Jørgensen,3 Jacob Haaber,4 Paw Jensen,5 Christian Poulsen,6 Dorthe Rønnov-Jessen,7 Robert S Pedersen,8 Per Pedersen,9 Mikael Frederiksen,10 Michael Pedersen,1 Peter de Nully Brown1 1Department of Hematology, Copenhagen University Hospital, Rigshospitalet, 2Department of Hematology, Copenhagen University Hospital, Herlev Hospital, Copenhagen, 3Department of Hematology, Aarhus University Hospital, Aarhus, 4Department of Hematology, Odense University Hospital, Odense, 5Department of Hematology, Aalborg University Hospital, Aalborg, 6Department of Hematology, Roskilde Hospital, Roskilde, 7Department of Hematology, Vejle Hospital, Vejle, 8Department of Hematology, Holstebro Hospital, Holstebro, 9Department of Hematology, Esbjerg Hospital, Esbjerg, 10Department of Hematology, Haderslev Hospital, Haderslev, Denmark Aim of database: The Danish National Lymphoma Registry (LYFO was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. Study population: The LYFO database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. Main variables: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each patient: a primary registration form, a treatment form, a relapse form, and a follow-up form. Variables are used to calculate six result quality indicators (mortality 30 and 180 days after diagnosis, response to first-line treatment, and survival estimates 1, 3, and 5 years after the time of diagnosis, and three process quality indicators (time from diagnosis until the start of treatment, the presence of relevant diagnostic markers, and inclusion rate in clinical protocols. Descriptive data: Approximately 23

  12. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  13. miRNA signature identification of retinoblastoma and the correlations between differentially expressed miRNAs during retinoblastoma progression.

    Science.gov (United States)

    Yang, Yang; Mei, Qi

    2015-01-01

    Retinoblastoma (RB) is a common pediatric cancer. The study aimed to uncover the mechanisms of RB progression and identify novel therapeutic biomarkers. The miRNA expression profile GSE7072, which includes three RB samples and three healthy retina samples, was used. After data normalization using the preprocessCore package, differentially expressed miRNAs (DE-miRs) were selected by the limma package. The targets of the DE-miRs were predicted based on two databases, followed by construction of the miRNA-target network. Pathway enrichment analysis was conducted for the targets of the DE-miRNAs using DAVID. The CTD database was used to predict RB-related genes, followed by clustering analysis using the pvclust package. The correlation network of DE-miRs was established. MiRNA expression was validated in another data set, GSE41321. In total, 24 DE-miRs were identified whose targets were correlated with the cell cycle pathway. Among them, hsa-miR-373, hsa-miR-125b, and hsa-miR-181a were highlighted in the miRNA-target regulatory network; 14 DE-miRs, including hsa-miR-373, hsa-miR-125b, hsa-miR-18a, hsa-miR-25, hsa-miR-20a, and hsa-let-7 (a, b, c), were shown to distinguish RB from healthy tissue. In addition, hsa-miR-25, hsa-miR-18a, and hsa-miR-20a shared the common target BCL2L11; hsa-let-7b and hsa-miR-125b targeted the genes CDC25A, CDK6, and LIN28A. Expression of three miRNAs in GSE41321 was consistent with that in GSE7072. Several critical miRNAs were identified in RB progression. Hsa-miR-373 might regulate RB invasion and metastasis, hsa-miR-181a might involve in the CDKN1B-mediated cell cycle pathway, and hsa-miR-125b and hsa-let-7b might serve as tumor suppressors by coregulating CDK6, CDC25A, and LIN28A. The miRNAs hsa-miR-25, hsa-miR-18a, and hsa-miR-20a might exert their function by coregulating BCL2L1.

  14. Hypoxia-induced miR-181b enhances angiogenesis of retinoblastoma cells by targeting PDCD10 and GATA6.

    Science.gov (United States)

    Xu, Xiaofang; Ge, Shengfang; Jia, Renbing; Zhou, Yixiong; Song, Xin; Zhang, He; Fan, Xianqun

    2015-06-01

    Previous findings showed that miR-181b is upregulated under hypoxic conditions in retinoblastoma cells. Since hypoxia is a common feature of retinoblastoma that affects tumor progression as well as tumor therapy, in the present study, we investigated the regulatory mechanism of miR-181b under hypoxic conditions, and examined the role of miR-181b in retinoblastoma responses to hypoxia (chemoresistance and angiogenesis) and possible downstream genes. The level of hypoxia-inducible factor-1α (HIF-1α) and miR-181b was detected to examine the link between them. Tube formation and cell cytotoxicity assays were used to clarify the effects of miR-181b on hypoxic responses of retinoblastoma cells. Bioinformatics analysis was performed to predict potential targets of miR-181b and western blotting was used to verify these targets. The results showed a significantly increased expression of HIF-1α in hypoxia-treated retinoblastoma cells. Downregulation of HIF-1α using a small-interfering RNA (siRNA) knockdown technology did not decrease the expression of miR-181b. Through gain- and loss-of-function studies, miR-181b was demonstrated to significantly stimulate the ability of capillary tube formation of endothelial cells. Programmed cell death-10 (PDCD10) and GATA binding protein 6 (GATA6) were identified as the target genes of miR‑181b. To the best of our knowledge, results of the present study provide the first evidence that miR-181b was upregulated by hypoxia in retinoblastoma in an HIF-1α-independent manner. miR-181b increased tumor angiogenesis of retinoblastoma cells. Additionally, miR-181b exerts its angiogenic function, at least in part, by inhibiting PDCD10 and GATA6. Thus, it is a new potentially useful therapeutic target for retinoblastoma.

  15. Identifying microRNAs that Regulate Neuroblastoma Cell Differentiation

    Science.gov (United States)

    2015-10-01

    3. Targeting the differentiation pathway in neuroblastoma differentiation therapy. Department of Chemistry and Biochemistry. Texas State University...Nielsen O, Skjodt K, Palaniyar N, Stein- hilber W, et al. Microfibril-associated protein 4 binds to surfactant protein A (SP-A) and colocalizes with SP-A in

  16. Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report

    Science.gov (United States)

    Leon-Soriano, Elena; Alfonso, Carolina; Yebenes, Laura; Garcia-Polo, Julio; Lassaletta, Luis; Gavilan, Javier

    2016-01-01

    Patient: Male, 41 Final Diagnosis: Olfactory neuroblastoma Symptoms: Left nasal obstruction • occasional left epistaxis • headache Medication: None Clinical Procedure: Nasal endoscopic examination • neck palpation • CT • bilateral endoscopic resection • MRI • PET-CT • postoperative radiotherapy Specialty: Otolaryngology Objective: Unusual clinical course Background: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant head and neck cancer thought to originate from the olfactory epithelium. It typically invades contiguous structures at presentation. We report a very rare case of multifocal and ectopic ONB. Case Report: A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses. Histopathological diagnosis after endoscopic resection established bilateral olfactory neuroblastoma of the ethmoid sinuses. The patient received postoperative radiotherapy. He remains free of disease 4 years after treatment. Conclusions: To the best of our knowledge this is the second documented case of multifocal ectopic olfactory neuroblastoma. Clinicians should consider ONB in the differential diagnosis of bilateral synchronous nasal and paranasal masses to avoid delayed diagnosis. Endoscopic resection of ONB could be an option in selected cases. PMID:27097989

  17. Thymic Neuroblastoma within a Thymic Cyst in an Adult

    Directory of Open Access Journals (Sweden)

    Yuichiro Ueda

    2012-08-01

    Full Text Available Case Presentation: A 65-year-old female patient with no clinical manifestations was hospitalized for examination and treatment of an anterior mediastinal tumor found at the time of a regular health checkup. Enhanced computed tomography (CT and magnetic resonance imaging revealed a cystic lesion containing a solid tumor. Positron emission tomography-CT demonstrated increased uptake in the solid lesion. Tumor resection with total thymectomy was performed. A pathological diagnosis of thymic neuroblastoma within a thymic cyst was made. Micorscopic examination revealed that tumor cells of the solid component were lined with thymic epithelial cells of the inner cyst wall. Furthermore, some tumor cells of the solid component had melanin granules. These findings suggest that this tumor arose from progenitors of the thymic epithelial cells with the potential to differentiate along neural lines. Conclusions: Neuroblastoma commonly occurs in children. However, the diagnosis of neuroblastoma in adults has been reported in several case reports. We report an adult case of histogenetically informative thymic neuroblastoma within a thymic cyst. There are no standard treatment strategies and chemotherapy protocols. Complete surgical resection might be important for a better outcome.

  18. Taurolidine cooperates with antineoplastic drugs in neuroblastoma cells.

    Science.gov (United States)

    Eschenburg, Georg; Luckert, Christian; Reinshagen, Konrad; Bergholz, Robert

    2014-11-01

    Neuroblastoma is the most common extracranial tumor in childhood. Outcome of stage 4 disease remains poor and the development of novel therapeutic approaches is thus urgently needed. Taurolidine (TRD), originally invented to avoid catheter infections, has shown to exhibit antineoplastic activity in various cancers. The growth of neuroblastoma cell lines is inhibited by TRD as recently demonstrated. Further analysis disclosed a significant negative growth effect of TRD on the four neuroblastoma cell lines SH-EP TET21N, SK-N-AS, SK-N-BE(2)-M17 and SK-N-SH. Detected IC50 (51-274 μM; 48 h) are promising and correspond to clinically-achievable plasma levels. Apoptosis was induced (76-86%; 48 h) in a time-dependent manner mediated by a simultaneous activation of the intrinsic and extrinsic pathways. This was confirmed by cleavage of caspases -3, -8 and -9 and abrogation of apoptosis by pan-caspase inhibition. Application of TRD resulted in a significant enhancement of cytotoxic drugs vincristine/doxorubicin (2/3 of 4 cell lines) making TRD a promising candidate to be included in neuroblastoma therapy regimens in the future.

  19. Sphingolipids in neuroblastoma : Their role in drug resistance mechanisms

    NARCIS (Netherlands)

    Sietsma, H; Dijkhuis, AJ; Kamps, W; Kok, JW

    2002-01-01

    Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g.,

  20. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes

    NARCIS (Netherlands)

    J. Molenaar (Jan); J. Koster (Jan); D. Zwijnenburg (Danny); P. van Sluis (Peter); L.J. Valentijn (Linda); I. van der Ploeg (Ida); M. Hamdi (Mohamed); J. van Nes (Johan); B.A. Westerman (Bart); J. van Arkel (Jennemiek); M.E. Ebus; F. Haneveld (Franciska); A. Lakeman (Arjan); L. Schild (Linda); P. Molenaar (Piet); P. Stroeken (Peter); M.M. van Noesel (Max); I. Øra (Ingrid); J.P. di Santo (James); H.N. Caron (Huib); E.M. Westerhout (Ellen); R. Versteeg (Rogier)

    2012-01-01

    textabstractNeuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (

  1. Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

    Directory of Open Access Journals (Sweden)

    Li ZR

    2012-05-01

    Full Text Available Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China*These authors contributed equally to this workBackground: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs on retinoblastoma and to investigate the potential mechanisms involved.Methods: Celastrol-loaded poly(ethylene glycol-block-poly(ε-caprolactone nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl-3-(4-nitrophenyl-5-(2,4-disulf-ophenyl-2H tetrazolium monosodium salt (WST-8 assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma.Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC50 of 17.733 µg/mL (celastrol-loading content: 7.36% after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65

  2. Tyrosine phosphorylation in human lymphomas

    NARCIS (Netherlands)

    Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

    2002-01-01

    In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

  3. Lymphoma risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence

    2014-01-01

    OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated...

  4. Lymphoma of the Urinary Bladder

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    Anthony Kodzo-Grey Venyo

    2014-01-01

    Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

  5. Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in retinoblastoma

    Indian Academy of Sciences (India)

    CHANGXIA DONG; SHAOYI LIU; YONGBIN LV; CHUNPING ZHANG; HEYING GAO; LIXIA TAN; HONG WANG

    2016-12-01

    Retinoblastoma is the most frequently occurring tumour in the eyes in early childhood. Novel targets that areimportant for the diagnosis or treatment of retinoblastoma could be valuable in increasing the survival rate of patientsaffected by this disease. Long non-coding RNAs (lncRNAs) are a recently discovered type of RNAs with no proteincodingfunction; yet it has become increasingly clear that lncRNAs are responsible for important gene regulatoryfunctions in various diseases. In this study, the expression of lncRNA HOTAIR was measured by qRT-PCR, andHOTAIR expression was found to be significantly upregulated in human retinoblastomas tissues as compared with thatin paracancerous tissues. Knockdown of HOTAIR restricted the proliferation and invasion of the more invasiveretinoblastoma Y79 cells, and led to G0/G1 arrest, possibly through inhibiting phospho-RB1, RB1 and CCNE.Furthermore, we found that the Notch signalling pathway was activated abnormally in retinoblastoma cell lines, whileknockdown of HOTAIR attenuated the endogenous Notch signalling pathway in vitro and in vivo. In addition,knockdown of HOTAIR could inhibit the tumour progression in a xenograft model of retinoblastoma. In summary,our findings indicate that HOTAIR may play important roles in retinoblastoma progression via Notch pathway.HOTAIR has the potential to enhance the development of novel targeted diagnostic and therapeutic approaches forretinoblastoma.

  6. Graphene Oxide Nanoribbons Induce Autophagic Vacuoles in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Emanuela Mari

    2016-11-01

    Full Text Available Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2 and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS, mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells.

  7. Diffuse Anterior Retinoblastoma with Globe Salvage and Visual Preservation in 3 Consecutive Cases.

    Science.gov (United States)

    Shields, Carol L; Lally, Sara E; Manjandavida, Fairooz P; Leahey, Ann M; Shields, Jerry A

    2016-02-01

    Diffuse anterior retinoblastoma is an exquisitely rare variant of retinoblastoma in which the tumor resides in the anterior segment of the eye, without apparent retinal involvement. Previously published cases have been managed with enucleation. We describe globe salvage and visual preservation in 3 consecutive cases using chemotherapy and radiotherapy. Retrospective case series. Three children with diffuse anterior retinoblastoma. Plaque radiotherapy plus intravenous chemotherapy. Globe and vision preservation. The mean patient age at presentation elsewhere was 5.7 years (median, 7; range, 3-7 years). There were 2 white female patients and 1 African American male patient. The initial observation by parents/caregiver was reduced vision (n = 1), red eye (n = 1), or cloudy eye (n = 1), and the initial finding by physician was iris tumor (n = 2) or hyphema (n = 1). Referring diagnosis was iris melanoma (n = 1), infectious endotheliitis (n = 1), and possible tumor (nonspecified) (n = 1). At our evaluation, visual acuity was 20/50 to 20/60 (n = 2) and fix no follow (n = 1). In all cases, the opposite eye was normal. Mean intraocular pressure was 20 mm Hg (median, 16; range, 15-30 mmHg). Our examination revealed solid iris tumor (n = 3), ciliary body involvement (n = 2), and anterior chamber seeding (n = 3). In no case was there choroidal or retinal tumor, vitreous seed or subretinal seed, or extrascleral extension. Clear corneal fine-needle aspiration biopsy confirmed the diagnosis as retinoblastoma in each case. Treatment included plaque radiotherapy (n = 3) plus additional systemic chemotherapy (n = 2). At mean follow-up of 35 months (median, 34; range, 20-51 months), there has been no recurrence, extrascleral extension, enucleation, metastasis, or death. In all 3 cases, cataract surgery was necessary at a mean interval of 16 months after complete and stable regression of retinoblastoma. The rare diffuse anterior form of retinoblastoma can be managed with globe

  8. [Malignant non-Hodgkin's lymphoma].

    Science.gov (United States)

    Bourrier, P; Grodner, F; Ruf, R; Texier, J; Cottencin, R; Cousteau, C; Deslandre, A; Gounant, C; Szpirglas, H; Laufer, J

    1983-01-01

    Rapid regression of all symptoms was obtained after moderate chemotherapy in two women aged 69 and 77 years respectively with malignant non-Hodgkin's lymphomas. Cervico-facial locations of these tumors are discussed in relation to definition, etiology, geographic factors, genetic markers, and associated immunologic disorders. Diagnosis requires a series of explorations including, obviously as a last resort, exploratory cervicotomy. Other regions may be involved and must be investigated, but lesions not affecting lymph nodes occur in only approximately 2 p. cent of patients with cervico-facial malignant non-Hodgkin's lymphoma (approximately 10 p. cent of all malignant non-Hodgkin's lymphomas). Other localizations include the hard palate, gums, sinuses, and salivary glands. Burkitt's lymphoma represents, on the contrary, 30 p. cent of malignant non-Hodgkin's lymphoma seen in European children. The different therapeutic modalities available are discussed.

  9. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-06-10

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  10. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  11. Lymphatic system and lymphoma

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930583 Analysis of therapeutic efficacy of com- bination chemotherapy and adjuvant radiothera-py in 207 cases of diffuse non—Hodgkin’s lym-phoma.YONG Weiben(勇威本),et al.BeijingCancer Res Instit,Beijing,100000. Chin J Hema-tol 1992;13(12):638—640.Two hundred and seven cases of diffuse non—Hodgkin’s lymphoma(D—NHL)were treatedwith combination chemotherapy(cyclophospha-mide,vincristine,procarbazine,prednisone andpingyingmycin or adriamycin)and adjuvant ra-diotherapy.Complete remission(CR)wasachieved in 94 of 207 patients(45.4%),partial

  12. Phase I trial of lestaurtinib for children with refractory neuroblastoma: a new approaches to neuroblastoma therapy consortium study.

    Science.gov (United States)

    Minturn, Jane E; Evans, Audrey E; Villablanca, Judith G; Yanik, Gregory A; Park, Julie R; Shusterman, Suzanne; Groshen, Susan; Hellriegel, Edward T; Bensen-Kennedy, Debra; Matthay, Katherine K; Brodeur, Garrett M; Maris, John M

    2011-10-01

    TrkB acts as an oncogenic kinase in a subset of human neuroblastomas. Lestaurtinib, a multi-kinase inhibitor with potent activity against Trk kinases, has demonstrated activity in preclinical models of neuroblastoma. Patients with refractory high-risk neuroblastoma received lestaurtinib twice daily for 5 days out of seven in 28-day cycles, starting at 70% of the adult recommended Phase 2 dose. Lestaurtinib dose was escalated using a 3 + 3 design. Pharmacokinetics and plasma phospho-TrkB inhibitory activity were evaluated in the first cycle. Forty-seven subjects were enrolled, and 10 dose levels explored starting at 25 mg/M(2)/dose BID. Forty-six subjects were evaluable for response, and 42 subjects were fully evaluable for determination of dose escalation. Asymptomatic and reversible grade 3-4 transaminase elevation was dose limiting in 4 subjects. Reversible pancreatitis (grade 2) was observed in 3 subjects after prolonged treatment at higher dose levels. Other toxicities were mild and reversible. Pharmacokinetic analyses revealed rapid drug absorption, however inter-patient variability was large. Plasma inhibition of phospho-TrkB activity was observed 1 h post-dosing at 85 mg/M(2) with uniform inhibition at 120 mg/M(2). There were two partial responses and nine subjects had prolonged stable disease at dose levels ≥ 5, (median: 6 cycles). A biologically effective and recommended phase 2 dose of 120 mg/M(2)/dose BID was established. Lestaurtinib was well tolerated in patients with refractory neuroblastoma, and a dose level sufficient to inhibit TrkB activity was established. Safety and signs of activity at the higher dose levels warrant further evaluation in neuroblastoma.

  13. FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma.

    NARCIS (Netherlands)

    Schreuder, M.I.; Hoefnagel, J.J.; Jansen, P.A.M.; Krieken, J.H.J.M. van; Willemze, R.; Hebeda, K.M.

    2005-01-01

    Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but

  14. FISH analysis of MALT lymphoma-specific translocations and aneuploidy in primary cutaneous marginal zone lymphoma.

    NARCIS (Netherlands)

    Schreuder, M.I.; Hoefnagel, J.J.; Jansen, P.A.M.; Krieken, J.H.J.M. van; Willemze, R.; Hebeda, K.M.

    2005-01-01

    Primary cutaneous marginal zone lymphomas (PCMZL) share histological and clinical characteristics with mucosa-associated lymphoid tissue (MALT) lymphomas suggesting a common pathogenesis. A number of recurrent structural and numerical chromosomal aberrations have been described in MALT lymphoma, but

  15. Integration of developmental and environmental signals into cell proliferation and differentiation through RETINOBLASTOMA-RELATED 1.

    Science.gov (United States)

    Harashima, Hirofumi; Sugimoto, Keiko

    2016-02-01

    Plants continuously form new organs during post-embryonic development, thus progression of the proliferative cell cycle and subsequent transition into differentiation must be tightly controlled by developmental and environmental cues. Recent studies have begun to uncover how cell proliferation and cell differentiation are coordinated at the molecular level through tight transcriptional regulation of cell cycle and/or developmental regulators. Accumulating evidence suggests that RETINOBLASTOMA-RELATED 1 (RBR1), the Arabidopsis homolog of the human tumor suppressor Retinoblastoma (Rb), functions as a molecular hub linking cell proliferation, differentiation, and environmental response. In this review we will discuss recent findings on cell cycle regulation, highlighting the emerging roles of RBR1 as a key integrator of internal differentiation cues and external stimuli into the cell cycle machinery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Immunohistochemical observation of anterior subcapsular cataract in eye with spontaneously regressed retinoblastoma.

    Science.gov (United States)

    Shirai, Kumi; Okada, Yuka; Saika, Shizuya

    2010-03-01

    We report the histological findings of secondary cataract in an eye with a spontaneously regressed retinoblastoma to obtain keys to clarify the mechanism of this phenomenon. During phacoemulsification, opacified anterior capsule was obtained, fixed in formalin, and embedded in paraffin. Paraffin sections of the specimen were histologically observed. Hematoxylin-eosin staining showed extracellular matrix accumulation in the extracted fibrous anterior subcapsular opacification. Immunohistochemistry revealed the presence of fibrous collagen types and cellular fibronectin. Presumed lens cells amid matrix were positively labeled for vimentin, alpha-smooth muscle actin, and phospho-Smad2. Histology of the fibrous anterior subcapsular opacification tissue showed the possibility of epithelial-mesenchymal transition of the lens epithelial cells in the secondary cataract following a spontaneously regressed retinoblastoma.

  17. 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.

  18. Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies

    Institute of Scientific and Technical Information of China (English)

    Susumu; Kohno; Shunsuke; Kitajima; Nobunari; Sasaki; Chiaki; Takahashi

    2016-01-01

    Carcinogenic transformation of somatic cells resembles nuclear reprogramming toward the generation of pluripotent stem cells.These events share eternal escape from cellular senescence,continuous self-renewal in limited but certain population of cells,and refractoriness to terminal differentiation while maintaining the potential to differentiate into cells of one or multiple lineages.As represented by several oncogenes those appeared to be first keys to pluripotency,carcinogenesis and nuclear reprogramming seem to share a number of core mechanisms.The retinoblastoma tumor suppressor product retinoblastoma(RB)seems to be critically involved in both events in highly complicated manners.However,disentangling such complicated interactions has enabled us to better understand how stem cell strategies are shared by cancer cells.This review covers recent findings on RB functions related to stem cells and stem cell-like behaviors of cancer cells.

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

    Science.gov (United States)

    Dean, Michael; Bendfeldt, Giovana; Lou, Hong; Giron, Veronica; Garrido, Claudia; Valverde, Patricia; Barnoya, Margarita; Castellanos, Mauricio; Jiménez-Morales, Silvia; Luna-Fineman, Sandra

    2014-08-28

    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.

  20. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    Science.gov (United States)

    2016-12-15

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  1. Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-01-26

    Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma

  2. Sesquiterpene lactones derived from Saussurea lappa induce apoptosis and inhibit invasion and migration in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Keiichi Tabata

    2015-04-01

    Full Text Available Neuroblastoma is among the most fatal of solid tumors in the pediatric age group, even when treated aggressively. Therefore, a new effective therapeutic drug(s for neuroblastoma is urgently needed. To clarify the anticancer effects of the sesquiterpene lactones dehydrocostus lactone and costunolide, derived from Saussurea lappa, we examined the cytotoxic and migration/invasion-inhibitory effects of these compounds against neuroblastoma cell lines. Both the compounds exerted significant cytotoxicity against the neuroblastoma cell lines IMR-32, NB-39, SK-N-SH, and LA-N-1. Evidence of cellular apoptosis, such as nuclear condensation and membrane inversion, were observed after treatment with these compounds. Both compounds induced caspase-7 activation and PARP cleavage as confirmed by Western blotting. Furthermore, the sesquiterpene lactones also suppressed invasion and migration of the neuroblastoma cells. These results suggest that dehydrocostus lactone and costunolide are promising candidates for being developed into novel anticancer drugs effective against neuroblastoma.

  3. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma.

    Science.gov (United States)

    Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theißen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

    2016-07-06

    Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.

  4. How I treat double-hit lymphoma.

    Science.gov (United States)

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  5. Prediction and Analysis of Retinoblastoma Related Genes through Gene Ontology and KEGG

    OpenAIRE

    Zhen Li; Bi-Qing Li; Min Jiang; Lei Chen; Jian Zhang; Lin Liu; Tao Huang

    2013-01-01

    One of the most important and challenging problems in biomedicine is how to predict the cancer related genes. Retinoblastoma (RB) is the most common primary intraocular malignancy usually occurring in childhood. Early detection of RB could reduce the morbidity and promote the probability of disease-free survival. Therefore, it is of great importance to identify RB genes. In this study, we developed a computational method to predict RB related genes based on Dagging, with the maximum relevance...

  6. Illumina next generation sequencing data and expression microarrays data from retinoblastoma and medulloblastoma tissues

    Science.gov (United States)

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

    2016-01-01

    Retinoblastoma (Rb) is a pediatric intraocular malignancy and probably the most robust clinical model on which genetic predisposition to develop cancer has been demonstrated. Since deletions in chromosome 13 have been described in this tumor, we performed next generation sequencing to test whether recurrent losses could be detected in low coverage data. We used Illumina platform for 13 tumor tissue samples: two pools of 4 retinoblastoma cases each and one pool of 5 medulloblastoma cases (raw data can be found at http://www.ebi.ac.uk/ena/data/view/PRJEB6630). We first created an in silico reference profile generated from a human sequenced genome (GRCh37p5). From this data we calculated an integrity score to get an overview of gains and losses in all chromosomes; we next analyzed each chromosome in windows of 40 kb length, calculating for each window the log2 ratio between reads from tumor pool and in silico reference. Finally we generated panoramic maps with all the windows whether lost or gained along each chromosome associated to its cytogenetic bands to facilitate interpretation. Expression microarrays was done for the same samples and a list of over and under expressed genes is presented here. For this detection a significance analysis was done and a log2 fold change was chosen as significant (raw data can be found at http://www.ncbi.nlm.nih.gov/geo/accession number GSE11488). The complete research article can be found at Cancer Genetics journal (Garcia-Chequer et al., in press) [1]. In summary here we provide an overview with visual graphics of gains and losses chromosome by chromosome in retinoblastoma and medulloblastoma, also the integrity score analysis and a list of genes with relevant expression associated. This material can be useful to researchers that may want to explore gains and losses in other malignant tumors with this approach or compare their data with retinoblastoma. PMID:26937470

  7. Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human retinoblastoma.

    Science.gov (United States)

    Singh, Lata; Pushker, Neelam; Saini, Neeru; Sen, Seema; Sharma, Anjana; Bakhshi, Sameer; Chawla, Bhavna; Kashyap, Seema

    2015-04-01

    Regulation of apoptosis is a complex process that involves a number of genes, including Bcl-2, Bcl-x, Bax and other Bcl-2 family members. The aim of the present study is to assess the expression of Bcl- 2 and Bax in retinoblastoma, and correlate them with clinical and histopathological parameters. The expression of Bcl-2 and Bax proteins were examined using immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction in a series of 60 prospective cases of primary retinoblastoma tissues. Immunohistochemistry showed expression of Bcl-2 in 40/60 (66.6%), whereas Bax expression was found only in 18/60 (30%) cases, and these correlated with mRNA expression. The Western blotting results also correlated well with the immunohistochemical expression of Bcl-2 (25 kDa) and Bax (21 kDa) proteins. Bcl-2 was expressed in 96% (24/25) of invasive tumours and in 45.7% (16/35) of non-invasive tumours. Expression of Bcl-2 significantly correlated with tumour invasiveness (P = 0.0274) and poor differentiation (P = 0.0163), whereas loss of Bax correlated with massive choroidal invasion and Pathological Tumor-Node-Metastasis (pTNM) (P = 0.0341). However, no correlation was found between Bax and Bcl-2 expression. Our findings suggest that these apoptotic regulatory proteins may serve as poor prognostic markers and can be used as a therapeutic target for the treatment of invasive retinoblastoma. Further functional studies are required to explore the role of Bax and Bcl-2 in retinoblastoma. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

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

    OpenAIRE

    2014-01-01

    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 tu...

  9. Focused ultrasound facilitated thermo-chemotherapy for targeted retinoblastoma treatment: a modeling study.

    Science.gov (United States)

    Wang, Shutao; Mahesh, Sankaranarayana P; Liu, Ji; Geist, Craig; Zderic, Vesna

    2012-07-01

    Retinoblastoma is the most common type of intraocular tumors in children. Currently, with early detection and improved systemic chemo-adjuvant therapies, treatment paradigm has shifted from survival to globe salvation/vision preservation. The objective of our work has been to explore the possible application of focused ultrasound (FUS) for targeted drug delivery in the posterior pole retinoblastoma. Specifically, theoretical models were implemented to evaluate the feasibility of using FUS to generate localized hyperthermia in retinal tumor areas, for potential triggering the chemotherapeutic agent deployment from heat-sensitive drug carriers. In-vitro experiments were conducted in tissue-mimicking phantoms with embedded excised rabbit eyes to validate the reliability of the modeling results. After confirming the reliability of our model, various FUS transducer parameters were investigated to induce maximal hyperthermia coverage in the tumor, while sparing adjacent eye structures (e.g. the lens). The evaluated FUS parameters included operating frequency, total acoustic power, geometric dimensions, transducer f-number, standoff distance, as well as different pulsing scenarios. Our modeling results suggest that the most suitable ultrasound frequency for this type of treatments was in the range of 2-3.5 MHz depending on the size of retinoblastoma. Appropriate transducer f-number (close to 1) and standoff distance could be selected to minimize the risks of over-heating undesired regions. With the total acoustic power of 0.4 W, 56.3% of the tumor was heated to hyperthermic temperature range (39-44 °C) while the temperature in lens was maintained below 41 °C. In conclusion, FUS-induced hyperthermia for targeted drug delivery may be a viable option in treatments of juxta-foveal or posterior pole retinoblastomas. Future in-vivo studies will allow us to determine the effectiveness and safety of the proposed approach. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. The retinoblastoma protein binds to a family of E2F transcription factors

    DEFF Research Database (Denmark)

    Lees, J A; Saito, M; Vidal, M;

    1993-01-01

    for E2F-2 and E2F-3 were mapped to 1p36 and 6q22, respectfully, confirming their independence from E2F-1. However, the E2F-2 and E2F-3 proteins are closely related to E2F-1. Both E2F-2 and E2F-3 bound to wild-type but not mutant E2F recognition sites, and they bound specifically to the retinoblastoma...

  11. Lymphoma caused by intestinal microbiota.

    Science.gov (United States)

    Yamamoto, Mitsuko L; Schiestl, Robert H

    2014-09-01

    The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT) lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  12. PATHOBIOLOGY OF HODGKIN LYMPHOMA

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    Claudio Agostinelli

    2014-06-01

    Full Text Available Hodgkin’s lymphoma is a lymphoid tumour that represents about 1% of all de novo neoplasms occurring every year worldwide. Its diagnosis is based on the identification of characteristic neoplastic cells within an inflammatory milieu. Molecular studies have shown that most, if not all cases, belong to the same clonal population, which is derived from peripheral B-cells. The relevance of Epstein-Barr virus infection at least in a proportion of patients was also demonstrated. The REAL/WHO classification recognizes a basic distinction between nodular lymphocyte predominance  HL (NLPHL and classic HL (CHL, reflecting the differences in clinical presentation, behavior, morphology, phenotype, molecular features as well as in the composition of their cellular background. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, mixed cellularity and lymphocyte depleted. Despite its well known histological and clinical features, Hodgkin's lymphoma (HL has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics and possible mechanisms of lymphomagenesis.

  13. Haemorrhage and intestinal lymphoma

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    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  14. Rituximab In Indolent Lymphomas

    Science.gov (United States)

    Sousou, Tarek; Friedberg, Jonathan

    2010-01-01

    Indolent Non Hodgkin's lymphoma (NHL) comprises a group of incurable, generally slow growing lymphomas highly responsive to initial therapy with a relapsing and progressive course. Rituximab, an anti CD-20 antibody, has had a large impact on treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials as well as data from the National Cancer Institute indicates that the overall survival of indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, it is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will also be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL however additional research is necessary to identify the optimal dosing schedule as well as patients most likely to respond to prolonged rituximab therapy. PMID:20350660

  15. Obinutuzumab in follicular lymphoma.

    Science.gov (United States)

    Martinez-Calle, N; Figueroa-Mora, R; Villar-Fernandez, S; Marcos-Jubilar, M; Panizo, C

    2016-12-01

    The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.

  16. Hodgkin Lymphoma: Diagnosis and Treatment.

    Science.gov (United States)

    Ansell, Stephen M

    2015-11-01

    Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents.

  17. The tumor suppressor gene retinoblastoma-1 is required for retinotectal development and visual function in zebrafish.

    Directory of Open Access Journals (Sweden)

    Michael Gyda

    Full Text Available Mutations in the retinoblastoma tumor suppressor gene (rb1 cause both sporadic and familial forms of childhood retinoblastoma. Despite its clinical relevance, the roles of rb1 during normal retinotectal development and function are not well understood. We have identified mutations in the zebrafish space cadet locus that lead to a premature truncation of the rb1 gene, identical to known mutations in sporadic and familial forms of retinoblastoma. In wild-type embryos, axons of early born retinal ganglion cells (RGC pioneer the retinotectal tract to guide later born RGC axons. In rb1 deficient embryos, these early born RGCs show a delay in cell cycle exit, causing a transient deficit of differentiated RGCs. As a result, later born mutant RGC axons initially fail to exit the retina, resulting in optic nerve hypoplasia. A significant fraction of mutant RGC axons eventually exit the retina, but then frequently project to the incorrect optic tectum. Although rb1 mutants eventually establish basic retinotectal connectivity, behavioral analysis reveals that mutants exhibit deficits in distinct, visually guided behaviors. Thus, our analysis of zebrafish rb1 mutants reveals a previously unknown yet critical role for rb1 during retinotectal tract development and visual function.

  18. Experimental research of RB94 gene transfection into retinoblastoma cells using ultrasound-targeted microbubble destruction.

    Science.gov (United States)

    Zheng, Min-Ming; Zhou, Xi-Yuan; Wang, Li-Ping; Wang, Zhi-Gang

    2012-06-01

    The purpose of this study was to explore the transfection of the recombinant expression plasmid pEGFP-C1/RB94 into human retinoblastoma cells (HXO-Rb44) using ultrasound-targeted microbubble destruction (UTMD). pEGFP-C1/RB94 was transfected into HXO-Rb44 in vitro by UTMD, with liposome as the positive control. After 24 to 72 h, the expression of the reporter gene enhanced green fluorescent protein (EGFP) was observed using fluorescent microscopy and flow cytometry. The cell viability of HXO-Rb44 was measured by a MTT assay. The mRNA and proteins of RB94, caspase-3 and Bax were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Moreover, the apoptosis rate and cell cycle progression of the cells were detected by flow cytometry. This study demonstrated that UTMD can enhance the transfection efficiency of RB94, which has an obvious impact on the inhibition of the growth process of retinoblastoma cells, suggesting that the combination of UTMD and RB94 compounds might be a useful tool for use in the gene therapy of retinoblastoma.

  19. Clinical features of children with retinoblastoma in Adam Malik Hospital, Medan, Indonesia

    Directory of Open Access Journals (Sweden)

    Bidasari Lubis

    2001-10-01

    Full Text Available We reviewed patents with retinoblastoma treated at the Department of Child Health, Adam Malik Hospital, Medan from January 1995 to December 1999. Clinical staging was based on Reese-Ellsworth classification (when the disease was limited to the eyeball or on St Jude Children's Research Hospital (when the disease has extended beyond the eyeball. A total 19 retinoblastoma patients were available, from which 9 were males. Fifteen patients were less than 5 years old, and the average age at diagnosis was 3 years 8 months. In most patients the disease started at the age of less than 5 years, and they presented themselves with advanced stage as usually seen in developing countries. In nine patients the retinoblastoma affected the right eye, 8 affected the left eye, and in 2 patients the tumor was bilateral. The most common presenting symptom on admission was proptosis. Pathological confirmation was obtained in all patients. Bone marrow puncture was done in 15 patients; of whom 13 showed bone marrow metastasis. Since 1998 the standard treatment for patients with proptosis in stage III or IV of the disease was pre-operative chemotherapy followed by enucleation, radiation and chemotherapy.

  20. Cloning and Sequence Analysis of Light Variable Region Gene of Anti-human Retinoblastoma Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Zhong; Yongping Li; Shuqi Huang; Bo Ning; Chunyan Zhang; Jianliang Zheng; Guanguang Feng

    2002-01-01

    Purpose: To clone the variable region gene of light chain of monoclonal antibody against human retinoblastoma and to analyze the characterization of its nucleotide sequence as well as amino acid sequence.Methods: Total RNA was extracted from 3C6 hybridoma cells secreting specific monoclonal antibody(McAb)against human retinoblastoma(RB), then transcripted reversely into cDNA with olig-dT primers.The variable region of the light chain (VL) gene fragments was amplified using polymeerase chain reaction(PCR) and further cloned into pGEM(R) -T Easy vector. Then, 3C6 VL cDNA was sequenced by Sanger's method.Homologous analysis was done by NCBI BLAST.Results: The complete nucleotide sequence of 3C6 VL cDNA consisted of 321 bp encoding 107 amino acid residues, containing four workframe regions(FRs)and three complementarity-determining regions (CDRs) as well as the typical structure of two cys residues. The sequence is most homological to a member of the Vk9 gene family, and its chain utilizes the Jkl gene segment.Conclusion: The light chain variable region gene of the McAb against human RB was amplified successfully , which belongs to the Vk9 gene family and utilizes Vk-Jk1 gene rearrangement. This study lays a good basis for constructing a recombinant antibody and for making a new targeted therapeutic agents against retinoblastoma.

  1. Aggressive cervical neuroblastoma with a rare paraneoplastic syndrome: A therapeutic dilemma

    Science.gov (United States)

    Qureshi, Sajid S.; Bhagat, Monica; Anam, Jay; Vora, Tushar

    2016-01-01

    Neuroblastoma is infrequently associated with paraneoplastic syndromes. Amongst the few, opsomyoclonus (Kinsbourne syndrome) is the most common neurological paraneoplastic syndrome and diarrhea secondary to increased secretion of vasoactive intestinal peptide (Kerner-Morrison syndrome), hormonal paraneoplastic syndrome. Hypothalamic dysfunction (HD) is a rare disorder and its manifestation as a paraneoplastic syndrome of neuroblastoma is uncommonly reported. We present an interesting case of an unrelenting cervical neuroblastoma associated with HD, which posed a therapeutic challenge. PMID:27695211

  2. RNAi-mediated stathmin suppression reduces lung metastasis in an orthotopic neuroblastoma mouse model.

    Science.gov (United States)

    Byrne, F L; Yang, L; Phillips, P A; Hansford, L M; Fletcher, J I; Ormandy, C J; McCarroll, J A; Kavallaris, M

    2014-02-13

    Metastatic neuroblastoma is an aggressive childhood cancer of neural crest origin. Stathmin, a microtubule destabilizing protein, is highly expressed in neuroblastoma although its functional role in this malignancy has not been addressed. Herein, we investigate stathmin's contribution to neuroblastoma tumor growth and metastasis. Small interfering RNA (siRNA)-mediated stathmin suppression in two independent neuroblastoma cell lines, BE(2)-C and SH-SY5Y, did not markedly influence cell proliferation, viability or anchorage-independent growth. In contrast, stathmin suppression significantly reduced cell migration and invasion in both the neuroblastoma cell lines. Stathmin suppression altered neuroblastoma cell morphology and this was associated with changes in the cytoskeleton, including increased tubulin polymer levels. Stathmin suppression also modulated phosphorylation of the actin-regulatory proteins, cofilin and myosin light chain (MLC). Treatment of stathmin-suppressed neuroblastoma cells with the ROCKI and ROCKII inhibitor, Y-27632, ablated MLC phosphorylation and returned the level of cofilin phosphorylation and cell invasion back to that of untreated control cells. ROCKII inhibition (H-1152) and siRNA suppression also reduced cofilin phosphorylation in stathmin-suppressed cells, indicating that ROCKII mediates stathmin's regulation of cofilin phosphorylation. This data demonstrates a link between stathmin and the regulation of cofilin and MLC phosphorylation via ROCK. To examine stathmin's role in neuroblastoma metastasis, stathmin short hairpin RNA (shRNA)\\luciferase-expressing neuroblastoma cells were injected orthotopically into severe combined immunodeficiency-Beige mice, and tumor growth monitored by bioluminescent imaging. Stathmin suppression did not influence neuroblastoma cell engraftment or tumor growth. In contrast, stathmin suppression significantly reduced neuroblastoma lung metastases by 71% (Pstathmin in hematogenous spread using a clinically

  3. Percutaneous transhepatic biliary drainage in an infant with obstructive jaundice caused by neuroblastoma.

    Science.gov (United States)

    Saettini, Francesco; Agazzi, Roberto; Giraldi, Eugenia; Foglia, Carlo; Cavalleri, Laura; Morali, Laura; Fasolini, Giorgio; Spotti, Angelica; Provenzi, Massimo

    2015-04-01

    Neuroblastoma presenting with obstructive jaundice is a rare event. Management of this condition includes surgery, chemotherapy, radiotherapy, temporary cholecystostomy tube, endoscopic retrograde cholangiopancreatography (ERCP), and internal biliary drainage (IBD). We herein describe our experience with one infant affected by neuroblastoma presenting with jaundice, who successfully underwent percutaneous transhepatic biliary drainage (PTBD). This report introduces PTBD as a viable treatment option for neuroblastoma and obstructive jaundice and provides a review of the pertinent literature.

  4. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Jingbo [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Paul, Pritha; Lee, Sora [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Qiao, Lan; Josifi, Erlena; Tiao, Joshua R. [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Chung, Dai H., E-mail: dai.chung@vanderbilt.edu [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

  5. Serial studies of serum dopamine-B-hydroxylase and urinary vanillylmandelic and homovanillic acids in neuroblastoma.

    Science.gov (United States)

    Brewster, M A; Berry, D H

    1979-01-01

    Recent reports have suggested that elevations of serum dopamine-B-hydroxylase (DBH) activity may correlate with diagnosis in neuroblastoma patients excreting vanillylmandelic acid (VMA). We have serially studied serum DBH and urinary homovanillic acid (HVA) and VMA excretion during the disease course of five patients with neuroblastoma. DBH activities did not indicate clinical course, therapies, or prognosis. Dilution studies revealed an age-related alteration in DBH effectors and they suggest that these may be different in neuroblastoma.

  6. Intermittent Hypoxia Regulates Stem-like Characteristics and Differentiation of Neuroblastoma Cells

    OpenAIRE

    Vasantha Kumar Bhaskara; Indra Mohanam; Jasti S Rao; Sanjeeva Mohanam

    2012-01-01

    BACKGROUND: Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas are derived from immature cells of the sympathetic nervous system and are characterized by clinical and biological heterogeneity. Hypoxia has been linked to tumor progression and increased malignancy. Intermittent hypoxia or repeated episodes of hypoxia followed by re-oxygenation is a common phenomenon in solid tumors including neuroblastoma and it has a significant influence on the outcome of...

  7. TRPM7 maintains progenitor-like features of neuroblastoma cells: implications for metastasis formation.

    Science.gov (United States)

    Middelbeek, Jeroen; Visser, Daan; Henneman, Linda; Kamermans, Alwin; Kuipers, Arthur J; Hoogerbrugge, Peter M; Jalink, Kees; van Leeuwen, Frank N

    2015-04-20

    Neuroblastoma is an embryonal tumor derived from poorly differentiated neural crest cells. Current research is aimed at identifying the molecular mechanisms that maintain the progenitor state of neuroblastoma cells and to develop novel therapeutic strategies that induce neuroblastoma cell differentiation. Mechanisms controlling neural crest development are typically dysregulated during neuroblastoma progression, and provide an appealing starting point for drug target discovery. Transcriptional programs involved in neural crest development act as a context dependent gene regulatory network. In addition to BMP, Wnt and Notch signaling, activation of developmental gene expression programs depends on the physical characteristics of the tissue microenvironment. TRPM7, a mechanically regulated TRP channel with kinase activity, was previously found essential for embryogenesis and the maintenance of undifferentiated neural crest progenitors. Hence, we hypothesized that TRPM7 may preserve progenitor-like, metastatic features of neuroblastoma cells. Using multiple neuroblastoma cell models, we demonstrate that TRPM7 expression closely associates with the migratory and metastatic properties of neuroblastoma cells in vitro and in vivo. Moreover, microarray-based expression profiling on control and TRPM7 shRNA transduced neuroblastoma cells indicates that TRPM7 controls a developmental transcriptional program involving the transcription factor SNAI2. Overall, our data indicate that TRPM7 contributes to neuroblastoma progression by maintaining progenitor-like features.

  8. General Information about Childhood Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ... Treatment Adult NHL Treatment AIDS-Related Lymphoma Treatment Mycosis Fungoides & Sézary Syndrome Treatment Primary CNS Lymphoma Treatment ...

  9. Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma

    Directory of Open Access Journals (Sweden)

    Wan-Ling Ho

    2016-09-01

    Full Text Available Abstract Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLea/x is dependent on the interaction with lectins. Lectins are expressed on the surface of immune cells and endothelial cells or exist as extracellular matrix proteins and soluble adhesion molecules. Expression of tumor-associated glycans is involved in the dysregulation of glycogenes, which mainly comprise glycosyltransferases and glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes are associated with malignant transformation. With better understanding of all aspects of cancer-cell glycomics, many tumor-associated glycans have been utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based therapeutics has been applied to cancers from breast, lung, gastrointestinal system, melanomas, and lymphomas but rarely to neuroblastomas (NBs. The success of anti-disialoganglioside (GD2, a glycolipid antigen antibodies sheds light on glycan-based therapies for NB and also suggests the possibility of protein glycosylation-based therapies for NB. This review summarizes our understanding of cancer glycobiology with a focus of how protein glycosylation and associated glycosyltransferases affect cellular behaviors and treatment outcome of various cancers, especially NB. Finally, we highlight potential applications of glycosylation in drug and cancer vaccine development for NB.

  10. Nano-Bio-Mechanics of Neuroblastoma Cells Using AFM

    Science.gov (United States)

    Bastatas, Lyndon; Matthews, James; Kang, Min; Park, Soyeun

    2011-10-01

    We have conducted an in vitro study to determine the elastic moduli of neurobalstoma cell lines using atomic force microscopy. Using a panel of cell lines established from neuroblastoma patients at different stages of disease progress and treatment, we have investigated the differences in elastic moduli during a course of cancer progression and chemotherapy. The cells were grown on the hard substrates that are chemically functionalized to enhance adhesion. We have performed the AFM indentation experiments with different applied forces from the AFM probe. For the purpose of the comparison between cell lines, the indentations were performed only on cell centers. The obtained force-distance curves were analyzed using the Hertz model in order to extract the elastic moduli. We have found that the elastic moduli of human neuroblastoma cells significantly varied during the disease progression. We postulate that the observed difference might be affected by the treatment and chemotherapy.

  11. New functional imaging modalities for chromaffin tumors, neuroblastomas and ganglioneuromas.

    Science.gov (United States)

    Ilias, Ioannis; Shulkin, Barry; Pacak, Karel

    2005-03-01

    Nuclear medicine modalities use radiolabeled ligands that either follow metabolic pathways or act on cellular receptors. Thus, they permit functional imaging of physiological processes and help to localize sites such as tumors that harbor pathological events. The application of positron emission tomography (PET) ligands to the specific pathways of synthesis, metabolism and inactivation of catecholamines found in chromaffin tumors, neuroblastomas and ganglioneuromas can be used to provide a more thorough localization of these types of tumor. Recent advances have been made in functional imaging to localize pheochromocytomas, paragangliomas, neuroblastomas and ganglioneuromas, including approaches based on PET with [(18)F]fluorodopamine, [(18)F]fluorohydroxyphenylalanine, [(11)C]epinephrine or [(11)C]hydroxyephedrine. Such functional imaging can complement computed tomography or magnetic resonance imaging and other scintigraphic techniques to localize these tumors before surgical or medical therapeutic approaches are considered.

  12. Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma

    Directory of Open Access Journals (Sweden)

    Lejla Mutapcic Vajzovic

    2011-02-01

    Full Text Available Lejla Mutapcic Vajzovic1, Timothy G Murray1, Mohammad A Aziz-Sultan2, Amy C Schefler1, Stacey Quintero Wolfe2, Ditte Hess1, Cristina E Fernandes3, Sander R Dubovy1,41Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Neurological Surgery, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 3Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA; 4Florida Lions Oculopathology Laboratory, Miami, FL, USA Purpose: The purpose of this study is to report the complication profile and safety evaluation of supraselective intra-arterial melphalan chemotherapy in children undergoing treatment with advanced retinoblastoma.Methods: Twelve eyes of 10 children with advanced retinoblastoma (Reese-Ellsworth Group Vb or International Classification Group D were treated with supraselective intra-ophthalmic artery infusion of melphalan. Eleven eyes of nine children had previously failed traditional management with systemic chemotherapy and laser ablation and underwent intra-ophthalmic artery infusion of melphalan as an alternative to enucleation. Serial ophthalmic examinations, retinal photography, and ultrasonographic imaging were used to evaluate treatment regime.Results: Ophthalmic artery cannulation was successfully performed in 12 eyes of 10 patients (total 16 times. Striking regression of tumor, subretinal and vitreous seeds were seen early in each case. No severe systemic side effects occurred. Grade III neutropenia was seen in one patient. No transfusions were required. Three patients developed a vitreous hemorrhage obscuring tumor visualization. One patient developed periocular edema associated with inferior rectus muscle inflammation per orbital MRI. This same patient had scattered intraretinal hemorrhages and peripapillary cotton wool spots consistent with a Purtscher’s-like retinopathy that resolved spontaneously. At the 6-month follow-up examination

  13. Tinospora cordifolia Induces Differentiation and Senescence Pathways in Neuroblastoma Cells.

    Science.gov (United States)

    Mishra, Rachana; Kaur, Gurcharan

    2015-08-01

    Children diagnosed with neuroblastomas often suffer from severe side as well as late effects of conventional treatments like chemotherapy and radiotherapy. Recent advances in understanding of molecular pathways involved in cellular differentiation and apoptosis have helped in the development of new therapeutic approach based on differentiation-based therapy of malignant tumours. Natural medicines with their holistic therapeutic approach are known to selectively eliminate cancer cells thus provide a better substitute for the conventional treatment modes. The current study was aimed to investigate the anti-cancer potential of aqueous ethanolic extract of Tinospora cordifolia (TCE) using IMR-32 human neuroblastoma cell line as a model system. TCE is highly recommended in Ayurveda for its general body and metal health-promoting properties. TCE treatment was seen to arrest the majority of cells in G0/G1 phase and modulated the expression of DNA clamp sliding protein (PCNA) and cyclin D1. Further, TCE-treated cells showed differentiation as revealed by their morphology and the expression of neuronal cell specific differentiation markers NF200, MAP-2 and NeuN in neuroblastoma cells. The differentiated phenotype was associated with induction of senescence and pro-apoptosis pathways by enhancing expression of senescence marker mortalin and Rel A subunit of nuclear factor kappa beta (NFkB) along with decreased expression of anti-apoptotic marker, Bcl-xl. TCE exhibited anti-metastatic activity and significantly reduced cell migration in the scratched area along with downregulation of neural cell adhesion molecule (NCAM) polysialylation and secretion of matrix metalloproteinases (MMPs). Our data suggest that crude extract or active phytochemicals from this plant may be a potential candidate for differentiation-based therapy of malignant neuroblastoma cells.

  14. Lipid mediators in the prevention and therapy of neuroblastoma

    OpenAIRE

    Gleissman, Helena

    2009-01-01

    Neuroblastoma is a cancer of the nervous system that mainly affects infants and young children. It is the most common solid extracranial tumor of childhood, and accounts for almost 10% of all childhood cancer deaths. Despite intense multimodal treatment consisting of surgery, chemotherapy, radiotherapy, and stem cell rescue, survival is only 50% in the high-risk group, and the overall survival is around 70%. We therefore need to improve existing treatment protocols and searc...

  15. Rapidly Evoluting Congenital Cystic Neuroblastoma in a Neonate

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Tae Jun; Kim, Myung Jun; Han, Seok Joo; Lee, Mi Jung [Severance Children' s Hospital, Yonsei University, College of Medicine, Seoul(Korea, Republic of)

    2012-08-15

    Perinatal detection of neonatal suprarenal masses has increased. Here, we report an unusual case of an adrenal cystic neuroblastoma that presented as a purely cystic lesion upon initial postnatal ultrasonography (US) and showed rapid evolution to a mixed cystic and solid mass during follow-up US and MRI. We suggest a short-term (two weeks) follow-up US for neonatal adrenal cystic lesions, even if they appear as purely cystic.

  16. Screening for neuroblastoma in the north of England.

    OpenAIRE

    Parker, L.; Craft, A W; G. Dale; Bell, S.; M Cole; McGill, A C; Seviour, J. A.; Smith, J.

    1992-01-01

    OBJECTIVE--To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN--Prospective study of mass screening in four clearly defined geographical areas. SETTING--Four health districts of the Northern region of England. SUBJECTS--20,829 babies aged 6 months, 92% of target population. INTERVENTIONS--Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME M...

  17. /sup 131/I-meta-iodobenzylguanidine scintigraphy of neuroblastomas

    Energy Technology Data Exchange (ETDEWEB)

    Munkner, T.

    1985-04-01

    Sixteen neuroblastoma patients have been studied by /sup 131/I-meta-iodobenzylguanidine (MIBG) scintigraphy. Three patients were possibly cured, and their scintigraphy results were normal. Thirteen patients had tumors and metastases demonstrated by /sup 131/I-MIBG, two of these patients had a normal vanillylmandelic acid (VMA) excretion level. One patient has been treated by /sup 131/I-MIBG, but died. /sup 131/I-MIBG was concentrated in other cells too, eg, in erythrocytes and platelets.

  18. Ultra-high Density SNParray in Neuroblastoma Molecular Diagnostics

    Directory of Open Access Journals (Sweden)

    Inge M. Ambros

    2014-08-01

    Full Text Available Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e. amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses: so called segmental chromosomal aberrations, i.e. gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as chromothripsis are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism (SNP arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

  19. Proton therapy for Hodgkin lymphoma.

    Science.gov (United States)

    Rutenberg, Michael S; Flampouri, Stella; Hoppe, Bradford S

    2014-09-01

    Hodgkin lymphoma has gone from an incurable disease to one for which the majority of patients will be cured. Combined chemotherapy and radiotherapy achieves the best disease control rates and results in many long-term survivors. As a result, a majority of long-term Hodgkin lymphoma survivors live to experience severe late treatment-related complications, especially cardiovascular disease and second malignancies. The focus of research and treatment for Hodgkin lymphoma is to maintain the current high rates of disease control while reducing treatment-related morbidity and mortality. Efforts to reduce late treatment complications focus on improvements in both systemic therapies and radiotherapy. Herein we review the basis for the benefits of proton therapy over conventional X-ray therapy. We review outcomes of Hodgkin lymphoma treated with proton therapy, and discuss the ability of protons to reduce radiation dose to organs at risk and the impact on the most significant late complications related to the treatment.

  20. Intracranial manifestations of malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Galanski, M.; Fahrendorf, G.; Urbanitz, D.; Beckmann, A.; Elger, C.

    1985-06-01

    Approximately 10% of patients with malignant lymphoma will show neurological symptoms at some time during the course of their illness. In non-Hodgkin lymphoma, CNS involvement is more frequent than in Hodgkin's disease. Diffuse histiocytic and poorly differentiated lymphomas, bone marrow involvement, advanced tumor stage and hematogenous spread are particular risk factors. Invasion of the spinal canal is the most common type of CNS involvement. Intracranial lesions, which are comparatively rare, may present as intracerebral metastases, epi- or subdural masses or focal or diffuse leptomeningeal disease. Lymphomatous leptomeningitis usually cannot be demonstrated by CT. On the other hand, dural and cerebral parenchymal lesions are sometimes highly characteristic of lymphoma as a result of their features and location.

  1. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  2. Nuclear medicine and multimodality imaging of pediatric neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Wolfgang Peter; Pfluger, Thomas [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Coppenrath, Eva [Ludwig-Maximilians-University of Munich, Department of Radiology, Munich (Germany)

    2013-04-15

    Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system and is metastatic or high risk for relapse in nearly 50% of cases. Therefore, exact staging with radiological and nuclear medicine imaging methods is crucial for defining the adequate therapeutic choice. Tumor cells express the norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG imaging has several disadvantages, such as limited spatial resolution, limited sensitivity in small lesions and the need for two or even more acquisition sessions. Most of these limitations can be overcome with positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new tracers, such as fluorodopa or somatostatin receptor agonists, have been tested for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are not sufficient for operative or biopsy planning. In this regard, a combination with morphological imaging is indispensable. This article will discuss strategies for primary and follow-up diagnosis in neuroblastoma using different nuclear medicine and radiological imaging methods as well as multimodality imaging. (orig.)

  3. Diagnosis of neonatal neuroblastoma with postmortem magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    James Davis, MD

    2017-03-01

    Full Text Available Postmortem magnetic resonance imaging (MRI is emerging as a valuable tool to accompany traditional autopsy and has potential for use in cases when traditional autopsy is not possible. This case report will review the use of postmortem MRI with limited tissue sampling to differentiate between metastatic neuroblastoma and hepatoblastoma which could not be clearly differentiated with prenatal ultrasound, prenatal MRI, or emergent postnatal ultrasound. The mother presented to our institution at 27 weeks gestation after an obstetric ultrasound at her obstetrician's office identified a large abdominal mass. Fetal ultrasonography and MRI confirmed the mass but were unable to differentiate between neuroblastoma and multifocal hepatoblastoma. The baby was delivered by cesarean section after nonreassuring heart tones led to an emergent cesarean section. The baby underwent decompressive laparotomy to relieve an abdominal compartment syndrome; however, the family eventually decided to withdraw life support. At this time, we performed a whole body postmortem MRI which further characterized the mass as an adrenal neuroblastoma which was confirmed with limited tissue sampling. Postmortem MRI was especially helpful in this case, as the patient’s family declined traditional autopsy.

  4. Diagnosis of neuroblastoma with I-131 meta-iodobenzylguanidine scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Odano, Ikuo; Ohsawa, Yoshihiro; Iwabuchi, Makoto; Sakai, Kunio; Hayashi, Mikio (Niigata Univ. (Japan). School of Medicine); Asami, Keiko; Utsumi, Jiro

    1991-01-01

    Pre- or post-operative I-131 meta-iodobenzylguanidine (I-131 MIBG) scans were reviewed for its diagnostic significance in neuroblastoma. The subjects were 18 patients with histologically proven neuroblastoma, who ranged in age from 6 months to 9 years. Abnormal uptake of I-131 MIBG was detected in all 10 patients showing positive urinary vanillylmandelic acid (VMA); there was a significant correlation between I-131 MIBG uptake and urinary VMA. For 10 patients undergoing preoperative I-131 MIBG scans, I-131 MIBG was taken up by primary tumors as small as one cm in diameter in 9 patients; the other one had negative urinary VMA. In detecting metastatic foci, the sensitivity of I-131 MIBG scans was 89% for the bone, 50% for the liver, 75% for the lymph nodes, and 38% for the bone marrow. In view of a high specificity, I-131 MIBG scintigraphy may be a useful approach to the localization of primary foci, as well as the diagnosis of metastasis and recurrence in neuroblastoma. (N.K.).

  5. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  6. A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-01-24

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  7. Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-07-10

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  8. Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients

    Science.gov (United States)

    2016-08-22

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III/IV Adult Diffuse Large Cell Lymphoma; Stage III/IV Follicular Lymphoma; Stage III/IV Mantle Cell Lymphoma

  9. microRNA-497 overexpression decreases proliferation, migration and invasion of human retinoblastoma cells via targeting vascular endothelial growth factor A

    Science.gov (United States)

    Li, Jianjun; Zhang, Yinghui; Wang, Xiuchao; Zhao, Ruibo

    2017-01-01

    The expression level and roles of microRNA-497 (miR-497) have been frequently reported in previous studies on cancer. However, its expression, function and associated molecular mechanisms in retinoblastoma remain unknown. In the present study, miR-497 expression levels in human retinoblastoma tissues, normal retinal tissues and retinoblastoma cell lines were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a Cell Counting Kit-8 assay, cell migration assay, cell invasion assay, western blot analysis and Dual-Luciferase reporter assay were used to explore the expression, functions and molecular mechanisms of miR-497 in human retinoblastoma. It was demonstrated that miR-497 was significantly downregulated in retinoblastoma tissues and cell lines compared with normal retinal tissues. Ectopic expression of miR-497 decreased the proliferation, migration and invasion of retinoblastoma cells. Furthermore, VEGFA was verified as a potential direct target of miR-497 in vitro. Taken together, the results indicate that miR-497 functions as a tumor suppressor in the carcinogenesis and progression of retinoblastoma via targeting VEGFA. miR-497 should be investigated as a potential therapeutic target for the treatment of retinoblastoma. PMID:28588740

  10. Primary lymphoma of the colon

    Directory of Open Access Journals (Sweden)

    Tauro Leo

    2009-01-01

    Full Text Available Primary lymphoma of the colon is a rare tumor of the gastrointestinal (GI tract and comprises only 0.2-1.2% of all colonic malignancies. The most common variety of colonic lymphoma is non-Hodgkin′s lymphoma (NHL. The GI tract is the most frequently involved site, accounting for 30-40% of all extra nodal lymphomas, approximately 4-20% of which are NHL. The stomach is the most common location of GI lymphomas, followed by the small intestine. Early diagnosis may prevent intestinal perforation; however, the diagnosis is often delayed in most cases. Therapeutic approaches described in two subsets include: Radical tumor resection (hemicolectomy plus multi-agent chemotherapy (polychemotherapy in early stage patients, biopsy plus multidrug chemotherapy in advanced stage patients. Radiotherapy is reserved for specific cases; surgery alone can be considered as an adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the sub mucosa. Although resection plays an important role in the local control of the disease and in preventing bleeding and/or perforation, it rarely eradicates the lymphoma by itself. Those with limited stage disease may enjoy prolonged survival when treated with aggressive chemotherapy.

  11. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  12. Expression of multidrug resistance-related markers in primary neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    吕庆杰; 董芳; 张锦华; 李晓晗; 马颖; 姜卫国

    2004-01-01

    Background Multidrug resistance is associated with a poor prognosis in various human cancers. However, the clinical significance of the expression of multidrug resistance-related markers in neuroblastoma is still on debate. In this study, the effect of the expression of p-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and lung resistance protein (LRP) in neuroblastoma was evaluated. Methods The streptavidin-biotin immunoperoxidase (SP) technique was used to evaluate the expression of P-gp, MRP, and LRP in 70 cases of untreated primary neuroblastoma. Results The frequencies of the expression of P-gp, MRP, and LRP were 61.4%, 38.6%, and 24.3%, respectively. A significant positive correlation was observed between P-gp and MRP expression (P=0.001), as well as between LRP and MRP expression (P=0.01). The rates of expression of P-gp and MRP were higher in tumors from patients aged greater than one year old than in tumors from patients aged less than 1 year old at time of diagnosis (P=0.01 and 0.018, respectively). MRP expression in tumors that had metastasized was significantly more frequent than in tumors that had not metastasized (P=0.015). The expression of all tested proteins showed a significant relationship with whether or not the tumor had differentiated (P=0.006, 0.000 or 0.001, respectively). MRP expression was significantly associated with a reduction in both median survival time and 2-year cumulative survival (P=0.02). By contrast, P-gp and MRP expression did not correlate with survival. According to Cox regression analysis, only the co-expression of P-gp and MRP had significant prognostic value (relative hazard, 3.513, P=0.033). Conclusions The intrinsic, multidrug resistance of neuroblastoma involves the combined effects of P-gp, MRP, and LRP. MRP expression may be an important factor determining prognosis in neuroblastoma.

  13. 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

  14. Synthesis of New Quinoxalines Containing an Oxirane Ring by the TDAE Strategy and in Vitro Evaluation in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Marc Montana

    2014-09-01

    Full Text Available Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. In order to obtain new compounds active on neuroblastoma cell lines, we investigated the reactivity of carbanion formed via TDAE in quinoxaline series. The new synthesized compounds were tested for their anti-proliferative activity on two neuroblastoma cell lines, and seven oxirane derivatives obtained interesting activities.

  15. Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

    Science.gov (United States)

    2017-08-14

    AIDS-Related Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Stage II Hodgkin Lymphoma; Stage IIA Hodgkin Lymphoma; Stage IIB Hodgkin Lymphoma; Stage III Hodgkin Lymphoma; Stage IIIA Hodgkin Lymphoma; Stage IIIB Hodgkin Lymphoma; Stage IV Hodgkin Lymphoma; Stage IVA Hodgkin Lymphoma; Stage IVB Hodgkin Lymphoma

  16. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    Science.gov (United States)

    2016-01-04

    Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  17. Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma

    Science.gov (United States)

    2016-04-25

    Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  18. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2016-04-18

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  19. 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

    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......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...

  20. TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells

    NARCIS (Netherlands)

    Boes, Marianne; Meyer-Wentrup, Friederike

    2015-01-01

    Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblast

  1. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma

    NARCIS (Netherlands)

    Spel, Lotte; Boelens, Jaap Jan; Van Der Steen, Dirk M.; Blokland, Nina J G; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H M; Boes, Marianne; Nierkens, Stefan

    2015-01-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20-40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neurobla

  2. PGK1 as Predictor of CXCR4 Expression, Bone Marrow Metastases and Survival in Neuroblastoma

    Science.gov (United States)

    von Loga, Katharina; Escherich, Gabriele; Wenke, Katharina; Izbicki, Jakob R.; Reinshagen, Konrad; Gros, Stephanie J.

    2013-01-01

    Background and Aim A close relationship between phosphoglycerate kinase 1 (PGK1) and the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) has been shown for several cancers. However, the role of PGK1 has not been investigated for neuroblastoma, and PGK1 might be a therapeutic target for this tumor entity. The aim of the current study was to evaluate the role of PGK1 expression in neuroblastoma patients, to determine the impact of PGK1 expression levels on survival, and to correlate PGK1 expression with CXCR4 expression and bone marrow dissemination. Materials and Methods Samples from 22 patients with neuroblastoma that were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated for expression of PGK1 and CXCR4 using immunohistochemistry. Results were correlated with clinical parameters, metastases and outcome of patients. Immunocytochemistry, proliferation and expression analysis of CXCR4 and PGK1 were performed in neuroblastoma cell lines. Results PGK1 is expressed in neuroblastoma cells. PGK1 expression is significantly positively correlated with CXCR4 expression and tumor dissemination to the bone marrow. Moreover the expression of PGK1 is significantly associated with a negative impact on survival in patients with neuroblastoma. PGK1 is downregulated by inhibition of CXCR4 in neuroblastoma cells. Conclusion PGK1 appears to play an important role for neuroblastoma, predicting survival and tumor dissemination. Further in vivo studies outstanding, it is a candidate target for novel therapeutic strategies. PMID:24376734

  3. PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Helen M Ameis

    Full Text Available BACKGROUND AND AIM: A close relationship between phosphoglycerate kinase 1 (PGK1 and the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1 has been shown for several cancers. However, the role of PGK1 has not been investigated for neuroblastoma, and PGK1 might be a therapeutic target for this tumor entity. The aim of the current study was to evaluate the role of PGK1 expression in neuroblastoma patients, to determine the impact of PGK1 expression levels on survival, and to correlate PGK1 expression with CXCR4 expression and bone marrow dissemination. MATERIALS AND METHODS: Samples from 22 patients with neuroblastoma that were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated for expression of PGK1 and CXCR4 using immunohistochemistry. Results were correlated with clinical parameters, metastases and outcome of patients. Immunocytochemistry, proliferation and expression analysis of CXCR4 and PGK1 were performed in neuroblastoma cell lines. RESULTS: PGK1 is expressed in neuroblastoma cells. PGK1 expression is significantly positively correlated with CXCR4 expression and tumor dissemination to the bone marrow. Moreover the expression of PGK1 is significantly associated with a negative impact on survival in patients with neuroblastoma. PGK1 is downregulated by inhibition of CXCR4 in neuroblastoma cells. CONCLUSION: PGK1 appears to play an important role for neuroblastoma, predicting survival and tumor dissemination. Further in vivo studies outstanding, it is a candidate target for novel therapeutic strategies.

  4. Scrotal hematoma, anemia, and jaundice as manifestations of adrenal neuroblastoma in a newborn

    NARCIS (Netherlands)

    Kreeftenberg, HG; Zeebregts, CJAM; Tamminga, RYJ; de Langen, ZJ; Zijlstra, RJ

    1999-01-01

    Clinically, a neuroblastoma presents mostly as an abdominal mass. Within the tumor, bleeding can be present, sometimes extending in to its surroundings. This case report describes a neuroblastoma, presenting as scrotal hematoma in a newborn boy, which initially raised the suspicion of a torsio

  5. Comparison of the Side Populations in Pretreatment and Postrelapse Neuroblastoma Cell Lines

    Science.gov (United States)

    2010-08-01

    needed if we are to improve outcomes in high- risk neuroblastoma. References [1] Maris JM, Hogarty MD, Bagatell R, and Cohn SL (2007). Neuroblastoma...stem– like cells are enriched partly but not exclusively. Endocrinology 148, 1797–1803. [26] Kondo T, Setoguchi T, and Taga T (2004). Persistence of

  6. Scrotal hematoma, anemia, and jaundice as manifestations of adrenal neuroblastoma in a newborn

    NARCIS (Netherlands)

    Kreeftenberg, HG; Zeebregts, CJAM; Tamminga, RYJ; de Langen, ZJ; Zijlstra, RJ

    1999-01-01

    Clinically, a neuroblastoma presents mostly as an abdominal mass. Within the tumor, bleeding can be present, sometimes extending in to its surroundings. This case report describes a neuroblastoma, presenting as scrotal hematoma in a newborn boy, which initially raised the suspicion of a torsio testi

  7. Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma

    NARCIS (Netherlands)

    Cuperus, R.; Leen, R.; Tytgat, G.A.M.; Caron, H.N.; van Kuilenburg, A.B.P.

    2010-01-01

    Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin,

  8. Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma

    NARCIS (Netherlands)

    Cuperus, R.; Leen, R.; Tytgat, G.A.M.; Caron, H.N.; van Kuilenburg, A.B.P.

    2010-01-01

    Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demo

  9. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma

    NARCIS (Netherlands)

    Bleeker, Gitta; Tytgat, Godelieve A M; Adam, Judit A; Caron, Huib N; Kremer, Leontien C M; Hooft, Lotty; van Dalen, Elvira C

    2015-01-01

    BACKGROUND: Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be use

  10. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

    2009-01-01

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining T-cel

  11. The NADPH oxidase inhibitor imipramine-blue in the treatment of Burkitt lymphoma.

    Science.gov (United States)

    Klingenberg, Marcel; Becker, Jürgen; Eberth, Sonja; Kube, Dieter; Wilting, Jörg

    2014-04-01

    Burkitt lymphoma is a rare malignancy arising from B cells. Current chemotherapeutic regimens achieve excellent overall survival rates in children, but less impressive rates in adults. There are cases with poor outcome caused by toxic effects of the therapy, tumor lysis syndrome, or metastatic spread of lymphomas to the central nervous system. Modulators of reactive oxygen species are currently discussed as potential drugs for the treatment of cancer. The NADPH oxidase 4 inhibitor imipramine-blue might satisfy the aforementioned requirements, and was studied here. We used MTT assay, crystal violet assay, and thymidine 3H-incorporation assay to analyze the effects of imipramine-blue on Burkitt lymphoma (BL2, BL2B95, BL30B95, BL41B95), neuroblastoma (KELLY, SH-SY5Y, SMS-KAN), cervix carcinoma (HeLa), breast cancer (MDA-MB231), angiosarcoma (AS-M), human embryonic kidney (HEK293WT), and nonmalignant (FLP1) cell lines. The effects of imipramine-blue on BL2B95 cells in vivo were investigated in xenografts on the chick chorioallantoic membrane (CAM). We report that imipramine-blue is a potent growth inhibitor for several cancer cell lines in vitro with IC(50) values comparable to those of doxorubicin (0.16-7.7 μmol/L). Tumor size of BL2B95 cells inoculated in the CAM was reduced significantly (P imipramine-blue. Lymphogenic dissemination of BL2B95 and the formation of blood and lymphatic vessels in experimental tumors were not affected. We show that imipramine-blue can be used to decrease the viability of cancer cell lines in vitro and in vivo. Imipramine-blue reduces the size of experimental Burkitt lymphoma significantly but does not affect the dissemination of BL2B95 cells, angiogenesis, and lymphangiogenesis.

  12. Genetically Engineered Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Indolent B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2014-08-04

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  13. Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

    Science.gov (United States)

    2016-09-12

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

  14. Lymphomagenesis in Hodgkin lymphoma.

    Science.gov (United States)

    Matsuki, Eri; Younes, Anas

    2015-10-01

    Hodgkin lymphoma (HL) accounts for approximately 0.6% of all new cancer cases, 10% of all lymphomas in the USA, leading to an approximate 9000 new cases per year. It is very unique in that the neoplastic Hodgkin and Reed-Sternberg (HRS) cells of classical HL account for only 1% of the tumor tissue in most cases, with various inflammatory cells including B-cells, T-cells, mast cells, macrophages, eosinophils, neutrophils, and plasma cells comprising the tumor microenvironment. Recent research has identified germinal center B-cells to be the cellular origin of HRS cells. Various transcription factor dysregulation in these neoplastic cells that explains for the loss of B-cell phenotype as well as acquisition of survival and anti-apoptotic features of HRS cells has been identified. Aberrant activation of nuclear factor-kappa B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and phosphoinositide 3-kinase (PI3K) pathways play a central role in HL pathogenesis. Both intrinsic genetic mechanisms as well as extrinsic signals have been identified to account for the constitutive activation of these pathways. The extrinsic factors that regulate the activation of transcription pathways in HRS cells have also been studied in detail. Cytokines and chemokines produced both by the HRS cells as well as cells of the microenvironment of HL work in an autocrine and/or paracrine manner to promote survival of HRS cells as well as providing mechanisms for immune escape from the body's antitumor immunity. The understanding of various mechanisms involved in the lymphomagenesis of HL including the importance of its microenvironment has gained much interest in the use of these microenvironmental features as prognostic markers as well as potential treatment targets. In this article, we will review the pathogenesis of HL starting with the cellular origin of neoplastic cells and the mechanisms supporting its pathogenesis, especially focusing on the

  15. Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-01

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  16. Adult Neuroblastoma Complicated by Increased Intracranial Pressure: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Patrick L. Stevens

    2014-01-01

    Full Text Available Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures. The patient was treated with systemic chemotherapy, I131 metaiodobenzylguanidine (MIBG radiotherapy, and autologous stem cell transplant (SCT. Unfortunately the patient’s response to therapy was limited and she subsequently died. We aim to review neuroblastoma in the context of increased intracranial pressure and the limited data of neuroblastoma occurring in the adult population, along with proposed treatment options.

  17. Ectopic olfactory neuroblastoma: report of four cases and a review of the literature.

    LENUS (Irish Health Repository)

    Wormald, R

    2011-04-01

    Our objective is to present a short series of four rare cases of ectopic olfactory neuroblastoma. Our methods present four case reports of ectopic olfactory neuroblastoma and a review of the literature for management and treatment of this disease. The results indicate short case series reports of ectopic olfactory neuroblastoma arising from the anterior ethmoidal sinuses, the nasopharynx, the lateral nasal wall and the floor of the nose. The discussion focuses on likely origins of ectopic olfactory neuroblastoma, its clinical features and management. We conclude that ectopic olfactory neuroblastoma is a rare disease. Treatment principles are the same for non-ectopic disease and guided by extension into adjacent structures such as the orbit or anterior cranial fossa and usually involves surgery with or without adjuvant radiotherapy.

  18. 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.

  19. 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.

  20. Follicular lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, E.; Prause, J.U.

    2015-01-01

    with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42–96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma...

  1. Cutaneous natural killer/T-cell lymphoma.

    Science.gov (United States)

    Radonich, Michael A; Lazova, Rossitza; Bolognia, Jean

    2002-03-01

    Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic findings.

  2. Managing Risk in Hodgkin Lymphoma.

    Science.gov (United States)

    Armitage, James O; Chen, Robert W; Moskowitz, Craig H; Sweetenham, John

    2015-02-01

    Approximately 90% of patients with limited-stage Hodgkin lymphoma are cured. The cure rate in advanced-stage Hodgkin lymphoma is dramatically better than it once was, but it is still lower than the rate in patients with limited disease. The choice of treatment is based on several factors, including symptoms, disease stage, extent of tumor burden, and prognosis. Positron emission tomography scanning can be used to assess the patient's stage of disease, which can allow further individualization of therapy. Traditional frontline treatment options include doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and, for high-risk patients, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Autologous stem cell transplantation cures approximately 50% of patients. The antibody-drug conjugate brentuximab vedotin is very active in relapsed/refractory Hodgkin lymphoma. Data presented at the 2014 meeting of the American Society of Hematology (ASH) showed that brentuximab vedotin was beneficial in several settings, including as consolidation therapy posttransplant in patients at high risk for relapse, as first-line salvage therapy in relapsed/refractory Hodgkin lymphoma prior to autologous hematopoietic cell transplantation, and in combination with bendamustine in relapsed/refractory disease. The ASH meeting also offered promising data on novel agents, such as the programmed cell death 1 (PD-1) inhibitors. In this monograph, 4 experts in the management of Hodgkin lymphoma discuss various aspects of the disease and provide their perspectives on the new data presented at the ASH meeting.

  3. Case presentation – thyroid lymphoma

    Directory of Open Access Journals (Sweden)

    Belkisa Izić

    2011-11-01

    Full Text Available Malignant tumors of the thyroid gland account for about 1% of thenewly diagnosed malignant tumors each year, and their incidence inwomen is twice the incidence in men. According to the WHO classification (2004 thyroid tumors are divided into: carcinoma of the thyroid, adenoma and similar tumors, and other thyroid tumors which include: teratomas, angiosarcomas, paragangliomas and others, as well as primary lymphomas and plasmacytomas. Primary thyroid lymphomasare defined as lymphomas which originate in the thyroid gland. This study presents the case of a 68-year-old patient with a thyroid lymphoma, which caused compression of the airways. In the patientpresented there was reduced activity of the thyroid gland. The dominant symptoms were: breathing difficulties, hoarse voice and the enlargement of the thyroid. An ultrasound examination was performedbefore surgery on the neck, which showed a multinodular thyroid,with compromised and compressed trachea to the right and rear. Anemergency surgical procedure was performed to reduce the tumor.Pathohistological diagnosis confirmed diffuse large B cell lymphoma.The aim of the study was to present a patient with a thyroid lymphoma, who had previously not had any immunological changes to the gland,that is, she had not had any chronic lymphocyte thyroiditis, but due to the compressive syndrome it was necessary to perform an emergencysurgical procedure to reduce the tumor.

  4. Ocular Salvage and Vision Preservation Using a Topotecan-Based Regimen for Advanced Intraocular Retinoblastoma.

    Science.gov (United States)

    Brennan, Rachel C; Qaddoumi, Ibrahim; Mao, Shenghua; Wu, Jianrong; Billups, Catherine A; Stewart, Clinton F; Hoehn, Mary Ellen; Rodriguez-Galindo, Carlos; Wilson, Matthew W

    2017-01-01

    Purpose To evaluate topotecan-based therapy for advanced intraocular retinoblastoma. Patients and Methods Twenty-seven patients with bilateral retinoblastoma (male patients, n = 14; median age, 8.4 months) received chemotherapy: two courses of topotecan plus vincristine followed by three alternating administrations of carboplatin and vincristine for two courses and topotecan plus vincristine for one course, with optional periocular carboplatin. Focal therapy was applied after cycle 2. Event-free survival was defined as avoidance of external-beam radiotherapy (EBRT) and enucleation. Results Of 54 eyes, 42 were Reese-Ellsworth group IV to V, and 37 were International Classification of Retinoblastoma group C to E. Eleven eyes were enucleated: one at diagnosis, nine with progressive disease including three eyes treated with EBRT, and one that developed neovascular glaucoma after completion of therapy. One patient was removed from protocol with prolonged infection in course 1; 26 patients (51 eyes) were analyzed. At 10 years, cumulative incidence of EBRT was 5.9% (SE ± 3), and event-free survival was 69.2% (SE ± 27.2). Ocular survival for Reese-Ellsworth group IV to V eyes was 77.5% (SE ± 21.2); it was 74.3% (SE ≥ 18.8) for International Classification group C to E eyes. Vision testing (median age, 7 years; range, 5 to 10 years) documented 20/70 vision or better in one eye of 23 patients; 19 (76%) of 25 patients demonstrated 20/40 vision or better in one eye. All patients experienced thrombocytopenia (41 episodes in 275 courses; 15%). There were 29 episodes of febrile neutropenia (10%). Grade 3 diarrhea was present in nine of 27 patients, and one patient had an allergic reaction to carboplatin. All patients are alive at median follow-up 7.4 years (range, 2.7 to 10 years). Conclusion Topotecan combined with vincristine, carboplatin, and aggressive focal therapies is an effective regimen for the treatment of advanced retinoblastoma and results in globe salvage with

  5. 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).

  6. Detection of Tumor Suppressor Gene and Oncogene in SO-Rb_(50) Human Retinoblastoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Retinoblastoma (Rb) is the most common malignant'cancer of eye. So-Rb_(50) is the first Rb cell line established in China in 1988. It has passed to the 387th passage now. We collected cells of the 327th passage of SO-Rb_(50), purified its genomic DNA and detected it with Rb and c-myc cDNA probes respectively (normal human white blood cells DNA was the control). We found the Rb gene was deleted while c-myc gene was amplified three times. This provides a basis for further study of the regulation of tumor ...

  7. 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

    activation. Here, we show that, in a series of human colorectal adenomas, those with deregulation of cyclin D1 and/or p16(Ink4a) showed little evidence of constitutive DNA damage response (DDR), contrary to cyclin E-overexpressing higher-grade cases. These observations were consistent with diverse cell...... 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...

  8. Primary central nervous system B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma.

    Science.gov (United States)

    Jiang, Liuyan; Li, Zhimin; Finn, Laura E; Personnet, David A; Edenfield, Brandy; Foran, James M; Jaeckle, Kurt A; Reimer, Ronald; Menke, David M; Ketterling, Rhett P; Tun, Han W

    2012-01-01

    B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new lymphoma entity which is recognized in the current World Health Organization (WHO) classification (2008). We report a case of a primary central nervous system lymphoma (PCNSL) with findings consistent with DLBCL/BL. It is characterized by a very aggressive clinical course, and a widespread multifocal involvement of the CNS. Our case shows that a DLBCL/BL can manifest in the CNS alone without any systemic involvement.

  9. Primary thyroid lymphoma: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo-Cheol; Han, Moon Hee E-mail: hanmh@radcom.snu.ac.kr; Kim, Keon Ha; Jae, Hwan Jun; Lee, Sang Hyun; Kim, Sam Soo; Kim, Kwang Hyun; Chang, Kee-Hyun

    2003-06-01

    Introduction: To evaluate the computed tomographic (CT) findings of primary thyroid lymphoma. Methods and material: The clinicopathological data and CT images of nine patients with primary thyroid lymphoma were retrospectively reviewed. The CT appearances were classified into three types: type 1, a solitary nodule surrounded by normal thyroid tissue; type 2, multiple nodules in the thyroid, and type 3, a homogeneously enlarged both thyroid glands with a reduced attenuation with or without peripheral thin hyperattenuating thyroid tissue. Results: All patients had a rapidly enlarging thyroid mass and coexistent Hashimoto's thyroiditis. One patient showed type 1 pattern, three type 2, and five type 3. Six patients had homogeneous tumor isoattenuating to surrounding muscles. The tumors had a strong tendency to compress normal remnant thyroid and the surrounding structure without invasion. Conclusion: Primary thyroid lymphoma should be included in the differential diagnosis when old female had a homogeneous thyroidal mass isoattenuating to muscles, which does not invade surrounding structures.

  10. Radiation therapy of follicular lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Koguchi, Masahiko; Nakamura, Naoki; Tsubokura, Takuji; Gomi, Koutarou; Yamashita, Takashi [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital; Shikama, Naoto

    2001-09-01

    The follicular lymphoma, exactly, the cancer of follicular center and germinal center B lymphocytes, is reviewed on its immunological, pathological and genetic diagnoses, epidemiology, clinical symptoms, prognosis factors, therapy and assessment of therapy effects together with respective therapy of follicular small cleaved and follicular mixed small cleaved and large cell lymphoma of grade I, II; and of follicular large cell lymphoma of grade III. The therapy is essentially the radiotherapy combined with chemotherapy and others, of which effect is mainly assessed by CT. In clinical application grade II, III, irradiation of X- and electron rays and their combination is done in a fractionated manner with the maximal dose of around 35 Gy. In clinical disease grade II, III, regimen of irradiation is not fixed. In III, IV, chemotherapy and immunotherapy are major. In recurrence and malignant transformation, there is a report of large dose chemotherapy + whole body irradiation + bone marrow transplantation. (K.H.)

  11. Sam68 is a novel marker for aggressive neuroblastoma

    Directory of Open Access Journals (Sweden)

    Zhao X

    2013-12-01

    Full Text Available Xiaohong Zhao,1,* Zuoqing Li,2,* Benfu He,3 Juncheng Liu,2 Suisheng Li,2 Li Zhou,2 Cuiling Pan,2 Zhe Yu,4 Zhe Xu21State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, 2Department of Pediatric Surgery, First Affiliated Hospital of Sun Yat-sen University, 3Oncology Department, PLA421 Hospital, 4Laura Biotech Co, Ltd, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Neuroblastoma (NB is the most common solid extracranial tumor in children. However, the molecular mechanism and progression of NB is largely unknown, and unfortunately, the prognosis is poor. Src-associated in mitosis with a molecular weight of 68 kDa (Sam68 is associated with carcinogenesis and neurogenesis. The present study aimed to investigate the clinical and prognostic significance of Sam68 in NB.Methods: The expression of Sam68 in immortalized normal epithelial cells, NB cell lines, and in four cases of paired NB tissue and adjacent normal tissue from the same patient was examined using Western blotting, reverse transcription-polymerase chain reaction (PCR and real-time reverse transcription-PCR. The proliferation of NB cells was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Furthermore, Sam68 protein expression was analyzed in 90 NB cases characterized as clinicopathological using immunohistochemistry. Statistical analyses were applied to evaluate the diagnostic value and associations of Sam68 with clinical parameters.Results: Western blotting and reverse transcription-PCR showed that the expression level of Sam68 was markedly higher in NB cell lines than in the immortalized normal epithelial cells at both messenger RNA and protein levels. The MTT assay revealed that Sam68 expression supported proliferation of NB cells. Sam68 expression levels were significantly up-regulated in tumor tissues in comparison to the

  12. Revealed: The spy who regulates neuroblastoma stem cells.

    Science.gov (United States)

    Vora, Parvez; Venugopal, Chitra; Singh, Sheila K

    2014-11-30

    Neuroblastoma (NB), an embryonal tumour of the sympathetic nervous system, is thought to originate from undifferentiated neural crest cells and is known to exhibit extremely heterogeneous biological and clinical behaviors. Occurring in very young children, the median age at diagnosis is 17 months and it accounts for 10% of all pediatric cancer mortalities. The standard treatment regimen for patients with high-risk NB includes induction and surgery followed by isotretinoin or Accutane (13-cis retinoic acid) treatment, which is shown to induce terminal differentiation of NB cells. However, molecular regulators that maintain an undifferentiated phenotype in NB cells are still poorly understood.

  13. Metastatic mandibular neuroblastoma: a rare cause of tooth mobility.

    Science.gov (United States)

    Kürklü, Esma; Emiroğlu, Halil Haldun; Kebudi, Rejin; Ozdaş, Didem Oner; Ayan, Inci; Görgün, Omer; Zülfikar, Bülent; Yekeler, Ensar; Gülsüm, A K

    2011-01-01

    Neuroblastoma (NBL), a malignant embryonic tumor derived from neural crest cells, is the most common tumor worldwide among children less than 1 year of age. Metastasis to the mandible is uncommon. This article reports the case of a 15-month-old male diagnosed with NBL with bone metastasis including the mandible which resulted in severe tooth mobility. Dentists or pediatricians should consider the primary or metastatic tumors of the maxillofacial region in the differential diagnosis in children presenting with premature loss of teeth related to tooth mobility.

  14. Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma.

    Science.gov (United States)

    Mao, Xinfang; Chen, Zhenghu; Zhao, Yanling; Yu, Yang; Guan, Shan; Woodfield, Sarah E; Vasudevan, Sanjeev A; Tao, Ling; Pang, Jonathan C; Lu, Jiaxiong; Zhang, Huiyuan; Zhang, Fuchun; Yang, Jianhua

    2017-01-03

    Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner. Afatinib also induced apoptosis and blocked EGF-induced activation of PI3K/AKT/mTOR signaling in all neuroblastoma cell lines tested. In addition, afatinib enhanced doxorubicin-induced cytotoxicity in neuroblastoma cells, including the chemoresistant LA-N-6 cell line. Finally, afatinib exhibited antitumor efficacy in vivo by inducing apoptosis in an orthotopic xenograft neuroblastoma mouse model. Taken together, these results show that afatinib inhibits neuroblastoma growth both in vitro and in vivo by suppressing EGFR-mediated PI3K/AKT/mTOR signaling. Our study supports the idea that EGFR is a potential therapeutic target in neuroblastoma. And targeting ErbB family protein kinases with small molecule inhibitors like afatinib alone or in combination with doxorubicin is a viable option for treating neuroblastoma.

  15. Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma

    Science.gov (United States)

    Mao, Xinfang; Chen, Zhenghu; Zhao, Yanling; Yu, Yang; Guan, Shan; Woodfield, Sarah E.; Vasudevan, Sanjeev A.; Tao, Ling; Pang, Jonathan C.; Lu, Jiaxiong; Zhang, Huiyuan; Zhang, Fuchun; Yang, Jianhua

    2017-01-01

    Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner. Afatinib also induced apoptosis and blocked EGF-induced activation of PI3K/AKT/mTOR signaling in all neuroblastoma cell lines tested. In addition, afatinib enhanced doxorubicin-induced cytotoxicity in neuroblastoma cells, including the chemoresistant LA-N-6 cell line. Finally, afatinib exhibited antitumor efficacy in vivo by inducing apoptosis in an orthotopic xenograft neuroblastoma mouse model. Taken together, these results show that afatinib inhibits neuroblastoma growth both in vitro and in vivo by suppressing EGFR-mediated PI3K/AKT/mTOR signaling. Our study supports the idea that EGFR is a potential therapeutic target in neuroblastoma. And targeting ErbB family protein kinases with small molecule inhibitors like afatinib alone or in combination with doxorubicin is a viable option for treating neuroblastoma. PMID:27902463

  16. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    Science.gov (United States)

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  17. Discordant lymphoma consisting of mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes: a case report

    National Research Council Canada - National Science Library

    Zhang, Chun; Yi, Yuanxue; Chen, Chunyan; Wang, Jianrong; Liu, Zhu

    2015-01-01

    .... Here, we report a case of discordant lymphoma in a 34-year-old female patient that involved mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes...

  18. Treatment options for ocular adnexal lymphoma (OAL

    Directory of Open Access Journals (Sweden)

    Victoria Mary Lendrum Cohen

    2009-11-01

    Full Text Available Victoria Mary Lendrum CohenSt. Bartholomew’s and Moorfields Eye Hospital, London UKAbstract: Most lymphomas that involve the ocular adnexal structure are low grade, B cell, non-Hodgkin’s lymphomas. The treatment depends upon the grade and stage of the disease. High grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade (extranodal marginal zone lymphoma can be successfully managed with local radiotherapy. Chlamydia psittaci infection is associated with low grade ocular lymphoma; however there is wide geographic variation in the strength of this association. Blanket antibiotic therapy is not advised unless there is proof of an infective agent. The monoclonal antibody, rituximab, may be successful for CD20 positive lymphoma, although it is likely that rituximab will have better long-term results when used in combination with systemic chemotherapy.Keywords: ocular adnexal lymphoma, mucosa associated lymphoid tissue, extranodal marginal zone lymphoma, Chlamydia psittaci, rituximab, radiotherapy, chemotherapy

  19. Imaging of non-hodgkin lymphomas

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods...... for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since...... interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance...

  20. Progranulin Deficiency Reduces CDK4/6/pRb Activation and Survival of Human Neuroblastoma SH-SY5Y Cells.

    Science.gov (United States)

    de la Encarnación, Ana; Alquézar, Carolina; Esteras, Noemí; Martín-Requero, Ángeles

    2015-12-01

    Null mutations in GRN are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). However, the influence of progranulin (PGRN) deficiency in neurodegeneration is largely unknown. In neuroblastoma cells, silencing of GRN gene causes significantly reduced cell survival after serum withdrawal. The following observations suggest that alterations of the CDK4/6/retinoblastoma protein (pRb) pathway, secondary to changes in PI3K/Akt and ERK1/2 activation induced by PGRN deficiency, are involved in the control of serum deprivation-induced apoptosis: (i) inhibiting CDK4/6 levels or their associated kinase activity by sodium butyrate or PD332991 sensitized control SH-SY5Y cells to serum deprivation-induced apoptosis without affecting survival of PGRN-deficient cells; (ii) CDK4/6/pRb seems to be downstream of the PI3K/Akt and ERK1/2 signaling pathways since their specific inhibitors, LY294002 and PD98059, were able to decrease CDK6-associated kinase activity and induce death of control SH-SY5Y cells; (iii) PGRN-deficient cells show reduced stimulation of PI3K/Akt, ERK1/2, and CDK4/6 activities compared with control cells in the absence of serum; and (iv) supplementation of recombinant human PGRN was able to rescue survival of PGRN-deficient cells. These observations highlight the important role of PGRN-mediated stimulation of the PI3K/Akt-ERK1/2/CDK4/6/pRb pathway in determining the cell fate survival/death under serum deprivation.

  1. 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.)

  2. 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.

  3. Splicing aberrations caused by constitutional RB1 gene mutations in retinoblastoma

    Indian Academy of Sciences (India)

    Vidya Latha Parsam; Mohammed Javed Ali; Santosh G Honavar; Geeta K Vemuganti; Chitra Kannabiran

    2011-06-01

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, exonic substitution and whole-exon deletions identified in genomic DNA of these patients. In addition, this study identified mutations in cases in which no mutations were detectable in the genomic DNA. One proband had mutation at the canonical splice site at +5 position of IVS22, and analysis of the transcripts in this family revealed skipping of exon 22 in three members of this family. In one proband, a missense substitution of c.652T > G (g.56897T > G; Leu218Val) in exon 7 led to splicing aberrations involving deletions of exons 7 and 8, suggesting the formation of a cryptic splice site. In two probands with no detectable changes in the genomic DNA upon screening of RB1 exons and flanking intronic sequences, transcripts were found to have deletions of exon 6 in one, and exons 21 and 22 in another family. In two probands, RNA analysis confirmed genomic deletions involving one or more exons. This study reveals novel effects of RB1 mutations on splicing and suggests the utility of RNA analysis as an adjunct to mutational screening of genomic DNA in retinoblastoma.

  4. Illumina next generation sequencing data and expression microarrays data from retinoblastoma and medulloblastoma tissues

    Directory of Open Access Journals (Sweden)

    A.J. García-Chequer

    2016-03-01

    We first created an in silico reference profile generated from a human sequenced genome (GRCh37p5. From this data we calculated an integrity score to get an overview of gains and losses in all chromosomes; we next analyzed each chromosome in windows of 40 kb length, calculating for each window the log2 ratio between reads from tumor pool and in silico reference. Finally we generated panoramic maps with all the windows whether lost or gained along each chromosome associated to its cytogenetic bands to facilitate interpretation. Expression microarrays was done for the same samples and a list of over and under expressed genes is presented here. For this detection a significance analysis was done and a log2 fold change was chosen as significant (raw data can be found at http://www.ncbi.nlm.nih.gov/geo/accession number GSE11488. The complete research article can be found at Cancer Genetics journal (Garcia-Chequer et al., in press [1]. In summary here we provide an overview with visual graphics of gains and losses chromosome by chromosome in retinoblastoma and medulloblastoma, also the integrity score analysis and a list of genes with relevant expression associated. This material can be useful to researchers that may want to explore gains and losses in other malignant tumors with this approach or compare their data with retinoblastoma.

  5. 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.

  6. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins.

    Science.gov (United States)

    Vilas, Jéssica M; Ferreirós, Alba; Carneiro, Carmen; Morey, Lluis; Da Silva-Álvarez, Sabela; Fernandes, Tânia; Abad, María; Di Croce, Luciano; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-02-20

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression.

  7. Ethnic variations of a retinoblastoma susceptibility gene (RB1) polymorphism in eight Asian populations

    Indian Academy of Sciences (India)

    Priya Kadam-Pai; Xin-Yi Su; Jasmin Jiji Miranda; Agustinus Soemantri; Nilmani Saha; Chew-Kiat Heng; Poh-San Lai

    2003-04-01

    An A → G single nucleotide polymorphism (SNP) at nucleotide 153,104 in the retinoblastoma susceptibility locus (RB1) at 13q14 was previously reported to be present only in Asians. In this study, we determined the distribution of this SNP in normal Southeast Asian populations (Chinese, Malay, Javanese, Thai, Filipino), in South Asian populations (Bangladeshi, Pakistani Pushtun and Indian) and in Chinese retinoblastoma cases and control subjects. The RB1 SNP was present in all populations at an overall frequency of ≤ 0.18. Heterozygosity was higher in the Southeast Asian groups (0.14–0.34) than in the South Asian groups (Bangladeshi and Indian) (0.04–0.06). Significant differences in allele frequencies were found between the two population groups. Interestingly, our Pakistani population comprised of ethnic Pushtuns from northwest Pakistan was significantly different from the neighbouring Bangladeshi and Indian populations. No significant difference was found between Chinese case patients and control subjects. This RB1 SNP appears to be an ethnic variant prevalent in Southeast Asian populations and may be useful for studying RB1 inheritance by pedigree analysis.

  8. Novel roles of plant RETINOBLASTOMA-RELATED (RBR) protein in cell proliferation and asymmetric cell division.

    Science.gov (United States)

    Desvoyes, Bénédicte; de Mendoza, Alex; Ruiz-Trillo, Iñaki; Gutierrez, Crisanto

    2014-06-01

    The retinoblastoma (Rb) protein was identified as a human tumour suppressor protein that controls various stages of cell proliferation through the interaction with members of the E2F family of transcription factors. It was originally thought to be specific to animals but plants contain homologues of Rb, called RETINOBLASTOMA-RELATED (RBR). In fact, the Rb-E2F module seems to be a very early acquisition of eukaryotes. The activity of RBR depends on phosphorylation of certain amino acid residues, which in most cases are well conserved between plant and animal proteins. In addition to its role in cell-cycle progression, RBR has been shown to participate in various cellular processes such as endoreplication, transcriptional regulation, chromatin remodelling, cell growth, stem cell biology, and differentiation. Here, we discuss the most recent advances to define the role of RBR in cell proliferation and asymmetric cell division. These and other reports clearly support the idea that RBR is used as a landing platform of a plethora of cellular proteins and complexes to control various aspects of cell physiology and plant development.

  9. 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.

  10. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins

    Science.gov (United States)

    Carneiro, Carmen; Morey, Lluis; Silva-Álvarez, Sabela Da; Fernandes, Tânia; Abad, María; Croce, Luciano Di; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-01-01

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression. PMID:25576924

  11. Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

    Science.gov (United States)

    2016-06-27

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

  12. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.

    Science.gov (United States)

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-08-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumor cells suppress T-cell proliferation through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine-deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34(+) progenitor proliferation. Finally, we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1-specific T-cell receptor and GD2-specific chimeric antigen receptor-engineered T-cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for patients with neuroblastoma. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumor and blood that leads to impaired immunosurveillance and suboptimal efficacy of immunotherapeutic approaches.

  13. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours.

    Science.gov (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Tadeo, Irene; Beckman, Siv; Sandén, Caroline; Jönsson, Jimmie; Erjefält, Jonas S; Berbegall, Ana P; Börjesson, Anna; Backman, Torbjörn; Øra, Ingrid; Navarro, Samuel; Noguera, Rosa; Gisselsson, David; Påhlman, Sven; Bexell, Daniel

    2016-06-01

    Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.

  14. Preclinical evaluation of engineered oncolytic herpes simplex virus for the treatment of neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Lauren A Gillory

    Full Text Available Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV, M002, had a significant increase in survival. M002 has deletions in both copies of the γ 1 34.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma.

  15. Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Neuroblastoma

    Science.gov (United States)

    Gillory, Lauren A.; Megison, Michael L.; Stewart, Jerry E.; Mroczek-Musulman, Elizabeth; Nabers, Hugh C.; Waters, Alicia M.; Kelly, Virginia; Coleman, Jennifer M.; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.; Beierle, Elizabeth A.

    2013-01-01

    Despite intensive research efforts and therapeutic advances over the last few decades, the pediatric neural crest tumor, neuroblastoma, continues to be responsible for over 15% of pediatric cancer deaths. Novel therapeutic options are needed for this tumor. Recently, investigators have shown that mice with syngeneic murine gliomas treated with an engineered, neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal neural cells. We hypothesized that M002 would also be effective in the neural crest tumor, neuroblastoma. We showed that M002 infected, replicated, and decreased survival in neuroblastoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly decreased tumor growth, and that this effect was augmented with the addition of ionizing radiation. Importantly, survival could be increased by subsequent doses of radiation without re-dosing of the virus. Finally, these studies showed that the primary entry protein for oHSV, CD111 was expressed by numerous neuroblastoma cell lines and was also present in human neuroblastoma specimens. We concluded that M002 effectively targeted neuroblastoma and that this oHSV may have potential for use in children with unresponsive or relapsed neuroblastoma. PMID:24130898

  16. Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification

    Science.gov (United States)

    Valentijn, Linda J.; Koster, Jan; Haneveld, Franciska; Aissa, Rachida Ait; van Sluis, Peter; Broekmans, Marloes E. C.; Molenaar, Jan J.; van Nes, Johan; Versteeg, Rogier

    2012-01-01

    Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization. PMID:23091029

  17. Improved therapy for neuroblastoma using a combination approach: superior efficacy with vismodegib and topotecan.

    Science.gov (United States)

    Chaturvedi, Nagendra K; McGuire, Timothy R; Coulter, Don W; Shukla, Ashima; McIntyre, Erin M; Sharp, John Graham; Joshi, Shantaram S

    2016-03-22

    Aberrant activation/expression of pathways/molecules including NF-kB, mTOR, hedgehog and polo-like-kinase-1 (PLK1) are correlated with poor-prognosis neuroblastoma. Therefore, to identify a most efficacious treatment for neuroblastoma, we investigated the efficacy of NF-kB/mTOR dual-inhibitor 13-197, hedgehog inhibitor vismodegib and PLK1 inhibitor BI2536 alone or combined with topotecan against high-risk neuroblastoma. The in vitro efficacy of the inhibitors alone or combined with topotecan on cell growth/apoptosis and molecular mechanism(s) were investigated. Results showed that as single agents 13-197, BI2536 and vismodegib significantly decreased neuroblastoma cell growth and induced apoptosis by targeting associated pathways/molecules. In combination with topotecan, 13-197 did not show significant additive/synergistic effects against neuroblastoma. However, BI2536 or vismodegib further significantly decreased neuroblastoma cell growth/survival. These results clearly showed that vismodegib combination with topotecan was synergistic and more efficacious compared with BI2536 in combination. Together, in vitro data demonstrated that vismodegib was most efficacious in potentiating topotecan-induced antineuroblastoma effects. Therefore, we tested the combined efficacy of vismodegib and topotecan against neuroblastoma in vivo using NSG mice. This resulted in significantly (pvismodegib and topotecan showed a significant enhanced antineuroblastoma efficacy by targeting associated pathways/molecules which warrants further preclinical evaluation for translation to the clinic.

  18. 506U78 in Treating Patients With Lymphoma

    Science.gov (United States)

    2013-01-15

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Small Intestine Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome

  19. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

    Science.gov (United States)

    Fadakar, Puran; Akbari, Abolfazl; Ghassemi, Fariba; Mobini, Gholam Reza; Mohebi, Masoumeh; Bolhassani, Manzar; Abed Khojasteh, Hoda; Heidari, Mansour

    2016-06-01

    Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment.

  20. 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...