Subject(s)
Humans , Male , Child , Pain/etiology , Hip Joint/diagnostic imaging , Neuroblastoma/diagnosis , Neuroblastoma/therapy , Tomography , Diagnosis, DifferentialABSTRACT
Introdução: El neuroblastoma es el tumor sólido extracraneal más frecuente en niños. Aproximadamente el 50 % de los pacientes son clasificados como de alto riesgo, con base en características clínicas, biológicas e histológicas. Objetivo: Describir a la población asistida en el Centro Hemato-Oncológíco Pediátrico (CHOP) del Centro Hospitalario Pereira Rossell (CHPR) con diagnóstico de neuroblastoma de alto riesgo, su tratamiento y sobrevida. Método: Estudio descriptivo y retrospectivo de todos los pacientes con neuroblastoma de alto riesgo diagnosticados en el CHOP entre el 2001 y el 2015. En el CHOP se ubica el Registro Nacional de Cáncer Pediátrico, así como también el Archivo de Historias Clínicas de todos los pacientes. Los datos son recolectados y analizados por el sector de estadística. Resultados: Se diagnosticaron 35 pacientes, de los cuales 20 (57%) eran varones con mediana de edad de 36,6 meses (5-93), localización suprarrenal 23 (66%) y 100% estadio IV. Metástasis, médula ósea y hueso: 27 (71%). Treinta y tres pacientes recibieron autotransplante de progenitores hematopoyéticos (TPH) (94%). Estatus previo a TPH, remisión completa: 19 (58 %), remisión parcial: 14 (42%). Mortalidad relacionada al tratamiento: 15 % y de recaídas: 68 %. Mediana de tiempo de recaída: 15 meses (3-52). La probabilidad de sobrevida global y sobrevida libre de eventos a 5 años fue de 37,8% ± 8,4 y 23,8% ± 7,3 (mediana de seguimiento 40 meses). Conclusión: A pesar del tratamiento intensivo y de las medidas de soporte adecuadas, el pronóstico en los niños con neuroblastoma de alto riesgo sigue siendo pobre en nuestro país. Es necesario incorporar nuevas estrategias terapéuticas aún no disponibles en nuestro medio.
Introduction: Neuroblastoma is the most common extracranial solid tumor in children. Approximately 50% of patients are classified as high risk on the basis of clinical, biological, and histological characteristics. Objective: To describe the population of patients diagnosed with high-risk neuroblastoma at the Centro Hemato-Oncológíco Pediátrico (CHOP, Center for Pediatric Hematology and Oncology) of the Centro Hospitalario Pereira Rossell (CHPR, Pereira Rossell Hospital), in terms of their treatment and survival. Method: Descriptive, retrospective study of all patients diagnosed with highrisk neuroblastoma at the CHOP between 2001 and 2015. The National Registry of Pediatric Cancer is located at the CHOP, as is the Archive of Patient Clinical Histories. The data are collected and analyzed by the statistics sector. Results: Among the 35 patients diagnosed, 20 (57%) were men, the median age was 36.6 months (range, 5-93 months), and the tumor had an adrenal location in 23 (66%). All of the tumors were classified as stage IV. Metastasis to the bone marrow or bone was seen in 27 (71%). Thirty-three patients (94%) received autologous hematopoietic stem-cell transplantation (HSCT). The status prior to HSCT was complete remission in 19 (58%) and partial remission in 14 (42%). The treatment-related mortality rate was 15%, and the relapse rate was 68%. The median time to relapse was 15 months (3-52 months). The probability of overall survival and 5-year event-free survival was 37.8% ± 8.4 and 23.8% ± 7.3 (median follow-up of 40 months), respectively. Conclusion: Despite intensive treatment and adequate support measures, the prognosis for high-risk neuroblastoma in children remains poor in Uruguay. There is a need to incorporate new therapeutic strategies not yet available in our country.
Introducción:O neuroblastoma é o tumor sólido extracraniano mais frequente em crianças. Aproximadamente 50% dos pacientes são classificados como de alto risco considerando as características clínicas, biológicas e histológicas. Objetivo: Descrever a população atendida no Centro Hemato-Oncológíco Pediátrico (CHOP) do Centro Hospitalario Pereira Rossell (CHPR) com diagnóstico de neuroblastoma de alto risco, seu tratamento e sobrevida. Método: Estudo descritivo, retrospectivo, de todos os pacientes com neuroblastoma de alto risco diagnosticados no CHOP, no período entre 2001 e 2015. O Registro Nacional de Câncer Pediátrico está localizado no CHOP, bem como o Arquivo de Histórias Clínicas de todos os pacientes. Os dados são coletados e analisados pelo setor estatístico. Resultados: Foram diagnosticados 35 pacientes. Vinte (57%) eram do sexo masculino. Mediana de idade: 36,6 meses (5-93). Localização suprarrenal: 23 (66%). Estádio IV 100%. Metástases, medula óssea e osso: 27 (71%). Trinta e três pacientes receberam transplante de células-tronco hematopoiéticas (TCTH) (94%). Status prévio a TCTH, remissão completa: 19 (58%), remissão parcial: 14 (42%). Incidência de mortalidade relacionada ao tratamento: 15% e de recaídas: 68%. Mediana do tempo de recaída: 15 meses (3-52). A probabilidade de sobrevida global e sobrevida livre de eventos aos cinco anos foi de 37,8% ± 8,4 e 23,8% ± 7,3 (mediana de seguimento 40 meses). Conclusão: Apesar do tratamento intensivo e medidas de suporte adequadas, o prognóstico em crianças com neuroblastoma de alto continua sendo pobre no Uruguai. É necessário incorporar novas estratégias terapêuticas que ainda não estão disponíveis em nosso meio
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Neuroblastoma/epidemiology , Uruguay/epidemiology , Survival Analysis , Retrospective Studies , Neoplasm Staging , Neuroblastoma/therapyABSTRACT
Background: Neuroblastoma is the third most common childhood cancer, after leukemia and brain tumors, and is the most common solid extra cranial tumor in children. The term neuroblastoma is commonly used to refer to a spectrum of neuroblastic tumors [including neuroblastomas, ganglioneuroblastomas, and ganglioneuromas] that arise from primitive sympathetic ganglion cells
Objective: The aim of this research is to study the epidemiological and clinical feature of neuroblastoma in a group of Iraqi infants and children who were admitted to the pediatric ward of Al-Khadhimyia Teaching Hospital
Patients and methods: The study was done over a period of three months from 1[st] of Feb. 2010 to the end of Apr. 2010. In reviewing all files, 18 cases were collected from the Pediatric Hemato-Oncology Consultation Clinic in Al-Khadhimyia Teaching Hospital, they were diagnosed and treated consequently in the pediatric ward / hemato-oncology unit over a period of 9 years [2002-2010]. Data regarding age, sex, residence, site of primary disease and clinical presentation were taken from the recording files in the pediatrics Hemato-Oncology Clinic. Methods used to diagnose our patients includes, fine needle aspiration of tumor mass, Bone marrow aspiration and biopsy of different sites. Chemotherapy was the main line of treatment
Results: The total number of studied cases was eighteen cases. The median age was 15 months with male to female ratio of [0.63:1], 9 cases [50%] were below 1 year. Abdominal mass was the commonest site of tumor 12 cases [67%], weight loss was the most common symptom 18 cases [100%] followed by abdominal distention 14 cases [78%], abdominal mass represent the most common sign in 12 cases [67%]. Stage IV was noticed in 9 cases [50%], 10 cases [56%] were a high risk group, 7 cases [38.8%] had bone marrow metastases, 6 cases [34%] finished treatment and survive, 4 cases [22%] relapsed, 2 cases [11%] died
Conclusion: The majority of cases were recognized during the first two years of age. Female were involved more than male. The outcome of treated cases was good and accepted. Abdominal mass is the commonest site, weight loss is the commonest symptoms
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Infant , Neuroblastoma/diagnosis , Neuroblastoma/therapy , Hospitals, Teaching , Infant , ChildABSTRACT
El neuroblastoma es el tumor maligno más frecuente en los lactantes. Su curso clínico es variable, desde la regresión espontánea a la progresión maligna, y los factores pronósticos son múltiples, como edad, estadio, amplificación de N-myc y ploidía tumoral. Se describen las características de todos los pacientes con neuroblastoma menores de 18 meses asistidos en CHOP. Pacientes y métodos: estudio observacional, descriptivo y retrospectivo en el período entre 31 de enero de 2000 y 31 de enero de 2011. El diagnóstico se realizó por histología y aspirado de médula ósea. Los pacientes se estadificaron por INSS; el tratamiento se decidió según estadio y riesgo. Resultados: se incluyeron 22 pacientes menores de 18 meses (52% de todos los neuroblastomas), con una media de edad de 9,6 meses. Once pacientes se encontraban en estadio 4. La localización más frecuente fue suprarrenal; presentaban metástasis 13 pacientes. Quince niños recibieron poliquimioterapia y 20 fueron tratados quirúrgicamente. La amplificación del genN-myc se demostró en tres pacientes. La sobrevida global fue de 77% y la sobrevida libre de enfermedad fuede 77%. Discusión y conclusiones: la mayor parte de los casosfueron diagnosticados en niños menores de 9 meses. Fueron más frecuentes los estadios 4 y 1. No se pudo demostrar asociación entre N-myc y estadio de enfermedad. La sobrevida fue excelent...
Subject(s)
Humans , Infant , Neuroblastoma/diagnosis , Neuroblastoma/physiopathology , Neuroblastoma/therapy , SurvivalABSTRACT
The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefly discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.
Subject(s)
Humans , Autophagy/physiology , Hedgehog Proteins/physiology , Neoplastic Stem Cells/pathology , Neuroblastoma/physiopathology , Transcription Factors/physiology , Cell Line, Tumor , Cell Proliferation , Neuroblastoma/pathology , Neuroblastoma/therapy , Signal TransductionABSTRACT
El neuroblastoma es el tumor maligno sólido extracraneal más común en niños. Sólo el 10 por ciento de los casos se diagnostican después de la primera década de vida. Presentamos una paciente afroamericana de 23 años, con una masa paravertebral en T3-T5, múltiples lesiones en los cuerpos vertebrales y una lesión expansiva en la región parietal derecha. El estudio inmmunohistoquímico (negativo para CD99, CD20, CD3 y desmina y positivo para cromogranina, sinaptofisina y NB84), confirmó el diagnóstico de neuroblastoma. La paciente fue sometida a 12 ciclos de quimioterapia recibiendo VAC (vincristina / doxorubicina/ cyclofosfamida) intercalada con ICE (ifosfamida/ mesna/ etoposido). La doxorubicina fue reemplazada por actinomicina en el séptimo ciclo. La paciente toleró bien la quimioterapia y está clínicamente estable.
Neuroblastoma is the most common extracranial solid malignancy in children but rarely described in adults, being 10 percent of all cases diagnosed after the first decade of life. We report a 23 year-old black woman with a mass at paravertebral region of T3-T5, multiple lesions in vertebral bodies and expanding skull-brain lesion at the right parietal region. Immunohistochemical analysis (negative for CD99, CD20, CD3 and desmin; and positive chromogranin, synaptophysin and NB84) confi rmed the diagnosis of neuroblastoma. The patient was submitted to 12 cycles of chemotherapy receiving VAC (vincristine/doxorubicin/cyclophosphamide) interspersed with ICE (ifosfamide/mesna/etoposide) and doxorubicin was replaced by actinomycin in the 7th cycle. She had good tolerance to this therapy, and has been clinically stable.
Subject(s)
Female , Humans , Young Adult , Brain Neoplasms/secondary , Neuroblastoma/pathology , Spinal Cord Compression/etiology , Spinal Cord Neoplasms/secondary , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Bone Neoplasms/secondary , Brain Neoplasms/therapy , Carboplatin/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Ifosfamide/administration & dosage , Mesna/administration & dosage , Neuroblastoma/therapy , Spinal Cord Neoplasms/therapy , Thoracic Vertebrae , Vincristine/administration & dosageABSTRACT
Objetivo: Discutir as principais características clínicas do neuroblastoma, linfoma e tumor de Wilms, contribuindo para o diagnóstico precoce destas doenças. Fonte de dados: Medline PubMed. Síntese dos dados: Na prática clínica o achado de tumores abdominais na infância é frequente. A maioria das massas é causada por doenças benignas. Eventualmente, neoplasias malignas da infância também se manifestam como tumor abdominal. Os autores discutem neste artigo as principais diferenças clínicas e laboratoriais dos três tumores abdominais malignos mais frequentes na infância: linfoma não Hodgkin, neuroblastoma e tumor renal de Wilms. Conclusão: Através da análise dos dados clínicos e do exame físico do paciente com tumor maligno abdominal, o pediatra pode traçar hipóteses diagnósticas e encaminhar precocemente a criança para centros especializados.
Subject(s)
Humans , Male , Female , Child , Adolescent , Lymphoma/diagnosis , Lymphoma/therapy , Neuroblastoma/diagnosis , Neuroblastoma/therapy , Wilms Tumor/diagnosis , Wilms Tumor/therapy , Child HealthSubject(s)
Child , Neuroblastoma/diagnosis , Neuroblastoma/drug therapy , Neuroblastoma/therapy , Thorax , Diagnosis, DifferentialABSTRACT
No presente trabalho, os autores relatam o caso de uma criança com neuroblastoma intrarenal, que foi, inicialmente,diagnosticado como tumor de Wilms. Pré-escolar, sexo feminino, com um ano e três meses, apresentava uma tumoração endurecida que ocupava o hipocôndrio esquerdo e se estendia até a região do mesogástrio, acompanhada de febre e palidez. O ultra-som do abdome total revelou massa intrarenal. A biópsia por agulha fina, em vários pontos de acesso tumoral, revelou um tumor de Wilms. Entretanto, não foi possível naquele momento realizar a imunohistoquímica (IHQ), face à escassez de material. Diante da gravidade da paciente, foi iniciado o protocolo SIOP por quatro semanas. Como não houve resposta clínica, foi indicada uma laparotomia exploradora, com ressecção parcial do tumor, sendo também, nesse momento, realizada punção aspirativa de medula óssea (MO). O exame histopatológico revelou neoplasia maligna de pequenas células mal diferenciadas. A IHQ foi negativa para WT-1 e positiva para NB-84, cromogranina e sinaptofisina. A biologia molecular revelou amplificação de N-myc. O mielograma identificou infiltração medular por pequenas células redondas. O neuroblastoma intrarenal é um tumor raro que se assemelha clínica e radiologicamente ao tumor de Wilms. Esse trabalho procura enfatizar a importância do emprego de análises imunohistoquímica e moleculares para o diagnóstico do neuroblastoma intrarenal.
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 mesogastric 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 scarcety 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 laparatomy 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 matastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographicallyresembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical andmolecular analysis in the diagnosis of intrarenal neuroblastoma.
Subject(s)
Humans , Female , Infant , Adrenal Gland Neoplasms , Neuroblastoma/diagnosis , Neuroblastoma/therapy , Wilms Tumor/diagnosis , Diagnosis, Differential , Genes, mycABSTRACT
El Neuroblastoma es uno de los tumores sólidos malignos más frecuentes en niños y puede aparecer en cualquiera de los sitios anatómicos a lo largo de la cadena ganglionar simpática, así como en la glándula suprarrenal. A diferencia de otros tumores embrionarios de niños, el pronóstico en este tipo de tumor sigue siendo incierto y está influido por una gran variedad de factores. El peor pronóstico de sobrevida se observa en estadio IV y en presencia de metástasis óseas corticales. El sitio de tumor primario también podría ser considerado predictivo de sobrevida, según algunos investigadores. Objetivo: determinar si existe relación entre la forma inicial de presentación clínica de aquellos pacientes en etapa IV con compromiso óseo y las posibilidades de tratamiento quirúrgico primario. Además, determinar la relación entre la localización del tumor primario y el pronóstico. Material y métodos: se realizó una revisión retrospectiva de 22 fichas de pacientes con neuroblastoma tratados en el Hospital Roberto del Río entre 1994 2004. Los datos se analizaron estadísticamente mediante pruebas Fisher- Irwing. Resultados: en 22 pacientes estudiados, la forma inicial de presentación clínica más frecuente fue la de aquellos tumores abdominales y pélvicos, seguida por tumores mediastínicos. La mayoría de los pacientes, al momento del diagnóstico, se encontraban en etapa I o en etapa IV (45 por ciento de los casos para cada etapa). De los casos que se diagnosticaron en la etapa I, la mayoría de los neuroblastomas se hallaban ubicados en mediastino. De los casos que se diagnosticaron que se encontraban en etapa IV, la mayoría tenían localización abdominal. Como tratamiento inicial a la mayoría de los casos, 36 por ciento (8), se le efectuó una biopsia del tumor; con similar frecuencia se realizó resección total del tumor como primer tratamiento (32 por ciento); en 4 casos se decidió comenzar tratamiento con quimioterapia y a 3 casos se le practicó resección parcial del tumor en primera instancia. Conclusiones: no se encontró relación estadísticamente significativa (p=>0.05) entre aquellos casos que tenían neuroblastoma en etapa IV con metástasis óseas corticales y efectuar la resección primaria del tumor.
Subject(s)
Humans , Child , Neuroblastoma , Neuroblastoma/surgery , Neuroblastoma/diagnosis , Neuroblastoma/therapy , ChileABSTRACT
Objetivos: Descrever caso de neuroblastorna em sua forma menos freqüente (estágio IV-S), com metástases avançadas em fígado e medula óssea em lactente de cinco meses, relatando as divergências entre as opiniões dos autores de uma extensa revisão de literatura em relação às condutas e aos resultados. Descrição: Lactente de cinco meses apresentou-se com febre e hepatomegalia a esclarecer. Ultra-sonografia abdominal demonstrou fígado com dimensões aumentadas, ecotextura heterogénea às custas de numerosas imagens hipoecóicas difusamente distribuídas e, na supra-renal direita, massa hiperecóica de contornos bem definidos, medindo, aproximadamente, 65 cm³. Biópsia de medula óssea e de fígado revelou neoplasia maligna de pequenas células redondas e azuis compatíveis com neuroblastoma. O tratamento consistiu de sete ciclos de quimioterapia. seguida pela ressecção do tumor. O exame anátomo-patológico evidenciou ganglioneuroblastoma, "intermixed". Comentários: Não na uma padronização de conduta em relação ao neuroblastoma estadiado como IV-S. Alguns autores sugerem que não se deve tratar esse tumor em pacientes menores de um ano, peia alta taxa de regressão espontânea. Outros consideram a quimioterapia a conduta mais adequada. A ressecção cirúrgica imediata ou após a quimioterapia é também controversa.
Objectives: A case of neuroblastoma in its less frequent form (stage IV-S) with advanced metastases in liver and bone marrow in a five-month-old infant is described. Description: The patient presented fever and hepatomegaly. Abdominal ultrasonography showed liver with augmented dimensions, heterogeneous echotexture due to numerous and diffusely distributed hypoechoic images. A 65 cm³ hyperechoic mass in right adrenal, with well-defined contours was detected. Biopsy of bone marrow and liver revealed malignant neoplasm of small round blue cells, compatible with neuroblastoma. Treatment consisted of seven chemotherapy cycles followed by tumor resection. Histological examination revealed intermixed ganglioneuroblastoma, Comments: A discussion on different approaches to treatment of I V-S stage neuroblastoma is made.
Subject(s)
Humans , Female , Infant , Liver/pathology , Liver Neoplasms , Neuroblastoma/therapy , Biopsy , Neoplasm Staging , Hepatomegaly , TomographyABSTRACT
Objetivo: estudar retrospectivamente o quadro clínico, aspectos epidemiológicos, características laboratoriais, genéticas e histológicas em crianças maiores de 1 ano, portadoras de neuroblastoma não disseminado, correlacionando-os com a evolução clínica e tentando definir fatores de risco que possam influir na sobrevida.Casuística e métodos: as informações foram obtidas a partir de 38 prontuários médicos...
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Clinical Evolution , Neuroblastoma/epidemiology , Prognosis , Neuroblastoma/genetics , Neuroblastoma/therapy , Retrospective Studies , Risk Factors , SurvivalABSTRACT
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirusmediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
Subject(s)
Animals , Humans , Mice , Apoptosis , Bystander Effect , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Connexin 43/biosynthesis , Gap Junctions , Genetic Therapy/methods , Gene Transfer Techniques , Immunohistochemistry , Neoplasm Transplantation , Neuroblastoma/therapy , Phosphorylation , Retroviridae/genetics , Simplexvirus/enzymology , Thymidine Kinase/genetics , Time FactorsABSTRACT
Bcr-abl antisense oligodeoxynucleotides (AS-ODNs) have provided evidence of an antileukemia effect when tested in vitro against Philadelphia-positive cells. In order to investigate the efficacy of AS-ODNs as purging agents in chronic myeloid leukemia (CML) patients, K562 cells, a human CML cell line, were treated in vitro with various types of AS-ODNs and interferon-alpha. Cells were treated in vitro for 0 and 36 hr with 40 microgram/mL of AS-ODNs, respectively, and incubated at 37 degrees C for 36 hr. Cytotoxic effects were measured by counting the number of viable cells as well as by MTT test. Clonogenic activities were evaluated by methylcellulose culture for 2 weeks. The effects of purging agents on the rearrangement of bcrabl gene were evaluated by RT-PCR. AS-ODNs inhibited the proliferation of K562 cells with time in cell count assay and MTT test. AS-ODNs were superior to INF-alpha in inhibiting clonogenic activity (recovery rate; 26.3% vs 64.0%). After incubation with bcr-abl AS-ODNs primers and mRNA isolated from K562 cells, positive bands were abolished, especially of b3a2 type and phosphorothioate type. Our results suggest that AS-ODNs mediated purging may be one of the efficient methods and that autograft may be an alternative treatment for allograft in high-risk group patients of CML if they do not have a stem cell donor.
Subject(s)
Humans , Bone Marrow Purging , Colony-Forming Units Assay , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Hematopoietic Stem Cells/physiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Neuroblastoma/therapy , Oligonucleotides, Antisense/metabolism , Oligonucleotides, Antisense/therapeutic use , Transplantation, Autologous , Tumor Cells, CulturedABSTRACT
Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Combined Modality Therapy , Korea , Myeloablative Agonists/therapeutic use , Neuroblastoma/mortality , Neuroblastoma/pathology , Neuroblastoma/therapy , Retrospective Studies , Stem Cell Transplantation , Survival Rate , Transplantation Conditioning , Transplantation, Autologous , Treatment OutcomeABSTRACT
Stage IV-S neuroblastoma [Blue Berry Muffin Baby] is a rare variety of neuroblastoma. In this report a three month old baby suffering from the disease is described
Subject(s)
Humans , Female , Neuroblastoma/therapy , Remission, Spontaneous , Infant, Newborn, Diseases , SyndromeABSTRACT
We used retroviral-mediated gene transfer of the human interleukin (IL)-2 gene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. Supernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-transduced, G-418 selected neuro-2a cells was assayed for human IL-2 production by ELISA kit. First, to estimate whether the local secretion of IL-2 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tumor growth was measured weekly. And to estimate whether IL-2 transfected neuroblastoma cells protect mice from tumor development after wild-type tumor cell challenge, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly. Finally, to estimate IL-2 effect on pre-established large tumor burdens, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice with established tumor and its growth was measured weekly. The IL-2 gene-transduced neuro-2a clones secreted 120.25-177.3 IU of IL-2 per ml per 10(6) cells during 24 hr. None of the mice injected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, while all of the mice injected with wild-type neuro-2a cells developed tumors. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with wild-type tumor cells. Finally, the size of large neuroblastomas decreased after IL-2-secreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-transduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.
Subject(s)
Humans , Mice , Animals , Antibody Formation , Gene Transfer Techniques , Immunization/methods , Interleukin-2/therapeutic use , Interleukin-2/genetics , Neoplasm Transplantation , Neuroblastoma/therapy , Neuroblastoma/prevention & control , Neuroblastoma/pathology , Neuroblastoma/genetics , Retroviridae/genetics , Tumor Cells, CulturedABSTRACT
To study stage IV-s congenital neuroblastoma in respect to their presentation, investigations, treatment and outcome. The records of 14 neonates with stage IV-s congenital neuroblastoma registered between 1986-1994 in the UK, were reviewed. The diagnosis was made by histological examination in nine neonates and elevated vanillylmandelic acid [VMA] and homovanillic acid [HVA] with ultrasonography [U/S] in the other five. Prenatal U/S diagnosis was done in two cases. Treatment varied from one center to another; chemotherapy in four cases, surgery in three, surgery plus chemotherapy one, radiotherapy one, and no treatment in five. The overall disease-free survival for 14 neonates was 93% at 104 months post diagnosis. One neonate died during the insertion of a central long line catheter. The follow up of 13 neonates showed no evidence of disease with no long-term sequelae of the disease or treatment. Neonates with stage IV-s congenital neuroblastoma have excellent prognosis compared to older children. Therefore, we need to adopt a new treatment strategy for this age group by doing some biological studies so as not to overtreat the good risk group, and to minimise the side effects of the treatment