Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I(131) MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBG-positive residual disease received 4.1-11.1 mCi/kg of I(131) MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m(2) followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I(131) MIBG: grade 2 or 3 mucositis developed in 13/17 patients treated with I(131) MIBG and in 9/15 treated without it. Grade 1-2 gastrointestinal toxicity occurred in 12/17 children given MIBG and in 5/15 of the controls. One child receiving I(131) MIBG developed transient interstitial pneumonia. Another child who also received I(131) MIBG after PBSC rescue developed fatal pneumonia after the third course of metabolic radiotherapy. Our experience indicates that MIBG can be included in the high-dose chemotherapy regimens followed by PBSC rescue for children with residual neuroblastoma taking up MIBG. Attention should be paid to avoiding lung complications. Prospective studies are needed to demonstrate the real efficacy of this treatment.
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PMID:Megatherapy combining I(131) metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma. 1131 84

The treatment of advanced neuroblastoma (NB) or Ewing's sarcoma (ES) is one of the major challenges in pediatric oncology. Both malignancies are refractory to conventional therapies and have an extremely poor prognosis. High-dose myeloablative radiochemotherapy with autologous bone marrow or peripheral blood stem cell rescue is one of the most aggressive treatments attempted for these diseases but is often undermined by residual tumor cells contaminating the graft. Thus, in this approach, purging of tumor cells from the graft is key to the prevention of relapse after transplantation. We investigated a novel approach to eliminate tumor cells from the bone marrow or peripheral blood stem cell graft without causing stem cell damage through the use of a conditionally replicative adenovirus (Ad). ES and NB are sensitive to Ad infection, and advanced NBs express a high level of the growth/differentiation factor midkine (MK). We confirmed in this study that ES cell lines (SK-ES-1 and RD-ES) are also sensitive to Ad infection and express high levels of MK. In contrast, CD34+ stem cells are refractory to Ad infection and express very little MK. A conditionally replicative Ad in which the expression of E1 is controlled by the MK promoter achieved good levels of viral replication in NB or ES and induced remarkable tumor cell killing. On the other hand, this virus caused no damage to CD34+ cells even after 3 h of infection at a dose of 1000 multiplicity of infection. We concluded that application of this replication-competent Ad to hematopoietic grafts could be a simple but effective procedure to achieve complete tumor cell purging.
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PMID:A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. 1169 8

Tumor cells frequently contaminate autologous stem cell products in patients having a variety of malignancies. Mobilized peripheral blood stem cells may be less contaminated with tumor cells than bone marrow harvests are, but they are still frequently infiltrated. Gene-marking studies using retroviral vectors provide evidence that tumor cells contained in autografts contribute to relapse in myeloid leukemia and neuroblastoma patients. Also clinical studies have shown that tumor cell contamination of autografts is associated with shortened disease-free survival; on the other hand, successful ex vivo purging of tumor cells is associated with superior clinical outcome. However, the presence of tumor cells in autografts or insufficient purging may correlate with the extent of systemic residual disease and/or tumor chemosensitivity; therefore, there is no direct evidence that reinfused tumor cells alone cause relapse. Particularly in patients having highly chemosensitive disease and no detected systemic residual disease following high-dose transplant chemotherapy, the relative number of tumor cells contained in autografts and eventually reinfused, may become a determining factor for clinical outcome. There are no randomized trials showing improved (disease-free) survival with purging. In the absence of such trials, the contribution of tumor cells in the stem cell autografts to subsequent relapse remains controversial.
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PMID:Tumor cell contamination in re-infused stem cell autografts: does it have clinical significance? 1185 99

Natural killer (NK)/lymphokine-activated killer (LAK) cell-based immunotherapy could be beneficial against major histocompatibility complex class I-negative tumor residual disease such as neuroblastoma (NB), provided that interleukin 2 (IL-2) or surrogate nontoxic NK cell stimulatory factors could sustain NK cell activation and survival in vivo. Here we show that human monocyte-derived dendritic cells (MD-DCs) promote potent NK/LAK effector functions and long-term survival, circumventing the need for IL-2. This study demonstrates (1) the feasibility of differentiating granulocyte colony-stimulating factor-mobilized hematopoietic peripheral blood stem cells (PBSCs) into high numbers of functional MD-DCs and NK/LAK cells in a series of 12 children with stage 4 neuroblastoma (NB); (2) potent DC-mediated NK cell activation in autologous settings; (3) the reciprocal capacity of NK/LAK cells to turn immature DCs into maturing cells electively capable of triggering NK cell functions; and (4) the unique capacity of maturing DCs to sustain NK cell survival, superior to that achieved in IL-2. These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell-based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation.
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PMID:Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients. 1223 69

A 5-year-old boy received CD34-positive HLA haplo-identical bone marrow transplantation from his father as treatment for refractory advanced neuroblastoma. He had residual disease in the para-aortic lymph nodes and multiple bones after the transplant. However, all of his residual disease had disappeared completely 3 years later. He developed grade I acute graft-versus-host disease (GVHD) but had no symptoms of chronic GVHD or any other complications. This case demonstrates the possibility of a graft-versus-tumor effect against neuroblastoma by HLA-mismatched allogeneic hematopoietic stem cell transplantation.
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PMID:Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. 1281 85

The case of a one-month-old patient admitted to the Department of Pediatrics (Medical and Health Science Center, Debrecen University) because of respiratory distress caused by a cervical mass compressing the upper respiratory pathways is presented. The mass could only be partially removed, the histological diagnosis proved to be neuroblastoma (SBCT: "small blue cell tumor"). Despite the fact that the DNA index of tumor cells (ploidy measurements) and the age of the patient suggested a favourable prognosis, the tumor continued to grow and metastases appeared. Because of symptoms of compression exerted on the respiratory system by the tumor, chemotherapy had to be applied. Since a standard OPEC/OJEC chemotherapeutic protocol proved to be not entirely effective and a residual tumor was still present, retinoic acid and interferon treatment was introduced. Presently, 4 years after the diagnosis, the patient is in complete remission and can be considered to be cured. The case presented here demonstrates that despite the favorable prognosis of the majority of infant neuroblastomas, in some cases the anatomic location of the tumor, leading to disturbance of vital functions, may serve as indication of chemotherapy. Our experience also proved the efficacy of retinoic acid and interferon treatment in relapsed neuroblastoma.
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PMID:[Cervical neuroblastoma in an infant]. 1510 2

Disseminated forms of neuroblastoma (NB), a tumor derived from neuroectodermal tissue, pose a major therapeutic challenge for pediatric oncology. By performing a comparative cDNA array analysis of metastatic neuroblasts versus primary xenograft from the human IGR-N-91 NB model, we were able to identify a set of downregulated developmental genes in metastatic neuroblasts. One of these genes was Wnt-5a, a member of the Wnt signaling pathway, known to be involved in the development of neural crest cells. Since we also found a significant decrease in Wnt-5a mRNA in unfavorable versus favorable categories in 37 primary NB tumors (P<0.007), we wondered whether retinoic acid (RA), which has a role in neural crest induction and differentiation, might reverse the aberrant negative regulation of Wnt-5a in metastatic malignant neuroblasts. Following treatment with 10 muM RA for 6 days, the MYCN-amplified IGR-N-91 cell lines underwent neuronal differentiation as assessed by reduced MYCN gene expression and neuritic extension. In these conditions, data showed an upregulation of Wnt-5a and PKC-theta; isoform expressions. Our study highlights, for the first time, the involvement of Wnt-5a, which has a role in embryonic and morphogenetic processes, in the response of malignant neuroblasts to RA. In conclusion, we demonstrated that RA, which is used in the treatment of high-risk NB patients with recurrent/residual disease in the bone marrow, is able to upregulate Wnt-5a gene expression.
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PMID:Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. 1559 17

Esthesioneuroblastoma (olfactory neuroblastoma) is a rare, malignant neoplasm that typically arises in the nasal vault, invades adjacent tissues, and causes locoregional (cervical lymph nodes) and distant metastases. Only two cases of tumors arising in the sellar region that had the histological characteristics of esthesioneuroblastoma have been reported in the literature to date. The authors present the case of a 35-year-old woman with secondary amenorrhea and a rapidly growing tumor located in the adenohypophysis. After total removal of the lesion through a transseptal-transsphenoidal approach, the histological examination revealed an esthesioneuroblastoma Grade II/III according to Hyams. Considering the particular location of the lesion and the absence of residual tumor on postoperative magnetic resonance imaging, no adjuvant therapy was performed. The patient remained free from tumor recurrence 2 years postoperatively. Because all published cases of this esthestoneuroblastoma have been large neuroblastic tumors of the pituitary gland arising in middle-aged women, pituitary neuroblastoma might represent a rare, specific clinicopathological entity.
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PMID:Esthesioneuroblastoma of the pituitary gland: a clinicopathological entity? Case report and review of the literature. 1559 68

The factors that affect survival in patients with stage 4 neuroblastoma vary. Several prospective and retrospective studies have provided conflicting conclusions regarding the benefit of combining aggressive chemotherapy with complete surgical resection. We analyzed our experience to evaluate the effect of complete surgical resection of the primary tumor on survival when disseminated disease has been controlled by chemotherapy. We retrospectively reviewed the medical records of 44 consecutive children with neuroblastoma treated between 1990 and 2000. Twenty-six children with stage 4 disease were enrolled. Most were treated with surgical resection combined with chemotherapy. The survival rate was compared based on the timing (primary versus delayed until chemotherapy had been given) and results of surgery (complete tumor resection, microscopic residual disease, and gross residual disease). The mean survival (52.8 months) of children with delayed complete surgical resection (CSR) was statistically superior to that of those with microscopic residual (20.8 months, p = 0.0111) or gross residual tumor (12.2 months, p = 0.0141). In the CSR group, 1-, 2-, 3-, and 5-year survival rates were 88%, 77%, 77%, and 65%, respectively, vs. 80%, 40%, 20%, and 0% in the microscopic residual group. In conclusion, complete resection of the primary tumor with no residual disease was associated with improved survival in children with advanced neuroblastoma whose metastatic disease had been controlled by chemotherapy.
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PMID:Complete surgical resection plus chemotherapy prolongs survival in children with stage 4 neuroblastoma. 1564 10

In localized neuroblastoma, the identification of patients requiring intensive treatment is still difficult. We retrospectively analyzed data of 280 single copy MYCN stage 2 and 3 neuroblastoma patients with gross residual tumor after initial surgery. The 3-year-event free survival of the total group was 83+/-2%, and 3-year-overall survival was 92+/-2%. Patients < or=1.5 years had a better outcome than older children. Deletions/imbalances of chromosome 1p were found in 9/90 patients and were associated with a higher event rate but not with a higher death rate. Aberrations of chromosome 11q in 14/91 patients were correlated with a higher event and death rate. Multivariate analysis identified 1p aberrations as important for event free survival and 11q aberrations for overall survival.
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PMID:Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q. 1601 35


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