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)

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.
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PMID:Status of allogeneic bone marrow transplantation in childhood in the GDR. 248 Feb 79

A genetically engineered fusion protein consisting of a human/mouse chimeric anti-ganglioside GD2 antibody (ch14.18) and recombinant human interleukin 2 (rhIL-2) was tested for its ability to target rhIL-2 to tumor sites and stimulate immune effector cells sufficiently to achieve effective tumor cell lysis in vivo. The ch14.18-IL-2 fusion protein proved more effective than equivalent doses of rhIL-2 in suppressing dissemination and growth of human neuroblastoma in an experimental hepatic metastases model of scid (severe combined immunodeficiency) mice reconstituted with human lymphokine-activated killer cells. The ch14.18-IL-2 fusion protein was also more proficient than equivalent doses of rhIL-2 in prolonging the life-span of these animals. This recombinant antibody-cytokine fusion protein may prove useful for future treatment of GD2-expressing human tumors in an adjuvant setting.
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PMID:A recombinant antibody-interleukin 2 fusion protein suppresses growth of hepatic human neuroblastoma metastases in severe combined immunodeficiency mice. 793 18

Several monoclonal antibodies (mAbs) were screened on different neuroblastoma cell lines to evaluate ricin A-chain immunotoxins for possible use against human neuroblastoma. Four mAbs were identified that exhibited high antitumor activity against neuroblastoma cell lines as measured in an indirect cytotoxicity assay. These mAbs, including 14G2a (antidisialoganglioside), ch14.18 (a humanized switch variant), BW704 (antidisialoganglioside), and chCE7 (anti-glycoprotein of M(r) 190,000), were subsequently linked via the bivalent linker N-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-piridyldithio++ +)toluene to deglycosylated ricin A chain. The most potent immunotoxin, 14G2a.dgA, inhibited the protein synthesis of neuroblastoma cell lines IMR5 and NMB by 50% at concentrations of 6 x 10(-12) M. To test the antitumor efficacy of these immunotoxins in vivo, we developed a disseminated human neuroblastoma model in severe combined immunodeficiency mice. Treatment of tumor-bearing mice with 14G2a.dgA 12 days after tumor challenge resulted in a significant prolongation of survival as compared with phosphate-buffered saline-treated controls (16.8 versus 6.5 weeks). We conclude that ricin A-chain immunotoxins might be of potential use in the treatment of human neuroblastoma.
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PMID:Antidisialoganglioside ricin A-chain immunotoxins show potent antitumor effects in vitro and in a disseminated human neuroblastoma severe combined immunodeficiency mouse model. 795 65

A major problem in the treatment of solid tumors is the eradication of established, disseminated metastases. Here we describe an effective treatment for established experimental hepatic metastases of human neuroblastoma in C. B.-17 scid/scid mice. This was accomplished with an antibody-cytokine fusion protein, combining the unique targeting ability of antibodies with the multifunctional activity of cytokines. An anti-(ganglioside GD2) antibody (ch14.18) fusion protein with interleukin-2 (ch14.18-IL2), constructed by fusion of a synthetic sequence coding for human interleukin-2 (IL-2) to the carboxyl end of the C-gamma1 gene of chl4.18, was tested for its therapeutic efficacy against xenografted human neuroblastoma in vivo. The ch14.18-IL2 fusion protein markedly inhibited growth of established hepatic metastases in SCID (severe combined immunodeficiency) mice previously reconstituted with human lymphokine-activated killer cells. Animals treated with ch14.18-IL2 showed an absence of macroscopic liver metastasis. In contrast, treatment with combinations of ch14.18 and recombinant IL2 at dose levels equivalent to the fusion protein only reduced the tumour load. Survival times of SCID mice treated with the fusion protein were more than double that of control animals. These results demonstrate that an immunotherapeutic approach using a cytokine targeted by an antibody to tumor sites is highly effective in eradicating the growth of established tumor metastases.
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PMID:Eradication of established hepatic human neuroblastoma metastases in mice with severe combined immunodeficiency by antibody-targeted interleukin-2. 862 May 25

Gene transfer is a potentially powerful tool for the treatment of a wide variety of diseases. The transfer of these genes is achieved by utilizing a variety of vectors, including retroviral, adenoviral, adeno-associated virus (AAV) and a number of non-viral mechanisms. Numerous studies have successfully demonstrated transduction of genes into target cells with a variety of vectors, and have provided 'proof-in-principle' that gene transfer can result in prolonged in vivo expression of transduced genes, albeit at low quantities. Furthermore, gene marking studies in acute myeloblastic leukemia (AML), chronic myeloid leukemia (CML) and neuroblastoma have elegantly demonstrated that gene-marked tumor cells contribute to relapse following autologous transplantation. However none of the studies examining the therapeutic benefit of gene therapy has definitively demonstrated a clinically meaningful benefit. Nonetheless, the results of studies involving gene transfer for severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), melanoma and lung cancer highlight the potential benefit of this strategy. This review will discuss mechanisms of achieving gene transfer into target cells. It will examine some of the pre-clinical and clinical results to date and will discuss some of the potential uses of gene transfer for therapeutic purposes.
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PMID:Gene transfer: a review of methods and applications. 983 7

Several lines of evidence now indicate that type 1 insulin-like growth factor receptor (IGF1R) function may be particularly important in the pathogenesis of the pediatric cancer neuroblastoma. Modulating the expression of specific genes involved in neuroblastoma tumorigenesis could provide a much needed alternative treatment strategy for poor prognosis disease. We now report construction of an antisense expression vector to the IGF1R that markedly reduces cellular IGF1R levels and inhibits the proliferation and clonogenicity of neuroblastoma cells in vitro but not that of IGF1R null cells. This antitumor activity is associated with the induction of apoptotic cell death in transfected cells, as measured by annexin V staining and flow cytometry. Direct injection of this vector into established tumors growing in syngeneic mice results in a marked inhibition of tumor growth with complete and durable tumor regression in one-half of the animals. This effect appears to be immunologically mediated in that vector injection of neuroblastoma tumors growing in severe combined immunodeficiency mice results in only modest delay of tumor growth. Our results suggest that inhibition of IGF1R expression by direct intratumoral delivery of an antisense construct could provide a novel therapeutic approach in the management of poor prognosis neuroblastoma.
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PMID:Inhibition of insulin-like growth factor I receptor expression in neuroblastoma cells induces the regression of established tumors in mice. 985 76

Stem cell transplantations were performed in 69 children at Siriraj Hospital over a ten year period. The source of stem cells was bone marrow (60), peripheral blood (3), or cord blood (6). The diseases treated included 35 thalassemias, 11 Burkitt's lymphoma, five non-Hodgkin's lymphoma, five aplastic anemia, eight acute leukemia, and one each of neuroblastoma, severe combined immunodeficiency, Wiskott-Aldrich syndrome, myelodysplastic syndrome, and pyruvate kinase deficiency. The success rate of stem cell transplantation in Thai children varied according to the underlying diseases of the patients, ranging from 50% in acute leukemia to 100% in aplastic anemia. The outcome of stem cell transplantation in 35 thalassemic children revealed 23 (79.4%) were cured, whereas three (10.3%) remain alive with disease and the other three (10.3%) died. The incidence of graft-versus-host disease was low hen compared with that of Western countries. It is concluded that bone marrow, peripheral blood and cord blood stem cell transplantation will be the treatment of choice and will be widely used in the future to cure many hematologic and malignant disorders in children.
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PMID:Bone marrow, peripheral blood and cord blood stem cell transplantation in children: ten years' experience at Siriraj Hospital. 988 40

Histone deacetylase inhibitors (HDACIs) inhibit the growth of a variety of transformed cells in culture. We demonstrated previously that the hybrid-polar HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) induces apoptosis of human neuroblastoma in vitro and is effective in lower doses when combined with retinoids. The current study investigates the effect of CBHA on the growth of human neuroblastoma in vivo, both alone and in combination with all-trans retinoic acid (atRA), using a severe combined immunodeficiency-mouse xenograft model. CBHA (50, 100, and 200 mg/kg/day) inhibited growth of SMS-KCN-69n tumor xenografts in a dose-dependent fashion, with 200 mg/kg CBHA resulting in a complete suppression of tumor growth. The efficacy of 50 and 100 mg/kg CBHA was enhanced by the addition of 2.5 mg/kg atRA. This dose of atRA was ineffective when administered alone. Treatment was accompanied by mild weight loss in all groups except the lowest dose of CBHA. Our results suggest HDACIs alone or combined with retinoids may have therapeutic utility for neuroblastoma.
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PMID:The histone deacetylase inhibitor, CBHA, inhibits growth of human neuroblastoma xenografts in vivo, alone and synergistically with all-trans retinoic acid. 1132 25

Homeostasis of the extracellular matrix is a delicate balance between degradation and remodeling, the balance being maintained by the interaction of activated matrix metalloproteinases (MMPs) and specific tissue inhibitors of matrix metalloproteinases (TIMPs). Up-regulation of MMP activity, favoring proteolytic degradation of the basement membrane and extracellular matrix, has been linked to tumor growth and metastasis, as well as tumor-associated angiogenesis, whereas inhibition of MMP activity appears to restrict these processes. We have used retroviral-mediated gene delivery to effect sustained autocrine expression of TIMP-3 in murine neuroblastoma and melanoma tumor cells in order to further examine the ability of TIMPs to inhibit angiogenesis in vivo. Growth of both histologic types of gene-modified tumor cells in severe combined immunodeficiency (SCID) mice was significantly restricted when compared with controls. Grossly, these tumors were small and had few feeding vessels. Histologic evaluation revealed that although tumors overexpressing TIMP-3 had an increased number of CD31(+) endothelial cells, these endothelial cells had not formed functional tubules, as evidenced by decreased vessel continuity and minimal pericyte recruitment. This effect appears to be mediated, in part, by decreased expression of vascular endothelial (VE)-cadherin by endothelial cells in the presence of TIMP-3 as seen both in an in vitro assay and in TIMP-3-overexpressing tumors. Taken together, these results demonstrate that overexpression of TIMP-3 can inhibit angiogenesis and associated tumor growth, and that the antiangiogenic effects of TIMP-3 appear to be mediated through the inhibition of functional capillary morphogenesis.
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PMID:Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model. 1238 38

Neuroblastoma is a pediatric tumor accounting for 15% of childhood cancer deaths and has a poor prognosis in children >1 year of age. We investigated the ability of apigenin, a nonmutagenic dietary flavonoid that has been shown to have antitumor effects in various tumor cell lines, to inhibit growth and induce apoptosis of the human neuroblastoma cell lines NUB-7, LAN-5, and SK-N-BE(2). Apigenin inhibited colony-forming ability and survival, and induced apoptosis of NUB-7 and LAN-5 cells. The presence of the C2-C3 double bond and the 4'-OH group on the flavonoid structure correlated with the growth-inhibitory potential of apigenin. Furthermore, apigenin inhibited NUB-7 xenograft tumor growth in anonobese diabetic/severe combined immunodeficiency mouse model, likely by inducing apoptosis. Apigenin did not inhibit survival of primary sympathetic neurons, suggesting that it is not toxic to nontransformed cells. The mechanism of action of apigenin seems to involve p53, as it increased the levels of p53 and the p53-induced gene products p21WAF1/CIP1 and Bax. Furthermore, apigenin (15-60 micromol/L) induced cell death and apoptosis of neuroblastoma cells expressing wild-type but not mutant p53. Apigenin increased caspase-3 activity and PARP cleavage, and Z-VAD-FMK, a broad-spectrum caspase-3 inhibitor, rescued NUB-7 cells from apigenin-mediated apoptosis indicating that apigenin induced apoptosis in acaspase-dependent manner. Overexpression of Bcl-X(L) rescued NUB-7 from apigenin-induced cell death, suggesting that Bax activity is important for the action of apigenin. Apigenin is thus a candidate therapeutic for neuroblastoma that likely acts by regulating a p53-Bax-caspase-3 apoptotic pathway.
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PMID:Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma. 1565 48


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