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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma remains a common and deadly childhood tumor, resistant to both surgical and chemo/radiotherapeutic intervention in its advanced stages. The role of immunotherapy in such cancers has yet to be defined. In previous work, we found that the addition of interferon gamma (IFN-gamma) to 3-day in vitro tissue cultures of the murine neuroblastoma C1300, led not only to the tumor's increased cell surface expression of the immunologically important major histocompatibility complex (MHC) class I antigen, but also to an increased susceptibility of such modified tumor to subsequent lymphokine activated killer (LAK) cell lysis. In this study, we sought to determine the in vivo applicability of these findings. Initial dose-response studies helped define a regimen of rIFN-gamma's administration that upregulated MHC class I without activating host natural killer (NK) activity. A/J mice bearing 7-day-old subcutaneous C1300 were randomized to receive daily morning injections of either 0, 25,000, 50,000, or 100,000 U of rIFN-gamma intraperitoneally for 6 days. Animals were killed at days 3, 6, and 9 after initiation of rIFN-gamma therapy, and tumors were excised, digested, and stained for both MHC class I and II expression. At the time of sacrifice, splenocytes from each animal were tested for NK cytotoxicity toward YAC (an NK-sensitive lymphoma) and C1300. These studies defined 3 days of therapy with 25,000 U as a "priming" dose that increased expression of class I with minimal impact on NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose interferon gamma renders neuroblastoma more susceptible to interleukin-2 immunotherapy. 190 48

The purpose of this study was to determine if a 3-day in vitro culture of the murine neuroblastoma C1300 with 500 U/mL of recombinant interferon gamma resulted in a protective crossreactivity to parent C1300. Twenty A/J mice received either a vaccine of 1 x 10(6) irradiated C1300 tumor cells intradermally or an equivalent inoculum of C1300 that had been incubated in recombinant interferon gamma (C1300*). One week later, all animals were rechallenged with 1 x 10(6) viable C1300. Animals immunized with C1300* had a significantly delayed early tumor incidence that translated into a survival advantage for the group. At the time of tumor rechallenge, a significantly increased level of nonspecific systemic immunity was conferred by the C1300* immunization. Thus, modification of tumor with recombinant interferon gamma before introduction as a vaccine may improve that vaccine's protective capability.
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PMID:Tumor immunization. Improved results after vaccine modified with recombinant interferon gamma. 210 10

The purpose of this study was to examine the susceptibility of NB-I human neuroblastoma cells to direct cellular cytotoxicity mediated by peripheral blood monocytes from pediatric cancer patients receiving chemotherapy. Nonactivated monocytes from patients showed spontaneous cytotoxicity to NB-I neuroblastoma cells (37 +/- 18%) but only marginal cytotoxicity to A375 melanoma cells (21 +/- 14%) at the effector:target cell ratio of 20:1. This spontaneous cytotoxicity to NB-I cells was observed only after greater than 24 h of cocultivation and was proportional to the effector:target cell ratio. Activation of monocytes by recombinant human interferon gamma (rIFN) (1 x 10(4) U/ml) consistently and strongly enhanced their tumoricidal activity to NB-I cells (87 +/- 6%) and this tumoricidal activity was even superior to that observed against A375 cells, which are known to be extremely sensitive to lysis by activated monocytes. In contrast, activation of monocytes by lipopolysaccharide (LPS, 1 microgram/ml) had no effect on monocyte-mediated lysis of NB-I cells, while A375 cells were equally lysed by rIFN- and LPS-activated monocytes, thus suggesting that different mechanisms are involved in the monocyte-mediated lysis of A375 melanoma and NB-I neuroblastoma cells. Susceptibility of the neuroblastoma cell line to monocyte-mediated cytotoxicity has not been reported so far and our results may have some clinical implication if this observation can be extended to other neuroblastoma cell lines as well.
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PMID:Susceptibility of NB-I neuroblastoma cells to tumoricidal activity of monocytes activated by gamma-interferon. 212 74

Human neuroblastoma (NRB) cell lines are markedly sensitive to natural killer (NK) cell lysis in vitro, but patients with NRBs have low or absent NK activity. This study evaluated the NK sensitivity of murine NRBs (C1300 and TBJ) in the regulation of NRB growth and determined the effects of recombinant (r) interferon gamma and recombinant interleukin 2 (rIL-2). Both basal (8% +/- 3% specific cytotoxicity) and induced (20% +/- 3%) NK lyses of C1300-NRB were observed. In vivo depletion of NK cells with anti-asialo GM-1 significantly enhanced growth of C1300-NRB and decreased survival. Treatment with r-interferon gamma or rIL-2 on days 1 through 3 after C1300-NRB inoculation significantly prolonged the mean tumor latency period, decreased the tumor growth rate, and enhanced in vitro NK killing of C1300-NRB and YAC-1. The effects of r-interferon gamma and IL-2 were abrogated by pretreatment with anti-asialo GM-1. These results demonstrated that NK cells form one important component of regulation of a murine NRB, but immunomodulation with potent lymphokines requires cooperation of more than one cell type.
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PMID:The influence of natural killer cells in neuroblastoma. 249

To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.
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PMID:Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. 251 80

Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class I molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon gamma (IFN gamma). Following IFN gamma treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer.
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PMID:Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest. 751 27

Based on our previous observations that neuroblastoma (NB) cells express fibroblast growth factor-2 (FGF-2; basic FGF) and respond to it [Janet T. et al. (submitted); Wewetzer K. et al. (1993) J. Neurosci. Res. 36, 209-215), we attempted to find to what extent selected cytokines [interleukin (IL)-1 beta and interferon gamma (IFN gamma)] may modulate FGF-mediated proliferative activity and differentiation. The NB cell lines IMR-32, SH-SY5Y, GIMEN and LAN-1 and colorimetric assays were used for the determination of cell numbers. IL-1 beta (and several other ILs, including IL-1 alpha, -2, -3, and 6) per se did not affect proliferation of any cell line studied. IFN gamma inhibited growth of GIMEN and LAN-1 cells, but was uneffective on IMR-32 and SH-SY5Y cells. FGF-2 was antimitogenic for GIMEN cells. IFN gamma reversed and IL-1 beta enhanced this antimitogenic effect of FGF-2. FGF-2 per se did not affect LAN-1 cells and did not modulate the growth inhibitory actions of IFN gamma on these cells. FGF-2 induced proliferation of IMR-32 and SH-SY5Y cells. This effect was not modulated by IFN gamma or IL-1 beta. These results suggest a heterogeneous response pattern of human NB cell lines towards the cytokines studied and complex interactions of FGF-2, IL-1 beta and IFN gamma.
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PMID:Interleukin-1 beta and interferon gamma interact with fibroblast growth factor-2 in the control of neuroblastoma cell proliferation and differentiation. 781 83

Neuroblastoma is one of the commonest solid tumors in children. Conventional therapeutic approaches, such as surgery, chemotherapy and radiotherapy, fail to control tumor progression in stage III and IV patients. The search for novel therapeutic strategies should necessarily take into account immunotherapy and gene therapy. Here the theoretical bases for the development of such approaches are discussed. Studies carried out with neuroblastoma (NB) cell lines have shown that neoplastic cells express a wide array of potential tumor associated antigens (TAA) but are devoid of HLA molecules which are necessary for TAA presentation to the host immune system. Transfection of NB cells with the interferon gamma gene appears a promising approach, since this cytokine up-regulates the expression of class I HLA molecules in NB cells. Other cytokines of potential interest for gene transfer studies are interleukin 2 (IL2) and interleukin 12 (IL12).
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PMID:[Rational bases for new approaches to the therapy of pediatric solid tumors: immunotherapy and gene therapy]. 797 43

The product of the nm23 gene has been proposed as a candidate tumour metastasis suppressor protein. A strong association has been observed between reduced expression of the nm23 gene and acquisition of metastatic behaviour in some tumour cells, including breast cancer and melanoma, but not in others, such as neuroblastoma and colon, cervical and thyroid cancers. During the early gestation period both human and murine trophoblast cells exhibit in vitro invasive properties similar to those of neoplastic cells. Such invasive properties, however, disappear in the late stage of gestation. In the present study, we examined the abundance of nm23 mRNA from various fetal-maternal interface tissues (uterus, decidua, placenta and embryo) during early (day 8), mid (day 14) and late (day 18) stages of gestation in CD1 mice, in order to determine whether nm23 plays any anti-invasive and/or biological roles during gestation. nm23 was found to be expressed in all the tissues during the early and mid stages of gestation. The expression levels were, however, variable among different tissues and development stages. In the early stage, nm23 mRNA levels were the highest and similar among tissues from the uterus, decidua, placenta and embryo. In the mid stage, the mRNA levels were reduced significantly in the uterus, decidua and placenta, but not in the embryo. In the late stage, nm23 mRNA was further reduced to the extent that it could not be seen in the decidua, was barely seen in the uterus and was weakly present in the placenta. However, the mRNA level of the embryo in the late stage was still high and similar to the early stage. We also examined nm23 expression in trophoblast cells from normal human term placenta and a highly metastatic human choriocarcinoma cell line, JAR. nm23 expression was significantly higher in JAR than in normal placenta, indicating that nm23 does not appear to have an anti-metastatic function in this cell line. Several cytokines--interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)--and prostaglandin E2 (PGE2) known to modulate tumour growth and metastasis were examined to determine whether they regulate nm23 expression in JAR in vitro. The B16F10 melanoma cell line was used as control. No effect was found in the JAR cell line, whereas TNF-alpha, IFN-gamma and PGE2 down-regulated nm23 expression in the B16F10 cell line.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential nm23 gene expression at the fetal-maternal interface. 808 Jul 27

Neuroblastoma (NB) is a major-histocompatibility-complex(MHC)-negative neuroectodermal tumour that is often infiltrated with lymphocytes. A detailed characterization of NB-associated tumour-infiltrating lymphocytes (TIL) has never been carried out. Here we have investigated the immunophenotype and the cytotoxic activities of TIL from nine and seven NB patients respectively. Furthermore, the T cell receptor (TcR) variability and the patterns of cytokine gene expression of fresh versus recombinant (r) interleukin (IL)-2-cultured TIL were studied in four NB cases. The results obtained showed the following: (1) freshly isolated TIL were comprised of a mixture of CD4+ and CD8+ T cells partially expressing HLA-DR and/or CD25. The CD4/CD8 ratio ranged from 0.5 to 5 in the different cases. Upon culture of TIL with rIL-2, an increased proportion of CD56+ and CD8+ lymphocytes was consistently observed; (2) IL-2-expanded TIL lysed natural-killer(NK)sensitive and lymphokine-activated-killer(LAK)-sensitive target cell lines; (3) reverse-transcriptase/polymerase-chain-reaction (RT-PCR) experiments showed that most TcR V beta genes were expressed both in fresh and in cultured TIL, suggesting that such cell populations were polyclonal; (4) interferon gamma, IL-4, IL-5, tumour necrosis factor (TNF) alpha, IL-8, IL-10 mRNA and, to a lesser extent, IL-2 mRNA were expressed by cultured TIL, as assessed by RT-PCR; the corresponding tumour samples consistently contained TNF alpha, IL-8 and IL-10 mRNA, whereas IL-2 and IFN gamma mRNA were faintly expressed in some NB tumours and IL-4 and IL-5 mRNA were never detected. A total of 90 clones were subsequently raised from IL-2-expanded TIL from six NB patients; 87/90 clones were of T cell lineage with a CD4+ or CD8+ immunophenotype, whereas the 3 remaining clones were of NK cell origin. Upon triggering of the CD3-TcR complex, 64% CD4+ and 77% CD8+ T cell clones killed the murine P815 mastocytoma cell line. Virtually no T cell clone lysed a LAK-sensitive NB cell line whereas 15% CD4+ and 17% CD8+ clones mediated NK-like activity against the K562 cell line. Finally, the patterns of cytokine production by CD4+ clones were roughly consistent with those of a T helper (TH) 1 profile and similar to those observed in CD8+ clones.
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PMID:Functional and molecular characterization of tumour-infiltrating lymphocytes and clones thereof from a major-histocompatibility-complex-negative human tumour: neuroblastoma. 864 Aug 45


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