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

Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome-inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed.
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PMID:Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo. 130 25

The effect of persistent measles virus infection on the expression of major histocompatibility complex (MHC) class I antigens was studied. Mouse neuroblastoma cells C1300, clone NS20Y, were persistently infected with the Edmonston strain of measles virus. The persistently infected cell line, NS20Y/MS, expressed augmented levels of both H-2Kk and H-2Dd MHC class I glycoproteins. Activation of two interferon(IFN)-induced enzymes, known to be part of the IFN system: (2'-5')oligoadenylate synthetase and double-stranded-RNA-activated protein kinase, was detected. Measles-virus-infected cells elicited cytotoxic T lymphocytes that recognized and lysed virus-infected and uninfected neuroblastoma cells in an H-2-restricted fashion. Furthermore, immunization of mice with persistently infected cells conferred resistance to tumor growth after challenge with the highly malignant NS20Y cells. The rationale for using measles virus for immunotherapy is that most patients develop lifelong immunity after recovery or vaccination from this infection. Patients developing cancer are likely to have memory cells. A secondary response induced by measles-virus-infected cells may therefore induce an efficient immune response against non-infected tumour cells.
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PMID:Persistent measles virus infection enhances major histocompatibility complex class I expression and immunogenicity of murine neuroblastoma cells. 134 54

The relationship between 6-hydroxydopamine (6-OHDA)-induced ablation of central and peripheral adrenergic neurons and in situ C-1300 murine neuroblastoma (MNB) tumor growth and catecholamine concentration were investigated. Destruction of central and/or peripheral adrenergic neurons was produced by the intracerebral and/or s.c. administration of 6-OHDA to neonatal A/J mice. Disaggregated MNB cells (1 x 10(6)) were implanted s.c. into each mouse 3 weeks after treatment with 6-OHDA or diluent. Tumor onset time (the time interval between implantation of MNB cells and detection of palpable tumor), tumor weight, tumor weight to body weight ratio, tumor growth rate constant and tissue catecholamine concentrations were determined. Central axotomy caused a significant increase in tumor onset time and decrease in tumor weight when compared to controls. However, neither the tumor weight to body weight ratio or tumor growth rate constant were significantly lowered. In contrast, a reduction in all tumor growth parameters was produced by peripheral axotomy, which differed significantly from centrally axotomized and control animals. The catecholamine concentration of MNB tumors excised from control and 6-OHDA-treated mice 8 days after tumor onset were determined. Norepinephrine and dopamine levels were elevated above controls in MNB tumors obtained from mice that had been either peripherally or peripherally and centrally axotomized; whereas, no change in tumor catecholamine concentrations was noted in centrally axotomized mice. This investigation has demonstrated that ablation of central as well as peripheral adrenergic innervation exerts an inhibitory effect on MNB tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of 6-hydroxydopamine-induced ablation of peripheral and central adrenergic axons on C-1300 murine neuroblastoma tumor growth and catecholamine concentration in the A/J mouse. 152 14

Nutrient substrates have been shown to enhance cell-mediated immunity, but their role as adjuvants to immunotherapy has not been previously determined. This study evaluated L-arginine as an essential substrate for optimal generation of lymphokine-activated killer (LAK) cells. This experiment also assessed supplemental dietary L-arginine as a means to potentiate the host antitumor response to interleukin-2 (IL-2) in a murine neuroblastoma (NRB) model. A/J mice received 1% arginine or isonitrogenous 1.7% glycine in addition to a regular diet 14 days before subcutaneous inoculation with C1300 NRB cells. Twenty-four hours later, animals received low (1 x 10(6) U/kg three times a day) or high (3 x 10(6) U/kg three times a day) doses of IL-2 or saline intraperitoneally for 4 days. On days 4 and 10 post-C1300 NRB inoculation, mice were killed for assessment of natural killer cell and tumor specific cytotoxicity. Remaining animals were followed for tumor incidence, tumor growth, and duration of host survival. Interleukin-2 therapy in mice receiving dietary arginine compared with those receiving glycine resulted in significantly augmented natural killer cell cytotoxicity (day 4) and generation of specific tumoricidal mechanisms (day 10). The addition of dietary arginine to low-dose IL-2 therapy significantly diminished C1300 NRB engraftment (p less than 0.05) and growth (p less than 0.001) and prolonged the duration of host survival (p less than 0.05) compared with the glycine treatment group. In vitro studies demonstrated that L-arginine is an essential substrate for optimal generation of LAK cells. Thus, supplemental dietary L-arginine enhances lymphocyte cytotoxic mechanisms and potentiates IL-2 immunotherapy.
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PMID:Enhancement of interleukin-2 immunotherapy with L-arginine. 154 2

We have investigated the effects of retinoic acid (RA), human recombinant gamma interferon (gamma-IFN), and the association of both agents on the growth of human neuroblastoma (NB) cells in [CD1(nu/nu)] nude mice. Two human NB cell lines, namely LAN-5 and GI-LI-N, were previously adapted to grow in syngeneic animals for 7 consecutive passages. At the eighth passage, only animals which developed 10-mm diameter tumors within 40 days from xenograft were admitted to the study. RA and/or gamma-IFN were administered subcutaneously 3-5 days per week for 3 consecutive weeks. The number of days necessary for each tumor mass to grow up to 20 mm diameter (in vivo doubling time, ivDT) was then evaluated. Tumor growth was significantly inhibited in gamma-IFN (P less than 0.005) and RA (P less than 0.05) treated mice grafted with GI-LI-N. The combination of the two agents did not further enhance ivDT. The tumor growth inhibition was not statistically significant in LAN-5 bearing mice treated with RA or gamma-IFN alone, while a synergistic effect between the two drugs was observed (P less than 0.05). We conclude that parenteral combined administration of RA and gamma-IFN may prove to be useful in inhibiting the growth of tumors derived from human NB cells resistant to single inducers.
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PMID:Gamma-interferon and retinoic acid synergize in inhibiting the growth of human neuroblastoma cells in nude mice. 173 46

The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A/J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P less than .05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P less than .02) compared with surgical controls. In addition, 30% of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14% had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.
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PMID:Chemoimmunotherapy in conjunction with surgery: strategies for management of murine neuroblastoma. 177 33

Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor-weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM.
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PMID:Comparison of acute and chronic protein-energy malnutrition on host antitumor immune mechanisms. 190 Nov 2

The in situ C-1300 murine neuroblastoma (MNB) tumor model was used to investigate the influence of exogenously administered nerve growth factor (NGF) on tumor growth and tissue catecholamine concentration in mice sympathectomized with 6-hydroxy-dopamine (6-OHDA) on postnatal days 4-10. Mice were implanted with 1 x 10(6) disaggregated MNB cells 3 days after termination of 6-OHDA administration. NGF (12-15 micrograms/mouse/day) treatment was initiated at the time of MNB cell implantation and continued until sacrifice of the animal. The time interval between tumor cell implantation and detection of palpable tumor (tumor onset time), transverse tumor diameter, tumor weight, tumor weight to body weight ratio, and tumor catecholamine concentration were determined. Neonatal sympathectomy caused a decrease in myocardial norepinephrine concentration of 88% compared with vehicle-treated animals as well as a significant reduction in total body and organ weight. Average body, brain, heart, and spleen weights were decreased 31%, 16%, 25%, and 42%, respectively, below control values. The daily injection of NGF, from the time of MNB tumor implantation to sacrifice, did not prevent these effects of chemical sympathectomy from being expressed. Tumor onset time following implantation of MNB cells was significantly increased in neonatally sympathectomized mice and was not altered by treatment with NGF. In contrast, the decrease in MNB tumor growth rate observed in sympathectomized mice was reversed by administration of NGF. Mean tumor weight and mean tumor to body weight ratio were 89% and 115% of comparable control values, respectively, in sympathectomized mice receiving exogenous NGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of nerve growth factor on C-1300 murine neuroblastoma tumor growth and catecholamine content in neonatally sympathectomized mice. 190 44

The effects of metoclopramide (MCP) and bromocriptine (BC) on the growth of neuroblastoma (NB) cells and their influence on the plasma membrane binding of several neurotransmitters were studied. In the first part of this study, in vitro experiments were done with three human and two murine NB cell lines. Dibutyryl cyclic 3',5'-adenosine monophosphate is known to differentiate NB cells in vitro and served as a reference substance during the experiments. MCP significantly reduced the replication rate in NB cells and increased cellular differentiation by morphological as well as by functional criteria. BC, in contrast, stimulated cell replication. Similar to dibutyryl cyclic 3',5'-adenosine monophosphate, MCP increased the binding capacity of the plasma membrane for the beta-adrenergic hormones dopamine and noradrenaline. In the second part, the effects of BC and MCP upon NB tumor growth were investigated in vivo in the mouse. Significant changes in tumor growth were induced; BC promoted and MCP inhibited the NB tumor growth in a dose-dependent relationship. The findings are discussed, along with the observed accompanying changes in serum copper and in the peripheral blood count.
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PMID:Influence of metoclopramide and bromocriptine upon the growth of human and murine neuroblastoma cells. 196 34

Gangliosides shed by tumor cells are implicated in modulating tumor formation. For example, rapid progression of human neuroblastoma tumors is associated with high circulating levels of shed GD2 ganglioside. To elucidate the kinetic and qualitative characteristics of tumor cell ganglioside shedding, which is difficult to accomplish in vivo, we examined this process in LAN-5 human neuroblastoma cells in vitro. Three major gangliosides, GD2, GM2 and GT1b, comprise 82% of the mean total of 38 nmol LBSA/10(8) cells. These molecules are shed very rapidly (1-3 pmol/10(6) cells per h, or approx. 0.5% of the total cell gangliosides per h). Quantitative and qualitative characteristics of ganglioside shedding are remarkably constant over a 40-fold range of cell density. Not only GD2, but every major carbohydrate species is shed, in proportion to its concentration in the cell, with slightly greater shedding of ceramide subspecies containing shorter chain fatty acids. These findings were confirmed in three other neuroblastoma cell lines, LAN-1, IMR and KCNR. We suggest that the high expression and rapid generalized shedding of human neuroblastoma tumor gangliosides results in significant in vivo accumulation of these biologically active molecules during tumor growth.
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PMID:Shedding of human neuroblastoma gangliosides. 203 38


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