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)

Intracisternal A-particles were isolated from three different myeloma lines in BALB/c mice and from cultured neuroblastoma cells of A/J origin. All preparations contained a major structural protein with an apparent molecular weight near 70,000 as estimated by electrophoretic mobility in sodium dodecyl sulfate-containing polyacrylamide gels. Solubilization of this component by sodium dodecyl sulfate was dependent on prior or concomitant treatment with sulfhydryl compounds. The size distribution of A-particle proteins was markedly different from that observed for extracellular murine leukemia and mammary tumor viruses. Rabbit antiserum was developed that reacted with the major A-particle protein in both complement fixation and immunodiffusion assays. The antigen was detected in isolated neuroblastoma A-particles, in cytoplasmic membrane fractions prepared from various mouse tumors known to contain intracisternal particles, but not in preparations from normal mouse cells, in samples of leukemia and mammary tumor virus, or in JLS-V9 cells infected with Rauscher leukemia virus. Conversely, isolated A-particles did not react in complement fixation or immunodiffusion assays with antisera against leukemia virus antigens.
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PMID:Some structural and antigenic properties of intracisternal A particles occurring in mouse tumors (complement fixation-immunodiffusion-neuroblastoma-plasma-cell tumor). 433 40

Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors.
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PMID:Inhibition of rate of tumor growth by creatine and cyclocreatine. 847 72

Estrogens are known to modulate the growth rate and differentiation state of a number of cells. In uterine, as well as in mammary tumor cells, estrogen-dependent proliferation and differentiation are correlated to a series of biochemical responses, including increased expression of proto-oncogenes such as: c-fos, c-jun and c-myc. Since estrogens were shown to regulate the proliferation and the differentiation state of cells of nervous origin, the aim of the present study was to investigate whether these effects were associated to changes in the expression of early genes. In the model system utilized, the human cell line SK-ER3, an increase in c-fos mRNA and Fos protein without change of c-jun and related genes mRNA concentration was observed after short term treatment with 17 beta-estradiol (E2). A significant decrease of c-fos, c-jun and jun-D proto-oncogene mRNA levels were found after prolonged hormonal treatment. The exposure to the hormone did not determine any change in N-myc expression. Since the three protooncogene mRNAs are rapidly induced following estrogen treatment in other cell systems and target tissues, it is concluded that the estrogen-induced differentiation of neuroblastoma cells is correlated to a pattern of expression of early genes that might be peculiar for the activity of this hormone in neural cells.
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PMID:Expression of early genes in estrogen induced phenotypic conversion of neuroblastoma cells. 874 25

CaMK-II (the (type II) multifunctional Ca2+/CaM-dependent protein kinase) has been implicated in diverse neuronal and non-neuronal functions, including cell growth control. CaMKII expression was evaluated in a variety of human tumor cell lines using RT-PCR (reverse transcriptase coupled polymerase chain reaction). PCR primers which flanked the CaMK-II variable domain were used so that all possible variants of the four mammalian CaMK-II genes (alpha, beta, gamma and delta) could be identified. 8 distinct CaMK-II isozymes were identified from human mammary tumor and neuroblastoma cell cDNA, each of which represented a variant of beta, gamma or delta CaMK-II. They included 2 beta isozymes (beta e, beta 'e), 4 gamma isozymes (gamma B, gamma C, gamma G, gamma H) and 2 delta isozymes (delta C, delta E) This is the first report of human beta and delta CaMK-II sequences. A panel of human cell types was then screened for these CaMK-II isozymes. As expected, cerebral cortex predominately expressed alpha, beta and delta A CaMK-II. In contrast, tumor cells, including those of neuronal origin, expressed an entirely different spectrum of CaMK-II isozymes than adult neuronal tissue. Tumor cells of diverse tissue origin uniformly lacked alpha CaMK-II and expressed 1-2 beta isozymes, at least 3 gamma isozymes and 1-2 delta isozymes. When compared to undifferentiated fibroblasts, beta e, beta'e, gamma G and gamma H were preferentially expressed in tumor cells. CaMK-II immunoblots also indicated that neuroblastoma and mammary tumor cells express isozymes of CaMK-II not present in their non-transformed cell or tissue counterpart. The identification of these new, potential tumor-specific CaMK-II variants supports previous indications that CaMK-II plays a role in growth control. In addition, these results provide insight into both splice variant switching and variable domain structural similarities among all CaMK-II isozymes.
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PMID:Identification of novel human tumor cell-specific CaMK-II variants. 906 Sep 99

We examined whether antitumor immunity could be generated by the inoculation of cytokine-producing murine neuroblastoma cells (C1300), and whether the immunity might be effective for the established tumors of wild-type (wt) cells. For that purpose, we transduced low immunogenic C1300 cells with interleukin-2 (IL-2), GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngeneic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 cells, although their in vitro growth rates were not affected by the transduction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did not develop tumors of wt cells inoculated subsequently, but formed tumors of irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of IL-2 or GM-CSF producers into immunocompetent mice generated tumor-specific acquired immunity. The induced immunity using IL-2 or GM-CSF producers was also effective in eradicating established subcutaneous tumors of wt cells and in reducing the number of preexisting metastatic foci in the liver. These data suggest a potential application of IL-2- or GM-CSF-producing syngeneic tumor cells for the treatment of low immunogenic neuroblastomas.
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PMID:Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors. 1050 49

Gene therapy of oral cancer will require expression of genes by promoters that are both powerful and relatively tumor specific. We compared the level of expression of a reporter gene from promoters of human cytomegalovirus (CMV), SV40 virus, mouse mammary tumor virus (MMTV), human papillomaviruses (HPV) types 16 and 18, and the human multi-drug-resistance gene (mdr1), in several lines of oral cancer cells. In the oral cancer cell line 686LN the rank order of expression levels was: CMV > SV40 > HPV > mdr1 > MMTV. Unlike in previous reports the mdr1 promoter was no more active in two cancer cell lines with mutations in the p53 gene than in two other lines with wild-type p53, and its expression level could not be increased by either doxorubicin or taxol. On the other hand, expression from the MMTV promoter was increased over 10-fold by the presence of 1 microM dexamethasone. Thus, by an appropriate choice of promoter and inducer a wide variety of expression levels, over a 3-log range, could be attained in 686LN cells. The oral cancer-specificity of each promoter was judged by comparing expression in the neuroblastoma line IMR32. The most specific promoters were those from papillomaviruses, which were up to 45 times more active in the oral cancer cells, and the least specific was the CMV promoter. In order to find if an HPV-derived promoter was sufficient to produce expression of a suicide phenotype the 686 promoter was cloned adjacent to the thymidine kinase gene of herpes simplex and the construct was expressed from an adenovirus vector. The vector reduced the growth of 686LN cells over a 5-day period by up to 32% when optimal concentrations of virus and ganciclovir were used. These data will be valuable in the design of new constructs for gene therapy of oral cancer.
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PMID:Strength and specificity of different gene promoters in oral cancer cells. 1074 75

We identified patterns of differentially-expressed genes in cell lines derived from several pediatric solid tumors. Affymetrix Human Cancer G110 Arrays, carrying 1,700 cancer-associated genes, were applied to a panel of 11 cell lines originating from Ewing tumors (ETs), neuroblastomas, and malignant melanoma of soft parts. Hierarchical clustering clearly differentiated these 3 entities and revealed groups of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific up-regulation in these cell lines, respectively. Whereas ET lines demonstrated increased expression of microtubule-associated protein tau (MAPT), protein phosphatase 1 regulatory subunit 1A (PPP1R1A), NIMA (never in mitosis gene a)-related kinase 2 (NEK2), and cyclin D1 (CCND1), neuroblastoma samples exhibited high expression of wingless-type mouse mammary tumor virus integration site family member 11 (WNT11), Drosophila frizzled homolog 2 (FZD2), and adenomatous polyposis coli (APC) which are involved in regulating free beta-catenin levels. These genes likely maintain tumor-specific characteristics and participate in key downstream regulatory mechanisms. We also correlated the expression levels of up-regulated genes in ETs with their chromosomal localization and compared these data to the comparative genomic hybridization profiles of the cell lines. We demonstrate that gains of genetic material contribute essentially to differential gene expression.
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PMID:Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays. 1183 53

The radiolabeled triplex-forming oligonucleotide (TFO) demonstrated the potential for sequence-specific DNA binding and destruction. In this study, by selecting the polypurine-polypyrimidine stretch (2950-2978) in the human N-myc gene as a target, the (111)In-labeled TFO targeting human N-myc gene (N-mycTFO(111)In) was tested for its cellular uptake and nuclear localization in vitro and in vivo. This is because the deregulated N-myc expression is strongly implicated in the pathogenesis of several important human malignancies, including breast carcinoma and neuroblastoma. N-mycTFO(111)In was bound selectively to the N-myc sequence in vitro. The total cellular uptake of TFO after the incubation of various normal and cancer cells with TFO for 24 h was 20-54.8% of the injected dose (%ID), and the nuclear localization was 6.59-30.0%ID, depending on cell lines. The highest cellular uptake was found in the human neuroblastoma SK-N-DZ (54.8%ID), human mammary ductal carcinoma T47-D (54%ID), human acute T cell leukemia Jurkat (54%ID), and multidrug-resistant human breast adenocarcinoma MCF7/TH (49.5%ID). The lowest was in the human normal mammary epithelium MCF10A (20.0%ID). The highest nuclear localization was found in MCF7/TH (30%ID) and SK-N-DZ (28.7%ID). The lowest was in MCF11A (6.59%ID). We next injected TFO into human mammary tumor-xenografted Balb/c nude mice. Tumor targeting of TFO in vivo reached its maximum peak 5 h after the intravenous injection in three types of tumor models. They are 21.0 +/- 3.23%ID per gram of tissue (%ID/g) for MCF7/TH, 7.77 +/- 2.11%ID/g for MCF7, and 4.53 +/- 1.20%ID/g for MCF10A. The TFO blood level decreased from 8.00 +/- 0.90%ID/g 15 min after the injection, to 1.30 +/- 0.30%ID/g after 19 h. The kidney TFO level increased rapidly from 5.93 +/- 0.94%ID/g after 15 min, to 25.1 +/- 5.60%ID/g after 19 h. A high TFO level (19.7-24.5%ID/g) in the liver was maintained until 19 h after the injection. Therefore, we suggest that the (111)In-labeled N-myc-targeting TFO, a promising modality for nanoexplosive gene therapy, could effectively target the nucleus of the multidrug-resistant breast carcinoma MCF7/TH in vitro and in vivo. It has approximately 130 min of half-life of blood TFO.
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PMID:Pharmacokinetics of (111)In-labeled triplex-forming oligonucleotide targeting human N-myc gene. 1224 59

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is involved in amyloid beta dependent neurotoxicity via the extrinsic pathway. Recently, several genes modulating TRAIL cytotoxicity have been characterized, providing evidence for a role of wingless-type mouse mammary tumor virus integration site family (Wnt), Jun-N-terminal kinase and other pathways in increased cell susceptibility to the cytokine. We investigated whether neurotoxic effects of TRAIL could be due to modulation of the Wnt signaling pathway. Western blot analysis of Wnt in SH-SY5Y human neuroblastoma cells showed significantly decreased Wnt expression in cultures treated with TRAIL. Correspondingly, both phosphorylation of glycogen synthase kinase 3 beta and degradation of cytoplasmic beta-catenin were increased, as well as phosphorylation of the tau protein, bringing about the picture of neuronal damage. As a counterproof of the interaction of TRAIL with the Wnt pathway, the addition of the specific glycogen synthase kinase 3 beta inhibitor SB216763 resulted in rescue of a significant percent of cells from TRAIL-induced apoptosis. The rescue was total when the caspase 8 inhibitor z-IETD-FMK was added in combination with SB216763. Results show that, probably, in addition to triggering caspase signaling, TRAIL also interferes with the Wnt pathway, additionally concurring to neuronal damage. These data suggest that the Wnt pathway substantially contributes to the TRAIL-related neurotoxicity and indicate the TRAIL system as a candidate target for pharmacological treatment of Alzheimer's disease and related disorders.
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PMID:TRAIL-related neurotoxicity implies interaction with the Wnt pathway in human neuronal cells in vitro. 1826 28

Human diseases such as Nijmegen breakage syndrome due to mutations in the NBS1 gene result in defects in resection of double strand breaks. NBS1 functions as part of the MRN complex which functions in homologous recombination and non-homologous end joining. NBS is a rare human autosomal recessive disorder caused by hypomorphic mutations. At the cellular level, NBS is characterized by radiosensitivity, chromosomal breakage and defective cell cycle checkpoints. NBS1 null mutations result in early embryonic lethality in mice, but NBS1 hypomorphic mutants are viable. Cells from these mice are defective in S phase and G2/M checkpoints. In humans, NBS1 polymorphisms have been associated with increased risk of breast cancer. MRN expression was reduced in the majority of breast tumors, and low expression of MRN correlated with increased histologic grade and estrogen receptor negativity. While these studies have shown NBS1 to be important in clinical outcomes of patients with breast cancer, mammary tumors are rare in the NBS1 haploinsufficient mouse. To better understand the role of NBS1 in mammary tumorigenesis, we examined the NBS1+/-;MMTV-neu mouse model. Mammary tumor latency was markedly increased in NBS1+/-;neu mice compared to NBS1+/+;neu control animals. This effect was due to increased apoptosis in early NBS1+/-;neu mammary tumors. However, NBS1+/-;neu mammary tumors were highly metastatic and demonstrated clear differences in gene expression profiles compared to control tumors. We concluded that NBS1 haploinsufficiency results in increased mammary tumor latency and metastasis.
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PMID:Haploinsufficiency of the Nijmegen breakage syndrome 1 gene increases mammary tumor latency and metastasis. 2257 91


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