Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein I kappa B, which inhibits the transcription factor NF-kappa B. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce I kappa B or inhibit activation of NF-kappa B by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kappa B by demonstrating that an oligonucleotide, containing the wild-type NF-kappa B-binding motif, inhibited formation of the NF-kappa B-DNA complexes whereas a mutated form of the NF-kappa B-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kappa B complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kappa B correlated with its inability to induce I kappa B and the ability of IL-1 to cause degradation of I kappa B, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kappa B.
...
PMID:Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B. 1043 51

We have identified a cytokine of the IL-6 family and named it novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3). NNT-1/BSF-3 cDNA was cloned from activated Jurkat human T cell lymphoma cells. Its sequence predicts a 225-aa protein with a 27-aa signal peptide, a molecular mass of 22 kDa in mature form, and the highest homology to cardiotrophin-1 and ciliary neurotrophic factor. The gene for NNT-1/BSF-3 is on chromosome 11q13. A murine equivalent to NNT-1/BSF-3 also was identified, which shows 96% homology to human NNT-1/BSF-3. NNT-1/BSF-3 mRNA is found mainly in lymph nodes and spleen. NNT-1/BSF-3 induces tyrosine phosphorylation of glycoprotein 130 (gp130), leukemia inhibitory factor receptor beta, and signal transducer and activator of transcription 3 in the SK-N-MC human neuroblastoma cells. NNT-1/BSF-3 shows activities typical of IL-6 family members. In vitro, it supports the survival of chicken embryo motor and sympathetic neurons. In mice, it induces serum amyloid A, potentiates the induction by IL-1 of corticosterone and IL-6, and causes body weight loss and B cell hyperplasia with serum IgG and IgM increase. NNT-1/BSF-3 is a gp130 activator with B-cell stimulating capability.
...
PMID:Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. 1050 Jan 98

Non-steroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of developing Alzheimer's disease (AD). Cyclooxygenase 2 (COX-2), one of the targets of NSAIDs, is increasingly expressed in neuronal cells in AD brain. In this study, of the cytokines that are found at increased levels in AD brain (interleukin (IL)-1alpha, IL-1beta, IL-6 and tumour necrosis factor (TNF)alpha), IL-1beta was found to induce COX-2 immunoreactivity and prostaglandin (PG) E2 secretion by human neuroblastoma cell line SK-N-SH. COX inhibitors indomethacin and BF389, as well as the glucocorticoid dexamethasone (DEX) and pyrrolidinedithiocarbamate, which is an inhibitor of nuclear factor kappaB as well as a potent antioxidant, inhibited IL-1beta induced PGE2 secretion. In addition, DEX reduced the IL-1beta induced COX-2 immunoreactivity in the same concentration as wherein it inhibited PGE2 secretion. Palmitoyl trifluormethyl ketone, an inhibitor of Ca(2+) independent phospholipase A2 (iPLA2) and a less potent inhibitor of cytosolic PLA2, dose-dependently reduced the IL-1beta induced PGE2 secretion. This suggests that the IL-1beta induced PGE2 secretion may depend on the availability of arachidonic acid. Although the physiological role of neuronal COX-2 still remains unclear, we suggest an interplay between glial derived IL-1 and neuronal upregulation of COX-2 expression in chronic neurodegenerative diseases, such as AD.
...
PMID:Interleukin-1beta induced cyclooxygenase 2 expression and prostaglandin E2 secretion by human neuroblastoma cells: implications for Alzheimer's disease. 1125 Jan 26

Nicastrin acts as a key regulator for presenilin (PS)-mediated gamma-secretase cleavage of beta-amyloid precursor protein by forming a functional complex with PS1 and PS2. Both TNF-alpha and IL-1, aberrantly produced by activated microglia and astrocytes, play a role in amyloidogenesis and neurodegeneration in the brains of Alzheimer's disease (AD) patients, while BDNF synthesized chiefly by neurons has been found to be substantially reduced in AD brains. To investigate the constitutive and cytokine/neurotrophic factor-regulated expression of nicastrin in human neural cells, its mRNA levels were studied by RT-PCR and northern blot analysis in SK-N-SH neuroblastoma cells, IMR-32 neuroblastoma cells, U-373MG astrocytoma cells, and NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N) following exposure to TNF-alpha, IL-1beta, BDNF, dibutyryl cyclic AMP, or phorbol 12-myristate 13-acetate. Nicastrin mRNA expression was identified in all human neural and nonneural cell lines and tissues examined. The levels of nicastrin mRNA, however, were unaltered in SK-N-SH, IMR-32, U-373MG, and NTera2-N cells by exposure to the factors tested, and unchanged in NTera2 cells during retinoic acid-induced neuronal differentiation. These results indicate that nicastrin mRNA is expressed constitutively in human neural cell lines, where its expression is not regulated at the transcriptional level by a battery of cytokines and growth/differentiation factors which are supposed to be involved in amyloidogenesis, neurodegeneration or neuroprotection in AD brains.
...
PMID:Nicastrin, a key regulator of presenilin function, is expressed constitutively in human neural cell lines. 1139 76

1. The role of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the mechanism of cell death induced by the human immunodeficiency virus type 1 (HIV-1) recombinant coat glycoprotein, gp120 IIIB, has been studied in the human CHP100 neuroblastoma cell line maintained in culture. 2. Death of neuroblastoma cells typically elicited by 10 pM gp120 or by human recombinant IL-1beta (10 ng x ml(-1)) has been minimized by the antagonist of IL-1 receptor, i.e. IL-1ra (0.5 and 50 ng x ml(-1), respectively), an endogenous molecule that antagonizes most of the biological actions of IL-1beta, or by an antibody (5 and 50 ng x ml(-1)) which blocks the human IL-1 receptor type I (IL-1RI). 3. ELISA experiments have established that gp120 enhances immunoreactive IL-1beta levels in the culture medium and this is prevented by exposure to the IL-1 converting enzyme (ICE) inhibitor t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone [Boc-Asp(OBzl)-CMK] used at a concentration (2.5 microM) which significantly (P<0.001) reduces cell death. 4. Death of CHP100 cells induced by gp120 is also prevented by acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK; 10-100 microM), a second inhibitor of ICE, supporting the concept that the viral protein stimulates the conversion of the 31 kDa pro-IL-1beta in to the 17 kDa mature cytokine which is then secreted to cause death. 5. In conclusion, our present data demonstrate that gp120 stimulates the secretion of IL-1beta which then triggers CHP100 neuroblastoma cell death via stimulation of IL-1 receptor type I.
...
PMID:HIV-1 coat protein gp120 stimulates interleukin-1beta secretion from human neuroblastoma cells: evidence for a role in the mechanism of cell death. 1170 56

Cell membrane dielectric properties of five different cultivated cell lines and human peripheral blood mononuclear cells (PBMC) were determined from dielectrophoretic crossover frequency measurements on a 5 x 5 microelectronic chip array. Based on distinct dielectric property differences between individual cell types, efficient cell separations were achieved by dielectrophoresis on this 5 x 5 array, which included separation of monocytic cells (U937) or human T cell leukemia virus type 1 (HTLV-1) tax-transformed cells (Ind-2) from PBMC, as well as separation of neuroblastoma cells (SH-SY5Y) from glioma cells (HTB). The purity of dielectrophoretically separated cells can be greater than 95%. Expression profiles of IL-1, TNF-alpha, and TGF-beta genes for U937 cells mixed with PBMC before and after the separation were determined by a means of electric field-facilitated hybridization on a 10 x 10 microelectronic chip array. By using the expression levels of pure U937 cells as a control, it was shown that the gene expression profiles of the postseparation cells were significantly different from those of the preseparation cell mixtures. The increase in gene expression levels for U937 cells upon lipopolysaccharide induction could be accurately determined only in the postseparation cells, while the preseparation samples masked these changes. Furthermore, by cultivating the separated HTB and SH-SY5Y cells and measuring expression of the stress-related gene c-fos, dielectrophoretic forces were shown to have little effect on cell survival and stress. The presented approach of using microelectronic chip arrays for both cell separation and gene expression profiling provides a great potential for accurate genetic analysis of specific cell subpopulations in heterogeneous samples.
...
PMID:Dielectrophoretic cell separation and gene expression profiling on microelectronic chip arrays. 1213 41

We evaluated the efficiency/tolerability of and the immunological changes induced by the adoptive immunotherapy (AIT) with IL-2-activated killer cells, and preparation of native cytokines from swine spleen (PSS) in treatment of 20 patients with advanced cancer (10 patients with primary lung cancer; 3 with metastatic melanoma; 2 with advanced neuroblastoma; 2 with ovarian cancer; renal cancer; gastric adenocarcinoma; and colorectal cancer). The partial/minor response of duration period 2-10 months was observed in 20% of patients. 2/4 patients, who underwent partial surgical tumor resection and following AIT course, sustained the event-free survival for more than 24 months. The response to the therapy was revealed in 4/10 patients with lung cancer, 2/2 patients with neuroblastoma, of whom each had ovarian and colorectal cancers. The evaluation of a dose of infused LAKcells as well as combined i.v./local (endobronchial or endoperitoneal) LAK administration were necessary to assure positive response in patients. The cytokine and/or side effects were moderate and the combined LAK-PSS infusions were generally well tolerated by the patients. The treatment was followed by activation of the patient immune system that included: (i) rebound in amount of peripheral blood lymphocytes; (ii) gain in amount of CD3(+) T cells and those CD4(+) helper/inducer; (iii) enchantment of lymphocyte proliferation and cytokine production (IL-2, IL-1, TNF-alpha). Being injected to patients in combination with LAK cells, cytokines related to PSS action and/or those, either exogenous or secondary, and released by in vitro and in vivo, activated lymphocytes and could cause the therapeutic effects.
...
PMID:IL-2-Activated Killer Cells and Native Cytokines in Treatment of Patients with Advanced Cancer. 1268 71

We screened for drugs that specifically interact with the 5'-untranslated region of the mRNA encoding the Alzheimer's amyloid precursor protein (APP). Our goal was to use newly discovered APP 5' UTR directed compounds to limit amyloid-beta (Abeta)-peptide output in cell culture systems. The APP 5' UTR folds into a stable RNA secondary structure (Gibbs free energy: DeltaG = -54.9 kcal/mol) and is an important regulator of the amount of APP translated in response to IL-1 (Nilsson et al., 1998; Rogers et al., 1999) and iron (Rogers et al., 2002). Seventeen drug "hits" were identified from a library of 1,200 FDA preapproved drugs (Rogers et al., 2002). Six of the original 17 compounds were validated for their capacity to suppress reporter gene expression in stable neuroblastoma transfectants expressing the dicistronic reporter construct shown in Fig. 2. These six leads suppressed APP 5' UTR driven luciferase translation while causing no effect on the translation of dicistronic GFP gene translated from a viral IRES (negative control to ensure specificity during drug screens). In this report, we show that paroxetine (serotonin reuptake blocker) and dimercaptopropanol (Hg chelator) exerted significant effects on APP expression (steady-state levels of APP), whereas Azithromycin altered APP processing. None of these three compounds altered APLP-1 expression. In the future, we will identify further novel compounds that influence Abeta levels, either via translation inhibition or by changing the activity of proteins coupled between APP translation and APP processing.
...
PMID:Drug discovery targeted to the Alzheimer's APP mRNA 5'-untranslated region: the action of paroxetine and dimercaptopropanol. 1450 Oct 7

In the retinoic acid-differentiated neuroblastoma SH-SY5Y cells, IL-1 induced binding activity of NFkappaB and up-regulated the expression and activity of MnSOD. The IL-1-elicited effects were partly reversed by IL-4 and IL-6. It is proposed that IL-4 and IL-6 may participate in the regulation of the imbalanced oxidant status induced by IL-1 in differentiated neuroblastoma cells. In the SH-SY5Y cell line, TNFalpha neither activated NFkappaB nor induced MnSOD expression and activity, but was capable of modulating the IL-1 effects. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFkappaB activation, down-regulated the expression and activity of MnSOD, which may suggest that the regulation of MnSOD by IL-1 in retinoic acid-differentiated neuroblastoma cells was mediated by the nuclear factor kappaB.
...
PMID:Cytokine action and oxidative stress response in differentiated neuroblastoma SH-SY5Y cells. 1451 47

The generation of splice variants has been reported for various plant resistance (R) genes, suggesting that these variants play an important role in disease resistance. Most of the time these R genes belong to the Toll and mammalian IL-1 receptor-nucleotide-binding site-leucine-rich repeat (TIR-NBS-LRR) class of R genes. In Phaseolus vulgaris, a resistance gene cluster (referred to as the B4 R-gene cluster) has been identified at the end of linkage group B4. At this complex resistance cluster, three R specificities (Co-9, Co-y and Co-z) and two R QTLs effective against the fungal pathogen Colletotrichum lindemuthianum, the causal agent of anthracnose, have been identified. At the molecular level, four resistance gene candidates encoding putative full-length, coiled-coil (CC)-NBS-LRR R-like proteins, with LRR numbers ranging from 18 to 20, have been previously characterized. In the present study, seven cDNA corresponding to truncated R-like transcripts, belonging to the CC-NBS-LRR class of plant disease R genes, have been identified. These seven transcripts correspond to a single gene named JA1tr, which encodes, at most, only five LRRs. The seven JA1tr transcript variants result from distinct post-transcriptional modifications of JA1tr, corresponding to alternative splicing events of two introns, exon skipping and multiple 'aberrant splicing' events in the open reading frame (ORF). JA1tr was mapped at the B4 R-gene cluster identified in common bean. These post-transcriptional modifications of the single gene JA1tr could constitute an efficient source of diversity. The present results provide one of the few reports of transcript variants with truncated ORFs resulting from a CC-NBS-LRR gene.
...
PMID:Distinct post-transcriptional modifications result into seven alternative transcripts of the CC-NBS-LRR gene JA1tr of Phaseolus vulgaris. 1566 Feb 37


<< Previous 1 2 3 Next >>

---