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)

A butenolide compound (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone (KNK-41), was shown to have strong anti-tumor activity. KNK-41 inhibited the proliferation of various kinds of human malignant tumor cells, such as HeLa (cervical carcinoma), HGC-27 (gastric cancer), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow cytometric analysis indicated that KNK-41 caused an arrest in G0/G1 phase of the cell cycle. However, it scarcely affected DNA synthesis and the level of c-myc mRNA. These results suggest that the growth-inhibitory effect of KNK-41 is the result of G0/G1 arrest and not of the suppression of DNA synthesis and/or c-myc expression.
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PMID:Inhibitory effects of (1E,3E,5E,7E)-5-hydroxy-4-(8-phenyl-1,3,5,7- octatetraenyl)-2(5H)-furanone on proliferation of human malignant tumor cells. 157 90

Natural carotene sample obtained from palm oil was proved to suppress the promoting stage of two-stage carcinogenesis of mouse skin, and also inhibit the proliferation of human malignant tumor cells, such as neuroblastoma GOTO cells, stomach cancer HGC-27 cells, and pancreatic cancer PANC-I cells. Among the major constituents of palm carotene, alpha-carotene showed stronger anti-proliferative effect than beta-carotene. The present results indicate that further investigation for not only beta-carotene but also other kinds of natural carotenes, such as alpha-carotene, should be carried out.
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PMID:[Anticarcinogenesis activity of natural carotenes]. 252 99

3'-methyl-3-hydroxy-chalcone (3'Me-3-C), a derivative of chalcone, inhibited the proliferation of various kinds of human malignant tumor cells, such as HGC-27 (gastric cancer), HeLa (cervical carcinoma), PANC-1 (pancreatic cancer) and GOTO (neuroblastoma). Flow-cytometric analysis of HGC-27 cells revealed that 3'Me-3-C perturbed the cell cycle, i.e., it delayed passage through the S phase, and/or caused arrest in the G0/G1 phase. 3'Me-3-C inhibited the binding of [6,7-3H]estradiol to type-II estrogen-binding sites dose-dependently, and altered the pattern of protein synthesis and phosphorylation, which may explain 3'Me-3-C-induced inhibition of cell proliferation. In addition, 3'Me-3-C also suppressed the promoting activity of 12-0-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.
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PMID:Inhibitory effects of 3'-methyl-3-hydroxy-chalcone on proliferation of human malignant tumor cells and on skin carcinogenesis. 837 34

DCC (deleted in colorectal cancer), a candidate tumor suppressor gene located in chromosome band 18q21.2, encodes a transmembrane protein of 1447 amino acids. Neogenin, a protein with nearly 50% amino acid identity to DCC, was recently identified because of its dynamic expression in the developing nervous system and gastrointestinal tract of the chicken. To explore a role for the human neogenin (NGN) gene in cancer, we have isolated cDNAs for two alternatively spliced forms of NGN, encoding proteins of 1461 and 1408 amino acids. Fluorescence in situ hybridization studies (FISH) localized NGN in chromosome band 15q22, a region infrequently affected by alterations in cancer. NGN transcripts of about 7.5 and 5.5 kb were detected in all adult tissues studied. In contrast to the frequent loss of DCC expression, no alterations in NGN expression were observed in more than 50 cancers studied, including glioblastoma, medulloblastoma, neuroblastoma, colorectal, breast, cervical and pancreatic cancer cell lines and xenografts. Based on their sequence conservation and similar expression during development, DCC and NGN may have related functions. However, the chromosomal location and ubiquitous expression of NGN in various human tumors suggest it is infrequently altered in cancer.
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PMID:Identification and characterization of neogenin, a DCC-related gene. 912 61

Shortening of telomeres along with an up-regulation of telomerase is implicated in the immortality of tumor cells. Targeting either telomeres or telomerase with specific compounds has been proposed as an anticancer strategy. Because telomerase activity and telomeres are found in normal cells, telomere or telomerase targeting agents could induce side effects in normal tissues. We evaluated the effects of telomere and telomerase interactive agents in human tumor and normal cell lines to try to determine the potential side effects those agents might induce in patients. Toxicity of the G-quadruplex interactive porphyrins (TMPyP4, TMPyP2) and azidothymidine (AZT) were tested using a cell-counting technique against normal human cell lines (CRL-2115 and CRL-2120, fibroblasts; NHEK-Ad, adult keratinocytes; CCL-241, small intestinal cells; NCM 460, colonic mucosal epithelial cells) and human tumor cell lines (MDA-MB 231 and Hs 578T, breast cancer; SK-N-FI, neuroblastoma; HeLa, cervix cancer; MIA PaCa-2, pancreatic cancer; HT-29 and HCT-116, colon cancer; DU 145, prostatic cancer cell line). Telomerase activity of these cell lines was measured by a non-PCR-based conventional assay. The effects of TMPgammaP2, TMPyP4, and AZT were also evaluated against normal human bone marrow specimens, using a granulocyte-macrophage colony-forming assay (CFU-GM). AZT showed very low cytotoxic effects against normal and tumor cell lines, with the IC50 values above 200 microM. The IC50 values for TMPyP2 and TMPyP4 in normal human cell lines were in the range of 2.9-48.3 microM and 1.7-15.5 microM, respectively, whereas in tumor cell lines the IC50 values were 11.4-53 microM and 9.0-28.2 microM, respectively. Within the tissue types, keratinocytes were more sensitive to TMPyP4 than fibroblasts, and small intestinal cells were more sensitive than colonic mucosal epithelial cells. The IC50 for TMPyP2 and TMPyP4 in the normal marrow colony-forming assays were 19.3 +/- 5.1 microM and 47.9 +/-1.0 microM, respectively. In conclusion, the in vitro cytotoxicity of the telomere interactive agent TMPyP4 is comparable in human tumor and normal cell lines, which indicates that TMPyP4 could have effects on normal tissues.
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PMID:Effect of telomere and telomerase interactive agents on human tumor and normal cell lines. 1074 25

Bombesin (BBS) is proved to have a wide variety of the pharmacologic effects, including effects on the release of gastrointestinal hormones and control of gastrointestinal motility. More recently, the role of BBS in tumor growth, cellular proliferation and inflammation has attracted attention. There is evidence that increased BBS receptor expression may be considered as a specific marker for small-cell lung cancer, colorectal adenocarcinoma, gastric and pancreatic cancer, prostate, ovarian and breast cancer, neuroblastoma, renal cell carcinoma, malignant melanoma and thyroid carcinoma. BBS expression was found to be correlated with the histological grade of the tumor. Similarly, BBS treatment significantly improves the healing of chronic gastric ulcers and ameliorates the severity of burn- or colitis-induced gut injury. Although there is much complexity still to be elucidated to understand fully the physiologic and pathologic roles of BBS-like peptides several clinical or experimental trials have addressed that circulating or tissue levels of BBS-like peptides or their receptor expression may be used as diagnostic or prognostic markers of neoplastic disease, and incorporation of BBS receptor antagonists in the treatment of human cancer could provide substantial benefit to the cancer patients. Moreover, trophic, anti-ulcerogenic and anti-inflammatory actions of exogenous BBS make this peptide a potential supplement in minimizing or reversing tissue damage against several injurious challenges. In conclusion, based on the evidence summarized herein, related to the mitogenic and anti-inflammatory effects of BBS-like peptides, further investigations are needed to derive the benefit of BBS-like peptides in pharmacologic strategies.
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PMID:Bombesin-like peptides: candidates as diagnostic and therapeutic tools. 1267 68

Human BCL9 gene is over-expressed in some cases of acute lymphoblastic leukemia (ALL) with t(1;14)(q21;q32). Drosophila segment polarity gene legless (lgs), encoding wingless-armadillo (WNT - beta-catenin) signaling molecule, is the homolog of human BCL9. Here, we identified and characterized human BCL9-like (BCL9L) gene as well as mouse Bcl9-like (Bcl9l) gene by using bioinformatics. Uncharacterized DLNB11 cDNA (AB094091.1) was derived from human BCL9L gene. Nucleotide sequence of mouse Bcl9l cDNA was determined in silico by assembling mouse ESTs BF464707, BQ258167, 5'-truncated BC003321 cDNA, and mouse genome clone RP24-308H8 (AC125129.5). Human BCL9L and mouse Bcl9l genes were found to consist of eight exons. Exon-intron structure was well conserved between human BCL9L and mouse Bcl9l genes. Human BCL9L (1499 aa) showed 94.0% and 34.8% total-amino-acid identity with mouse Bcl9l (1494 aa) and human BCL9, respectively. Six domains (B9H1-B9H6) were conserved among mammalian BCL9 family proteins. B9H1 and B9H2 domains, and N-terminal part of B9H3 domain were identical to HD1, HD2, and HD3 domains conserved between human BCL9 and Drosophila lgs. B9H4, B9H5 and B9H6 were novel domains. B9H4 domain was characterized by multiple Ser-Pro repeats. Human BCL9L mRNA was expressed in fetal brain, adult lung, amygdala, eye, prostate, and also in several types of tumors including pancreatic cancer, prostate cancer, head and neck tumor and embryonal tumor. BCL9L gene was located between BLR1 and UPK2 genes within the commonly deleted region of neuroblastoma at human chromosome 11q23.3. This is the first report on human BCL9L and mouse Bcl9l.
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PMID:Identification and characterization of human BCL9L gene and mouse Bcl9l gene in silico. 1296 48

Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs) specific for TrpRS is important for development of tools for TrpRS monitoring. A molecular characterization of two mAbs raised in mice, using purified, enzymatically active bovine TrpRS as the inoculating antigen, is presented in this report. These IgG1 antibodies are specific for bovine, human and rabbit but not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32-Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry. This epitope covers a significant part of N-terminal extension that suggested to be proteolytically deleted in vivo from the full-length TrpRS whereas remaining COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure. Using computer algorithm, this epitope is attributed to COOH-terminal residues Asp409-Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to correlate with growth rates of neuroblastoma and pancreatic cancer cells. Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in hippocampus of Alzheimer's disease brain.
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PMID:Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease. 1661 81

Mutations in the CDKN2A gene underlie melanoma susceptibility in as many as 50% of melanoma kindreds in selected populations, and several CDKN2A founder mutations have been described. Inherited mutations in CDKN2A have been found to be associated with other, non-melanoma cancers including pancreatic cancer (PC) and neural system tumors (NST). Here we report a novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy. A subset of melanoma kindreds positive for this mutation displayed PC and neuroblastoma. E27X generates a premature stop codon, leading to dramatically reduced protein levels of p16 and leaving p14ARF unaltered. As PC and NSTs have been postulated to be preferentially associated with CDKN2A mutations located in exon 2 and/or affecting p14ARF alone, the position of E27X in exon 1alpha provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition.
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PMID:Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma. 1689 9

The possibility of links between psychosocial factors and cancer incidence and progression has generated considerable scientific and public interest. Tachykinins, including substance P, neurokinin A and B, hemokinin-1 and endokinins, are a family of neuropeptides, acting through three types of transmembrane G-protein coupled receptors denoted NK1, NK2 and NK3. Besides their role as neurotransmitters in peripheral and central nervous system, tachykinins and their receptors are also expressed in several non neuronal cells contributing to the fine connections between nervous systems and peripheral organ system such as respiratory, cardiovascular, immune, endocrine, gastrointestinal and genitourinary. Being so much involved in regulating physiological functions, they, of course, can concur to pathological conditions including cancer. Tachykinins can act on different steps of carcinogenesis. Tumors expressing NK receptors, such as astrocytoma, glioma, neuroblastoma, pancreatic cancer and melanoma, can misuse tachykinin-induced signaling, operating in normal cells, to promote proliferation and survival of cancer cells and to release cytokines and soluble mediators favoring tumor growth. In neuroblastoma, breast and prostate carcinomas tachykinins facilitate tumor metastatic infiltration in the bone marrow. In neuroendocrine carcinoma, tachykinins are responsible of symptoms associated with these pathologies including flushing, diarrhea, wheezing and right heart disease. In addition, regardless tumor histology, tachykinins may favor cancer incidence and metastatic progression by influencing blood flux and neovascularization in tumor formation as well as inducing immunosuppression mediated by neurogenic inflammation due to stress or surgery. However, the precise involvement of tachykinins in cancer pathologies and the potentiality to become effective pharmacological drug targets remain to be fully defined.
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PMID:Tachykinins and their receptors in human malignancies. 1691 32


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