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)

In tumor specimens such as those from neuroblastoma, ovarian, and lung carcinoma patients, the prevalence of extrachromosomal circular DNA molecules harboring amplified genes has been well established. In some cases, the amplified genes have been identified as oncogenes, and their increased expression appears to contribute to the maintenance and progression of the malignancy. The aim of this study was to investigate the effect of fractionated radiation treatment, given in daily doses similar to those administered clinically, on the stability of extrachromosomal circular DNA molecules in cancer cells. Our studies were conducted with multidrug-resistant KB cells, which harbor extrachromosomal copies of the multidrug resistance gene (MDR1) almost exclusively on circular DNA molecules of approximately 750 and 1500 kb pairs. This size range is representative of extrachromosomal circular DNA molecules that have been shown to harbor amplified oncogenes in vivo. Exponentially growing MDR KB cells were exposed to 1400 and 2800 cGy ionizing radiation administered in 7 and 14 fractions, respectively, at 200 cGy per fraction/day. A statistically significant decrease in MDR1 extrachromosomal gene copy number was reproducibly detected in the irradiated cells compared with unirradiated cells passaged for the duration of the experiment in the absence of radiation treatment. This decrease was accompanied by a reduction in multidrug resistance and in P-glycoprotein levels, as determined by clonogenic dose-response assays and Western analyses, respectively. P-glycoprotein is a multidrug transporter encoded by the MDR1 gene. Fluorescence in situ hybridization studies further determined that extrachromosomal circular DNA loss correlated to the entrapment of these DNA molecules in radiation-induced micronuclei. These results indicate that radiation-induced loss of extrachromosomally amplified genes from tumor cells via their entrapment in micronuclei contributes to the improved therapeutic response observed for some cancers.
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PMID:Fractionated ionizing radiation accelerates loss of amplified MDR1 genes harbored by extrachromosomal DNA in tumor cells. 973 94

The H-rev107 tumour suppressor was isolated as a gene specifically expressed in rat fibroblasts resistant toward malignant transformation by the activated HRAS gene (Sers et al., 1997; Hajnal et al., 1994). Here we describe the human homologue of the rat H-rev107 gene. The predicted rat and human proteins are highly conserved exhibiting an overall amino acid identity of 83%. The H-REV107-1 gene is ubiquitously expressed with the exception of haematopoetic cells and tissues. In contrast, H-REV107-1 mRNA was found only in eight of 27 cell lines derived from mammary carcinoma, lung carcinoma, gastric carcinoma, kidney carcinoma, melanoma, neuroblastoma and other tumours. The H-REV107-1 protein was not detectable in any of these tumour cells. Loss of H-REV107-1 expression was not restricted to cultured human tumour cell lines, but also found in primary squamous cell carcinomas. Gross structural aberrations of the H-REV107-1 gene were absent in tumorigenic cell lines. Thus, the block to H-REV107-1 expression is achieved both at the level of transcription and translation. By fluorescence in situ hybridisation the human H-REV107-1 gene was localised to chromosome 11q11-12.
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PMID:Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12. 977 74

Hel-N1 and HuD belong to the elav gene family and encode neuron-specific RNA-binding proteins that are temporally regulated in neural development. Recently, these genes have been detected in small cell lung carcinoma, a neuroendocrine tumor, with HuD down-regulated in poorly differentiated, variant subsets. We, therefore, sought to determine: (a) the extent to which Hel-N1 and HuD are expressed in neuroblastoma (NB); and (b) whether the individual patterns of expression are associated with clinical features of the tumor. We used a sensitive and quantitative RNase protection assay that reliably distinguishes between these homologous genes, and with it we show that Hel-N1 and HuD transcripts were detected in 100% of cultured cells (11 of 11) and 97% of primary tumor samples (35 of 36). Densitometric quantification of transcripts indicated that the levels of HuD and Hel-N1 varied in all samples. In primary NB tissue, samples that expressed the highest Hel-N1 or HuD levels were N-myc unamplified. With HuD, the level in unamplified primary tumors was significantly higher than that of amplified tumors (0.80 +/- 0.12 versus 0.33 +/- 0.12, P < 0.02). HuD expression in prognostically favorable tumor stages was also significantly higher than unfavorable stages (0.98 +/- 0.19 versus 0.47 +/- 0.08, P < 0.03). In summary, the ubiquitous detection of HuD and Hel-N1 in NB indicates that they are molecular neuronal markers of this tumor. Furthermore, high HuD mRNA levels may predict a clinically favorable outcome.
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PMID:Neuron-specific hel-N1 and HuD as novel molecular markers of neuroblastoma: a correlation of HuD messenger RNA levels with favorable prognostic features. 981 74

Although not structurally related, the pleiotropic cytokines interleukin-7 (IL-7) and interleukin-15 (IL-15) share a variety of biological functions including stimulation and maintenance of cellular immune responses. Cytokines, such as IL-7 or IL-15, elaborated by cells in situ, e.g. cancer cells, may be involved in shaping the quality of anti-tumor directed immune responses. We have analysed the constitutive and IFN-gamma-inducible expression of IL-15 or IL-7 mRNA, protein expression, and protein secretion in human tumor cell lines of distinct origin. IL-15 mRNA expression was detected in renal cell carcinoma (RCC), small cell lung carcinoma (SCLC), glioblastoma, neuroblastoma, mesothelioma cells and in EBV-transformed B-lymphocytes. IL-7-specific transcripts could be detected in colorectal cancer and in renal cell cancer cell lines. Immunohistochemical analysis demonstrated cytosolic IL-15 protein expression in renal cell cancer cells without apparent IL-15 protein secretion in vitro. Time kinetic analyses revealed that IFN-gamma mediated increase of IL-15 mRNA expression was transcriptionally regulated and dependent on de novo protein synthesis. However, enhanced IL-15 mRNA expression did not lead to effective protein secretion. In contrast, IL-7 mRNA expression in renal cell cancer or in colorectal cancer was associated with effective protein secretion which could be augmented by IFNgamma-treatment. These data suggest that both IL-7 and IL-15 mRNA are expressed in renal cell cancer, but exclusively IL-7 may be elaborated by tumor cells in situ. IL-15 regulation appears to be tightly controlled both at the transciptional and post-transcriptional level. Appropriate stimuli leading to effective IL-15 secretion from tumor cells may aid in modulating cellular immune responses directed against cancer.
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PMID:Constitutive and IFN-gamma regulated expression of IL-7 and IL-15 in human renal cell cancer. 986 5

The mammalian achaete-scute homologue, MASH-1, is crucial for early development of the sympathetic nervous system and is transiently expressed in sympathetic neuroblasts during embryogenesis. Here we report that the human homologue (HASH-1) was expressed in all analyzed cell lines (6/6) derived from the sympathetic nervous system tumor neuroblastoma. The majority of small-cell lung carcinoma (4/5) cell lines tested expressed HASH-1, while other nonneuronal/non-neuroendocrine cell lines were negative. Induced differentiation of neuroblastoma cells resulted in HASH-1 downregulation. This occurred concomitant with induction of neurite outgrowth and expression of the neuronal marker genes GAP-43 and neuropeptide Y. Constitutive expression of exogenous HASH-1 did not alter the capacity of the neuroblastoma cells to differentiate in response to differentiation-inducing agents. It is concluded that moderate HASH-1 expression does not compromise the capacity of these cells to differentiate.
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PMID:Human achaete-scute homologue 1 (HASH-1) is downregulated in differentiating neuroblastoma cells. 1008 Sep 36

The biotransformation of nociceptin/orphanin FQ (NOFQ) by enzyme activity isolated from U1690 human lung carcinoma and SH-SY5Y human neuroblastoma cell lines, and from rat brain cortex cells in primary culture was investigated. The identification and quantification of the cleavage products were performed using electrospray ionization mass spectrometry linked to size-exclusion chromatography. The effect of chronic morphine treatment of the cells (5 days) on NOFQ biotransformation was also studied. It was found that major products generated from NOFQ were the amino-terminal peptides N1-9 and N1-13. The pattern of NOFQ biotransformation was quite similar for all three cell cultures. However, different proportions of the formed peptides were noted. The cleavage was inhibited by EDTA, PMSF, Hg2+, Cu2+ and Zn2+. Dynorphin A2-13 inhibited NOFQ cleavage in a manner suggesting competition of the two peptides for the same enzyme. Chronic morphine treatment of the cell cultures resulted in a substantial increase in the enzyme activity, leading to higher levels of the major fragments and accumulation of N1-12 and the shorter peptides N1-5, N1-6. Since the effect of morphine treatment of the cells was blocked by naloxone, it is likely that it was receptor specific. Taken together, the findings suggest that a metallosensitive endopeptidase, the activity of which is increased by chronic morphine treatment of the cells, is responsible for the biotransformation of NOFQ with fragments N1-9 and N1-13 being the major products.
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PMID:Biotransformation of nociceptin/orphanin FQ by enzyme activity from morphine-naive and morphine-treated cell cultures. 1008 6

Somatostatin (SS) and SS analogues inhibit the growth of various kinds of endocrine and exocrine cells via the SS receptor (SSTR). Carcinoid tumor is representative of the tumors treatable by SS analogues. We examined the expression of SSTR2A by immunohistochemical and in situ hybridization methods with a specific antibody against a synthesized 20-amino acid peptide of the COOH terminus of human SSTR2A and oligonucleotide probes in 62 endocrine tumors of various kinds: pancreatic endocrine tumor; carcinoid; neuroendocrine carcinoma; medullary thyroid carcinoma; pheochromocytoma; and small cell carcinoma of the lung, neuroblastoma, and ganglioneuroma. SSTR2A was expressed in 87% of these tumors and at both primary and metastatic sites. The immunohistochemical reactivity of SSTR2A was strong on the cell membrane and less intense in the cytoplasm of the tumor cells. SSTR2A mRNA was also detected in the tumor cells. The results indicate the usefulness of SSTR2A analogues for the treatment of neuroendocrine tumors, even metastatic ones: metastatic carcinoids, metastatic pheochromocytomas, tumors that adhered to large vessels, and neuroendocrine carcinomas.
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PMID:Immunohistochemical expression of somatostatin type 2A receptor in neuroendocrine tumors. 1058 62

An automated rare event detection system (Rare Event Imaging System) is described for the recognition of cancer cells that appear at low frequencies (1 in 1 million) in peripheral blood (PB) or bone marrow (BM). The instrumentation includes an automated fluorescence microscope (Nikon Microphot-FXA) with a cooled charge coupled device camera and a 60-MHz Pentium personal computer. Main features of the system are rapid analysis of large microscopic fields, including a total cell count, detection of fluorescently labeled cells, and a display of digitally stored images of the detected cells. Furthermore, the X,Y coordinates of each identified object are stored and can be recalled for morphological analysis of the cell using higher magnification or different fluorescent filter sets. The preparation of the blood or BM samples for automated analysis consists of lysis of the RBCs, attachment of sample cells onto adhesion slides, fixation, and fluorescent labeling with anticytokeratin antibodies. Cytokeratin-positive cells, however, were detected in 17% of the samples from healthy blood donors using this procedure (mean number, approximately 7/10(6) mononuclear cells in positive samples). To improve the specificity of the rare event detection, a double-labeling protocol combining intracellular cytokeratin with epithelial cell adhesion molecule (Ep-CAM) (breast, ovarian, colon, and lung carcinoma antigen) or disialo-ganglioside (GD2) antigen (small cell lung carcinoma, neuroblastoma, melanoma antigen) was developed. Examples of doubly labeled cultured cells and cancer cells from breast and small cell lung cancer patients are shown. Using the double-labeling protocol, no "positive" cells were seen in samples of healthy blood donors. Automated rare event detection (cytokeratin single-staining) was applied to 355 PB, BM, and stem cell (SC) samples from breast cancer patients before autologous BM transplantation. Cytokeratin-positive cells were found in 52% of BM, 35% of PB, and 27% of SC samples at frequencies of 1-1020 positive cells/10(6) mononuclear cells, thereby establishing the efficacy of the technique in the detection of rare cancer cells in hematopoietic tissue samples of cancer patients.
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PMID:Detection and analysis of cancer cells in blood and bone marrow using a rare event imaging system. 1069 May 21

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.
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PMID:Mutation analysis of P73 and TP53 in Merkel cell carcinoma. 1073 53

A variety of inflammatory and neoplastic scalp lesions are encountered in surgical pathology. However, the literature on fine-needle aspirations (FNAs) of the scalp is exceedingly rare. We report on a series of 70 FNAs involving cutaneous and subcutaneous lesions on the scalp. A total of 70 fine-needle aspirations of cutaneous and subcutaneous scalp lesions was reviewed to identify patterns of metastasis to the scalp and to demonstrate the effectiveness of FNA in diagnosing these lesions. There were 42 male and 28 female patients, ranging in age from 29-91 yr (mean, approximately 61 yr). Sixty-one patients had a previous history of malignancy. Of these aspirates, 59 were neoplastic, consistent with the patient's known primary. One case was an abscess, and the remaining case was unsatisfactorvy for cytologic evaluation. Follow-up biopsy revealed granulomatous inflammation. The most common primary tumor to metastasize to the scalp was lung carcinoma, which was seen in 18 cases, followed by hematopoietic malignancies in 14 cases. Melanoma was identified in 6 cases, head and neck tumors in 5 cases, renal malignancies in 4 cases, gastrointestinal tumors in 3 cases, sarcoma in 3 cases, breast and prostate malignancy in 2 cases each, and an olfactory neuroblastoma and meningioma in 1 case each. The remaining 9 aspirates were from patients who did not have a previous history of malignancy. These included 6 benign aspirates consisting of 3 epidermal inclusion cysts, 2 lipomas, and 1 neurofibroma. Two aspirates were malignant and included 1 primary squamous-cell carcinoma and 1 metastatic adenocarcinoma of unknown origin. The remaining case was unsatisfactory for cytologic evaluation. Follow-up biopsy of this lesion showed noncaseating granulomas. Of the aspirates from patients with a previous history of malignancy, 97% were neoplastic. Lung carcinoma and hematopoietic malignancies were the most common neoplasms that metastasized to the scalp. Since the scalp is a common site for metastasis, awareness of this fact is useful to both oncologists and dermatologists. It must be understood that FNA can provide a rapid and accurate diagnosis in the evaluation of scalp masses.
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PMID:Fine-needle aspiration of scalp lesions. 1090 30


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