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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low oxygen tension is a feature of many physiologic and pathologic conditions, including wound healing, fibrosis, and neoplasia. Increasing evidence suggests that low oxygen tension induces the transcription of a number of genes, and that this process depends on the cellular context. The proteins synthesized from these genes enable cells to adapt to the hypoxic environment and/or to fulfill their functional roles. The regulatory regions responsible for the induction of erythropoietin gene transcription and synthesis in response to hypoxia/anemia appear to be cis-acting deoxyribonucleic acid sequences located within the 5' and 3' flanking regions of the erythropoietin gene. Other proteins induced by hypoxia include cytokines (platelet-derived growth factor-beta chain, endothelin-1, transforming growth factor-beta), enzymes (tyrosine hydroxylase, glycolytic enzymes), and stress proteins. The molecular mechanisms of the hypoxia-induced expression of these genes are poorly understood. A heme protein may act as the oxygen tension sensor, or the redox state of certain nuclear transcription factors may function as second messengers.
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PMID:Gene expression in low oxygen tension. 832 8

Neuroblastoma (NB) is a tumor which arises from neural crest cells. In the developing neural crest cells, the induction of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase is more delayed than that of tyrosine hydroxylase and dopamine-beta-hydroxylase. If NB cells are arrested in an early stage of neural crest development, the induction of DOPA decarboxylase is insufficient and the accumulation and secretion of DOPA can be caused. The biochemically immature phenotype is thought to represent the undifferentiated characteristics of the cells and might correlate with the grade of malignancy. To investigate whether the hypothesis is clinically applicable or not, we have measured plasma DOPA, dopamine and urinary catecholamine metabolites in NB patients. The levels of plasma DOPA, dopamine, urinary homovanillic acid (HVA) and vanillactic acid (VLA) were significantly higher in patients with unfavorable NBs and the higher plasma DOPA level was significantly associated with the patients' age (> 1 year old), tumor stage (III, IV) and DNA diploidy. Serial determination of plasma DOPA was a good monitor of the disease course. These results are compatible with the hypothesis on DOPA decarboxylase deficiency and DOPA secretion in undifferentiated, unfavorable NBs. In conclusion, the plasma DOPA can be used to predict patients' prognosis as well as to follow up patients with NB.
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PMID:3,4-dihydroxyphenylalanine (DOPA) decarboxylase deficiency and resultant high levels of plasma DOPA and dopamine in unfavorable neuroblastoma. 852 65

Olfactory neuroblastoma (ONB) is a malignant tumor of the nasal mucosa whose histogenesis is unclear. A relationship to neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is based on morphologic similarities and the expression of similar neural antigens. However, the clinical presentation of ONB differs from that of NB, and MYCN amplification characteristic of NB is not observed. We have therefore examined the relationship of this malignancy to other classes of neural tumors. In previous studies, two ONB cell lines demonstrated cytogenetic features and patterns of protooncogene expression suggestive of a relationship to the Ewing sarcoma family of childhood peripheral primitive neuroectodermal tumors (pPNETs). The pPNETs show t(11;22)(q24;q12) or t(21;22)(q22;q12) chromosomal translocations fusing the EWS gene from 22q12 with either the FL11 gene on 11q24 or the ERG gene on 21q22. We therefore analyzed ONBs for the presence of pPNET-associated gene fusions. Both cell lines showed rearrangement of the EWS gene, and fluorescence in situ hybridization (FISH) of each case demonstrated fusion of EWS and FL11 genomic sequences. Moreover, both lines expressed EWS/FL11 fusion transcripts with in-frame junctions between exon 7 of EWS and exon 6 of FL11 as described for pPNETs. We identified similar gene fusions in four of six primary ONB cases. None of the cases expressed tyrosine hydroxylase, a catecholamine biosynthetic enzyme widely expressed in NB. Our studies indicate that ONB is not a NB but is a member of the pPNET family.
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PMID:Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma. 857 10

The ability of PC12 cells to regenerate processes is substantially enhanced in vitro if they have been previously exposed to nerve growth factor (NGF-primed), compared to cells that have not been exposed (NGF-naive). These studies were carried out to determine if the enhanced neuritogenic ability of NGF-primed cells is retained following transplantation. NGF-naive or NGF-primed PC12 cells were transplanted into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and allowed to survive for 2 weeks. Mice were given daily injections of cyclosporin A (CyA) to prevent anti-species graft rejection. The transplanted PC12 cells were visualized by tyrosine hydroxylase immunoreactivity. The NGF-naive transplanted cells formed dense clusters and large tumor masses in more than half the animals. Only a few of the naive PC12 cells had short processes. In contrast, many of the transplanted NGF-primed PC12 cells had processes. Furthermore, fewer of the animals transplanted with primed cells produced tumor masses in the striatum compared to animals that received NGF-naive cells. Transplantation of NGF-naive PC12 cells leads to a significant increase in the number of dopaminergic neurons in the host substantia nigra (SN) compared to MPTP-treated animals. The increase of host dopaminergic neurons was not statistically significant when NGF-primed PC12 cells were used. Following MPTP treatment and PC12 cell transplantation, injection of CyA did not affect the dopaminergic neurons in the host SN. These data suggest that exposure of cells to trophic factors, prior to transplantation, can enhance their level of differentiation and integration into the host brain.
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PMID:The effect of prior in vitro exposure of donor cells to trophic factors in neurotransplantation. 859 97

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
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PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neuro-differentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.
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PMID:Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression. 866 78

The presence of a non-small cell lung carcinoma (NSCLC)-related gene or genes on chromosome band 11p15.5 is of particular interest, given the specific loss of heterozygosity (LOH) measured in this region for lung as well as many other pediatric and adult neoplasms. We have undertaken high-density polymorphic marker analysis in 30 matched normal and NSCLC tumor samples using 11 PCR-based polymorphic markers positioned approximately every 2-3 cM throughout 11p15.5. These studies have confirmed the presence of two distinct regions of LOH for NSCLC in 11p15.5. In 9 of 13 (69%) tumors with measurable LOH, allelic deletion was restricted to 11p15.5, indicating that whole chromosome 11 loss is not a common event in NSCLC. Furthermore, one-half of these tumors showed independent deletion events for each LOH region, while the remaining tumor regions of LOH extended to include all four markers in between. Only two tumors showed LOH for the more telomeric region alone. Furthermore, the location of these two potentially distinct tumor suppressor genes has been significantly refined to a 3-cM area in the telomeric region between D11S1363 and tyrosine hydroxylase (TH) and a 10-cM area in the more proximal part of 11p15.5 between D11S988 and D11S926. Interestingly, the telomeric region of LOH in NSCLC overlaps with the reported location of one of two breast carcinoma-related tumor suppressor genes, but the proximal allelic deletion area for these two tumor types are clearly distinct. Our studies suggest that chromosome band 11p15.5 harbors a minimum of three separate loci, the loss of which is implicated in these two common adult neoplasms.
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PMID:High-density marker analysis of 11p15.5 in non-small cell lung carcinomas reveals allelic deletion of one shared and one distinct region when compared to breast carcinomas. 867 40

Two cases of duodenal gangliocytic paraganglioma were studied by means of immunocytochemical methods using 41 kinds of antibodies. The tumors consisted of three histological types; carcinoid, ganglioneuroma and paraganglioma. Tumors of both cases exhibited immunoreactivity to at least one or as many as three of the following: calcitonin, calcitonin-gene related peptide, endocrine granule constituent, Leu7, neuropeptide Y and basic fibroblast growth factor. In addition, these tumors were also immunopositive for neuron specific enolase, S-100 protein, neurofilament protein, pancreatic polypeptide, chromogranin A, somatostatin, leuenkephalin, substance P and vasoactive intestinal peptide, as has been described in previous reports. In one case, tumor cells were immunopositive for adrenocorticotropin, bombesin, gastrin releasing peptide, myelin basic protein, neuroendocrine marker and tyrosine hydroxylase. Moreover, paraganglioma cells of tumors showed both argyrophilia and argentaffinity. These results suggest that duodenal gangliocytic paraganglioma may originate from embryonic neuroinsular complex.
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PMID:Two cases of duodenal gangliocytic paraganglioma: immunocytochemical characteristics. 882 94

Pheochromocytomas in mice are rare tumors, and their expression of functional markers has not previously been assessed. In this study, 29 spontaneously occurring mouse pheochromocytomas were characterized morphologically and immunohistochemically to determine whether there are functional correlates to previously described morphological features and to provide a database for comparison with tumors that arise in genetically engineered animals. The tumors were derived from 28 mice 828-1,489 days old, of three genotypes. Considerable cytological and architectural polymorphism was observed both within and between tumors. Most of the tumor cells were comparable in size to normal chromaffin cells or were larger. Small basophilic cells, which are the predominant cell type in rat pheochromocytomas, were usually in the minority. All of the tumors and most of the cells within individual tumors expressed immunoreactive tyrosine hydroxylase (TH). The tumors were variably positive for phenylethanolamine-N-methyltransferase (PNMT) and chromogranin A (CGA). There did not appear to be a global association of specific cytological features with expression of TH, PNMT, or CGA, although cells of similar appearance often shared similar immunoreactivities within individual tumors. Small basophilic cells could be either PNMT-positive or PNMT-negative. The frequency, morphology, and immunophenotype of mouse pheochromocytomas suggest that the mouse may be more appropriate than the rat as a model for human adrenal medullary pathology. In addition, the expression of immunoreactive PNMT by mouse pheochromocytomas suggests that these tumors are a potential source of epinephrine-producing cell lines, for which adequate models currently do not exist.
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PMID:Immunohistochemical and morphological characterization of spontaneously occurring pheochromocytomas in the aging mouse. 888 77

Polymer-encapsulated dopamine-secreting cell grafting is one of the most promising approaches for the treatment of Parkinson's disease. We microencapsulated dopamine secreting PC12 cells into agarose/poly(styrene sulfonic acid) complex and grafted them into the xenogeneic brain without immunosuppression. Dopamine secretion from the encapsulated cells was confirmed by high-performance liquid chromatography (HPLC) analysis before grafting. A large number of encapsulated PC12 cells survived in the brain 1 mo after transplantation and these cells were immunoreactive to tyrosine hydroxylase (TH) antibody, suggesting that these cells were secreting dopamine into the brain. There was no apparent immunological rejection or tumor formation. We concluded that microencapsulated PC12 cells survive in the xenogeneic brain without immunosuppression, and this grafting procedure is expected to be applied for the treatment of Parkinson's disease in the near future in combination with stereotaxic thalamotomy or pallidotomy.
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PMID:Preliminary report of polymer-encapsulated dopamine-secreting cell grafting into the brain. 888 22


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