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)

Interferon-gamma-induced tryptophan metabolism of human macrophages was compared to ten human neoplastic cell lines of various tissue origin and to normal dermal human fibroblasts. Tryptophan and metabolites were determined in supernatants of cultures, after incubation for 48 h, by high-performance liquid chromatography with ultraviolet and fluorescence detection. With the exception of two cell lines (Hep G 2, hepatoma and CaCo 2, colon adenocarcinoma) in all of the ten other cells and cell lines tryptophan degradation was induced by interferon-gamma. Five of these ten formed only kynurenine (SK-N-SH, neuroblastoma; T 24, J 82, bladder carcinoma; A 431, epidermoid carcinoma; normal dermal fibroblasts), three formed kynurenine and anthranilic acid (U 138 MG, glioblastoma; SK-HEP-1, hepatoma; A 549, lung carcinoma). Only one line, A 498 (kidney carcinoma) showed the same pattern of metabolites as macrophages (kynurenine, anthranilic acid and 3-hydroxyanthranilic acid). Interferon-gamma regulated only the activity of indoleamine 2,3-dioxygenase. All other enzyme activities detected were independent of interferon-gamma, as shown by the capacity of the cells to metabolize L-kynurenine or N-formyl-L-kynurenine. Increasing the extracellular L-tryptophan concentration resulted in a marked induction of tryptophan degradation by macrophages. Contrarily, a significant decrease of the tryptophan degrading activity was observed when the extracellular L-tryptophan concentration was increased 2-fold with SK-N-SH, T 24 and J 82, 4-fold with A 431 and A 549 and 10-fold with U 138 MG and SK-HEP-1. The activity was unaffected by extracellular L-tryptophan with dermal fibroblasts and A 498. Though interferon-gamma was the most potent inducer of tryptophan metabolism, interferon-alpha and/or -beta showed small but distinct action on some of the cells. In all cells which reacted to interferon-gamma by enhanced expression of class I and/or class II major histocompatibility complex antigens tryptophan degradation was also inducible. These results demonstrate that induction of indoleamine 2,3-dioxygenase is a common feature of interferon-gamma action, that the extent of this induction is influenced by extracellular L-tryptophan concentrations and that indoleamine 2,3-dioxygenase is the only enzyme in the formation of 3-hydroxyanthranilic acid from tryptophan which is regulated by interferon-gamma.
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PMID:Characteristics of interferon induced tryptophan metabolism in human cells in vitro. 250 Sep 76

At least two subtypes of alpha-2 adrenergic receptors have been identified on the basis of antagonist affinities as determined mainly by radioligand binding assays. The human platelet and the HT29 human colonic adenocarcinoma cell contain alpha-2A adrenergic receptors, whereas the neonatal rat lung and the NG108 neuroblastoma X glioma hybrid cell contain the alpha-2B adrenergic receptor. Using the attenuation of the cyclic AMP accumulation as a functional assay, the affinities of various antagonists for the alpha-2 adrenergic receptor were determined in HT29 and NG108 cell lines. Dose-response curves to 5-bromo-6-(2-imidazoline-2-yl-amino)quinoxaline (UK 14,304) an alpha-2 adrenergic agonist, were generated in the absence and presence of three concentrations of various antagonists. Schild regressions were used to determine pA2 values and then dissociation constants (KB value) were calculated. Whereas phentolamine and yohimbine were equipotent at the receptor in the two cell lines, 2-(2,4-(O-methoxyphenyl)-piper-azin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4H)- isoquinolindione (ARC-239) and prazosin were 100- and 30-fold more potent in the NG108 cell line than in the HT29 cell. These potency ratios determined from functional experiments are the same as those obtained from radioligand binding experiments. These functional data are consistent with the previous and more extensive binding data, and thus support the existence and definition of alpha-2A and alpha-2B adrenergic receptor subtypes.
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PMID:Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype. 255 31

In order to study whether cell fusion would modify the DNA copy number of an amplified oncogene, somatic cell hybrids were made between the human neuroepithelioma cell line MCIXC and HeLaCOT human adenocarcinoma cells. MCIXC contains approximately 21 copies of the c-myc oncogene and HeLaCOT contains approximately 5 copies relative to the control. All hybrid clones investigated displayed a marked decrease in the number of copies of c-myc DNA (an average of 5 copies), while the level of c-myc RNA in the hybrids was similar to that found in both parents. All eight hybrid clones were found to be completely nontumorigenic even though both parent cells formed tumors in 100% of the nude mice treated by injection. This loss of oncogene amplification in the hybrids was shown not to be due to either heterogeneity of c-myc amplification in the MCIXC parent or segregation of a copy of the chromosome 22 from the hybrids. This loss most likely resulted from the breakdown of a homogeneously staining region (containing the amplified gene copies) into double minutes, which were subsequently lost from the cells. The HeLaCOT cell line was also fused to the human neuroblastoma BE(2)C, which contains approximately 123 copies of the N-myc oncogene relative to control. Ten hybrid clones were found to contain an average of 47 copies of N-myc DNA, significantly less than the 91 copies predicted had no loss occurred. These BE(2)C x HeLaCOT hybrids expressed on average about 15% the N-myc RNA seen in the BE(2)C parent and, as with the MCIXC x HeLaCOT hybrids, were found to be completely nontumorigenic. However, upon passage in culture, one BE(2)C x HeLaCOT hybrid eventually became tumorigenic. This hybrid also displayed reduced copies of N-myc DNA in comparison to its parent hybrid but surprisingly showed a 2-fold increase in N-myc RNA. Thus, the expression of N-myc, but not the amplification state of either myc gene, appears to correlate with the tumorigenicity of the cells.
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PMID:Modification of myc gene amplification in human somatic cell hybrids. 256 70

With the aid of a highly specific murine monoclonal antibody, F12, an immunofluorescence method was elaborated that allowed sensitive and specific detection of the ganglioside antigen fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) in different types of human lung cancer and normal tissues. Nineteen of 21 cases of small cell lung cancer were positive with the F12 immunofluorescence method as compared to 2 of 10 squamous epithelial cell lung cancers and 1 of 5 large cell lung cancer specimens. Specimens of lung adenocarcinoma (8 cases) and bronchial carcinoid (3 cases) were all negative, as were 2 examined cases of neuroblastoma. No fucosyl-GM1 could be detected in normal lung and bronchus. However, in thymus, spleen, and lamina propria of the small intestine sparsely distributed clusters of small round cells were stained as well as intramural ganglionic cells of the small intestine and islet cells of the pancreas. All other normal tissues tested were negative. Results obtained with immunofluorescence closely agreed with immunochemical determination of fucosyl-GM1 in lipid extracts of tissues. Our findings suggest that fucosyl-GM1 is strongly associated with small cell cancer of the lung and demonstrate that this tumor-associated antigen can be detected with high sensitivity and specificity with an immunofluorescence method based on the use of the F12 monoclonal antibody.
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PMID:Immunohistological detection of fucosyl-GM1 ganglioside in human lung cancer and normal tissues with monoclonal antibodies. 264 49

Neuroblastoma is one of the most common solid tumors of childhood and is notable for its ability to spontaneously regress and, in some instances, to differentiate to less malignant ganglioneuromas. Since immune mechanisms may account for these phenomena, identification of in vivo immune responses to tumor cell surface antigens may be important to the progression of the disease. As determined by analysis on the fluorescence-activated cell sorter, sera from 10 of 18 neuroblastomas patients were found to contain antibodies to a cell surface antigen present on subpopulations of cells from human neuroblastoma cell lines maintained in vitro. Eight human neuroblastoma cell lines were examined and found to vary in reactivity with sera. Induction of differentiation of cell lines with retinoic acid (RA) in vitro resulted in most cell lines bearing higher percentages of positive cells but with a decreased mean cell fluorescence. Preliminary Western blot analysis of lysates of the human cell lines NMB/N7, SMS-KAN, and SK-N-MC showed two principal antigen bands on reducing gels. Comparison of sera from different individuals on lysates of cell lines showed reactivity principally with bands of 105-110 kD and 65-70 kD and an additional minor band of slightly lower molecular weight with the higher titer sera. The ability of different sera to recognize a common antigen pattern suggests that this represents an immunodominant cell surface antigen. Examination of reactivity of other cell lines in this system showed that positive sera reacted with all neuroblastoma lines examined, one neuroepithelioma (SK-N-MC), two melanoma lines (MeWo, G361), and one adrenal-derived adenocarcinoma (SW-13).
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PMID:Recognition of an in vivo immune response to human neuroblastoma modulation of antigen expression by retinoic acid. 268 27

Five human tumor cell lines were grown as multicellular tumor spheroids (MTS) to determine whether multicellular tumor spheroids derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences paralleled clinical behavior. Multicellular tumor spheroids of two neuroblastoma, one lung adenocarcinoma, one melanoma, and a squamous cell carcinoma of the oral tongue, were studied in terms of growth delay, calculated cell survival, and spheroid control dose50 (SCD50). Growth delay and cell survival analysis for the tumor cell lines showed sensitivities that correlated well with clinical behavior of the tumor types of origin. Similar to other studies on melanoma multicellular tumor spheroids our spheroid control dose50 results for the melanoma cell line deviated from the general pattern of sensitivity. This might be due to the location of surviving cells, which prohibits proliferation of surviving cells and hence growth of melanoma multicellular tumor spheroids. This study demonstrates that radiosensitivity of human tumor cell lines can be evaluated in terms of growth delay, calculated cell survival, and spheroid control dose50 when grown as multicellular tumor spheroids. The sensitivity established from these evaluations parallels clinical behavior, thus offering a unique tool for the in vitro analysis of human tumor radiosensitivity.
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PMID:Radiosensitivity of different human tumor cells lines grown as multicellular spheroids determined from growth curves and survival data. 280 34

Monoiodo-[125I-Tyr3]neurotensin (NT) bound to a high affinity, low capacity binding component and a lower affinity, high capacity component in rat brain synaptic membranes. The antihistamine H1 agent levocabastine, which bears no structural relationship to NT, selectively and totally inhibited NT binding to its low affinity binding sites. The IC50 for levocabastine was 7 nM. Lowering the temperature of the binding assay from 25 to 4 degrees C markedly reduced the affinity of the high affinity NT binding site but did not affect the ability of levocabastine to discriminate between high and low affinity NT binding sites in rat brain membranes and tissue sections. Radioautographic studies of [125I-Tyr3]NT binding to rat brain tissue sections in the absence and presence of levocabastine revealed markedly different regional distributions of the two NT binding components. The levocabastine-sensitive NT binding site was present in membranes from rat and mouse brain but absent from rabbit brain membranes and from human brain tissue sections. It was also absent from mouse neuroblastoma N1E115 and human colonic adenocarcinoma HT29 cell membranes, two cell lines which have previously been shown to possess NT receptors functionally coupled to intracellular second messenger-generating systems. These findings are discussed in the light of the known properties of the high and low affinity NT binding sites in rat brain.
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PMID:Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals markedly different radioautographic distribution. 288 70

In summary, carcinoma is the most frequent cancer that metastasizes to the skin; lung cancer in men and breast cancer in women. Clinically distinctive patterns of cutaneous metastasis of epithelial origin include alopecia neoplastica, pulsatile nodules, Sister Mary Joseph's nodules, morpheaform, and cellulitis-like lesions. Biopsying these lesions reveals adenocarcinoma, squamous cell carcinoma, or anaplastic carcinoma. The type of histologic pattern seen can be a clue to the organ of origin giving rise to the cutaneous metastasis. Skin that is damaged allows for circulating malignant cells, often of epithelial or leukemic origin, to lodge and proliferate locally (inflammatory oncotaxis). The commonest form of leukemia to affect the skin of elderly males is chronic lymphocytic leukemia. However, when leukemia involves the mucous membranes, acute myeloid leukemia (acute monocytic and acute myelomonocytic leukemia) is the most likely diagnosis. When papules, nodules, or plaques develop on the head, neck, or torso in a middle-aged male accompanied by lymphadenopathy, there must be a high index of suspicion that these lesions are metastatic lymphomatous deposits. Definitive histologic diagnosis on a skin biopsy specimen is difficult. In this situation, it is best to rely on histologic patterns seen in lymphoid tissue along with cellular marker studies. An elderly patient having bone pain, anemia, elevated blood calcium level, and renal failure along with purplish or skin-colored nodules and plaques on the trunk has a good chance of having multiple myeloma. Biopsying these lesions is most certain to reveal atypical plasma cells, and blood immunoelectrophoresis will demonstrate characteristic monoclonal gammopathy. There are two malignancies seen in children under 3 years of age that often times affect the skin in a characteristic fashion. Letterer-Siwe disease, which is distinguished from other histocytic disorders by its cell of origin, the Langerhans cell, clinically shows maculopapular and erosive lesions distributed in a seborrheic pattern. Neuroblastoma derived from cells of the neural crest demonstrates clinically widespread bluish papulonodules. Kaposi's sarcoma, a multifocal vascular malignancy, has a wide spectrum of clinical expression. Those patients who are immunocompromised secondary to concomitant disease or immunosuppressive therapy are more susceptible to a disseminated fulminant course accompanied by opportunistic infection. In conclusion, although specific signs of internal malignancy are less common than nonspecific ones, they are just as important; if the clinician managing the cancer patient is familiar with these clues to internal disease, proper patient management will ensue.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Specific cutaneous manifestations of internal malignancy. 307 47

The clinical and pathologic features of 43 dogs with neoplasia of the rostral cerebrum were reviewed. Primary brain tumors included meningioma, astrocytoma, neuroblastoma, oligodendroglioma, and ependymoma. Other tumors that secondarily affected these areas included solitary hemangiosarcoma, nasal neuroendocrine carcinoma, nasal cell adenocarcinoma, nasal squamous cell carcinoma, and nasal neurofibrosarcoma. Older dogs were usually affected (mean, 10 years), and meningioma was the most frequent tumor type. Thirty-one dogs (72% of total) had a late-onset (greater than 5 years of age) of either generalized seizures or behavior abnormalities, or both, with an initially normal neurologic examination. In these 31 dogs, a mean time of 78 days (range, 2 to 400 days) elapsed from the onset of seizures or behavior change to the detection of a persistently abnormal neurologic examination. In all 43 dogs, the time from the detection of neurologic deficits to death or euthanasia and necropsy ranged from 1 to 63 days (mean, 13 days). On the basis of this review, it appears that dogs with late-onset seizures or behavior change, or both, should be suspected of having tumors involving the rostral cerebrum, despite the absence of persistent neurologic deficits commonly associated with cerebral tumors. Further, the onset of abnormalities in the neurologic examination and the time of death seem to occur within predictable time periods.
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PMID:Clinical signs of tumors affecting the rostral cerebrum in 43 dogs. 322 60

The monoclonal islet cell antibody HISL-19 was generated after immunization of BALB/c mice with human islet cell preparations. Besides reactivity with all cells of the human pancreatic islet, MAb HISL-19 also reacted with other cells of the diffuse neuroendocrine system, including anterior pituitary cells, C cells of the thyroid, endocrine cells of the gut and bronchus, the adrenal medulla, and central and peripheral neurons. In this study the authors screened a series of 53 neuroendocrine and 71 nonneuroendocrine tumors for their reactivity with MAb HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and Paraplast-embedded sections. MAb HISL-19 reacted strongly with all insulomas (10), carcinoids (8), C-cell carcinomas of the thyroid (8), pituitary adenomas (6), neuroendocrine carcinomas of the skin (4), paragangliomas of the carotid body (3), and pheochromocytomas (2) tested. Neuroblastomas (3), oat-cell carcinomas of the lung (2), and melanomas (4) exhibited only very few immunoreactive cells scattered throughout the tumor or remained unstained with MAb HISL-19. With the exception of one lobular carcinoma of the breast (1/3), one adenocarcinoma of the endometrium (1/4), and one adenocarcinoma of the stomach (1/6), nonneuroendocrine tumors were negative with MAb HISL-19. Biochemical findings obtained by SDS-PAGE, "Western" immunoblotting, immunoaffinity chromatography, and absorption experiments indicate that the MAb HISL-19-defined antigen is not related to neuron specific enolase. Because the epitope recognized by MAb HISL-19 is well preserved in formalin-fixed and routinely processed tissues, this monoclonal antibody finds potential applications in diagnostic pathology as an indicator for neuroendocrine cells and their neoplasms.
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PMID:Monoclonal antibody HISL-19 as an immunocytochemical probe for neuroendocrine differentiation. Its application in diagnostic pathology. 351 56


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