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

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct "primary" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.
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PMID:Glioblastoma multiforme: morphology and biology. 21 8

Malignant rhabdoid tumors (MRT) are characterized by unique neoplastic cells demonstrating phenotypic diversity. By using the reverse transcriptase-polymerase chain reaction, we have detected expression of various genes before and after differentiation induction with four different agents in four established MRT cell lines (TM87-16, STM91-01, TTC642, and TTC549). The agents used in this study were all-trans retinoic acid (RA), 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-3, or interferon-gamma. Before and after induction, c-myc, IGF-II, IGF-I receptor, and IGF-II receptor were constitutively expressed by all four cell lines. The neurofilament medium-size (NF-M) was constitutively expressed by the TM87-16 and TTC642, and the S100 protein alpha subunit was expressed by TM87-16, TTC642, and TTC549. Chromogranin A was expressed by TM87-16 only after treatment with either TPA or RA. MyoD, N-myc, tyrosine hydroxylase, N-CAM, trkA, and the S100 protein beta subunit were not expressed by any cell line before or after induction with these agents. All the MRT cell lines in this study except TM87-16 were highly resistant to differentiation induction. The proliferating cells in TM87-16 and TTC642 expressed mRNA profiles characteristic of neuroectoderm.
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PMID:Gene expression of malignant rhabdoid tumor cell lines by reverse transcriptase-polymerase chain reaction. 955 92

Using both tumor specimen and cultured tumor cells, we have studied the differentiation of a pineocytoma by light and electron microscopy (EM) and immunohistochemical demonstration of glial, neuronal and neuroendocrine markers. Only interstitial cells were labeled with anti-glial fibrillary acidic protein and anti-S100 protein antibodies. Synaptophysin, neurofilaments and tau labeling was found in cells forming the pineocytomatous rosettes. Some cells also bound the anti-tryptophan hydroxylase antibody (TPOH), but no staining was seen after application of anti-chromogranin A or S-antigen antibodies. EM provided evidence for neurosensory differentiation demonstrating the presence of vesicle-crowned rodlets, cilia (9+0) and fibrous filaments. In culture, tumor cells proliferated slowly and showed positive immunolabeling for vimentin and TPOH. Expression of mRNA coding for TPOH, serotonin N-acetyltransferase, hydroxyindole-O-methyl-transferase and c-myc was found in the tumor using reverse transcriptase-polymerase chain reaction. These results demonstrate neuronal differentiation of this pineocytoma and suggest that the neoplastic pineal cells are capable of synthesizing serotonin and melatonin.
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PMID:Immunohistochemical, ultrastructural, biochemical and in vitro studies of a pineocytoma. 960 Jun

The h-mts1 (S100A4) is a member of the S100 gene family, coding for a calcium-binding protein. It is a metastasis-associated gene whose expression shows strong correlation with the proliferative potential and invasive and metastatic ability of cancers. In a proportion of human intraductal carcinomas of the breast, a shorter variant h-mts1 transcript (h-mts1v) of approximately 450 nucleotides is expressed. We have characterized the transcript using reverse transcriptase-polymerase chain reaction employing exon-specific oligonucleotides. We show here that the noncoding exon 1a/1b is lost in the variant cDNA. Exons 2 and 3, which code for the protein, seem to be present in the variant isoform. The RT-PCR products obtained using exons 2- and 3-specific oligonucleotides showed a high degree of sequence homology with exons 2 and 3 of the h-mts1 gene. The expression of the variant transcript could be influencing disease progression, albeit not as effectively as the normal unspliced h-mts1 transcript.
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PMID:Characterization of a splice variant of metastasis-associated h-mts1 (S100A4) gene expressed in human infiltrating carcinomas of the breast. 988 67

We report 15 primary renal neoplasms with morphologic, immunohistochemical, and molecular features identical to those of synovial sarcoma. These tumors form a distinct subset of the entity previously designated as embryonal sarcoma of the kidney. Most were diagnosed between the ages of 20 and 50 years. On gross examination, tumors are large, partially necrotic, and usually contain smooth-walled cysts. Microscopically, tumors are characterized by mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Grossly identified cysts are lined by mitotically inactive polygonal eosinophilic cells with apically oriented nuclei ("hobnailed epithelium"). The spindle cells are immunoreactive for vimentin, often immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100, or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These findings are consistent with monophasic, spindled synovial sarcoma encircling dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks. An additional case demonstrated the characteristic t(X; 18) translocation on cytogenetic analysis, but adequate material to perform molecular studies was not available in this case or the remaining 11 cases. Primary renal synovial sarcoma is a distinctive clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion transcripts.
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PMID:Primary renal synovial sarcoma: molecular and morphologic delineation of an entity previously included among embryonal sarcomas of the kidney. 1093 49

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is important for virion infectivity. Previous studies have shown that vif-defective virions exhibit structural abnormalities in the virus core and are defective in the ability to complete proviral DNA synthesis in acutely infected cells. We developed novel assays to assess the relative stability of the core in HIV-1 virions. Using these assays, we examined the role of Vif in the stability of the HIV-1 core. The integrity of the core was examined following virion permeabilization or removal of the lipid envelope and treatment with various triggers, including S100 cytosol, deoxynucleoside triphosphates, detergents, NaCl, and buffers of different pH to mimic aspects of the uncoating and disassembly process which occurs after virus entry but preceding or during reverse transcription. vif mutant cores were more sensitive to disruption by all triggers tested than wild-type cores, as determined by endogenous reverse transcriptase (RT) assays, biochemical analyses, and electron microscopy. RT and the p7 nucleocapsid protein were released more readily from vif mutant virions than from wild-type virions, suggesting that the internal nucleocapsid is less stably packaged in the absence of Vif. Purified cores could be isolated from wild-type but not vif mutant virions by sedimentation through detergent-treated gradients. These results demonstrate that Vif increases the stability of virion cores. This may permit efficient viral DNA synthesis by preventing premature degradation or disassembly of viral nucleoprotein complexes during early events after virus entry.
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PMID:Role of Vif in stability of the human immunodeficiency virus type 1 core. 1107

Three (propositus) cases of basal cell carcinoma (BCC) showing endocrine differentiation at the immunohistochemical level were studied using reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the presence of mRNA of chromogranin A. Moreover, 20 (consecutive) cases of BCC were studied with immunohistochemistry alone using chromogranin A, synaptophysin, S100 protein, cytokeratin 20, and neuron-specific enolase antibodies (NSE). The three propositus cases of BCC showed positive results when RT-PCR for mRNA of chromogranin A was performed. Eleven out of 20 consecutive cases of BCC were focally positive for chromogranin A antibody. These results confirm the presence of endocrine differentiation in BCC, demonstrated both with immunohistochemistry and with RT-PCR.
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PMID:[Endocrine differentiation in basocellular carcinoma]. 1143 14

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.
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PMID:Molecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients. 1151 19

Last year the Melanoma Group of the European Organization for Research and Treatment of Cancer (EORTC-MG) completed accrual (1418 patients) for trial EORTC 18952, a three-arm phase III trial evaluating adjuvant therapy with two different intermediate doses of interferon (IFN) alfa-2b versus observation for stage IIB-III melanoma. About 25% of the patients entered the trial with tumor-positive sentinel nodes (SNs). Prognosis was significantly better in SN-positive patients than in patients with palpable regional node involvement (P < .00001). Subsequently the EORTC-MG embarked on two large phase III trials of adjuvant therapy based on the tumor status of the SN. In trial EORTC 18961 for stage II melanoma, GM2-KLH/QS-21 vaccination is compared with observation (1300 patients); in trial EORTC 18991 for stage III melanoma, 5-year treatment with pegylated interferon alfa-2b (PEG-Intron) is compared with observation (900 patients). Translational research projects will compare SN assessment by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the relative accuracy of each method and its correlation to relapse and survival of patients with stage II melanoma. In stage III patients, a similar workup of the most proximal nonsentinel node in the full lymph-node dissection specimen will indicate the accuracy of each methodology to detect nodal metastasis beyond the SN and the prognostic significance thereof. These findings will be correlated to the results of sequential blood testing by RT-PCR and by tumor marker assays for S100, TA90, and angiostatin. In addition, tumor-positive and tumor-negative SNs will be assessed for activated cytotoxic T lymphocytes and downregulation of dendritic cell functions.
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PMID:The EORTC melanoma group translational research program on prognostic factors and ultrastaging in association with the adjuvant therapy trials in stage II and stage III melanoma. European Organization for Research and Treatment of Cancer. 1159 96

The molecular immune response of the pulpal tissue during chronic carious infection is poorly characterized. Our objective was to examine the expression of potential molecular mediators of pulpal inflammation, correlate their levels with disease severity, and determine the cellular localization of key molecules. Results indicated that there was significantly increased transcriptional activity in carious compared to healthy pulp, and the increase correlated positively with disease severity. Semiquantitative reverse transcriptase PCR analysis in 10 carious and 10 healthy pulpal tissue samples of the S100 family members S100A8, S100A9, S100A10, S100A12, and S100A13; the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8, IL-6, and epithelial cell-derived neutrophil attractant 78 (ENA-78); and the structural protein collagen-1alpha indicated that all genes tested, with the exception of S100A10, were more abundantly expressed in carious teeth. In addition, we found that the closer the carious lesion front was to the pulpal chamber the higher the expression was for all genes except S100A10. Multiple-regression analysis identified a significant positive correlation between the expression levels of S100A8 and IL-1beta, ENA-78, and IL-6 and between collagen-1alpha and S100A8, TNF-alpha, IL-1beta, IL-8, IL-6, and ENA-78. Immunohistochemical studies in carious pulpal tissue indicated that S100A8 and the S100A8/S100A9 complex were predominantly expressed by infiltrating neutrophils. Gene expression analyses in immune system cells supported these findings and indicated that bacterial activation of neutrophils caused upregulation of S100A8, S100A9, and S100A13. This study highlights the complex nature of the molecular immune response that occurs during carious infection.
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PMID:S100 and cytokine expression in caries. 1521 55


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