Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In embryonal human cell culture there was found the biological activity of DNA preparations, obtained from peripheral blood cells of acute leukemia patients, which was manifested in the production of virus-like RNA-containing particles, as evidenced by the radioisotope analysis findings and by the reverse transcriptase content in these particles. Also, a rapid growth of the cultures was noted. The DNA preparations from rhabdomyosarcoma, neurinoma and synovial sarcoma in man would cause only an enhancement of human embryonal cell cultures growth. No production of virus-like particles in the latter was noted.
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PMID:[Search for viral genetic information in human tumor DNA by means of transfection]. 8 6

Recent cloning of the t(11;22) region has led to the detection of a number of sequences involved in the breakpoints by substituting a sequence which encodes a putative RNA binding domain for that of the DNA binding domain of the human homologue of murine FLI-1. Several tumours display consistent translocation at t(11;22) (q24;q12), a finding that suggests these fusion transcripts could be expressed and detected by reverse transcriptase polymerase chain reaction amplification. To date, only a small number of Ewing's sarcomas (Es) and peripheral neuroectodermal tumours (pPNET) of bone have been tested with this novel molecular biology approach. In this study, we confirmed the presence of the three putative chimaeric transcripts on 7 cases of Es and pPNET sarcomas of bone and soft tissue, providing 100% positivity for the tested tumours. For comparative purposes, a number of other neuroectodermal tumours were analysed with negative results: esthesioneuroblastoma, retinoblastoma, Schwannoma. A primitive soft tissue sarcoma (ectomesenchymoma) with a 22 chromosome rearrangement did not express any transcript, nor did a number of non-neuroectodermal small round cell sarcomas of soft tissue (rhabdomyosarcomas) and bone (microcellular osteosarcoma), conventional bone sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and synovial sarcomas. These results reinforce the value of molecular biology techniques for the correct assessment of histology difficult evaluable neoplasms, such as the group of small round cell tumours within the Es family.
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PMID:EWS/FLI-1 rearrangement in small round cell sarcomas of bone and soft tissue detected by reverse transcriptase polymerase chain reaction amplification. 752 96

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
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PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Trk receptors have been identified by immunohistochemical methods in primitive neuroectodermal tumor (PNET)/Ewing's sarcoma (ES). However, the presence of different members of the Trk family of receptors in PNET/ES has not been specified. We have examined whether Trk A, B, and C receptors are specifically expressed in ES both with and without features of neural differentiation. Ten ES tumors (five primary tumors of bone and five extraosseous tumors transplanted into nude mice) were investigated for expression of Trk receptors by immunohistochemistry and reverse transcription-polymerase chain reaction. One primary ES and the five grafted ES tumors exhibited signs of neural differentiation; the remaining four primaries were undifferentiated ES. Other tumor types were analyzed as controls; they included three neuroblastomas (NB), two lymphomas, and single cases of pheochromocytoma (PHEO), schwannoma (SCHW), osteosarcoma, and carcinoma of breast, colon, and kidney. Trk receptors were detected in paraffin-embedded tumor tissue sections by means of a pan-Trk polyclonal antibody raised against the 14 carboxy-terminal residues of gp140trk, and trk A, B, and C transcripts were specifically detected by polymerase chain reaction-based amplification on cDNAs derived from tumor RNA with MuLV reverse transcriptase. Reactivity to the pan-Trk antibody was exhibited by six ES tumors, the three NBs, and the single PHEO and SCHW cases; immunoreactivity was restricted to differentiated tumors, in the case of ES. Tumor types positive for immunostaining were also distinguished by containing transcripts of TRK genes. However, the trk A, B, and C expression pattern of ES differed from that of NBs, PHEO, and SCHW. Transcripts of trk A, B, and C were detected in seven, four, and one case of ES, respectively, and in five, two, and five cases of NB, PHEO, and SCHW, respectively. Interestingly, all differentiated ES tumors contained trk A transcripts. Tumors of neuroectodermal phenotype and/or derivation were thus characterized by a distinct consensus expression pattern: trk A+/B-/C+ for differentiated ES and trk A+/B-/C+ for NB-PHEO-SCHW. These results indicate that the TRK gene family is frequently activated in ES; they also suggest that Trk A receptor is a feature of ES with neural differentiation, whereas Trk B and C receptors seem to be present in undifferentiated ES.
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PMID:Activation of TRK genes in Ewing's sarcoma. Trk A receptor expression linked to neural differentiation. 902 32

A 19-year-old:female patient with malignant schwannoma in the right knee was treated by combination chemotherapy including lipophilic anticancer compounds (cyclophosphamide, doxorubicin, vincristine and dacarbazine). The tumor was radically removed after chemotherapy, but metastatic lesions were noted in the right inguinal nodes. The patient died due to the cachexic state six months after surgery. In human neoplasm, P-glycoprotein (P-Gp) encoded by human multidrug resistance gene MDR1 is known to be related with multidrug resistant phenotype. Northern blot analysis revealed apparent MDR1 expression in the metastatic lesion, while the primary lesion showed faint MDR1 expression detected by only reverse transcriptase-polymerase chain reaction. P-Gp positive tumor cells were immunohistochemically detected both in the metastatic lesion and the primary lesion. The P-Gp-positive tumor cells in the metastatic lesion showed anaplastic features with highly atypical nuclei. These results suggest that MDR1 overexpression is related to the multidrug resistance phenomenon in the malignant schwannoma with morphological differences.
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PMID:A case of malignant schwannoma with overexpression of multidrug resistance gene (MDR1) after chemotherapy. 921 1

Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In neoplastic conditions. Schwann cells from experimentally-induced schwannomas appear to retain their responsiveness to nerve growth factor (NGF), although the role of neurotrophins in the neoplastic process in poorly understood. In this study, human neoplastic Schwann cells (five cases of acoustic schwannoma and two cases of malignant peripheral nerve sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied the 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be the present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RNA for NGF and NT-3 was detected by reverse transcriptase in situ polymerase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of either ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred during the neoplastic transformation of Schwann cells. In benign schwannomas, such changes are likely to reflect the loss of axonal contact, while in MPNST they may be related to a complete derangement of cell machinery in the tumour cells.
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PMID:Human neoplastic Schwann cells: changes in the expression of neurotrophins and their low-affinity receptor p75. 936 63

Telomerase activity was examined in intracranial tumors and compared with gene expression of the two core components of telomerase--the reverse transcriptase subunit (hTERT) and the RNA subunit (hTR)--and the proliferative index. We investigated 32 tumors across three to five sampled regions (20 meningiomas, 1 acoustic schwannoma, 1 pituitary adenoma, 8 gliomas, and 2 medulloblastomas). Telomerase activity was demonstrated by the telomeric repeat amplification protocol (TRAP) assay in seven (22%) intracranial tumors (four malignant brain tumors, two atypical meningiomas and one ependymoma) but could not be detected in the 18 (100%) benign meningiomas. hTERT and hTR mRNA were detected using reverse-transcription polymerase chain reaction (RT-PCR). hTERT mRNA was present in 20 (63%) intracranial tumors. Whereas hTERT mRNA transcripts were consistently low or absent in meningiomas, malignant brain tumors exhibited elevated hTERT mRNAs. Multiple regions of glioblastomas showed differences in telomerase activity and in the presence of hTERT mRNA. RT-PCR analysis revealed, for the first time in intracranial tumors, the presence of hTERT mRNA spliced products, corresponding to full-length mRNA as well as spliced mRNAs with critical reverse transcriptase motifs deleted. Only tumors with marked telomerase activity showed all hTERT spliced messages simultaneously. The absence of a positive correlation between telomerase activity and hTERT mRNA could not be attributed to the presence of hTERT spliced variants. We found a significant correlation between telomerase activity scores and Ki-67 proliferation index. A positive association is also seen between Ki-67 staining and the degree of hTERT mRNA expression. This shows that there seems to be a relationship between telomerase activity or the degree of hTERT expression and proliferation rate in intracranial tumors.
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PMID:Telomerase activity and expression of telomerase reverse transcriptase correlated with cell proliferation in meningiomas and malignant brain tumors in vivo. 1156 58

Mutation detection in the neurofibromatosis type 2 (NF2) gene is challenging because when combining mutation detection methods such as single-strand conformational polymorphism and heteroduplex analysis, denaturing gradient gel electrophoresis, and direct sequencing of aberrant polymerase chain reaction (PCR) fragments only 30 to 60% of the constitutional mutations are detected. Because large deletions and complete chromosome rearrangements are also described methods such as microarray-comparative genomic hybridization and fluorescence in situ hybridization are also used. The one type of mutation often missed corresponds to deletions encompassing one or few exons. To detect this type we have developed a swift and reliable method. We perform a gene dosage analysis with two fluorescent multiplex PCR assays that amplify 15 of the 17 NF2 exons. The labeled PCR products are quantified and gene dose is calculated with respect to controls. We tested the reliability of this method with DNA from eight NF2 patients with known heterozygous NF2 deletions, eight controls and four unknown NF2 patients. In all of the patients with known heterozygous deletions we found in several exons a reduction of gene dosage to 50 to 69%. In one NF2 patient with previously unknown mutation and a severe phenotype we found the gene dosage of two exons reduced by 50% indicating a deletion of these two exons on one allele. This finding was validated by reverse transcriptase-PCR on fibroblast and schwannoma cell cultures of this patient and cDNA sequencing. Our gene dosage assay will detect deletions of one or more exons as well as gross deletions of the whole coding region of the gene. It can complement the existing screening methods because it is faster and easier.
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PMID:Sensitive detection of deletions of one or more exons in the neurofibromatosis type 2 (NF2) gene by multiplexed gene dosage polymerase chain reaction. 1568 80

A 33-year-old female presented with a rare synovial sarcoma manifesting as a painful 12 x 15 mm tumor in the median palmar carpus. Preoperative neurological examination detected only radiating spontaneous pain in her right radial palm and decreased right grasping power. Magnetic resonance (MR) imaging confirmed the presence of the tumor. The preoperative diagnosis was schwannoma originating from the right median nerve. Subcapsular removal of the tumor was performed for preservation of the nerve function. However, postoperative histological and immunohistochemical studies suggested synovial sarcoma originating from the median nerve. No systemic metastasis was detected and the residual tumor capsule was totally removed. Local radiation therapy of 40 Gy, 2 Gy per day, was administered. Fourteen months later, local recurrence was detected on MR imaging. Total removal of the recurrent tumor was performed. Synovial sarcoma was finally diagnosed by the identification of SYT-SSX1 fusion gene transcripts using reverse transcriptase-polymerase chain reaction with a frozen tumor tissue sample.
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PMID:Intraneural synovial sarcoma originating from the median nerve. 1829 77