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)

This report describes an intra-abdominal desmoplastic small round-cell tumor in a 29-year-old man that significantly differed from the classically described appearances of this unique tumor. It showed extensive papillary areas, no necrosis, and very little desmoplasia. The latter was limited, paucicellular, and present in areas separate from the papillary structures. Also, areas of back-to-back, single-cell infiltration, which mimicked lobular breast carcinoma, were present. These epithelial features suggested the diagnosis of adenocarcinoma or peculiar mesothelioma. But, the immunohistochemical features (tumor cells positive for keratin, desmin, and vimentin) were more consistent with an intra-abdominal desmoplastic small round-cell tumor. The diagnosis became clear after application of reverse transcriptase-polymerase chain reaction techniques to formalin-fixed, paraffin-embedded tissue, which showed the presence of a 100-base pair product containing the fusion junction of Ewing's sarcoma-1 exon 7 to Wilms' tumor-1 exon 8. This feature is considered unique to intra-abdominal desmoplastic small round-cell tumors. This case illustrates the less common histologic findings that can be found in intra-abdominal desmoplastic small round-cell tumor. This deviation from the classic histologic findings may be an expression of an uncommon morphologic variant and/or partially produced by the effects of prior chemotherapy. In either event, only by illustrating the various histologic appearances of intra-abdominal desmoplastic small round-cell tumor are the chances increased for the accurate diagnosis of this aggressive neoplasm with a poor prognosis.
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PMID:Intra-abdominal desmoplastic small round-cell tumor: expansion of the pathologic profile. 878 11

The Wilms tumor suppressor gene (WT1) is mutated in a number of cases of Wilms' tumor as well as in mesothelioma and leukemia. It encodes a transcription factor derived from any one of four alternate transcripts. WT1 has a restricted pattern of expression within the body and within the hemopoietic system its expression is limited to primitive leukemias and a number of leukemic cell lines. Given the overexpression of WT1 in leukemias, we have addressed the question of whether this gene is expressed within the normal hemopoietic system. Mononuclear bone marrow (BM) cells obtained from normal donors were separated by fluorescence-activated cell sorting (FACS) into "primitive" (CD34+) and "mature" (CD34-) cell populations. Total RNA extracted from these cells was subjected to reverse transcriptase polymerase chain reaction (RT-PCR) using primers based on the WT1 sequence, to examine the expression of this gene within the hemopoietic system. Phenotypic purity of cells was guaranteed by performing single-cell sorting followed by RT-PCR to define the precise cellular phenotypes that express WT1. Expression of WT1 was detected in cells bearing the CD34+ phenotype but not in those cells lacking expression of CD34. In addition, single-cell analysis revealed that expression of WT1 occurred in the candidate stem cell-containing population of hemopoietic cells which have the phenotype CD34+ CD38-. Moreover, the single-cell RT-PCR analysis also demonstrated that differential expression of alternate transcripts of WT1 occurs between hemopoietic progenitor cells with the same phenotype. In conclusion, expression of WT1 is limited to early progenitors of the blood system, which suggests that this gene plays a critical role in hemopoietic development.
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PMID:Expression of the Wilms' tumor gene (WT1) in normal hemopoiesis. 940 89

The vascular endothelial growth factor (VEGF) family is a novel regulator of endothelial cell proliferation. We assessed the mRNA expression of VEGF, VEGF type C (VEGF-C) and their receptors together with the microvessel density (VD) and microlymphatic vessel density (LVD) in pursuit of their connection and prognostic value in malignant pleural mesothelioma (MPM). We used four human MPM cell lines, 54 MPM tumours and five normal pleural tissues. Expression levels for receptors and ligands were assessed by semiquantitative reverse transcriptase polymerase chain reaction analysis. Microvessels were highlighted by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzyme-histochemistry for 5'-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C and VEGFRs were high in all MPM cell lines. The percentages of tumours with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for fms-like tyrosine kinase (flt)-1, 42.6% (23/54) for kinase insert domain-containing recepter (KDR) and 59.3% (32/54) for flt-4. Significant positive correlations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumour tissues. The association between LVD and VEGF-C expression level was especially strong (P< 0.0001, r= 0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation, however, was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGFNEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumour, and assessment of vascularity may be a useful prognostic indicator for MPM patients.
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PMID:VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. 1048 12

Asbestos is a ubiquitous naturally occurring fiber causing multiple cancers and fibroproliferativedisease. The mechanisms of epithelial cell hyperplasia, a hallmark of the initiation of lung cancers by asbestos, have been unclear. We demonstrate here that mice expressing a dominant-negative mutant epidermal growth factor receptor (EGFR) under the control of the human lung surfactant protein-C promoter exhibit decreased pulmonary epithelial cell proliferation without alterations in asbestos-induced inflammation. In contrast to transgene-negative littermates, inhalation of asbestos by mice expressing the mutant EGFR does not result in early and elevated expression of early response proto-oncogenes (fos/jun or activator protein 1 family members). Additionally, quantitative reverse transcriptase-PCR analysis for levels of c-jun and c-fos in bronchiolar epithelium isolated by laser capture microdissection demonstrates increases in expression of these genes in asbestos-exposed epithelial cells. Results show that the EGFR mediates both asbestos-induced proto-oncogene expression and epithelial cell proliferation, providing a rationale for modification of its phosphorylation in preventive and therapeutic approaches to lung cancers and mesothelioma.
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PMID:A mutant epidermal growth factor receptor targeted to lung epithelium inhibits asbestos-induced proliferation and proto-oncogene expression. 1215 12

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.
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PMID:Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling. 1592 Jan 67

Human telomerase detected by in situ hybridization has been demonstrated to be a useful tool for the diagnosis of malignancy and has also been tested by reverse transcriptase-polymerase chain reaction in several tumors such as hepatic cell carcinoma, melanoma, colonic carcinoma, gastric carcinoma, biliary carcinoma, breast carcinoma, mesothelioma, lung carcinoma, female tract carcinoma, and prostatic carcinoma. A monoclonal antibody (clone Tel-24) that allows for the detection of human telomerase reverse transcriptase (hTERT) in paraffin blocks of archival material has recently been developed. Carcinomas of cervix, endometrium, and breast have been studied by this method, but its value in prostatic carcinoma has not been explored; for that reason, we studied benign and malignant prostatic lesions by immunohistochemistry using paraffin embedded tissue. The aim of the study was to define the sensitivity and specificity of hTERT in prostate cancer, in comparison with alpha-methylacyl-coenzyme A racemase (AMACR) (P504-S). Fifty-five specimens of diverse prostatic lesions were selected for study (43 needle biopsies and 12 transurethral resections); there were 61 malignancies (47 infiltrating carcinomas and 14 high-grade prostatic intraepithelial neoplasias [PIN]) and 29 benign lesions (10 basal cell hyperplasias, 12 nodular hyperplasias, 4 chronic prostatitis, and 3 atrophic glands). Signal for hTERT nucleolar was detected in 31 of 47 infiltrating adenocarcinomas, in 11 of 14 PIN, and in none of 27 benign lesions (sensitivity, 71%; specificity, 100%). Diffuse cytoplasmic positivity for AMACR was found in 37 of 41 infiltrating adenocarcinomas, in 7 of 7 PIN, and in 6 of 22 benign lesions (sensitivity, 91%; specificity, 72%). These results indicate that hTERT is highly specific of malignancy, with no false-positive cases; however, it had lower sensitivity than AMACR.
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PMID:Human telomerase and alpha-methylacyl-coenzyme A racemase in prostatic carcinoma. A comparative immunohistochemical study. 1684 61

We report production of a monoclonal antibody against the hRRM2 subunit of ribonucleotide reductase and immunohistochemistry (IHC) staining of human cancer tissues available in paraffin block. BALB/c mice were immunized with purified hRRM2 protein, and splenocytes from these mice were fused with mice myeloma cell lines by using standard hybridoma production techniques. Resulting hybridomas producing anti-hRRM2 antibodies were screened by enzyme-linked immunosorbent assay (ELISA). The specificity was determined by limiting serial dilutions. Clones were chosen for antibody production based on their activities on paraffin-embedded human tissues. They were then isotyped and shown to produce immunoglobulin M (IgM) antibodies against hRRM2. Using these antibodies, we performed Western blot on oropharyngeal KB cancer cell lines and immunohistochemistry staining of available paraffin-embedded cancer tissues. Interestingly, cancer tissues stained positive with the anti-hRRM2 antibody but not normal tissues. Colon, stomach, liver, lung, pancreatic, and breast cancer had the strongest staining. No staining was identified on astrocytoma, mesothelioma, or myeloma. Our findings were validated with data from reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrating overexpression of hRRM2 in breast cancer tissues compared to matched noncancer tissues. We propose that IHC with this monoclonal anti-hRRM2 antibody may be useful for ribonucleotide reductase research and as a biomarker for tumorgenesis.
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PMID:Production of a monoclonal antibody against the hRRM2 subunit of ribonucleotide reductase and immunohistochemistry study of human cancer tissues. 1704 81

Synovial Sarcoma consistently harbors t(X;18) resulting in SS18-SSX1, SS18-SSX2 and rarely SS18-SSX4 fusion transcripts. Of 328 cases included in our study, synovial sarcoma was either the primary diagnosis or was very high in the differential diagnosis in 134 cases: of these, amplifiable cDNA was obtained from 131. SS18-SSX fusion products were found in 126 (96%) cases (74 SS18-SSX1, 52 SS18-SSX2), using quantitative and 120 by conventional reverse transcriptase-polymerase chain reaction (RT-PCR). One hundred and one cases in a tissue microarray, analyzed by fluorescence in situ hybridization (FISH), revealed that 87 (86%) showed SS18 rearrangement: four RT-PCR positive cases, reported as negative for FISH, showed loss of one spectrum green signal, and 15 cases had multiple copies of the SS18 gene: both findings are potentially problematic when interpreting results. One of three cases, not analyzed by RT-PCR reaction owing to poor quality RNA, was positive by FISH. SS18-SSX1 was present in 56 monophasic and 18 biphasic synovial sarcoma: SS18-SSX2 was detected in 41 monophasic and 11 biphasic synovial sarcoma. Poorly differentiated areas were identified in 44 cases (31%). There was no statistically significant association between biphasic, monophasic and fusion type. Five cases were negative for SS18 rearrangement by all methods, three of which were pleural-sited neoplasms. Following clinical input, a diagnosis of mesothelioma was favored in one case, a sarcoma, not otherwise specified in another and a solitary fibrous tumor in the third case. The possibility of a malignant peripheral nerve sheath tumor could not be excluded in the other two cases. We concluded that the employment of a combination of molecular approaches is a powerful aid to diagnosing synovial sarcoma giving at least 96% sensitivity and 100% specificity but results must be interpreted in the light of other modalities such as clinical findings and immunohistochemical data.
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PMID:Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. 1733 49

The diagnosis of sarcomatoid mesothelioma is still a worldwide challenge and it is often difficult, both clinically and by morphological analysis, to differentiate sarcomatoid mesothelioma from synovial sarcoma, the most frequent intrathoracic sarcoma. To confirm the absence of the synovial sarcoma translocation t(X; 18) (SYT-SSX) in sarcomatoid mesothelioma, and to test its usefulness differentiating sarcomatoid mesothelioma from synovial sarcoma, 28 tumours were examined using the reverse transcriptase-polymerase chain reaction. RNA was extracted from paraffin blocks using standard methods, reverse-transcribed and PCR performed. Molecular analysis completed in two independent laboratories showed that sarcomatoid mesothelioma samples were negative for the t(X-18). This result confirms the usefulness of this analysis in differentiating sarcomatoid mesothelioma from synovial sarcoma.
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PMID:SYT-SSX fusion is absent in sarcomatoid mesothelioma allowing its distinction from synovial sarcoma of the pleura. 1750 90

Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth and proliferation of tumours of the lung and pleura, through the generation of kinin peptides that signal through the kinin B(1) (BDKRB1) and B(2) (BDKRB2) receptors. The development and progression of cancer results from genetic mutations, as well as epigenetic changes that include methylation of DNA at CpG islands. The aim of this study was to assess whether expression of the kallikrein-kinin genes in lung cancer and mesothelioma cells is regulated by DNA methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry showed differences in the basal expression of the kallikrein-kinin genes and proteins in lung carcinoma and mesothelioma cells, compared with non-malignant lung epithelial and mesothelial cells, respectively. Following treatment with the demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was consistently increased in both lung carcinoma and mesothelioma cells, whereas KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of the kallikrein-kinin genes will enhance understanding of their role in carcinogenesis and provide insights into the importance of kallikreins as tumour biomarkers.
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PMID:Effects of the demethylating agent, 5-azacytidine, on expression of the kallikrein-kinin genes in carcinoma cells of the lung and pleura. 2190 90


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