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)

Fibronectin (FN), a matrix glycoprotein, has been shown to undergo alternative splicing exclusively during organogenesis and tumorigenesis. One such splice variant, extradomain-B (ED-B) FN, is normally absent in normal adult tissues and is proposed to be a marker of tumoral angiogenesis. The present study was aimed at elucidating whether ED-B FN is expressed in non-small cell lung carcinomas and whether such aberrant expression correlates with tumoral angiogenesis. Frozen tissues from 28 non-small cell lung carcinomas (consisting of both squamous cell carcinomas and adenocarcinomas) along with paired normal tissue samples were collected from the tissue bank collection of the Department of Pathology, London Health Sciences Center, Canada. Frozen tissue specimens were subjected to RNA extraction and real time reverse transcriptase-polymerase chain reaction (RT-PCR) with respect to total and ED-B FN isoform expression. In addition, paraffin-embedded tissue sections from the same cases were collected for histological analysis using ED-B FN antibody. Tumor tissues were further stained with CD34 antibody and analyzed semiquantitatively for tumor microvessel density. The results demonstrate up-regulation of ED-B FN mRNA levels in lung tumor tissues as compared to paired normal tissues. Furthermore, ED-B FN expression was localized specifically to tumor cells and was found to correlate with tumor microvessel density. These findings provide evidence of possible involvement of ED-B FN in pulmonary tumoral angiogenesis. Furthermore, ED-B FN may potentially be used as a diagnostic marker and a target for antiangiogenic therapy.
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PMID:ED-B fibronectin in non-small cell lung carcinoma. 1620 24

The BCR-ABL oncoprotein of chronic myelogenous leukemia (CML) localizes to the cell cytoplasm, where it activates proliferative and antiapoptotic signaling pathways. We previously reported that the combination of the ABL kinase inhibitor imatinib mesylate (IM) and the nuclear export inhibitor leptomycin B (LMB) traps BCR-ABL inside the nucleus, triggering the death of the leukemic cells. To evaluate the efficacy of the combination of IM and LMB on human cells we collected CD34-positive cells from 6 healthy donors and myeloid progenitors from 35 patients with CML. The sequential addition of IM and LMB generated the strongest reduction in the proliferative potential of the leukemic cells, with limited toxicity to normal myeloid precursors. Furthermore, nested reverse transcriptase-polymerase chain reaction (RT-PCR) analysis on colonies representative of each experimental condition demonstrated that the combination of IM and LMB was the most effective regimen in reducing the number of BCR-ABL-positive colonies. The efficacy of the 2-drug association was independent of the clinical characteristics of the patients. Our results indicate that strategies aimed at the nuclear entrapment of BCR-ABL efficiently kill human leukemic cells, suggesting that the clinical development of this approach could be of significant therapeutic value for newly diagnosed and IM-resistant CML patients.
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PMID:BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B. 1624 86

Previously, we demonstrated that enforced activation of signal transducer and activator of transcription 5 (STAT5A) in human cord blood (CB)-derived stem/progenitor cells results in enhanced self-renewal and impaired myelopoiesis. The present study identifies C/EBPalpha as a critical component that is down-regulated by STAT5. Microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis on STAT5A(1*6)-transduced CD34(+) cells identified C/EBPalpha as the most prominently down-regulated gene. To determine the cell-biological relevance of these observations, a 4-OHT-inducible C/EBPalpha-ER protein was co-expressed with the STAT5A(1*6) mutant in CB CD34(+) cells using a retroviral approach. Re-expression of C/EBPalpha in STAT5A(1*6) cells resulted in a marked restoration of myelopoiesis. The proliferative advantage imposed on CD34(+) cells by STAT5A(1*6) depended on the down-modulation of C/EBPalpha, as reintroduction of C/EBPalpha induced a quick cell-cycle arrest and the onset of myeloid differentiation. Long-term culture-initiating cell (LTC-IC) frequencies were elevated from 0.8% +/- 0.6% to 7.8% +/- 1.9% by STAT5A(1*6) as compared with controls, but these elevated LTC-IC frequencies were strongly reduced upon re-introduction of C/EBPalpha in STAT5A(1*6) cells, and no second cobble-stone area-forming cells (CAFCs) could be generated from double-transduced cells. Enumeration of progenitors revealed that the number of colony-forming cells (CFCs) was reduced more than 20-fold when C/EBPalpha was co-expressed in STAT5A(1*6) cells. Our data indicate that down-modulation of C/EBPalpha is a prerequisite for STAT5-induced effects on self-renewal and myelopoiesis.
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PMID:STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic stem/progenitor cells involves down-modulation of C/EBPalpha. 1645 47

Earlier reports on a putative precursor cell population in adipose tissue showed differentiation along several mesodermal lineages, leading some to think that adipose tissue can be a source of cells applicable in regenerative medicine. However, characterizations of these adipose-derived precursor cells (ADPC) in the 3-dimensional (3-D) environment, especially within the area of bone-specific composite scaffolds, have been lacking. In this study, ADPC plated on culture flasks or seeded on medical grade polycaprolactone-tricalcium phosphate scaffolds (mPCL-CaP) were able to differentiate along the osteogenic lineages in both 2-D and 3-D environments as assessed with immunohistochemistry of osteo-related proteins, reverse transcriptase-polymerase chain reactions and alkaline phosphatase assay. The mPCL-CaP scaffolds provided adipose-derived cells (ADC) with a suitable environment as determined by DNA and metabolic assays, light, confocal and scanning electron microscopy. Flow cytometry revealed ADC to be CD29+, CD44+, CD73+, CD90+ and CD14-, CD31-, CD34-, CD45-, CD71-, and therefore showed the absence of hematopoietic stem cells but possibly the presence of pericytes and mescenchymal stem cells with osteogenic potential. The results of this study demonstrated the potential of using ADPC in combination with mPCL-CaP scaffolds for bone regenerative medicine.
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PMID:Characterization of osteogenically induced adipose tissue-derived precursor cells in 2-dimensional and 3-dimensional environments. 1665 24

Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-gamma]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2K(d) determinants. In contrast, apart from H-2L(d[LOW]) display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except for inducible CD117([LOW]) expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90.1 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95([LOW]) expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I(+[LOW])/class II-) and CD (CD34+/CD80-/CD86-/CD95L-) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue-specific plasticity is unknown.
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PMID:Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines. 1683 18

The translocation t(12;22) involves MN1 and TEL and is rarely found in acute myeloid leukemia (AML). Recently, it has been shown in a mouse model that the fusion protein MN1-TEL can promote growth of primitive hematopoietic progenitor cells (HPCs) and, in cooperation with HOXA9, induce AML. We quantified MN1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 142 adult patients with AML with normal cytogenetics treated uniformly in trial AML-SHG 01/99. AML samples were dichotomized at the median MN1 expression. High MN1 expression was significantly correlated with unmutated NPM1 (P < .001), poor response to the first course of induction treatment (P = .02), a higher relapse rate (P = .03), and shorter relapse-free (P = .002) and overall survivals (P = .03). In multivariate analysis, MN1 expression was an independent prognostic marker (P = .02) in addition to age and Eastern Cooperative Oncology Group (ECOG) performance status. Excluding patients with NPM1(mutated)/FLT3ITD(negative), high MN1 expression was associated with shorter relapse-free survival (P = .057). MN1 was highly expressed in some patients with acute lymphoblastic but not chronic lymphocytic or myeloid leukemia. MN1 was highly expressed in HPCs compared with differentiated cells and was down-regulated during in vitro differentiation of CD34(+) cells, suggesting a functional role in HPCs. In conclusion, our data suggest MN1 overexpression as a new prognostic marker in AML with normal cytogenetics.
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PMID:High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. 1691 23

This pilot study was performed to determine whether MYCN expression warrants further investigation as a tumor marker to detect low levels of residual neuroblastoma (NB). Seven NB cell lines and 30 bone marrow (BM) samples from patients with high-risk NB were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) for MYCN expression, and for the established NB marker tyrosine hydroxylase. MYCN was expressed in all 7 NB cell lines, but not in normal peripheral blood, CD34 cells, or BM. In dilution studies using cell lines with or without DNA amplification of MYCN, 1 NB cell in 10 to 10 nucleated blood cells was detectable by RT-PCR. MYCN was identified in all 21 BM samples in which tumor cells were identified by histologic examination, including 4 samples in which tyrosine hydroxylase was not detected. Additionally, expression of both markers was detected in 5 samples that were negative by histology but presumably contained low levels of tumor cells, consistent with the greater sensitivity of RT-PCR compared with morphologic methods. Detection of MYCN RNA was independent of MYCN DNA amplification status. The selective expression of MYCN in tumor cells, and the sensitivity of detection of MYCN by RT-PCR noted in this and other studies, supports further evaluation of MYCN as a NB marker for molecular detection of minimal residual disease.
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PMID:Pilot study to evaluate MYCN expression as a neuroblastoma cell marker to detect minimal residual disease by RT-PCR. 1702 22

Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are multifunctional matricellular glycoproteins. Recent experimental studies suggested that Hevin and SPARC together diminish angiogenesis, but their significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed to correlate SPARC and Hevin expression with angiogenesis and clinicopathological features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens were assessed by immunostaining, immunoblotting, and quantitative reverse transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA levels were significantly higher in tumours than in non-tumourous livers. A significant correlation between tumour SPARC and Hevin mRNA levels was found. Moreover, SPARC protein localized in the tumour sinusoidal area correlated significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC and Hevin proteins were detected in clinical samples. Truncated SPARC protein localized in the tumour sinusoidal area correlated significantly with tumour MVD. On the other hand, overexpression of full-length SPARC in tumour xenografts in athymic nude mice significantly delayed tumour growth, and this delay was related to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC cells was related to the presence of tumour encapsulation and the absence of hepatitis B surface antigen in clinical samples. Overexpression of Hevin in tumour xenografts also significantly delayed tumour growth. In conclusion, this study has shown that SPARC and Hevin are upregulated in HCC compared with non-tumourous liver, and that they are inter-related at both mRNA and protein levels. Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour progression.
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PMID:SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma. 1702 19

We compared the gene expression profile of adult acute lymphoblastic leukemia (ALL) to normal hematopoietic and non-ALL samples using oligonucleotide arrays. Connective tissue growth factor (CTGF) was the highest overexpressed gene in B-cell ALL compared with the other groups, and displayed heterogeneous expression, suggesting it might have prognostic relevance. CTGF expression was examined by quantitative reverse transcriptase-polymerase chain reaction (ORT-PCR) on 79 adult ALL specimens. CTGF expression levels were significantly increased in ALL cases with B-lineage (P < .001), unfavorable cytogenetics (P < .001), and blasts expressing CD34 (P < .001). In a multivariate proportional hazards model, higher CTGF expression levels corresponded to worsening of overall survival (OS; hazard ratio 1.36, for each 10-fold increase in expression; P = .019). Further studies are ongoing to confirm the prognostic value of CTGF expression in ALL and to investigate its role in normal and abnormal lymphocyte biology.
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PMID:Connective tissue growth factor (CTGF) expression and outcome in adult patients with acute lymphoblastic leukemia. 1717 Jan 28

Aberrant micro RNA (miRNA) expression has been described in human malignancies including B-cell lymphomas. We here report BCR-ABL- and c-MYC-dependent regulation of miRNA expression in chronic myeloid leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific quantitative real-time reverse transcriptase-polymerase chain reaction (miR-qRT-PCR). In 3 bcr-abl-positive cell lines, expression of miRNAs encoded within the polycistronic miR-17-92 cluster is specifically down-regulated (2- to 5-fold) by both imatinib treatment and anti-BCR-ABL RNA interference (RNAi). In addition, anti-c-MYC RNAi reduces miR-17-92 expression in K562 cells in which miRNAs can specifically repress reporter gene expression, as demonstrated by specific miRNA inhibition with antagomirs. Furthermore, lentivirus-mediated overexpression of polycistronic miRNAs in K562 cells confers increased proliferation, partial resistance against anti-c-MYC RNAi, and enhanced sensitivity to imatinib-induced cell death. Finally, we determined miR-17-92 expression in purified normal (n = 4), early chronic-phase (CP) (n = 24), and blast-crisis (BC) (n = 7) CML CD34(+) cells and found up-regulation of polycistronic pri-miRNA transcripts in CML and mature miRNAs in CP but not in BC CML. These data are in accordance with a BCR-ABL-c-MYC-miR-17-92 pathway that mediates enhanced miRNA expression in CP but not BC CML CD34(+) cells. Altered miRNA expression may contribute to the pathophysiology of the disease and may provide potential targets for therapeutic intervention.
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PMID:Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. 1728 33


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