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)

Differentiation inhibitory factor (nm23 protein) inhibited the induction of differentiation of mouse myeloid leukemia M1 and WEHI-3BD+ and human erythroleukemia HEL, KU812, and K562 cells. Block of differentiation may be associated with the aggressive behavior of leukemia. To examine the role of nm23 in human myeloid leukemia, we investigated the relative levels of nm23-H1, nm23-H2, and c-myc transcripts in 42 patients with acute myelogenous leukemia (AML), and in 5 with chronic myelogenous leukemia at chronic phase by reverse transcriptase polymerase chain reaction. The expression of nm23-H1 and -H2 but not of c-myc in AML was significantly higher than that in normal blood cells. Among AMLs, acute monocytic leukemia (presentation with AML-M5 morphology) was especially associated with elevated nm23-H1 and -H2 mRNA levels. On the other hand, the elevated levels of c-myc expression in AML-M5 were less evident. An analysis of correlation between nm23 expression and clinicopathological parameters showed that resistance to initial chemotherapy is associated with increased nm23-H1 mRNA levels and that a high initial white blood cell count is associated with increased nm23-H2 mRNA levels. Elevated nm23-H1 mRNA levels were associated with significantly reduced the overall survival of AML, especially of AML-M5 patients. The present results indicate that nm23-H1 and -H2 are overexpressed in AML and especially nm23-H1 gene expression predicts the prognosis of AML, especially of AML-M5.
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PMID:Differentiation inhibitory factor nm23 as a new prognostic factor in acute monocytic leukemia. 889 23

The differentiation inhibitory factor nm23 inhibits the differentiation of murine and human myeloid leukemia cells. The inhibition of differentiation may be associated with the aggressive behavior of leukemia. To clarify the role of nm23 in human myeloid leukemia, we investigated the relative levels of nm23-H1, nm23-H2 and c-myc transcripts in bone marrow and blood samples from 110 patients with acute myeloid leukemia (AML) using the reverse transcriptase polymerase chain reaction. The expression levels of nm23-H1 and nm23-H2 in these AML samples were significantly higher than in normal blood cells, and a higher level of nm23-H1 expression was correlated with poor prognosis for AML patients. Analysis of the correlation between nm23 expression and clinical parameters demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and reduced overall survival. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly influenced the prognosis of patients with AML, particularly in AML-M5.
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PMID:Differentiation inhibitory factor Nm23 as a prognostic factor for acute myeloid leukemia. 1003 98

Alteration of psoriasin (S100A7) expression has previously been identified in association with the transition from preinvasive to invasive breast cancer. In this study we have examined persistence of psoriasin mRNA and protein expression in relation to prognostic factors in a cohort of 57 invasive breast tumors, comprising 34 invasive ductal carcinomas and 23 other invasive tumor types (lobular, mucinous, medullary, tubular). We first developed an IgY polyclonal chicken antibody and confirmed specificity for psoriasin by Western blot in transfected cells and tumors. The protein was localized by immunohistochemistry predominantly to epithelial cells, with both nuclear and cytoplasmic staining, as well as occasional stromal cells in psoriatic skin and breast tumors; however, in situ hybridization showed that psoriasin mRNA expression was restricted to epithelial cells. In breast tumors, higher levels of psoriasin measured by reverse transcriptase-polymerase chain reaction and Western blot (93% concordance) were significantly associated with estrogen and progesterone receptor-negative status (P < 0.0001, P = 0.0003), and with nodal metastasis in invasive ductal tumors (P = 0. 035), but not with tumor type or grade. Psoriasin expression also correlated with inflammatory infiltrates (all tumors excluding medullary, P = 0.0022). These results suggest that psoriasin may be a marker of aggressive behavior in invasive tumors and are consistent with a function as a chemotactic factor.
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PMID:Psoriasin (S100A7) expression and invasive breast cancer. 1059 35

Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.
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PMID:Correlative immunohistochemical and reverse transcriptase polymerase chain reaction analysis of somatostatin receptor type 2 in neuroendocrine tumors of the lung. 1071 13

Tissue hypoxia is a characteristic property of cervical cancers that makes tumors resistant to chemo- and radiation therapy. Erythropoietin (Epo) is a hypoxia-inducible stimulator of erythropoiesis. Acting via its receptor (EpoR), Epo up-regulates bcl-2 and inhibits apoptosis of erythroid cells and rescues neurons from hypoxic damage. In addition to human papillomavirus infection, increased bcl-2 expression and decreased apoptosis are thought to play a role in the progression of cervical neoplasia. Using reverse transcriptase-polymerase chain reaction and Western blotting we showed that HeLa and SiHa cervical carcinoma cells and human cervical carcinomas express EpoR, and that hypoxia enhances EpoR expression. Exogenous Epo stimulated tyrosine phosphorylation and inhibited the cytotoxic effect of cisplatin in HeLa cervical carcinoma cells. Using immunohistochemistry, we examined the expression of Epo, EpoR, p16, hypoxia-inducible factor (HIF)-1alpha, and bcl-2 in benign and dysplastic cervical squamous epithelia and invasive squamous cell carcinomas (ISCCs). EpoR expression in benign epithelia was confined to the basal cell layers, whereas in dysplasias it increasingly appeared in more superficial cell layers and showed a significant correlation with severity of dysplasia. Diffuse EpoR expression was found in all ISCCs. Expression of Epo and HIF-1alpha was increased in dysplasias compared to benign epithelia. Focal Epo and HIF-1alpha expression was seen near necrotic areas in ISCCs, and showed correlation in their spatial distribution. Significant correlation was found between expression of EpoR, and p16 and bcl-2 in benign and dysplastic squamous epithelia. Our results suggest that increased expression of Epo and EpoR may play a significant role in cervical carcinogenesis and tumor progression. Hypoxia-inducible Epo signaling may play a significant role in the aggressive behavior and treatment resistance of hypoxic cervical cancers.
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PMID:Hypoxia-inducible erythropoietin signaling in squamous dysplasia and squamous cell carcinoma of the uterine cervix and its potential role in cervical carcinogenesis and tumor progression. 1275 37

Clinical and histopathological evaluations are inadequate for assessing biological aggressiveness and regrowth potential in benign pituitary adenomas. To develop reliable and prognostically informative means of predicting behavior remains an intractable problem. Telomerase, a reverse transcriptase that extends telomere length, may facilitate tumorigenesis and tumor immortality. In the present study, we investigated the telomerase activity of pituitary adenomas, and attempted to assess the value of telomerase expression for predicting their clinical course. In total, 31 (30 patients) benign pituitary adenoma samples including 8 recurrent adenomas were studied. Telomerase expression was evaluated by polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay and telomerase activity levels were quantitated by improved PCR enzyme-linked immunosorbent assay (ELISA). The data were analyzed in relation to clinical course which was reviewed at 4-5.5 years (median follow-up time, 52.5 months) after surgery. The relative values of the telomerase expression for predicting the clinical course were compared with the MIB-1 antigen-based proliferative cell index (PCI) and p53 immunoreactivity which have recently been suggested to correlate with aggressive behavior in pituitary adenomas. Overall, telomerase expression was detected in 13% of the adenomas (4 tumor tissues, 3 patients). These adenomas comprised large, invasive, and functioning adenomas. The number of telomerase-positive adenomas was small; however, the PCI was higher in cases with telomerase expression (4 tumor tissues; mean, 4.2 +/- 2.4%) than in those without it (27 tumor tissues; 1.4 +/- 1.3%) (p = 0.01). One tumor with detectable telomerase expression, which did not undergo additional pharmacological or radiotherapeutic intervention after first surgery, recurred rapidly despite gross total surgical resection, although the PCI of both the primary and recurrent adenomas was not high. Detection of telomerase expression may represent an additional useful means of identifying aggressive behavior, complementing the histopathological evaluation of benign-appearing pituitary adenomas.
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PMID:Telomerase activity in pituitary adenomas: significance of telomerase expression in predicting pituitary adenoma recurrence. 1282 19

Matrix metalloproteinase-2 (MMP-2) plays important roles in cancer development and aggression. Our previous studies revealed a strong association between the MMP-2 -1306C/T polymorphism and risk of several cancers. A novel -735C/T polymorphism in MMP-2 promoter has been identified but the function is undefined. This study examined our hypothesis that these two polymorphisms might have functional relevance and impact on risk of esophageal squamous cell carcinoma in the context of haplotype. Genotypes and haplotypes were analyzed in 527 cases and 777 controls and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The function of the polymorphisms was examined by electrophoretic mobility shift assays, luciferase gene expression assays, and reverse transcriptase-PCR analyses. It was found that the -735C-->T transition disrupts an Sp1 site and displays a lower promoter activity. The C(-1306)-C(-735) haplotype had 7-fold increased luciferase expression and 3.7-fold increased MMP-2 mRNA levels in esophageal tissues compared with the T(-1306)-T(-735) haplotype. A case-control analysis revealed a 1.52-fold (95% CI = 1.17-1.96) or 1.30-fold (95% CI = 1.04-1.63) excess risk of developing esophageal squamous cell carcinoma for the -1306CC or -735CC genotype carriers compared with noncarriers, respectively. A greater association was observed between elevated risk of developing esophageal squamous cell carcinoma and C(-1306) or C(-735) allele containing haplotypes, with the risk being highest for the C(-1306)-C(-735) haplotype compared with the T(-1306)-T(-735) haplotype (OR = 6.53; 95% CI = 2.78-15.33). The C(-1306)-C(-735) haplotype was also associated with increased risk for distant metastasis of esophageal squamous cell carcinoma (OR = 3.34; 95% CI = 1.16-9.63). These findings suggest that the C(-1306)-C(-735) haplotype in the MMP-2 promoter contributes to risk of the occurrence and metastasis of esophageal squamous cell carcinoma by increasing expression of MMP-2.
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PMID:Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. 1549 91

While most human T-cell leukemia virus type-I (HTLV-I)-infected T cells express abundant class II antigens, some aggressive-type adult T-cell leukemia (ATL) cells lose their expression. To investigate the significance of the class II antigen of HTLV-I infected cells, the progressiveness of HTLV-I-infected long-term cultured T-cell lines was evaluated, and then their antigen-presenting capacity was examined using a superantigen, staphylococcus enterotoxin B (SEB). Among the cell lines derived from peripheral blood, HPB-ATL-T (ATL-T), HPB-ATL-2 (ATL-2) and HPB-ATL-O were more progressed than Tax exclusively expressing HPB-CTL-I (CTL-I), because the former deleted p16 gene (polymerase chain reaction (PCR)) and strongly transcribed survivin (reverse transcriptase-PCR). Notably, interferon gamma-independent loss of class II expression of ATL-T and ATL-2 was found. In antigen-presenting experiments, however, both cell lines induced SEB-dependent significant T-cell proliferation estimated by [(3)H] thymidine uptake. No class II-re-expressed ATL-2 cells were observed in the SEB-presenting cultures by indirect immunofluorescence, and only minimum inhibition of SEB-dependent T-cell response by anti-human leukocyte antigen (HLA)-DR monoclonal antibody was observed. These findings suggest that both ATL-T and ATL-2 very effectively present SEB to T cells less dependently on class II molecules. These less immunogenic leukemic cells of aggressive ATL may contribute to disease aggression.
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PMID:Human leukocyte antigen-class II-negative long-term cultured human T-cell leukemia virus type-I-infected T-cell lines with progressed cytological properties significantly induce superantigen-dependent normal T-cell proliferation. 1587 24

Studies have shown that BIRC7, a new member of inhibitor of the apoptosis protein family, is expressed in fetal tissues and most solid tumors in humans. However, there are no reported data concerning BIRC7 expression in lymphomas. We investigated the expression of BIRC7, survivin, Bcl-2, Bax, p53 and p170 proteins in 167 cases of non-Hodgkin's lymphoma (NHL) and 10 cases of non-specific lymphadenitis by tissue microarray-based immunohistochemistry. BIRC7 mRNA in three cell lines and 16 cases of NHL were detected by reverse transcriptase-polymerase chain reaction. BIRC7 protein was exhibited in the cytoplasm of cells in 25 (31%) of 80 cases of B-NHLs, 32 (37%) of 87 cases of T-NHLs, and none in non-specific lymphadenitis. The positive rate of BIRC7 was lower than that of survivin in almost all types of NHL with no significant differences, and similar to that of Bcl-2, Bax or p53. There was no correlation of protein expression between BIRC7 and any other detected markers, except p170 in T-NHL (P < 0.001). BIRC7 expression did not correlate with clinic pathologic factors such as sex, age, stage and grade, but overexpression of BIRC7 was positively correlated with aggression of NHL cells (P < 0.05). BIRC7 mRNA expressed in six (38%) of 16 cases of NHLs. BIRC7 mRNA expression was approximately consistent with BIRC7 protein in NHL. Our results indicate that the BIRC7 gene might play a role in the development and aggression of NHL and that the inhibition of BIRC7 expression may be important in NHL treatment.
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PMID:Expression of BIRC7 protein and mRNA in non-Hodgkin's lymphoma. 1684 Feb 3

Synovial sarcoma is a soft tissue sarcoma with clearly defined histologic, immunophenotypic, and molecular features. It occurs predominantly in the extremities of young adults but has been reported in many other anatomic sites. Histologically, it is classified as biphasic, monophasic, and poorly differentiated. The latter category, which includes tumors with a rhabdoid morphology, has been associated with a more aggressive behavior. Generally, the biphasic variant does not pose any diagnostic problem because of its typical histologic appearance; in contrast, the monophasic and poorly differentiated variants may represent a diagnostic challenge because their microscopic features can be confused with those of other spindle cell tumors with rhabdoid features. The application of molecular techniques, such as reverse transcriptase polymerase chain reaction to detect the fusion transcript associated with the characteristic t(X;18) translocation of synovial sarcoma, has enabled the confirmation of this diagnosis, even in cases of unusual localization, such as the one we present here.
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PMID:Primary synovial sarcoma of the kidney with rhabdoid features. 1791 54


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