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)

Paternal allele-specific expression is identified for the insulin-like growth factor 2 (IGF2) gene. Relaxation or loss of IGF2 imprinting, however, has been reported in several neoplasms. We studied the expression of IGF2 mRNA in 35 squamous cancers of the esophagus and searched for the presence or absence of relaxation of IGF2 imprinting. In 28 (80%) cases, IGF2 mRNA was overexpressed in the tumor tissues (T) compared to the normal tissues (N). The patients whose tumor invaded the adventitia showed a higher T/N ratio than those whose tumor was restricted to the musculi propria layer. Heterozygosity was determined by using the Apa I polymorphism in exon 9. Thirteen of 35 cases showed heterozygosity. In these 13 cases, a similar analysis was performed on cDNA obtained by reverse transcriptase-polymerase chain reaction. Consequently, 7 cases disclosed relaxation of IGF2 imprinting in the tumor tissue. The cases of esophageal cancer with relaxation of IGF2 imprinting showed a higher T/N ratio and deeper invasion than those without relaxation. The results suggest that overexpression of IGF2 mRNA plays an important role in esophageal cancer and, in certain cases, is associated with relaxation of IGF2 imprinting.
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PMID:Relaxation of insulin-like growth factor 2 gene imprinting in esophageal cancer. 894 13

We reported that human esophageal cancer cell lines (ECC) (YES-1, -2, -3, -4, -5, and -6) produced interleukin-6 (IL-6). We, therefore, investigated the growth effects ([3H]thymidine uptake assay and direct cell count) of IL-6 on these ECC. IL-6 receptor (R) and GP-130 mRNA were detected in all the ECC, using reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and IL-6R was detected in one (YES-3) by immunohistochemical staining. IL-6, anti-IL-6 monoclonal antibody (mAb), or anti-IL-6R mAb caused no reproducible enhancement or suppression of [3H]thymidine uptake by all six ECC. Direct cell count also revealed that the growth enhancement or suppression by IL-6, anti-IL-6 mAb, or anti-IL-6R mAb was relatively small. Particularly, there was no significant sensitivity of YES-3 cells, which definitely produce IL-6 and express IL-6R for IL-6, anti-IL-6 mAb, or anti-IL6R mAb. These results suggest that some esophageal cancers may produce IL-6 and express IL-6R. However, no major interactions between IL-6 and the growth of human esophageal cancer cell lines were detected in this study.
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PMID:The influence of interleukin-6 on the growth of human esophageal cancer cell lines. 897 1

FHIT (fragile histidine triad gene), a candidate tumor suppressor gene, was recently identified and cloned at chromosome 3p14.2. Alterations of this gene have been reported in a number of primary human tumors, including colorectal, esophageal, gastric and lung carcinomas. However, some reports have found no abnormalities in this gene. We investigated a total of 63 primary esophageal tumors, nine esophageal cancer cell lines and 17 ulcerative colitis-associated neoplasms (UCANs) for alterations of FHIT. In 13 esophageal tumors, we employed overlapping reverse transcriptase-PCRs (RT-PCRs) to amplify and sequence the complete open reading frame of FHIT. One of 13 primary esophageal tumors analysed by RT-PCR expressed no detectable FHIT transcript; the remaining 12 expressed normal-sized transcripts with wild-type open reading frame sequences. In an additional 50 esophageal tumors, the polymorphic microsatellite loci D3S1300 and D3S1313 were used to evaluate loss of heterozygosity (LOH) at 3p14.2. Eleven of these 50 tumors showed LOH at one or both loci. In all these 11 tumors, genomic PCR and direct sequencing of FHIT exons 5-9 was performed. This analysis revealed that none of these 11 primary esophageal tumors contained any alterations in the FHIT open reading frame or adjacent intron sequences. Finally, among 17 UCANs, the in vitro synthesized protein (IVSP) assay detected no truncated protein products, nor were there any abnormalities in size or DNA sequence of FHIT RT-PCR products. However, in six of nine esophageal carcinoma cell lines, no FHIT RT-PCR product was detectable using either of the overlapping primer sets. Genomic PCR and direct sequencing of exons 5-9, also performed in these nine cell lines, revealed wild-type sequence in eight cell lines; however, one cell line contained no exon 5 PCR product. This cell line also lacked detectable FHIT transcript. These data suggest that the open reading frame of FHIT is not important in the development or progression of most primary esophageal carcinomas or UCANs, although lack of expression of the FHIT transcript may be common in esophageal cancer-derived cell lines. The possibility of an additional tumor suppressor gene at chromosome 3p14.2 remains to be evaluated.
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PMID:FHIT gene alterations in esophageal cancer and ulcerative colitis (UC). 923 82

The telomere and the enzyme telomerase in esophageal cancer have been poorly investigated. We present here aspects of the telomere and telomerase in esophageal cancer in relation to cell proliferation, differentiation and chemosensitivity to anticancer drugs. The telomere length (mean length of telomere restriction fragments; TRF), telomerase activity (TA), and human telomerase RNA (hTR) expression in a panel of 13 human esophageal cancer cell lines, squamous in origin, was examined by Southern blotting, the telomeric repeat amplification protocol (TRAP), and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Cell proliferation expressed by the doubling time, cell differentiation determined by the keratin 13 and/or 14 expression, and chemosensitivity to cisplatin (CDDP) and 5-fluorouracil (5-FU) were compared with telomere-related factors. TRF shortening, the up-regulation of TA, and hTR expression was seen in all 13 cell lines. The TA correlated positively with the telomere length and negatively with the hTR expression. The doubling times of the cell lines and the telomere-related factors did not show any significant relation. The TA in the keratin 13/14-negative cell lines was significantly higher than that of the keratin 13-positive cell lines. The cells with short telomere tended to be resistant to CDDP whereas the cells with higher TA tended to be more sensitive to CDDP; 5-FU showed no relation to any telomere-related factors. Therefore, the activation of TA in esophageal squamous cell carcinoma is regulated by cell differentiation but not by cell proliferation, cells with high TA are more sensitive to CDDP, and cells with short telomere require a CDDP dose escalation.
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PMID:Telomere length, telomerase activity and telomerase RNA expression in human esophageal cancer cells: correlation with cell proliferation, differentiation and chemosensitivity to anticancer drugs. 967 57

Esophagitis is a major limiting factor in the treatment of lung cancer by radiation alone or in combination with chemotherapy. We have previously demonstrated that intraesophageal injection of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) complex into C3H/HeNsd mice blocks irradiation-induced esophagitis. To determine whether the human esophagus can be similarly transfected, normal human esophageal sections obtained from the margins of esophagectomy specimens from esophageal cancer patients were transfected in vitro with alkaline phosphatase (AlkP)-PL complex and stained for AlkP activity, and the percent of cells expressing AlkP was calculated. At 24 hr after transfection with 20 or 200 microgram of AlkP-PL complex, 55.0% and 85.8% of esophageal epithelial cells expressed detectable AlkP, respectively. Other sections transfected with MnSOD-PL complex showed transgene mRNA by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay and increased MnSOD biochemical activity for at least 96 hr after transfection. Irradiated MnSOD-PL complex-transfected sections demonstrated a significantly decreased percentage of apoptotic cells when compared to irradiated control sections. Following 1,000 cGy, MnSOD-PL-treated samples showed 7.5 +/- 2.8% and 33.3 +/- 7.3% apoptotic cells at 24 and 48 hr compared to 53.6 +/- 6.9% and 59.0 +/- 13.8% for nontransfected controls (P < 0.0001 and P < 0.1175). After 2,000 cGy, results at 24 and 48 hr were 25.0 +/- 7.6% and 66.9 +/- 4.9% for MnSOD-transfected sections compared to 65.6 +/- 4.3% and 90.0 +/- 4.1% for control sections (P < 0.0001 and P = 0.0353), respectively. Thus, human esophageal sections can be transfected with MnSOD-PL complex in vitro and thereby protected against ionizing irradiation-induced apoptosis. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 128-137 (2000).
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PMID:Plasmid/liposome transfer of the human manganese superoxide dismutase transgene prevents ionizing irradiation-induced apoptosis in human esophagus organ explant culture. 1090 Apr 24

Recently, mammalian heparanase was cloned, and its probable function in tumor progression was reported. However, its expression in human clinical cancers has not been fully studied. Thus we determined the heparanase mRNA expression in 30 esophageal cancer cell lines and 144 clinical samples including 38 esophageal squamous cell carcinomas, 71 gastric adenocarcinomas, and 35 colorectal adenocarcinomas. The fresh surgical specimens of cancer tissue (T) and its paired normal tissue (N) were used. The heparanase mRNA was evaluated by reverse transcriptase-polymerase chain reaction, and the T/N expression ratio was determined in clinical cases. All 30 esophageal cancer cell lines expressed heparanase mRNA. The T/N ratio was determined as high (> or =1.3), equal (0.8 approximately 1.2) or low (< or = 0.7) in each clinical case. In cases of esophageal cancer, 7 showed high, 10 equal and 21 low expression. In cases of colorectal cancer, 3 showed high, 16 equal and 16 low expression. On the other hand, 42 showed high, 22 equal and 7 low expression in cases of gastric cancer. The frequency of high expression cases was greater in gastric cancer than in esophageal or colorectal cancers (p < 0.05). There were no differences in clinicopathologic factors including prognosis between high and low expression cases of each cancer. Our mRNA study of heparanase indicated that its expression status was different among gastrointestinal cancers. The clinical and pathological impact was low compared to other proteinases, although further studies are recommended for final conclusion.
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PMID:Heparanase expression in clinical digestive malignancies. 1129 76

Application of recombinant adenoviral vectors for cancer gene therapy is currently limited due to lack of specificity for tumor cells. For gastric and esophageal adenocarcinoma, we present here that the relative abundant expression of the primary adenovirus receptor, coxsackie/adenovirus receptor (CAR), on normal epithelium compared to carcinoma favors the transduction of the epithelium. As such, to achieve specific transduction of cancer cells, targeting approaches are required that ablate the binding of the virus to CAR and redirect the virus to tumor-specific receptors. By immunohistochemistry and reverse transcriptase polymerase chain reaction assays, we demonstrate a marked difference in expression of the human epithelial cell adhesion molecule (EpCAM) between normal and (pre)malignant lesions of the stomach and esophagus. Based on this, we explored the feasibility of using EpCAM to achieve gastric and esophageal adenocarcinoma selective gene transfer. Adenoviral vectors redirected to EpCAM using bispecific antibodies against the adenovirus fiber-knob protein and EpCAM specifically infected gastric and esophageal cancer cell lines. Using primary human cells, an improved ratio of tumor transduction over normal epithelium transduction was accomplished by the EpCAM-targeted vectors. This study thus indicates that EpCAM-targeted adenoviral vectors may be useful for gastric and esophageal cancer-specific gene therapy in patients.
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PMID:Selective gene delivery toward gastric and esophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors. 1147 54

p63 is a recently identified homologue of the tumor suppressor gene TP53, which encodes multiple isotypes with transactivating, death-inducing and dominant-negative activities. p63 is expressed in basal cells of squamous epithelia and many kinds of tumors. To explore the penetrance of p63 in esophageal cancer, we analyzed p63 expression in squamous cell carcinomas, adjacent dysplasia and histologically normal mucosa of the esophagus by combination of immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the DeltaNp63 mRNA was easily detectable in all malignant and histologically normal tissues, whereas TAp63 presented extremely low or no expression. The p63 protein was highly expressed in 50 of 51 tumor tissues without significant difference in gender, age, stage and grade. Ten of 11 dysplasia exhibited strong p63 staining in all abnormal cells. Interestingly, p63 expression was observed in 96% (45/47) histologically normal epithelia adjacent to the cancerous tissues but only in 47% (14/30) mucosa far from tumors. Most of the epithelia far from tumors showed weaker staining than that adjacent to the cancerous tissues. In all the histologically normal epithelia with p63 expression, irrespective of the distance from the tumors, immunohistochemical reaction was restricted to the basal and suprabasal cell layers. Our data suggested that DeltaNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease.
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PMID:Elevated expression of p63 protein in human esophageal squamous cell carcinomas. 1244 98

Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated the clinical significance of bone marrow micrometastases in patients with esophageal cancer. Bone marrow samples from 57 patients with esophageal cancer, who underwent esophagotomy, were investigated by specific RT-PCR for carcinoembryonic antigens (CEA). A total of 40 out of 57 patients (70.1%) were positive for CEA mRNA in the bone marrow. Among curatively resected cases, 34 of 50 patients (68.0%) were positive for CEA. Ten of 13 T1 patients (76.9%) were positive for CEA. Although the CEA-positive rate was high, there was no significant correlation between CEA positivity and any clinical characteristics. Among the 40 CEA-positive patients, 50% have shown recurrence so far. Detection of cancer cells in the bone marrow by RT-PCR may not always correspond to the malignant potential or other characteristics of the tumor. CEA-positive 'micrometastases' might actually represent isolated circulating tumor cells without much biological significance.
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PMID:Clinical significance of bone marrow micrometastases in esophageal cancer. 1556 72

Telomerase activity is observed in approximately 90% of human cancer including esophageal squamous cell cancer. Normal somatic cells do not display telomerase activity on a regular basis. The major mechanism to regulate telomerase activity in human cells is the transcriptional control of the catalytic subunit, the human reverse transcriptase gene hTERT. However, the manner in which telomerase activity is regulated during malignant transformation and whether this regulation is influenced by single genetic alterations important in this process are not well understood. In this study we investigated the transcriptional regulation and activity of human telomerase in a cellular model representing important known genetic alterations observed in esophageal cancer. We characterized the respective cells with regard to their telomere biology and telomerase expression, transcriptional regulation using promoter--as well as electrophoretic mobility shift assay--analyses and their promoter methylation status. We could demonstrate that telomerase expression and subsequent activity are differentially regulated in the progression from normal esophageal epithelial cells to genetically defined esophageal cells harboring a specific genetic alteration frequently found in esophageal cancer and compared those changes with esophageal cancer cells. Whereas primary esophageal cells are mainly regulated by Sp1, in cells harboring a genetic alteration as cyclin D1 overexpression other transcription factors like E2F and c-myc as well as promoter methylation influence hTERT transcription. This model demonstrates that the transcriptional regulation of telomerase is influenced by a given genetic alteration important in esophageal cancer, and therefore provides new insight in telomerase regulation during carcinogenesis.
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PMID:Differential transcriptional regulation of human telomerase in a cellular model representing important genetic alterations in esophageal squamous carcinogenesis. 1595 20


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