Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether cancer cell dissemination results from incisional biopsy, we tried to detect squamous cell carcinoma (SCC) cells in peripheral blood before and after incisional biopsy by means of cytokeratin 19 (CK19) reverse-transcriptase polymerase chain reaction (RT-PCR). The study population consisted of 20 patients with oral SCC; 10 were given incisional biopsies followed by radical excision (the incisional biopsy group), and the remaining 10 were treated by excisional biopsy alone (the excisional biopsy group). Ten non-oral cancer patients with benign oral lesions served as controls. Five-ml blood aspirates collected before and after incision were used for CK19 RT-PCR. Two (20.0%) of 10 patients from the incisional biopsy group were positive for CK19 transcripts in their peripheral blood drained 15 min after incision. In contrast, CK19 transcript was not detected either in the excisional biopsy group or in controls. Surgical invasiveness for oral cancer, including incisional biopsy, causes dissemination of cancer cells into circulation, resulting in increased risk of metastasis.
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PMID:Dissemination of cancer cells into circulation occurs by incisional biopsy of oral squamous cell carcinoma. 1094 45

Current advances in biomolecular technology allow precise genetic fingerprinting of specific cells responsible for the pathogenesis of human diseases. This study demonstrates the feasibility of generating target samples from laser capture microdissection (LCM) tissues suitable for hybridization of high-density oligonucleotide arrays for gene expression profiling. RNA was successfully isolated by LCM from three paired specimens of oral cancer and linearly amplified using T7 RNA polymerase. Evaluation of the cDNA revealed that five of five cellular maintenance transcripts are detected. Biotinylated cRNA was generated and hybridized to the human Test 1 GeneChip probe arrays, which demonstrated that the RNA is of sufficient quality and integrity to warrant further analysis. Subsequent hybridization of the samples to the HuGenFL GeneChip probe arrays revealed that 26.5%-33.0% of the approximately 7000 represented genes are expressed in each of the six samples. These results demonstrate that LCM-generated tissues can generate sufficient quality cRNA for high-density oligonucleotide microarray analysis, an important step in determining comprehensive gene expression profiling using this high-throughput technology.
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PMID:Laser capture microdissection-generated target sample for high-density oligonucleotide array hybridization. 1099 67

Sentinel node navigation surgery (SNNS) has received considerable attention for its role in deciding whether to perform neck dissection in patients with early oral cancer. However, diagnostic accuracy and its intraoperative availability of results remain important concerns. First, we shortened the examination time required for genetic diagnosis. Second, we assessed the quality of the extracted mRNA. Third, 10 patients with early N0 oral cancer underwent SNNS, using our new technique for genetic diagnosis to determine whether neck dissection was required. The examination time of our one-step reverse-transcriptase polymerase chain reaction method using a minicolumn and LightCycler was successfully shortened to 2 h, permitting intraoperative genetic diagnosis. The extracted mRNA was of high quality. Six sentinel nodes in four patients were diagnosed to be metastatic on genetic diagnosis; these patients underwent neck dissection. The other six patients avoided unnecessary surgery. We conclude that intraoperative genetic diagnosis of micrometastasis holds promise of being a sensitive method that can be used to support SNNS.
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PMID:Intraoperative real-time genetic diagnosis for sentinel node navigation surgery. 1533 80

Small interfering RNAs (siRNAs) are potentially powerful tools for therapeutic gene regulation. DNA cassettes encoding RNA polymerase III promoter-driven hairpin siRNAs allow long-term expression of siRNA in targeted cells. A variety of viral vectors have been used to deliver such cassettes to cells. Here we report on the development and use of a self-complementary recombinant adeno-associated virus (scAAV) vector for siRNA delivery into mammalian cells. We demonstrate that this modified vector efficiently delivers siRNA into multidrug-resistant human breast and oral cancer cells and suppresses MDR1 gene expression. This results in rapid, profound, and durable reduction in the expression of the P-glycoprotein multidrug transporter and a substantial reversion of the drug-resistant phenotype. This research suggests that scAAV-based vectors can be very effective agents for efficient delivery of therapeutic siRNA.
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PMID:Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector. 1577 55

Nucleophosmin (NPM1) is a multifunctional protein involved in the regulation of centrosome duplication, ribosome biogenesis, genomic stability, histone chaperone function, and transcription. Overexpression of NPM1 is associated with cancers of diverse histological origins. Here, we have found that p300-mediated acetylation of NPM1 modulates its subcellular localization and augments its oncogenic potential. Acetylated NPM1 is predominantly localized in the nucleoplasm, where it associates with transcriptionally active RNA polymerase II. Deacetylation of NPM1 is brought about by human SIRT1 and reduces its transcriptional activation potential. Remarkably, increased levels of acetylated NPM1 were found in grade II and III oral squamous cell carcinoma (OSCC) patient samples. Small interfering RNA (siRNA)-mediated knockdown of NPM1 in an OSCC cell line, followed by microarray analysis and chromatin immunoprecipitation experiments, revealed that some of the genes involved in oral cancer malignancy are regulated by NPM1 and have acetylated NPM1 localized at their promoters. Either suppression of p300 by siRNA or mutation of acetylatable lysine residues of NPM1 resulted in reduced occupancy of acetylated NPM1 on the target gene promoter concomitant with its decreased transcript levels. These observations suggest that acetylated NPM1 transcriptionally regulates genes involved in cell survival and proliferation during carcinogenesis.
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PMID:Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional activation of genes implicated in oral cancer manifestation. 1958 Dec 89