Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunostaining of cell cycle-related antigens, especially Ki-67, DNA polymerase alpha, and proliferating cell nuclear antigen, has become an important method to assess the proliferative activity of tumors. These three nuclear antigens were studied by immunohistochemical analysis of cytologic smears. These smears were obtained by scraping the cut surface of 10 cases of esophageal squamous cell carcinoma and were fixed and prepared by different methods. The results were compared with those of tissue sections to apply the immunocytochemical findings of these antigens to cytology specimens. Smears that were placed on Denhardt- or Neoprene-coated slides and subsequently fixed in 4% paraformaldehyde and methanol exhibited the best cell adherence to the slides, had minimal loss of antigenicity, and had good preservation of cell morphologic features for all three antigens examined. The percentage of positive tumor cells in the cytology smear was generally in good agreement with that in the tissue section. For these three antigens, proliferating cell nuclear antigen demonstrated a much higher percentage of positive cells than either Ki-67 or DNA polymerase alpha, in both the smears and the tissue sections. In summary, Ki-67, DNA polymerase alpha, and proliferating cell nuclear antigen can be immunolocalized successfully in cytology smears and may become another parameter to assess the proliferative activity of tumors in the field of diagnostic pathology.
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PMID:The proliferative cell fraction in cytology specimens. A study of human esophageal carcinoma. 135 40

The activities of orotate phosphoribosyltransferase (OPRT), cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd) kinase, thymidine (dThd) kinase, Urd and dThd phosphorylases, and DNA polymerase were examined in the eight human lung squamous cell carcinomas and five lung adenocarcinomas, and five tumor-adjacent normal lung tissues. All of these enzymes are involved in pyrimidine nucleotide synthesis. The metabolism of 5-fluorouracil (5-FU) was determined. The levels of these enzymes, except for OPRT, were high in tumor tissues and almost the same between lung squamous cell carcinomas and adenocarcinomas, with no statistical difference. The activities for phosphorylation and degradation of 5-FU were similar in each tissue type of tumor. As 5-FU is incorporated into tumor cells and is metabolized actively to 5-FU nucleotides in squamous cell carcinoma tissues, at almost the same level seen in adenocarcinoma tissues, this drug should have a wide clinical application.
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PMID:Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas. 216 41

The polymerase chain reaction (PCR) was used to investigate samples from Indonesian and Swedish patients with cervical intraepithelial neoplasia grade III (CIN III), squamous cell carcinoma or adenocarcinoma of the cervix for the presence of a transforming fragment (BC 24) of herpes simplex virus type 2 (HSV-2) DNA. The PCR test for HSV-2 DNA was more sensitive than the infectivity endpoint titer in a cell culture system and no cross reactivity was found with either varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human papillomavirus 16 or 18, or human genomic DNA. Using this PCR test, 2 out of 5 cases with CIN III, 10 of 71 squamous cell carcinomas, and 3 of 11 adenocarcinomas of the uterine cervix were found to contain DNA sequences homologous to the BC 24 fragment of the HSV-2 genome. Only two of the samples containing this transforming region of the HSV-2 DNA were positive in a PCR assay for the HSV-2 DNA polymerase gene. The great majority of the HSV-2 BC 24 DNA positive (12 of 15) came from the Indonesian group of patients. All 15 CIN III or cancer samples positive for the HSV-2 BC 24 fragment were also positive for papillomavirus DNA. In line with observations made by others, our data support the hypothesis that HSV infection could represent one of several possible oncogenic cofactors leading to cervical carcinoma. The HSV cofactor might be more important in the Indonesian than in the Swedish population.
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PMID:Detection of the BC 24 transforming fragment of the herpes simplex virus type 2 (HSV-2) DNA in cervical carcinoma tissue by polymerase chain reaction (PCR). 779 6

The effect of the DNA polymerase inhibitors adenine 9-beta-arabinofuranoside (ara-A), cytosine 1-beta-arabinofuranoside (ara-C), and aphidicolin on X-radiation sensitivity was studied in a group of exponentially growing squamous cell carcinoma cell lines. The tumour cell lines varied in radiation sensitivity, with D0 (radiation sensitivity) values ranging from 1.0 to 3.9 Gy. The addition of non-toxic concentrations of ara-A 30 min before irradiation and removal 30 min after irradiation potentiated cell killing in five of eight cell lines. Four of these five responsive cell lines were relatively radioresistant lines, having D0 > 2.0 Gy. One of the cell lines was more radiosensitive (D0 = 1.4 Gy). Ara-A was also effective in potentiating killing in the radioresistant cell lines even when added 60 min after irradiation. Pre- or post-treatment with ara-A had no effect on X-ray sensitivity of the other three relatively sensitive cell lines (D0 ranging from 1.0 to 1.3 Gy). Both ara-C and aphidicolin were effective in potentiating X-ray sensitivity in JSQ-3, a relatively resistant cell line that was sensitized by ara-A treatment, but they had no effect on the X-ray sensitivity of SCC-61, a relatively radiosensitive cell line that was insensitive to ara-A effects on X-ray response. At the concentrations used, the polymerase inhibitors were equally effective in inhibiting DNA synthesis.
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PMID:Enhancement of X-ray toxicity in squamous cell carcinoma cell lines by DNA polymerase inhibitors. 791 17

The versatility of non-radioactive cell-cycle analysis in detecting endogenous nuclear antigens of the proliferating cells was evaluated. Optimal conditions for immunostaining varied in fixation and pretreatment procedures among antigens, bromodeoxyuridine (BrdU), Ki-67 epitope, DNA polymerase alpha and PCNA. A significant correlation between BrdU labeling index (LI) was observed in each positive ratio (PR, positive/total neoplastic cells) for nuclear antigens in tumor-sections which had been labeled in vivo with BrdU. The best correlation was observed in Ki-67 PR (y = 1.26x + 2.5; y = Ki-67 PR; x = BrdU LI; r = 0.97). To determine its prognostic value, Ki-67 analysis was applied to the surgically resected lung tumors. Ki-67 PR were different according to the histologic types of the tumors: 47.8 +/- 3.4% in small cell carcinoma; 29.5 +/- 3.5% in squamous cell carcinoma; 28.3 +/- 4.7% in large cell carcinoma; 15.2 +/- 1.8% in adenocarcinoma and 0.1 +/- 0.1% in mature carcinoid tumor. When the mean value was used to divide each type to a higher or lower proliferative activity (15% Ki-67 PR for adenocarcinoma and 30% for squamous cell carcinoma), the group with the lower Ki-67 PR showed a significantly more favorable prognosis than that of a higher ratio. Ki-67 PR was not correlated with other pathologic factors such as size, lymph node metastasis or pleural involvement. Non-radioactive cell-cycle analysis was feasible and useful for detecting endogenous nuclear antigens even in the lung tumors, particularly when the analysis was coupled with histologic typing.
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PMID:Cell-cycle analysis detecting endogenous nuclear antigens: comparison with BrdU-in vivo labeling and an application to lung tumors. 834 8

The ends of chromosomes, or telomeres, consist of short repeated sequences that are synthesized by a ribonucleoprotein-DNA polymerase called telomerase. The RNA component of telomerase is essential for enzyme activity. The maintenance of telomere length by telomerase has been proposed to be essential for cellular viability and to play an important role in cellular senescence and immortalization. We are interested in using the mouse as a model system for the study of telomerase. We studied telomerase activity and expression of the mouse telomerase RNA component (mTR) in two different transgenic mouse models of multistage tumorigenesis: models of islet cell carcinoma and squamous cell carcinoma. In both tumour models, telomerase activity was detected only in late-stage tumours, whereas the telomerase RNA was present at higher than normal levels in pre-neoplastic stages and increased further in late-stage tumours. However, the RNA levels did not parallel the amounts of telomerase activity detected, suggesting that regulation of telomerase activity does not correlate with the regulation of its RNA component. These results establish a direct correlation between progression to late-stage tumours and induction of telomerase activity, and suggest that the initial upregulation of telomerase RNA is an early event. To address the role of telomerase during normal mouse development and tumour formation, we have constructed a knockout mouse for the mouse telomerase RNA, mTR-/-. These mice and the cell lines derived from them are telomerase deficient.
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PMID:Mouse models for the study of telomerase. 952 57

The ends of human chromosomes (telomeres) consist of tandem repeats of the sequence TTAGGG. Telomeres lose up to 200 base pairs of DNA per cell division due to the inability of DNA polymerase to completely replicate the chromosomal ends. Chromosomal shortening ultimately leads to senescence and cell death in normal cells. However, some immortal cells do not lose telomeric sequence during DNA replication. Many human carcinoma lines are immortal in vitro, suggesting that these cells have a mechanism for maintaining the ends of their chromosomes. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA onto chromosomes using its RNA component as a template. To elucidate potential mechanisms for telomerase regulation, we tested human squamous cell carcinoma lines (SCCs) for telomerase activity. All SCC lines expressed high levels of telomerase activity. Synchronization in specific cell cycle phases caused marked reduction in telomerase activity in G0 and S, but not in G1 or M. Reduction in telomerase activity correlated with induction of Rb protein in these phases. Overexpression of full length Rb resulted in significant downregulation of telomerase activity. However, expression of an Rb N-terminal oligomerization domain deletion construct, a C-terminal DNA binding domain deletion construct, or a pocket domain mutant failed to downregulate telomerase activity. We concluded that functionally intact Rb was required for cell cycle-dependent downregulation of telomerase activity in SCC lines.
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PMID:Intact functional domains of the retinoblastoma gene product (pRb) are required for downregulation of telomerase activity. 1032 Jul 73

In order to test the hypothesis that Epstein-Barr virus (EBV) may be a cofactor for oral squamous cell carcinoma (OSCC) the authors evaluated tumour cells from OSCC of 108 patients without HIV infection, for the presence of EBV DNA by polymerase chain reaction. The sequences of oligonucleotides used in the amplification and hybridization included a set for the DNA polymerase region. The amplification was detected using an ELISA assay with peroxidase. EBV DNA was detected in 17.59% of the tumours. Inhibition studies showed that the ability to detect EBV DNA was not affected by the pathological material, suggesting that the negative PCR results in these samples were not caused by PCR inhibitors in the biopsy. Results revealed that 63.1% of the tumours (12 cases) were DNA positive affecting the lateral margin of the tongue, and were statistically significant (p < 0.001; chi 2). In the pool of tumours with EBV DNA only 26.3% (5 of 19 cases) were well differentiated OSCCs whereas the remaining 73.7% (14 of 19 cases) were moderately and poorly differentiated OSCCs, with a statistical significance of p = 0.08; chi 2. This study suggests a relationship between OSCC and EBV.
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PMID:Epstein-Barr virus and oral squamous cell carcinoma in patients without HIV infection: viral detection by polymerase chain reaction. 1034 99

Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) was performed in skin from patients with various malignant and nonmalignant skin diseases using anti-PCNA monoclonal antibodies. The malignant diseases included squamous cell carcinoma (SCC), adult T lymphotrophic leukemia (ATL), mycosis fungoides, malignant melanoma and malignant lymphoma, and the nonmalignant diseases included severe treatment-resistant atopic dermatitis (AD), psoriasis vulgaris, verruca vulgaris, and others. The percentage of PCNA-positive cells (the labeling index, LI) was highest for the malignant diseases (56.5+/-7.1%). The LIs for severe treatment-resistant AD, psoriasis, and verruca vulgaris were also significantly higher than those for the normal control or nonlesional skin of the patients. The PCNA LIs were, however, not significantly elevated in eczema and contact dermatitis. The high PCNA LIs in severe AD and psoriasis vulgaris were considerably lower in the skin improved by treatment. Labeling with Ki67, a nuclear protein expressed in cycling cells, was also performed in skin from subsets of each patient group. The results were very similar to those found with PCNA labeling. PCNA-positive cells were found throughout the dermis as well as the basal layer in the malignant diseases, whereas they were found only in the basal layer in the nonmalignant diseases. The results suggest that in human skin diseases, the extent of staining for PCNA, which is a cofactor of DNA polymerase-delta and is essential for cell proliferation, correlates with the extent to which the disease is treatment-resistant. In addition, our findings suggest that the PCNA LI and distribution of PCNA-positive cells in the skin may be helpful in the early diagnosis of skin malignancies.
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PMID:Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in malignant and nonmalignant skin diseases. 1048 11

We assessed the status of P53 in 32 surgically treated non-small cell lung cancers (NSCLC) by using yeast functional assay. For functional assay, total RNA extracted from fresh-frozen specimens was reverse transcribed and P53 cDNAs were PCR-amplified using Pfu DNA polymerase (Stratagene). The transcriptional competence of the P53 cDNA was then tested in a yeast reporter strain. 20 of the 32 (69%) NSCLC patients contained mutant P53 in the yeast functional assay with the higher frequency in squamous cell carcinoma (14/17, 82%) than in adenocarcinoma (5/10, 50%) and large cell carcinoma (3/5, 60%) (p<0.01, chi2 test). No significant difference was observed with respect to the TNM. Preliminary survival analysis showed that patients scoring positive for the yeast test had shorter disease-free survival (median = 10 months) than those that scored negative (median > 21 months). Our results suggest that yeast functional assay is not only an improved method to examine the status of P53, but might hopefully improve understanding of the role of mutant P53 in the clinical evaluation of NSCLC.
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PMID:Detection of P53 abnormalities in non-small cell lung cancer by yeast functional assay. 1137 99


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