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Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the de novo pyrimidine biosynthetic pathway in the MCF7 breast cancer cells was 4.4-fold higher than that in normal MCF10A breast cells. Moreover, while pyrimidine biosynthesis in MCF10A was tightly regulated, increasing as the culture matured and subsequently down-regulated in confluency, the biosynthetic rate in MCF7 cells remained elevated and invariant in all growth phases. The flux through the pathway is regulated by carbamoyl phosphate synthetase, a component of the multifunctional protein, CAD. The intracellular CAD concentration was 3.5- to 4-fold higher in MCF7 cells, an observation that explains the high rate of pyrimidine biosynthesis but cannot account for the lack of growth-dependent regulation. In MCF10A cells, up-regulation of the pathway in the exponential growth phase resulted from MAP kinase phosphorylation of CAD Thr456. The pathway was subsequently down-regulated by dephosphorylation of P approximately Thr456 and the phosphorylation of CAD by PKA. In contrast, the CAD P approximately Thr456 was persistently phosphorylated in MCF7 cells, while the PKA site remained unphosphorylated and consequently the activity of the pathway was elevated in all growth phases. In support of this interpretation, inhibition of MAP kinase in MCF7 cells decreased CAD P approximately Thr456, increased PKA phosphorylation and decreased pyrimidine biosynthesis. Conversely, transfection of MCF10A with constructs that elevated MAP kinase activity increased CAD P approximately Thr456 and the pyrimidine biosynthetic rate. The differences in the CAD phosphorylation state responsible for unregulated pyrimidine biosynthesis in MCF7 cells are likely to be a consequence of the elevated MAP kinase activity and the antagonism between MAP kinase- and PKA-mediated phosphorylations.
Int J Cancer 2004 Apr 20
PMID:Breakdown of the regulatory control of pyrimidine biosynthesis in human breast cancer cells. 1499 69

We constructed a mini chamber system that was able to maintain cell culture on a microscope for long periods. It is a modified closed system with medium perfusion and CO2 circulation. The closed CO2 circulation and ample air inside the chamber distinguish it from other closed systems. Using different cell lines, the system was shown to be able to support long-term, time-lapse recording. After 229 hours of time-lapse recording, A2058 cells (a melanoma cell line) became overconfluent but still multiplied. Many CAD cells (a murine neuron-like cell line) still moved their cell bodies and kept their neurite-like processes after 28 days of recording. The entire healing process of a scratch-wounded 124 (a bladder cancer cell line) monolayer can be monitored. Such a modified closed system should find many applications in developmental biology, cell biology, and cancer biology where long-term, time-lapse recording is required or when the health of cells is important.
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PMID:Mini chamber system for long-term maintenance and observation of cultured cells. 1572 33

Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in actively proliferating cells and cancer cells. B23 is a tumor marker and exerts its oncogenic effect through binding and suppressing numerous tumor suppressors. NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in anaplastic large cell lymphoma (ALCL), fuses the N-terminus of B23 to the intracellular tyrosine kinase domain of ALK, provoking lymphomas by stimulating various mitogenic proteins including PI 3-kinase and PLC-gamma1. Overexpression of B23 inhibits apoptosis, while knockdown of B23 induces cell death. However, whether B23 is directly involved in blocking apoptotic machinery remains elusive. B23 is recently identified as a nuclear PI(3,4,5)P3 binding protein through a PI(3,4,5)P3 column and NGF-treated PC12 nuclear extracts. B23 has been shown to mediate the anti-apoptotic effects of NGF by inhibiting DNA fragmentation activity of CAD. B23 mutants that cannot associate with PI(3,4,5)P3 fail to prevent DNA fragmentation, indicating that PI(3,4,5)P3/B23 complex regulates the anti-apoptotic activity of NGF in the nucleus. Identification of a small molecule mediating the anti-apoptotic action of B23 unveils a novel therapeutic target for treatment of B23 amplified cancers.
Cancer Biol Ther 2005 Sep
PMID:Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis. 1610 50

Colon cancer is one of the leading causes of cancer deaths in the developed countries. Most colon cancers can be prevented if precursor colon polyps are detected and removed. Virtual colonoscopy, or CT colonography, has shown promise to be the future screening tool for polyp detection, with a number of studies performed at academic institutions showing high sensitivity and specificity. Two main factors limiting CT colonography in general use are its excessive interpretation time and the variable sensitivity among readers. This article discusses the potential of computer-aided detection to address these problems. We also review the current state of research in this field and the future roles and challenges of CAD for CT colonography.
Cancer Imaging 2005 Aug 23
PMID:Computer-aided detection for virtual colonoscopy. 1615 12

Radiological modalities, especially CT, mainly provide morphological and structural information with high spatial resolution covering large volumes. Novel developments, which are predominantly MR-based, also deliver 'functional' information, which can be used for individual characterisation of tumour biology. Both aspects and modalities, additionally complemented by ultrasound, have to be combined in the radiological workflow of cancer patients including volumetric visualisation, information extraction from multimodal imaging, quantitative surrogates, intelligent interpretation assistance and image-guided procedures. Based on volumetric visualisation and the generation of 3D+t maps, CAD tools have to address registration of different image series from different modalities, and extraction of quantitative surrogates. The latter will then serve tumour characterisation, therapeutic decision-making, image-guided procedures and efficacy evaluation.
Cancer Imaging 2005 Jun 21
PMID:Multimodal imaging and computer assisted diagnosis for functional tumour characterisation. 1615 19

We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P<0.0001). While weak signals were detected in the SP samples by real time PCR, the differences between SE and SP specimens were 148 fold for tags and 390 fold for BCCs. These differences were highly significant (P<0.0001). These findings suggest that methylation commences in UV exposed skin at a relatively early age and occurs in skin prior to the onset of recognizable preneoplastic changes.
Cancer Lett 2007 Jan 08
PMID:Sun exposure related methylation in malignant and non-malignant skin lesions. 3000 86

Curcumin is a natural pigment that has been shown to induce cell death in many cancer cells; however, the death mode depends on the cell type and curcumin concentration. Here we show that, in Jurkat cells, 50 micromol/L curcumin severely lowers cell survival and induces initial stage of chromatin condensation. It also induces caspase-3, which is sufficient to cleave DNA fragmentation factor 45 [DFF45/inhibitor of caspase-activated DNase (ICAD)], the inhibitor of DFF40/CAD endonuclease. However, the release of DFF40/CAD from its inhibitor does not lead to oligonucleosomal DNA degradation in curcumin-treated cells. Moreover, curcumin treatment protects cells from UVC-induced oligonucleosomal DNA degradation. In biochemical experiments using recombinant DFF activated with caspase-3, we show that curcumin inhibits plasmid DNA and chromatin degradation although it does not prevent activation of DFF40/CAD endonuclease after its release from the inhibitor. Using DNA-binding assay, we show that curcumin does not disrupt the DNA-DFF40/CAD interaction. Instead, molecular modeling indicates that the inhibitory effect of curcumin on DFF40/CAD activity results from curcumin binding to the active center of DFF40/CAD endonuclease.
Mol Cancer Ther 2006 Apr
PMID:Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. 1664 63

This paper presents a study of the analysis of breast density in missed cancer cases and the effect of tissue density on cancer detection. A total of 100 missed cancer cases were collected. The breast density tissue was segmented with a statistical-based method. A set of tests was then applied to examine: (1) the differences in density between the mammograms at the detected stage and that at missed stage; (2) the density difference between the cancerous mammograms and their contra-lateral normal mammograms in the missed cancer cases; (3) the effect of breast density on CAD cancer detection. The results demonstrate that breast density is an important factor affecting not only radiologist's reading but also CAD performance. In order to improve early detection of breast cancer, a special effort should be directed to the high dense breast cases in CAD system design.
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PMID:Computerized analysis of tissue density effect on missed cancer detection in digital mammography. 1683 64

Previously it was shown that horizontal DNA transfer between mammalian cells can occur through the uptake of apoptotic bodies, where genes from the apoptotic cells were transferred to neighbouring cells phagocytosing the apoptotic bodies. The regulation of this process is poorly understood. It was shown that the ability of cells as recipient of horizontally transferred DNA was enhanced by deficiency of p53 or p21. However, little is known with regard to the regulation of DNA from donor apoptotic cells. Here we report that the DNA fragmentation factor/caspase-activated DNase (DFF/CAD), which is the endonuclease responsible for DNA fragmentation during apoptosis, plays a significant role in regulation of horizontal DNA transfer. Cells with inhibited DFF/CAD function are poor donors for horizontal gene transfer (HGT) while their ability of being recipients of HGT is not affected.
Br J Cancer 2006 Dec 18
PMID:Regulation of mammalian horizontal gene transfer by apoptotic DNA fragmentation. 1714 78

This study is part of the research of improving early detection of breast cancer in screening mammograms by focusing on computerized analysis and detection of cancers missed by radiologists. It is directed to the analysis of breast density in missed cancer cases and the effect of tissue density on cancer detection. A total of 100 missed cancer cases were collected which were used to generate three different datasets including mammograms with missed cancer, mammograms with screening-detected cancer and normal mammograms. A statistical-based method was applied to segment the breast density tissue. The percentage of the segmented density tissue area out of the whole breast area is calculated as the index of breast density. A set of tests was applied to examine (1) the differences in density between the mammograms at the detected stage and that at missed stage, (2) the density difference between the normal mammograms and the cancerous mammograms; (3) the effect of breast density on CAD cancer detection. The results demonstrate that (1) no significant difference in breast density between the detected and missed stages; (2) the density of cancerous mammograms is significantly higher than normal mammograms; (3) similar to mammogram screening by radiologists, the lesions occurred in dense breasts are more likely to be missed in CAD detection especially at their early stage.
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PMID:Breast Tissue Density and CAD Cancer Detection in Digital Mammography. 1728 39


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