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

Many studies have indicated that the E-cadherin (E-CAD) expression loss is associated with the loss of cellular differentiation and increased cellular invasiveness and can be correlated with poor prognosis in urothelial carcinoma (UC) of the urinary bladder. The aim of this study was to define the role of E-CAD mRNA expression on recurrence, progression and survival in UC of the urinary bladder over a long follow-up period. From 30 patients with bladder UC, enrolled in our previous study, 27 were selected for this study. All patients were re-analyzed in terms of clinical and tumor characteristics, tumor pathological analysis and tumor E-CAD mRNA expression. The data were correlated to 12-year follow-up results. Significant correlations between stage (p=0.002), grade (p=0.008) and E-CAD mRNA expression were reported. E-CAD did not show any correlation in predicting recurrence or progression in bladder UC. The survival analysis demonstrated a significant relationship (p=0.019) between patients with expressed E-CAD mRNA levels and cancer-specific survival. Multivariate analysis demonstrated that expression of E-CAD mRNA levels is an independent prognostic factor in terms of cancer-specific survival in UC of the urinary bladder (p=0.002). Our study is the first to demonstrate that mRNA extraction and Northen blot analysis is to be considered a reliable method to evaluate E-CAD mRNA levels for predicting survival rate in patients affected by urothelial bladder cancers. We stress that a long follow-up period is needed to evaluate the role of molecular factors in predicting prognosis in patients affected by bladder UC.
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PMID:E-cadherin mRNA expression analysis in evaluating the natural history of urothelial bladder cell carcinoma: results from a long-term follow-up study. 1734 38

The need for quantified knowledge and decision-support tools to handle complex radiation therapy (RT) imaging and informatics data is becoming steadily apparent. Lessons can be learned from current CAD applications in radiology. This paper proposes a methodology to develop this quantified knowledge and decision-support tools to facilitate RT treatment planning. The methodology is applied to cancer patient cases treated by intensity modulated radiation therapy (IMRT). The use of the "inverse treatment planning" and imaging intensive nature of IMRT allows for the development of such image-assisted tools for supporting decision-making thus providing better workflow efficiency and more precise dose predictions.
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PMID:Image-assisted knowledge discovery and decision support in radiation therapy planning. 1736 94

High-dose chemotherapy followed by autologous blood stem cell transplantation is the standard treatment for myeloma patients. In this study, CAD (cyclophosphamide, adriamycin, dexamethasone) chemotherapy and a single dose of pegfilgrastim (12 mg) was highly effective in mobilizing peripheral blood stem cells (PBSCs) for subsequent transplantation, with 88% of patients (n = 26) achieving the CD34+ cell harvest target of > or = 7.50 x 10(6) CD34+ cells/kg body weight, following a median of two apheresis procedures (range 1-4) and with first apheresis performed at a median day 13 after CAD application (range 10-20). Patients treated with pegfilgrastim showed a reduced time to first apheresis procedure from mobilization compared with filgrastim-mobilized historical matched controls (n = 52, P = 0.015). The pegfilgrastim mobilization regimen allowed for transplantation of a median of 3.58 x 10(6) CD34+ cells/kg body weight while leaving sufficient stored cells for a second high-dose regimen and back-ups in most patients. Engraftment following transplantation was comparable to filgrastim, with a median time of 14 days to leucocyte > or =1.0 x 10(9)/l (range 10-21) and 11 days to platelets > or = 20 x 10(9)/l (range 0-15). The results of this study thus provide further support for the clinical utility of pegfilgrastim for the mobilization of PBSC following chemotherapy in cancer patients scheduled for transplantation.
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PMID:Efficient mobilization of peripheral blood stem cells following CAD chemotherapy and a single dose of pegylated G-CSF in patients with multiple myeloma. 1745 Jan 82

The Endeavor zotarolimus-eluting stent (ZES; Medtronic Vascular, Santa Rosa, CA) has been found to provide event-free clinical outcomes to 2 years for the treatment of symptomatic CAD by suppressing neointimal proliferation of the target lesion. The clinical outcomes of patients treated with the Endeavor ZES were evaluated at 4 years after implantation. One hundred consecutive patients with symptomatic ischemic heart disease due to de novo stenotic lesions of native coronary arteries were treated with the Endeavor ZES at 8 centers according to a standardized procedure. At 4 years, 3 patients were lost to follow-up analysis. The incidence of major adverse cardiac events (MACE; defined as death, myocardial infarction, emergent cardiac surgery, or repeat revascularization of the target lesion) was 2% at 4 months, 2% at 1 year, 3% at 2 years, 6.1% at 3 years, and 7.2% at 4 years. The difference in these rates was due to 4 deaths caused by cancer (metastatic melanoma, metastatic adenocarcinoma, small-cell cancer of the bladder, and lung carcinoma). From 2-4 years, there was an additional reported case of target lesion revascularization (TLR). A single case of stent thrombosis occurred at 10 days after the index procedure but no cases occurred thereafter. The treatment of patients with symptomatic CAD due to de novo lesions in native coronary arteries with the Endeavor ZES has sustained clinical benefits to 4 years, with very low rates of MACE and TLR.
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PMID:Four-year clinical follow-up after implantation of the endeavor zotarolimus-eluting stent: ENDEAVOR I, the first-in-human study. 1795 Aug 33

Secreted protein, acidic and rich in cysteines (SPARC) is a secreted protein associated with increased aggressiveness of different human cancer types. In order to identify downstream mediators of SPARC activity, we performed a 2-DE proteomic analysis of human melanoma cells following antisense-mediated downregulation of SPARC expression. We found 23/504 differential spots, 15 of which were identified by peptide fingerprinting analysis. Three of the differential proteins (N-cadherin (N-CAD), clusterin (CLU), and HSP27) were validated by immunoblotting, confirming decreased levels of N-CAD and CLU and increased amounts of HSP27 in conditioned media of cells with diminished SPARC expression. Furthermore, transient knock down of SPARC expression in melanoma cells following adenoviral-mediated transfer of antisense RNA confirmed these changes. We next developed two different RNAs against SPARC that were able to inhibit in vivo melanoma cell growth. Immunoblotting of the secreted fraction of RNAi-transfected melanoma cells confirmed that downregulation of SPARC expression promoted decreased levels of N-CAD and CLU and increased secretion of HSP27. Transient re-expression of SPARC in SPARC-downregulated cells reverted extracellular N-CAD, CLU, and HSP27 to levels similar to those in the control. These results constitute the first evidence that SPARC, N-CAD, CLU, and HSP27 converge in a unique molecular network in melanoma cells.
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PMID:Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells. 1799 31

The objective of this study was to develop a CAD system for the classification of hysteroscopy images of the endometrium based on color texture analysis for the early detection of gynaecological cancer. A total of 416 Regions of Interest (ROIs) of the endometrium were extracted (208 normal and 208 abnormal) from 40 subjects. RGB images were gamma corrected and were converted to the HSV and YCrCb color systems. The following texture features were extracted for each channel of the RGB, HSV, and YCrCb systems: (i) Statistical Features, (ii) Spatial Gray Level Dependence Matrices and (iii) Gray Level Difference Statistics. The PNN statistical learning and SVM neural network classifiers were also investigated for classifying normal and abnormal ROIs. Results show that there is significant difference (using the Wilcoxon Rank Sum Test at a=0.05) between the texture features of normal and abnormal ROIs of the endometrium. Abnormal ROIs had higher gray scale median, variance, entropy and contrast and lower gray scale median and homogeneity values when compared to the normal ROIs. The highest percentage of correct classifications score was 79% and was achieved for the SVM models trained with the SF and GLDS features for differentiating between normal and abnormal ROIs. Concluding, a CAD system based on texture analysis and SVM models can be used to classify normal and abnormal endometrium tissue. Further work is needed to validate the system in more cases and organs.
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PMID:Color based texture--classification of hysteroscopy images of the endometrium. 1800 93

Available data suggest that early detection of breast cancer by mammography screening can reduce mortality by about 25%. Intensified monitoring of women with a family history of breast cancer and regular general screening have recently been introduced in Germany. The screening program is expected to be fully established by 2008. Following its successful introduction (participation rates between 65 and 80%), the German screening program will be conducted and evaluated in accordance with the European guidelines. At least in the screening trials that were conducted prior to the now established screening program the quality criteria were more than fulfilled (e.g. cancer detection rate in Bremen 8.7, Wiesbaden 9.4, Weser-Ems region 8.3/1000). Additional parameters that can be taken into account for quality assurance are the overdiagnosis bias, lead time bias, length bias and selection bias. Moreover, there are some factors that are specific to the German program compared with the breast cancer screening programs already established in other countries. One of these is the intensified screening program for high-risk women (ca. 5% of all carcinomas) and as a result fewer women with an increased genetic risk of breast cancer will be represented in the general screening program. The German screening program involves only a few university centers and hospital-based physicians, which may have adverse effects on research and development as well as mammography training in the future. Therefore, the screening program should also provide for the investigation of new techniques or emerging techniques (e.g. CAD systems in screening mammography) in the future.
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PMID:[Mammography screening in Germany]. 1803 Apr 41

Genomic instability during hepatocarcinogenesis causes changes in signal transduction network. Strategies for identification of new markers/therapeutic targets include discovery of early molecular changes during hepatocarcinogenesis, relevant to preneoplastic lesions progression to full malignancy in rodent models, and evaluation of these changes in human hepatocellular carcinomas (HCCs). Activation of ERB receptor family, MAPK, JAK-STAT, beta-Catenin cascades, c-Myc targets, iNOS-IKK/MAT1A-NF-kB axis, Ornithine decarboxylase, Cyclins and CDKs occurs in human and rodent hepatocarcinogenesis. This is associated with downregulation of the cell cycle inhibitors p16(INK4A) and p53 and TGF-beta/SMAD signaling. Oncosuppressor genes, including p16(INK4A), E-CAD, and DLC-1 are often hypermethylated in humans and rodents. Moreover, protection of cell cycle from p16(INK4A) inhibition by upregulation of CDC37, HSP90, and CRM1 correlates to HCC progression. A body of evidence indicates that inhibition of key genes of aforementioned signaling pathways by antisense or siRNA approaches or specific inhibitors restraints growth of in vitro cultured or in vivo xenografted HCCs. Efforts are currently dedicated to improve transduction efficiency. HCC cells may escape gene therapy by various mechanisms. Attempts to overcome this difficulty include discovery of new therapeutic targets, gene therapy directed to different molecular targets essential for tumor cell survival and specifically directed to HCC subtypes.
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PMID:Dissection of signal transduction pathways as a tool for the development of targeted therapies of hepatocellular carcinoma. 1847 8

DNA fragmentation factor is a heterodimer complex of the nuclease CAD and its specific inhibitor ICAD, which can be activated during apoptosis to induce DNA fragmentation. Although ICAD expression levels have been quantified in a variety of human cancer cells, the mechanism of ICAD gene regulation remains unknown. In this study, we identified a 106-bp TATA-less region upstream of the transcription start site as a basal promoter of the human ICAD gene. An E-Box motif, which binds transcription factors of the basic helix-loop-helix/leucine zipper family, is responsible for transcriptional activity, as demonstrated using mutated promoter-reporters. A chromatin immunoprecipitation assay further demonstrated that Myc binds to an endogenous ICAD promoter. The functional importance of Myc in the regulation of ICAD transcription was also demonstrated by knock-down of c-Myc and N-Myc gene expression, as well as their ectopic expression. Structural analysis of the human ICAD promoter and identification of factors which regulate its activity might further our understanding of the biological role of ICAD with respect to regulation of apoptosis and cancer development.
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PMID:Identification and characterization of the human inhibitor of caspase-activated DNase gene promoter. 1850 May 56

The very high sensitivity and increased specificity of breast and prostate MRI, due to recent technical advances, enables more lives to be saved due to earlier diagnosis. Demand for breast MRI continues to increase due to the American Cancer Society's 2007 guidelines, recognition of its benefit by breast surgeons, and requests from patients at high risk due to dense breast tissue, family history, or other factors. With these more recent additions of perfusion,diffusion,and spectroscopy to anatomic information, prostate MRI is being more readily accepted by urologists as part of the staging evaluation for the appropriate subset of patients with prostate cancer, or pre-diagnosis evaluation for specific subsets of patients. Imaging facilities contemplating a breast and/or prostate MRI program need to consider potential demand, staffing, necessary equipment, a CAD system for study interpretation and reporting, and insurance reimbursement management.
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PMID:Breast and prostate MRI: new frontiers in women and men's imaging. 1857 19


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