Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The average Korean diet is low in total fat, cholesterol, animal protein, and sugar, and high in total carbohydrate, and adequate in total protein. More foods are derived from vegetables than in any comparable Western countries. The nutritional status of Korean is good without evidence of any gross nutritional deficiency. The leading causes of death, currently, form a unique ranking of malignancies, accidents, and cerebrovascular diseases. Korean diet may account for the strikingly low incidence of heart disease. Studying the relationship between diet and these diseases may greatly aid our understanding of their pathogenesis and lead to improved prevention and treatment. Current changes in the Korean diet are a decreasing proportion of carbohydrates with increasing proportions of fat and animal protein and an increased content of cholesterol. The ratio of polyunsaturated to saturated fatty acid of Korean diet seems to fall in desirable range. The changes in plasma cholesterol levels and CAD mortality among Korean in the past 20 years seem to be a reflection of changes in diet. Similar changes could be seen in the Japanese population. In Korea, the incidence of CAD is still low compared with that in western countries. Recently, a slightly increased incidence of CAD has been observed in Korea. Thus, establishment of reliable biochemical markers and their cut-off values are needed for the Korean population. Several methods including TC, TG, HDL-C, LDL-C, HDL-C/TC, LDL-C/TC, LDL-C/HDL-C, Apo A-I, Apo B and Apo A-I/B for CAD were examined and found that Apo A-I/B ratio was a good biochemical marker for CAD in Korea. In the future, the Korean diet will probably continue to change. The changes are being influenced by economic development that have been emerging and growing stronger since 1980 and that will probably continue to be potent. The effect of these changes upon CAD is not clear at the present time. To detect a changing incidence of CAD and to evaluate the significance of diet will require continued close observation and use of more specific and sensitive methods. The Korean experience with diet and plasma lipids will be potentially valuable in appraising CAD of both developing and technically developed countries.
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PMID:Changes of plasma lipids and biochemical markers for coronary artery disease in Korea. 848 39

Between January 1988 and June 1992, 35 patients with primary anaplastic large cell lymphoma (ALCL)CD30+ were referred to one of the institutions participating in GISL (Gruppo Italiano per lo Studio dei Linformi). 16 patients were treated with ProMACE-CytaBOM, two with MACOP-B, one with CHOP and one with LSA2-L2. As of November 1990, all newly diagnosed patients were treated with MOPP/EBV/CAD hybrid. 27 (77%) cases of ALCL CD30+ and 8 (23%) cases of Hodgkin's-related (HR) lymphoma CD30+ were diagnosed. Extranodal disease was present in 22 cases (63%), and 8 patients (23%) had primary bone marrow involvement. Twenty-three complete remissions (CR) (66%), six partial remissions (PR) (17%) and six no remissions (NR) (17%) were achieved with induction therapy. Results achieved with ProMACE-CytaBOM and MOPP/EBV/CAD hybrid were comparable. The overall response rate (CR+PR) was 85% for patients with classic ALCL CD30+ and 87% for those with HR lymphoma CD30+. The 3 year estimated overall survival rate was 66% and the 3 year relapse free survival rate was 65% for the entire group. The only significant favourable prognostic factor was the achievement of CR with initial therapy. Our findings suggest that ALCL (CD30+/Ki-1+) has a clinical outcome similar to aggressive non-Hodgkin's lymphoma (NHL). The use of an anthracycline-containing regimen will provide a change of cure in approximately 65% of cases.
Eur J Cancer 1995 Oct
PMID:Anaplastic large cell lymphoma (CD30+/Ki-1+). Analysis of 35 cases followed at GISL centres. 854 Oct 96

Defects in cell cycle control and increased genomic instability, including gene amplification, often occur during cancer development. Cyclin D1 plays a pivotal role in G1, and this gene is frequently amplified and overexpressed in several types of human cancer. This study demonstrates that ectopic overexpression of cyclin D1 in a rat liver epithelial cell line markedly increased the yield of cells containing amplified copies of the CAD gene. This effect was associated with a loss of G1-S checkpoint control, although the cyclin D1-overexpressing cells had a normal p53 gene. The capacity of cyclin D1 to enhance gene amplification may contribute to the process of genomic instability during tumor development.
Cancer Res 1996 Jan 01
PMID:Overexpression of cyclin D1 enhances gene amplification. 854 70

The invasion-suppressor molecule E-cadherin (E-CAD) can be regulated at multiple levels: synthesis, processing and stability of mRNA; synthesis, processing and stability of protein; localization and posttranslational modification of protein; binding to catenins (E-CAD-associated proteins); and size and charge of cell surface glycosaminoglycans. Loss of E-CAD antigen and of E-CAD function in vivo has been observed with cell lines that homogeneously expressed functional E-CAD in vitro. These observations led to the idea that factors in the host may downmodulate E-CAD on the cancer cells, thereby promoting cell invasion. Nude mouse cancers that were homogeneously E-CAD-positive and noninvasive in vitro, formed by epithelioid MDCK or NMuMG cells, stained heterogeneously for E-CAD; such cancers were invasive and metastatic. The in vivo downmodulation appeared to be transient. Ex vivo cultures from primary cancers, as well as from metastases, produced homogeneously E-CAD-positive and noninvasive cells. Downmodulation did not occur when cells were micro-encapsulated and then implanted in the mouse, suggesting a role for immediate cancer cell-host cell contact. Similar in vitro/in vivo/ex vivo experiments with mouse MO4 fibrosarcoma cells, transfected with E-CAD cDNA under the control of a b-actin promotor, showed downregulation at the transcriptional or mRNA stability level. This downregulation was rapidly reversible upon ex vivo culture of the tumor cells. TGF-bl and IGF-I were found, respectively, to downregulate and upregulate the expression or the function of E-CAD. We speculate that IGF-1 restores the function of E-CAD through interaction of the IGF-I tyrosine kinase receptor with the catenin-actin cytoskeletal complex. In human cancers, immunohistochemistry has revealed changes in E-cadherin that agree with the experimental data on transient downmodulation of the invasion-suppressor function of E-cadherin by host factors.
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PMID:Downregulation in vivo of the invasion-suppressor molecule E-cadherin in experimental and clinical cancer. 898 64

Ribonucleotide reductase is a highly regulated, cell cycle-controlled activity that plays an important role in DNA synthesis and repair. Recent studies have shown that elevated expression of the rate-limiting R2 component of ribonucleotide reductase increases Raf-1 protein activation and mitogen-activated protein kinase activity and acts as a novel malignancy determinant in cooperation with activated oncogenes like H-ras. We show that hydroxyurea-resistant mouse L cells with elevated R2 gene expression and increased ribonucleotide reductase activity exhibit significantly decreased sensitivities to the chemotherapeutic compounds N-(phosphonacetyl)-L-aspartate (PALA) and methotrexate (MTX). Furthermore, BALB/c 3T3 cells containing a retroviral expression vector encoding the R2 sequence also showed decreased sensitivity to PALA and MTX when compared to cells containing the same vector but without the R2 coding region. Colonies that developed in the presence of PALA or MTX contained amplifications of the CAD or dihydrofolate reductase genes and exhibited wild-type p53 function as determined in sequence-specific p53 binding activity assays. NIH-3T3 cells containing the R2 retroviral expression vector also showed significantly decreased sensitivity to hydroxyurea and MTX but not to PALA. Furthermore, NIH-3T3 cells transfected with a vector containing the R2 sequence in antisense orientation exhibited increased sensitivity to hydroxyurea, PALA, and MTX. Similarly, mouse 10T1/2 cells that are highly transformed and drug resistant due to alterations in H-ras and a mutant oncogenic form of p53 exhibited significant increases in sensitivity to hydroxyurea, PALA, and MTX when transfected with a vector containing the R2 sequence in antisense orientation and compared to cells containing the same vector without the antisense sequence. These results indicate that altered expression of the R2 component is capable of significantly modifying drug sensitivity properties of tumor cells. We hypothesize that this occurs, at least in part, through a mechanism of increased genetic instability that is independent of direct p53 mutation or loss and involves R2 stimulation of the mitogen-activated protein kinase signal pathway.
Cancer Res 1997 Nov 01
PMID:Ribonucleotide reductase R2 gene expression and changes in drug sensitivity and genome stability. 935 52

p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative Auto-CAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.
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PMID:Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity. 949 92

Several chemical agents appear to be useful in primary prevention of CAD and cancer. Randomized trials have found that in specific patient subgroups, tamoxifen and raloxifene decreased the occurrence of breast cancer, and lovastatin and aspirin decreased the frequency of CAD events. Secondary analysis of randomized primary-prevention studies has supported the use of vitamin E and selenium in cancer prevention.
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PMID:Preventing heart disease and cancer. What randomized, primary-prevention studies show. 1056 Apr 73

In rodent cells, resistance to PALA (N-phosphonacetyl-L-aspartate) has always been found associated with amplification of the CAD gene (carbamyl-P synthetase, aspartate transcarbamylase, dihydro-orotase). We describe two PALA resistant Chinese hamster mutant cell lines in which amplification of the CAD gene was not present. The PALA resistant phenotype was stable when the cells were grown in non-selective medium. However, after prolonged growth in the presence of the same drug concentration used for selection, cells with increased CAD gene copy number and higher levels of resistance overrode the original population. In these cell populations, a heterogeneous organization of the CAD genes was revealed by fluorescence in situ hybridization on mitotic chromosomes indicating that the additional copies of the gene were generated in several ways, such as non-disjunction and breakage-fusion-bridge cycles. The clastogenic effect of PALA, evidenced as chromosomal aberrations in the cells grown in the presence of the drug, could have favored the late onset of the amplified mutants. It is tempting to speculate that, during the expansion of tumor populations, different drug resistance mechanisms, including gene amplification, could occur in succession and lead to the generation of cells highly resistant to chemotherapeutic agents.
Cancer Lett 2000 Mar 31
PMID:Late onset of CAD gene amplification in unamplified PALA resistant Chinese hamster mutants. 1070 33

CAD methods may provide radiologists with tools to obtain more accurate diagnoses for lung cancer. Considerable effort has been devoted to developing CAD tools for CXR; however, these are limited by the fundamental constraints of the projective CXR modality. CT provides far more detailed information that can be exploited better by CAD systems. There has been very little work done in this area to date, although the basic technology has already been developed through the more extensive research in the computer vision areas supported by industry and the military. Initial prototype CT CAD systems have been described that are highly effective in detecting small pulmonary nodules and in predicting malignancy of nodules. CT is now achieving momentum in the study of lung cancer. It has taken time for this modality to gain acceptance because of several factors: higher radiation dose, higher cost, and the novelty of use in this application. It is important to note that the technology for CT scanners is still rapidly evolving. As the speed, resolution, and cost of CT scanners continue to improve, computer techniques for the measurement and analysis of nodules will also achieve corresponding improvements in accuracy and diagnostic utility. Future knowledge-based CT CAD systems will provide detailed analysis of the related conditions of the lungs, such as emphysema, and diagnostic analysis of nodules. The issue is not whether CAD will improve the performance and capabilities of the radiologist, but at what rate their development and the corresponding improvement will occur. Current prototype CAD systems may be considered as tools. As such they will improve the performance of the user/radiologist if they are well engineered and if the user understands their capabilities and limitations. These systems need to be improved by knowledge-based engineering, which is notoriously difficult to implement robustly and requires model refinement and optimization based on a large database of cases. Research should be directed at developing these methods rather than comparing prototype systems with current practices. Future performance should be expected to exceed that of today's grand masters.
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PMID:Computer-aided diagnosis for lung cancer. 1085 57

The view that chemical or physical oncogenesis and tumor therapy resistance represent different parts of common cellular alterations gained considerable attractiveness, because it explains the inherent unreponsiveness of many tumors. Viruses are potent oncogenes and are causally linked to approximately one-fifth of all human malignancies. Whether viral oncogenesis exerts comparable effects was less clear. Recent progress in experimental research provided ample evidence that viruses affect response of tumor cells toward anti-cancer drugs and irradiation. Resistance to cytostatic drugs and radiation develops by alterations at the drug-target sites (i.e., DNA or specific target proteins), upstream (i.e., detoxification mechanisms), or downstream of them (i.e., programmed cell death). Viruses interfere with specific cellular genes at these three levels. Viral proteins induce the expression and expression of drug resistance genes, that is, MDR1, DHFR, or CAD. Viral interactions with the tumor suppressor genes (p53, pRB) abrogate cell cycle arrests and disturb DNA repair of drug- and radiation-induced DNA lesions. The readiness to commit cellular suicide (apoptosis) is also affected by viral genes. The connection between viral oncogenesis and the response of tumor cells to treatment adds a new dimension to tumor biology and may have important consequences for oncological treatment modalities in the future.
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PMID:Impact of viral oncogenesis on responses to anti-cancer drugs and irradiation. 1100 11


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