Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1974 and 1986, 576 patients (284 limited and 292 extensive stages) were treated at this institution. To keep multiagent chemotherapy (CT) at a uniform intensity, patients who received (a) combined modality approach of both multiagent chemotherapy and thoracic radiotherapy (RT) and (b) greater than or equal to 3 cycles of multiagent chemotherapy (greater than or equal to 3 drugs), were chosen for this analysis. Out of 284 patients with limited Stage small-cell lung carcinoma, there were 154 such patients who met these strict criteria, and the treatment methods for the remaining 130 patients were as follows: (a) chemotherapy alone with radiotherapy reserved for local failure (47 pts); (b) radiotherapy alone (20 pts); (c) surgery +/- adjuvant chemotherapy or radiotherapy (37 pts); (d) modified chemotherapy plus radiotherapy (26 pts). During the 12-year period, the therapeutic factors have evolved. Radiation-dose was increased from 30-40 Gy (time dose fractionation 49-66) in 1974-1977 to 44-52 Gy (time dose fractionation 73-86) in 1978-1986. The target volume for radiotherapy included the primary lesion with a 2-cm margin of normal lung and the mediastinum. Chemotherapy program also evolved from COP, CAV (1974-1977) to MACC, VCE-VCA, PCE-ACE (1978-1986). Fifty of 154 patients (32%) developed loco-regional recurrence (infield failure) and 98% (49/50) of these patients exhibited this by 2.5 years. Survival data of 154 patients were as follows: (a) Median survival time (MST) was 12 M; (b) actuarial survival rates at 2 and 5 years were 21% and 8%, respectively. Fifty percent of these patients died within 12 months (MST 12 M) and were not exposed to the full length of the risk period for loco-regional failure. To take into account the duration of exposure to the risk period, actuarial method was employed to measure the probability of loco-regional failure. Loco-regional failure rates at 2.5 years were 37%, 39%, 49%, 79%, and 84% for 50 Gy, 45 Gy, 40 Gy, 35 Gy, and 30 Gy, respectively. The difference between the recurrence rates of 37% and 79% by 50 Gy and 35 Gy was statistically significant, p less than 0.05. Although the recurrence rates of 37% and 49% by 50 Gy and 40 Gy were not statistically different, there was a strong trend of a better control rate of loco-regional carcinoma by higher radiation doses. The time to recurrence seems also shorter with lower radiation-dose than that of higher radiation doses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: an update. 254 6

Low activity of angiotensin converting enzyme (ACE) has been reported in patients with smoking related diseases, such as chronic bronchitis, emphysaema and carcinoma of the lung [1] but this has not been reported in healthy, chronic smokers. Serum ACE was measured in 40 healthy cigarette smokers and in 42 healthy non-smokers. The mean value was significantly lower in the smokers. Hence a non-smokers. The mean value was significantly lower in the smokers. Hence a patient's smoking habits should be taken into consideration when assessing the significance of his serum ACE levels.
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PMID:Serum angiotensin converting enzyme activity in cigarette smokers. 300 66

The paper presents the results of quantitative changes in the activity of some most important oxidative-reductive enzymes in lung carcinoma cells. The histo- and cytospectrophotometric studies were carried out on the operation material removed from 32 patient with lung carcinoma including 12 cases of squamous cell carcinoma, 12 cases of adenocarcinoma, 4 cases of undifferentiated large cell and 4 cases of undifferentiated small cell carcinoma. Statistically significant increases in the activity of G-6-PDH, NADP-D and LDH were observed in a decreasing degree of tumour differentiation with a simultaneous relative decrease in the activity of SDH, MDH NAD-D and alpha-GPDH. When the activity of oxidoreductases was compared in tumours having the structure of squamous cell carcinoma and adenocarcinoma, a higher activity of LDH, SDH and alpha-GPDH in squamous cell carcinoma and high activity of G-6-PDH and NADP-D in adenocarcinoma were observed. Statistically significant differences in the activity of carbohydrate metabolism enzymes in small cell carcinoma and other histological forms of lung cancer were found: a significant increase in G-6-PDH and LDH and relative decline in the activity of SDH and alpha-GPDH. In all the examined histological forms of lung cancer there was a complete agreement in the results of histo- and cytospectrophotometric examinations of the activity of the main oxidative-reductive enzymes.
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PMID:[Histocytospectrophotometric characteristics of lung cancer]. 625 7

Microvascular endothelial cells (MVEC), which differ from large vessel endothelial cells, have been isolated successfully from lungs of various species, including man. However, contamination by nonendothelial cells remains a major problem in spite of several technical improvements. In view of the organ specificity of MVEC, endothelial cells should be derived from the tissue involved in the diseases one wishes to study. Therefore, to investigate some of the immunopathological mechanisms leading to acute respiratory distress syndrome (ARDS), we have attempted to isolate lung MVEC from patients undergoing thoracic surgery for lung carcinoma and patients dying of ARDS. The method described here includes four main steps: (1) full digestion of pulmonary tissue with trypsin and collagenase, (2) aggregation of MVEC induced by human plasma, (3) Percoll density centrifugation, and (4) selection and transfer of MVEC after local digestion with trypsin/EDTA under light microscopy. Normal and ARDS-derived lung MVEC purified by this technique presented contact inhibition (i.e., grew in monolayer), and expressed classical endothelial markers, including von Willebrand factor (vWF), platelet endothelial cell adhesion molecule 1(PECAM-1, CD31), and transcripts for the angiotensin converting enzyme (ACE). The cells also formed capillarylike structures, took up high levels of acetylated low-density lipoprotein (Ac-LDL), and exhibited ELAM-1 inducibility in response to TNF. Contaminant cells, such as fibroblasts, smooth muscle cells, or pericytes, were easily recognized on the basis of morphology and were eliminated by selection of plasma-aggregated cells under light microscopy. The technique presented here allows one to study the specific involvement and contribution of pulmonary endothelium in various lung diseases.
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PMID:An improved method for isolation of microvascular endothelial cells from normal and inflamed human lung. 971 12

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

Recent work from this laboratory demonstrated that apoptosis of pulmonary alveolar epithelial cells (AEC) in response to Fas requires angiotensin II (ANGII) generation de novo and binding to its receptor (Wang et al., 1999b, Am J Physiol Lung Cell Mol Physiol 277:L1245-L1250). These findings led us to hypothesize that a similar mechanism might be involved in the induction of AEC apoptosis by TNF-alpha. Apoptosis was detected by assessment of nuclear and chromatin morphology, increased activity of caspase 3, binding of annexin V, and by net cell loss inhibitable by the caspase inhibitor ZVAD-fmk. Purified human TNF-alpha induced dose-dependent apoptosis in primary type II pneumocytes isolated from rats or in the AEC-derived human lung carcinoma cell line A549. Apoptosis in response to TNF-alpha was inhibited in a dose-dependent manner by the nonselective ANGII receptor antagonist saralasin or by the nonthiol ACE inhibitor lisinopril; the inhibition of TNF-induced apoptosis was maximal at 50 microgram/ml saralasin (101% inhibition) and at 0.5 microgram/ml lisinopril (86% inhibition). In both cell culture models, purified TNF-alpha caused a significant increase in the mRNA for angiotensinogen (ANGEN), which was not expressed in unactivated cells. Transfection of primary cultures of rat AEC with antisense oligonucleotides against ANGEN mRNA inhibited the subsequent induction of TNF-stimulated apoptosis by 72% (P < 0.01). Exposure to TNF-alpha increased the concentration of ANGII in the serum-free extracellular medium by fivefold in A549 cell cultures and by 40-fold in primary AEC preparations; further, exposure to TNF-alpha for 40 h caused a net cell loss of 70%, which was completely abrogated by either the caspase inhibitor ZVAD-fmk, lisinopril, or saralasin. Apoptosis in response to TNF-alpha was also completely inhibited by neutralizing antibodies specific for ANGII (P < 0.01), but isotype-matched nonimmune immunoglobulins had no significant effect. These data indicate that the induction of AEC apoptosis by TNF-alpha requires a functional renin/angiotensin system (RAS) in the target cell. They also suggest that therapeutic control of AEC apoptosis in response to TNF-alpha is feasible through pharmacologic manipulation of the local RAS.
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PMID:Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo. 1102 47

The primary targets for SARS-CoV infection are the epithelial cells in the respiratory and intestinal tract. The angiotensin-converting enzyme 2 (ACE-2) has been identified as a functional receptor for SARS-CoV. ACE-2 has been shown to be expressed at the apical domain of polarized Calu-3 cells. In this report, interferon alfacon 1 was examined for inhibitory activities against SARS-CoV on human lung carcinoma epithelial Calu-3 cell line and the other three African green monkey kidney epithelial cell lines. Interferon alfacon 1 demonstrated significant antiviral activity in neutral red uptake assay and virus yield reduction assay. The data might provide an important insight into the mechanism of pathogenesis of SARS-CoV allowing further development of antiviral therapies for treating SARS infections.
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PMID:Interferon alfacon 1 inhibits SARS-CoV infection in human bronchial epithelial Calu-3 cells. 1840 49