Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objectives of this study were to investigate: 1) the activity of pseudocholinesterase (PChE) in patients with uterine cervical cancer in different stages (uterine cervical carcinoma in stages II b and III and recurrent cervical carcinoma in stages III and IV a,b) and to compare it to the enzyme activity in patients with benign tumour of the uterus, and 2) the effects of radiotherapy on enzyme activity in those patients with uterine cervical carcinoma for which the chosen treatment was radical radiotherapy. Thirty patients with uterine cervical carcinoma in stages II b and III (Group A), sixteen patients with recurrent cervical carcinoma in stages III and IV a,b (Group B) and thirty-eight patients with benign tumours of the uterus (control, Group C) were evaluated and their PChE activity was determined prior to any treatment (pre-therapy enzyme activity). All eighty-four patients were free of any liver disease. The results have shown that the patients of Group A had the pre-therapy PChE activity practically identical to those in group C, but patients of Group B had significantly lower values of PChE with respect to enzyme activities of Groups A and C (p < 0.001). That is to say, PChE activity was influenced by the extent to which the malignancy had spread. Radical radiotherapy (up to 8 weeks in doses higher than 50 Gy into point A; average 80 Gy) which was the chosen treatment only for patients from group A did not cause a significant inhibition of PChE activity in any patients in comparison with their control values. With regard to the role of PChE in hydrolysis of succinylcholine, our results about the influence of the malignant disease and the radiotherapy on PChE activity are clinically significant.
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PMID:Plasma cholinesterase activity in patients with uterine cervical cancer during radiotherapy. 1121 5

Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous expression of cholinesterase and acetylcholine sensitive receptors (nicotinic, muscarinic). Both receptor populations interact with more or less all cellular signalling pathways. Thus, non-neuronal acetylcholine can be involved in the regulation of basic cell functions like gene expression, proliferation, differentiation, cytoskeletal organization, cell-cell contact (tight and gap junctions, desmosomes), locomotion, migration, ciliary activity, electrical activity, secretion and absorption. Non-neuronal acetylcholine also plays a role in the control of unspecific and specific immune functions. Future experiments should be designed to analyze the cellular effects of acetylcholine in greater detail and to illuminate the involvement of the non-neuronal cholinergic system in the pathogenesis of diseases such as acute and chronic inflammation, local and systemic infection, dementia, atherosclerosis, and finally cancer.
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PMID:The biological role of non-neuronal acetylcholine in plants and humans. 1124 68

The effect of malignant tumor growth on host's megakaryocytopoiesis and platelet production was studied in mice bearing transplantable Dalton's lymphoma. Tumor growth was paralleled by thrombocytosis, neutrophilia, and anemia. Platelet 51Cr half-life was normal but incorporation of 75Selenomethionine into circulating platelets was significantly enhanced in the tumor bearers suggesting stimulated thrombopoiesis while platelet life span remained unchanged. Megakaryocytes and their precursors, the small acetyl cholinesterase positive cells, were found in increased numbers in the bone marrow (BM) and particularly in the spleen where five to eight-fold rise was observed at the log phase of tumor growth. In addition, a remarkable increase in the number of megakaryocyte progenitors (CFU-MK and MK CFU-S) was observed both in the BM and spleen. Stimulation of these progenitors was more pronounced in the spleen than in the marrow, and the change was noticeable even from the third day of tumor bearing. Therefore, the results suggest that thrombocytosis associated with the growth of this experimental lymphoma was due to accelerated platelet production following stimulated megakaryocytopoiesis especially in the spleen.
J Exp Clin Cancer Res 2000 Dec
PMID:Stimulation of megakaryocytopoiesis and platelet production during growth of an experimental lymphoma. 1127 30

The progress in cellular engineering offers novel approaches for anti-cancer therapies. To investigate the effectiveness of potential therapies efficient screening methods are required. We propose an impedance measurement system which enables the use of multicellular spheroid models in bioelectronic screening systems either for non destructive life-time diagnostic or anti-cancer therapies. A biohybrid sensor system is created comprising gene-manipulated T47D clone 11 breast carcinoma spheroids positioned hydrodynamically in a capillary system with electrodes. A novel approach employing an antisense-5'butyrylcholinesterase expression system is probed on reaggregated tumor cells under simulated microgravity, inhibiting the gene transcription and translation of the embryonic proliferation marker butyrylcholinesterase expressed in different tumor types. Alterations in the morphology of cell aggregates e.g. apoptosis or necrosis can be detected by impedance spectroscopy monitoring the electric behavior of membranes and extracellular space with a high resolution and reproducibility. The hydrodynamic positioning of 3D in vitro cell aggregates and the short time for the measurements represent an innovative method for a synchronized multicapillary screening system. The combination of the measuring system with a bioreactor enables cyclic life time recordings of impedance spectra for monitoring the cell aggregate properties for a long period.
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PMID:A multicellular spheroid-based sensor for anti-cancer therapeutics. 1139 Feb 13

Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation.
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PMID:A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition. 1140 58

We have previously reported that long-term treatment with clarithromycin (CAM) increased the median survival of patients with non-small cell lung cancer, and improved various clinical parameters in these patients. In the present study, CAM was administered to 33 patients with unresectable primary non-small cell lung cancer, who had received chemotherapy, radiotherapy or both (basic cancer therapy). Patients with clinical backgrounds matched to the CAM group, who did not receive CAM treatment, were included into this study as a control group (non-CAM group). CAM treatment was initiated 4 weeks after the basic cancer therapy. The non-CAM group did not receive a placebo. Before and after the 3-month treatment with CAM, body weight, serum levels of interleukin-6 (IL-6, a cytokine which, together with TNF-alpha, plays a crucial role in the development of cancer cachexia), total protein, albumin, cholinesterase and hemoglobin were measured for the evaluation of the patients' clinical status. There were no statistically significant differences in serum levels of IL-6 between the CAM group before the treatment and the non-CAM group. After 3 months of CAM treatment, serum levels of IL-6 significantly decreased. In contrast, body weight, cholinesterase, and hemoglobin increased to a significant extent. Among these four parameters, however, the decrease in serum IL-6 levels was only statistically correlated with the increase in body weight, but not with that in other parameters. Furthermore, CAM-treated patients whose serum IL-6 levels were decreased after 3 months of treatment survived longer: there was a statistically significant correlation between the decrease in serum IL-6 and survival time. In contrast, in the non-CAM group, these parameters did not change significantly during the study. These results suggest that CAM may reduce the progression of cancer-associated cachexia.
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PMID:Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. 1178 60

Many drugs interact with neuromuscular blocking drugs and often enhance the induced block; this is of clinical importance for volatile anaesthetics, antimicrobials, magnesium and some more specific drugs. Difficulty in reversing the block occurs with calcium-channel blockers and polymyxin. Phenytoin, carbamazepine and other anticonvulsants may cause resistance to neuromuscular blocking drugs. Moreover, clinically important interactions are found between individual neuromuscular blockers. Giving succinylcholine after a non-depolarizing neuromuscular blocking drug prolongs the onset of succinylcholine; when non-depolarizing drugs are administered after succinylcholine their effects are prolonged. The succinylcholine block is prolonged when the drug is administered during recovery from pancuronium or following neostigmine reversal. Drugs or diseases that decrease the activity of plasma cholinesterase may prolong a succinylcholine-induced block. Finally, liver dysfunction, renal failure, disturbances of acid-base balance, change in temperature and neurological diseases all have an effect on the profile of the neuromuscular blocking drugs; the response to an induced block may be altered in patients under intensive care and those with cancer. Although knowledge of the most important theoretical interactions of neuromuscular blocking drugs is favourable, the anaesthetist should be aware that pharmacological interactions can lead to an unpredictable induced neuromuscular block in many cases in daily clinical practice. Therefore anaesthetists should become familiar with the use of neuromuscular transmission monitoring in order to manage the block correctly.
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PMID:Interactions of neuromuscular blocking drugs. 1179 68

Organophosphate-based pesticides have been associated with pathology and chromosomal damage in humans. There are also epidemiologic links with cancer. The few screening tests for low-level occupational exposure are of doubtful sensitivity; this investigation evaluated four methods. Blood samples were studied from 10 farmers before and after occupational exposure to organophosphate-based pesticides and five unexposed controls. The standard cholinesterase test was insensitive to the exposure (P=0.815). However, a significant increase in Howell-Jolly bodies within erythrocytes was observed (P=0.001). Cytogenetic studies on routine and aphidicolin-induced blood cultures revealed that following organophosphate exposure the total number of gaps and breaks on human chromosomes was significantly increased (P=0.004 and P=0.0006, respectively). We concluded that Howell-Jolly body and fragile site analysis were sensitive indicators of nuclear damage resulting from low-level occupational exposure to organophosphate. Such nuclear damage could be implicated in carcinogenesis. The development of bladder cancer is one such example.
Cancer Genet Cytogenet 2002 Mar
PMID:Organophosphate-based pesticides and genetic damage implicated in bladder cancer. 1194 36

Environmental substances may be involved in the etiology of breast cancers. Many studies have found an association between cancer in humans and exposure to agricultural pesticides. Organophosphorous pesticides have been used to control mosquito plagues. Parathion and malathion, organophosphorous pesticides are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Their primary target of action in insects is the nervous system whereby they inhibit the enzyme acetylcholinesterase at synaptic junction. Atropine is a parasympatholytic alkaloid used as an antidote to acetylcholinesterase inhibitors. We have established an experimental breast cancer model, where epithelial cells in the rat mammary gland underwent a stepwise transformation into malignant cells by exposure to pesticides (Cabello et al, 2001). The aim of this work was to examine whether pesticides were able to induce progression of malignant transformation of a human breast epithelial cell line, MCF7. These results showed that parathion and malathion increased PCNA and induced mutant p53 protein expression of MCF7 cells in comparison to controls and atropine inhibited such action. These results indicated that organophosphorous pesticides can induce more changes in this malignant breast cell line, inducing another step in the progression of the transformation process and atropine on the other hand inhibited the effect of such substances.
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PMID:Organophosphorous pesticides in breast cancer progression. 1276 45

Although FDA-approved Alzheimer's disease (AD) treatment strategies (cholinesterase inhibitors and memantine) offer proven benefits, providers recognize unmet needs beyond what is currently available. Consequently there is a significant use of anecdotal yet unproven combinations for treating AD in practice. Based on the best evidence, combination drug therapy is the standard of care for treating other medical conditions such as malignancies, human immunodeficiency virus (HIV), and hypertension. We review recent combination drug therapy studies in AD. To date, the best evidence-based combination strategy is for moderate-to-severe AD, in which the addition of memantine to stable donepezil therapy was found to benefit cognition, behavior, and function. In milder stages of AD, the benefit of combination drug therapy has not been demonstrated. This review highlights the urgent need to systematically test additional rational drug combinations and the need for future trials to enroll adequate sample sizes and utilize relevant and sensitive outcome measures.
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PMID:Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? 1594 60


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