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

Many of the discoveries of multidrug resistance (MDR) have resulted from studies using drug-resistant cultured tumor cell lines as experimental models. To date, there has been no report on the detailed characterization of such a cell line from renal cell carcinoma (RCC). By long-term exposure of an established RCC (RCC8701) to increasing concentrations of adriamycin, we established a series of subcultures that were considerably more resistant to the cytotoxic effect of this drug. Biological morphology and cell cycles were analyzed by morphometry and flow cytometry. The chemoresistance index of cells were measured by methyl tetrazolium assay. For evaluation of the expression of MDR-related protein (MRP), mdr-1, glutathione transferase (GST-pi), and topoisomerase II mRNAs, the reverse transcription-polymerase chain reaction was used. Membranous expression of mdr-1-related p-glycoprotein was analyzed by immunofluorescence cytometry. The intracellular content of both glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were measured using a capillary electrophoresis method. Compared with parent cells, the resistant sublines had a slower growth rate and lower confluent density. They were smaller and mixed with giant cells in different sizes and with different numbers of nucleoli. Flow cytometric analyses showed that resistant cells had a greater percentage of cells in the G2/M phase. The resistant cells, RCC8701/ADR800, were 122 times more resistant to adriamycin and 238 times more resistant to epirubicin than the parent cells. The resistant cells also demonstrated cross-resistance to cisplatin and 5-fluorouracil. In addition to MRP, the contents of mRNA coding for mdr-1, GST-pi, and topoisomerase II in the MDR sublines were higher than in the native cell line. A higher content of cytoplasmic GSH and G-6-PDH were found in the resistant cells; however, the expression of the MDR-related membranous glycoprotein, p-glycoprotein, was not raised. The adriamycin-induced MDR sublines may be used as an experimental system for the search of a means to overcome drug resistance and elucidate possible mechanisms of acquired MDR involved in human renal cancer.
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PMID:Establishment and characterization of renal cell carcinoma cell lines with multidrug resistance. 1085 Jun 29

Analysis of epidemiological, cohort and randomized studies of antihypertensive drugs containing reports of development of malignant neoplasms shows that long term use of some antihypertensive drugs while preventing cardiovascular complications has been associated with increased risk of malignancies. Most convincing evidence exists for association between the use of diuretics and renal cancer. Association between the use of reserpine and breast cancer in women, between atenolol and some types of cancer in elderly men also can not be ruled out. There is no proof of existence of either negative or positive correlation between malignant neoplasia and long-term use of calcium antagonists, angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
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PMID:[Antihypertensive drugs and malignant neoplasia]. 1249 52

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.
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PMID:Future direction of renal positron emission tomography. 1635 95