Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past 7 years, single photon emission computed tomography (SPECT) has evolved from an interesting nuclear medicine technique rarely performed because of technical difficulties into a valuable clinical tool in the management of cancer cases. The development of stable multidetector instruments with collimators and gantries specifically designed for SPECT and the introduction of new radiopharmaceuticals recently approved by the U.S. Food and Drug Administration have rapidly moved SPECT from the field of clinical investigation to clinical practice. SPECT is a valuable addition to other tomographic modalities capable of displaying the physiology of disease as well as anatomy. In this work the authors describe the role of SPECT in a cancer center and, in particular, how they use it to solve clinical problems. They also review the published literature, when appropriate. The authors have found SPECT of particular value in evaluation of myocardial ischemia, in differentiating tumor recurrence from posttherapy changes in the lymphomas, in tumor diagnosis and surveillance, and in separating hemangioma from malignant lesions in the liver.
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PMID:SPECT in the evaluation of cancer patients: not quo vadis; rather, ibi fere summus. 156 25

This paper presents an arteriovenous hemangioma of the interventricular septum in a patient with symptoms of ischemic heart disease. The MR, two-dimensional echocardiographic and selective left coronary arteriographic characteristics of the lesion are described.
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PMID:MR appearance of an arteriovenous hemangioma of the interventricular septum. 314 3

Clinical trials of cardiovascular gene therapy, whether using viral (53%) or nonviral (47%) vectors, have thus far disclosed no evidence indicative of inflammatory or other complications, including death, directly attributable to the vector used. Indeed, despite the fact that initial trials of cardiovascular gene therapy targeted patients with end-stage vascular disease, including critical limb ischemia and refractory myocardial ischemia, the mortality for patients enrolled in clinical trials of cardiovascular gene therapy reported to date compares favorably with mortality for similar groups of patients in contemporary controlled studies of medical or interventional therapies. The most common morbidity reported after cardiovascular gene transfer is lower extremity edema; in contrast to data involving genetically engineered mice, however, evidence of life- or limb-threatening edema has not been described in any patients, including patients after gene transfer for myocardial ischemia. Concerns regarding the potential for angiogenic cytokines to promote the progression of atherosclerosis are not supported by angiographic follow-up of patients with coronary or peripheral vascular disease. The levels and duration of gene expression investigated for therapeutic angiogenesis transfer have been unassociated with hemangioma formation. Likewise, there is little evidence from either preclinical or clinical studies to support the notion that the administration of angiogenic growth factors, per se, is sufficient to stimulate the growth of neoplasms. Patients enrolled in clinical studies of angiogenic cytokines, including patients with diabetes and a previous history of retinopathy, have disclosed no evidence to suggest that ocular pathology is a risk of angiogenic growth factor gene transfer.
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PMID:Assessment of risks associated with cardiovascular gene therapy in human subjects. 1153 99

Intramyocardial injection of genes encoding angiogenic factors could provide a useful approach for the treatment of ischemic heart disease. However, uncontrolled expression of angiogenic factors in vivo may cause some unwanted side effects, such as hemangioma formation, retinopathy, and arthritis. It may also induce occult tumor growth and artherosclerotic plaque progression. Because hypoxia-inducible factor 1 is up-regulated in a variety of hypoxic conditions and it regulates gene expression by binding to a cis-acting hypoxia-responsive element (HRE), we propose to use HRE, found in the 3' end of the erythropoietin gene to control gene expression in ischemic myocardium. A concatemer of nine copies of the consensus sequence of HRE isolated from the erythropoietin enhancer was used to mediate hypoxia induction. We constructed two adeno-associated viral vectors in which LacZ and vascular endothelial growth factor (VEGF) expressions were controlled by this HRE concatemer and a minimal simian virus 40 promoter. Both LacZ and VEGF expression were induced by hypoxia and/or anoxia in several cell lines transduced with these vectors. The functions of these vectors in ischemic myocardium were tested by injecting them into normal and ischemic mouse myocardium created by occlusion of the left anterior descending coronary artery. The expression of LacZ gene was induced eight times and of VEGF 20 times in ischemic myocardium compared with normal myocardium after the viral vector transduction. Hence, HRE is a good candidate for the control of angiogenic factor gene expression in ischemic myocardium.
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PMID:Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model. 1208 14

Angiogenic gene therapy for stable angina is aimed at promoting new blood vessel formation in the heart, thus providing enhanced cardiac perfusion, symptom relief, increased exercise capacity, improved quality of life, and reduced risk of coronary events. Ad5FGF-4 is a replication-deficient serotype 5 adenovirus encoding the gene for fibroblast growth factor-4 (FGF-4) driven by a cytomegalovirus promoter. In preclinical studies using a pig model of myocardial ischemia, a single intracoronary infusion of Ad5FGF-4 improved cardiac contractile function and regional blood flow in the ischemic region during stress. These effects were apparent after 2 weeks and maintained for > or =12 weeks. Histologic evidence of capillary angiogenesis was observed. FGF-4 gene expression was detected in the heart but not at extracardiac sites. Placebo-controlled trials in humans with chronic stable angina indicate that Ad5FGF-4 increases treadmill exercise duration and improves stress-related ischemia measured by perfusion sestamibi single-photon emission computed tomography. More patients receiving Ad5FGF-4 than placebo reported complete resolution of their angina and no nitroglycerin use. Ad5FGF-4 gene therapy was well tolerated. The administration procedure did not cause any adverse events, although mild, transient fever, a transient modest fall in platelet count, and a transient mild elevation in hepatic enzymes and uric acid levels occurred in a few patients. This adverse event profile concurs with other adenoviral gene trials. There was no evidence of myocarditis, retinal neovascularization, or angioma formation. FGF-4 was not detected in venous blood. Larger clinical trials will assess Ad5FGF-4 with regard to cardiovascular prognosis, symptom relief, and safety profile in patients with chronic stable angina.
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PMID:Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease. 1461 23

Neovascularization induced by vascular endothelial growth factor (VEGF) represents an appealing approach for treating ischemic heart disease. However, VEGF therapy has been associated with transient therapeutic effects and potential risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone marrow are a promising source for tissue regeneration and repair. In order to achieve a safe and persistent angiogenic effect, we have explored the potential of autologous MSCs transplantation to enhance angiogenesis and cardiac function of ischemic hearts. One week after myocardial infarction induced by occlusion of left anterior descending artery, autologous MSCs expanded in vitro was administrated intramyocardially into the infarct area of the same donor rats. By 2 months, MSCs implantation significantly elevated VEGF expression levels, accompanied by increased vascular density and regional blood flow in the infarct zone. The neovascularization resulted in a decreased apoptosis of hypertrophied myocytes and markedly improved the left ventricular contractility (ejection fraction: 79.9+/-7.6% vs. 37.2+/-6.9% in control animals). Therefore, mechanisms underlying MSCs improvement of cardiac functions may involve neovascularization induced by differentiation of MSCs to endothelial cells and para-secretion of growth factors, in addition to the apoptosis reduction and previously reported cardiomyocytes regeneration. Two months after cell transplantation, there are significant improvement of left ventricular function. Hence, autologous MSCs transplantation may represent a promising therapeutic strategy free of ethical concerns and immune rejection, for neovascularization in ischemic heart diseases.
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PMID:Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. 1468 95