Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective phase II study, 102 women with advanced breast cancer were treated with low doses of cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) at weekly intervals by intravenous injection. Seventy-five patients were evaluable for treatment response and the overall response rate was 52% (95% confidence interval, 41-63%). Of the evaluable patients, 15% had complete response and 37% had partial response. The median survival after therapy was 15.6 months, the median time to progression was 6.8 months and the median duration of response was 9.1 months. The main toxicities were mild vomiting and moderate myelosuppression. There was only 1 patient who experienced heart failure. Weekly CAF appears to have an efficacy with tolerable side effects comparable to standard CAF with an every-3-week schedule.
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PMID:Weekly CAF chemotherapy for advanced breast cancer patients. 921 53

This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival.
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PMID:[Bleomycin, adriamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma: long-term survival rate and complications]. 971 Oct 76

We describe a case of postoperative congestive heart failure in a young woman of physical class ASA 1, following breast cancer surgery. Preoperatively she had been treated with doxorubicin (Adriamycin) 450 mg.m-2, total dose, associated with breast and ovarian radiotherapy. This association was probably the cause of postoperative heart failure. Twenty-four hours after surgery, a two-dimensional echocardiography showed a severe left ventricular dysfunction, whereas preoperative clinical assessment was unremarkable. Doxorubicin cardiotoxicity can be acute, subacute and delayed as in our case. Clinical assessment and ECG are not sensitive indicators of such cardiac damage. Preoperative echography is the technique of choice for the evaluation of the cardiac status of a patient treated with a high cumulative dose of doxorubicin and mediastinal irradiation.
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PMID:[Acute cardiogenic postoperative edema after doxorubicin (adriamycin) chemotherapy]. 975 Jun 82

Doxorubicin is cardiotoxic and its use must be monitored carefully. Incidence of refractory cardiac failure is shown to increase once the cumulative dose exceeds 450 mg/m2. However, significant decline of ejection fraction (EF) may occur even at lower dose levels. EF was monitored using Multigated Radionuclide Angiography (MUGA) scan of all consecutive lung cancer patients, treated with Doxorubicin based regimens. Thirteen of 82 patients showed a significant (more than 15%) decline of left ventricular EF. The dose of doxorubicin producing this decline ranged between 91-180 mg/m2. Actual decline in EF ranged between 16-45%. Only 5 of 13 patients developed symptoms attributable to the cardiac disease. Doxorubicin can alter EF significantly in lung cancer patients at levels well below which are considered 'safe'. The reason for massive decline in ejection fraction in these patients has been hypothesized.
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PMID:Doxorubicin cardiomyopathy in lung cancer patients. 981 76

Cardiac toxicity is a major factor that limits the use of anthracyclines in cancer chemotherapy. Heart failure frequently develops in patients treated with doxorubicin (Adriamycin), when they receive a cumulative dose greater than 500 mg/m2. To make a mouse model for gene therapy designed to prevent this toxic effect, we have produced transgenic mice overexpressing the human cDNA for the multiple drug resistance (h-mdr1) gene driven by 2.12 kb of the 5' flanking region of the rat alpha-cardiac myosin (aCM) heavy chain gene. Two lines of transgenic mice expressed the transgene at a high level in heart muscle. Transgenic and control animals were treated with Adriamycin intravenously at either a single dose of 10 mg/kg or a cumulative dose of 30 mg/kg in three injections. Subsequent light and electron microscopic examination of heart tissue demonstrated degenerative changes in control mice that were absent in transgenic animals at both doses. These results show that expression of the alphaCM/h-mdr1 transgene in heart confers protection from the toxic effect of Adriamycin and suggest that such constructs, if employed effectively in cardiac gene therapy protocols, could allow a more aggressive use of anthracyclines in the treatment of cancer.
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PMID:Cardiac resistance to adriamycin in transgenic mice expressing a rat alpha-cardiac myosin heavy chain/human multiple drug resistance 1 fusion gene. 1036 58

Adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a variety of cancers, but its usefulness is seriously curtailed by the risk of developing heart failure. Available laboratory evidence suggests that an increase in oxidative stress, brought about by increased free radical production and decreased myocardial endogenous antioxidants, plays an important role in the pathogenesis of heart failure. Adriamycin-induced apoptosis and hyperlipidemia may also be involved in the process. Probucol, a lipid-lowering drug and an antioxidant, completely prevents the occurrence of heart failure by reducing oxidative stress as well as by the modulation of apoptosis and high lipid concentrations. Thus, combined therapy with adriamycin and probucol has a high potential for optimizing the treatment of cancer patients.
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PMID:Adriamycin-induced heart failure: mechanism and modulation. 1088 30

Beta-blockade consistently improves myocardial systolic function in patients with both nonischemic and ischemic cardiomyopathy. The effects of beta-blockade on Adriamycin-induced cardiomyopathy (ACM), however, are unknown. We retrospectively evaluated the effects of beta-blockade on patients with ACM by using a case-controlled design. The control group consisted of 16 consecutively chosen age- and sex-matched patients with idiopathic dilated cardiomyopathy (IDC) who were treated with beta-blockers. Patients with ACM had a baseline mean left ventricular ejection fraction (LVEF) of 28%, which improved to 41% (P = .041) after treatment with beta-blockers. The control group had a baseline mean LVEF of 26%, which improved to 32% (P = .015) after treatment. The mean duration of beta-blocker therapy in the Adriamycin and control groups was 8 and 9 months, respectively. The degree of improvement between the 2 groups was not significantly different. Beta-blockers have a beneficial effect on cardiac function in patients with ACM, which is at least comparable with other forms of heart failure with systolic dysfunction.
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PMID:Beta-blockade in adriamycin-induced cardiomyopathy. 1090 85

Doxorubicin, a broad-spectrum antitumor antibiotic, causes dose-dependent cardiomyopathy and heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving doxorubicin-induced superoxide anion production have been proposed. In this study, we show that bicarbonate, a physiologically relevant tissue component, greatly amplified doxorubicin-induced cardiomyocyte injury. Bicarbonate also enhanced inactivation of aconitase, a crucial tricarboxylic acid cycle enzyme, in cardiomyocytes exposed to doxorubicin. The cell-permeable superoxide dismutase mimetic, Mn(III)tetrakis (4-benzoic acid) porphyrin, reversed doxorubicin-induced cardiomyocyte injury. Bicarbonate enhanced the inactivation of purified mitochondrial aconitase in the xanthine/xanthine oxidase system, generating superoxide. The results suggest that bicarbonate amplifies the prooxidant effect of superoxide. Bicarbonate also caused an increased loading of cardiomyocytes with doxorubicin. We conclude that the bicarbonate-mediated increase in doxorubicin toxicity is due to increased intracellular loading of doxorubicin in cardiomyocytes and subsequent exacerbation of superoxide-mediated cardiomyocyte injury.
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PMID:Bicarbonate exacerbates oxidative injury induced by antitumor antibiotic doxorubicin in cardiomyocytes. 1104 80

The dose-dependent cardiomyopathy and heart failure due to adriamycin have been shown to be due to increased oxidative stress and loss of myocytes. We examined the incidence of myocardial apoptosis as well as changes in the expression of apoptotic regulatory gene products in an established animal model of adriamycin cardiomyopathy. Rats were treated with adriamycin (cumulative dose, 15 mg/kg), and the hearts were examined for apoptosis as well as expression of Bax, caspase 3, and Bcl-2 at 0, 4, 10, 16, and 21 days after the treatment. A significant increase in the incidence of apoptosis was seen at 4 days, followed by a decline at 10 and 16 days of posttreatment. At 21 days, the number of apoptotic cells increased again and included cells of the conducting system. Expression of Bax corresponded to these biphasic changes, whereas the converse was true for the expression of Bcl-2. The latter peaked at 10 days followed by a decline at 16 and 21 days. The Bax/Bcl-2 ratio also correlated with the incidence of apoptosis. Expression of caspase 3 correlated with increased apoptosis, but only at early time points. Probucol (cumulative dose, 120 mg/kg), a known antioxidant as well as promoter of endogenous antioxidants, significantly reduced the incidence of apoptosis as well as expression of Bax. Adriamycin-induced hemodynamic changes were also prevented by probucol. These data suggest that adriamycin-induced apoptosis is mediated by oxidative stress and may play a role in the development of heart failure.
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PMID:Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. 1129 92

We previously reported that cardiomyocytes produce endothelin (ET)-1 and that the tissue level of ET-1 markedly increased in failing hearts in rats with chronic heart failure. Because the level of plasma ET-1 also increased progressively in patients with breast cancer who received doxorubicin (Dox; Adriamycin), which possesses cardiotoxicity, we hypothesized that ET-1 plays a role in the pathophysiology of cardiomyocytes injured by Dox. In this study, we investigated the effect of ET-1 on the cytotoxicity of Dox in primary cultured neonatal rat cardiomyocytes. The results showed that ET-1 effectively attenuated Dox-induced acute cardiomyocyte cytotoxicity (24-h incubation with Dox) evaluated by in vitro cell toxicity assay [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase release]. The cytoprotective effect of ET-1 was mediated via ET(A) receptors, because pretreatment with the ET(A)-receptor antagonist BQ123 completely suppressed the cytoprotective effect of ET-1, whereas the ET(B)-receptor antagonist BQ788 did not. The cytoprotective effect of ET-1 was abolished by pretreatment with cycloheximide or staurosporine. These results suggest that a protein molecule(s), which is synthesized de novo by the stimulation of protein kinase pathway, is involved in the cytoprotective effect of ET-1. ET-1 increased the expression of an endogenous antioxidant, manganese superoxide dismutase (Mn-SOD), in the cardiomyocytes, as demonstrated by a Western blotting analysis. Pretreatment with an antisense oligodeoxyribonucleotide of Mn-SOD markedly attenuated the cytoprotective effect of ET-1 on the Dox-induced cytotoxicity. However, under conditions of prolonged incubation with Dox (48 h), ET-1 did not affect Dox-induced cardiomyocyte cytotoxicity in culture. These results suggest that ET-1 prevents the early phase of Dox-induced cytotoxicity via the upregulation of the antioxidant Mn-SOD through ET(A) receptors in cultured cardiomyocytes.
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PMID:A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes. 1129 60


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