Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial injury results in exposure of medial smooth muscle cells and adventitial fibroblasts to multiple growth factors that bind to specific cell surface receptors. These in turn activate second messengers and induce expression of immediate-early genes within minutes to hours after ligand binding to the receptor. Activation of the immediate-early genes results in passage of the stimulated cell from its nonproliferating, quiescent G0 state to the first phase of the cell cycle (G1). Coordination of the events that occur during the cell cycle is effected by a series of cyclin-dependent kinases and requires inactivation of several "tumor suppressor genes," including p53, p21, p16, p15, p27, and the retinoblastoma gene Rb, that inhibit the kinase activity of the cyclin/Cdk complexes. An understanding of the factors that regulate signal transduction, cell cycle progression, and programmed cell death has suggested several novel therapeutic strategies including (1) antisense oligonucleotide inhibition of proto-oncogene expression, (2) the use of molecular decoys or pharmacological therapies to block specific steps required for cell cycle progression, and (3) gene transfer of tumor suppressor genes. The apparent success of several of these strategies in animal models of restenosis suggests that these molecular therapies may play a valuable role in preventing intimal hyperplasia and restenosis after balloon angioplasty and vascular stenting.
Prog Cardiovasc Dis
PMID:The role of proto-oncogenes in coronary restenosis. 932 28

The number of mutant p53 protein-positive tumor cells in primary non-small cell lung carcinoma (NSCLC) cases were quantitated by flow cytometry (FCM) and the relationships of these data to various factors were evaluated. Furthermore, the method of quantitating telomerase activity was investigated. Forty patients with primary lung carcinoma encountered between December 1995 and December 1997 were investigated. Among these cases, telomerase activity was measured. Using PAb421, cells were reacted with fluorescent antibody and fluorescence was quantitated by FCM. Fluorescence index (FI) was estimated in relation to the positivity rates of negative controls and were quantitatively evaluated. FI values of normal lung tissue were obtained from normal lung tissue excised from young patients with pulmonary bulla. Values that were 2SD or more above the mean value of normal lung tissue (> 2.19) were regarded as mutant p53-positive, and 14 (35.0%) of 40 lung carcinoma cases were positive by this criterion. Of 13 poorly differentiated carcinoma cases, seven cases (53.8%) were positive, which was significantly high. Furthermore, the telomerase activity was converted to numerical values in 40 cases using the telomelic repeat amplication protocol (TRAP) method as well as the total product generated (TPG) method. The mean TPG value of the 40 cases was 75.21 +/- 15.63. Among these cases, the mean value of fourteen p53-positive cases was 124.49 +/- 37.19, which was higher than that of 26 negative cases, 48.68 +/- 10.88, showing a significant difference. The method used in this study was considered a useful method that allows accurate and objective evaluation of mutant p53 expression. It was suggested that mutant p53 expression may affect the degree of tumor cell differentiation. Consequently, it was confirmed in this study that mutant p53 expression and telomerase activity were closely associated in lung cancer.
Ann Thorac Cardiovasc Surg 1999 Oct
PMID:Analysis of mutant p53 and telomerase activity in non-small cell lung cancer. 1055 Jul 14

Apoptosis and proliferation of myocytes were studied in human heart failure (HF). Endomyocardial samples from the right ventricle of 38 patients with terminal HF were compared with 10 traffic accident victims without a history of cardiovascular disease. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of p53, bcl-2, proliferation cell nuclear antigen (PCNA), and proliferation marker MIB-1. Apoptosis of cardiomyocytes, which was not p53-dependent, was present in 0.07 % of myocytes in HF, whereas no apoptotic myocytes were found in the control group (p < 0.01). An increased expression of bcl-2 was found in HF compared to controls (p < 0.01), yet bcl-2 failed to protect myocytes from apoptosis. Increased expression of proliferation markers was found in myocytes in HF compared to controls (PCNA labeling: 3.7% vs. 1.2%, p < 0.01; MIB-1 labeling: 0.1% vs. 0%, p< 0.01). Nevertheless, no mitotic figures in cardiomyocytes were found in our specimens. The volume density of interstitium was 22% in HF vs. 10% in the control group (p < 0.01). In conclusion, apoptosis of cardiomyocytes and fibrosis play an important role in HF, whereas clinical importance and the rate of myocyte proliferation remain to be determined.
Cardiovasc Pathol
PMID:Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies. 1098 14

This study aimed to investigate the features of cell death occurring in aortocoronary saphenous vein bypass grafts. Human aortocoronary saphenous vein bypass grafts with angiographic luminal stenosis of > 75% were explanted from 14 patients at redo coronary artery bypass grafting. Proteins associated with apoptotic pathways were identified immunohistochemically using antibodies to Bcl-2, Fas, BAX, p53 and CPP32. Cells undergoing DNA fragmentation were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). DNA synthesis was investigated using the antibody to proliferating cell nuclear antigen (PCNA). Ultrastructural features of cell death were examined by electron microscopy. Anti-apoptotic (Bcl-2) and pro-apoptotic (Bax, p53, CPP32 and Fas) proteins were expressed throughout the graft wall, but marked differences in the characteristics of cell death were noted between atherosclerotic and non-atherosclerotic areas of the intima. In atherosclerotic areas, pro-apoptotic proteins were widely expressed, but ultrastructural analysis failed to identify cells showing typical features of apoptosis. In these areas, necrotic cells were frequently observed, with negative correlation of Bcl-2 expression with TUNEL. Pro-apoptotic proteins showed no correlation with TUNEL. In contrast, in non-atherosclerotic areas of vein grafts, the expression of both anti-apoptotic (Bcl-2) and pro-apoptotic proteins (p53, Bax and CPP32) correlated with TUNEL. In atherosclerotic areas, non-atherosclerotic intimal areas, and in the underlying media, the numbers of TUNEL+ cells correlated with PCNA positivity. Ultrastructurally, apoptotic bodies and features of necrosis were observed in non-atherosclerotic areas of grafts. The present observations indicate that in atherosclerotic areas, cell death occurs mainly by necrosis, while in non-atherosclerotic areas, cell death occurs by both necrosis and apoptosis. An imbalance between DNA fragmentation and DNA synthesis may contribute to graft instability and failure.
Cardiovasc Surg 2001 Aug
PMID:Expression of apoptosis-related proteins and structural features of cell death in explanted aortocoronary saphenous vein bypass grafts. 1142 Jan 55

Lung cancer with a solitary metastasis to the stomach occurred in a 65-year-old man, surgically treated for gastric metastasis was followed by pulmonary resection. The gastric metastasis accompanied by upper gastrointestinal hemorrhage. After total gastrectomy to control this hemorrhage, a left lower lobectomy with a partial resection of the lingular segment and combined resection of the chest wall were done. Histopathological features of both the primary tumor in the left lower lobe and the gastric tumor were poorly differentiated adenocarcinoma, and showed the same immunoreactivities of p53 protein, carcinoembryonic antigen and keratin. These results indicate that the gastric tumor was a metastasis originated from the lung cancer.
Ann Thorac Cardiovasc Surg 2001 Jun
PMID:Lung cancer with p53 expression and a solitary metastasis to the stomach: a case report. 1148 Oct 23

From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.
Asian Cardiovasc Thorac Ann 2002 Mar
PMID:Cardiac myxoma and myxosarcoma: clinical experience and immunohistochemistry. 1207 62

Although the understanding of how toxicants alter cardiac ion-channel function has matured rapidly over the past 20-30 yr, little is known about how xenobiotics may alter the signaling pathways of cardiac myocyte growth and death. Signaling molecules and pathways responsible for the growth of cardiac myocytes include the mitogen-activated protein kinases (MAPKs), janus kinase-signal transducer and activator of transcription (JAK-STATs), nuclear receptor signaling, calcineurin, and the mobilization of free calcium. Signaling molecules and pathways responsible for programmed cardiac myocyte death include the death receptors, mitochondrial proteins, p53 tumor suppressor protein, ceramide signaling, and caspases. Overlap or "crosstalk" between the various growth and death pathways in the myocardium is evident, and these pathways likely exist in a delicate balance where, for example, slight reductions in growth signaling may favor pathways leading to cardiac myocyte apoptosis. Several classical cardiotoxicants are now known to alter signaling pathways in cardiac myocytes; however, the significance of these effects is not entirely clear. Furthermore, xenobiotics that alter the interstitium or extracellular matrix, or both, may significantly alter signaling pathways in cardiac myocytes. The goal of this review is to summarize current findings regarding the interaction of xenobiotics with myocardial signal transduction pathways in the hope of stimulating new insights and highlighting important areas for future research.
Cardiovasc Toxicol 2002
PMID:Interaction of xenobiotics with myocardial signal transduction pathways. 1218 77

Widespread external and internal changes in body morphology have long been known to be hallmarks of the process of metamorphosis. However, more subtle changes, particularly at the molecular level, are only now beginning to be understood. A number of transcription factors have recently been shown to alter expression either in levels of message or in isoforms expressed. In this article, we describe a dramatic increase in the expression of the homeobox gene HoxA5 in the heart and aorta of the Mexican axolotl Ambystoma mexicanum during the process of thyroxin-induced metamorphosis. Immunohistochemical analysis with anti-HoxA5 antibody in thyroxin-induced metamorphosing animals showed a pattern of expression of HoxA5 comparable to that in spontaneously metamorphosing animals. Further, by in situ hybridization, we were able to show significant qualitative differences in the expression of this gene within the heart. Maximum HoxA5 expression occurred at the midpoint of metamorphosis in the myocardium, whereas the hearts of completely metamorphosed animals had the highest levels of expression in the epicardium and endocardium. In the aorta, smooth-muscle cells of the tunica media as well as cells of the tunica adventitia had an increase in expression of HoxA5 with thyroxin-induced metamorphosis. HoxA5 expression significantly changed in cells of the aorta and ventricle with treatment by thyroid hormone. HoxA5, a positive regulator of p53, may be involved with the apoptotic pathway in heart remodeling during amphibian metamorphosis.
Cardiovasc Toxicol 2001
PMID:Expression of HoxA5 in the heart is upregulated during thyroxin-induced metamorphosis of the Mexican axolotl (Ambystoma mexicanum). 1221 75

Benign fibrous histiocytoma of the trachea is a rare neoplasm. We reported 2 cases, one aged 3 years and one 5 years, with endotracheal fibrous histiocytoma showing no clinical evidence of malignancy. Two segments of the trachea were resected and an end-to-end anastomosis was done in 1 case and circular resection of the left bronchi and carinoplasty for the other. Pathologically, both tumors consisted of spindle cells arranged in storiform and fascicular patterns. Immunohistochemically, tumor cells stained for vimentin and CD68 but were negative for P53. These cellular features and immunohistochemical findings indicate benign fibrous histiocytoma of the trachea. No recurrence was seen.
Jpn J Thorac Cardiovasc Surg 2002 Nov
PMID:Benign fibrous histiocytoma of the trachea. 1247 73

Cigarette smoking as an addictive habit has accompanied human beings for more than 4 centuries. It is also one of the most potent and prevalent environmental health risks human beings are exposed to, and it is responsible for more than 1000 deaths each day in the United States. With recent research progress, it becomes clear that cigarette smoking can cause almost all major diseases prevalent today, such as cancer or heart disease. These detrimental effects are not only present in active smokers who choose the risk, but also to innocent bystanders, as passive smokers, who are exposed to cigarettes not-by-choice. While the cigarette-induced harm to human health is indiscriminate and severe, the degree of damage also varies from individual to individual. This intersubject variability in cigarette-induced pathologies is partly mediated by genetic variants of genes that may participate in detoxification process, eg, cytochrome P450 (CYP), cellular susceptibility to toxins, such as p53, or disease development. Through population studies, we have learned that certain CYP1A1 variants, such as Mspl polymorphism, may render the carriers more susceptible to cigarette-induced lung cancer or severe coronary atherosclerosis. The endothelial nitric oxide synthase intron 4 rare allele homozygotes are more likely to have myocardial infarction if they also smoke. In vitro experimental approach has further demonstrated that cigarettes may specifically regulate these genes in genotype-dependent fashion. While we still know little about genetic basis and molecular pathways for cigarette-induced pathological changes, understanding these mechanisms will be of great value in designing strategies to further reduce smoking in targeted populations, and to implement more effective measures in prevention and treatment of cigarette-induced diseases.
Prog Cardiovasc Dis
PMID:Genetic influence on cigarette-induced cardiovascular disease. 1270 94


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