Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. We used immunohistochemistry to study the expression of E-cad in 50 adenoid cystic carcinomas (ACCs) in salivary glands to evaluate correlations with clinicopathologic parameters and patient survival. Absent or low E-cad expression was observed more frequently in solid than in cribriform or tubular carcinomas. E-cad expression also was significantly correlated with histologic grade and the growth pattern. In addition, ACCs showing low or absent E-cad expression were more frequently larger than 4 cm in diameter, and distant metastases developed more frequently. Reduced expression correlated with shorter disease-free intervals and actuarial survival rates. Univariate and multivariate analysis identified tumor stage and E-cad expression as the only 2 parameters predictive of the disease-free interval. E-cad expression and tumor stage, grade, and type of growth were significant prognostic factors for survival in univariate analysis, while tumor stage, type of growth, and E-cad expression were the only significant covariates in multivariate analysis. These findings indicate that the loss of E-cad has an important role in the natural history of ACC, as it is associated with loss of differentiation and development of metastases. We also provide evidence that E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC, together with clinical stage and type of growth at the periphery of the tumor.
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PMID:Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity. 989 53

The guidelines for publishing economic evaluations require a statement of the economic importance of the analysis and the viewpoint from which it has been carried out, as well as specification of at least two alternative programmes or interventions, the form of economic evaluation, the outcome measure, the method of costing, the time horizon and adjustment for timing of costs and benefits (e.g. by a discount factor), and the allowance for uncertainties (e.g. by implementation of a sensitivity analysis). The decision analysis can be based on clinical trial data, on retrospective or administrative databases, or on modelling. The choice of outcome measures is the key issue in an economic evaluation. In cost-effectiveness analysis, benefits are usually measured in natural units. This is the form of economic evaluation most frequently used in nuclear medicine. Endpoints of effectiveness applied in studies in this field have been procedures avoided, procedures initiated, cardiac events, survival probability, morbidity, quality of life and protracted or failed surgical procedures. In other instances, surrogate endpoints have been used such as metastases detected, staging, viability or tumour response. This, however, limits comparability of cost-effectiveness considerably, as proof of a change in the health outcome cannot be obtained. Measures of utility such as QALYs (quality-adjusted life years) have so far only been applied for decision tree analysis. Useful examples of economic evaluation studies in nuclear medicine are presented here for fluorodeoxyglucose positron emission tomography (FDG-PET) in the preoperative staging of non-small cell lung cancer, for FDG-PET in differentiating indeterminate solitary pulmonary nodules, for somatostatin receptor scintigraphy in detecting metastases of carcinoid tumours, for routine preoperative scintigraphy with sestamibi in patients with parathyroid adenoma, for periodic measurement of thyroid-stimulating hormone in detecting mild thyroid failure, for diagnostic algorithms including a lung scan in patients with suspected pulmonary embolism, for myocardial perfusion imaging as an incremental prognostic factor in patients with coronary artery disease, and for the use of radioiodine as first-line therapy of Graves' hyperthyroidism and of toxic nodular goitres. Further evaluations of effectiveness or utility should be carried out within a multidisciplinary framework to ensure that nuclear medical procedures are included in the general management guidelines.
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PMID:Economic evaluation studies in nuclear medicine: the need for standardization. 1036 54

In-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.
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PMID:Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody. 1059 8

PET and SPECT are molecular imaging techniques that use radiolabeled molecules to image molecular interactions of biological processes in vivo. PET imaging technologies have been developed to provide a pathway to the patient from the experimental paradigms of biological and pharmaceutical sciences in genetically engineered and tissue transplanted mouse models of disease. PET provides a novel way for molecular therapies and molecular diagnostics to come together in the discovery of molecules that can be used in low mass amounts to image the function of a target and, by elevating the mass, to pharmacologically modify the function of the target. In both cases, the molecules are the same or analogs of each other. PET can be used to titrate drugs to their sites of action within organ systems in vivo and to assay biological outcomes of the processes being modified in the mouse and the patient. The goal is to provide a novel way to improve the rates of discovery and approval of radiopharmaceuticals and pharmaceuticals. Extending this relationship into clinical practice can improve drug use by providing molecular diagnostics in concert with molecular therapeutics. Diseases are biological processes, and molecular imaging with PET is sensitive and informative to these processes. This sensitivity is exemplified by the detection of disease with PET without evidence of anatomic changes on CT and MRI. These biological changes are seen early in the course of disease, even in asymptomatic stages, as illustrated by the metabolic abnormalities detected with PET and FDG in Huntington's and familial Alzheimer's diseases 7 and 5 y, respectively, before symptoms appear. Differentiation of viable from nonviable tissue is fundamentally a metabolic question, as shown by the use of PET to differentiate patients with coronary artery disease who will benefit from revascularization from those who will not. Although beginning within a specific organ, cancer is a systemic disease the most devastating consequences of which result from metastases. Whole-body PET imaging with FDG enables inspection of glucose metabolism in all organ systems in a single examination to improve the detection and staging of cancer, selection of therapy, and assessment of therapeutic response. In lung and colorectal cancers, melanoma, and lymphoma, PET FDG improves the accuracy of detection and staging from 8% to 43% over conventional work-ups and results in treatment changes in 20%-40% of the patients, depending on the clinical question. Approximately 65% are upstaged because unsuspected metastases are detected, and 35% are downstaged because a structural diagnosis of lesions is changed from malignant to benign. Similar results are now being shown for other cancers. The main difference between CT, sonography, MRI, and PET or SPECT is not technologic but, rather, a difference between detecting and characterizing a disease by its anatomic features as opposed to its biology. The importance and success of developing new molecular imaging probes is increasing as PET becomes integral to the study of the integrative mammalian biology of disease and as molecular therapies targeting the biological processes of disease are developed.
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PMID:PET: the merging of biology and imaging into molecular imaging. 1076 68

Although a considerable amount of effort has been placed on discovering the etiologies of cancer, the majority of the basic cancer research existing today has focused on understanding the molecular mechanism of tumor formation and metastasis. Metastatic spread of tumors continues to be a major obstacle to successful treatment of malignant tumors. Approximately 30% of those patients diagnosed with a solid tumor have a clinically detectable metastasis and for the remaining 70%, metastases are continually being formed throughout the life of the tumor. Even after the tumor is excised, the threat of death is attributable to the metastasis that may occur through the remaining tumor cells. In addition, treating the metastasis often proves futile since metastasis often vary in size, composition, and anatomical location. New treatments blocking the formation of metastasis will provide greater chances of survival for cancer patients. One family of enzymes that has been shown over the years to play a role in tumor progression is the matrix metalloproteinase (MMP) family. The main function of MMPs, also known as matrixins, is degradation of the extracellular matrix physiologic function involving MMPs include wound healing, bone resorption and mammary involution. MMPs, however, also contribute to pathological conditions including rheumatoid arthritis, coronary artery disease, and cancer. Tumor cells are believed to utilize the matrix degrading capability of these enzymes to spread to distant sites. In addition, MMPs also are thought to promote the growth of these tumor cells once they have metastasized. This review will discuss the role of MMPs and their inhibitors in tumor invasion, angiogenesis and metastasis with special emphasis on the gelatinases, MMP-2 and MMP-9.
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PMID:The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. 1134 15

Inflammatory breast carcinoma (IBC) is characterized by florid tumor emboli within lymphovascular spaces termed lymphovascular invasion (LVI). Using a human-scid model of IBC (MARY-X), we have demonstrated using retrovirally-mediated dominant-negative E-cadherin mutant approaches (H-2K(d)-E-cad), that the tumor cell embolus (IBC spheroid) forms on the basis of an intact and overexpressed E-cadherin/alpha, beta-catenin axis which mediates tumor cell-tumor cell adhesion analogous to the embryonic blastocyst and accounts for the compactness of the embolus. The tumor cell embolus (IBC spheroid), in contrast, fails to bind the surrounding vascular endothelial cells both in vitro and in vivo because of markedly decreased sialyl-Lewis X/A carbohydrate ligand-binding epitopes on its overexpressed MUC1 which are necessary for binding endothelial cell E-selectin. This tumor cell-endothelial cell aversion further contributes to the compactness of the IBC spheroid and its passivity in metastasis dissemination. This passivity is manifested by a dramatic increase in metastatic pulmonary emboli following palpation of the primary tumor. In assessing this passivity of metastatic dissemination, we compared the effects of palpation on MARY-X with the effects of palpation on a derived dominant-negative E-cadherin mutant (H-2K(d)-E-cad), as well as other well known human tumoral xenografts exhibiting no (MCF-7, T47D), low (MDA-MB-231, MDA-MB-468) or high (C8161, M24(met)) levels of spontaneous metastasis but no LVI. Palpation of each xenograft similarly increased intratumoral pressure by 200% (10-->30 mmHg) but dramatically increased the numbers and sizes of pulmonary metastases 10-100-fold (P<0.001) only in MARY-X. The mechanism of this effect was through an immediate post-palpation release of circulating tumor emboli detected 2-3 min after palpation (P<0.01) by human cytokeratin 19 RT-PCR of extracted RNA from 300 microl of murine blood. Although circulating human tumor cell-derived growth factors (IGF-I, IGF-II, TGF-alpha and TGF-beta) and angiogenic factors (VEGF and bFGF) were detected by ELISA in murine serum of MARY-X, palpation did not further increase the circulating levels of these factors (P>0.1). Our findings support the cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in IBC.
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PMID:Cooperative role of E-cadherin and sialyl-Lewis X/A-deficient MUC1 in the passive dissemination of tumor emboli in inflammatory breast carcinoma. 1203 65

The aim of this study was to define whether or not the impaired expression of CD44, E-cadherin (E-cad), and beta-catenin (beta-cat) correlates with the clinical evolution and prognosis of oral cancer. Ninety-three primary oral squamous cell carcinomas (OSCCs) with tumour-adjacent normal and/or dysplastic mucosa, 30 associated metastases, and 12 recurrences were immunostained for CD44s, -v3, -v4, -v5, -v6, -v7, -v9, E-cad, and beta-cat. In non-neoplastic epithelium, all molecules investigated were constitutively expressed in the basal layers. In the majority of dysplasias, immunoreactivity for all adhesion molecules was increased, but there was restricted loss for CD44s, E-cad, and beta-cat in a few cases. In carcinomas, a striking accumulation of CD44s, v3, v4, v9 and a loss of E-cad/beta-cat were observed at the invasive tumour front. In metastases and recurrences, besides a loss of CD44s, v4, v7, and E-cad, a significant increase of v9 was recorded, whereas CD44v5 and v6 remained unchanged. Clinically, reduced expression of CD44v3, E-cad, and changes of CD44v9 phenotype within the primary tumours correlated significantly with poor prognosis; decreased beta-cat expression was a predictive marker for nodal metastases. These findings indicate that there is some perturbed expression of adhesion molecules during the stepwise course of oral carcinogenesis and tumour progression. Distinct phenotypic alterations project poor prognosis, while others predict metastasis. Some of these restricted molecular changes may serve as potential targets for future antibody-based tumour therapy.
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PMID:Gains and losses of adhesion molecules (CD44, E-cadherin, and beta-catenin) during oral carcinogenesis and tumour progression. 1237 67

Coronary artery ectasia (CAE) is a rare form of coronary artery disease. It has previously been shown that nitrate derivatives induce exertional angina in patients with CAE. Furthermore, there is limited data about the effects of other anti-ischemic agents in CAE. The aim of this study was to investigate the effect of trimetazidine on exercise performance in patients with CAE. The study population consisted of 56 patients with isolated CAE (32 males, mean age: 58 +/- 9 years). The presence of myocardial ischemia was evaluated by treadmill exercise test. The exercise test was positive in 49 patients at baseline and in 27 patients during trimetazidine therapy (P < 0.01). The exercise test induced angina in all of the patients who have had a positive test result. Significant ST depressions were observed in 42 and 23 patients before and after the treatment, respectively (P < 0.01). The extent of ST depression at peak exercise was significantly lower on trimetazidine (0.9 +/- 0.5 vs 1.5 +/- 0.6 mm, P < 0.01). With trimetazidine, the exercise duration increased from 7.8 +/- 2.1 to 8.7 +/- 2.4 min (P = 0.04) and cardiac work-load also increased from 8.9 +/- 2.3 to 10.4 +/- 2.1 mets (P < 0.01). The results suggest that trimetazidine can relieve exercise-induced angina and improve exercise performance in patients with CAE.
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PMID:Effect of trimetazidine on exercise performance in patients with coronary artery ectasia. 1290 28

Cardiac disease may occur as direct complications of heart tumors or indirect complications of malignancies related to antineoplastic therapy. While primary cardiac neoplasias are rare, metastases to various cardiac structures are common. Cardiac tumors may cause a wide variety of clinical signs and symptoms. Benign myxomas are the most common primary tumors and often can be cured by total excision. Nearly all primary cardiac malignancies are sarcomas with a poor prognosis. The cardiotoxicity of anticancer agents can lead to significant complications that can affect patients being treated for various noncardiac neoplasias. Cancer treatment, most frequently anthracyclines, but also trastuzumab, cyclophosphamide and others may compromise cardiac function. The severity of such toxicity depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, the presence of any underlying cardiac condition, and the patient's demographics. Moreover, toxicity can be affected by current or previous treatment with other antineoplastic agents or by concomitant irrradiation. Cardiotoxic effects can occur immediately during administration of the drug, or they may not manifest themselves until months or years after the patient has been treated. Radiation ports that include the heart may produce late coronary artery disease or constrictive pericarditis. Since cardiovascular disease and cancer are both common, precise knowledge of therapeutic interactions and complications is warranted.
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PMID:[Cardiac disease in patients with tumors and tumor therapy]. 1680 15

Rheumatoid arthritis (RA) is a chronic disabling autoimmune inflammatory disease of unknown aetiology with a prevalence of about 1% in most parts of the world. As a result of the debilitating nature of the disease, sufferers struggle with the simple activities of daily living and frequently fail to remain in full time employment. Furthermore, the mortality associated with the disease is equivalent to that seen in triple vessel coronary artery disease. Over the 10-15 years, advances in understanding the mechanisms of RA pathogenesis based on studies of human cells and animal models of arthritis have led to the identification of new targets for therapeutic intervention. Despite these advances, a significant proportion of patients continue to exhibit disease which is refractory to such therapy. As an alternative to anti-cytokine therapy, formation of new blood vessels ('angiogenesis') represents a potentially attractive target for therapy in RA. Angiogenesis has been a putative target in cancer since it was first linked to tumour growth and metastases in the 1970s. A number of significant advances have been made in the development of anti-cancer therapy using such an approach. This review focuses on the potential for targeting angiogenesis in RA, building upon the experience of angiogenesis inhibition in the oncological setting. Through this we hope to emphasise the potential value of anti-angiogenic therapy in RA and identify future directions for optimising treatment of this disabling disease.
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PMID:Angiogenesis as a therapeutic target in arthritis: lessons from oncology. 1684 63


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