Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 22 patients with different solid tumours refractory to previous chemotherapy were treated between May 1985 and December 1986 (osteosarcoma, 7; Wilms' tumour, 6; rhabdomyosarcoma, 2; Ewing's sarcoma, 2; non-Hodgkin's lymphoma, 2; retinoblastoma, 1; cavum lymphoepithelioma, 1; dyktioma, 1). Patients were aged between 3 and 20 years (mean, 10.6 years). There was a 3.4:1 male-to-female ratio. The treatment consisted of ifosfamide given i.v. as a single agent at a dose of 3,000 mg/m2 over 1 h on days 1 and 2. Mesna was given as a uroprotector at 600 mg/m2 every 4 h, up to a total of 13 doses. The courses were repeated every 3 weeks. Every patient except those with osteosarcoma had previously received cyclophosphamide. There were 3 (13.6%) complete responses (CRs) in 2 osteosarcomas and 1 abdominal non-Hodgkin's lymphoma, lasting 12, 8 and 2 months, respectively; 4 (18.2%) partial responses (PRs) in 2 Wilms' tumours, 1 Ewing's sarcoma and 1 abdominal non-Hodgkin's lymphoma; 4 absences of remission (ARs); and 11 (50%) cases of progressive disease (PD). In all, 81 courses were given, and the toxicities found were leukopenia (less than 2,000 leukocytes) in 15 courses, thrombocytopenia in 3, microhaematuria in 7, neurotoxicity in 8, fever in 8 and hypertension in 2. The overall response rate (31.8%) was encouraging and the toxicity, acceptable and reversible. These results demonstrate that ifosfamide should be considered for introduction into phase III protocols for the treatment of solid malignancies in children.
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PMID:Phase II study of ifosfamide as a single drug for relapsed paediatric patients. 250 55

We report 3 new cases of diffuse infiltrating retinoblastoma, and we review the 21 cases of the literature. Clinical features are typical but must not be confused with uveitis. The average age of onset is about 7 years, later than the usual retinoblastoma. Clinical features associate ocular redness, pseudo hypopion, iris nodules, clusters on the pupil and in the anterior chamber, opacities on the posterior face of the cornea. Hypertension appears resistant to medical treatment. The vitreous is hazy but the retina is still visible. The ophthalmoscopic examination reveals exudates covering the peripheric retina, and gray infiltrated retina. Usually there is no focal tumour mass, but totally diffuse tumoral infiltration. Echographic examination does not reveal calcification as in typical retinoblastoma. Neoplastic cells are demonstrated in anterior chamber paracentesis. Cytologic examination of aqueous humor aspirates may be misinterpreted and should be evaluated carefully. Because of tumor cells seeding, lactate dehydrogenase assay is of diagnostic value, prior to considering definitive therapy. None of the tumors were bilateral. The prognosis after enucleation appears good.
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PMID:[Diffuse infiltrating retinoblastoma]. 269 64

A 10-month-old boy who presented with strabismus and symptoms of intracranial hypertension was found to have a pineoblastoma and a unilateral ocular retinoblastoma. Despite enucleation of the eye, subtotal removal of the pineoblastoma, and craniospinal axis irradiation, the patient died 6 months later from disseminated intracranial neoplasm. As there was no clinical evidence of bilateral retinoblastoma, this case may represent a forme fruste of the trilateral retinoblastoma complex. The clinicopathological features of this unusual syndrome are reviewed.
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PMID:Concurrent pineoblastoma and unilateral retinoblastoma: a forme fruste of trilateral retinoblastoma? 404 65

Bilateral retinoblastoma was diagnosed in a 12-month-old boy. The left eye was enucleated; the choroid and the optic nerve were not invaded by the tumour. The right eye had three lesions: one was photocoagulated, and the other two were irradiated. Two years later, symptoms and signs of intracranial hypertension prompted computerized tomography, which demonstrated a mass in the pineal region and secondary hydrocephalus. The right eye showed papilledema but no evidence of tumour activity in the three retinal scars. Radiation therapy and chemotherapy had only a transient effect, and the child died at 42 months of age. At autopsy the pineal region and the third ventricle were found to be replaced by a pinealoblastoma with retinomatous differentiation. Only 11 other cases of pinealoblastoma associated with bilateral (heritable) retinoblastoma have been reported. The embryologic relationship between the pineal gland and the retina has given rise to the concept of trilateral retinoblastoma, a concept important in the investigation and follow-up of patients with bilateral retinoblastoma.
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PMID:Trilateral retinoblastoma: bilateral retinoblastoma with pinealoblastoma. 671 68

Although responsible for only approximately one-third of the overall myocardial mass, the interstitial fibroblasts of the heart serve a fundamental role in establishing the functional integrity of myocardium and are the major source of myocardial extracellular matrix production. Their importance in clinical medicine is underscored by the observation that fibroblast numbers increase in response to several pathologic circumstances that are associated with an increase in extracellular matrix production, such as long standing hypertension and myocardial injury/infarction. Up to the present time, however, there has been little information available on either the kinetics of the cardiac fibroblast cell cycle, or the fundamental mechanisms that regulate its entry into and exit from the cell cycle. Previous work from our laboratory examining the effects of interleukin (IL)-1beta on myocardial growth and gene expression in culture indicated that cardiac fibroblasts have a diminished capacity to synthesize DNA in response to mitogen in the presence of this cytokine. The mechanism of IL-1beta action was not clear, however, and could have resulted from action at several different points in the cell cycle. The investigations described in this report indicate that IL-1beta exerts its effect on the fibroblast cell cycle at multiple levels through altering the expression of cardiac fibroblast cyclins, cyclin-dependent kinases, and their inhibitors, which ultimately affect the phosphorylation of the retinoblastoma gene product.
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PMID:Cardiac fibroblasts arrest at the G1/S restriction point in response to interleukin (IL)-1beta. Evidence for IL-1beta-induced hypophosphorylation of the retinoblastoma protein. 974 52

Loss of activity of the p53 tumor suppressor gene product has been postulated in the pathogenesis of human restenosis. Although the antioncogenes p53 and retinoblastoma (Rb) susceptibility gene have been reported to play a pivotal role in cell cycle progression in various cells, the role of p53 and Rb in the growth of human vascular smooth muscle cells (VSMC) has not yet been clarified. We used antisense strategy against p53 and Rb genes by the viral envelope-liposomal method. Transfection of antisense p53 oligodeoxynucleotides (ODN) alone resulted in an increase in DNA synthesis compared with control (P<0.01). Similarly, transfection of antisense Rb ODN alone resulted in a higher DNA synthesis rate than control (P<0.01). Moreover, increase in VSMC number was only induced by transfection of antisense p53 ODN alone or cotransfection of p53/Rb ODN (P<0.01), whereas a single transfection of antisense Rb ODN had little effect on cell number. Therefore, we hypothesized that this discrepancy is due to the induction of apoptosis mediated by p53. Interestingly, apoptotic cells were markedly increased in VSMC transfected with antisense Rb ODN alone, accompanied by the induction of p53 protein. The number of apoptotic cells was attenuated by cotransfection of antisense p53 ODN (P<0.01). We finally examined the molecular mechanisms of apoptosis induced by the absence of Rb. In VSMC transfected with antisense Rb ODN, bax, a promoter of apoptosis, was significantly increased in VSMC transfected with antisense Rb ODN (P<0.01), whereas bcl-2 and Fas did not play a pivotal role in the induction of apoptosis. Overall, these data first demonstrated that the antioncogenes p53 and Rb negatively regulated the cell cycle in VSMC, suggesting that the modulation of their activity may mediate VSMC growth such as that in restenosis and atherosclerosis. The presence of p53 plays a pivotal role in the regulation of apoptosis in human VSMC growth, probably through the bax pathway. These results provide evidence that p53 is a functional link between cell growth and apoptosis in VSMC.
Hypertension 1999 Aug
PMID:Inhibition of the p53 tumor suppressor gene results in growth of human aortic vascular smooth muscle cells. Potential role of p53 in regulation of vascular smooth muscle cell growth. 1045 40

The classic dogma, still prevalent in cardiology, that the adult myocardium is a terminally differentiated tissue unable to produce new cardiomyocytes needs to be revised in light of recent results. In human and experimental animals there is now incontrovertible evidence that new myocytes are continuously generated throughout life in response to physiological and pathological stimuli. Moreover, the elucidation of mechanisms responsible for the hypertrophic response indicate similarity and overlap with the mechanisms involved in cell death by apoptosis as well as cell growth. During cardiac development, from birth to adulthood, there is a balance between the stimuli induce cell growth -by hypertrophy and hyperplasia- on one hand and those that induce programmed cell death on the other. In human and experimental animals it has been well documented that pathological conditions, such as diabetes and hypertension, can increase dramatically the rate of cell death. Moreover, high rates of cell death have been measured in normal adult human hearts and those of mice and rats. No surprisingly, these values increase significantly with age and high in senescence. By themselves, these high rates of normal cell death provide a very compelling argument in favor of cardiomyocyte regeneration. Without cell renewal, these rates of cell death would be incompatible with survival because the heart would disappear before early adulthood. As expected, direct measurement of rates of new cell formation in adult hearts demonstrate high rates of cell renewal that compensate for cell death. Thus, the heart is in continuous cellular turnover with new myocardial cells replacing the older ones. Experiments with fetal mouse cardiocytes shows that the retinoblastoma protein is responsible for the cardiocyte withdrawal from the cell cycle during development. The identification in the adult heart of a subpopulation of quiescent cells that have many of the characteristics of stem cells able to rapidly enter the cell cycle and generate new cardiocytes is yet another evidence that the heart continuously produces new cardiocytes to replace those that disappear either by apoptosis or necrosis.Surprisingly, stem cells other that those from the heart are able to produce new cardiocytes and repopulate the myocardium. We have used bone marrow stem cells injected into the border zone of post-coronary occlusion necrosis. Remarkably, these cells have proven to be very effective in generating new myocardium in the necrotic zone that is integrated to the rest of the muscle and irrigated by new vessels. These results demonstrate that stem cells provide a new avenue for the generation of new contractile tissue. This approach could prove useful in the treatment of chronic cardiac failure and post-ischemic necrosis.
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PMID:[Generation of new cardiomyocytes in the adult heart: Prospects of myocardial regeneration as an alternative to cardiac transplantation]. 1141 43

There is currently intense interest in the development of gene therapy for cardiovascular disease. The stimulation of therapeutic angiogenesis for ischemic heart disease has been one of the areas of greatest promise. Encouraging results have been obtained with the angiogenic cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in animal models, leading to clinical trials in ischemic heart disease. VEGF also has therapeutic potential in a second area of cardiovascular gene therapy, the enhancement of arterioprotective endothelial functions to prevent postangioplasty restenosis and bypass graft arteriopathy. The endothelial cell growth and survival functions of VEGF promote endothelial regeneration, whereas VEGF-induced endothelial production of NO and prostacyclin inhibits vascular smooth muscle cell proliferation. Inhibition of neointimal hyperplasia may also be achieved by gene transfer of endothelial NO synthase (eNOS), PGI synthase, or cell cycle regulators (retinoblastoma, cyclin or cyclin-dependent kinase inhibitors, p53, growth arrest homeobox gene, fas ligand) or antisense oligonucleotides to c-myb, c-myc, proliferating cell nuclear antigen, and transcription factors such as nuclear factor kappaB and E2F. An improved understanding of etiologically complex pathologies involving the interplay of genes and the environment, such as atherosclerosis and systemic hypertension, has led to the identification of new targets for gene therapy, with the potential to alleviate inherited genetic defects such as familial hypercholesterolemia. The use of vasodilator gene overexpression and antisense knockdown of vasoconstrictors to reduce blood pressure in animal models of systemic and pulmonary hypertension offers the prospect of gene therapy for human hypertensive disease. The renin-angiotensin system has been the target of choice for antihypertensive strategies because of its wide distribution and additional effects on fibrinolytic and oxidative stress pathways. Gene therapy in cardiovascular disease has an exciting future but remains at an early stage. Further developments in gene transfer vector technology and the identification of additional target genes will be required before its full therapeutic potential can be realized.
Hypertension 2001 Nov
PMID:Gene therapy for cardiovascular disease: a case for cautious optimism. 1171 25

Various pathological disorders have been associated with primary aldosteronism, including glucagonoma, phaeochromocytoma and primary hyperparathyroidism. In this report, a case of adrenal myelolipoma (a rare non-functioning tumour composed of mature adipose tissue and normal haematopoietic elements similar to bone marrow cells), aldosterone-producing adenoma and a pituitary microadenoma coexisting in a 62-year-old man with a 15-year history of arterial hypertension, previous ablation of an autonomously-functioning thyroid adenoma, multiple lipomas and an heterozygosity of the retinoblastoma (RB) susceptibility gene is reported. We believe that this case probably represents another variant of the multiple neoplasia syndrome and we speculate that structural alteration of the RB gene may play a role in the tumorogenesis.
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PMID:A rare combination consisting of aldosterone-producing adenoma and adrenal myelolipoma in a patient with heterozygosity for retinoblastoma (RB) gene. 1513 74

Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective alpha(1)-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G(0)-G(1) cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to alpha-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the alpha-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory kappaB (IkappaB)-alpha expression, and nuclear factor-kappaB transcription and decreased basal and TNFalpha-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective alpha(1)-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its alpha-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-kappaB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
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PMID:Alpha1-adrenergic receptor antagonists: novel therapy for pituitary adenomas. 1602 Apr 84


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