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)

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.
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PMID:Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. 190 97

Angiogenesis plays a pivotal role not only in wound healing and tumor progression but also in diabetic angiopathy, arteriosclerosis, and collateral formation of obstructive vascular diseases. Vascular endothelial growth factor (VEGF) is now thought to be an endothelium-specific and potent angiogenic factor. We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from porcine brain, is produced by endothelial cells and proposed that CNP can exert control over vascular tone and growth as a local vascular regulator. In the present study, we examined the effect of VEGF on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP we developed. VEGF (1 to 100 ng/mL) dose-dependently suppressed CNP secretion from cultured bovine endothelial cells, and 100 ng/mL VEGF suppressed endothelial CNP secretion to 28% of control levels (31.7 +/- 5.5 versus 8.9 +/- 0.8 fmol/mL, vehicle versus VEGF). VEGF also suppressed CNP mRNA expression in endothelial cells 9 hours after administration. In contrast, basic fibroblast growth factor (20 ng/mL), an endothelium-nonspecific angiogenic factor, significantly stimulated CNP secretion by 290%. These results indicate that VEGF can regulate vascular tone and growth in the process of angiogenesis through suppression of endothelial secretion of CNP, which is an endothelium-derived vasorelaxing and growth-inhibitory peptide.
Hypertension 1996 Mar
PMID:Vascular endothelial growth factor suppresses C-type natriuretic peptide secretion. 861 45

Pheochromocytoma and paraganglioma of childhood are rare neuroendocrine tumors. Urinary catecholamine measurements, metaiobenzylguanidine (MIBG) scanning, computed tomographic scanning, and magnetic resonance imaging have greatly facilitated diagnosis. Prognosis after surgical resection is excellent. In this retrospective series collected from French oncology centers, the risk of tumor progression was studied in order to assess prognostic factors and the optimal diagnostic and therapeutic management. Medical records of 24 children with paraganglioma were reviewed. This tumor occurred at a median age of 12.5 years and in most cases was revealed by arterial hypertension. The diagnosis was made by the demonstration of urinary excretion of catecholamines and their metabolites. Six patients had bilateral adrenal pheochromocytomas; two patients had extra-adrenal paragangliomas. In eight patients, the paraganglioma occurred as a familial disease. Surgical excision was the only therapeutic procedure. With a follow-up of 5.2 years, 14 of the patients are still in first complete remission and 6 have developed metastases or shown tumor progression. Despite a high long-term survival rate, the risk of malignancy and of multifocal involvement is of concern and is associated with a significant rate of late events. The outcome depends on adequacy of tumor resection and must be serially assessed.
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PMID:Pheochromocytoma and paraganglioma in children: a report of 24 cases of the French Society of Pediatric Oncology. 926 73

Brainstem gliomas are a heterogeneous group of tumors whose prognosis and treatment depend not only on the histologic features but also on the location within the brainstem. Magnetic resonance imaging allows the recognition of a distinct type of brainstem glioma of the tectal region of the midbrain, leading to aqueductal compression and hydrocephalus. The radiologic appearance of these tumors is usually rather uniform, with a characteristic nonenhancing thickening of the tectal plate. Because of its protracted course, no further treatment is necessary beyond cerebrospinal fluid diversion and close clinicoradiologic follow-up. The authors report two children with tectal plate gliomas of unusual but strikingly similar appearance. They present a clinical picture suggestive of intracranial hypertension without localizing signs. Magnetic resonance images reveal hydrocephalus related to the presence of perfectly circular lesions, hypointense on T1 and hyperintense on T2, which could be mistaken for parasitic cysts or represent dilated rostral portions of the sylvian aqueduct. After the cerebrospinal fluid diversion procedures, no further treatment was given, with one of the patients being monitored for 10 years and the other for 8 months, without tumor progression. These patients demonstrate that tectal gliomas, despite sharing a good prognosis, may have various patterns of growth, leading to unusual radiologic appearances that may pose diagnostic difficulties.
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PMID:Globular glioma of the tectum. 1042 37

Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes. We conclude that the majority of phenotypes attributed to the monomeric G protein RhoA and mediated by its effector, Rho-kinase (ROK), reflect Ca2+ sensitization: inhibition of myosin II dephosphorylation in the presence of basal (Ca2+ dependent or independent) or increased MLCK activity. We outline the pathway from receptors through trimeric G proteins (Galphaq, Galpha12, Galpha13) to activation, by guanine nucleotide exchange factors (GEFs), from GDP. RhoA. GDI to GTP. RhoA and hence to ROK through a mechanism involving association of GEF, RhoA, and ROK in multimolecular complexes at the lipid cell membrane. Specific domains of GEFs interact with trimeric G proteins, and some GEFs are activated by Tyr kinases whose inhibition can inhibit Rho signaling. Inhibition of MLCP, directly by ROK or by phosphorylation of the phosphatase inhibitor CPI-17, increases phosphorylation of the myosin II regulatory light chain and thus the activity of smooth muscle and nonmuscle actomyosin ATPase and motility. We summarize relevant effects of p21-activated kinase, LIM-kinase, and focal adhesion kinase. Mechanisms of Ca2+ desensitization are outlined with emphasis on the antagonism between cGMP-activated kinase and the RhoA/ROK pathway. We suggest that the RhoA/ROK pathway is constitutively active in a number of organs under physiological conditions; its aberrations play major roles in several disease states, particularly impacting on Ca2+ sensitization of smooth muscle in hypertension and possibly asthma and on cancer neoangiogenesis and cancer progression. It is a potentially important therapeutic target and a subject for translational research.
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PMID:Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. 1450 7

Most clear cell renal cell cancer (RCC) is caused by biallelic loss of the von Hippel-Lindau gene. One consequence of this loss is up-regulation of vascular endothelial growth factor via a pathway involving accumulation of hypoxia inducible factor. Vascular endothelial growth factor, a potent angiogenic factor, is secreted by many human cancers, but clear cell RCC as a group produces particularly high levels and has a highly vascular histologic appearance. In a randomized, placebo-controlled, double-blind trial, we tested the use of a neutralizing antibody to vascular endothelial growth factor, bevacizumab, in patients with metastatic RCC. At 3 or 10 mg/kg every 2 weeks, toxic effects were minimal, with hypertension and proteinuria the most substantial events. There were four partial responses (10% response rate) and a highly substantial prolongation of time to tumor progression in patients who received the higher dose of bevacizumab. With a crossover design and very sensitive criteria for disease progression, no difference in survival was shown. Four patients have been undergoing long-term bevacizumab therapy without tumor progression for 3 to 5 years. Three have substantial proteinuria but retain normal renal function. A small pilot trial combining bevacizumab and thalidomide showed no unexpected toxic effects. Future trials should consider combination therapies and strategies in which patients are treated through initial disease progression with antiangiogenic agents such as bevacizumab.
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PMID:Bevacizumab for patients with metastatic renal cancer: an update. 1544 32

Desmoplastic infantile ganglioglioma (World Health Organization grade I) is a rare neoplasm. Despite their common large size and spectacular radiologic and histologic features, the prognosis after surgical resection is good. We present a new case of this tumor in a 14-month-old boy with a recent history of intracranial hypertension. Magnetic resonance imaging revealed a large tumor involving the left collateral trigone with dilatation of the lateral ventricles. Surgery revealed two separate solid tumors: one in the left falco-tentorial region and the other in the left rolandic area. Microscopic examination showed a proliferation of neoplastic astrocytes in reticulin-rich desmoplastic stroma associated with scattered ganglion cells. One year after surgery follow-up magnetic resonance imaging did not show tumor progression.
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PMID:Desmoplastic infantile ganglioglioma: a rare tumor with an unusual presentation. 1549 34

Medical management of cerebral edema and elevated intracranial pressure (ICP) is a critical component of perioperative care in neurosurgical practice. Traumatic brain injury, arterial infarction, venous hypertension/infarction, intracerebral hemorrhage, subarachnoid hemorrhage, tumor progression, and postoperative edema can all generate clinical situations in which ICP management is a critical determinant of patient outcomes. Although osmotic agents are among the most fundamental tools to control ICP, prospective data to establish clear guidelines on their use are lacking. Hypertonic saline is emerging as an alternative to mannitol. Early data suggest that indications for each agent may ultimately depend on ICP etiology.
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PMID:Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic saline. 1663 96

Insulin resistance is a worldwide risk factor for the two most dangerous human disease groups; namely, for cardiovascular lesions and malignancies. The insulin resistance syndrome have five basic criteria: hyperglycemia, visceral obesity, elevated serum triglyceride level, low HDL-cholesterol level (dyslipidemia) and hypertension. Each of these criteria alone are risk factors for cancer, and they mean together a multiple risk. Insulin resistance of the liver, skeletal muscles, and fatty tissue leads to a reactive hyperinsulinemia by the increased secretory activity of the beta-cells. Insulin has diverse metabolic effects, and at the same time is a growth factor. It enhances the production and mitogenic activity of other, insulin-like growth factors, and leads to pathological cell proliferation. In the uncompensated phase of insulin resistance hyperglycemia appears, which promotes tumor genesis by several pathways. The elevated serum glucose level is advantageous for the increased DNA synthesis of the tumor cells. It provokes deliberation of free radicals, which will cause derangement of both the DNA and the enzymes having a role in the repair mechanisms. Hyperglycemia leads to a nonenzymatic glycation of protein structures, and the glycated products enhance the deliberation of free radicals, cytokines and growth factors. Insulin resistance means an enhanced risk for breast, pancreas, liver, colon, bladder, prostate and oral cavity cancers. The moderately increased fasting glucose level is also a risk factor for breast, stomach and colon cancers, even without manifestation of type 2 diabetes. Insulin resistance promotes tumor progression as well. In cancer patients with hyperglycemia or type 2 diabetes, the rate of tumor recurrence, metastatic spread and fatal outcome is higher as compared with the tumor patients without metabolic disease. The correlation between insulin resistance and tumor promotion reveals new possibilities in the prevention and treatment of cancer. The healthy diet, physical activity and weight loss increase insulin sensitivity, and decrease the risk for both cardiovascular diseases and malignancies.
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PMID:[Correlations of insulin resistance and neoplasms]. 1688 76

On January 26, 2006, sunitinib (Sutent) received regular approval as monotherapy for the treatment of patients with gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate (Gleevec). Time-to-tumor progression (TTP) of sunitinib-treated patients was superior to that of placebo-treated patients. Median TTP of sunitinib-treated patients was 27.3 weeks, compared with 6.4 weeks for placebo-treated patients (p < .0001). Partial responses were observed in 6.8% of sunitinib-treated patients and no placebo-treated patients. Sunitinib also received accelerated approval on January 26, 2006, as monotherapy for treatment of advanced renal cell carcinoma (RCC). In two single-arm trials of sunitinib in patients with metastatic RCC, partial responses were observed in 25.5% (95% confidence interval [CI], 17.5, 34.9) and 36.5% (95% CI, 24.7, 49.6) of patients. Median response durations in the two trials were 27.1 weeks (95% CI, 24.4, incalculable) and 54 weeks (95% CI, 34.3, 70.1). Treatment-emergent adverse events in sunitinib-treated patients included diarrhea, mucositis, skin abnormalities, altered taste, electrolyte abnormalities, hypertension, and diminution in left ventricular ejection fraction. Cardiac safety of sunitinib in patients with preexisting cardiac abnormalities remains unknown. Based on nonclinical findings, physicians prescribing sunitinib should monitor for adrenal insufficiency in patients who undergo stressors such as surgery, trauma, or severe infection. Caution should be exercised when administering sunitinib in combination with known CYP3A4 inducers or inhibitors.
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PMID:Food and Drug Administration drug approval summary: Sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. 1722 5


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