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)

As the human genome is sequenced and annotated, an important step in future genetic studies of complex traits and diseases will be the identification of relevant candidate genes. To enable such compilations, it would be useful to collate all necessary and available genetic information for each candidate gene. To this end, we have created a web tool (http://genome.cwru.edu/gist/gist.html+ ++) to allow the rapid cataloging of currently available genetic data. This tool, called GIST (or "Gene Information Search Tool"), allows an investigator to search the major genomic databases containing gene and marker information from a single query point. To prove the utility of GIST, a catalog of 150 hypertension candidate genes was created. This resource collates all available nucleotide and amino acid sequence data, expression data, chromosomal map location, and genetic marker interval for each gene, collected from on-line databases. These data can be used to guide genetic studies of hypertension.
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PMID:GIST: A web tool for collecting gene information. 1101 64

A gastrointestinal stromal tumor of the stomach mimicking an adrenal tumor in a 67-year-old woman is reported. The patient sought medical attention for left flank pain in December 2001. A spherical calcification was evident in the left hypochondrium in an abdominal radiography, and computed tomography revealed a mass 8 cm in diameter at the upper pole of the left kidney. She then was admitted to our hospital. Physical examination and laboratory screening showed hypertension, diabetes mellitus and slight hemoconcentration. Endocrine examination showed normal serum adrenal hormone concentrations. Magnetic resonance imaging again demonstrated the mass, which showed enhancement along its margins after intravenous contrast administration. With a preoperative diagnosis of adrenal tumor, we performed total resection. The pediculated tumor, arising from the stomach, showed c-kit immunohistochemical staining permitting a histopathological diagnosis of gastrointestinal stromal tumor.
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PMID:[Gastrointestinal stromal tumor of the stomach mimicking adrenal tumor: a case report]. 1568 56

Adrenal myelolipoma is a rare, benign and biochemically inactive tumor. It is usually diagnosed incidentally by radiological methods and is known to be associated with obesity, hypertension, endocrinological disorders and some malignancies. We report herein the association of a myelolipoma with a gastrointestinal stromal tumor. To our knowledge this is the first report of such an association to date. A 67-year-old male patient admitted to our clinic with abdomimal pain and fever; he had a history of hypertension and diabetes mellitus. In physical examination, a mass involving the right quadrants was palpated. Computerized tomography revealed a right retroperitoneal mass, probably originating from the kidney or cecum. In laparotomy, the tumor (12 cm radius and 1500 g) localized on the superior of right kidney was excised. Abdomen exploration revealed another mass with 10 cm radius 100 cm distal to the ligamentum of Treitz and segmental jejunal resection and anastomosis were applied. The pathological diagnosis was reported as myelolipoma for the retroperitoneal mass and leiomyosarcoma for the jejunal mass. Myelolipoma is a benign tumor, involving mature fat and hematopoietic stem cells. Pathogenesis is still not clear and the microscopical characteristics are hematopoietic, lipoid, and reticuloid cells and megakaryocytes. Myelolipomas are reported to be associated with some other malignancies (especially renal), but this is the first report showing the association with a leiomyosarcoma. Therefore, leiomyosarcoma should also be one of the possible associations kept in mind by the physician in the diagnosis and treatment of myelolipomas.
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PMID:Giant adrenal myelolipoma associated with small bowel leiomyosarcoma: a case report. 1683 Feb 97

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

Cardio-ankle vascular index (CAVI) has been established as a marker of arterial stiffness, which is increased in hypertensive patients. CAVI reflects the stiffness of the aorta, femoral artery, and tibial artery. Sunitinib, multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activities, has been proved effective in patients with gastrointestinal stromal tumors. However, the treatment with sunitinib is often complicated by side effects such as hypertension. We describe an 84-year-old woman with gastrointestinal stromal tumor, who showed changes in arterial stiffness preceding the appearance of hypertension in the early phase after sunitinib initiation. The patient received sunitinib (50 mg given daily) for gastrointestinal stromal tumor. We assessed the influence of sunitinib on arterial stiffness every 7 days by measuring CAVI. The CAVI, which reflects arterial stiffness, was increased from 9.95 at baseline to 11.65 at 7 days after the initiation of sunitinib, whereas the blood pressure remained unchanged (117/72 and 119/76 mmHg). At 14 days after sunitinib initiation, the blood pressure was increased to 159/89 mmHg, indicating the occurrence of hypertension, while the CAVI was 11.90, the similar level detected at 7 days. Subsequently, sunitinib treatment was discontinued, because of the marked decrease in blood platelets. Both blood pressure and CAVI, together with blood platelets, were restored to the baseline values at 12 days after cessation of sunitinib. In conclusion, the increase in the CAVI preceded the appearance of sunitinib-induced hypertension. Arterial stiffness assessed by CAVI may be useful for early detection of sunitinib-induced hypertension.
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PMID:Early detection of hypertension in a patient treated with sunitinib by measuring cardio-ankle vascular index. 1947 67

Angiogenesis is essential for normal tissue and even more so for solid malignancies. At present, inhibition of tumor angiogenesis is a major focus of anticancer drug development. Bevacizumab, a humanized antibody against VEGF, was the first antiangiogenic agent to be approved for advanced non-small cell lung cancer, breast cancer and colorectal cancer. The most commonly observed adverse events are hypertension, proteinuria, bleeding and thrombosis. Sunitinib, a small molecule blocking intracellular VEGF, KIT, Flt3 and PDGF receptors, which regulate angiogenesis and cell growth, is approved for the treatment of advanced renal cell cancer (RCC) and malignant gastrointestinal stromal tumor. The most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue, hypothyroidism and hypertension. Sorafenib, an oral multikinase inhibitor, is approved for the second-line treatment of advanced RCC and upfront treatment of advanced hepatocellular carcinoma. Most common adverse events with sorafenib are dermatologic (hand-foot skin reaction, rash, desquamation), fatigue, diarrhea, nausea, hypothyroidism and hypertension. More recently, cardiovascular toxicity has increasingly been recognized as a potential adverse event associated with sunitinib and sorafenib treatment. Elderly patients are at increased risk of thromboembolic events when receiving bevacizumab, and potentially for cardiac dysfunction when receiving sunitinib or sorafenib. The safety of antiangiogenic drugs is of special concern when taking these agents for longer-term adjuvant or maintenance treatment. Furthermore, newer investigational antiangiogenic drugs are briefly reviewed.
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PMID:Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. 1994 Apr 66

Patients diagnosed with advanced gastrointestinal stromal tumor (GIST) are currently treated with oral tyrosine kinase inhibitors (TKIs). Imatinib mesylate is the standard first-line treatment, and sunitinib malate is administered second-line for patients who are intolerant or progress on imatinib. Imatinib has recently been approved for adjuvant treatment of GIST patients who have a significant risk for relapse. In both the metastatic and adjuvant settings, patients may be on these TKIs for many years. Low plasma imatinib levels have been reported to be associated with a short median time to progression of advanced GIST, stressing the importance of maintaining optimal drug levels. We summarize management of the most frequent and clinically significant adverse effects of imatinib and sunitinib in the treatment of GIST in the context of current guidelines, published literature, and the experience of three large GIST referral centers. The adverse events reviewed include nausea and vomiting, diarrhea, skin rash, musculoskeletal complaints, fatigue, hemorrhage, edema, hand-foot skin reaction, skin and hair discoloration, mucositis, hypertension, cardiac toxicity, hypothyroidism, liver transaminase changes, and hematological toxicity of imatinib and sunitinib. Potential drug-drug interactions with each respective agent are also discussed. With prudent use of supportive care measures, many side effects can be managed without dose reduction or interruption of treatment. On the other hand, individualized tailoring of the dose is often required to manage severe toxicity, such as painful hand-foot skin reactions, fatigue, hepatotoxicity, or cardiac toxicity. Management of many TKI-related adverse effects require further evaluation in prospective clinical trials.
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PMID:Practical management of tyrosine kinase inhibitor-associated side effects in GIST. 2057 50

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases--such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas--considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is tyically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities mandate prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.
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PMID:Novel multitargeted anticancer oral therapies: sunitinib and sorafenib as a paradigm. 2109 May 21

Kinase inhibitors have emerged as an important new class of agents for the treatment of diverse tumors. Sunitinib malate is a small-molecule, oral, multi-kinase inhibitor approved for use in treating renal cell carcinoma and gastrointestinal stromal tumor. It has also demonstrated efficacy in treating pancreatic neuroendocrine tumors and is being evaluated for the treatment of other cancers. Initially developed for its inhibition of the vascular endothelial growth factor (VEGF) signaling pathway, sunitinib has been associated with hypertension and heart failure. This review examines the incidence and severity of these adverse events, relevant findings from other agents that inhibit VEGF signaling, the mechanisms underlying these effects, and suggestions for their clinical management. Hypertension is a common adverse effect that is usually easily managed. The associated heart failure is less common; it can be reversible but must be actively monitored and managed. Mechanistic insights suggest that an attentive clinical strategy for hypertension could prevent severe cardiotoxicity.
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PMID:Sunitinib, hypertension, and heart failure: a model for kinase inhibitor-mediated cardiotoxicity. 2193 79

A 70-year-old woman with a submucosal gastric tumor was referred to our hospital for surgical treatment. Upon examination, it was found that she had hypertension, and abdominal computed tomography revealed swelling on both adrenal glands. The patient was examined with gamma camera imaging and iodine-123 metaiodobenzylguanidine (MIBG), because her hypertension was thought to be due to a suspected adrenomedullary tumor. The planar image showed an unexpected abnormal uptake of MIBG in the upper abdomen. On single-photon emission computed tomographic images, the area of abnormal tracer uptake was thought to correspond to the known gastric tumor. The surgical procedure and histological assessments revealed that the gastric tumor was a gastrointestinal stromal tumor (GIST). MIBG can accumulate in GISTs as well as in neuroendocrine tumors of the medulla of the adrenal glands. Although the cause of radiolabeled MIBG uptake in GISTs is uncertain, further studies are necessary to establish the significance of MIBG scintigraphy in GIST imaging.
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PMID:Unusually increased metaiodobenzylguanidine uptake in a gastrointestinal stromal tumor of the stomach. 2264 61


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