Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pazopanib, which is being developed by GlaxoSmithKline plc, is an oral, second-generation multi-targeted tyrosine kinase inhibitor that targets VEGFR, platelet-derived growth factor receptor and c-kit, key proteins responsible for tumor growth and survival. Pazopanib exhibited good potency against all of the human VEGFRs and closely related tyrosine receptor kinases in vitro, and demonstrated antitumor activity in several human tumor xenografts, including renal cell carcinoma (RCC), and breast and lung cancer. In phase I and II clinical trials, pazopanib was generally well tolerated with the main side effects being hypertension, fatigue or gastrointestinal disorders. Pazopanib alone caused a decrease in tumor size and stable disease in a significant number of patients, including those with RCC, NSCLC and gynecological tumors. The combination of pazopanib with lapatinib was effective in patients with breast cancer. At the time of publication, pazopanib monotherapy was being evaluated in phase III trials in patients with RCC and as combination therapy with lapatinib in patients with breast cancer. In addition, phase I and II trials were being conducted to assess pazopanib alone or in combination with a range of chemotherapeutics in patients with solid tumors or multiple myeloma.
...
PMID:Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. 1903 39

ABT-869 is a novel multitargeted inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases (RTKs) with potent antiangiogenic properties that slow tumor progression. Vascular endothelial growth factor receptor blockade has been shown to produce hypertension. Atrasentan is a potent and selective endothelin (ETA) receptor antagonist that lowers blood pressure and affects tumor growth. To assess the utility of ETA receptor blockade in controlling hypertension with RTK inhibition, we evaluated the ability of atrasentan to block hypertension with ABT-869 in conscious, telemetry-instrumented rats. Changes in mean arterial pressure (MAP) and heart rate (HR) were evaluated using mean values and the area under the curve (AUC). Atrasentan (0.5, 1.5, and 5.0 mg kg(-1) d(-1) for 5 days) elicited dose-dependent decreases in MAP-AUC (-16.7 +/- 1.3, -20.94 +/- 3.68, and -30.12 +/- 3.57 mm Hg x day, respectively) compared with vehicle. ABT-869 (1, 3, 10, 30 mg kg(-1) d(-1) for 5 days) increased MAP compared with vehicle (MAP-AUC values of -5.52 +/- 3.75, 12.7 +/- 8.4, 37.5 +/- 4.4, and 63.8 +/- 3.3 mm Hg x day, respectively). Pretreatment with atrasentan (5 mg/kg for 5 days) prevented and abolished the hypertensive effects of ABT-869. Thus, ETA receptor blockade effectively alleviated hypertension with RTK inhibition and may serve a dual therapeutic role by preventing hypertension and slowing tumor progression.
...
PMID:ETA receptor blockade with atrasentan prevents hypertension with the multitargeted tyrosine kinase inhibitor ABT-869 in telemetry-instrumented rats. 1918 29

ABT-869 [N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea] is a novel multitargeted inhibitor of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinase family members. ABT-869 demonstrates tumor growth inhibition in multiple preclinical animal models and in early clinical trials. VEGF receptor inhibition is also associated with reversible hypertension that may limit its benefit clinically. To evaluate optimal therapeutic approaches to prevent hypertension with VEGF receptor inhibition, we characterized the dose-dependent effects of seven antihypertensive agents from three mechanistic classes [angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs)] on hypertension induced by ABT-869 in conscious telemetry rats. We report that ABT-869-induced hypertension can be prevented and reversed with subtherapeutic or therapeutic doses of antihypertensive drugs with a general rank order of ACEi > ARB > CCB. In SCID mice, the ACE inhibitor, enalapril (C(20)H(28)N(2)O(5) x C(4)H(4)O(4)) at 30 mg/kg, prevented hypertension, with no attenuation of the antitumor efficacy of ABT-869. These studies demonstrate that the adverse cardiovascular effects of the VEGF/PDGF receptor tyrosine kinase inhibitor, ABT-869, are readily controlled by conventional antihypertensive therapy without affecting antitumor efficacy.
...
PMID:Effect of the multitargeted receptor tyrosine kinase inhibitor, ABT-869 [N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea], on blood pressure in conscious rats and mice: reversal with antihypertensive agents and effect on tumor growth inhibition. 1925 83

Vandetanib is a novel, orally available inhibitor of different intracellular signaling pathways involved in tumor growth, progression, and angiogenesis: vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and REarranged during Transfection tyrosine kinase activity. Phase I clinical trials have shown that vandetanib is well tolerated as a single agent at daily doses < or =300 mg. In the phase II setting, negative results were observed with vandetanib in small cell lung cancer, metastatic breast cancer, and multiple myeloma. In contrast, three randomized phase II studies showed that vandetanib prolonged the progression-free survival (PFS) time of patients with non-small cell lung cancer (NSCLC) as a single agent when compared with gefitinib or when added to chemotherapy. Rash, diarrhea, hypertension, fatigue, and asymptomatic QTc prolongation were the most common adverse events. Antitumor activity was also observed in medullary thyroid cancer. Four randomized phase III clinical trials in NSCLC are exploring the efficacy of vandetanib in combination with docetaxel, the Zactima in cOmbination with Docetaxel In non-small cell lung Cancer (ZODIAC) trial, or with pemetrexed, the Zactima Efficacy with Alimta in Lung cancer (ZEAL) trial, or as a single agent, the Zactima Efficacy when Studied versus Tarceva (ZEST) and the Zactima Efficacy trial for NSCLC Patients with History of EGFR-TKI chemo-Resistance (ZEPHYR) trials. Based on a press release by the sponsor of these trials, the PFS time was longer with vandetanib in the ZODIAC and ZEAL trials; the ZEST trial was negative for its primary superiority analysis, but was successful according to a preplanned noninferiority analysis of PFS. Ongoing phase II and III clinical trials will better define the appropriate schedule, the optimal setting of evaluation, and the safety of long-term use of vandetanib.
...
PMID:Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: current status and future directions. 1934 11

Angiogenesis is essential for tumor growth, invasion and metastasis, and is mediated, at least in part, by a large family of VEGF ligands and receptors. Ramucirumab, which is being developed by ImClone Systems Inc, is a fully human mAb that binds human VEGFR-2, thus blocking VEGF binding and inhibiting angiogenesis. Proof-of-concept preclinical studies with the mouse mAb DC-101 supported this hypothesis, and ramucirumab inhibited cell proliferation in vitro, as well as tumor progression in mouse xenograft models of human cancer. Ramucirumab was well tolerated on weekly and fortnightly schedules in phase I clinical trials in patients with advanced cancers; mechanism-related DLTs were hypertension and deep venous thrombosis. Stable disease was also observed in several patients treated on either schedule, and several patients on the weekly schedule exhibited partial responses. At the time of publication, ramucirumab was undergoing assessment in phase II trials as a monotherapy in hepatocellular, renal cell and ovarian carcinomas. Ramucirumab was also in phase II trials in combination with dacarbazine in melanoma, with mitoxantrone/prednisone in prostate cancer, with carboplatin/paclitaxel in NSCLC and with oxaliplatin/folinic acid/5-fluorouracil in colorectal cancer. A phase III trial in combination with docetaxel in breast cancer was also ongoing. Pending results from these trials, ramucirumab may be a useful addition to current antiangiogenic therapies. The results are awaited with interest.
...
PMID:Ramucirumab, a fully human mAb to the transmembrane signaling tyrosine kinase VEGFR-2 for the potential treatment of cancer. 1951 49

Cushing's syndrome during pregnancy is rare, and rather than being of pituitary origin most patients exhibit ACTH-independent adrenal hypercortisolism. In some cases the syndrome has spontaneously resolved post partum, suggesting the presence of a pregnancy-associated stimulatory factor(s). We describe a case with aberrant adrenal LH/hCG receptors in a large adrenal tumor as a possible explanation for cortisol hypersecretion and tumor growth in Cushing s syndrome during pregnancy. A 27-yr-old woman presented with hypertension and diabetes mellitus in early pregnancy. Investigations revealed hypercortisolemia, suppressed ACTH-levels, and a 6.4- cm right adrenal tumor. The tumor was successfully removed by laparoscopy at 26th week of pregnancy. Hypercortisolism and hypertension resolved post-operatively. The tumor displayed higher LH/hCG receptor mRNA and protein positivity than adjacent normal adrenal tissue as examined by in situ hybridization and immunocytochemistry. High physiological levels of hCG, in conjunction with aberrant adrenal LH/hCG receptor overexpression, may have contributed to the development of Cushing's syndrome in pregnancy.
...
PMID:Adrenocorticotropin-independent Cushing's syndrome in pregnancy related to overexpression of adrenal luteinizing hormone/human chorionic gonadotropin receptors. 1963 97

Milk and colostrum is a rich source of proteins/peptides which have crucial roles in both neonates and adults. Milk bioactive proteins and peptides are potential health-enhancing nutraceuticals for food. Many bioactive peptides/proteins may be used as nutraceuticals, for example, in the treatment of cancer, asthma, diarrhea, hypertension, thrombosis, dental diseases, as well as mineral malabsorption, and immunodeficiency. The following components of milk are of particular interest in the recent years: 1) Lactoferrin [Lf] has antibacterial, antifungal, antiviral, antiparasite and antitumor activities and accelerates immunomodulatory properties. Lf is a potent inhibitor for several enveloped and naked viruses, such as rotavirus, enterovirus and adenovirus. Lf is resistant to tryptic digestion and breast-fed infants excrete high levels of faecal Lf, so that its effect on viruses replicating in the gastrointestinal tract is of great interest. 2) Casein has been protective in experimental bacteremia by eliciting myelopoiesis. Casein hydrolyzates were also protective in diabetic animals, reduced the tumor growth and diminished colicky symptoms in infants. 3) A Proline rich polypeptide [PRP] revealed variety of immunotropic functions, including promotion of T-cell activation and inhibition of autoimmune disorders such as multiple sclerosis. 4) alpha-Lactalbumin [LA] demonstrates antiviral, antitumor and anti-stress properties. 5) Lactoperoxidase shows antibacterial properties. 6) Lysozyme is effective in treatment of periodentitis and prevention of tooth decay. Taken together, milk-derived proteins and peptides are bio-available and safe for the prevention and treatment of various disorders in humans and may play a complementary [natural agents] rather than a substitutional role to the toxic synthetic pharmacological drugs.
...
PMID:Molecular and biotechnological advances in milk proteins in relation to human health. 1968 55

Angiotensin II (AT-II) is a peptide that plays an important role in the renin-angiotensin-aldosterone (RAA) system. Traditionally, the RAA system has been related with states of systemic hypertension and hypoperfusion as a counterbalance mechanism. Recently, AT-II has been studied for its properties in the process of fibrosis in several organs, especially in the liver. AT-II is capable to stimulate the activated hepatic stellate cells, which increase expression of profibrogenic molecules like tumor growth factor-beta, tissue inhibitor of metalloproteinase-1 and collagen I, among others. At the same time, AT-II is implied in the hemodynamic balance of cirrhosis and portal hypertension. Due to its profibrogenic and vasoactive properties, blockade of AT-II actions constitutes an important therapeutic target to inhibit fibrotic processes and reduction of risk of complications of portal hypertension as well. Some drugs like angiotensin-converting enzyme inhibitors or the angiotensin II receptor blockers have been studied as alternatives for the treatment of patients with cirrhosis with promising results. Nonetheless, additional research is required in order to consider these drugs as a part of the integral treatment of the patient with cirrhosis and portal hypertension.
...
PMID:Role of angiotensin II in liver fibrosis-induced portal hypertension and therapeutic implications. 1973 16

Despite recent advances in chemotherapy, including the development of irinotecan and oxaliplatin, survival of patients with advanced colorectal cancer remains suboptimal. Thanks to an increased understanding of the biologic basis of cancer, investigators are turning to molecularly targeted therapy to further improve outcome. Current research in colorectal cancer focuses on inhibiting the epidermal growth factor receptor and vascular endothelial growth factor. Both are essential to tumor growth and frequently over-expressed in colorectal cancer cells. Epidermal growth factor receptor pathways promote survival of tumor cells through cell proliferation, differentiation, migration, adhesion, and transformation and inhibition of apoptosis, whereas the vascular endothelial growth factor is a key mediator of angiogenesis and may have other biologic roles. Recent phase II and III results show the feasibility and activity of inhibiting both by using monoclonal antibodies in combination with chemotherapy in patients with advanced colorectal cancer. Cetuximab (an epidermal growth factor receptor antibody) plus irinotecan yields an increased overall response in patients with irinotecan-refractory colorectal disease. In previously untreated patients, irinotecan/5-fluoruoracil/leucovorin plus cetuximab also generates an increased overall response rate. Randomized trials of the humanized anti-vascular endothelial growth factor antibody (rhuMAb vascular endothelial growth factor) plus chemotherapy yielded increased overall response rates and median survival times compared with chemotherapy alone. The primary toxicity of cetuximab is an acneform skin rash; rhuMAb vascular endothelial growth factor causes mild hypertension and may cause perturbations in coagulation. Treatment with either does not appear to exacerbate chemotherapy-related toxicity.
...
PMID:Emerging therapies for metastatic colorectal cancer: focus on EGFR and VEGF inhibition. 1978 Feb 48

Overexpression of vascular endothelial growth factor (VEGF) by tumor cells promotes angiogenesis, which correlates with progressive tumor growth and poor outcomes in many types of cancer. Bevacizumab inhibits VEGF to promote regression of tumor vessels by limiting blood supply and tumor growth, enhancing delivery of chemotherapy, and inhibiting formation of new vessels. Combined with chemotherapy, bevacizumab prolongs progression-free and overall survival over chemotherapy alone in patients with metastatic carcinoma of the colon and rectum; unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC); and metastatic HER2-negative breast cancers (mBC). Side effects, including hypertension, proteinuria, bleeding, arterial thrombotic events, and impaired wound healing, can be clinically significant, particularly in patients with risk factors. To optimize patient outcomes, nurses should understand bevacizumab's role in cancer therapy, recognize symptoms of toxicity, and manage its side effects. This article describes the rationale for bevacizumab in the treatment of metastatic colorectal cancer, NSCLC, and mBC and discusses patient selection, treatment duration, and side-effect management to support the role of oncology nurses in caring for, educating, and enhancing treatment adherence among patients with cancer receiving bevacizumab. Two case studies are presented as examples of the complex scenarios nurses may encounter regarding these issues.
...
PMID:Oncology nursing in a new era: optimizing treatment with bevacizumab. 1979 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---