Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a platform for the comparative profiling of urine using reversed-phase liquid chromatography-mass spectrometry (LC-MS) and multivariate statistical data analysis. Urinary compounds were separated by gradient elution and subsequently detected by electrospray Ion-Trap MS. The lower limit of detection (5.7-21 nmol/L), within-day (2.9-19%) and between-day (4.8-19%) analytical variation of peak areas, linearity (R2: 0.918-0.999), and standard deviation for retention time (<0.52 min) of the method were assessed by means of addition of seven 3-8 amino acid peptides (0-500 nmol/L). Relating the amount of injected urine to the area under the curve (AUC) of the chromatographic trace at 214 nm better reduced the coefficient of variation (CV) of the AUC of the total ion chromatogram (CV = 10.1%) than relating it to creatinine (CV = 38.4%). LC-MS data were processed, and the common peak matrix was analyzed by principal component analysis (PCA) after supervised classification by the nearest shrunken centroid algorithm. The feasibility of the method to discriminate urine samples of differing compositions was evaluated by (i) addition of seven peptides at nanomolar concentrations to blank urine samples of different origin and (ii) a study of urine from kidney patients with and without proteinuria. (i) The added peptides were ranked as highly discriminatory peaks despite significant biological variation. (ii) Ninety-two peaks were selected best discriminating proteinuric from nonproteinuric samples, of which 6 were more intense in the majority of the proteinuric samples. Two of these 6 peaks were identified as albumin-derived peptides, which is in accordance with the early rise of albumin during glomerular proteinuria. Interestingly, other albumin-derived peptides were nondiscriminatory indicating preferential proteolysis at some cleavage sites.
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PMID:Comparative urine analysis by liquid chromatography-mass spectrometry and multivariate statistics: method development, evaluation, and application to proteinuria. 1720 64

Several drugs currently in development target the vascular endothelial growth factor (VEGF) pathway, a validated target in the treatment of non-small cell lung cancer (NSCLC). Most clinical trial data generated to date have been with either bevacizumab, a monoclonal antibody to VEGF, or small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase activity (sunitinib, sorafenib, and ZD6474). VEGF Trap, an engineered soluble receptor made from extracellular domains of VEGFR1 and VEGFR2, binds to all isoforms of VEGF and to placental growth factor. VEGF Trap binds to VEGF-A and VEGF-B with markedly higher affinity than bevacizumab. The toxicities seen in phase I trials of s.c. and i.v. administration of VEGF Trap, hypertension and proteinuria, are similar to those seen with other molecules that target the VEGF pathway. In the s.c. VEGF Trap phase I trial, significant radiographic improvement was observed in a patient with heavily pretreated NSCLC. Ongoing phase I trials are evaluating combinations of VEGF Trap with platinum-based doublets and single-agent docetaxel. The activity of single-agent VEGF Trap in NSCLC is being assessed in a multicenter phase II trial.
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PMID:Vascular endothelial growth factor trap in non small cell lung cancer. 1767 Nov 53

Hypertension, proteinuria, thromboembolic or bleeding events are well-recognized complications occurring while targeting VEGF pathway. Wound healing dysfunctions have also been described in patients undergoing major surgery. For the first time, we report wound healing delay after central venous access following DCF-VEGF-Trap. VEGF-Trap may affect both angiogenesis and reepithelialization which are necessary to the normal repair process.
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PMID:Wound healing delay after central venous access following DCF/VEGF-trap therapy. 1922 94

During the last decade we have assisted in the development of new therapeutic strategies for the treatment of ovarian cancer, based on the best knowledge of molecular biology. One of the most promising strategies under investigation is antiangiogenic therapy. Bevacizumab is a monoclonal humanised antibody targeting vascular endothelial growth factor (VEGF), which has shown antitumour activity in ovarian cancer in preclinical models as well as in clinical trials, both in monotherapy and in combination with other therapies. Currently, ongoing phase III trials are testing bevacizumab as a front-line therapy with carboplatin and paclitaxel. Bevacizumab has been generally well tolerated with mild frequent toxicities (proteinuria, hypertension and bleeding). However, the drug may result in other uncommon, but potentially life-threatening side effects, such as arterial thromboembolism, wound healing complications, and gastrointestinal perforation or fistulae, which should be considered when the drug is administered. Other new therapeutic antiangiogenic strategies that include small-molecule tyrosine kinase inhibitors, antibodies neutralising the VEGF receptor (VEGFR) and soluble VEGFR hybrids (VEGF Trap) are being investigated with promising early results.
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PMID:Current status of anti-angiogenic agents in the treatment of ovarian carcinoma. 1977 93

Proteinuria is a dose-related side-effect occurring after inhibition of vascular endothelial growth factor (VEGF) signalling and may reflect severe glomerular damage. The inhibition of the VEGF signalling axis induces downexpression or suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or glomerular thrombotic microangiopathy, the main-associated kidney disease. A MEDLINE search was carried out using the following criteria: (1) all MEDLINE listings as of 01-01-2000 with abstracts; (2) English language; and (3) Humans. The following phrases were used to query the database: (proteinuria) AND (anti-VEGF OR VEGF inhibition OR bevacizumab OR sunitinib OR sorafenib OR VEGF Trap OR axitinib OR pazopanib OR AZ 2171). The references of each article identified were carefully reviewed for additional reference. The incidence of mild and asymptomatic proteinuria ranges from 21% up to 63%, but heavy proteinuria has been reported in up to 6.5% of renal cell carcinoma patients. Although discontinuation of anti-VEGF agent induced significant reduction, persistence of proteinuria is common. Although angiotensinconverting-enzyme inhibitors and/or angiotensin receptor blockers seem to be preferred, no specific recommendation for an antiproteinuric agent can be made in this context because there are no controlled studies addressing the subject. Periodic monitoring of urinary protein should be carried out in anti-VEGF-treated patients and patients showing proteinuria need special referral to nephrologists.
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PMID:VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management. 2000 22

The use of vascular endothelial growth factor (VEGF)-targeted agents for treating cancer has increased dramatically over recent decades. These drugs provide considerable benefits in terms of progression-free (PFS) or overall (OS) survival for cancer patients. Of particular importance to clinicians treating cancer patients by using VEGF-targeted agents is VEGF-inhibition-induced hypertension, proteinuria, thrombosis and hemorrhage. Aflibercept is a new, successful example of targeting VEGF for therapy of solid tumors. Though results from phase I and II clinical trials demonstrated aflibercept is well tolerated, it inevitably has severe adverse effects unique to this class of agents. In this review, we discuss the adverse effects associated with aflibercept (VEGF Trap), focusing on vascularassociated hypertension, proteinuria, hemorrhage, and thrombosis, and further discuss the mechanisms, significance, and potential management of these adverse effects.
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PMID:Aflibercept (VEGF Trap): one more double-edged sword of anti-VEGF therapy for cancer? 2070 50

Recent advances in understanding the importance of angiogenesis to tumor growth and distant metastasis has driven the development of antiangiogenic therapies for the treatment of non-small-cell lung cancer (NSCLC). The anti-vascular endothelial growth factor (VEGF) monoclonal antibody, bevacizumab, is the only US Food and Drug Administration-approved antiangiogenic agent for advanced NSCLC. Accumulated safety data with bevacizumab in NSCLC shows that patients are at risk for hemorrhage, venous thromboembolism, hypertension, and proteinuria. Investigational agents that target VEGF via a different mechanism (such as aflibercept [VEGF Trap]) or simultaneously inhibit multiple molecular pathways involved in angiogenesis (ie, multitargeted tyrosine kinase inhibitors [TKIs]) and vascular disrupting agents (VDAs) that target existing tumor vasculature are in various stages of clinical development for NSCLC, and safety profiles are emerging for these classes of agents. This review describes the molecular rationale for targeting angiogenic pathways in anticancer therapy and summarizes safety and tolerability data from clinical trials of bevacizumab or aflibercept in combination with chemotherapy and the investigational TKIs and VDAs in patients who have advanced NSCLC.
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PMID:Safety profile and tolerability of antiangiogenic agents in non-small-cell lung cancer. 2205 89

For a few years, new targeted therapies have been used for metastatic cancers, targeting VEGF and its receptors and improving patients' survival for metastatic carcinoma (kidney, GIST, breast, colorectal). The objective of these treatments is to block either circulating VEGF (bevacizumab; VEGF-Trap), or tyrosine kinase receptors (especially the VEGF receptor) (sorafenib, sunitinib, brivanib, imatinib, etc.). Indeed, VEGF stimulates endothelial cell proliferation and then tumour growth and metastasis. However, all these antiangiogenic drugs share similar side effects, most frequently gastrointestinal disturbance, skin toxicity and hypertension. Hypertension seems to be especially frequent in case of good response. Renal side effects have probably been underestimated in the first place and their exact frequency is not known, needing some specific trials and registries. Proteinuria, thrombotic microangiopathies and acute renal failures have been reported: renal biopsies might be necessary for precise evaluation of renal damages. Physiopathology seems very close to preeclampsia. Good collaboration between oncologists, nephrologists and cardiologists is therefore crucial in order to continue these targeted therapies safely for the patients.
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PMID:[Renal toxicity of anti-VEGF (corrected) targeted therapies]. 2341 Sep 50

Abnormal B cells, which produce antibodies against self-antigens, play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). B-cell activating factor (BAFF) is closely associated with abnormal B cells and participates in B cell-mediated autoimmune diseases; thus, neutralizing BAFF is an effective method for treating these diseases. Our group designed a novel fusion protein, BAFF-Trap, that contains the BAFF-binding domains of two BAFF receptors (TACI and BAFF-R) and the Fc domain of human IgG1. In this study, we showed that BAFF-Trap significantly decreased the autoantibody levels, BAFF concentrations and B cells numbers in MRL/lpr mice. BAFF-Trap suppressed the expression of pro-inflammatory cytokines in the kidney and decreased the frequencies of T cell subsets and dendritic cells. Furthermore, BAFF-Trap reduced proteinuria and IgG deposition, relieved glomerular damage in the kidney, and markedly improved the survival rate of mice. These results indicated that BAFF-Trap may be a potential drug for the treatment of SLE.
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PMID:A novel BAFF antagonist, BAFF-Trap, effectively alleviates the disease progression of systemic lupus erythematosus in MRL/lpr mice. 3325 74