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)

Tumor angiogenesis is a hallmark of advanced cancers and an attractive treatment target in multiple solid tumors. In the past 5 years anti-angiogenic therapies have seen a rapid ascent into mainstream clinical practice. For head and neck cancer (HNC), definitive evidence in the form of a pivotal trial is still pending. Nevertheless, preclinical and early clinical data support a central role of angiogenesis for HNC: up to 90% of HNCs express angiogenic factors such as vascular endothelial growth factor (VEGF) and the respective receptors (VEGFR1-3), and multiple studies support the prognostic implications of angiogenic markers for this tumor. Contrary to concerns that anti-angiogenic therapies could increase hypoxia and thereby treatment resistance, anti-angiogenic therapies in preclinical models appear to overcome resistance and preclinically synergize with traditional therapies, eg, radiation. Clinical use of anti-angiogenic agents for HNC, including bevacizumab, sorafenib, sunitinib, and others, is currently limited to clinical trials, and several larger trials are still ongoing. Single-agent anti-angiogenic drugs so far have not shown activity in unselected HNC patients, with a response rate of less than 4% for the small molecule anti-angiogenics sorafenib and the investigational agent SU5416. On the other hand, combinations of anti-angiogenic drugs with other treatments (analogous to other solid tumors) appear promising; for example, the combination of bevacizumab with the EGFR inhibitor erlotinib showed a response rate of 14.6%. Studies of bevacizumab with chemotherapy (phase III Eastern Cooperative Oncology Group [ECOG] trial) and in combination with chemoradiation are currently ongoing. The side effect profile is comparable to what has been observed in other tumor types and include hypertension, proteinuria, and thrombotic and hemorrhagic events. With the intense research effort preclinically and clinically, and some encouraging early results, anti-angiogenic therapies and biomarkers appear to be poised to play an important role in the treatment of HNC in the near future.
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PMID:Targeting angiogenesis in head and neck cancer. 1854 42

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that is currently validated for treatment and has shown survival benefit in various cancers, particularly non-small cell lung cancer. However, a very specific toxicity profile has been observed with bevacizumab. This article presents data from the literature concerning hypertension and proteinuria, and provides recommendations for the management of these toxicities.
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PMID:[Bevacizumab and arterial hypertension or proteinuria: management]. 1877 32

The renal renin-angiotensin system plays a major role in determining the rate of chronic renal disease progression. Treatment with activators of the vitamin D receptor retards the progression of experimental chronic renal disease, and vitamin D is known to suppress the renin-angiotensin system in other organs. Here we determined if the beneficial effects of paricalcitol (19-nor 1,25-dihydroxyvitamin D(2)) were associated with suppression of renin-angiotensin gene expression in the kidney. Rats with the remnant kidney model of chronic renal failure (5/6 nephrectomy) were given two different doses of paricalcitol thrice weekly for 8 weeks. Paricalcitol was found to decrease angiotensinogen, renin, renin receptor, and vascular endothelial growth factor mRNA levels in the remnant kidney by 30-50 percent compared to untreated animals. Similarly, the protein expression of renin, renin receptor, the angiotensin type 1 receptor, and vascular endothelial growth factor were all significantly decreased. Glomerular and tubulointerstitial damage, hypertension, proteinuria, and the deterioration of renal function resulting from renal ablation were all similarly and significantly improved with both treatment doses. These studies suggest that the beneficial effects of vitamin D receptor activators in experimental chronic renal failure are due, at least in part, to down-regulation of the renal renin-angiotensin system.
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PMID:Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. 1914 59

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF(165)b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF(165)-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means+/-S.E.M. plasma VEGF(165)b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF(165)b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90+/-1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40+/-0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF(165)b levels were lower than in the normotensive group (0.467+/-0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF(165)b concentrations were greater than normal in both pre-eclamptic (3.75+/-2.24 ng/ml) and normotensive (10.58 ng/ml+/-3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF(165)b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20+/-0.07 and 1.27+/-0.18 ng/ml) and sEng (4.4+/-0.18 and 4.1+/-0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF(165)b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF(165)b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.
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PMID:Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia. 1907 60

Intraocular delivery of anti-vascular endothelial growth factor (VEGF) therapies is now used widely to treat age-related macular degeneration, and is currently undergoing evaluation in clinical trials for treatment of diabetic retinopathy. An important aspect of anti-VEGF treatment is that while the agents are injected into the vitreous cavity, they may be absorbed systemically, thus potentially affecting systemic VEGF levels. Systemic VEGF-A and the interplay between membrane-bound VEGF receptors and the soluble form of VEGF-R1 are key to angiogenesis, vasculogenesis, neurogenesis and hemodynamics. These cellular processes are regulated by complicated negative and positive feedback loops, many of which are disrupted and altered in diabetes. The VEGF protein, mRNA, as well as the actual VEGF receptor levels, appear to be impaired in diabetes in microvascular and macrovascular vessel beds. What is not clear is the exact role and influence that these levels have on an organ's function. In some organ systems, elevated VEGF levels act as a pathologic angiogenic stimulus (i.e., ocular neovascularization) whereas in others, low levels of VEGF activity leads to pathology (i.e., cardiomyopathy, wound healing and peripheral neuropathy). Diabetic patients have a higher risk of hypertension and proteinuria, two surrogate markers of systemic VEGF inhibition. Certain intraocular anti-VEGF treatments could therefore have an adverse effect in this population by possibly affecting circulating and organ-specific VEGF and VEGF receptor levels.
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PMID:Vascular endothelial growth factor and diabetic complications. 1892 76

Targeted and biological therapies have been investigated as methods of improving anticancer therapy. One approach to targeted therapy is to inhibit tumor angiogenesis, which has a critical role in the development of cancer. However, the potential for further improvement in outcomes is likely to be limited by its nephrotoxic side effects such as urinary protein and hypertension. Among the anti-angiogenesis inhibitors, the humanized monoclonal antibody, bevacizumab, directed against VEGF(vascular endothelial growth factor), is the first anti-angiogenic agent to be approved for cancer therapy, but it has a high frequency of these side effects. Hypertension could be due to a reduction of eNOS activity and rarefaction of microvessels in various tissues and organs induced by VEGF inhibition. Bevacizumab also induces proteinuria, glomerular endothelial cell detachment and suppression of nephrin, an important protein for the maintenance of the glomerular slit diaphragm, sometimes leading to nephritic syndrome and/or thrombotic microangiopathy in the glomeruli. Periodic monitoring of blood pressure and urinary protein should be necessary in patients on anti- VEGF agents. Patients showing nephrotoxicities need special referral to nephrologists and to be treated using proper anti-hypertension drugs.
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PMID:[Nephrotoxicity--proteinuria and hypertension--]. 1893 64

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. The use of bevacizumab has shown survival benefit in variety of cancers. However, a specific toxicity profile has been observed with bevacizumab such as hypertension, proteinuria, gastrointestinal perforation and arterial thrombosis. Non-small-cell lung cancer is often associated with thrombotic event therefore guidelines are expected to prescribe bevacizumab in this population. This article presents data from literature about the thrombotic risk and provides recommendations for the use of anticoagulant and antiaggregant treatments.
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PMID:[Thrombo-embolic risks and bevacizumab: data from the literature and recommendations for the use of anticoagulants and antiaggregants]. 1897 8

Bevacizumab (Avastin) is a humanized monoclonal antibody that inhibits the activity of vascular endothelial growth factor (VEGF), a key molecule controlling tumour blood vessel formation (angiogenesis). By inhibiting VEGF and thus tumour angiogenesis, bevacizumab inhibits tumour growth and survival. In patients with metastatic colorectal cancer (CRC), first-line use of bevacizumab in combination with fluoropyrimidine-based chemotherapy improves outcomes compared with chemotherapy alone. The side-effect profile of bevacizumab does not overlap with that of conventional chemotherapy, and it does not significantly exacerbate chemotherapy-induced adverse events. Specific side-effects of special interest for bevacizumab include hypertension, proteinuria, arterial thromboembolic events, wound-healing complications, bleeding events and gastrointestinal perforation. Oncology nurses are key to early recognition and management of side-effects, in addition to having a key role in patient education, facilitating the optimal use of bevacizumab and thus survival of patients with metastatic CRC.
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PMID:Managing patients with metastatic colorectal cancer on bevacizumab. 1898 14

Pre-eclampsia, a pregnancy complication characterized by hypertension and proteinuria, is still a major cause of neonatal and maternal mortality, and acute and long-term morbidities for both mother and neonate. There is mounting evidence that an imbalance between angiogenic factors, such as VEGF (vascular endothelial growth factor) or PlGF (placental growth factor), and factors inhibiting angiogenesis, such as sFlt1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), are closely related to the pathogenesis of pre-eclampsia. In the present issue of Clinical Science, Bills and co-workers report that VEGF(165)b, an alternative splice variant of the VEGF pre-mRNA, is up-regulated in women with normal pregnancy and that this increase was delayed or diminished in women who developed pre-eclampsia. Thus this protein could serve (alone or in combination with other parameters) as a new marker for risk assessment in terms of pre-eclampsia.
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PMID:Angiogenic factors and pre-eclampsia: an early marker is needed. 1882 76

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.
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PMID:Vascular biology of preeclampsia. 1908 23


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