Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker

Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration. Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cance

UvA-DARE (Digital Academic Repository) Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker

Abstract Background: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that &apos;&apos;true&apos;&apos; circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis

Tunable Nanostructures and Crystal Structures in Titanium Oxide Films

Controllable nanostructures in spin coated titanium oxide (TiO2) films have been achieved by a very simple means, through change of post deposition annealing temperature. Electron beam imaging and reciprocal space analysis revealed as-deposited TiO2films to be characterized by a dominant anatase phase which converts to the rutile form at 600 °C and reverts to the anatase modification at 1,200 °C. The phase changes are also accompanied by changes in the film microstructure: from regular nanoparticles (as-deposited) to nanowires (600 °C) and finally to dendrite like shapes at 1,200 °C. Photoluminescence studies, Raman spectral results, and X-ray diffraction data also furnish evidence in support of the observed solid state phase transformations in TiO2

Electrospray Ionization with High-Resolution Mass Spectrometry as a Tool for Lignomics: Lignin Mass Spectrum Deconvolution

Capability to characterize lignin, lignocellulose, and their degradation products is essential for development of new renewable feedstocks. Electrospray ionization high-resolution time-offlight mass spectrometry (ESI HR TOF MS) method was developed expanding the lignomics toolkit while targeting the simultaneous detection of low and high molecular weight (MW) lignin species. The effect of a broad range of electrolytes and various ionization conditions on ion formation and ionization effectiveness was studied using a suite of mono-, di- and triarene lignin model compounds as well as intact lignin. Contrary to the previous studies, the positive ionization mode was found to be more effective for methoxy-substituted arenes and polyphenols, i.e., species of a broadly varied MW structurally similar to the native lignin. For the first time, we report an effective formation of multiply charged species of lignin with the subsequent mass spectrum deconvolution in the presence of 100 mmol·L-1 formic acid in the positive ESI mode. The developed method enabled the detection of lignin species with an MW between 150 and 9,000 Da or higher, depending on the mass analyzer. The obtained Mn and Mw values of 1,500 and 2,500 Da, respectively, were in good agreement with those determined by gel permeation chromatography. Furthermore, the deconvoluted ESI mass spectrum was similar to that obtained with matrixassisted laser desorption/ionization (MALDI) TOF MS, yet featuring a higher signal-to-noise ratio. The formation of multiply charged species was confirmed with ESI ion mobility HR Q-TOF MS

[New antibiotics: an overview]

The worldwide rapid increase in antibiotic resistance means that new therapeutic measures are urgently needed. Older antibiotics, such as colistin, fosfomycin, minocycline, mecillinam and temocillin, which had fallen from grace due to the development of more effective and less toxic drugs are now of renewed interest in the treatment of infections caused by multiresistant bacteria. Two new glycopeptides (oritavancin and dalbavancin) and a new oxazolidinone (tedizolid) are now registered for the treatment of acute skin and soft-tissue infections. In the treatment of infections caused by Gram-negative bacteria, cephalosporins are combined with beta-lactamase inhibitors which protect them from various beta-lactamases and also make them effective against extended spectrum beta-lactamase-producing bacteria. Examples of these are ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. Results of preclinical research on the effectiveness of new antibiotics are hopeful. There has been a great increase in investment in the development of new antimicrobials. Also, regulatory agencies have accelerated their assessment of these new - and urgently needed - drugs

[New antibiotics: an overview]

Item does not contain fulltextThe worldwide rapid increase in antibiotic resistance means that new therapeutic measures are urgently needed. Older antibiotics, such as colistin, fosfomycin, minocycline, mecillinam and temocillin, which had fallen from grace due to the development of more effective and less toxic drugs are now of renewed interest in the treatment of infections caused by multiresistant bacteria. Two new glycopeptides (oritavancin and dalbavancin) and a new oxazolidinone (tedizolid) are now registered for the treatment of acute skin and soft-tissue infections. In the treatment of infections caused by Gram-negative bacteria, cephalosporins are combined with beta-lactamase inhibitors which protect them from various beta-lactamases and also make them effective against extended spectrum beta-lactamase-producing bacteria. Examples of these are ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. Results of preclinical research on the effectiveness of new antibiotics are hopeful. There has been a great increase in investment in the development of new antimicrobials. Also, regulatory agencies have accelerated their assessment of these new - and urgently needed - drugs

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids. These alterations may affect many aspects of antiretroviral pharmacokinetics. Some drug characteristics may result in subtherapeutic exposure and the potential related risk of treatment failure and resistance. Antiretrovirals that require low pH, administration of fatty meals, longer intestinal exposure, and an enterohepatic recirculation for their absorption may be most impacted by bariatric surgery procedures. Additionally, some antiretrovirals can interact with the polyvalent cations in supplements or drugs inhibiting gastric acid, thereby preventing their use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on the basis of drug characteristics solely proved to be challenging, therefore pharmacokinetic studies remain crucial in this population. Here, we discuss general implications of bariatric surgery on antiretroviral outcomes in people living with HIV as well as drug properties that are relevant for the choice of antiretroviral treatment in this special patient population. Additionally, we summarise studies that evaluated the pharmacokinetics of antiretrovirals post-bariatric surgery. Finally, we performed a comprehensive analysis of theoretical considerations and published pharmacokinetic and pharmacodynamic data to provide recommendations on antiretrovirals for people living with HIV undergoing bariatric surgery