Thromboembolic events in patients treated with anti-angiogenic drugs

Induction of neo-angiogenesis is a fundamental step in many pathological conditions. The therapeutic value of inhibiting angiogenesis is an interesting area of research in oncology, with vascular endothelial growth factor (VEGF) being the most suitable anti-angiogenic target. In the last decade a number of anti-VEGF drugs have demonstrated, especially in combination with standard chemotherapy, clinical efficacy in the treatment of different solid tumor types. As data from clinical trials on anti-VEGF drugs are becoming available, it is increasingly recognized that VEGF, in addition to being a permeability, proliferation, and migration factor, is also a maintenance and protection factor for endothelial cells, being capable of regulating multiple biological functions, i.e. the production of vasoactive mediators and the expression of components of the thrombolytic and coagulation pathways. Consequently, the disturbance of vascular homeostasis by blocking VEGF may lead to endothelial dysfunction and adverse vascular effects, such as venous and arterial thromboembolic events. In preclinical models angiogenesis and the increased expression of VEGF has been associated to altered expression of proinflammatory genes. These genes may be regulated in a biphasic manner, and it is possible that anti-VEGF therapy may disrupt a negative feedback loop that leads to potential in situ thrombus formation. Accordingly, combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was recently associated with an increased risk of thromboembolism. The present review considers the biological mechanisms and clinical impact of thromboembolic complications during anti-angiogenic treatments in cancer patients

Percutaneous combined therapy for painful sternal metastases: a radiofrequency thermal ablation (RFTA) and cementoplasty protocol

Radiofrequency thermal ablation (RFTA) has recently been introduced for the treatment of painful bone metastases. We report the outcome of one combined protocol session of percutaneous RFTA and cementoplasty on a painful sternal breast cancer metastasis of a 66-year-old patient

Non-steroidal anti-inflammatory drugs in cancer prevention and therapy

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) can be regarded as an effective approach for cancer chemoprevention, as demonstrated by a bulk of clinical and experimental evidence. However, the clinical use of these drugs as chemopreventive agents is limited by many open questions about the optimal drug, dose, duration of therapy and knowledge about the mechanism(s) by which these drugs act. In particular, the recent data on cardiovascular toxicity of coxibs has posed some limitations on the use of NSAIDs for cancer chemoprevention in the general population. The situation is different in certain genetically susceptible subgroups, such as in individuals with genetic mutations associated with hereditary nonpolyposis colon cancer (HNPCC) or familiar adenomatous polyps (FAP) in whom lifetime risk increases up to 70-90% and in whom the benefit of a chemopreventive drug might justify its use even in the presence of adverse effects

Caregiver distress in the early phases of cancer

Principal caregivers (PCs) of cancer patients experience high levels of stress that may significantly impact their quality of life (QoL). PCs' QoL during early phases of the disease (when patients were still on chemotherapy) were assessed

Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab

The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients

An Artificial Intelligence Approach to Detect Visual Field Progression in Glaucoma Based on Spatial Pattern Analysis.

Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P \u3c 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns

Ultrathin 2 nm gold as ideal impedance-matched absorber for infrared light

Thermal detectors are a cornerstone of infrared (IR) and terahertz (THz) technology due to their broad spectral range. These detectors call for suitable broad spectral absorbers with minimalthermal mass. Often this is realized by plasmonic absorbers, which ensure a high absorptivity butonly for a narrow spectral band. Alternativly, a common approach is based on impedance-matching the sheet resistance of a thin metallic film to half the free-space impedance. Thereby, it is possible to achieve a wavelength-independent absorptivity of up to 50 %, depending on the dielectric properties of the underlying substrate. However, existing absorber films typicallyrequire a thickness of the order of tens of nanometers, such as titanium nitride (14 nm), whichcan significantly deteriorate the response of a thermal transducers. Here, we present the application of ultrathin gold (2 nm) on top of a 1.2 nm copper oxide seed layer as an effective IR absorber. An almost wavelength-independent and long-time stable absorptivity of 47(3) %, ranging from 2 $\mu$m to 20 $\mu$m, could be obtained and is further discussed. The presented gold thin-film represents analmost ideal impedance-matched IR absorber that allows a significant improvement of state-of-the-art thermal detector technology

Prognostic value of carcinoembryonic antigen and vascular endothelial growth factor tumor tissue content in colorectal cancer

This study was designed to assess the prognostic significance of the combined measurement of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) tissue content with respect to relapse-free and overall survival of patients with colorectal cancer (CRC)

Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde