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

Rainfall validates MODIS-derived NDVI as an index of spatio-temporal variation in green biomass across non-montane semi-arid and arid Central Asia

As satellite-derived normalized difference vegetation index (NDVI) is related to vegetation biomass, it may provide a proxy for habitat quality across extensive species ranges where ground-truth data are scarce. However, NDVI may have limited accuracy in sparsely-vegetated arid and semi-arid environments due to signal contamination by substrate reflectance. To validate NDVI as a vegetation proxy in the low-altitude deserts of Central Asia, we examine its response to precipitation across the migratory corridor of Asian Houbara. NDVI increases with precipitation, both spatially (adj. R2 = 0.58, p < 0.001) and temporally (mean adj. R2 across n=244, 1 degree cells = 0.44; GLMM across cells p < 0.001). More vegetated regions show a stronger temporal response of vegetation biomass for a given precipitation increment (slope of NDVI to precipitation in per cell temporal models increases with inter-annual mean NDVI; adj. R2 = 0.38, p < 0.001), reinforcing the conclusion that NDVI provides a proxy for vegetation abundance. The strong signature of rainfall shows MODIS NDVI offers a potentially powerful proxy for spatial and temporal variation in arid and semi-arid vegetation at a resolution of 1 degree and 1 year over the houbara's breeding and wintering range, and probably also at finer spatial resolutions

A computational multiscale approach to couple hygro-mechanical responses of large-scale masonry walls

We present a computational multiscale approach to the nonlinear problems of humidity diffusion and mechanical damage of large-scale masonry walls, and their coupling in terms of the effects of the humidity diffusion on the mechanical response and the effects of the mechanical degradation on the diffusion process. Such an approach allows us to recover, both efficiently and accurately, the complex nonlinear response of large-scale walls, which are in general hard to be solved by means of standard numerical tools. Two representative tests of two- and three-storey walls are here analyzed, and the corresponding results reported and commented, aiming to show how samples like these can potentially serve as reference solutions for more applicative purposes

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

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

CEA and CYFRA 21-1 as prognostic biomarker and as a tool for treatment monitoring in advanced NSCLC treated with immune checkpoint inhibitors

Aims: To assess prognostic value of pre-therapy carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) blood levels in non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICIs) and their early change as predictor of benefit. Materials and methods: This is a retrospective cohort study including patients with stage IIIB–IV NSCLC who received anti PD-1/PD-L1 in first or advanced lines of therapy in two institutions. A control cohort of patients treated only with chemotherapy has been enrolled as well. Results: A total of 133 patients treated with nivolumab or atezolizumab were included in the test set, 74 treated with pembrolizumab first line in the validation set and 89 in the chemotherapy only cohort. CYFRA 21-1 &gt;8 ng/mL was correlated with overall survival (OS) in the test set, validation set and in univariate and multivariate analysis (pooled cohort hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.24–2.93, p 0.003). Early 20% reduction after the third cycle was correlated with OS for CEA (HR 0.12; 95% CI 0.04–0.33; p &lt; 0.001), and for CYFRA 21-1 (HR 0.19; 95% CI 0.07–0.55; p 0.002) Conclusions: CYFRA 21-1 pre-therapy assessment provides clinicians with relevant prognostic information about patients treated with ICI. CEA and CYFRA 21-1 repeated measures could be useful as an early marker of benefit

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

Obesity and Breast Cancer: Interaction or Interference with the Response to Therapy?

Background: Aromatase inhibitors (AI) are widely used for treating hormone-sensitive breast cancer (BC). Obesity, however, due to aromatase-mediated androgen conversion into estradiol in the peripheral adipose tissue, might impair AI inhibitory capacity. We aimed at identifying a cut-off of body mass index (BMI) with significant prognostic impact, in a cohort of stage I-II BC patients on systemic adjuvant therapy with AI. Methods: we retrospectively evaluated routinely collected baseline parameters. The optimal BMI cut-off affecting disease-free survival (DFS) in AI-treated BC patients was identified through maximally selected rank statistics; non-linear association between BMI and DFS in the AI cohort was assessed by hazard-ratio-smoothed curve analysis using BMI as continuous variable. The impact of the BMI cut-off on survival outcomes was estimated through Kaplan-Meier plots, with log-rank test and hazard ratio estimation comparing patient subgroups. Results: A total of 319 BC patients under adjuvant endocrine therapy and/or adjuvant chemotherapy were included. Curve-fitting analysis showed that for a BMI cut-off &gt;29 in AI-treated BC patients (n = 172), DFS was increasingly deteriorating and that the impact of BMI on 2-year DFS identified a cut-off specific only for the cohort of postmenopausal BC patients under adjuvant therapy with AI. Conclusion: in radically resected hormone-sensitive BC patients undergoing neoadjuvant or adjuvant chemotherapy and treated with AI, obesity represents a risk factor for recurrence, with a significantly reduced 2-year DFS