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

longitudinal assessment of neutrophil to lymphocyte ratio nlr from diagnosis until death reveals a biphasic trend in metastatic pancreatic adenocarcinoma patients

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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 >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

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

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

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

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

Polynuclear Complexes: Two Amino-Phenol Macrocycles Spaced by Several Linear Polyamines; Synthesis, Binding Properties, and Crystal Structure

The synthesis and characterization of the new polytopic ligands 1,14-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,115-trien-6-yl)-3,6,9,12-tetraazatetradecane L1, 1,15-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,115-trien-6-yl)-3,6,10,13-tetraazapentadecane L2, and 1,16-bis(3,6,9-triaza-15-hydroxybicyclo[9.3.1]pentadeca-11,13,115-trien-6-yl)-3,7,10,14-tetraazahexadecane L3, containing two equal amino-phenol macrocycles spaced by several linear tetraamines, are reported. The basicity and coordination behavior toward the Cu(II) ion were potentiometrically determined in aqueous solution at 298.1 K. All the ligands show similar acid-base properties behaving as octaprotic bases in the examined pH range (pH = 2-12). The acid protons of L1-L3 cannot be removed under the experimental conditions used; thus, the main deprotonated species obtainable in aqueous solution are the neutral ligands, having amphionic character as demonstrated by UV-vis experiments. These species are able to form mono-, di-, and trinuclear Cu(II) complexes having stoichiometry [CuL]2+, [Cu2L]4+, and [Cu3L]6+, respectively, that can lose one or two protons giving rise to [CuH-1L]+, [Cu2H-2L]2+, and [Cu3H-2L]4+. Depending on the used ligand to metal molar ratio, the mono-, di-, or trinuclear species prevail over the others in solution. Both di- and trinuclear complexes are able to add secondary ligands (such as OH-), and in some cases two Cu(II) can cooperate to stabilize themby coordinating the guest in a bridged conformation. The structure of the [Cu2L3]4+ cation was resolved by X-ray analysis of the {[Cu2L3](ClO4)4 3 3H2O}2 3 H2O crystalline complex. It shows that each Cu(II) is penta-coordinated by one phenolate oxygen, two amine functions, belonging to one macrocyclic unit, and two amine functions of the spacer; in this species the distance between the two Cu(II) is about 5.3 Å

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