Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect

The Italian fund for Alzheimer's and other dementias: strategies and objectives to face the dementia challenge

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper

Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LARVMAT-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P = .004) and mediastinal plus unilateral neck (P = .02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P = .02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P = .038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach. (C) 2015 Elsevier Inc. All rights reserved

Inclusion of heart substructures in the optimization process of volumetric modulated arc therapy techniques may reduce the risk of heart disease in Hodgkin's lymphoma patients

Background and purpose: Radiotherapy is an effective treatment for Hodgkin's lymphoma (HL), but increases the risk of long term complications as cardiac events and second cancers. This study aimed to reduce the risk of cardiovascular events through an optimization of the dose distribution on heart substructures in mediastinal HL patients with the adoption of different volumetric modulated arc therapy (VMAT) techniques, while maintaining the same risk of second cancer induction on lungs and breasts. Materials and methods: Thirty patients (15 males and 15 females, 15 bulky lesions) treated between 2012 and 2017 at our institution were selected. Disease extent was mediastinum plus neck (n = 10), mediastinum plus unilateral axilla (n = 10) and mediastinum alone (n = 10). Lungs, breasts, whole heart and sub-structures (coronary arteries, valves and chambers) were contoured as organs at risk and included in the optimization process. A “first-generation” multi-arc butterfly VMAT (B-VMAT) planning solution was compared to a full-arc butterfly VMAT (FaB-VMAT) approach, consisting of a full arc plus a non-coplanar arc. Lifetime attributable risk (LAR) of second breast and lung cancer and relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. Results: FaB-VMAT resulted in lower mean dose to whole heart (7.6 vs 6.9 Gy, p = 0.003), all coronary arteries (16.1 vs 13.5 Gy, p < 0.001), left ventricle (4.2 vs 3.4 Gy, p = 0.007) and in lower V20Gy to the lungs (15% vs 14%, p = 0.008). A significant lower RR for CAD and CHF was observed for FaB-VMAT. The risk of second breast and lung cancer was comparable between the two solutions, with the exception of female patients with mediastinal bulky involvement, where B-VMAT resulted in lower mean dose (2.8 vs 3.5 Gy, p = 0.03) and V4Gy (22% vs 16%, 0.04) to breasts, with a significant reduction in LAR (p = 0.03). Conclusions: FaB-VMAT significantly decreased the RR for CAD and CHF compared to B-VMAT, with almost the same overall risk of lung and breast cancer induction. These results are influenced by the different anatomical presentations, supporting the need for an individualized approach