Search

Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity. Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing

Although no data is quantifying exactly the number of informal caregivers in Italy, according to a 2018 ISTAT survey there are more than 12 million people between the ages of 18 and 64 who take care of a family member (Istat, 2018) and the figure is continuously growing. This has led scholars to investigate the positive and negative aspects of being a caregiver. Within this framework, the research project named "For caregiver, not caregiving" was born, addressed to HR managers and corporate welfare providers to identify policies that can support the caregiver in the work-life balance and more specifically e) Understanding the policies and organizational practices promoted by providers and HR managers to promote caregivers' careers f) To understand the providers' and HR managers' views on caregivers' career development g) To investigate the role of care providers and HR in supporting caregivers in the performance of their care tasks and their career development h) To investigate in depth the caregivers' experiences following the pandemic. These objectives were explored through qualitative methodology. The sample consisted of 20 respondents, 10 from human resources management of large companies and 10 from corporate welfare providers. The research showed how caregiver employees experience a balance between the work and personal spheres, thanks to work-life balance practices and the services and products offered by companies. Furthermore, it emerged how there should be fruitful interaction between corporate welfare providers, human resources management, and employee caregivers to enhance life experiences that lead to acquiring different skills useful in the working world.

Nell’ambito degli approcci ai sistemi di welfare e ai servizi alla persona, accanto alla più nota contrapposizione tra modelli assistenzialistici e modelli che prefigurano l’empowerment, la sussidiarietà e la co-produzione (Donati e Colozzi, 2005; Lodigiani e Pesenti, 2014), possiamo ritrovare una significativa contrapposizione tra modelli centrati sull’individuo (caratteristici del welfare state) e modelli centrati sulle relazioni costitutive della persona (Think family model). Questi ultimi faticano tuttavia ad affermarsi, in quanto la diffusione dei modelli universalistici di welfare si è generalmente accompagnata con un orientamento alla defamilization , ovvero a considerare gli individui indipendenti dalle relazioni familiari, vedendo nella solidarietà familiare e intergenerazionale più un vincolo all’autorealizzazione individuale (e in particolare alla parità di genere) che una possibile risorsa per il benessere personale e relazionale. Adottare lo sguardo Think family, al contrario, significa comprendere la stretta interconnessione esistente tra bisogni e risorse dei diversi individui entro le relazioni familiari; da ciò deriva che qualsiasi intervento/politica deve superare una visione focalizzata sui diritti/opportunità dell’individuo, considerandolo invece in relazione con la complessità del contesto familiare e valorizzando la capacità della famiglia di mediare tra le esigenze dei suoi componenti e di mettere a sistema le risorse di cui dispone, capitalizzandole. Perché questo pensiero prenda piede, tuttavia, si rende necessario un cambiamento culturale (think family), unitamente al superamento di ostacoli strutturali, giuridici, organizzativi, economici, fiscali che rallentano o impediscono il passaggio da Think family ad Act Family. Nell’approccio Think family, Act Family la famiglia si presenta come cornerstone nella pianificazione, attuazione e valutazione di interventi/politiche, e ciò ha un duplice significato: da una parte, promuovere i

La fase di invecchiamento rappresenta un momento critico caratterizzato da cambiamenti nella vita quotidiana e nelle relazioni sociali dei soggetti. La solitudine e l’isolamento sociale emergono come indicatori significativi di una transizione all’età anziana più soggetta a fragilità biologiche, psicologiche e relazionali. Il contributo si concentra sulla transizione all’età anziana e il suo impatto sulle reti sociali e familiari dei soggetti coinvolti. L’obiettivo dell’analisi è comprendere, attraverso la voce degli anziani e delle loro persone di riferimento, la qualità delle reti di supporto e di sostegno durante questa transizione. Mediante la lente del capitale sociale, il lavoro contribuisce alla comprensione di come le risorse e le relazioni vengono messe in gioco per affrontare le sfide dell’invecchiamento e come la qualità dei legami influenza il presente e il futuro degli individui coinvolti.

Brain metastasis (BM) represents a clinical challenge for patients with advanced HER2 + breast cancer (BC). The monoclonal anti-HER2 antibody trastuzumab (TZ) improves survival of BC patients, but it has low central nervous system penetrance, being ineffective in treating BM. Previous studies showed that ferritin nanoparticles (HFn) may cross the blood brain barrier (BBB) through binding to the transferrin receptor 1 (TfR1). However, whether this has efficacy in promoting the trans-BBB delivery of TZ and combating BC BM was not studied yet. Here, we investigated the potential of HFn to drive TZ brain delivery and promote a targeted antitumor response in a murine model of BC BM established by stereotaxic injection of engineered BC cells overexpressing human HER2. HFn were covalently conjugated with TZ to obtain a nanoconjugate endowed with HER2 and TfR1 targeting specificity (H-TZ). H-TZ efficiently achieved TZ brain delivery upon intraperitoneal injection and triggered stable targeting of cancer cells. Treatment with H-TZ plus docetaxel significantly reduced tumor growth and shaped a protective brain microenvironment by engaging macrophage activation toward cancer cells. H-TZ-based treatment also avoided TZ-associated cardiotoxicity by preventing drug accumulation in the heart and did not induce any other major side effects when combined with docetaxel. These results provided in vivo demonstration of the pharmacological potential of H-TZ, able to tackle BC BM in combination with docetaxel. Indeed, upon systemic administration, the nanoconjugate guides TZ brain accumulation, reduces BM growth and limits side effects in off-target organs, thus showing promise for the management of HER2 + BC metastatic to the brain.

Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We tested the BDC-HFn solubility, stability, and ability to cross a blood-brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. Results: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Conclusions: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.

It's an annual review on leave policies

The Italian Government implemented different containment measures at the various phases of the pandemic. This has profoundly transformed people’s lives, both from the point of view of family and significant relationships, and at work, substantially modifying the relationship between these two significant areas. In this chapter, we will first present an overview of the containment measures implemented to tackle the spreading of the virus and outline their main policies, their contents, aims, and underlying focus. Then we will focus on consequences for women. With the emergence of the Covid 19 emergency in the early 2020s, the media immediately started to highlight the likely future increase in cases of violence against women in the home due to the increased risk of lockdown and the difficulties for victims living with their abuser to report and seek support services. A second theme is the impact on family and work responsibilities integration. Several studies in Italy, including a longitudinal survey conducted by the authors, have shown how the emergency and containment measures impacted both personal/parental and work spheres, producing adverse effects on the specific group of working parents, especially women. Using a longitudinal approach, with data collected in three waves (April, July, and December 2020), we assess the consequences of the Working From Home policy, showing that wellbeing decreased and work-life conflict increased with time and that working parents found the first lockdown particularly challenging

La pandemia ha cambiato profondamente la vita quotidiana e il modo di lavorare delle persone. Le misure di distanziamento per contenere la diffusione del virus hanno aumentato i tassi di disoccupazione e portato a livelli senza precedenti il lavoro da casa. Inoltre, il drammatico spostamento della responsabilità di cura dell'infanzia e di didattica dalle istituzioni formali alle famiglie ha messo i genitori sotto un enorme stress. Per i genitori che lavorano, l'aumento del carico di lavoro educativo e di cura ha portato cambiamenti radicali nei confini tra lavoro e famiglia, risultando in una sovrapposizione unica di ruoli genitoriali e lavorativi. Non sorprende dunque che i tassi di natalità si siano abbassati drasticamente e che i tassi di occupazione rilevino un numero record di genitori che lasciano il lavoro o pensano di farlo (McKinsey, 2021). Risulta dunque fondamentale capire come sostenere i genitori lavoratori. Questo contributo presenta i dati di alcuni studi quantitativi e qualitativi condotti a partire da Marzo 2020 sui lavoratori in Italia, in seno al progetto CAREER (CARE for womEn woRk). Particolare attenzione è stata posta sulle differenze di genere in quanto studi provenienti da paesi diversi attestano un impatto differenziale del Covid-19 nelle donne e in particolare il pesante costo pagato dalle madri lavoratrici. Il quadro che ne emerge è complesso e non privo di ambivalenze, ma ciò che risulta fondamentale è ripensare in questo mutato scenario al complesso rapporto tra famiglia e lavoro, non più in termini di bilanciamento, ma piuttosto come un intreccio complesso di ambiti i cui confini sia fisici che psicologici sono ora del tutto annullati

Purpose: Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci. Materials and Methods: We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots (P@QD-MdC NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model. Results: Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, P@QD-MdC NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to P@QD-MdC NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice. Conclusion: P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.

Neoadjuvant chemotherapy has been established as the standard of care for HER2-positive breast cancer since it allows cancer down-staging, up to pathological complete response. The standard of care in the neoadjuvant setting for HER2-positive breast cancer is a combination of highly cytotoxic drugs such as anthracyclines and the anti-HER2 monoclonal antibody. Despite this cocktail allows a pathological complete response in up to 50%, their co-administration is strongly limited by intrinsic cardiotoxicity. Therefore, only a sequential administration of anthracyclines and the anti-HER2 treatment is allowed. Here, we propose the anthracycline formulation in H-Ferritin nanocages as promising candidate to solve this unmet clinical need, thanks to its capability to increase anthracyclines efficacy while reducing their cardiotoxicity. Treating a murine model of HER2-positive breast cancer with co-administration of Trastuzumab and H-Ferritin anthracycline nanoformulation, we demonstrate an improved tumor penetration of drugs, leading to increased anticancer efficacy and reduced of cardiotoxicity.

L’intreccio invisibile tra le relazioni familiari e lavorative Nel contesto sociale contemporaneo, gli ambiti e le sfere di vita delle persone sono sempre più interconnessi tra loro, in particolare la famiglia e il lavoro. Tale intreccio può essere adeguatamente compreso attraverso una concezione relazionale della persona, che la considera un unicum pur nei suoi molteplici ruoli – familiari e professionali – e inserita in reti di relazioni significative. Questo contributo intende offrire una riflessione sul tema adottando non un approccio individuale, ma una prospettiva relazionale, prendendo in considerazione la dimensione di coppia come dispositivo di mediazione nella relazione tra famiglia e lavoro, il capitale sociale come risorsa sia sul versante familiare che professionale e gli scambi tra le generazioni nei due ambiti di vita. Vengono presentati i risultati della ricerca “Talenti senza età”, realizzata nel 2018, su un campione di 12.746 dipendenti senior, tra i 50 e i 70 anni, di 34 aziende italiane di diversi settori., The invisible interweaving between family and work relationships In the contemporary social context, people’s life domains are increasingly connected with one another, especially the family and work domains. This interweaving can be adequately understood through a relational conception of the person, who is considered as an unicum despite playing multiple roles ‒ family and professional ‒ and embedded in networks of significant relationships. This contribution will offer a reflection on the topic not by using an individual perspective, but rather, a relational approach, taking into consideration the element of the couple as a mediator between family and work relationship, social capital as a resource both from a family and professional point of view, and exchanges between generations in the two life domains. Moreover, results from the project ‘‘Talents without age” will be presented, a project carried out in 2018 on a sample of 12,746 senior employees aged between 50 and 70 working in 34 Italian companies from different sectors.

it's an annual review on leave policies

La Direzione Generale Famiglia, Solidarietà Sociale, Disabilità e Pari opportunità della Regione Lombardia ha affidato al Centro di Ateneo Studi e Ricerche sulla Famiglia dell’Università Cattolica la realizzazione di una ricerca il cui obiettivo di carattere generale è quello di raccogliere spunti e idee innovative dai territori e da chi lavora sul campo, nell’ottica di ripensare le politiche regionali per la famiglia e di avviare sul territorio nuove esperienze di intervento per l famiglie. La ricerca ha implicato il coinvolgimento di persone con differenti competenze e provenienze, caratterizzate tutte da una significativa e prolungata esperienza nel campo delle politiche e degli interventi per la famiglia intese in senso ampio (famiglia con bambini, adolescenti, giovani, fragilità, conciliazione famiglia lavoro, famiglie con anziani o disabili, ecc.). Il modello a cui si è fatto riferimento è quello del Family Impact Lens. Attraverso l’uso di specifiche metodologie, quali la tecnica Delphi, integrata con la Scala delle Priorità Obbligate, illustrate nel paragrafo successivo, è stato realizzato un percorso che ha portato a circoscrivere in modo sempre più preciso alcune proposte condivise dagli stakeholders coinvolti e che sono state oggetto di discussione nell’ambito dei convegni e dei laboratori svoltisi nell’estate 2021 e che hanno visto la partecipazione di enti appartenenti al pubblico e al privato sociale della Lombardia.

Monoclonal antibodies (mAbs) have been developed to improve the treatment of cancer patients. They are able to target certain cancer antigens and possess multiple relevant mechanisms of action (i) modifying the host response to the malignant cells, (ii) delivering cytotoxic moieties, (iii) redirecting T cells towards the cancer to reduce cancer progression inducing an anti-tumour immune response [1, 2]. The research of different formats of antibody fragments, such as single chain variable fragment (scFv), Fab, nanobody, bispecific antibody, bifunctional antibody and half-chain antibodies (HC-mAbs) has been focused on the discovery of valuable alternatives to the nanoconjugation of entire mAbs, which could be able to maintain their functional potential [3]. Many monoclonal antibodies approved for therapeutic purposes or are under clinical investigation. Among them, Cetuximab (CTX): a recombinant human/mouse chimeric monoclonal antibody which binds to the tyrosine-kinase Epidermal Growth Factor Receptor (EGFR). It acts by blocking the dimerization of EGFR thus inhibiting downstream signalling pathways. CTX-based treatments suffer of several limitations: inadequate pharmacokinetics, short circulation half-life, low tumour penetration and activation of the autoimmune response [4]. In this context, the rise of nanotechnology has offered new opportunities of treatment with mAbs, exploiting new strategies of conjugation to nanoparticles (NPs) or of incorporation within nanocarriers in order to overcome the major limitations of the mAbs-based conventional therapy [5]. Here, we investigated the effect of a CTX-nanoconjugate on triple negative breast cancer (TNBC). TNBC is a particularly aggressive subtype of breast cancer characterized by high heterogeneity and different molecular expression profiles, which make even more difficult the establishment of targeted therapy to control tumour growth [6]. The majority of TNBCs cell lines are characterized by the overexpression of E

It's an annual review on leaves

Cancer-associated fibroblasts (CAFs) are key actors in regulating cancer progression. They promote tumor growth, metastasis formation, and induce drug resistance. For these reasons, they are emerging as potential therapeutic targets. Here, with the aim of developing CAF-targeted drug delivery agents, we functionalized H-ferritin (HFn) nanocages with fibroblast activation protein (FAP) antibody fragments. Functionalized nanocages (HFn-FAP) have significantly higher binding with FAP+ CAFs than with FAP cancer cells. We loaded HFn-FAP with navitoclax (Nav), an experimental Bcl-2 inhibitor pro-apoptotic drug, whose clinical development is limited by its strong hydrophobicity and toxicity. We showed that Nav is efficiently loaded into HFn (HNav), maintaining its mechanism of action. Incubating Nav-loaded functionalized nanocages (HNav-FAP) with FAP+ cells, we found significantly higher cytotoxicity as compared to non-functionalized HNav. This was correlated with a significantly higher drug release only in FAP+ cells, confirming the specific targeting ability of functionalized HFn. Finally, we showed that HFn-FAP is able to reach the tumor and to target CAFs in a mouse syngeneic model of triple negative breast cancer after intravenous administration. Our data show that HNav-FAP could be a promising tool to enhance specific drug delivery into CAFs, thus opening new therapeutic possibilities focused on tumor microenvironment.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel promising strategy toward triple-negative breast cancer (TNBC). TNBC is a breast cancer subtype that represents one of the main clinical challenges in cancer treatment due to its heterogeneity, biological behavior, invasiveness and poor prognosis. Moreover, it often shows genomic instability and/or BRCA mutations. However, clinical results obtained with PARP inhibitors are controversial, and no benefits were demonstrated in case of wild type BRCA, possibly due to poor bioavailability and inadequate nuclear delivery [1-4]. Nanotechnology could overcome these major limitations with the development of nanocaged-drugs. Among these, the most promising is represented by H-ferritin (HFn): natural protein-based nanoparticles with native capability of targeting tumor cells thanks to its specific interaction with the TfR1, which is overexpressed in tumor cells. HFn are constituted of self-assembling human H-ferritin monomers arranged in a hollow structure. HFn also possess some other unique features very appealing from the clinical point of view: i) uniform cage architecture, which allows the precise control of the amount of encapsulated drugs; ii) negligible toxicity and immunogenicity; iii) stability in physiological environment as a result of their protein nature, which increases circulation time, protects the cargo molecule from degradation and improves bioavailability[5-7]. The aim of this study was to assess the anticancer efficacy of H-Ferritin nanoformulated Olaparib (HOla) vs. free Olaparib (Ola) on BRCA-mutated and non mutated TNBC cells exploiting both the natural targeting of H-ferritin toward the transferrin receptor-1 and also its physiological tropism toward the nuclear compartment. BRCA-mutated HCC1937 cells and BRCA-wild type MDA MB-231 and MDA MB-468 cells were treated with HOla or Ola in vitro. All TNBC cell lines over-expressed TfR-1 and were succesfully recognized by H-Ferritin, displaying a fast i

Evaluation of acute colitis relies on invasive endoscopic examination to assess the presence and the severity of the disease, and on aspecific radiological signs of bowel inflammation, such as contrast enhancement of bowel wall thickening. Consequently, the current best clinical management only offers an approximation of the real clinical scenario, and has a negative impact on the quality of life of patients. An accurate stadiation of inflammatory bowel diseases for assessment of response to therapies or indication for surgery remains challenging. Here, mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) was investigated as a reliable and specific target of active bowel inflammation, to be exploited for site-specific nanotheranostics in a preclinical murine model of colitis. MAdCAM-1 is a cell adhesion molecule, which is upregulated on gut endothelium in case of inflammation at very early stages of the disease, and is responsible for T cells recruitment in involved bowel tracts. Moreover, it is finely related to activity of inflammatory bowel diseases and correlates with response to therapy. Anti-MAdCAM-1 antibodies were conjugated to the surface of smart and safe delivery nanoparticles, consisting of a manganese oxide core endowed with paramagnetic properties. The aim of the study was to assess the in vivo targeting efficacy and the accuracy of these innovative low-toxic MAdCAM-1-targeted nanoparticles, specifically designed to detect active bowel inflammation foci at early stages of the disease. Manganese oxide nanoparticles revealed good stability and polydispersity. Their negligible citotoxicity was demonstrated on endothelial cell cultures by analysis of viability and apoptosis, and on blood samples by hemolysis assay. Colitis was induced in mice by oral treatment with dextran sulfate sodium, and MAdCAM-1 overexpression was assessed on the intestinal vascular endothelium by immunohistochemistry and western blotting. Fluorescent anti-MAdCAM-1 nanoparticles wer

It's an annual review on leave policies and research

Il contributo presenta un programma di enrichment proposto in una azienda: il Relationship Antistress Programme (RAP). Il RAP si ispira alla letteratura sull’enrichment familiare e all’approccio relazionale simbolico di Scabini e Cigoli. Attraverso una metodologia rigorosa il programma si pone l’obiettivo di ridurre lo stress e di promuovere l’identità integrata della persona

Systemic chemotherapy has not significantly reduced clinical demand for triple negative breast cancer (TNBC) treatments. To address the need for more effective therapy, the use of nonviral nanoparticles is explored to deliver suicide gene therapy as valuable alternative to protect nucleic acids in the bloodstream and improve their tumor uptake. Biocompatible cationic lipid nanoparticles are developed as a novel delivery system of a suicide plasmid gene encoding saporin. Active targeting is accomplished by taking advantage of nanoparticle functionalization with U11 peptide, designed to be directed toward urokinase plasminogen activator receptor, limiting off-target toxicity. The antitumor effect of U11-lipid-protamine-DNA (U11-LPD) nanoparticles are tested in TBNC cells, showing a strong prevalence of targeted versus nontargeted nanoparticles in terms of uptake kinetics and proliferation inhibition. Transfection of green fluorescent protein (GFP) plasmid in MDA-MB-231 cells is demonstrated. U11-LPD nanoparticles administered by retro bulbar injection exhibit excellent tumor tropism in TNBC orthotopic xenograft mice and effectively transfect TNBC cells with saporin plasmid resulting in tumor mass reduction. No systemic toxicity or organ damage is discovered after repeated treatments with nanoparticles. The findings suggest that systemic administration of targeted LPD nanoparticles to deliver saporin safely allows for active inhibition of cancer progression even in the absence of specific promoter gene sequences.

La pluralizzazione delle forme familiari e la non linearità dei percorsi costitutivi rappresentano il cambiamento più rilevante che oggi riscontriamo rispetto alla vita familiare: se fino pochi decenni fa la transizione alla vita familiare seguiva una precisa sequenza normativa (fidanzamento, matrimonio religioso o civile e nascita del primo figlio), oggi i percorsi di coppia sono molteplici e non lineari. Nonostante ciò, nel 2018 gli italiani continuano ad attribuire molta importanza alla famiglia d’origine e/o d’elezione (90,5%) e a riporre in essa una completa fiducia (85,4%). All’interno di tale framework, prenderemo in esame i percorsi di coppia (par. 2), gli atteggiamenti nei confronti del matrimonio (par. 3), i valori più importanti da trasmettere ai figli (par. 4) e le rappresentazioni dei ruoli di genere (par. 5). L’analisi longitudinale delle diverse rilevazioni dell’indagine EVS consentirà di mettere in luce gli elementi di continuità e discontinuità emersi negli ultimi quarant’anni.

Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.

il contributo intende tracciare una analisi del sistema legislativo italiano in materia di congedi

Nowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment.

Targeted therapies have profoundly changed the clinical prospect in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. In particular, the anti-HER2 monoclonal antibody trastuzumab represents the gold standard for the treatment of HER2+ breast cancer patients. Its contribution in dampening cancer progression is mainly attributed to the antibody-dependent cell-mediated cytotoxicity (ADCC) rather than HER2 blockade. Here, multiple half chains of trastuzumab were conjugated onto magnetic iron oxide nanoparticles (MNP-HC) to develop target-specific and biologically active nanosystems to enhance anti-HER2 therapeutic potential. HER2 targeting was assessed in different human breast cancer cell lines, where nanoparticles triggered site-specific phosphorylation in the catalytic domain of the receptor and cellular uptake by endocytosis. MNP-HC induced remarkable antiproliferative effect in HER2+ breast cancer cells, exhibiting enhanced activity compared to free drug. Accordingly, nanoparticles induced p27kip1 expression and cell cycle arrest in G1 phase, without loosing capability to prime ADCC. Finally, MNP-HC affected viability of trastuzumab-resistant cells, suggesting interference with the resistance machinery. Our findings indicate that multiple arrangement of trastuzumab half chain on the nanoparticle surface enhances anticancer efficacy in HER2+ breast cancer cells. Powerful inhibition of HER2 signaling could promote responsiveness of resistant cells, thus suggesting ways for drug sensitization.

Successful application of nanoconjugates either in vitro or in vivo does depend on the design strategy used for their development. In this chapter, we focus on the most important factors that need to be taken into account to optimize nanoparticle biofunctionalization and provide an overview of recent approaches yielding the efficient and orientation-controlled immobilization of complex molecules, including peptides and proteins. In addition, we discuss on the elements that cooperate with ligand orientation in affecting the biological activity of nanoconjugates. Indeed, the control of ligand orientation on the nanoparticle surface is of crucial importance in determining the affinity of the immobilized biomolecules toward the biological target. However, the ability of a nanoconjugate to recognize its target is even strongly affected by other important items, including (1) multivalency as a result of ligand density and organization; (2) conformational changes potentially occurring on binding of ligands to the nanoparticle; (3) thermodynamic and kinetic factors related to the interaction of the ligand with the nanoparticle surface; and (4) interaction between nanoparticle and its surrounding environment to form the so-called "protein corona." Altogether, these five issues are the driving force in the specificity and selectivity of designed nanoconjugates toward their target, and, as a consequence, define their potential utility for biomedical application. Therefore, a careful control on the abovementioned "magic five" contributions is needed to improve the quality standard of the next-generation nanomedicines. In addition to the illustrated nanobioconjugation strategies, we emphasize that all these features need to be carefully optimized when assessing the biological effects of synthetic nanoparticles designed for biomedical purposes.

The use of therapeutic monoclonal antibodies (mAbs) has revolutionized cancer treatment. The conjugation of mAbs to nanoparticles has been broadly exploited to improve the targeting efficiency of drug nanocarriers taking advantage of high binding efficacy and target selectivity of antibodies for specific cell receptors. However, the therapeutic implications of nanoconjugation have been poorly considered. In this study, half-chain fragments of the anti-EGFR mAb cetuximab were conjugated to colloidal nanoparticles originating stable nanoconjugates that were investigated as surrogates of therapeutic mAbs in triple negative breast cancer (TNBC). Three TNBC cell lines were selected according to EGFR expression, which regulates activation of MAPK/ERK and PI3K/Akt pathways, and to distinctive molecular profiling including KRAS, PTEN, and BRCA1 mutations normally associated with diverse sensitivity to treatment with cetuximab. The molecular mechanisms of action of nanoconjugated half-chain mAb, including cell targeting, interference with downstream signaling pathways, proliferation, cell cycle, and apoptosis, along with triggering of ADCC response, were investigated in detail in sensitive and resistant TNBC cells. We found that half-chain mAb nanoconjugation was able to enhance the therapeutic efficacy and improve the target selectivity against sensitive, but unexpectedly also resistant, TNBC cells. Viability assays and signaling transduction modulation suggested a role of BRCA1 mutation in TNBC resistance to cetuximab alone, whereas its effect could be circumvented using half-chain cetuximab nanoconjugates, suggesting that nanoconjugation not only improved the antibody activity but also exerted different mechanisms of action. Our results provide robust evidence of the potential of half-chain antibody nanoconjugates in the treatment of TNBC, which could offer a new paradigm for therapeutic antibody administration, potentially allowing improved curative efficiency and reduce

Large international surveys have been used to investigate relevant topics, including family life, gender roles and care. Such topics are addressed with ad hoc scales and variables, covering many countries, thus allowing useful comparisons. However, in researching fathers, qualitative methods (narrative and biographic) have largely been used because they allow a deeper investigation of actions and motivations but also due to a lack of detailed questions on fatherhood or small numbers of items in large-scale surveys. This chapter starts from a question on why and how to investigate fathers from a quantitative perspective, using existing large and sophisticated surveys proving a big amount of interesting data (without costs) that, however, are not built to merely investigate fatherhood. The aim of this chapter is to provide an analysis of how existing large data sets - not specifically focused on fathers –can nevertheless be used by scholars to learn more about fathers and fathering: a brief overview of the topic, scales and aspects of fatherhood and gender roles will be discussed in three relevant surveys (the European Values Study, the Generations & Gender Programme, and International Social Survey Programme) providing critical methodological considerations regarding researching fathers.