Explore the vast range of titles available.

Background Based on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment. Methods Gold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Ir en -AuSiO 2 _COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Ir en -AuSiO 2 _Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models. Results We show efficient capability of Ir en -AuSiO 2 _Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR + tumor/PDGFRβ + stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors. Conclusions Our study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.

Laura Cerchia ORCID: orcid.org/0000-0002-7633-79321 Show authors Journal of Experimental & Clinical Cancer Research volume 43, Article number: 243 (2024) Cite this article 119 Accesses Metrics details The Original Article was published on 26 March 2024 Correction: J Exp Clin Cancer Res 43, 92 (2024) https://doi.org/10.1186/s13046-024-03014-x Following publication of the original article [1], the authors identified an error Figure 7A, middle panel immunohistochemical EGFR staining. Incorrect Figure 7 Fig. 7 figure 1 Anticancer activity of Iren-AuSiO2_Aptamer nanoplatforms on 3D patient-derived breast cancer organoids. No statistically significant variations among Iren-AuSiO2_Scr and untreated were obtained Full size image Correct Figure 7 Fig. 7 figure 2 Anticancer activity of Iren-AuSiO2_Aptamer nanoplatforms on 3D patient-derived breast cancer organoids.

We report the design and development of a novel multifunctional nanostructure, RB-AuSiO2_HSA-DOX, where tri-modal cancer treatment strategies—photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy—luminescent properties and targeting are integrated into the same scaffold. It consists of a gold core with optical and thermo-plasmonic properties and is covered by a silica shell entrapping a well-known photosensitizer and luminophore, Rose Bengal (RB). The nanoparticle surface was decorated with Human Serum Albumin (HSA) through a covalent conjugation to confer its targeting abilities and as a carrier of Doxorubicin (DOX), one of the most effective anticancer drugs in clinical chemotherapy. The obtained nanostructure was fully characterized through transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-visible spectroscopy, with a homogeneous and spherical shape, an average diameter of about 60 nm and negative ζ-potential value Singlet oxygen generation and photothermal properties were explored under green light irradiation. The interaction between DOX-HSA anchored on the nanoplatform was investigated by fluorescence spectroscopy and compared to that of DOX-HSA, pointing out different accessibility of the drug molecules to the HSA binding sites, whether the protein is free or bound to the nanoparticle surface. To the best of our knowledge, there are no studies comparing a drug–HSA interaction with that of the same protein anchored to nanoparticles. Furthermore, the uptake of RB-AuSiO2_HSA-DOX into MDA-MB-231 mammary cells was assessed by confocal imaging, highlighting—at early time of incubation and as demonstrated by the increased DOX luminescence displayed within cells—a better internalization of the carried anticancer drug compared to the free one, making the obtained nanostructure a suitable and promising platform for an anticancer multimodal approach.

Accumulation of advanced glycation end products (AGEs) on biopolymers accompanies cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development of early onset Parkinson’s Disease (PD) caused by loss-of-function of DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, we find that lysosomal proteolysis is impaired, causing AGEs to accumulate, α-synuclein (α-syn) phosphorylation to increase, and proteins to aggregate. We demonstrated these processes are at least partly driven by astrocytes, as DJ1 loss reduces their capacity to provide metabolic support and triggers acquisition of a pro-inflammatory phenotype. Consistently, in co-cultures, we find that DJ1-expressing astrocytes are able to reverse the proteolysis deficits of DJ1 knockout midbrain neurons. In conclusion, astrocytes’ capacity to clear toxic damaged proteins is critical to preserve neuronal function and their dysfunction contributes to the neurodegeneration observed in a DJ1 loss-of-function PD model. The protein DJ1, encoded by the PARK7 gene, is causally linked to development of early-onset PD. Here the authors observed that the loss of DJ1 function in midbrain organoids led to astrocyte dysfunction, impairing protein clearance, accumulation of α-synuclein.

Background Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. Methods Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher’ exact test and the Mann–Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. Results At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM ( p  = 0.003) and 172.9 in MPM patients ( p  = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM ( p  = 0.003) and 88% in MPM patients ( p  = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed ( p  = 0.913), while there was a significant trend toward lower titers by increasing age ( p  < 0.001) and in disease cohorts with respect to controls (MM: p  < 0.001 and MPM: p  < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients ( p  = 0.003). No swabs resulted positive on each time point. No safety concerns were observed. Conclusions BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).

Precision medicine has driven a major change in the treatment of many forms of cancer. The discovery that each patient is different and each tumor mass has its own characteristics has shifted the focus of basic and clinical research to the singular individual. Liquid biopsy (LB), in this sense, presents new scenarios in personalized medicine through the study of molecules, factors, and tumor biomarkers in blood such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes and circulating tumor microRNAs (ct-miRNAs). Moreover, its easy application and complete absence of contraindications for the patient make this method applicable in a great many fields. Melanoma, given its highly heterogeneous characteristics, is a cancer form that could significantly benefit from the information linked to liquid biopsy, especially in the treatment management. In this review, we will focus our attention on the latest applications of liquid biopsy in metastatic melanoma and possible developments in the clinical setting.

Background Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related prevalence, clinical presentation and prognostic impact are unresolved. We detailed CVI in a cohort of children diagnosed with PMD over two decades at a tertiary referral centre. Results We enrolled 86 PMD patients (M/F = 30/56; mean age 6.4 ± 8.58 years). CVI was detected in 31 patients (36%), with mean age at onset of 5.7 ± 7.8 years including the pre- and neonatal phase in 14, often representing the first sign of PMD (42% of those with CVI). Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). Hypertrophic, non-compaction and dilated cardiomyopathies were the prevalent disorders, although pulmonary arterial hypertension was also found. Adverse cardiac events (heart failure, resuscitated cardiac arrest, ICD/PM implantation, sudden death) occurred in 19% of children with CVI over a follow-up period of 5.4 ± 4.3 years. All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p  < 0.01); female sex, age at onset < 5 years, acute heart failure at presentation and diabetes also proved independent predictors of outcome. Conclusion Cardiovascular involvement occurred in over one-third of children diagnosed with PMD, often at a very early age, and was associated with adverse prognosis. Final outcome of PMD-related CVI was influenced by the specific underlying aetiology, suggesting the need for tailored management of heart failure and sudden death prevention.

Particle film technology is an environmentally sustainable crop protection method, offering an alternative to chemical pesticides for disease control. Copper-based compounds have long been central to the management of bacterial and fungal diseases, particularly in organic agriculture. However, due to their environmental persistence, their use has been increasingly restricted by European regulations, making the management of widespread diseases such as Olive Knot (Pseudomonas savastanoi pv. savastanoi) and Downy Mildew (Plasmopara viticola) more difficult. The LIFE Microfighter project addresses this problem by testing a novel Zeo-Biopesticide (ZBp), in which natural zeolite serves as a carrier for the beneficial bacterium Pseudomonas synxantha DLS65. Field trials conducted in high-rainfall areas of Emilia-Romagna (Italy) evaluated the product’s distribution and persistence on olive and grape leaves through ESEM (Environmental Scanning Electron Microscopy) observations, its ability to retain the microorganism, and its effectiveness for disease control. Results showed that ZBp significantly reduced Olive Knot incidence compared to both the untreated control and Cu-based treatments (p < 0.05), supporting its potential as an alternative for bacterial disease management, while showing no statistically significant difference compared to the control in either the incidence or severity of Downy Mildew (p > 0.05). Its persistence and adherence to plant surfaces, which could influence its overall field performance, were affected by environmental conditions, particularly rainfall.

We describe a 14-month-old boy, with a previous diagnosis of propionic acidemia (PA) by expanded newborn screening, who, admitted for a suspected metabolic crisis, tested positive for SARS-CoV-2. Since propionic acidemia was diagnosed, the patient has followed the recommended diet for this inborn error of metabolism. Although propionic acidemia patients are at a high risk of suffering metabolic crises, frequently associated with permanent clinical complications, psychomotor development of this patient was normal. The SARS-CoV-2 infection (at about 1 year of age) caused the patient’s first metabolic crisis. However, his clinical course was in keeping with a mild clinical form of COVID-19, and he recovered without experiencing severe clinical consequences. We describe this patient in order to improve the knowledge about follow up of PA patients identified by newborn screening and to increase the limited number of reports of SARS-CoV-2 infection in children with comorbidities, especially inborn errors of metabolism.

Catheter ablation (CA) has become a validated technique for treating patients with symptomatic or paroxysmal atrial fibrillation (AF), as recommended by the latest 2024 European society of cardiology (ESC) guidelines, class II level A. The procedure is also recommended for patients with persistent AF without major risk factors for AF recurrence, as an alternative to antiarrhythmic medications class I or III. However, CA carries the risk of AF recurrence in 30–35% of patients, sometimes after the procedure. Multiple factors impact the onset, maintenance, and recurrence of AF after CA, including clinical, biohumoral, echocardiographic, genetic, and lifestyle factors. Beyond traditional predictors, emerging factors such as obstructive sleep apnea syndrome, chronic renal failure, chronic lung disease, physical activity patterns, gut microbiota composition, and epicardial fat thickness significantly influence outcomes. Therefore, optimizing patient’s selection for CA is an important strategy to minimize the risk of AF recurrence. Many echocardiographic parameters emerged as predictors of AF recurrence post-CA, but none stood out as a potential single factor. These factors include traditional markers such as left atrial size by 2D echocardiography, LV ejection fraction, LV diastolic function parameters as well as myocardial deformation addressed by the recently developed speckle tracking analysis. Additionally, the duration and type of AF represent fundamental risk factors, with longstanding persistent AF showing significantly higher recurrence rates compared to paroxysmal forms. Novel biomarkers including MR-proANP, caspase-8, hsa-miR-206, and neurotrophin-3 show promise in enhancing risk prediction capabilities. The aim of this review is to explore the most relevant echocardiographic parameters, including myocardial deformation, that could accurately predict recurrence of AF after CA, while also examining the role of emerging clinical and biochemical predictors in comprehensive patient selection strategies.