Publications by authors named "Fonte R"

Introduction: The treatment of glioblastoma is hindered by the blood-brain barrier (BBB) and rapid drug clearance by the immune system. To address these challenges, we propose a novel drug delivery system using liposomes modified with cell membrane fragments. These modified liposomes can evade the immune system, cross the BBB, and accumulate in tumor tissue through homotypic targeting, thereby delivering drugs like paclitaxel and carboplatin more effectively.

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  • Radiofrequency ablation (RFA) is a safe treatment for benign thyroid nodules, but it carries a risk of injury to the recurrent laryngeal nerve (RLN), which can affect voice function.
  • The study highlights the use of flexible laryngoscopy (FL) to monitor vocal cord (VC) function during RFA, ensuring safety before treating the second nodule in a patient with hyperthyroidism.
  • The findings suggest that using FL is an effective way to minimize RLN injury risk during both single and bilateral RFA treatments, even when the patient is awake.
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Objective: Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking.

Materials And Methods: The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed.

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Small-cell lung cancer (SCLC) cases represent approximately 15% of all lung cancer cases, remaining a recalcitrant malignancy with poor survival and few treatment options. In the last few years, the addition of immunotherapy to chemotherapy improved clinical outcomes compared to chemotherapy alone, resulting in the current standard of care for SCLC. However, the advantage of immunotherapy only applies to a few SCLC patients, and predictive biomarkers selection are lacking for SCLC.

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  • This study focuses on optimizing treatments for metastatic melanoma (MM) by developing cell membrane (CM)-modified nanoparticles (NPs) using microfluidics, which enhance drug delivery and targeting.
  • The researchers performed a direct membrane fusion process using synthetic liposomes and CM from MM cell lines, loading these hybrid liposomes with targeted agents like cobimetinib and lenvatinib.
  • Results showed that these hybrid liposomes had significantly better targeting and effectiveness against MM cells compared to standard liposomes or free drugs, while demonstrating low toxicity.
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Background: Clinical drawback in checkpoint inhibitors immunotherapy (ICI) of metastatic melanoma (MM) is monitoring clinical benefit. Soluble forms of PD1(sPD1) and PD-L1(sPD-L1) and extracellular vesicles (EVs) expressing PD1 and PD-L1 have recently emerged as predictive biomarkers of response. As factors released in the blood, EVs and soluble forms could be relevant in monitoring treatment efficacy and adaptive resistance to ICI.

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Cervical cancer (CC) is characterized by genomic alterations in DNA repair genes, which could favor treatment with agents causing DNA double-strand breaks (DSBs), such as trabectedin. Hence, we evaluated the capability of trabectedin to inhibit CC viability and used ovarian cancer (OC) models as a reference. Since chronic stress may promote gynecological cancer and may hinder the efficacy of therapy, we investigated the potential of targeting β-adrenergic receptors with propranolol to enhance trabectedin efficacy and change tumor immunogenicity.

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  • The V600E mutation in the BRAF gene in metastatic melanoma leads to increased activation of Erk1/2 and a better response to combinations of BRAFi (BRAF inhibitors) and MEKi (MEK inhibitors).
  • A rare tandem mutation involving BRAF, specifically V600 and K601, results in a different drug response and shows decreased sensitivity to the BRAFi Vemurafenib when tested in patient-derived organoids (PDOs).
  • By inhibiting Notch signaling alongside BRAFi and MEKi treatment, researchers observed an improved antitumor response in these specific cases, highlighting the importance of personalized treatment approaches for rare mutations in melanoma patients.
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Background: The immunotherapy with immune checkpoints inhibitors (ICI) has changed the life expectancy in metastatic melanoma (MM) patients. Nevertheless, several patients do not respond hence, the identification and validation of novel biomarkers of response to ICI is of crucial importance. Circulating extracellular vesicles (EVs) such as PD-L1 EV mediate resistance to anti-PD1, instead the role of PD1 EV is not fully understood.

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  • Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges for delivering anticancer drugs due to its unique environment and drug resistance.
  • A new pH-responsive drug delivery system (DDS), called Gem@TpHResMic, is developed to effectively deliver the chemotherapy drug Gemcitabine (Gem) specifically to PDAC cells by targeting the high expression of uPAR.
  • In laboratory models, this DDS showed better drug release and greater anti-cancer effects compared to free Gem by damaging DNA and inducing apoptosis, suggesting potential for overcoming drug resistance in PDAC, with further in vivo research needed.
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The evolution of a bovine coronavirus (BCoV) natural infection in a calf persistently infected with bovine viral diarrhea virus (BVDV) was described. The infected calf developed intermittent nasal discharge, diarrhea and hyperthermia. The total number of leukocytes/mL and the absolute differential number of neutrophils and lymphocytes resulted within the normal range, but monocytes increased at T28 (time 28 post-infection).

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In the attempt to understand the origin of autoantibody (AAb) production in patients with and at risk for type 1 diabetes (T1D), multiple studies have analyzed and reported alterations in T follicular helper (Tfh) cells in presymptomatic AAb subjects and patients with T1D. Yet, whether the regulatory counterpart of Tfh cells, represented by T follicular regulatory (Tfr) cells, is similarly altered is still unclear. To address this question, we performed analyses in peripheral blood, spleen, and pancreatic lymph nodes (PLN) of organ donor subjects with T1D.

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Aims: We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers.

Methods And Results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.

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Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity.

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Vitamin D is used to reduce cancer risk and improve the outcome of cancer patients, but the vitamin D receptor (VDR; also known as the calcitriol receptor) pathway needs to be functionally intact to ensure the biological effects of circulating calcitriol, the active form of vitamin D. Besides estrogen receptor alpha (ERα), estrogen-related receptor alpha (ERRα) has also been shown to interfere with the VDR pathway, but its role in the antitumor and transactivation activity of calcitriol is completely unknown in breast cancer (BC). We observed that ERRα functionally supported the proliferation of BC cell lines and acted as a calcitriol-induced regulator of VDR.

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Background: Emerging evidence has highlighted the importance of extracellular vesicle (EV)-based biomarkers of resistance to immunotherapy with checkpoint inhibitors in metastatic melanoma. Considering the tumor-promoting implications of urokinase-type plasminogen activator receptor (uPAR) signaling, this study aimed to assess uPAR expression in the plasma-derived EVs of patients with metastatic melanoma to determine its potential correlation with clinical outcomes.

Methods: Blood samples from 71 patients with metastatic melanoma were collected before initiating immunotherapy.

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The limited literature on the cost of various recycling methodologies for thermoset composites sets the background of this work, focusing mainly on the identification of an upper and lower economic value of glass fibre recovered from wind turbine blades recycling. The study briefly reviews the materials used by various original equipment manufacturers (OEM) for wind turbine blades. Successively, it provides an overview of the various recycling methods with interest in recovered materials, mechanical and physical properties, which are used, for estimating a maximum expected value.

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  • The study investigates how the Notch and MAPK pathways interact and contribute to resistance against MEK inhibitors in BRAF metastatic melanoma and GNAQ uveal melanoma cells.
  • Combining MEK inhibitor cobimetinib with Notch inhibitor nirogacestat shows a synergistic effect in BRAF melanoma and GNAQ uveal melanoma but an antagonistic effect in BRAF wild-type melanoma.
  • The combination treatment leads to enhanced cell cycle arrest, increased apoptosis, and reduced cell migration by significantly inhibiting Notch signaling and affecting key regulatory proteins.
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The spread of the SARS-CoV-2 infection among population has imposed a re-organization of healthcare services, aiming at stratifying patients and dedicating specific areas where patients with suspected COVID-related respiratory disease could receive the necessary health care assistance while waiting for the confirmation of the diagnosis of COVID-19 disease. In this scenario, the pathway defined as a "grey zone" is strongly advocated. We describe the application of rules and pathways in a regional context with low diffusion of the infection among the general population in the attempt to provide the best care to respiratory patients with suspected COVID-19.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state.

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Standard chemotherapy for soft tissue sarcomas has shown limited efficacy. Here, we sought to evaluate whether β-adrenergic receptor (β-AR) signalling contributed to the progression of sarcomas and therapy resistance. To assess the translational potential of β-adrenergic receptors, we performed immunohistochemical detection of β1-AR, β2-AR and β3-AR in leiomyosarcoma, liposarcoma and angiosarcoma tissue specimens, reporting the results scored for the intensity.

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Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5) and conventional (CXCR5) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls.

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Purpose: The aim of the present study was to retrospectively evaluate the efficacy of interstitial laser photocoagulation (ILP) ablation of thyroid nodules during a 6-year follow-up period and to identify possible predictors of the final outcome.

Methods: Forty-three outpatients (38 women) were assigned to ILP therapy. The study group included euthyroid patients with benign thyroid nodules.

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Over the past several years there has been much debate with regards to the prognostic and clinical significance of pancreatic ductal adenocarcinoma (PDAC) with lymph nodes metastasis. The PDAC gene expression knowledge and the biologic alterations underlying the lymph node involvement convey a clinical implication in dealing with the theranostic window. To this end, we provide an original bioinformatic dissection of the gene expression differences of PDAC according to the nodal involvement from a large public available dataset.

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IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100 000, but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria.

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