Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.

Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck.

Impact of a two step antimicrobial stewardship program in a paediatric haematology and oncology unit.

Objective: To describe the implementation of a multi-step antimicrobial stewardship program in a haemato-oncology and stem cell transplantation program unit. Methods: Pre-post quasi-experimental study with two interrupted time-series analyses, conducted between 01/01/2019 and 31/12/2022 in the Paediatric Haemato-Oncology Unit of the Padua Paediatric Hospital. The interventions were: (1) 02/2020: dissemination of febrile neutropenia clinical pathways, (2) April 2021: provision of the clinical pathways via a customized App (Firstline.

Vaccine-related influenza virus B infection in a child with an undiagnosed B-cell acute lymphoblastic leukemia.

We report a case of Influenza type B (lineage Yamagata) infection in a child who received the live attenuated influenza virus vaccine before being diagnosed with B-cell acute lymphoblastic leukemia. The patient developed a mild disease that persisted for 18 days and resolved without antiviral treatment. The prolonged infection of an attenuated virus in an immunocompromised host might pose a risk of reversion or evolution to a more pathogenic strain.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

Background: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres.

Copper chelation reduces early collagen deposition and preserves saliva secretion in irradiated salivary glands.

Radiation therapy is a first-line treatment for head and neck cancer; however, it typically leads to hyposalivation stemming from fibrosis of the salivary gland. Current strategies to restore glandular function are dependent on the presence of residual functional salivary gland tissue, a condition commonly not met in patients with extensive fibrotic coverage of the salivary gland resulting from radiation therapy. Fibrosis is defined by the pathological accumulation of connective tissue ( extracellular matrix) and excessive deposition of crosslinked (fibrillar) collagen that can impact a range of tissues and given that collagen crosslinking is necessary for fibrosis formation, inhibiting this process is a reasonable focus for developing anti-fibrotic therapies.

SARS-CoV-2 Infection in the Pediatric Oncology Population: The Definitive Comprehensive Report of the Infectious Diseases Working Group of AIEOP.

Objective: The objective of this study was to assess the clinical impact and outcome of the SARS-CoV-2 infection on children with cancer or those who received a hematopoietic stem cell transplantation.

Methods: AIEOP (Italian Association of Pediatric Hematology and Oncology) performed a nationwide multicenter observational cohort study, including consecutive patients between April 2020 and November 2022.

Results: Twenty-five Italian centers participated and 455 patients were enrolled.

Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.

Cu (Cu) is essential for several biochemical pathways due to its role as a catalytic cofactor or allosteric regulator of enzymes. Its import and distribution are tightly controlled by transporters and metallochaperones and Cu homeostasis is maintained by balancing Cu uptake and export. Genetic diseases are caused by impaired Cu transporters CTR1, ATP7A, or ATP7B but little is known about the regulatory mechanisms by which these proteins meet the fluctuating demands of Cu in specific tissues.

APOE expression and secretion are modulated by mitochondrial dysfunction.

Mitochondria influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the electron transport chain caused upregulation of the Alzheimer's disease risk factor apolipoprotein E (APOE) and other secretome components. Indirect disruption of the electron transport chain by gene editing of SLC25A mitochondrial membrane transporters as well as direct genetic and pharmacological disruption of either complexes I, III, or the copper-containing complex IV of the electron transport chain elicited upregulation of APOE transcript, protein, and secretion, up to 49-fold.

Pigmentation and TYRP1 expression are mediated by zinc through the early secretory pathway-resident ZNT proteins.

Tyrosinase (TYR) and tyrosinase-related proteins 1 and 2 (TYRP1 and TYRP2) are essential for pigmentation. They are generally classified as type-3 copper proteins, with binuclear copper active sites. Although there is experimental evidence for a copper cofactor in TYR, delivered via the copper transporter, ATP7A, the presence of copper in TYRP1 and TYRP2 has not been demonstrated.

FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery.

Recent studies have uncovered the therapeutic potential of elesclomol (ES), a copper-ionophore, for copper deficiency disorders. However, we currently do not understand the mechanism by which copper brought into cells as ES-Cu(II) is released and delivered to cuproenzymes present in different subcellular compartments. Here, we have utilized a combination of genetic, biochemical, and cell-biological approaches to demonstrate that intracellular release of copper from ES occurs inside and outside of mitochondria.

Pediatric cancer and hematopoietic stem cell transplantation patients requiring renal replacement therapy: results of the retrospective nationwide AIEOP study.

In children affected by malignancies and/or who received hematopoietic stem cell transplantation (HSCT), acute kidney injury (AKI) may occur causing a high mortality rate, despite the implementation of renal replacement therapy (RRT). We performed a nationwide, multicenter, retrospective, observational cohort study including consecutive patients between January 2010 and December 2019. One hundred and fourteen episodes of AKI requiring RRT coming from nine different Italian centers were included.

Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.

Purpose: To develop a mouse model of human dry eye disease (DED) for investigation of sex differences in autoimmune-associated dry eye pathology.

Methods: Ocular surface disease was assessed by quantifying corneal epithelial damage with lissamine green stain in the NOD.H-2h4,IFNγ-/-,CD28-/- (NOD.

Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP).

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed.

Consensus on COVID-19 Vaccination in Pediatric Oncohematological Patients, on Behalf of Infectious Working Group of Italian Association of Pediatric Hematology Oncology.

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures.

Connecting copper and cancer: from transition metal signalling to metalloplasia.

Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient.

Deep Neural Network Driven Speech Classification for Relevance Detection in Automatic Medical Documentation.

The automation of medical documentation is a highly desirable process, especially as it could avert significant temporal and monetary expenses in healthcare. With the help of complex modelling and high computational capability, Automatic Speech Recognition (ASR) and deep learning have made several promising attempts to this end. However, a factor that significantly determines the efficiency of these systems is the volume of speech that is processed in each medical examination.

Ceruloplasmin as a source of Cu for a fungal pathogen.

Copper is an essential metal for virtually all organisms, yet little is known about the extracellular sources of this micronutrient. In serum, the most abundant extracellular Cu-binding molecule is the multi‑copper oxidase ceruloplasmin (Cp). Cp levels increase during infection and inflammation, and pathogens can be exposed to high Cp at sites of infection.

Copper metabolism as a unique vulnerability in cancer.

The last 25 years have witnessed tremendous progress in identifying and characterizing proteins that regulate the uptake, intracellular trafficking and export of copper. Although dietary copper is required in trace amounts, sufficient quantities of this metal are needed to sustain growth and development in humans and other mammals. However, copper is also a rate-limiting nutrient for the growth and proliferation of cancer cells.

Systemic Fusariosis: A Rare Complication in Children with Acute Lymphoblastic Leukemia.

species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host's immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of infection in a 9-year-old child with acute lymphoblastic leukemia (ALL).

Trimers Conjugated to Fibrin Hydrogels Promote Salivary Gland Function.

New strategies for tissue engineering have great potential for restoring and revitalizing impaired tissues and organs, including the use of smart hydrogels that can be modified to enhance organization and functionality of the salivary glands. For instance, monomers of laminin-111 peptides chemically conjugated to fibrin hydrogel (LM-FH) promote cell cluster formation in vitro and salivary gland regeneration in vivo when compared with fibrin hydrogel (FH) alone; however, LM-FH produce only weak expression of acinar differentiation markers in vivo (e.g.

P2Y receptors mediate nucleotide-induced EGFR phosphorylation and stimulate proliferation and tumorigenesis of head and neck squamous cell carcinoma cell lines.

Objectives: To assess functional expression of the P2Y nucleotide receptor (P2YR) in head and neck squamous cell carcinoma (HNSCC) cell lines and define its role in nucleotide-induced epidermal growth factor receptor (EGFR) transactivation. The use of anti-EGFR therapeutics to treat HNSCC is hindered by intrinsic and acquired drug resistance. Defining novel pathways that modulate EGFR signaling could identify additional targets to treat HNSCC.

Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess.

Copper (Cu) is an essential, yet potentially toxic nutrient, as illustrated by inherited diseases of copper deficiency and excess. Elevated expression of the ATP7A Cu exporter is known to confer copper tolerance, however, the contribution of metal-binding metallothioneins is less clear. In this study, we investigated the relative contributions of ATP7A and the metallothioneins MT-I and MT-II to cell viability under conditions of Cu excess or deficiency.