Discovery of Orally Available Prodrugs of Itaconate and Derivatives.

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.

MAPK pathway activating alteration and immunotherapy efficacy in squamous cell lung carcinoma: results from the randomized, prospective SQUINT trial.

Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.

Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.

Atherosclerosis and the Bidirectional Relationship Between Cancer and Cardiovascular Disease: From Bench to Bedside, Part 2 Management.

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a "syndemic" nature to these chronic diseases.

From infection to immortality: The role of HPV and telomerase in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of malignancies with multifactorial aetiologies. High-risk human papillomavirus (hrHPV) infections, particularly HPV16, and the dysregulation of telomerase activity, specifically through its catalytic subunit, telomerase reverse transcriptase (TERT) are among the key contributors to HNSCC development and progression. HPV promotes oncogenesis via the E6 and E7 oncoproteins, which inactivate tumour suppressors TP53 and RB1, leading to unchecked cellular proliferation.

: a Python package for simplifying cBioPortal data access in cancer research.

Objectives: In recent years, the rise of big data and artificial intelligence has led to an increasing expansion of databases and web services in biomedical research. cBioPortal is one of the most widely used platforms for accessing cancer genomic and clinical data. The primary objective of this study was to develop a tool that simplifies programmatic interaction with cBioPortal's web service.

Burden of Disease of Breast Cancer in Italy: A Real-World Data Analysis.

Background: Breast cancer (BC) constitutes a significant public health challenge in Italy, with a considerable impact on healthcare resources and societal costs. Despite advancements in diagnostics and therapies, the economic burden of BC remains substantial, necessitating a comprehensive evaluation to inform healthcare policy and resource allocation. The aim of this study is to estimate both direct health costs and social security costs related to BC.

Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study.

Unlabelled: The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton & Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives.

Follow-up of early breast cancer in a public health system: A 2024 AIGOM consensus project.

Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs.

Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages.

Background: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet.

Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait.

Context.—: Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited.

Communication in oncology between healthcare providers, patients, the scientific community, and the media: recommendations from the Italian Association of Medical Oncology (AIOM).

Aim: To identify barriers between health and communication in oncology in order to promote the best possible practice. The areas of communication to be focused on are communication directly with the patient, communication within the scientific community, and communication with the media.

Material And Methods: A working group including eminent experts from the national mass media, healthcare system, and patients' advocacy has been established on behalf of the Italian Association of Medical Oncology (AIOM), with the aim of developing suitable recommendations for the best communication in oncology.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs.

The engagement of temporal attention in left spatial neglect.

Previous literature showed how left spatial neglect arises from an asymmetrical distribution of spatial attention. However, it was also suggested that left spatial neglect might be partially caused or at least worsened by non-spatial attention disorders of the right-lateralized stimulus-driven attentional fronto-parietal network. Here, we psychophysically tested the efficiency of temporal attentional engagement of foveal perception through meta-contrast (Experiment 1) and "attentional" masking (Experiment 2) tasks in patients with right-hemisphere stroke with left neglect (N+), without left neglect (N-) and matched healthy controls (C).

Intramolecular Hydrogen Bonding Based CEST MRI Contrast Agents As an Emerging Design Strategy: A Mini-Review.

Intramolecular hydrogen bonding-based chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) contrast agents represent an innovative design strategy aiming to overcome limitations in diamagnetic CEST (diaCEST) MRI contrast agent specificity and also those associated with traditional metal-based MRI contrast agents. Ward and Balaban's proposal of small diamagnetic compounds marked a paradigm shift in contrast-based radiologic research, inspiring extensive investigations since 2000. These contrast agents leverage labile hydrogen bonds, serving as chemical exchange sites to induce saturation of water.

Embryo Quality Conditions the Secretory Profile of Tolerogenic Dendritic Cell DC-10 During the Peri-Implantation Period.

Problem: The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)-10 profile, a DC subset with high IL-10 production. Since the implantation process implies an embryo-endometrium-immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality.

Method Of Study: Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl-cAMP (Dec) was stimulated with human embryo-conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group).

Monitoring changing patterns in HER2 addiction by liquid biopsy in advanced breast cancer patients.

Background: During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.

The emotional states and associated behavioral responses (flexible-adaptive behaviors vs. inflexible-maladaptive behaviors) of cancer patients during the SARS-CoV-2 outbreak: A multi-center cross-sectional study in Italy.

Objective: Distress during SARS-CoV-2 outbreak affected also cancer patients' well-being. Aim of this study was to investigate patient' reactions and behavior (flexible-adaptive vs. inflexible-maladaptive) during the SARS-CoV-2 outbreak.

Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view.

Background:  Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies.

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO).

Background: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted.

Infants' reorienting efficiency depends on parental autistic traits and predicts future socio-communicative behaviors.

Attentional reorienting is dysfunctional not only in children with autism spectrum disorder (ASD), but also in infants who will develop ASD, thus constituting a potential causal factor of future social interaction and communication abilities. Following the research domain criteria framework, we hypothesized that the presence of subclinical autistic traits in parents should lead to atypical infants' attentional reorienting, which in turn should impact on their future socio-communication behavior in toddlerhood. During an attentional cueing task, we measured the saccadic latencies in a large sample (total enrolled n = 89; final sample n = 71) of 8-month-old infants from the general population as a proxy for their stimulus-driven attention.

Preventing Bone Loss in Breast Cancer Patients: Designing a Personalized Clinical Pathway in a Large-Volume Research Hospital.

Background: We assess the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and design a personalized clinical pathway to reduce bone loss in an Italian research hospital.

Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy.