TLR4 Downregulation Identifies High-Risk HPV Infection and Integration in H-SIL and Squamous Cell Carcinomas of the Uterine Cervix.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix.

TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review).

The tumour suppressor factor p53 plays an essential role in regulating numerous cellular processes, including the cell cycle, DNA repair, apoptosis, autophagy, cell metabolism and immune response. TP53 is the most commonly mutated gene in human cancers. These mutations are primarily non‑synonymous changes that produce mutant p53 proteins characterized by loss of function, a dominant negative effect on p53 tetramerisation and gain of function (GOF).

The Role of Telemedicine in Children with Obstructive Sleep Apnea Syndrome (OSAS): A Review of the Literature.

The advent of telemedicine marked a significant turning point in the healthcare landscape, introducing a revolutionary approach to the delivery of medical care. Digital technologies easily connect health professionals and patients, overcoming geographical and temporal barriers. Telemedicine has been used for sleep disorders including obstructive sleep apnea syndrome (OSAS) since the mid-1990s.

Cross-reactive CD8 T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs).

Background: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP).

Method: A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers.

Integrated plasma metabolomics and lipidomics profiling highlights distinctive signature of hepatocellular carcinoma in HCV patients.

Background: Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis.

Reactivation of telomerase reverse transcriptase expression in cancer: the role of TERT promoter mutations.

Telomerase activity and telomere elongation are essential conditions for the unlimited proliferation of neoplastic cells. Point mutations in the core promoter region of the telomerase reverse transcriptase (TERT) gene have been found to occur at high frequencies in several tumour types and considered a primary cause of telomerase reactivation in cancer cells. These mutations promote TERT gene expression by multiple mechanisms, including the generation of novel binding sites for nuclear transcription factors, displacement of negative regulators from DNA G-quadruplexes, recruitment of epigenetic activators and disruption of long-range interactions between TERT locus and telomeres.

Telemedicine and Its Application in Cystic Fibrosis.

The care of cystic fibrosis (CF) traditionally consists of regular visits to the clinic where a multidisciplinary team can visit the patient, adjust treatments and monitor the disease. During the COVID-19 pandemic when access to hospitals and medical environments was very limited, the role of telemedicine was crucial to keep in touch with patients with chronic diseases such as CF. Increasing evidence demonstrates that electronic health can successfully support healthcare professionals in the management of people with CF.

Non-Classical HLA Class 1b and Hepatocellular Carcinoma.

A number of studies are underway to gain a better understanding of the role of immunity in the pathogenesis of hepatocellular carcinoma and to identify subgroups of individuals who may benefit the most from systemic therapy according to the etiology of their tumor. Human leukocyte antigens play a key role in antigen presentation to T cells. This is fundamental to the host's defense against pathogens and tumor cells.

Microorganisms-derived antigens for preventive anti-cancer vaccines.

Cancer prevention is one of the aim with the highest priority in order to reduce the burden of cancer diagnosis and treatment on individuals as well as on healthcare systems. To this aim, vaccines represent the most efficient primary cancer prevention strategy. Indeed, anti-cancer immunological memory elicited by preventive vaccines might promptly expand and prevent tumor from progressing.

Molecular mimicry and cancer vaccine development.

Background: The development of cancer immunotherapeutic strategies relies on the identification and validation of optimal target tumor antigens, which should be tumor-specific as well as able to elicit a swift and potent anti-tumor immune response. The vast majority of such strategies are based on tumor associated antigens (TAAs) which are shared wild type cellular self-epitopes highly expressed on tumor cells. Indeed, TAAs can be used to develop off-the-shelf cancer vaccines appropriate to all patients affected by the same malignancy.

Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients.

Background: The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients.

Methods: We included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine.

Telomerase: a good target in hepatocellular carcinoma? An overview of relevant preclinical data.

Introduction: The expression of telomerase reverse transcriptase (TERT) in liver is restricted to rare cells, that are able to replace senescent hepatocytes and regenerate tissue in response to hepatic damage, while becoming extinguished in differentiated progeny cells. TERT gene is permanently activated in liver neoplasms from the very early stage of the hepatocarcinogenesis mainly through the accumulation of genetic alterations, virus-related insertional mutagenesis and somatic mutations in the TERT promoter region. Several lines of evidence suggest that telomerase, beyond the canonical function of telomeres elongation, has multiple oncogenic activities in cancer cells and may represent a promising therapeutic target in hepatocellular carcinoma (HCC).

The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi's sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene.

Antigenic molecular mimicry in viral-mediated protection from cancer: the HIV case.

Background: People living with HIV/AIDS (PLWHA) show a reduced incidence for three cancer types, namely breast, prostate and colon cancers. In the present study, we assessed whether a molecular mimicry between HIV epitopes and tumor associated antigens and, consequently, a T cell cross-reactivity could provide an explanation for such an epidemiological evidence.

Methods: Homology between published TAAs and non-self HIV-derived epitopes have been assessed by BLAST homology.

Multidrug-Resistant Bacteria in Children and Adolescents with Cystic Fibrosis.

In patients with cystic fibrosis (CF), multidrug-resistant (MDR) bacteria can predispose to exacerbations, limit the effectiveness of antibiotic treatments and promote the progression of lung disease. The aim of this retrospective study was to compare pulmonary exacerbations (Pex), hospitalizations, lung function and nutritional status in a group of children and adolescents with CF colonized by MDR bacteria and in a noncolonized control group. Overall, 7/54 pediatric patients (12.

Bimodal antibody-titer decline following BNT162b2 mRNA anti-SARS-CoV-2 vaccination in healthcare workers of the INT - IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy).

Background: Both SARS-CoV-2 mRNA-based vaccines [BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)] have shown high efficacy, with very modest side effects in limiting transmission of SARS-CoV-2 and in preventing the severe COVID-19 disease, characterized by a worrying high occupation of intensive care units (ICU), high frequency of intubation and ultimately high mortality rate. At the INT, in Naples, only the BNT162b2/Pfizer vaccine has been administered to cancer patients and healthcare professionals aged 16 and over. In the present study, the antibody response levels and their decline were monitored in an interval of 6-9 months after vaccine administration in the two different cohorts of workers of the INT - IRCCS "Fondazione Pascale" Cancer Center (Naples, Italy): the group of individuals previously infected with SARS-CoV-2 and vaccinated with a single dose; and that of individuals negative for previous exposure to SARS-CoV-2 vaccinated with two doses 21 days apart.

Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis.

Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response.

Molecular mimicry between tumor associated antigens and microbiota-derived epitopes.

Background: The gut microbiota profile is unique for each individual and are composed by different bacteria species according to individual birth-to-infant transitions. In the last years, the local and systemic effects of microbiota on cancer onset, progression and response to treatments, such as immunotherapies, has been extensively described. Here we offer a new perspective, proposing a role for the microbiota based on the molecular mimicry of tumor associated antigens by microbiome-associated antigens.

Mutations in the telomerase reverse transcriptase promoter and PIK3CA gene are common events in penile squamous cell carcinoma of Italian and Ugandan patients.

Penile carcinoma develops either through human papillomavirus (HPV) related or unrelated carcinogenic pathways. Genetic alterations and nucleotide changes in coding regions (ie, TP53, CDKN2A, PIK3CA and NOTCH1) are main cancer driver events either in HPV positive or in HPV negative tumours. We investigated the presence of hotspot nucleotide mutations in TERT promoter (TERTp) and PIK3CA exon 9 and their relationship with HPV status in 69 penile cancer cases from Italian and Ugandan patients.

Virus-like Particles as Preventive and Therapeutic Cancer Vaccines.

Virus-like particles (VLPs) are self-assembled viral protein complexes that mimic the native virus structure without being infectious. VLPs, similarly to wild type viruses, are able to efficiently target and activate dendritic cells (DCs) triggering the B and T cell immunities. Therefore, VLPs hold great promise for the development of effective and affordable vaccines in infectious diseases and cancers.

Novel Molecular Targets for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, only a few treatments are available, most of which are effective only for the early stages of the disease. Therefore, there is an urgent needing for potential markers for a specifically targeted therapy.