Publications by authors named "Maria Napolitano"

Article Synopsis
  • Circulating Tumor Cells (CTCs) are rare cancer cells that can lead to metastasis; a new gel (CLG) containing CXCL12 was created to attract and study these cells, particularly those expressing CXCR4 that facilitate invasion.
  • Different cancer cell lines (colon, renal, lung, and ovarian) were tested on the gel, revealing that the CXCL12-loaded gel significantly enhanced the ability of CTCs to infiltrate compared to an empty gel.
  • In a clinical trial, CTCs were successfully isolated from patients with ovarian and lung cancers using the CLG, showing promising results in identifying metastatic cells and understanding their behavior.
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  • The study aims to determine factors that predict sensitivity to nivolumab in patients with metastatic renal cell carcinoma (mRCC) by analyzing immune cell profiles, specifically peripheral blood NK cells and regulatory T-cells (Tregs).
  • A total of 57 mRCC patients and 62 healthy donors were analyzed for various immune cell characteristics over the first year of treatment, using statistical methods to identify key predictors.
  • Results indicated that KIR2DL2/DL3+ NK cells and Helios+ Tregs at pretreatment serve as important predictors of nivolumab response, with specific thresholds related to overall survival (OS) and progression-free survival (PFS) showing their potential significance in treatment outcomes.
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  • CXCR4 plays a significant role in regulating the trafficking of T regulatory cells (Tregs), and the new antagonist R54 was tested on Tregs from renal cell carcinoma (RCC) patients.
  • In the study, R54 was found to impair the function of peripheral blood Tregs, decreasing their frequency and secretion of inhibitory cytokines while increasing effector T cell secretion of IFN-γ.
  • The results suggest that targeting CXCR4 with R54 could effectively inhibit Treg activity in the tumor microenvironment of RCC by affecting key signaling pathways and Treg characteristics.
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Background: Dysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy antibiotics in pancreatic cancer patients colonized by the Escherichia coli and Klebsiella pneumoniae.

Objective: In this study, we investigated the microbial communities that colonize tumours and which bacteria could aid in diagnosing pancreatic and biliary cancer and managing bile-colonized patients.

Methods: A retrospective study on positive bile cultures of 145 Italian patients who underwent cholangiopancreatography with PC and EPC cancer hospitalized from January 2006 to December 2020 in a QA-certified academic surgical unit were investigated for aerobic/facultative-anaerobic bacteria and fungal organisms.

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Background And Aims: Nonanesthesiologist-administered propofol (NAAP) is increasingly accepted, but data are limited on drug administration using target-controlled infusion (TCI) in clinical practice. TCI adjusts the drug infusion based on patient-specific parameters, maintaining a constant drug dose to reduce the risk of adverse events (AEs) because of drug overdosing and to enhance patient comfort. The aims of this study were to assess the rate of AEs and to evaluate patient satisfaction with NAAP using TCI in a retrospective cohort of 18,302 procedures.

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Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community.

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Background: Colorectal lesions (CRLs) <10 mm found at colonoscopy tend towards "diagnose-and-leave" or "resect-and-discard" strategies based on real-time Kudo glandular pit-pattern's assessment using i-Scan. However, i-Scan has not yet been validated for Kudo's classification. We aimed to assess whether, in routine colonoscopy, i-Scan without magnification and optical enhancement (M-OE) reliably differentiates hyperplastic polyps (HPs) from other serrated lesions (SLs) and conventional adenomas (CAs), and, among SLs, HPs from sessile serrated lesions (SSLs) and traditional or unknown serrated adenomas (TSAs, USAs), in Kudo type II CRLs<10 mm, according to ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) recommended negative predictive value (NPV) threshold for adenomas.

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Background And Purpose: While HCC is an inflammation-associated cancer, CRLM develops on permissive healthy liver microenvironment. To evaluate the immune aspects of these two different environments, peripheral blood-(PB), peritumoral-(PT) and tumoral tissues-(TT) from HCC and CRLM patients were evaluated.

Methods: 40 HCC and 34 CRLM were enrolled and freshly TT, PT and PB were collected at the surgery.

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Synthetic nucleic acid interactors represent an exciting research field due to their biotechnological and potential therapeutic applications. The translation of these molecules into drugs is a long and difficult process that justifies the continuous research of new chemotypes endowed with favorable binding, pharmacokinetic and pharmacodynamic properties. In this scenario, we describe the synthesis of two sets of homo-thymine nucleopeptides, in which nucleobases are inserted in a peptide structure, to investigate the role of the underivatized amino acid residue and the distance of the nucleobase from the peptide backbone on the nucleic acid recognition process.

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Article Synopsis
  • The study focuses on rare regressive genetic mutations in colorectal cancer (CRC) that are linked to a unique oligometastatic status, which is seen as a sign of better survival outcomes.
  • Using various methods, including genetic testing and flow cytometry, the researchers evaluated 140 metastatic CRC patients and found that oligometastatic patients had significantly better survival rates compared to those with polymetastatic disease.
  • The findings suggest that certain immune cells (CD3/CD8 lymphocytes) from oligometastatic patients show enhanced cytotoxicity against colon cancer cells with specific mutations, indicating potential avenues for monitoring and treatment.
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Upadacitinib is a selective small molecule that inhibits Janus kinase (JAK) type 1. This molecule is administrated orally and is currently approved for the treatment of rheumatoid arthritis, atopic dermatitis, and psoriatic arthritis. Upadacitinib has been approved by the United States Food and Drug Administration for the induction and maintenance therapy of moderate-to-severe ulcerative colitis (UC) and is under investigation by the European Medicines Agency.

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This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers' expression, their association with other variables and prognostic value.

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Background: Colorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with high-microsatellite instability, high tumor mutation burden, and intratumoral lymphocytic infiltration. Programmed death-ligand 1 (PD-L1)/PD-1 signaling was described in solid tumor cells.

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Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia.

Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant'Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals.

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Background: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions ("abscopal effect") through stimulation of anti-tumor immune effects ("radiation-induced immunity").

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Rationale: About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance.

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Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs.

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The chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R.

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Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration.

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Article Synopsis
  • The study investigates the effectiveness of new CXCR4 antagonists in enhancing the efficacy of anti-PD-1 therapy to improve T-cell access to the tumor microenvironment, which is crucial for overcoming tumor immune resistance.
  • Two mouse models of cancer (MC38 colon cancer and B16 melanoma) were used to test the effects of combined treatment with anti-PD-1 and Pep R (a CXCR4 antagonist), showing significant reductions in tumor volume compared to treatments with either agent alone.
  • Results indicated that the combination treatment not only decreased tumor size but also increased the presence of Granzyme B-positive immune cells that are important for tumor rejection, while also reducing immunosuppressive Fox
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Background: Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).

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Development of distant metastasis relies on interactions between cancer and stromal cells. CXCL12, also known as stromal-derived factor 1α (SDF-1α), is a major chemokine constitutively secreted in bone marrow, lymph nodes, liver and lung, playing a critical role in the migration and seeding of neoplastic cells. CXCL12 activates the CXCR4 receptor that is overexpressed in several human cancer cells.

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