Publications by authors named "Massimo Libra"

The disruption of the epigenetic patterns and its impact on gene expression is recognized as a critical factor in the initiation and progression of cancer. Altered patterns of DNA methylation, histone modifications, and non-coding RNA expression are distinctive features of tumorigenesis. These dynamic shifts in the epigenetic landscape during oncogenic transformation are intricately linked to tumor heterogeneity, the sustained capacity for self-renewal, and the ability to undergo multi-lineage differentiation.

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One of the leading causes of cancer-related death in women is breast cancer (BC). BC is a heterogeneous tumor. Although tissue biopsy is the gold standard for the diagnosis of BC, often tissue specimens are not informative enough about the tumor heterogeneity.

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The oral microbiota plays a pivotal role in maintaining oral health, but its dysbiosis has been increasingly implicated in the development of systemic diseases, including cancer. Emerging evidence highlights the potential contribution of oral microorganisms to carcinogenesis in the oral cavity and distant organs, such as the lungs, pancreas, and genitourinary tract. This review explores the mechanisms through which the oral microbiota influences cancer development and treatment response, mainly driven by microbial translocation, systemic inflammation, immune modulation, and the release of carcinogenic metabolites.

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MicroRNAs (miRNAs) are important regulators of gene expression and their dysregulation is involved in various diseases, including tumors. Among these, colorectal cancer (CRC) is the result of both genetic and epigenetic alterations with miRNAs playing a key pathogenetic role. Although numerous studies have investigated the most frequently dysregulated miRNAs in CRC, there is still no consensus on the specific role of individual miRNAs in the mechanisms leading to tumorigenesis, tumor progression, and the development of chemoresistance.

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Recent advances in screening programs and the development of innovative therapeutic strategies have significantly improved the clinical outcomes of cancer patients. However, many patients still experience treatment failure, primarily due to inherent or acquired drug resistance mechanisms. This challenge underscores the urgent need for novel therapeutic targets for the effective treatment of malignancies, as well as cancer-specific biomarkers to enhance early diagnosis and guide interventions.

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Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and one of the leading causes of cancer death worldwide. Despite diagnostic and therapeutic advances, CRC mortality remains high, especially in industrialized countries. Numerous studies have highlighted the pathogenetic role of altered microRNA (miRNA) expression among the various factors contributing to the development and progression of colorectal cancer (CRC).

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Background: Cancer onset and progression are driven by genetic and epigenetic alterations leading to oncogene activation and the silencing of tumor suppressor genes. Among epigenetic mechanisms, DNA methylation (methDNA) is gaining growing interest in cancer. Promoter hypomethylation is associated with oncogene activation while intragenic methDNA can be involved in transcriptional elongation, alternative spicing, and the activation of cryptic start sites.

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Article Synopsis
  • Non-coding RNAs (ncRNAs) play a significant role in regulating cellular processes, and their altered expression is linked to prostate cancer (PCa), affecting disease initiation and response to treatment.
  • This study focused on evaluating the effectiveness of specific RNAs, particularly miRNAs, in differentiating PCa from benign prostatic hyperplasia (BPH) using unfiltered urine samples from 100 patients.
  • The findings indicated that certain miRNAs (like miR-27b-3p and miR-574-3p) are more reliable biomarkers for PCa than long RNAs, with combined miRNA profiles providing even better diagnostic accuracy, highlighting the potential of these non-invasive markers in clinical practice.
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Glioblastoma (GBM) represents an aggressive brain tumor, characterized by intra- and inter-tumoral heterogeneity and therapy resistance, leading to unfavourable prognosis. An increasing number of studies pays attention on the regulation of ferroptosis, an iron-dependent cell death, as a strategy to reverse drug resistance in cancer. However, the debate on whether this strategy may have important implications for the treatment of GBM is still ongoing.

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Recently, the mounting integration of probiotics into human health strategies has gathered considerable attention. Although the benefits of probiotics have been widely recognized in patients with gastrointestinal disorders, immune system modulation, and chronic-degenerative diseases, there is a growing need to evaluate their potential risks. In this context, new concerns have arisen regarding the safety of probiotics as some strains may have adverse effects in humans.

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Health-related quality of life (HRQoL) represents one of the most concerning aspects for cancer patients. The Healthy Eating Index (HEI) is an a priori diet quality index directly associated with health outcomes and HRQoL in cancer survivors in North American populations. We evaluated, in a Mediterranean population, the baseline associations between HEI-2015 and HRQoL in 492 women with breast cancer recruited in a DEDiCa lifestyle trial.

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Oral lichen planus (OLP) is a chronic inflammatory autoimmune disease of the oral cavity with malignant potential affecting 1.01% of the worldwide population. The clinical patterns of this oral disorder, characterized by relapses and remissions of the lesions, appear on buccal, lingual, gingival, and labial mucosa causing a significant reduction in the quality of life.

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DNA methylation is an epigenetic modification that plays a key role in several cellular processes mediating the fine regulation of gene expression. Aberrant DNA methylation is observed in a wide range of pathologies, including cancer. Since these DNA modifications are transferred to the cell progenies and are stable over the time, the analysis of DNA methylation status has been proposed for diagnostic and prognostic purposes in cancer.

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Breast cancer (BC), a complex disease with several influencing factors, is significantly impacted by dietary habits. The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has gained attention as a potential therapeutic approach, but its effects on BC remain unclear. This review seeks to summarize the current knowledge on the principles of the KD, its metabolic influence on BC cells, and the findings of recent clinical trials, in order to elucidate the potential therapeutic role of the KD in BC management.

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Article Synopsis
  • Lip, oral, and pharyngeal cancers pose significant global health challenges, making it essential to analyze their burden for effective health policies.
  • The study utilized data from the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study to assess cancer incidence, mortality, and life years lost across 204 countries, linking these to socio-demographic factors.
  • Findings revealed approximately 370,000 cases and 199,000 deaths for lip and oral cavity cancer, and 167,000 cases and 114,000 deaths for other pharyngeal cancers in 2019, with smoking being the leading risk factor for these cancers, especially in low and middle SDI regions.
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Article Synopsis
  • The study investigates the potential link between specific types of dietary prebiotics (like inulin and galactooligosaccharides) and the risk of upper digestive tract cancers.
  • Research was based on an analysis of data from Italian case-control studies conducted between 1992 and 2009, including nearly 1,500 cancer patients and over 4,000 controls.
  • Results showed no significant association between prebiotic intake and the risk of cancers in the oral cavity, nasopharynx, and esophagus, indicating that consuming these fibers may not impact these particular types of cancer.
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Several therapeutic strategies for cancer treatments have been developed with time, and significant milestones have been achieved recently. However, with these novel therapies, not all cancer types respond and in the responding cancer types only a subset is affected. The failure to respond is principally the result that these cancers develop several mechanisms of resistance.

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The oncogenic transformation is driven by genetic and epigenetic alterations influencing cancer cell fate. These alterations also result in metabolic reprogramming by modulating the expression of membrane Solute Carrier (SLC) transporters involved in biomolecules trafficking. SLCs act as tumor suppressors or promoters influencing cancer methylome, tumor growth, immune-escape, and chemoresistance.

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The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance.

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Background: Few studies have investigated the role of the phosphodiesterase type 5A (PDE5A) isoenzyme in female genital tissue disorders, exclusively taken from cadavers, as well as the epigenetic mechanisms responsible for the regulation of PDE5A levels.

Aim: The aim was to study the in vivo association between microRNA (miRNA) expression and the expression levels of PDE5A in women with female genital arousal disorder (FGAD) compared with healthy women.

Methods: Premenopausal women affected by FGAD (cases) and sexually healthy women (control group) underwent microbiopsy of the periclitoral anterior vaginal wall for the collection of tissue samples.

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Lung cancer (LC) represents the second most diagnosed tumor and the malignancy with the highest mortality rate. In recent years, tremendous progress has been made in the treatment of this tumor thanks to the discovery, testing, and clinical approval of novel therapeutic approaches. Firstly, targeted therapies aimed at inhibiting specific mutated tyrosine kinases or downstream factors were approved in clinical practice.

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Despite aggressive therapeutic regimens, glioblastoma (GBM) represents a deadly brain tumor with significant aggressiveness, radioresistance and chemoresistance, leading to dismal prognosis. Hypoxic microenvironment, which characterizes GBM, is associated with reduced therapeutic effectiveness. Moreover, current irradiation approaches are limited by uncertain tumor delineation and severe side effects that comprehensively lead to unsuccessful treatment and to a worsening of the quality of life of GBM patients.

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Forkhead box protein P3 (FOXP3) is known to orchestrate the development and maintenance of T regulatory cells, a cell population specialized in immune suppression and peripheral immune tolerance. FOXP3 activity is fine-tuned through its interaction with several protein-binding partners. By using IntAct database, we retrieved three physical binary interactors: E3 ubiquitin-protein ligase CHIP, Zfp-90, and nuclear receptor ROR-α.

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Background: Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells.

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