Publications by authors named "Alfieri R"

Article Synopsis
  • - Esophageal cancer is a deadly type of cancer, accounting for 5% of cancer-related deaths, with two main types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the latter of which is less studied.
  • - The study used advanced single-cell RNA sequencing to identify immune cell types and genes that influence anti-tumor responses in EAC, assessing their potential to predict patient outcomes post-surgery.
  • - The findings suggest new immunological biomarkers for EAC that can help personalize treatment strategies, improve prognosis predictions, and aid in patient follow-up after surgery.
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Background: Radical esophagectomy, including thoracic duct resection (TDR), has been proposed to improve regional lymphadenectomy and possibly reduce the risk of locoregional recurrence. However, because of its impact on immunoregulation, some authors have expressed concerns about its possible detrimental effect on long-term survival. The purpose of this review was to assess the influence of TDR on long-term survival.

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The approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based combinations as the new standard of care for affected patients. Nonetheless, monotherapy with antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib or sunitinib, still represents a first-line treatment option for selected patients belonging to the favorable risk group according to the International mRCC Database Consortium (IMDC) model. After TKI monotherapy, the main second-line option is represented by ICI monotherapy with the anti-Programmed Death Receptor 1(PD-1) nivolumab.

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Objective: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT).

Background: Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival.

Methods: This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020.

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The long noncoding RNA TERRA is transcribed from telomeres in virtually all eukaryotes with linear chromosomes. In humans, TERRA transcription is driven in part by promoters comprising CpG dinucleotide-rich repeats of 29 bp repeats, believed to be present in half of the subtelomeres. Thus far, TERRA expression has been analyzed mainly using molecular biology-based approaches that only generate partial and somehow biased results.

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Article Synopsis
  • Lung cancer, particularly lethal pulmonary adenocarcinomas, often shows mutations in the EGFR gene, making understanding tumor behavior and treatment important.
  • Researchers utilized genetically engineered mice to study how tumors evolve and interact with their surrounding environment, identifying specific vulnerable cells and their communication with other cells in the tumor microenvironment.
  • The drug Unesbulin, a tubulin binding agent, was found to decrease tumor growth and alter the interactions within the tumor environment, suggesting it could be a promising therapeutic strategy for treating EGFR-mutant lung cancers.
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Osimertinib, a tyrosine kinase inhibitor targeting mutant EGFR, has received approval for initial treatment in patients with Non-Small Cell Lung Cancer (NSCLC). While effective in both first- and second-line treatments, patients eventually develop acquired resistance. Metabolic reprogramming represents a strategy through which cancer cells may resist and adapt to the selective pressure exerted by the drug.

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Article Synopsis
  • Osimertinib, an EGFR tyrosine kinase inhibitor, is effective for treating EGFR-mutated Non-Small Cell Lung Cancer (NSCLC), but patients often develop resistance, which is not fully understood.
  • This study found that resistant NSCLC cells had higher levels of glycosylceramides, specifically glucosylceramides (GlcCers), and inhibiting the enzyme GCS led to significant anti-cancer effects, including cell cycle arrest and apoptosis.
  • Furthermore, in animal models, the GCS inhibitor PDMP notably suppressed tumor growth, suggesting that targeting ceramide metabolism could be a promising strategy for overcoming osimertinib resistance in NSCLC patients.
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In the last few years, a tremendous advancement has been made in the therapeutical management of several diseases with an increasing need for parental drug administration. To avoid repeated venous insertions and the patient's anxiety related to these procedures, it is now common practice to insert a catheter to leave it in place for a longer time. However, these procedures may generate some complications, such as failure of insertion, embolization, and infection.

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Background: Monoclonal antibodies (ICI) targeting the immune checkpoint PD-1/PD-L1 alone or in combination with chemotherapy have demonstrated relevant benefits and established new standards of care in first-line treatment for advanced non-oncogene addicted non-small cell lung cancer (NSCLC). However, a relevant percentage of NSCLC patients, even with high PD-L1 expression, did not respond to ICI, highlighting the presence of intracellular resistance mechanisms that could be dependent on high PD-L1 levels. The intracellular signaling induced by PD-L1 in tumor cells and their correlation with angiogenic signaling pathways are not yet fully elucidated.

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Background: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.

Methods: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples.

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Background: Cell-cycle regulators are mutated in approximately 40% of all cancer types and have already been linked to worse outcomes in non-small cell lung cancer adenocarcinomas treated with osimertinib. However, their exact role in osimertinib resistance has not been elucidated.

Objective: In this study, we aimed to evaluate how the CDK4/6-Rb axis may affect the sensitivity to osimertinib.

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Cardiovascular diseases (CVDs), such as arterial hypertension, myocardial infarction, stroke, heart failure, atrial fibrillation, etc., still represent the main cause of morbidity and mortality worldwide. They significantly modify the patients' quality of life with a tremendous economic impact.

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Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone.

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Chromosomal instability (CIN) is very frequent in gastroesophageal adenocarcinoma (GEA) and it is characterized by deletions/mutations resulting in p53 nuclear accumulation, as revealed by immunohistochemistry (IHC), which considers the cases with "high" staining levels to be positive. Aiming to improve aberrant detection, droplet digital PCR (ddPCR) was used to evaluate deletion in formalin-fixed, paraffin-embedded DNA (FFPE-DNA) and cell-free DNA (cfDNA). To further investigate the mutational profile, next-generation sequencing (NGS) was performed in a subset of FFPE samples.

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Angiogenesis is crucial for cancer progression. While several anti-angiogenic drugs are in use for cancer treatment, their clinical benefits are unsatisfactory. Thus, a deeper understanding of the mechanisms sustaining cancer vessel growth is fundamental to identify novel biomarkers and therapeutic targets.

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Females have a lower probability to develop somatic cancers and a better response to chemotherapy than males. However, the reasons for these differences are still not well understood. The X-linked gene TSPY-Like 2 (TSPYL2) encodes for a putative tumor suppressor protein involved in cell cycle regulation and DNA damage response (DDR) pathways.

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The abdominal aortic aneurysm (AAA) is a potentially fatal asymptomatic disease. It progresses silently with clinical complications that, when they occur, constitute a very serious event, frequently resulting in the patient's exitus. As a result, early detection and treatment are critical because the right therapeutic strategy can halt the disease's natural progression.

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Background: Malignant pleural mesothelioma is a pathology with no effective therapy and a poor prognosis. Our previous study demonstrated an in vitro inhibitory effect on mesothelioma cell lines of both the lysate and secretome of adipose tissue-derived Mesenchymal Stromal Cells. The inhibitory activity on tumor growth has been demonstrated also : five million Mesenchymal Stromal Cells, injected , produced a significant therapeutic efficacy against MSTO-211H xenograft equivalent to that observed after the systemic administration of paclitaxel.

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In tumors, the multi drug resistance phenomenon may occur through the efflux of chemotherapeutic drugs out of cancer cells, impeding their accumulation, and eventually reducing their toxicity. This process is mediated by transporters overexpressed in the plasma membranes of tumor cells, among which is the P-glycoprotein/multidrug resistance 1/ATP-binding cassette B1 (P-gp/MDR1/ABCB1). The aim of this study was to explore the effect of a new molecule, called AIF-1, on ABCB1 activity.

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Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are rare primary malignant liver cancers in children and young adults. HB is the most common and accounts for about 70 % cases; it is usually diagnosed during the first 3 years of life. Instead, pediatric HCC is uncommon, and it is associated with a poor prognosis.

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