Search results for "LUDI"
showing 10 items of 753 documents
Synergistic effects of neurons and astrocytes on the differentiation of brain capillary endothelial cells in culture
2003
Brain capillary endothelial cells form a functional barrier between blood and brain, based on the existence of tight junctions that limit paracellular permeability. Occludin is one of the major transmembrane proteins of tight junctions and its peripheral localization gives indication of tight junction formation. We previously reported that RBE4.B cells (brain capillary endothelial cells), cultured on collagen IV, synthesize occludin and correctly localize it at the cell periphery only when cocultured with neurons. In the present study, we describe a three-cell type-culture system that allowed us to analyze the combined effects of neurons and astrocytes on differentiation of brain capillary …
OP0205 Gut Dysbiosis in Patients with HLA-B27+ Ankylosing Spondylitis is Associated with Ileitis, Down-Regulation of Tight Junction Proteins, Increas…
2015
Background Intestinal dysbiosis has been recently demonstrated in the inflamed ileum of AS patients. Objectives To study the ileal localization of bacteria in AS patients and their relationship with local and systemic immune responses. Methods Consecutive gut biopsies obtained from 30 HLA-B27 + AS patients and 20 normal subjects were histologically classified in normal histology, acute inflammation and chronic inflammation. Giemsa and Silver stains were used to visualize bacteria and characterize their morphology. Intestinal bacteria were scored on the basis of the numbers of bacteria and their aggregation in clusters. The ileal expression and tissue distribution of claudin-2 and 4, Zonulin…
Messing Up the Cancer Stem Cell Chemoresistance Mechanisms Supported by Tumor Microenvironment
2021
Despite the recent advances in cancer patient management and in the development of targeted therapies, systemic chemotherapy is currently used as a first-line treatment for many cancer types. After an initial partial response, patients become refractory to standard therapy fostering rapid tumor progression. Compelling evidence highlights that the resistance to chemotherapeutic regimens is a peculiarity of a subpopulation of cancer cells within tumor mass, known as cancer stem cells (CSCs). This cellular compartment is endowed with tumor-initiating and metastasis formation capabilities. CSC chemoresistance is sustained by a plethora of grow factors and cytokines released by neighboring tumor…
Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities
2020
Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to th…
HER2 Signaling and Breast Cancer Stem Cells: The Bridge behind HER2-Positive Breast Cancer Aggressiveness and Therapy Refractoriness
2021
Simple Summary Breast cancer (BC) is not a single disease, but a group of different tumors, and altered HER2 expression defines a particularly aggressive subtype. Although HER2 pharmacological inhibition has dramatically improved the prognosis of HER2-positive BC patients, there is still an urgent need for improved knowledge of HER2 biology and mechanisms underlying HER2-driven aggressiveness and drug susceptibility. Emerging data suggest that the clinical efficacy of molecularly targeted therapies is related to their ability to target breast cancer stem cells (BCSCs), a population that is not only self-sustaining and able to differentiate into distinct lineages, but also contributes to tum…
Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells
2022
Despite advances in the curative approach, the survival rate of advanced colorectal cancer (CRC) patients is still poor, which is likely due to the emergence of cancer cell clones resistant to the available therapeutic options. We have already shown that CD44v6-positive CRC stem cells (CR-CSCs) are refractory toward standard anti-tumor therapeutic agents due to the activation of the PI3K pathway together with high HER2 expression levels. Tumor microenvironmental cytokines confer resistance to CR-CSCs against HER2/PI3K targeting by enhancing activation of the MAPK pathway. Here, we show that the CSC compartment, spared by BRAF inhibitor-based targeted therapy, is associated with increased ex…
Colorectal Cancer Stem Cells and Cell Death
2011
Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem-like cells (CSCs), which survive conventional anticancer treatments, hanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) a…
Intratumoral Heterogeneity, Its Contribution to Therapy Resistance and Methodological Caveats to Assessment
2014
Cancer is one of the most urgent health issues of today. According to WHO, the number of cancer cases is expected to increase by 75% in the next two decades (1). Despite some remarkable achievements in the fields of cancer prevention and early detection, the goal of developing effective anti-cancer therapies still remains unmet. Tumor recurrence due to treatment resistance is the most common cause of death from cancer. Delineating cellular and molecular mechanisms underlying tumor recurrence is of prime importance for the ability to improve the efficacy of existing therapies and develop new strategies to cancer treatment.
Dissecting the Mechanism of Action of Spiperone—A Candidate for Drug Repurposing for Colorectal Cancer
2022
Approximately 50% of colorectal cancer (CRC) patients still die from recurrence and metastatic disease, highlighting the need for novel therapeutic strategies. Drug repurposing is attracting increasing attention because, compared to traditional de novo drug discovery processes, it may reduce drug development periods and costs. Epidemiological and preclinical evidence support the antitumor activity of antipsychotic drugs. Herein, we dissect the mechanism of action of the typical antipsychotic spiperone in CRC. Spiperone can reduce the clonogenic potential of stem-like CRC cells (CRC-SCs) and induce cell cycle arrest and apoptosis, in both differentiated and CRC-SCs, at clinically relevant co…
Le ricerche di Aldo Visalberghi in campo didattico
2021
Il capitolo presenta gli interessi principali di studio e di ricerca di Aldo Visalberghi, preceduti da una breve parentesi biografica: delinea alcuni aspetti del pensiero di John Dewey quali fonti di ispirazione del pedagogista triestino; descrive la pedagogia esperienziale come sapere didattico-educativo da lui sostenuto; sintetizza il suo interesse per la valutazione nel processo educativo; descrive le variabili del condizionamento sociale nell’educazione scolastica da lui individuate; rileva la dimensione formativa della ricerca da lui valorizzata; evidenzia il valore sociale che Visalberghi attribuiva all’insegnamento e all’apprendimento; sottolinea il carattere ludiforme che egli asseg…