678 research outputs found
I BET on anti-FGFR to fight cancer resistance
No full textGraphical Abstract L. Altucci and R. Benedetti discuss the study by Chua et al (in this issue of EMBO Molecular Medicine), in which co‐targeting of FGFR signaling increases the responses of metastatic uveal melanoma to BET inhibitors
A key HDAC6 dependency of ARID1A-mutated ovarian cancer
No full textMutations in AT rich interactive domain 1A (ARID1A) are common in ovarian cancers. A study now shows that HDAC6 activity is required for survival of ovarian cancer cells bearing ARID1A mutations. HDAC6 inhibition selectively promotes apoptosis of ARID1A-inactivated cells, supporting the use of HDAC6 inhibition in the treatment of clear cell ovarian cancer
Characterization of the biological role of RIPK2 in carcinogenesis
No full textBackground. Cell survival, inflammation and cell death are the main processes involved in cellular homeostasis. The deregulation of these events can lead to the onset of several pathologies, including cancer. Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) plays a key signalling role in host defence, inflammation as well as in regulated cell death (1). Till now, it is known that RIPK2, through its CARD functional domain, is able to trigger the activation of NF-kB or the MAP kinase pathway playing a fundamental role in the immune response and inflammation (2) but little scientific evidence explain the direct involvement of the protein kinase in cancer, particularly in haematological malignancies (3). Hence, more studies are necessary to better clarify its involvement in tumorigenesis and metastasis. Aim: The aim of our work is to better define the biological role of RIPK2 in cancer with a particular focus in leukaemia, in order to clarify its molecular mechanisms. Here we also provide a deeper insight into the molecular mechanism of action of new epi-drugs, highlighting their ability to directly target RIPK2. Methods: To achieve the various objectives, we have made use of RT-qPCR, Western Blot, Flow Cytometry, Immunoprecipitation, Immunofluorescence. Results. RIPK2 is differentially expressed in tumour cell lines. In particular, we focused our attention on two myeloid cell lines (U-937 and HL-60) with a different degree of differentiation for subsequent proteomic analyses and cellular localization studies. Furthermore, RIPK2 appears to be modulated after the treatment with a previously characterized epi-drug, highlighting the possible involvement of RIPK2 in the cell death process. Conclusions. The effects observed by the compound strengthen its potential role as an anti-tumor agent in leukaemia mediated by RIPK2 expression. However, further molecular and enzymatic investigations will be necessary to better understand the biological role of RIPK2 in carcinogenesis, especially in hematological malignancies
IMMUNOMODULATORY ACTIVITY OF POLYPHENOLIC EXTRACTS FROM STRAWBERRY CULTIVARS
No full textBackground: In recent years, strawberry has received much attention for its high nutritional value and potential benefits for human health due to its rich phytochemical profile and low observed toxicity1. Previous research has shown that polyphenols have anti-inflammatory, antimicrobial, antioxidant, anticarcinogenic, diabetic, and neuroprotective properties2. However, their individual effects on different cell signalling pathways remain to be elucidated3.
Aim: This study will aim to investigate the immunomodulatory activity of four strawberry cultivars (Marimbella, Red Sara, Gioelita, Melissa) in order to identify their potential anticancer role.
Methods: Strawberry extracts were used to treat in vitro cellular models of THP1-derived macrophages induced with lipopolysaccharides (LPS). Techniques as Western blot, qRT-PCR, flow cytometry, Griess assay were additionally performed.
Results. Given the strong interaction between immune cells and the tumour microenvironment in mediating the inflammatory response, we determined i) the release of specific pro-inflammatory and anti-inflammatory mediators into the tumour microenvironment, ii) the inhibition of both nitric oxide (NO) synthesis and intracellular levels of reactive oxygen species (ROS), and iii) the modulation of regulated cell death pathways (RCD) involved in inflammation.
Conclusions: Defining the immunomodulatory effects induced by polyphenolic extracts of strawberry cultivars will provide useful information on the restoration of the compromised immune system in cancer. This scenario highlights the fundamental role of phenolic substances in exerting anti-tumour mechanisms
NETosis in pathologies: a preliminary study for NETs detection in vitro
No full textBackground: Neutrophils are the major participants in NETosis, a novel kind of regulated cell death (RCD) that has recently emerged. As a result, neutrophils not only serve as the initial line of defense for the host, but they also help to mediate the new RCD by releasing neutrophil extracellular traps (NETs).1 NETosis is characterized by sequence of events: intracellular membranes disintegrate and proteases from granules enter the nucleus, followed by hypercitrullination of histones, chromatin decondensation and extrusion of nuclear material from the cell. Then, NETs decorated by decondensed chromatin, modified histones and granular enzymes are released from cells. 2
Physiologically, NETs entrap bacteria and provide a natural defence against inflammation but an exacerbated release of NETs markers can exert pro-thrombotic and pro-inflammatory effects and are resulted implicated in many diseases such as hyperglycaemia, diabetes and its complications. 3
Aim: The project has the purpose to to study in depth NETosis pathway and its implications in pathogenesis. Specifically, will be characterize the epi-modulation of NETs formation in samples derived from cancer and diabetic patients.
Materials and methods: differentiation of HL60 FOR 5 days with Dimethyl sulfoxide or All-trans retinoic acid. May Grunwald Giemsa staining. Immunofluorescence staining Anti-MPO and H3cit. Flow based assay to detect NETs. ROS assay.
Result: several methods have been developed o investigate NETosis. NETs formation has been identified after epi drugs induction.
The methods we are using to detect NETs and to evaluate NETosis markers are efficient to study NETosis in blood samples from patients.
Conclusions: NETosis is a recent discovered RCD that resulted de-regulated in many pathologies. The characterization of NETosis mechanism and complete understanding of NETosis role in pathogenesis could provide new prognostic markers and novels therapeutic targets
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