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  1. Article ; Online: Deletion of TNF in Winnie- APC Min/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer

    Giulio Verna / Marina Liso / Elisabetta Cavalcanti / Raffaele Armentano / Alessandro Miraglia / Vladia Monsurrò / Marcello Chieppa / Stefania De Santis

    International Journal of Molecular Sciences, Vol 23, Iss 15145, p

    2022  Volume 15145

    Abstract: Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their ... ...

    Abstract Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie- Apc Min/+ line. We characterized the new Winnie- APC Min/+- TNF-KO line through macroscopical and microscopical analyses. Surprisingly, the latter demonstrated that the deletion of Tnf in Winnie- Apc Min/+ mice resulted in an initial reduction in dysplastic lesion incidence in 5-week-old mice followed by a faster disease progression at 8 weeks. Histological data were confirmed by the molecular profiling obtained from both the real-time PCR analysis of the whole tissue and the RNA sequencing of the macrodissected tumoral lesions from Winnie- APC Min/+- TNF-KO distal colon at 8 weeks. Our results highlight that TNF could exert a dual role in CAC, supporting the promotion of neoplastic lesions onset in the early stage of the disease while inducing their reduction during disease progression.
    Keywords colon cancer ; inflammation ; animal models ; ulcerative colitis ; TNF ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

    Giulio Verna / Marina Liso / Elisabetta Cavalcanti / Giusy Bianco / Veronica Di Sarno / Angelo Santino / Pietro Campiglia / Marcello Chieppa

    International Journal of Molecular Sciences, Vol 22, Iss 8349, p

    2021  Volume 8349

    Abstract: Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory ... ...

    Abstract Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs ( Slpi , Hmox1, and AP-1 ).
    Keywords quercetin ; dendritic cells ; plasmacytoid ; cytokines ; slpi ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: miR-369-3p modulates inducible nitric oxide synthase and is involved in regulation of chronic inflammatory response

    Viviana Scalavino / Marina Liso / Elisabetta Cavalcanti / Isabella Gigante / Antonio Lippolis / Mauro Mastronardi / Marcello Chieppa / Grazia Serino

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: Abstract Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. In our previous study, we identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing ... ...

    Abstract Abstract Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. In our previous study, we identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing C/EBP-β, TNFα and IL-6 production. With the aim of gaining further insight into the biological function of miR-369-3p during acute inflammatory response, in the present study we identified novel gene targets of miR-369-3p and demonstrated the suppressive ability of these genes on the inflammatory dendritic cells. Bioinformatic analyses revealed that iNOS is a potential target of miR-369-3p. We demonstrated that the ectopic induction of miR-369-3p markedly reduced iNOS mRNA and protein as well as NO production. Moreover, we found that the upregulation of miR-369-3p decreased the release of TNFα, IL-6, IL-12, IL-1α, IL-1β in response to LPS, and increased the production of anti-inflammatory cytokines such as IL-10 and IL-1RA. In addition, LPS-induced nuclear translocation of NF-kB was inhibited by miR-369-3p. Levels of miR-369-3p were decreased in human inflamed regions of human intestine obtained from IBD patients. Our results provide novel additional information on miR-369-3p as a potential core of the signaling regulating the inflammatory response. These findings suggest that miR-369-3p should be considered as a potential target for the future development of new molecular therapeutic approaches.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Association of Alpha B-Crystallin Expression with Tumor Differentiation Grade in Colorectal Cancer Patients

    Cristina Pagano / Giovanna Navarra / Patrizia Gazzerro / Mario Vitale / Maria Notarnicola / Maria Gabriella Caruso / Elisabetta Cavalcanti / Raffaele Armentano / Chiara Laezza / Maurizio Bifulco

    Diagnostics, Vol 11, Iss 896, p

    2021  Volume 896

    Abstract: Alpha B-crystallin (CRYAB, HSPB5) belongs to the small heat shock protein (HSP) family and is highly expressed in various human cancers, suggesting a crucial role in tumor progression. However, few studies have examined CRYAB expression in colorectal ... ...

    Abstract Alpha B-crystallin (CRYAB, HSPB5) belongs to the small heat shock protein (HSP) family and is highly expressed in various human cancers, suggesting a crucial role in tumor progression. However, few studies have examined CRYAB expression in colorectal cancer (CRC). In the present study, we investigated the relationship between CRYAB expression and the clinicopathological features of CRC samples. We comparatively analyzed CRYAB protein expression in 111 CRC tissues and normal adjacent colonic tissue, observing that it was significantly lower in CRC tissues than in corresponding non-cancerous tissues. Moreover, immunohistochemical analysis showed a significant correlation between CRYAB expression and high histological grade G3 ( p = 0.033). In summary, our results point to its possible application as a prognostic biomarker in CRC patients.
    Keywords Alpha-β-crystallin ; colorectal adenocarcinoma ; hystological grade ; tissues samples ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCII low CD11c + CD11b + F4/80 + Cells

    Giulio Verna / Marina Liso / Stefania De Santis / Manuela Dicarlo / Elisabetta Cavalcanti / Alberto Crovace / Annamaria Sila / Pietro Campiglia / Angelo Santino / Antonio Lippolis / Grazia Serino / Alessio Fasano / Marcello Chieppa

    International Journal of Molecular Sciences, Vol 21, Iss 4, p

    2020  Volume 1353

    Abstract: Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they ... ...

    Abstract Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c + MHCII hi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1 , and decreased IRF8 expression.
    Keywords dendritic cells ; inflammation ; iron overload ; bone marrow ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice

    Manuela Dicarlo / Gabriella Teti / Giulio Verna / Marina Liso / Elisabetta Cavalcanti / Annamaria Sila / Sathuwarman Raveenthiraraj / Mauro Mastronardi / Angelo Santino / Grazia Serino / Antonio Lippolis / Anastasia Sobolewski / Mirella Falconi / Marcello Chieppa

    International Journal of Molecular Sciences, Vol 20, Iss 22, p

    2019  Volume 5771

    Abstract: Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic ... ...

    Abstract Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.
    Keywords inflammatory bowel diseases ; quercetin ; small intestinal organoids ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Winnie- APC Min/+ Mice

    Stefania De Santis / Giulio Verna / Grazia Serino / Raffaele Armentano / Elisabetta Cavalcanti / Marina Liso / Manuela Dicarlo / Sergio Coletta / Mauro Mastronardi / Antonio Lippolis / Angela Tafaro / Angelo Santino / Aldo Pinto / Pietro Campiglia / Alex Y. Huang / Fabio Cominelli / Theresa T. Pizarro / Marcello Chieppa

    International Journal of Molecular Sciences, Vol 21, Iss 2972, p

    A Spontaneous Model of Colitis-Associated Colorectal Cancer Combining Genetics and Inflammation

    2020  Volume 2972

    Abstract: 1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we ... ...

    Abstract (1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with Apc Min/+ mice. (3) Results: The resulting Winnie- Apc Min/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie- Apc Min/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie- Apc Min/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.
    Keywords colorectal cancer ; murine model ; inflammation ; Aberrant Crypt Foci ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 333
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Administration Timing Is the Best Clinical Outcome Predictor for Adalimumab Administration in Crohn's Disease

    Mauro Mastronardi / Margherita Curlo / Elisabetta Cavalcanti / Osvaldo Burattini / Renato Cuppone / Romina Tauro / Stefania De Santis / Grazia Serino / Pasqua Letizia Pesole / Elisa Stasi / Maria Lucia Caruso / Rossella Donghia / Vito Guerra / Pietro Giorgio / Marcello Chieppa

    Frontiers in Medicine, Vol

    2019  Volume 6

    Abstract: Biological intervention for Crohn's Disease (CDs) patients, mainly using anti-TNF antibodies, is often an efficient therapeutic solution. Nonetheless, data defining the administration timing to maximize the chances of clinical remission are lacking. The ... ...

    Abstract Biological intervention for Crohn's Disease (CDs) patients, mainly using anti-TNF antibodies, is often an efficient therapeutic solution. Nonetheless, data defining the administration timing to maximize the chances of clinical remission are lacking. The objective of this “real-life” retrospective study was to evaluate if early Adalimumab (ADA) administration (<12 months) was an efficient strategy to improve patients' clinical outcome. This single center study included 157 CD patients, of which 80 received the first ADA administration within the first 12 months from the diagnosis. After 1 year of therapy, clinical remission was observed in 50.32% of patients, mucosal healing in 37.58%. Clinical remission was observed in 66.25% of the early ADA administration patients vs. 33.77% of the late (>12 months) (p < 0.001); mucosal healing was observed in 53.75% of the early vs. 20.78% of the late (p < 0.001). Dose escalation was required for 30.00% of the early vs. 66.23% of the late (<0.01). In the early ADA administration group, 7.50% patients were considered non-responders at the end of the follow-up vs. 22.08% patients in the late administration group. These findings highlighted that early ADA administration (within 1 year of diagnosis) improves the clinical response and mucosal healing, and reduces the loss of response rate and need for dose escalation.
    Keywords Crohn's disease ; biological agents anti-TNF ; Adalimumab ; clinical outcome ; clinical remission ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

    Elisabetta Cavalcanti / Elisa Vadrucci / Francesca Romana Delvecchio / Francesco Addabbo / Simona Bettini / Rachel Liou / Vladia Monsurrò / Alex Yee-Chen Huang / Theresa Torres Pizarro / Angelo Santino / Marcello Chieppa

    PLoS ONE, Vol 9, Iss 2, p e

    2014  Volume 88898

    Abstract: Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal ... ...

    Abstract Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation in CD8+ T Cells in Renal Cell Carcinoma Patients

    Elisabetta Cavalcanti / Margherita Gigante / Vito Mancini / Michele Battaglia / Pasquale Ditonno / Carmela Capobianco / Raffaele I. Cincione / Francesco P. Selvaggi / Wolfgang Herr / Walter J. Storkus / Loreto Gesualdo / Elena Ranieri

    Journal of Biomedicine and Biotechnology, Vol

    2010  Volume 2010

    Abstract: To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed ... ...

    Abstract To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneic CD8+ T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responder CD8+ T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution of CD8+ T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specific CD8+ effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC.
    Keywords Biotechnology ; TP248.13-248.65 ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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