31 results on '"Daveri E"'
Search Results
2. Phosphorylation-independent mTORC1 inhibition by the autophagy inducer Rottlerin
- Author
-
Torricelli, C., Daveri, E., Salvadori, S., Valacchi, G., Ietta, F., Muscettola, M., Carlucci, F., and Maioli, E.
- Published
- 2015
- Full Text
- View/download PDF
3. Is impaired response to PD-1 blockers of high serum PD-1 patients related to immune complexes?
- Author
-
Daveri, E, Luison, E, Vallacchi, V, Vergani, B, Leone, B, Garassino, M, Figini, M, Rivoltini, L, Daveri E., Luison E., Vallacchi V., Vergani B., Leone B. E., Garassino M. C., Figini M., Rivoltini L., Daveri, E, Luison, E, Vallacchi, V, Vergani, B, Leone, B, Garassino, M, Figini, M, Rivoltini, L, Daveri E., Luison E., Vallacchi V., Vergani B., Leone B. E., Garassino M. C., Figini M., and Rivoltini L.
- Published
- 2021
4. Is impaired response to PD-1 blockers of high serum PD-1 patients related to immune complexes?
- Author
-
Daveri, E., Luison, E., Vallacchi, V., Vergani, B., Leone, B.E., Garassino, M.C., Figini, M., and Rivoltini, L.
- Published
- 2021
- Full Text
- View/download PDF
5. 491P Lipid-engulfed macrophages at the root of gut carcinogenesis
- Author
-
Daveri, E., primary, Sorrentino, L., additional, Vergani, B., additional, Cattaneo, L., additional, Lalli, L., additional, Cosimelli, M., additional, Vitellaro, M., additional, Huber, V., additional, Cova, A., additional, Gariboldi, M., additional, Belfiore, A., additional, Leone, B.E., additional, Milione, M., additional, and Rivoltini, L., additional
- Published
- 2021
- Full Text
- View/download PDF
6. 970P Assessment of anti-PD-1 antibody and immune complex binding to Fcγ receptors and clinical implications
- Author
-
Daveri, E., primary, Luison, E., additional, Vallacchi, V., additional, Vergani, B., additional, Leone, B.E., additional, Garassino, M.C., additional, Figini, M., additional, and Rivoltini, L., additional
- Published
- 2021
- Full Text
- View/download PDF
7. Assessment of anti-PD-1 antibody and immune complex binding to Fc gamma receptors and clinical implications
- Author
-
E. Daveri, E. Luison, V. Vallacchi, B. Vergani, B.E. Leone, M.C. Garassino, M. Figini, L. Rivoltini
- Published
- 2021
- Full Text
- View/download PDF
8. Non-conventional rottlerin anticancer properties
- Author
-
Maioli, E., primary, Daveri, E., additional, Maellaro, E., additional, Ietta, F., additional, Cresti, L., additional, and Valacchi, G., additional
- Published
- 2018
- Full Text
- View/download PDF
9. Metabolism and Immune Modulation in Patients with Solid Tumors: Systematic Review of Preclinical and Clinical Evidence
- Author
-
Elena Daveri, Claudio Vernieri, Roberto Mele, Luca Porcu, Vanesa Gregorc, Stefano Cascinu, Chiara Lazzari, Licia Rivoltini, Alessandra Bulotta, Aurora Mirabile, Maria Grazia Viganò, Mirabile, A., Rivoltini, L., Daveri, E., Vernieri, C., Mele, R., Porcu, L., Lazzari, C., Bulotta, A., Vigano, M. G., Cascinu, S., and Gregorc, V.
- Subjects
0301 basic medicine ,Cancer Research ,Arginine ,medicine.medical_treatment ,cancer metabolism ,Review ,Bioinformatics ,lcsh:RC254-282 ,immune response ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Medicine ,Microbiome ,Immune response ,immune-nutrition ,Nutrition ,business.industry ,Lipid metabolism ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer metabolism ,Glutamine ,Metabolic pathway ,030104 developmental biology ,nutrition ,Oncology ,Docosahexaenoic acid ,030220 oncology & carcinogenesis ,Immune-nutrition ,immunotherapy ,business - Abstract
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients’ nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.
- Published
- 2020
10. Is impaired response to PD-1 blockers of high serum PD-1 patients related to immune complexes?
- Author
-
Marina Chiara Garassino, E. Luison, Biagio Eugenio Leone, Barbara Vergani, M. Figini, E. Daveri, V. Vallacchi, Licia Rivoltini, Daveri, E, Luison, E, Vallacchi, V, Vergani, B, Leone, B, Garassino, M, Figini, M, and Rivoltini, L
- Subjects
business.industry ,Programmed Cell Death 1 Receptor ,High serum ,MEDLINE ,Neoplasms, Second Primary ,Antigen-Antibody Complex ,Hematology ,B7-H1 Antigen ,Immune system ,Text mining ,Oncology ,Immunology ,Humans ,Medicine ,business ,Melanoma ,Human - Full Text
- View/download PDF
11. Outcomes of chemotherapy/chemoradiation vs. R2 surgical debulking vs. palliative care in nonresectable locally recurrent rectal cancer.
- Author
-
Sorrentino L, Scardino A, Battaglia L, Vigorito R, Sabella G, Patti F, Prisciandaro M, Daveri E, Gronchi A, Belli F, and Guaglio M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Treatment Outcome, Chemoradiotherapy methods, Aged, 80 and over, Rectal Neoplasms therapy, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Rectal Neoplasms mortality, Palliative Care methods, Neoplasm Recurrence, Local, Cytoreduction Surgical Procedures methods
- Abstract
Locally recurrent rectal cancer is resected with clear margins in only 50% of cases, and these patients achieve a three-year survival rate of 50%. Outcomes and therapeutic strategies for nonresectable locally recurrent rectal cancer have been much less explored. The aim of the study was to assess the three-year progression-free survival and the three-year overall survival in locally recurrent rectal cancer patients treated by chemotherapy/chemoradiation only vs. chemotherapy/chemoradiation and R2 surgical debulking vs. palliative care. A total of 86 patients affected by nonresectable locally recurrent rectal cancer were included: three-year progression-free survival was 15.8% with chemotherapy/chemoradiation vs. 20.3% with R2 surgical debulking (Log-rank p=0.567), but both rates were higher than best palliative care (0.0%, Log-rank p=0.0004). Three-year overall survival rates were respectively 62.0%, 70.8% and 0.0% (Log-rank p<0.0001). Chemotherapy/chemoradiation (HR 0.33, p=0.028) and R2 surgical debulking with or without chemotherapy/chemoradiation (HR 0.23, p=0.005) were independent predictors of improved progression-free survival on multivariate analysis. In conclusion, both chemotherapy/chemoradiation alone and R2 surgery with or without chemotherapy/chemoradiation provide a survival benefit over palliative care in nonresectable locally recurrent rectal cancer. However, considering that pelvic debulking is burdened by a high rate of complications, and considering its negligible impact on progression-free survival and overall survival when associated to medical therapy, surgery should be avoided in this setting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
12. Management of patients with locally recurrent rectal cancer with a previous history of distant metastases: retrospective cohort study.
- Author
-
Sorrentino L, Daveri E, Belli F, Vigorito R, Battaglia L, Sabella G, Patti F, Randon G, Pietrantonio F, Vernieri C, Scaramuzza D, Villa S, Milione M, Gronchi A, Cosimelli M, and Guaglio M
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Neoplasm Metastasis, Adult, Rectal Neoplasms pathology, Neoplasm Recurrence, Local
- Published
- 2024
- Full Text
- View/download PDF
13. Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.
- Author
-
Illescas O, Ferrero G, Belfiore A, Pardini B, Tarallo S, Ciniselli CM, Noci S, Daveri E, Signoroni S, Cattaneo L, Mancini A, Morelli D, Milione M, Cordero F, Rivoltini L, Verderio P, Pasanisi P, Vitellaro M, Naccarati A, and Gariboldi M
- Subjects
- Humans, Inflammation genetics, Inflammation prevention & control, Leukocyte L1 Antigen Complex, Pilot Projects, MicroRNAs genetics, Neoplasms
- Abstract
Background: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut., Methods: Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches., Results: Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes., Conclusions: Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet., Clinical Trial Number Registration: NCT04552405, Registered in ClinicalTrials.gov., Competing Interests: Conflicts of interest No relevant conflicts of interest exist for all the authors. No funding sources had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
14. Impact of Microscopically Positive (≤1 mm) Distal Margins on Disease Recurrence in Rectal Cancer Treated by Neoadjuvant Chemoradiotherapy.
- Author
-
Sorrentino L, Sileo A, Daveri E, Battaglia L, Guaglio M, Centonze G, Sabella G, Patti F, Villa S, Milione M, Belli F, and Cosimelli M
- Abstract
Background: The adequate distal resection margin is still controversial in rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). The aim of this study was to assess the impact of a distal margin of ≤1 mm on locoregional recurrence-free survival (LRRFS)., Methods: Among 255 patients treated with nCRT and surgery at the National Cancer Institute of Milan, 83 (32.5%) had a distal margin of ≤1 mm and 172 (67.5%) had a distal margin of >1 mm. Survival analyses were performed to assess the impact of distal margin on 5-year LRRFS, as well as Cox survival analysis. The role of distal margin on survival was analyzed according to different tumor regression grades (TRGs)., Results: The overall 5-year LRRFS rate was 77.6% with a distal margin of ≤1 mm vs. 88.3% with a distal margin of >1 mm (Log-rank p = 0.09). Only stage ypT4 was an independent predictor of worse LRRFS (HR 15.14, p = 0.026). The 5-year LRRFS was significantly lower in TRG3-5 patients with a distal margin of ≤1 mm compared to those with a distal margin of >1 mm (68.5% vs. 84.2%, p = 0.027), while no difference was observed in case of TRG1-2 ( p = 0.77)., Conclusions: Low-responder rectal cancers after nCRT still require a distal margin of >1 mm to reduce the high likelihood of local relapse.
- Published
- 2023
- Full Text
- View/download PDF
15. Extracellular vesicles in anti-tumor immunity.
- Author
-
Vergani E, Daveri E, Vallacchi V, Bergamaschi L, Lalli L, Castelli C, Rodolfo M, Rivoltini L, and Huber V
- Subjects
- Humans, Immunotherapy, Immunity, Cell Line, Tumor, Extracellular Vesicles metabolism
- Abstract
To what extent extracellular vesicles (EVs) can impact anti-tumor immune responses has only started to get unraveled. Their nanometer dimensions, their growing number of subtypes together with the difficulties in defining their origin hamper their investigation. The existence of tumor cell lines facilitated advance in cancer EV understanding, while capturing information about phenotypes and functions of immune cell EVs in this context is more complex. The advent of immunotherapy with immune checkpoint inhibitors has further deepened the need to dissect the impact of EVs during immune activation and response, not least to contribute unraveling and preventing the generation of resistance occurring in the majority of patients. Here we discuss the factors that influence anddrive the immune response in cancer patients in the context of cancer therapeutics and the roles or possible functions that EVs can have in this scenario. With immune cell-derived EVs as leitmotiv, we will journey from EV discovery and subtypes through physiological and pathological functions, from similarities with tumor EVs to measures to revert detrimental consequences on immune responses to cancer., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
16. Pathologic complete response after neoadjuvant chemotherapy/(re)chemoradiation for pelvic relapse of rectal cancer undergoing complex pelvic surgery: more frequent than expected?
- Author
-
Sorrentino L, Daveri E, Sabella G, Battaglia L, Milione M, Rivoltini L, and Cosimelli M
- Subjects
- Chemoradiotherapy methods, Humans, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Rectum pathology, Retrospective Studies, Treatment Outcome, Neoadjuvant Therapy methods, Rectal Neoplasms pathology
- Abstract
Purpose: To estimate the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy/(re)chemoradiation and its impact on survival in locally recurrent rectal cancer (LRRC) and to identify predictors of pCR or differences between neoadjuvant treatments., Methods: Among 394 LRRC patients treated at the National Cancer Institute of Milan (Italy), 74 (27.8%) were treated with neoadjuvant chemotherapy with or without (re)chemoradiation before surgery. The pCR rate was estimated, and its impact on 5-year survival was evaluated with the Kaplan-Meier survival method. Univariate analysis was performed to find pre-treatment predictors of pCR., Results: After surgery, in 12 (16.2%) patients, a pCR was observed. All patients who reached pCR had R0 margins after surgery; among the 62 non-pCR patients, R0 margins were obtained in 29 (46.8%) cases only (p = 0.0004). pCR patients showed a significantly higher 5-year overall survival compared to non-pCR cases (33.3% vs. 21.0%, p = 0.045) and a trend toward better 5-year re-local recurrence-free survival. On univariate analysis, no predictor of pCR was found in the present study based on pre-treatment features., Conclusion: Since pCR is significantly associated to R0 resection and 5-year overall survival, pCR could be a target for LRRC cure. However, pCR is currently unpredictable based on pre-treatment features., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
17. Low baseline neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict increased overall survival in locally recurrent rectal cancer despite R1 margins.
- Author
-
Daveri E, Sorrentino L, Lalli L, Guaglio M, Battaglia L, Cattaneo L, Sabella G, Milione M, Rivoltini L, Cosimelli M, and Belli F
- Subjects
- Blood Platelets, Humans, Lymphocytes, Margins of Excision, Neoplasm Recurrence, Local, Prognosis, Retrospective Studies, Neutrophils, Rectal Neoplasms
- Abstract
Background: Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown., Aims: Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients., Methods: 184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status., Results: NLR >3.9 (hazard ratio [HR] 3.96, P = 0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P < 0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery., Conclusion: NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases., Competing Interests: Conflict of interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
18. 3D models for melanoma γδ T cell-based immunotherapy.
- Author
-
Huber V, Vallacchi V, Daveri E, and Vergani E
- Subjects
- Humans, Receptors, Antigen, T-Cell, gamma-delta, Immunotherapy, Melanoma therapy
- Published
- 2022
- Full Text
- View/download PDF
19. A randomized placebo-controlled cross-over study on the effects of anthocyanins on inflammatory and metabolic responses to a high-fat meal in healthy subjects.
- Author
-
Cremonini E, Daveri E, Iglesias DE, Kang J, Wang Z, Gray R, Mastaloudis A, Kay CD, Hester SN, Wood SM, Fraga CG, and Oteiza PI
- Subjects
- Blood Glucose metabolism, Cross-Over Studies, Diet, High-Fat adverse effects, Healthy Volunteers, Humans, Insulin, Leukocytes, Mononuclear metabolism, Anthocyanins pharmacology, Anthocyanins therapeutic use, Endotoxemia metabolism
- Abstract
This study investigated the effects of supplementation with a cyanidin- and delphinidin-rich extract (CDRE) on the postprandial dysmetabolism, inflammation, and redox and insulin signaling, triggered by the consumption of a high fat meal (HFM) in healthy individuals. Participants (n = 25) consumed a 1026-kcal HFM simultaneously with either the CDRE providing 320.4 mg of anthocyanins (90% cyanidin and delphinidin) or placebo. Diets were randomly assigned in a double blind, placebo-controlled crossover design. Blood was collected prior to (fasted, time 0), and for 5 h after meal consumption; plasma, serum, and peripheral blood mononuclear cells (PBMC) were isolated. AC metabolites were detected in serum as early as 30 min after CDRE consumption. The CDRE mitigated HFM-induced endotoxemia, reducing increases in plasma LPS and LPS-binding protein. The CDRE also reduced other events associated with HFM-triggered postprandial dysmetabolism including: i) plasma glucose and triglyceride increases; ii) TNFα and NOX4 upregulation in PBMC; and iii) JNK1/2 activation in PBMC. The CDRE did not significantly affect HFM-mediated increases in plasma insulin, GLP-1, GLP-2, GIP, and LDL- and HDL-cholesterol, and IKK phosphorylation in PBMC. In summary, dietary AC, i.e. cyanidin and delphinidin, exerted beneficial actions against unhealthy diets by modulating the associated postprandial dysmetabolism, endotoxemia, alterations of glycemia and lipidemia, and redox and insulin signaling., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
20. Preventive Anti-inflammatory Diet to Reduce Gastrointestinal Inflammation in Familial Adenomatous Polyposis Patients: A Prospective Pilot Study.
- Author
-
Belfiore A, Ciniselli CM, Signoroni S, Gariboldi M, Mancini A, Rivoltini L, Morelli D, Masci E, Bruno E, Macciotta A, Ricci MT, Daveri E, Cattaneo L, Gargano G, Apolone G, Milione M, Verderio P, Pasanisi P, and Vitellaro M
- Subjects
- Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli surgery, Adolescent, Adult, Aged, Anti-Inflammatory Agents administration & dosage, Child, Colectomy, Colorectal Neoplasms genetics, Colorectal Neoplasms prevention & control, Enteritis genetics, Enteritis pathology, Female, Gastritis genetics, Gastritis pathology, Humans, Italy, Male, Middle Aged, Pilot Projects, Treatment Outcome, Young Adult, Adenomatous Polyposis Coli diet therapy, Diet, Mediterranean, Enteritis prevention & control, Gastritis prevention & control
- Abstract
Familial adenomatous polyposis (FAP) is an autosomal-dominant hereditary condition associated with germline mutations in the adenomatous polyposis coli gene. Patient management involves prophylactic surgery and intensive life-long endoscopic surveillance. Diet is a major concern for patients with FAP, who are generally free of symptoms before surgery but tend to have issues related to bowel function postoperatively. We hypothesized that a low-inflammatory diet based on the principles and recipes of the Mediterranean diet would reduce markers of local and systemic inflammation. Twenty-eight patients with FAP over 18 years of age who underwent rectum-sparing prophylactic colectomy and were included in our surveillance program participated in a pilot dietary intervention study. Blood and stool samples at baseline (T0), at the end of the dietary intervention (T1, three months), and at the end of the study (T2, six months after T0) were collected. Gastrointestinal inflammation markers including fecal calprotectin, cyclooxygenase-2, and 15-hydroxyprostaglandin dehydrogenase were evaluated. Serum calprotectin, insulin, insulin-like growth factor-1, C-reactive protein, and glycated hemoglobin were also assessed. Significant changes in serum calprotectin, insulin, and insulin-like growth factor-1 levels occurred over time. Borderline significant changes were observed in the neutrophil-lymphocyte ratio. These changes were noticeable immediately at the end of the 3-month active dietary intervention (T1). A significant increase in 15-hydroxyprostaglandin dehydrogenase expression in the normal crypts of matched samples was also observed between T0 and T2. This pilot study supports the hypothesis that a low-inflammatory diet can modulate gastrointestinal markers of inflammation in individuals with FAP. PREVENTION RELEVANCE: Cancer is known to be related to inflammatory conditions. This study suggests that anti-inflammatory dietary intervention may potentially prevent adenomas and cancer in FAP patients by reducing systemic and tissue inflammatory indices., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
- View/download PDF
21. (-)-Epicatechin and Anthocyanins Modulate GLP-1 Metabolism: Evidence from C57BL/6J Mice and GLUTag Cells.
- Author
-
Cremonini E, Daveri E, Mastaloudis A, and Oteiza PI
- Subjects
- Animals, Glucose metabolism, Insulin metabolism, Male, Mice, Mice, Inbred C57BL, RNA, Messenger genetics, Anthocyanins pharmacology, Catechin pharmacology, Glucagon-Like Peptide 1 metabolism
- Abstract
Background: Generated in intestinal L cells through cleavage of proglucagon (Gcg), glucagon-like peptide 1 (GLP-1) is secreted and rapidly inactivated by dipeptidyl peptidase IV (DPP-IV). GLP-1 regulates insulin secretion and overall glucose homeostasis. The capacity of dietary bioactives to increase GLP-1 circulating levels, and therefore increase insulin secretion and glucose metabolism, has gained significant interest of late., Objectives: We evaluated the effects of (-)-epicatechin (EC) and different anthocyanins (ACs) and AC metabolites on GLP-1 metabolism in mice and on GLUTag cells., Methods: We fed 6-week-old C57BL/6J male mice a control diet or a control diet supplemented with either 40 mg AC or 20 mg EC/kg body weight for 14 weeks (AC) or 15 weeks (EC). Intestinal mRNA levels of Gcg and Dpp-iv were measured. In vitro, GLUTag cells were incubated in the presence or absence of different ACs, the AC metabolite protocatechuic acid (PCA), and EC. GLP-1 secretion and the main pathways involved in its release were assessed., Results: Long-term supplementation with EC or AC increased mouse GLP-1 plasma concentrations (55% and 98%, respectively; P < 0.05). In mice, 1) EC and AC increased Gcg mRNA levels in the ileum (91%) and colon (41%), respectively (P < 0.05); and 2) AC lowered ileum Dpp-iv mRNA levels (35%), while EC decreased plasma DPP-IV activity (15%; P < 0.05). In GLUTag cells, 1) cyanidin, delphinidin, PCA, and EC increased GLP-1 secretion (53%, 33%, 53%, and 68%, respectively; P < 0.05); and 2) cyanidin, delphinidin, EC, and PCA increased cyclin adenosine monophosphate levels (25-50%; P < 0.05) and activated protein kinase A (PKA; 100%, 50%, 80%, and 86%, respectively; P < 0.05)., Conclusions: In mice, EC and ACs regulated different steps in GLP-1 regulation, leading to increased plasma GLP-1. Cyanidin, delphinidin, PCA, and EC promoted GLP-1 secretion from GLUTag cells by activating the PKA-dependent pathway. These findings support the beneficial actions of these flavonoids in sustaining intestinal and glucose homeostasis through the modulation of the GLP-1 metabolism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Published
- 2021
- Full Text
- View/download PDF
22. Prediction of R0/R+ surgery by different classifications for locally recurrent rectal cancer.
- Author
-
Sorrentino L, Belli F, Guaglio M, Daveri E, and Cosimelli M
- Subjects
- Humans, Pelvis, Rectum surgery, Recurrence, Neoplasm Recurrence, Local, Rectal Neoplasms surgery
- Abstract
A widely adopted classification system for locally recurrent rectal cancer (LRRC) is currently missing, and the indication for surgery is not standardized. To evaluate all the published classification systems in a large monocentric cohort of LRRC patients, assessing their capability to predict a radical (R0) resection. A total of 152 consecutive LRRC patients treated at the National Cancer Institute of Milan (NCIM) from 2009 to 2017 were classified according to Pilipshen, Mayo Clinic, Memorial Sloan-Kettering Cancer Center (MSKCC), Wanebo, Yamada, Boyle, Dutch TME Trial, Royal Marsden and National Cancer Institute of Milan (NCIM) classification systems. Central location of LRRC was significantly predictive of R0 resection across all classification systems. R + resection was predicted by the "anterior" category of MSKCC (OR 2.66, p = 0.007), the "S2b" (OR 3.50, p = 0.04) and the "S3" (OR 2.70, p = 0.01) categories of NCIM, "pelvic disease through anastomosis" of Pilipshen (OR 2.89, p = 0.002), "fixed at 2 sites" of Mayo Clinic (OR 2.68, p = 0.019), and "TR4" of Wanebo (OR 3.39, p = 0.002). The NCIM was the most predictive classification for R0 surgery. The NCIM classification seems to be superior among the others in predicting R0 surgery. Generally, lateral invasive and high sacral invasive relapses are associated with reduced probability of R0 surgery and unfavorable outcomes.
- Published
- 2021
- Full Text
- View/download PDF
23. Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway.
- Author
-
Daveri E, Adamo AM, Alfine E, Zhu W, and Oteiza PI
- Subjects
- Caco-2 Cells, Cell Line, Tumor, Epidermal Growth Factor metabolism, ErbB Receptors, Humans, Oxidation-Reduction, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Signal Transduction, Colorectal Neoplasms drug therapy, Proanthocyanidins pharmacology
- Abstract
Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells. This work investigated if Hex could exert anti-CRC effects through its capacity to regulate the EGFR pathway. In proliferating Caco-2 cells, Hex acted attenuating EGF-induced EGFR dimerization and NADPH oxidase-dependent phosphorylation at Tyr 1068, decreasing EGFR location at lipid rafts, and inhibiting the downstream activation of pro-proliferative and anti-apoptotic pathways, i.e. Raf/MEK/ERK1/2 and PI3K/Akt. Hex also promoted EGFR internalization both in the absence and presence of EGF. While Hex decreased EGFR phosphorylation at Tyr 1068, it increased EGFR Tyr 1045 phosphorylation. The latter provides a docking site for the ubiquitin ligase c-Cbl and promotes EGFR degradation by lysosomes. Importantly, Hex acted synergistically with the EGFR-targeted chemotherapeutic drug Erlotinib, both in their capacity to decrease EGFR phosphorylation and inhibit cell growth. Thus, dietary PAC could exert anti-CRC actions by modulating, through both redox- and non-redox-regulated mechanisms, the EGFR pro-oncogenic signaling pathway. Additionally, Hex could also potentiate the actions of EGFR-targeted drugs., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
24. microRNAs Shape Myeloid Cell-Mediated Resistance to Cancer Immunotherapy.
- Author
-
Daveri E, Vergani E, Shahaj E, Bergamaschi L, La Magra S, Dosi M, Castelli C, Rodolfo M, Rivoltini L, Vallacchi V, and Huber V
- Subjects
- Drug Resistance, Neoplasm genetics, Epigenesis, Genetic, Humans, Immunomodulation genetics, Immunosuppression Therapy, Immunotherapy, Myeloid-Derived Suppressor Cells immunology, Myeloid-Derived Suppressor Cells metabolism, Neoplasms metabolism, Neoplasms therapy, Tumor Escape immunology, MicroRNAs genetics, Myeloid Cells immunology, Myeloid Cells metabolism, Neoplasms genetics, Neoplasms immunology
- Abstract
Immunotherapy with immune checkpoint inhibitors can achieve long-term tumor control in subsets of patients. However, its effect can be blunted by myeloid-induced resistance mechanisms. Myeloid cells are highly plastic and physiologically devoted to wound healing and to immune homeostasis maintenance. In cancer, their physiological activities can be modulated, leading to an expansion of pro-inflammatory and immunosuppressive cells, the myeloid-derived suppressor cells (MDSCs), with detrimental consequences. The involvement of MDSCs in tumor development and progression has been widely investigated and MDSC-induced immunosuppression is acknowledged as a mechanism hindering effective immune checkpoint blockade. Small non-coding RNA molecules, the microRNAs (miRs), contribute to myeloid cell regulation at different levels, comprising metabolism and function, as well as their skewing to a MDSC phenotype. miR expression can be indirectly induced by cancer-derived factors or through direct miR import via extracellular vesicles. Due to their structural stability and their presence in body fluids miRs represent promising predictive biomarkers of resistance, as we recently found by investigating plasma samples of melanoma patients undergoing immune checkpoint blockade. Dissection of the miR-driven involved mechanisms would pave the way for the identification of new druggable targets. Here, we discuss the role of these miRs in shaping myeloid resistance to immunotherapy with a special focus on immunosuppression and immune escape., (Copyright © 2020 Daveri, Vergani, Shahaj, Bergamaschi, La Magra, Dosi, Castelli, Rodolfo, Rivoltini, Vallacchi and Huber.)
- Published
- 2020
- Full Text
- View/download PDF
25. Metabolism and Immune Modulation in Patients with Solid Tumors: Systematic Review of Preclinical and Clinical Evidence.
- Author
-
Mirabile A, Rivoltini L, Daveri E, Vernieri C, Mele R, Porcu L, Lazzari C, Bulotta A, Viganò MG, Cascinu S, and Gregorc V
- Abstract
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.
- Published
- 2020
- Full Text
- View/download PDF
26. Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?
- Author
-
Mennitto A, Huber V, Ratta R, Sepe P, de Braud F, Procopio G, Guadalupi V, Claps M, Stellato M, Daveri E, Rivoltini L, and Verzoni E
- Abstract
The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells' (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.
- Published
- 2020
- Full Text
- View/download PDF
27. Anthocyanins protect the gastrointestinal tract from high fat diet-induced alterations in redox signaling, barrier integrity and dysbiosis.
- Author
-
Cremonini E, Daveri E, Mastaloudis A, Adamo AM, Mills D, Kalanetra K, Hester SN, Wood SM, Fraga CG, and Oteiza PI
- Subjects
- Caco-2 Cells, Dysbiosis, Endotoxemia drug therapy, Endotoxemia etiology, Endotoxemia metabolism, Goblet Cells metabolism, Humans, Mucin-2 genetics, Mucin-2 metabolism, NF-kappa B metabolism, Oxidative Stress drug effects, Permeability drug effects, Signal Transduction, Anthocyanins pharmacology, Diet, High-Fat adverse effects, Gastrointestinal Microbiome drug effects, Gastrointestinal Tract drug effects, Gastrointestinal Tract metabolism, Oxidation-Reduction, Protective Agents pharmacology
- Abstract
The gastrointestinal (GI) tract can play a critical role in the development of pathologies associated with overeating, overweight and obesity. We previously observed that supplementation with anthocyanins (AC) (particularly glycosides of cyanidin and delphinidin) mitigated high fat diet (HFD)-induced development of obesity, dyslipidemia, insulin resistance and steatosis in C57BL/6J mice. This paper investigated whether these beneficial effects could be related to AC capacity to sustain intestinal monolayer integrity, prevent endotoxemia, and HFD-associated dysbiosis. The involvement of redox-related mechanisms were further investigated in Caco-2 cell monolayers. Consumption of a HFD for 14 weeks caused intestinal permeabilization and endotoxemia, which were associated with a decreased ileum expression of tight junction (TJ) proteins (occludin, ZO-1 and claudin-1), increased expression of NADPH oxidase (NOX1 and NOX4) and NOS2 and oxidative stress, and activation of redox sensitive signals (NF-κB and ERK1/2) that regulate TJ dynamics. AC supplementation mitigated all these events and increased GLP-2 levels, the intestinal hormone that upregulates TJ protein expression. AC also prevented, in vitro, tumor necrosis factor alpha-induced Caco-2 monolayer permeabilization, NOX1/4 upregulation, oxidative stress, and NF-κB and ERK activation. HFD-induced obesity in mice caused dysbiosis and affected the levels and secretion of MUC2, a mucin that participates in intestinal cell barrier protection and immune response. AC supplementation restored microbiota composition and MUC2 levels and distribution in HFD-fed mice. Thus, AC, particularly delphinidin and cyanidin, can preserve GI physiology in HFD-induced obesity in part through redox-regulated mechanisms. This can in part explain AC capacity to mitigate pathologies, i.e. insulin resistance and steatosis, associated with HFD-associated obesity., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
28. Cyanidin and delphinidin modulate inflammation and altered redox signaling improving insulin resistance in high fat-fed mice.
- Author
-
Daveri E, Cremonini E, Mastaloudis A, Hester SN, Wood SM, Waterhouse AL, Anderson M, Fraga CG, and Oteiza PI
- Subjects
- Animals, Fatty Liver drug therapy, Fatty Liver etiology, Fatty Liver metabolism, Fatty Liver pathology, Inflammation etiology, Inflammation metabolism, Inflammation pathology, Male, Mice, Inbred C57BL, Obesity etiology, Obesity metabolism, Obesity pathology, Oxidation-Reduction drug effects, Signal Transduction drug effects, Anthocyanins therapeutic use, Diet, High-Fat adverse effects, Inflammation drug therapy, Insulin Resistance, Obesity drug therapy, Oxidative Stress drug effects
- Abstract
Consumption of diets high in fat and/or fructose content promotes tissue inflammation, oxidative stress, and insulin resistance, activating signals (e.g. NF-κB/JNK) that downregulate the insulin cascade. Current evidence supports the concept that select flavonoids can mitigate obesity and type 2 diabetes (T2D). This work investigated if supplementation with the anthocyanidins (AC) cyanidin and delphinidin could attenuate the adverse consequences of consuming a high fat diet (HFD) in mice. Consumption of an AC-rich blend mitigated HFD-induced obesity, dyslipidemia and insulin resistance (impaired responses to insulin and glucose). HFD-fed mice were characterized by increased liver lipid deposition and inflammation, which were also attenuated upon AC supplementation. HFD caused liver oxidative stress showing an increased expression of NADPH oxidases, generators of superoxide and H
2 O2 , and high levels of oxidized lipid-protein adducts. This was associated with the activation of the redox sensitive signals IKK/NF-κB and JNK1/2, and increased expression of the NF-κB-regulated PTP1B phosphatase, all known inhibitors of the insulin pathway. In agreement with an improved insulin sensitivity, AC supplementation inhibited oxidative stress, NF-κB and JNK activation, and PTP1B overexpression. Thus, cyanidin and delphinidin consumption either through diet or by supplementation could be a positive strategy to control the adverse effects of Western style diets, including overweight, obesity, and T2D. Modulation of inflammation, oxidative stress, and NF-κB/JNK activation emerge as relevant targets of AC beneficial actions., (Copyright © 2018. Published by Elsevier B.V.)- Published
- 2018
- Full Text
- View/download PDF
29. (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance.
- Author
-
Cremonini E, Wang Z, Bettaieb A, Adamo AM, Daveri E, Mills DA, Kalanetra KM, Haj FG, Karakas S, and Oteiza PI
- Subjects
- Animals, Caco-2 Cells, Fatty Liver metabolism, Humans, Intestinal Mucosa metabolism, Intestines drug effects, Male, Mice, Inbred C57BL, Permeability drug effects, Catechin therapeutic use, Diet, High-Fat adverse effects, Fatty Liver prevention & control, Insulin Resistance, Protective Agents therapeutic use
- Abstract
Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2-20mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption., (Copyright © 2017. Published by Elsevier B.V.)
- Published
- 2018
- Full Text
- View/download PDF
30. Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells.
- Author
-
Ietta F, Maioli E, Daveri E, Gonzaga Oliveira J, da Silva RJ, Romagnoli R, Cresti L, Maria Avanzati A, Paulesu L, Barbosa BF, Gomes AO, Roberto Mineo J, and Ferro EAV
- Subjects
- Autophagy drug effects, Cell Line, Humans, Protein Biosynthesis drug effects, Acetophenones pharmacology, Antiprotozoal Agents pharmacology, Benzopyrans pharmacology, Toxoplasma drug effects, Toxoplasma growth & development, Trophoblasts parasitology
- Abstract
Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. Toxoplasma gondii, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against Toxoplasma infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased Toxoplasma growth in infected cells. Although autophagy was synergically promoted by Toxoplasma infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and Toxoplasma in host protein translation, mediated by mTOR inhibition and eIF2α phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving Toxoplasma of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against Toxoplasma infection and encourage the development of Rottlerin-based new therapeutic formulations.
- Published
- 2017
- Full Text
- View/download PDF
31. Antiproliferative Effect of Rottlerin on Sk-Mel-28 Melanoma Cells.
- Author
-
Daveri E, Valacchi G, Romagnoli R, Maellaro E, and Maioli E
- Abstract
Melanoma is the most aggressive and chemoresistant form of skin cancer. Mutated, constitutively active B-RAF is believed to play a crucial role, although the selective B-RAF inhibition has shown poor clinical success, since phenomena of resistance usually occur, likely arising from additional genetic aberrations, such as loss of function of p53 and PTEN, overexpression of cyclin D1, hyperactivation of NF-κB, and downregulation of p21/Cip1. Since all of them are present in the Sk-Mel-28 melanoma cells, this cell line could be an ideal, albeit hard to study, model to develop new therapeutic strategies. In the current study, we tested the cytostatic action of Rottlerin on Sk-Mel-28 melanoma cells, on the basis of the known Rottlerin effects on the main proliferative signaling pathways. We presented evidence that the drug inhibits cell growth by an Akt- and p21/Cip1-independent mechanism, involving the dual inhibition of ERK and NF-κB and downregulation of cyclin D1. In addition, we found that Rottlerin increases ERK phosphorylation, but, surprisingly, this resulted in decreased ERK activity. Pull-down experiments, using Rottlerin-CNBr-conjugated Sepharose beads, revealed that Rottlerin binds to ERK, independently from its phosphorylation status. This direct interaction could in part explain the paradoxical blockage of ERK downstream signaling and growth arrest. We would like to dedicate this paper to the memory of our friend and colleague, prematurely deceased, Claudia Torricelli, who actively contributed to this project.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.