28 results on '"Samantha Pesce"'
Search Results
2. Supplementary Figures from Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
- Author
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Filippo de Braud, Licia Rivoltini, Davide Bedognetti, Giancarlo Pruneri, Valter Torri, Giovanni Apolone, Valter Daniel Longo, Marco Foiani, Saverio Minucci, Mario Paolo Colombo, Giulia Bianchi, Giuseppe Capri, Marina Chiara Garassino, Secondo Folli, Cristina Ferraris, Angela Maria Rizzo, Paola Antonia Corsetto, Raghvendra Mall, Paola Frati, Samantha Pesce, Agata Cova, Paola Squarcina, Viviana Vallacchi, Salvatore Cortellino, Arta Ajazi, Federica Zanardi, Valeria Cancila, Claudia Chiodoni, Luca Lalli, Antonino Belfiore, Gianmaria Frigè, Darawan Rinchai, Alessandra Raimondi, Fabio Iannelli, Andrea Vingiani, Veronica Huber, Francesca Ligorio, Giovanni Fucà, and Claudio Vernieri
- Abstract
Supplementary Figures
- Published
- 2023
3. Data from Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
- Author
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Filippo de Braud, Licia Rivoltini, Davide Bedognetti, Giancarlo Pruneri, Valter Torri, Giovanni Apolone, Valter Daniel Longo, Marco Foiani, Saverio Minucci, Mario Paolo Colombo, Giulia Bianchi, Giuseppe Capri, Marina Chiara Garassino, Secondo Folli, Cristina Ferraris, Angela Maria Rizzo, Paola Antonia Corsetto, Raghvendra Mall, Paola Frati, Samantha Pesce, Agata Cova, Paola Squarcina, Viviana Vallacchi, Salvatore Cortellino, Arta Ajazi, Federica Zanardi, Valeria Cancila, Claudia Chiodoni, Luca Lalli, Antonino Belfiore, Gianmaria Frigè, Darawan Rinchai, Alessandra Raimondi, Fabio Iannelli, Andrea Vingiani, Veronica Huber, Francesca Ligorio, Giovanni Fucà, and Claudio Vernieri
- Abstract
In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments.Significance:Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy.This article is highlighted in the In This Issue feature, p. 1
- Published
- 2023
4. Supplementary Methods from Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
- Author
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Filippo de Braud, Licia Rivoltini, Davide Bedognetti, Giancarlo Pruneri, Valter Torri, Giovanni Apolone, Valter Daniel Longo, Marco Foiani, Saverio Minucci, Mario Paolo Colombo, Giulia Bianchi, Giuseppe Capri, Marina Chiara Garassino, Secondo Folli, Cristina Ferraris, Angela Maria Rizzo, Paola Antonia Corsetto, Raghvendra Mall, Paola Frati, Samantha Pesce, Agata Cova, Paola Squarcina, Viviana Vallacchi, Salvatore Cortellino, Arta Ajazi, Federica Zanardi, Valeria Cancila, Claudia Chiodoni, Luca Lalli, Antonino Belfiore, Gianmaria Frigè, Darawan Rinchai, Alessandra Raimondi, Fabio Iannelli, Andrea Vingiani, Veronica Huber, Francesca Ligorio, Giovanni Fucà, and Claudio Vernieri
- Abstract
Supplementary Methods
- Published
- 2023
5. SupplementaryTables S7-S16 from Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
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Filippo de Braud, Licia Rivoltini, Davide Bedognetti, Giancarlo Pruneri, Valter Torri, Giovanni Apolone, Valter Daniel Longo, Marco Foiani, Saverio Minucci, Mario Paolo Colombo, Giulia Bianchi, Giuseppe Capri, Marina Chiara Garassino, Secondo Folli, Cristina Ferraris, Angela Maria Rizzo, Paola Antonia Corsetto, Raghvendra Mall, Paola Frati, Samantha Pesce, Agata Cova, Paola Squarcina, Viviana Vallacchi, Salvatore Cortellino, Arta Ajazi, Federica Zanardi, Valeria Cancila, Claudia Chiodoni, Luca Lalli, Antonino Belfiore, Gianmaria Frigè, Darawan Rinchai, Alessandra Raimondi, Fabio Iannelli, Andrea Vingiani, Veronica Huber, Francesca Ligorio, Giovanni Fucà, and Claudio Vernieri
- Abstract
Supplementary Table S7-S16
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- 2023
6. Supplementary Figure Legends 1-6 from Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
- Author
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Paola Allavena, Maurizio D'Incalci, Alberto Mantovani, Juan Carlos Tercero, Carlos Maria Galmarini, Manuela Nebuloni, Angela Greco, Silvana Pilotti, Eva Tarantino, Emanuela Virdis, Alessandro Gronchi, Paolo G. Casali, Roberta Sanfilippo, Federica Grosso, Fabio Pasqualini, Samantha Pesce, Eugenio Erba, Michele Tavecchio, Matteo Simone, Roberta Frapolli, and Giovanni Germano
- Abstract
Supplementary Figure Legends 1-6 from Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
- Published
- 2023
7. Supplementary Figures 1-6 from Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
- Author
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Paola Allavena, Maurizio D'Incalci, Alberto Mantovani, Juan Carlos Tercero, Carlos Maria Galmarini, Manuela Nebuloni, Angela Greco, Silvana Pilotti, Eva Tarantino, Emanuela Virdis, Alessandro Gronchi, Paolo G. Casali, Roberta Sanfilippo, Federica Grosso, Fabio Pasqualini, Samantha Pesce, Eugenio Erba, Michele Tavecchio, Matteo Simone, Roberta Frapolli, and Giovanni Germano
- Abstract
Supplementary Figures 1-6 from Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
- Published
- 2023
8. Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
- Author
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Samantha Pesce, Luca Lalli, Giovanni Fucà, Angela Maria Rizzo, Arta Ajazi, Giancarlo Pruneri, Paola Squarcina, Viviana Vallacchi, Licia Rivoltini, Marco Foiani, Valeria Cancila, Salvatore Cortellino, Cristina Ferraris, Davide Bedognetti, Federica Zanardi, Alessandra Raimondi, Claudio Vernieri, Gianmaria Frigè, Andrea Vingiani, Darawan Rinchai, Francesca Ligorio, Giovanni Apolone, Valter D. Longo, Valter Torri, Giulia Bianchi, Saverio Minucci, Marina Chiara Garassino, Claudia Chiodoni, Filippo de Braud, Raghvendra Mall, Paola Frati, Giuseppe Capri, Fabio Iannelli, Antonino Belfiore, Agata Cova, Mario P. Colombo, Secondo Folli, Veronica Huber, and Paola Antonia Corsetto
- Subjects
Male ,Myeloid ,medicine.medical_treatment ,Antineoplastic Agents ,Breast Neoplasms ,Pharmacology ,Transcriptome ,Immune system ,medicine ,Cytotoxic T cell ,Humans ,Prospective Studies ,business.industry ,Growth factor ,Cancer ,Metabolism ,Fasting ,Middle Aged ,medicine.disease ,Clinical trial ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Female ,business ,Colorectal Neoplasms - Abstract
In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments. Significance: Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy. This article is highlighted in the In This Issue feature, p. 1
- Published
- 2021
9. Selective modulation of immune transcripts in extracellular vesicles from plasma of renal cell carcinoma patients receiving nivolumab
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Eriomina Shahaj, Pierangela Sepe, Elena Verzoni, Monica Rodolfo, Filippo de Braud, Massimo Di Nicola, Paola Squarcina, Samantha Pesce, Luca Lalli, Veronica Huber, Alessia Mennitto, Melanie Claps, Agata Cova, Viviana Vallacchi, Simona Frigerio, Elisabetta Vergani, Giuseppe Procopio, Licia Rivoltini, and Filippo Pietrantonio
- Subjects
Selective modulation ,Cancer Research ,Immune system ,Oncology ,business.industry ,Renal cell carcinoma ,Cancer research ,bacteria ,Medicine ,Nivolumab ,business ,medicine.disease ,Extracellular vesicles - Abstract
719 Background: Patients (pts) displaying a full-fledged immune response show high levels of circulating extracellular vesicles (EVs) containing immune transcripts that might be transferred to neighboring cells to amplify immune responses, as in autoimmunity and transplantation. We hypothesized EV immune transcripts could reflect immune activation in cancer pts receiving immunotherapy with immune checkpoint inhibitors (ICI). These RNA-containing EVs may surrogate immune functionality and represent a plasma transcriptional signature of adaptive immunity that can be readily detected by liquid biopsy. Methods: Blood samples from metastatic renal cell cancer pts,treated with ICI nivolumab (n=8) or tyrosine kinase inhibitor cabozantinib (n=9) were collected at baseline, week 4 and 12. EV-RNA was isolated from plasma with membrane affinity spin columns and evaluated for CD274(PD-L1), IFNG, PDCD1 (PD-1), CD3 and GZMB (granzyme B) transcripts by qRT-PCR. Results: All pts showed a statistically significant increase of CD3, IFNG, GZMB, PD-1 and PD-L1 immune transcripts in plasma EVs, evidenced at 4 and 12 weeks of therapy. Treatment subgroup analysis revealed an upregulation of CD3, IFNG, GZMB and PD-1 transcripts only in plasma EVs of patients receiving nivolumab that was more evident in those showing clinical benefit (4/8), while PD-L1 increased significantly during cabozantinib treatment. Upon comparing transcripts with soluble proteins, PD-L1 displayed similar kinetics, while PD-1 increased only as transcript but not as protein, given its potential sequestration by the anti-PD-1 antibody. This effect was detectable only in nivolumab but not in cabozantinib treated pts. Conclusions: Monitoring immune transcripts carried by plasma EVs holds promise as potential tool to assess the entity of the ongoing immune activation during immunotherapy. Plasma EVs may be exploited as indicators of immune response and help to predict clinical efficacy at early on-treatment time points. This approach based on plasma EVs might represent a starting point for the development of a novel strategy to study immune responses in clinical setting.
- Published
- 2020
10. Evaluation of Mediators Associated with the Inflammatory Response in Prostate Cancer Patients Undergoing Radiotherapy
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Sergio Villa, Paola Allavena, Riccardo Valdagni, Valentina Zuco, Nice Bedini, Elisa Campi, Alessandro Cicchetti, Federica Palorini, Samantha Pesce, S. Morlino, Nadia Zaffaroni, Barbara Avuzzi, Tiziana Rancati, Maria Emanuela Visentin, Tiziana Magnani, and Marzia Pennati
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Chemokine ,Article Subject ,medicine.medical_treatment ,Clinical Biochemistry ,CCL2 ,03 medical and health sciences ,Basal (phylogenetics) ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Radiation Injuries ,Molecular Biology ,Chemokine CCL2 ,Aged ,lcsh:R5-920 ,biology ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Biochemistry (medical) ,Interleukin-8 ,Prostatic Neoplasms ,General Medicine ,PTX3 ,Middle Aged ,medicine.disease ,Radiation therapy ,Serum Amyloid P-Component ,030104 developmental biology ,C-Reactive Protein ,030220 oncology & carcinogenesis ,biology.protein ,Clinical Study ,Tumor necrosis factor alpha ,Radiotherapy, Intensity-Modulated ,lcsh:Medicine (General) ,business ,Abdominal surgery ,Interleukin-1 - Abstract
A recent “hot topic” in prostate cancer radiotherapy is the observed association between acute/late rectal toxicity and the presence of abdominal surgery before radiotherapy. The exact mechanism is unclear. Our working hypothesis was that a previous surgery may influence plasma level of inflammatory molecules and this might result in enhanced radiosensitivity. We here present results on the feasibility of monitoring the expression of inflammatory molecules during radiotherapy. Plasma levels of a panel of soluble mediators associated with the inflammatory response were measured in prostate cancer patients undergoing radical radiotherapy. We measured 3 cytokines (IL-1b, IL-6, and TNF alpha), 2 chemokines (CCL2 and CXCL8), and the long pentraxin PTX3. 20 patients were enrolled in this feasibility evaluation. All patients were treated with IMRT at 78 Gy. 3/20 patients reported grade 2 acute rectal toxicity, while 4/20 were scored as grade 2 late toxicity. CCL2 was the most interesting marker showing significant increase during and after radiotherapy. CCL2 levels at radiotherapy end could be modelled using linear regression including basal CCL2, age, surgery, hypertension, and use of anticoagulants. The 4 patients with late toxicity had CCL2 values at radiotherapy end above the median value. This trial is registered with ISRCTN64979094.
- Published
- 2018
11. Differential role of Interleukin-1 and Interleukin-6 in K-Ras-driven pancreatic carcinoma undergoing mesenchymal transition
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Imran Siddiqui, Paola Allavena, Fabio Pasqualini, Federica Marchesi, Alberto Mantovani, Silvia Schiarea, Chiara Chiabrando, Chiara Porta, Marco Erreni, Samantha Pesce, and Mohammad Azhar Kamal
- Subjects
0301 basic medicine ,Oncology ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,emt ,therapeutic antibodies ,Inflammation ,lcsh:RC254-282 ,03 medical and health sciences ,Pancreatic tumor ,oncogene ,Internal medicine ,Pancreatic cancer ,medicine ,Immunology and Allergy ,Interleukin 6 ,Original Research ,cancer immunotherapy ,biology ,Oncogene ,Chemistry ,Mesenchymal stem cell ,Interleukin ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Cytokine ,inflammation ,Cancer research ,biology.protein ,medicine.symptom ,lcsh:RC581-607 - Abstract
K-Ras mutations are a hallmark of human pancreatic adenocarcinoma (PDAC) and epithelial-mesenchymal-transition (EMT) is a driver of progression. Oncogenic K-Ras causes the constitutive activation of NF-kB and the switch-on of an inflammatory program, which further fuels NF-kB and STAT3 activation. In this study we investigated how inflammatory pathways triggered by oncogenic K-Ras are regulated in human pancreatic cancer cells with distict epithelial or mesenchymal phenotype. Our results demonstrate that in cells with epithelial features, K-Ras driven inflammation is under the control of IL-1, while in cells undergoing EMT, is IL-1 independent. In pancreatic tumor cells with EMT phenotype, treatment with IL-1R antagonist (Anakinra) did not inhibit inflammatory cytokine production and tumor growth in mice. In these cells IL-6 is actively transcribed by the EMT transcription factor TWIST. Targeting of mesenchymal pancreatic tumors in vivo with anti-IL-6RmAb (RoActemra) successfully decreased tumor growth in immunodeficient mice, inhibited the inflammatory stroma and NF-kB-p65 and STAT3 phosphorylation in cancer cells. The results confirm that IL-1 is an important driver of inflammation in epithelial pancreatic tumors; however, tumor cells undergoing EMT will likely escape IL-1R inhibition, as IL-6 is continuously transcribed by TWIST. These findings have implications for the rational targeting of inflammatory pathways in human pancreatic cancer.
- Published
- 2018
12. Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients
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Maurizio Infante, Emanuele Voulaz, Edoardo Bottoni, G Chiesa, Valentina Errico, Alessandro Montanelli, Silvio Cavuto, Emanuela Morenghi, Alberto Mantovani, Eliseo Passera, Marta Monari, Paola Allavena, Cecilia Garlanda, Daniel Solomon, Serenella Valaperta, Daoud Rahal, Marco Alloisio, Manuela Bossi, Massimo Roncalli, Samantha Pesce, and Manuela Nebuloni
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pathology ,education.field_of_study ,Receiver operating characteristic ,biology ,business.industry ,Population ,C-reactive protein ,Area under the curve ,Cancer ,Malignancy ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Internal medicine ,medicine ,biology.protein ,Biomarker (medicine) ,Lung cancer ,business ,education - Abstract
There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.
- Published
- 2015
13. Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients
- Author
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Maurizio, Infante, Paola, Allavena, Cecilia, Garlanda, Manuela, Nebuloni, Emanuela, Morenghi, Daoud, Rahal, Massimo, Roncalli, Silvio, Cavuto, Samantha, Pesce, Marta, Monari, Serenella, Valaperta, Alessandro, Montanelli, Daniel, Solomon, Edoardo, Bottoni, Valentina, Errico, Emanuele, Voulaz, Manuela, Bossi, Giuseppe, Chiesa, Eliseo, Passera, Alberto, Mantovani, and Marco, Alloisio
- Subjects
Male ,Lung Neoplasms ,NSCLC ,PTX3 ,biomarker ,inflammation ,Aged ,Area Under Curve ,Biomarkers, Tumor ,C-Reactive Protein ,Carcinoma, Non-Small-Cell Lung ,Enzyme-Linked Immunosorbent Assay ,Female ,Humans ,Immunohistochemistry ,Kaplan-Meier Estimate ,Middle Aged ,Prognosis ,Proportional Hazards Models ,ROC Curve ,Sensitivity and Specificity ,Serum Amyloid P-Component ,Non-Small-Cell Lung ,Tumor ,Carcinoma ,Biomarkers - Abstract
There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.
- Published
- 2016
14. Antitumor and Anti-inflammatory Effects of Trabectedin on Human Myxoid Liposarcoma Cells
- Author
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Roberta Frapolli, Juan Carlos Tercero, Maurizio D'Incalci, Samantha Pesce, Paola Allavena, Eva Tarantino, Angela Greco, Roberta Sanfilippo, S. Pilotti, Fabio Pasqualini, Federica Grosso, Carlos M. Galmarini, Matteo Simone, Emanuela Virdis, Manuela Nebuloni, Alessandro Gronchi, Paolo G. Casali, Eugenio Erba, Michele Tavecchio, Giovanni Germano, and Alberto Mantovani
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Chemokine ,Mice ,Tetrahydroisoquinolines ,Chemokine CCL2 ,Trabectedin ,Tumor ,Cell Death ,Cell Cycle ,Liposarcoma ,Alkylating ,Immunohistochemistry ,Primary tumor ,Liposarcoma, Myxoid ,CD ,Serum Amyloid P-Component ,C-Reactive Protein ,Oncology ,Differentiation ,Inflammation Mediators ,medicine.drug ,Antigens, Differentiation, Myelomonocytic ,Antineoplastic Agents ,Dioxoles ,Biology ,Animals ,Antigens, CD ,Antineoplastic Agents, Alkylating ,Cell Line, Tumor ,Humans ,Interleukin-6 ,Interleukin-8 ,Macrophages ,Xenograft Model Antitumor Assays ,Cell Line ,medicine ,Antigens ,Myxoid liposarcoma ,Tumor microenvironment ,Myelomonocytic ,medicine.disease ,Immunology ,Cancer cell ,Cancer research ,biology.protein ,Myxoid ,Ovarian cancer - Abstract
Inflammatory mediators present in the tumor milieu may promote cancer progression and are considered promising targets of novel biological therapies. We previously reported that the marine antitumor agent trabectedin, approved in Europe in 2007 for soft tissue sarcomas and in 2009 for ovarian cancer, was able to downmodulate the production of selected cytokines/chemokines in immune cells. Patients with myxoid liposarcoma (MLS), a subtype characterized by the expression of the oncogenic transcript FUS-CHOP, are highly responsive to trabectedin. The drug had marked antiproliferative effects on MLS cell lines at low nanomolar concentrations. We tested the hypothesis that trabectedin could also affect the inflammatory mediators produced by cancer cells. Here, we show that MLS express several cytokines, chemokines, and growth factors (CCL2, CCL3, CCL5, CXCL8, CXCL12, MIF, VEGF, SPARC) and the inflammatory and matrix-binder protein pentraxin 3 (PTX3), which build up a prominent inflammatory environment. In vitro treatment with noncytotoxic concentrations of trabectedin selectively inhibited the production of CCL2, CXCL8, IL-6, VEGF, and PTX3 by MLS primary tumor cultures and/or cell lines. A xenograft mouse model of human MLS showed marked reduction of CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels, and partial decrease of PTX3 after trabectedin treatment. Similar findings were observed in a patient tumor sample excised after several cycles of therapy, indicating that the results observed in vitro might have in vivo relevance. In conclusion, trabectedin has dual effects in liposarcoma: in addition to direct growth inhibition, it affects the tumor microenvironment by reducing the production of key inflammatory mediators. Cancer Res; 70(6); 2235–44
- Published
- 2010
15. Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer
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Federica Marchesi, Marco Erreni, Samantha Pesce, Giuseppe Di Caro, Marco Montorsi, Michele Carvello, Matteo Sacchi, Jelena Todoric, Antonino Spinelli, and Paola Allavena
- Subjects
0301 basic medicine ,Oncology ,Male ,Colorectal cancer ,Physiology ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Biochemistry ,0302 clinical medicine ,Surgical oncology ,Recurrence ,Immune Physiology ,Medicine and Health Sciences ,Medicine ,Postoperative Period ,Stage (cooking) ,lcsh:Science ,Immune Response ,Innate Immune System ,Multidisciplinary ,Acute-phase protein ,Hematology ,Prognosis ,Body Fluids ,Blood ,030220 oncology & carcinogenesis ,Cytokines ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,Anatomy ,Inflammation Mediators ,Colorectal Neoplasms ,Research Article ,medicine.medical_specialty ,Inflammatory Diseases ,Immunology ,Inflammation ,Surgical and Invasive Medical Procedures ,Blood Plasma ,Proinflammatory cytokine ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,Biomarkers, Tumor ,Humans ,Aged ,Neoplasm Staging ,Colorectal Cancer ,Tumor microenvironment ,business.industry ,lcsh:R ,Cancers and Neoplasms ,Biology and Life Sciences ,Proteins ,Correction ,Acute Phase Proteins ,Molecular Development ,medicine.disease ,030104 developmental biology ,Immune System ,lcsh:Q ,business ,Developmental Biology ,Follow-Up Studies - Abstract
Background Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients. Methods Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0–IV CRC and associated with post-operative disease recurrence. Results Cox multivariate analysis showed that combined high levels (≥ROC cut off-value) of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13–65.1)] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P
- Published
- 2015
16. The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination
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Imran Siddiqui, Federica Marchesi, Samantha Pesce, Andrea Doni, Cristiano Rumio, Diego Morone, Paolo Bianchi, Giulia Marelli, Alberto Mantovani, Fabio Grizzi, Massimo Roncalli, Luigi Laghi, Marco Erreni, Paola Allavena, and Giuseppe Celesti
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Chemokine ,Colorectal cancer ,Immunology ,CX3C Chemokine Receptor 1 ,Fluorescent Antibody Technique ,Mice, Nude ,Kaplan-Meier Estimate ,Biology ,Polymerase Chain Reaction ,Disease-Free Survival ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Lymphocytes, Tumor-Infiltrating ,Intestinal mucosa ,CX3CR1 ,medicine ,Fluorescence Resonance Energy Transfer ,Immunology and Allergy ,Animals ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,CX3CL1 ,Proportional Hazards Models ,Chemokine CX3CL1 ,medicine.disease ,Prognosis ,Immunohistochemistry ,Cell aggregation ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,Female ,Receptors, Chemokine ,Colorectal Neoplasms ,Transcriptome - Abstract
Human colorectal cancer (CRC) is a frequent neoplasia in Western countries, and its metastatic progression is a major cause of cancer-related death. In search of specific molecules upregulated in CRC, with possible clinical relevance, we performed a differential gene-profiling analysis in surgery-derived CRC samples and adjacent uninvolved intestinal mucosa. The chemokine CX3CL1 and its specific receptor CX3CR1 were significantly upregulated in tumors. Higher expression of CX3CL1 and CX3CR1 was confirmed by immunohistochemistry in 100 CRC tumor samples (stages I–III). Unexpectedly, high immune scores of CX3CL1 did not correlate with the density of tumor-infiltrating CD3+ T cells or CD68+ macrophages. Coexpression of ligand and receptor by tumor cells (axis-positive tumors) significantly associated with longer disease-free (p = 0.01) and disease-specific survival (p = 0.001). Conversely, axis-negative tumors (with low expression of both ligand and receptor) had increased risk of tumor relapse (p = 0.02), and increased likelihood of metachronous metastasis (p = 0.001), including after stage adjustment (p = 0.006). Transduction of CX3CL1 and CX3CR1 in CRC tumor cell lines induced cell aggregation that strongly inhibited in vitro migration in chemotaxis assays. In a mouse model of spleen–liver metastases, cancer dissemination to liver was dramatically reduced in CX3CL1-CX3CR1–expressing tumors, and ligand–receptor interaction was confirmed in cancer cells in vivo by fluorescence resonance energy transfer analysis. In conclusion, tumoral expression of the CX3CL1-CX3CR1 chemokine axis functions as a retention factor, increasing homotypic cell adhesion and limiting tumor spreading to metastatic sites. Lack or low levels of expression of CX3CL1-CX3CR1 by tumor cells identifies a group of CRC patients at increased risk of metastatic progression.
- Published
- 2015
17. Correction: Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer
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Samantha Pesce, Giuseppe Di Caro, Federica Marchesi, Antonino Spinelli, Paola Allavena, Michele Carvello, Marco Erreni, Matteo Sacchi, Jelena Todoric, and Marco Montorsi
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Multidisciplinary ,Colorectal cancer ,business.industry ,lcsh:R ,lcsh:Medicine ,medicine.disease ,Marie curie ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,media_common.cataloged_instance ,lcsh:Q ,European union ,lcsh:Science ,business ,030215 immunology ,media_common - Abstract
There is an error in the Funding section. The first sentence should read: The work was supported by 16230 Associazione Italiana per la ricerca sul cancro, Marie Curie Actions European Union to GDC.
- Published
- 2016
18. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer
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Francesca Bergomas, Samantha Pesce, Fabio Grizzi, Federica Marchesi, Paola Allavena, Luigi Laghi, Alberto Mantovani, and Andrea Doni
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Cancer Research ,Pathology ,medicine.medical_specialty ,Follicular dendritic cells ,immune infiltration ,High endothelial venules ,Innate lymphoid cell ,ectopic lymphoid tissue ,Inflammation ,Biology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Article ,Immune system ,medicine.anatomical_structure ,Lymphatic system ,Oncology ,colon cancer ,medicine ,Lymphopoiesis ,medicine.symptom ,B cell - Abstract
Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.
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- 2011
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19. Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for M2-polarization, influencing tumor cell motility
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Samantha Pesce, Marco Fabbri, Alberto Mantovani, Silvia Schiarea, Fabio Pasqualini, Graziella Solinas, Chiara Chiabrando, Paola Allavena, Manuela Liguori, Manuela Nebuloni, and Luca Zammataro
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Stromal cell ,Immunology ,Metastasis ,Extracellular matrix ,Cell Movement ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,Immunology and Allergy ,Humans ,Neoplasm Invasiveness ,Osteopontin ,Neoplasm Metastasis ,Cells, Cultured ,Cell Line, Transformed ,Tumor microenvironment ,biology ,Macrophages ,Cell Polarity ,Cell Differentiation ,medicine.disease ,HCT116 Cells ,Coculture Techniques ,Cell biology ,Fibronectins ,Neoplasm Proteins ,Fibronectin ,Culture Media, Conditioned ,Cancer cell ,biology.protein ,Neoplastic cell ,Cytokines ,HT29 Cells - Abstract
Tumor-associated macrophages (TAMs) are key orchestrators of the tumor microenvironment directly affecting neoplastic cell growth, neoangiogenesis, and extracellular matrix remodeling. In turn, the tumor milieu strongly influences maturation of TAMs and shapes several of their features. To address the early macrophage (Mϕ) differentiation phase in a malignant context, we mimicked a tumor microenvironment by in vitro coculturing human blood monocytes with conditioned media from different cancer cell lines. Only 2 out of 16 tumor cell lines induced Mϕ differentiation due to secreted M-CSF isoforms, including high molecular mass species. A global gene profiling of tumor-conditioned Mϕ was performed. Comparison with other datasets (polarized M1-Mϕ, M2-Mϕ, and TAMs isolated from human tumors) highlighted the upregulation of several genes also shared by TAM and M2-polarized Mϕ. The most expressed genes were selenoprotein 1, osteoactivin, osteopontin, and, interestingly, migration-stimulating factor (MSF), a poorly studied oncofoetal isoform of fibronectin. MSF (present in fetal/cancer epithelial and stromal cells but not in healthy tissues) was never identified in Mϕ. MSF production was confirmed by immunohistochemistry in human TAMs. MSF was induced by M-CSF, IL-4, and TGFβ but not by proinflammatory stimuli. RNA and protein analysis clearly demonstrated that it is specifically associated with the M2 polarization of Mϕ. Tumor-conditioned Mϕ-derived MSFs strongly stimulated tumor cell migration, thus contributing to the motile phenotype of neoplastic cells. In conclusion, MSF is a new molecule associated with the M2 polarization of Mϕ and expressed by TAMs. Its biological function may contribute to Mϕ-mediated promotion of cancer cell invasion and metastasis.
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- 2010
20. Human glioma tumors express high levels of the chemokine receptor CX3CR1
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Lorenzo Bello, Sergio M. Gaini, Mario Zavanone, Marco Locatelli, Samantha Pesce, Leonardo Boiocchi, Stefano Ferrero, Paola Allavena, Filippo Martinelli Boneschi, and Alberto Mantovani
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Male ,Pathology ,medicine.medical_specialty ,Chemokine ,Chemokine receptor CCR5 ,Clinical Biochemistry ,Immunology ,CX3C Chemokine Receptor 1 ,Chemokine receptor ,CX3CR1 ,medicine ,Immunology and Allergy ,Humans ,RNA, Messenger ,CX3CL1 ,Receptor ,biology ,Microglia ,Brain Neoplasms ,Glioma ,Middle Aged ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Logistic Models ,biology.protein ,Cancer research ,Female ,Receptors, Chemokine - Abstract
The chemokine receptor CX3CR1 and its cognate ligand CX3CL1 (also known as fractalkine), are involved in central nervous system pathophysiology, in particular, in the cross-talk between neurons and microglia. It was therefore important to investigate the expression of CX3CR1 in gliomas, the most frequently occurring, malignant brain tumors. In a consecutive series of 70 patients with primary, central nervous glial tumors, CX3CR1 was highly expressed in tumor cells as assessed by RT-PCR mRNA and protein levels, and by immunohistochemistry, while the corresponding normal cells were negative. Receptor immuno-positivity did not correlate with histology, grade, chromosomal (1p,19q) deletion, or with methylation of the DNA repair gene promoter MGMT (O6-methylguanine-DNA methyltransferase). Thus, CX3CR1 expression is a frequent event in gliomas, irrespective of tumor classification and clinical severity. The molecular basis underlying CX3CR1 up-regulation and its functional biological significance remain to be determined.
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- 2010
21. Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours
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F. Pecori Giraldi, Giovanni Lasio, Samantha Pesce, L. Pagliardini, Paola Maroni, Marco Losa, Francesco Cavagnini, Pecori Giraldi, F., Pesce, S., Maroni, P., Pagliardini, L., Lasio, G., Losa, M., and Cavagnini, F.
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Male ,Pituitary gland ,Protein Precursor ,Corticotropin-Releasing Hormone ,Endocrinology, Diabetes and Metabolism ,Cell Culture Techniques ,Drug Evaluation, Preclinical ,Dexamethasone ,Cushing syndrome ,Endocrinology ,Peptide Fragment ,Thyrotropin-Releasing Hormone ,Cells, Cultured ,medicine.anatomical_structure ,ACTH-Secreting Pituitary Adenoma ,Cushing's disease ,Female ,Cell Culture Technique ,hormones, hormone substitutes, and hormone antagonists ,Endocrine gland ,Human ,Adenoma ,endocrine system ,medicine.medical_specialty ,Down-Regulation ,Adrenocorticotropic hormone ,Biology ,Endocrine and Autonomic System ,Cellular and Molecular Neuroscience ,Hormone Antagonists ,Thyroid-stimulating hormone ,Anterior pituitary ,Adrenocorticotropic Hormone ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Animals ,Humans ,Protein Precursors ,Dose-Response Relationship, Drug ,Endocrine and Autonomic Systems ,Pituitary tumour ,Animal ,medicine.disease ,Peptide Fragments ,PreproTRH(178-199) ,Rats ,ACTH ,Hormone Antagonist ,Rat ,Corticotropic cell - Abstract
Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)-release inhibitor. Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing's disease. The present study aimed to test the effect of preproTRH(178-199) in human tumoural corticotrophs. Twenty-four human ACTH-secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 n. m preproTRH(178-199). ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%). Parallel experiments were performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 n. m ppTRH: 70 ± 4% control at 4 h and 83 ± 5% control at 24 h; for 100 n. m ppTRH: 70 ± 4% control at 4 h and 85 ± 5% control at 24 h), whereas a mild and short-lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178-199) was more evident in macroadenomas and significantly correlated with sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of incubation. The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback. This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178-199) as a regulator of ACTH secretion. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd.
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- 2010
22. Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH-secreting pituitary adenomas in vitro
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Samantha Pesce, Andrea Saccani, Marco Losa, F. Pecori Giraldi, Francesco Cavagnini, L. G. Bucciarelli, Massimo Scacchi, Pecori Giraldi, Francesca, Bucciarelli, L. G., Saccani, A., Scacchi, M., Pesce, S., Losa, M., and Cavagnini, F.
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Cortisol secretion ,Adenoma ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Pituitary gland ,Corticotropin-Releasing Hormone ,Endocrinology, Diabetes and Metabolism ,Peptide Hormones ,Adrenocorticotropic hormone ,Biology ,In Vitro Techniques ,Endocrine and Autonomic System ,Cellular and Molecular Neuroscience ,Corticotropin-releasing hormone ,Endocrinology ,Anterior pituitary ,Adrenocorticotropic Hormone ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Animals ,Humans ,Corticotroph ,Pituitary ACTH Hypersecretion ,Corticotrophs ,Pituitary tumour ,Animal ,In Vitro Technique ,Endocrine and Autonomic Systems ,Pituitary ACTH hypersecretion ,digestive, oral, and skin physiology ,Middle Aged ,medicine.disease ,Ghrelin ,ACTH ,Rats ,medicine.anatomical_structure ,ACTH-Secreting Pituitary Adenoma ,Peptide Hormone ,Rat ,Cushing's disease ,Female ,Corticotropic cell ,hormones, hormone substitutes, and hormone antagonists ,Human - Abstract
Ghrelin is a brain-gut peptide with wide-ranging endocrine, metabolic, cardiovascular and neural effects. Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH-releasing effect of GH secretagogues is even greater in patients with pituitary ACTH-secreting tumours. Furthermore, these tumours synthesize ghrelin itself, suggesting an intrapituitary ghrelin circuit. The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit. Nine ACTH-secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10-100nM human ghrelin or with 10nM human corticotrophin-releasing hormone (CRH). Control experiments were performed in rat anterior pituitary primary cultures. ACTH secretion was assessed after 4h and 24h incubation by immunometric assay. After 4h of incubation with ghrelin, medium ACTH concentrations were two- to ten-fold higher compared to ACTH concentrations in unstimulated wells. The ACTH-releasing effect of ghrelin was significantly less than the response elicited by 10nM CRH (up to 40-fold) Similar results were obtained after 24h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures. The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushing's disease in vivo is due, at least in part, to its action on the pituitary tumour. However, the reversal of the response pattern reported in vivo, with ghrelin proving a lesser stimulant than CRH in vitro, suggests that additional, suprapituitary mechanisms are involved in the in vivo response. Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas. © 2007 The Authors. Journal Compilation © 2007 Blackwell Publishing Ltd.
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- 2007
23. 869 A Novel Sierological Inflammatory Score As Possible Prognostic Marker in Colorectal Cancer
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Giuseppe Di Caro, Paola Allavena, Samantha Pesce, Antonino Spinelli, Federica Marchesi, Marco Montorsi, Marco Erreni, Michele Carvello, and Matteo Sacchi
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Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Colorectal cancer ,Internal medicine ,Gastroenterology ,medicine ,business ,medicine.disease - Published
- 2015
24. Inflammation triggered by oncogenic KRasG12V in pancreatic tumor cells
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Imran Siddiqui, Marco Erreni, Hemant M. Kocher, Federica Marchesi, Paola Allavena, Samantha Pesce, and Alberto Mantovani
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Oncology ,medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,Mgmt expression ,Inflammation ,medicine.disease ,digestive system diseases ,Stable Disease ,Pancreatic tumor ,Internal medicine ,Promoter methylation ,Ki67 index ,Medicine ,medicine.symptom ,business ,neoplasms ,Objective response - Abstract
s / Pancreatology 14 (2014) S1eS129 S66 Results: 43 patients (21 men, 58(27-84) years) with WDPNET, grade 1 (6 pts) or 2 (37 pts) were included. Objective response(OR), stable disease and progression rates were 39,5% (17pts), 41.9% (18pts) and 18.6% (8pts) respectively. Median MGMT score was 49 [0300]. MGMT expression was associated with radiological response (p1⁄40.02) and PFS (p1⁄40.003). OR was associated with a low MGMT score ( 80 vs. 27% > 120). MGMT promoter methylation was not associated with MGMT expression or PFS. Conclusion: MGMT expression can predict OR and PFS in TEM-treated patients with low Ki67 index WDPNET.
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- 2014
25. W1767 Expression and Function of the Chemokine CX3CL1 and Its Receptor Cx3cr1 in Human Colorectal Cancer
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Alberto Malesci, Graziella Solinas, Fabio Grizzi, Giuseppe Celesti, Marco Erreni, Luigi Laghi, Paolo Bianchi, Paola Allavena, Alberto Mantovani, and Samantha Pesce
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Oncology ,medicine.medical_specialty ,Chemokine ,Hepatology ,biology ,business.industry ,Colorectal cancer ,Gastroenterology ,Mouse model of colorectal and intestinal cancer ,medicine.disease ,Internal medicine ,CX3CR1 ,medicine ,biology.protein ,Receptor ,business ,CX3CL1 ,Function (biology) - Published
- 2010
26. Carney's complex with acromegaly as the leading clinical condition
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E. Lavezzi, Samantha Pesce, Giorgio Bertola, Letizia Maria Fatti, Francesca Pecori Giraldi, Francesco Cavagnini, Massimo Scacchi, and Giovanni Balza
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medicine.medical_specialty ,Endocrinology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Acromegaly ,MEDLINE ,Medicine ,business ,medicine.disease ,Settore MED/13 - Endocrinologia - Published
- 2007
27. Role of Macrophage Targeting in the Antitumor Activity of Trabectedin
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Maurizio D'Incalci, Nico van Rooijen, Ilaria Fuso Nerini, Cristina Belgiovine, Roberta Mortarini, Carlos M. Galmarini, Sarah Uboldi, Fabio Pasqualini, Paola Allavena, Sergio Marchini, Luca Beltrame, Roberta Sanfilippo, Paolo G. Casali, Silvana Pilotti, Roberta Frapolli, Manuela Liguori, Manuela Nebuloni, Massimo Zucchetti, Achille Anselmo, Samantha Pesce, Eugenio Erba, Giovanni Germano, Alberto Mantovani, Andrea Anichini, Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis
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Cancer Research ,Myeloid ,Angiogenesis ,Fibrosarcoma ,Apoptosis ,Monocytes ,Immunoenzyme Techniques ,Carcinoma, Lewis Lung ,Mice ,Tetrahydroisoquinolines ,Tumor Cells, Cultured ,Myeloid Cells ,Cytotoxicity ,Trabectedin ,Ovarian Neoplasms ,Caspase 8 ,Phagocytes ,Cultured ,Neovascularization, Pathologic ,Blotting ,Chemistry ,Flow Cytometry ,Alkylating ,Tumor Cells ,medicine.anatomical_structure ,Oncology ,Female ,Signal transduction ,Western ,Animals ,Antineoplastic Agents, Alkylating ,Blotting, Western ,Cell Proliferation ,Dioxoles ,Humans ,Macrophages ,Signal Transduction ,medicine.drug ,Antineoplastic Agents ,medicine ,Neovascularization ,Pathologic ,Lewis Lung ,Monocyte ,Carcinoma ,Cell Biology ,Immunology ,Cancer research - Abstract
SummaryThere is widespread interest in macrophages as a therapeutic target in cancer. Here, we demonstrate that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes. In four mouse tumor models, trabectedin caused selective depletion of monocytes/macrophages in blood, spleens, and tumors, with an associated reduction of angiogenesis. By using trabectedin-resistant tumor cells and myeloid cell transfer or depletion experiments, we demonstrate that cytotoxicity on mononuclear phagocytes is a key component of its antitumor activity. Monocyte depletion, including tumor-associated macrophages, was observed in treated tumor patients. Trabectedin activates caspase-8-dependent apoptosis; selectivity for monocytes versus neutrophils and lymphocytes is due to differential expression of signaling and decoy TRAIL receptors. This unexpected property may be exploited in different therapeutic strategies.
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28. Functional TRAIL receptors in monocytes and tumor-associated macrophages: A possible targeting pathway in the tumor microenvironment
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Manuela Liguori, Cristina Belgiovine, Marina Sironi, Paola Allavena, Francesca Bergomas, Fabio Grizzi, Samantha Pesce, Fabio Pasqualini, Alberto Mantovani, Chiara Buracchi, Liguori, M, Buracchi, C, Pasqualini, F, Bergomas, F, Pesce, S, Sironi, M, Grizzi, F, Mantovani, A, Belgiovine, C, and Allavena, P
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0301 basic medicine ,TRAIL ,Inflammation ,Monocytes ,law.invention ,TNF-Related Apoptosis-Inducing Ligand ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,law ,Neoplasms ,Tumor Microenvironment ,medicine ,Animals ,Humans ,TRAIL receptors ,Molecular Targeted Therapy ,Fibrosarcoma ,Receptor ,Cells, Cultured ,Tumor microenvironment ,tumor-associated macrophages ,business.industry ,Macrophages ,apoptosis ,TRAIL , tumor-associated macrophages ,medicine.disease ,In vitro ,Mice, Inbred C57BL ,Receptors, TNF-Related Apoptosis-Inducing Ligand ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,Apigenin ,Immunology ,Recombinant DNA ,targeting macrophages ,medicine.symptom ,business ,Signal Transduction ,Research Paper - Abstract
// Manuela Liguori 1 , Chiara Buracchi 1 , Fabio Pasqualini 1 , Francesca Bergomas 1 , Samantha Pesce 1 , Marina Sironi 1 , Fabio Grizzi 1 , Alberto Mantovani 1, 2 , Cristina Belgiovine 1, * , Paola Allavena 1, 2, * 1 Department of Immunology and Inflammation, IRCCS-Humanitas Clinical and Research Center, 20089 Rozzano, Milano, Italy 2 Humanitas University, 20089 Rozzano, Milano, Italy * These authors have contributed equally to this work Correspondence to: Cristina Belgiovine, email: cristina.belgiovine@humanitasresearch.it Paola Allavena, email: paola.allavena@humanitasresearch.it Keywords: TRAIL, TRAIL receptors, apoptosis, tumor-associated macrophages, targeting macrophages Received: February 17, 2016 Accepted: April 06, 2016 Published: May 13, 2016 ABSTRACT Despite the accepted dogma that TRAIL kills only tumor cells and spares normal ones, we show in this study that mononuclear phagocytes are susceptible to recombinant TRAIL via caspase-dependent apoptosis. Human resting monocytes and in vitro -differentiated macrophages expressed substantial levels of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2), while neutrophils and lymphocytes mostly expressed the non-signaling decoy receptor (TRAIL-R3). Accordingly, exclusively monocytes and macrophages activated caspase-8 and underwent apoptosis upon recombinant TRAIL treatment. TRAIL-Rs were up-regulated by anti-inflammatory agents (IL-10, glucocorticoids) and by natural compounds (Apigenin, Quercetin, Palmitate) and their treatment resulted in increased TRAIL-induced apoptosis. In mice, the only signaling TRAIL-R (DR5) was preferentially expressed by blood monocytes rather than neutrophils or lymphocytes. In both mice and humans, Tumor-Associated Macrophages (TAM) expressed functional TRAIL-R, while resident macrophages in normal tissues did not. As a proof of principle, we treated mice bearing a murine TRAIL-resistant fibrosarcoma with recombinant TRAIL. We observed significant decrease of circulating monocytes and infiltrating TAM, as well as reduced tumor growth and lower metastasis formation. Overall, these findings demonstrate that human and murine monocytes/macrophages are, among leukocytes, uniquely susceptible to TRAIL-mediated killing. This differential susceptibility to TRAIL could be exploited to selectively target macrophages in tumors.
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