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Pancreatic Neoplasms: HELP
Articles by Erica Dugnani
Based on 13 articles published since 2010
(Why 13 articles?)
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Between 2010 and 2020, E. Dugnani wrote the following 13 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma. 2016

Belli, Carmen / Piemonti, Lorenzo / D'Incalci, Maurizio / Zucchetti, Massimo / Porcu, Luca / Cappio, Stefano / Doglioni, Claudio / Allavena, Paola / Ceraulo, Domenica / Maggiora, Paola / Dugnani, Erica / Cangi, Maria Giulia / Garassini, Greta / Reni, Michele. ·Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Diabetes Research Institute, San Raffaele Scientific Institute, 20132, Milan, Italy. · Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy. · Department of Radiology, San Raffaele Scientific Institute, 20132, Milan, Italy. · Pathology Unit, San Raffaele Scientific Institute, 20132, Milan, Italy. · Department Immunology and Inflammation, IRCCS Clinical and Research Institute Humanitas, 20089, Rozzano, Milan, Italy. · Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. reni.michele@hsr.it. ·Cancer Chemother Pharmacol · Pubmed #26666646.

ABSTRACT: PURPOSE: No standard salvage chemotherapy has been identified for metastatic pancreatic adenocarcinoma (mPA), and there is an urgent need for active agents against this disease. This phase II trial explored the activity of trabectedin in mPA progressing after gemcitabine-based first-line chemotherapy. METHODS: Patients with gemcitabine-resistant disease received trabectedin 1.3 mg/m(2) as a 3-h intravenous continuous infusion every 3 weeks until disease progression or unacceptable toxicity or for a maximum of 6 months. The primary endpoint was progression-free survival rate at 6 months (PFS-6). Since trabectedin modulates the production of selected inflammatory mediators, this study also aimed to identify inflammatory biomarkers predictive for response to trabectedin. RESULTS: Between February 2011 and February 2012, 25 patients received trabectedin. PFS-6 was 4%, median PFS 1.9 months (range 0.8-7.4), and median overall survival 5.2 months (range 1.1-24.3). Grade >2 toxicity consisted of neutropenia in 44% of patients, febrile neutropenia and thrombocytopenia both in 12%, anemia in 8%, fatigue in 12%, and AST and ALT increase in 8 and 4%, respectively. Trabectedin was shown to modulate the production of inflammatory mediators, and at disease progression, levels of a subgroup of cytokines/chemokines were modified. Furthermore, tissue analysis identified 30 genes associated with better prognosis. CONCLUSIONS: Although it has shown some ability to modulate inflammatory process, single-agent trabectedin had no activity as salvage therapy for mPA.

2 Clinical Trial (Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial. 2016

Reni, Michele / Dugnani, Erica / Cereda, Stefano / Belli, Carmen / Balzano, Gianpaolo / Nicoletti, Roberto / Liberati, Daniela / Pasquale, Valentina / Scavini, Marina / Maggiora, Paola / Sordi, Valeria / Lampasona, Vito / Ceraulo, Domenica / Di Terlizzi, Gaetano / Doglioni, Claudio / Falconi, Massimo / Piemonti, Lorenzo. ·Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it reni.michele@hsr.it. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. piemonti.lorenzo@hsr.it reni.michele@hsr.it. ·Clin Cancer Res · Pubmed #26459175.

ABSTRACT: PURPOSE: We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action. EXPERIMENTAL DESIGN: We designed an open-label, randomized, phase II trial to assess the efficacy of adding metformin to a standard systemic therapy with cisplatin, epirubicin, capecitabine, and gemcitabine (PEXG) in patients with metastatic pancreatic cancer. Patients ages 18 years or older with metastatic pancreatic cancer were randomly assigned (1:1) to receive PEXG every 4 weeks in combination or not with 2 g oral metformin daily. The primary endpoint was 6-months progression-free survival (PFS-6) in the intention-to-treat population. RESULTS: Between August 2010 and January 2014, we randomly assigned 60 patients to receive PEXG with (n = 31) or without metformin (n = 29). At the preplanned interim analysis, the study was ended for futility. PFS-6 was 52% [95% confidence interval (CI), 33-69] in the control group and 42% (95% CI, 24-59) in the metformin group (P = 0.61). Furthermore, there was no difference in disease-free survival and overall survival between groups. Despite endocrine metabolic modifications induced by metformin, there was no correlation with the outcome. Single-nucleotide polymorphism rs11212617 predicted glycemic response, but not tumor response to metformin. Gene expression on tumor tissue did not predict tumor response to metformin. CONCLUSIONS: Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy. See related commentary by Yang and Rustgi, p. 1031.

3 Article Glucose metabolism during tumorigenesis in the genetic mouse model of pancreatic cancer. 2019

Pasquale, Valentina / Dugnani, Erica / Liberati, Daniela / Marra, Paolo / Citro, Antonio / Canu, Tamara / Policardi, Martina / Valla, Libera / Esposito, Antonio / Piemonti, Lorenzo. ·Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Division of Genetics and Cell biology, Genomic Unit for the diagnosis of human pathologies, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Department of Radiology, Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. piemonti.lorenzo@hsr.it. · Vita-Salute San Raffaele University, Milan, Italy. piemonti.lorenzo@hsr.it. ·Acta Diabetol · Pubmed #30989379.

ABSTRACT: AIM: More than 40% of pancreatic ductal adenocarcinoma (PDAC) patients have glucose intolerance or diabetes. The association has led to two hypotheses: PDAC causes diabetes or diabetes shares risk factors for the development of PDAC. In order to elucidate the relationship between diabetes and PDAC, we investigated the glucose metabolism during tumorigenesis in the LSL-Kras METHODS: Male and female KPCs have been fed with standard diet (SD) or high-fat diet (HFD). The imaging-based 4-class tumor staging was used to follow pancreatic cancer development. Not fasting glycemia, 4-h fasting glycemia, insulin, C-peptide, glucose tolerance after OGTT and abdominal fat volume were measured during tumorigenesis. RESULTS: PDAC development did not lead to an overt diabetic phenotype or to any alterations in glucose tolerance in KPC fed with SD. Consumption of HFD induced higher body weight/abdominal fat volume and worsened glucose homeostasis both in control CRE mice and only in early tumorigenesis stages of the KPC mice, excluding that the cancer development itself acts as a trigger for the onset of dysmetabolic features. CONCLUSION: Our data demonstrate that carcinogenesis in KPC mice is not associated with paraneoplastic diabetes.

4 Article Gene expression analysis of embryonic pancreas development master regulators and terminal cell fate markers in resected pancreatic cancer: A correlation with clinical outcome. 2018

Dugnani, Erica / Sordi, Valeria / Pellegrini, Silvia / Chimienti, Raniero / Marzinotto, Ilaria / Pasquale, Valentina / Liberati, Daniela / Balzano, Gianpaolo / Doglioni, Claudio / Reni, Michele / Gandolfi, Alessandra / Falconi, Massimo / Lampasona, Vito / Piemonti, Lorenzo. ·Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Division of Genetics and Cell Biology, Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: piemonti.lorenzo@hsr.it. ·Pancreatology · Pubmed #30293872.

ABSTRACT: BACKGROUND: Despite the recent introduction of new drugs and the development of innovative multi-target treatments, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. Even when PDAC is resectable, the rate of local or widespread disease recurrence remains particularly high. Currently, reliable prognostic biomarkers of recurrence are lacking. We decided to explore the potential usefulness of pancreatic developmental regulators as biomarkers of PDAC relapse. METHODS: We analyzed by quantitative real-time PCR the mRNA of selected factors involved either in pancreatic organogenesis (ISL1, NEUROD1, NGN3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1 and PTF1α) or associated with terminally committed pancreatic cells (CHGA, CHGB, GAD2, GCG, HNF6α, INS, KRT19, SYP) in 17 PDAC cell lines and in frozen tumor samples from 41 PDAC patients. RESULTS: High baseline levels of the ISL1, KRT19, PAX6 and PDX1 mRNAs in PDAC cell lines, were risk factors for time-dependent xenograft appearance after subcutaneous injection in CD1-Nude mice. Consistently, in human PDAC samples, high levels of KRT19 mRNA were associated with reduced overall survival and earlier recurrence. Higher levels of PDX1 or PAX6 mRNAs were instead associated with a higher frequency of local recurrence. CONCLUSIONS: Our findings suggest that selected factors associated with pancreas development or its terminal differentiation might be implicated in mechanisms of PDAC progression and/or metastatic spread and that the measurement of their mRNA in tumors might be potentially used to improve patient prognostic stratification and prediction of the relapse site.

5 Article Four-class tumor staging for early diagnosis and monitoring of murine pancreatic cancer using magnetic resonance and ultrasound. 2018

Dugnani, Erica / Pasquale, Valentina / Marra, Paolo / Liberati, Daniela / Canu, Tamara / Perani, Laura / De Sanctis, Francesco / Ugel, Stefano / Invernizzi, Francesca / Citro, Antonio / Venturini, Massimo / Doglioni, Claudio / Esposito, Antonio / Piemonti, Lorenzo. ·Division of Immunology, Transplantation and Infectious diseases, Diabetes Research Institute, Milan, Italy. · Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Via Olgettina, Milan, Italy. · Division of Genetics and Cell Biology, Genomic Unit for the diagnosis of human pathologies, IRCCS San Raffaele Scientific Institute, Via Olgettina, Milan, Italy. · University Hospital and Department of Medicine, Immunology Section, Verona, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Via Olgettina, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. ·Carcinogenesis · Pubmed #30052815.

ABSTRACT: Background: The widely used genetically engineered mouse LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre, termed KPC, spontaneously develops pancreatic cancer mirroring all phases of the carcinogenesis but in asynchronous manner. Preclinical studies need defined criteria for the enrollment of the KPC sharing the same stage of carcinogenesis. Aim: To define a tumor-staging criteria using magnetic resonance (MR) and ultrasound (US) and then to correlate the imaging stage with overall survival of KPC mice. Methods: Forty KPC (2- to 5-month-old mice) were imaged by axial fat-saturated T2-weighted sequences at MR and by brightness mode US to establish criteria for tumor staging. Immunohistopathology was used to validate imaging. A second cohort of 25 KPC was used to correlate imaging stage with survival by Kaplan-Meier analysis. Results: We defined a four-class tumor staging system ranking from stages 1 to 4. Stage 1 was described as radiologically healthy pancreas; precursor lesions were detectable in histology only. Cystic papillary neoplasms, besides other premalignant alterations, marked stage 2 in the absence of cancer nodules. Stages 3 and 4 identified mice affected by overt pancreatic cancer with size <5 or ≥5 mm, respectively. Regarding the prognosis, this staging system correlated with disease-related mortality whatever may be the KPC age when they staged. Conclusion: This imaging-based four-class tumor staging is an effective and safe method to stage pancreatic cancer development in KPC. As a result, regardless of their age, KPC mice can be synchronized based on prognosis or on a specific phase of tumorigenesis, such as the early but already radiologically detectable one (stage 2).

6 Article No evidence of pancreatic ductal adenocarcinoma specific autoantibodies to Ezrin in a liquid phase LIPS immunoassay. 2018

Liberati, Daniela / Marzinotto, Ilaria / Brigatti, Cristina / Dugnani, Erica / Pasquale, Valentina / Reni, Michele / Balzano, Gianpaolo / Falconi, Massimo / Piemonti, Lorenzo / Lampasona, Vito. ·Division of Genetics and Cell Biology, Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. · Vita-Salute San Raffaele University, Italy. ·Cancer Biomark · Pubmed #29660901.

ABSTRACT: BACKGROUND: Sensitive and specific biomarkers of Pancreatic Ductal Adenocarcinoma (PDAC) are desperately needed to allow early diagnosis and improve patient's survival. Ezrin autoantibodies were recently described as present in 93% of PDAC patients and 40% of healthy subjects who later developed PDAC. However, another prospective study failed to replicate these findings. Both studies were based on the use of a solid phase ELISA immunoassay. OBJECTIVE: We aimed at re-evaluating the usefulness of Ezrin autoantibodies as PDAC biomarkers using the Luciferase Immuno Precipitation System (LIPS), an alternative immunoassay format that found successful application for the measurement of autoantibodies against pancreatic autoantigens. METHODS: We produced a Nanoluciferase™ tagged Ezrin (NLuc-Ezrin). NLuc-Ezrin was then used as antigen in LIPS to test for Ezrin autoantibodies patients affected by PDAC (n= 40), other pancreatic diseases (OPD, n= 50), and healthy controls (n= 60). RESULTS: Overall, binding in liquid phase to Ezrin by serum antibodies was rare and low titer. Furthermore, we did not find statistically significant differences in the prevalence of Ezrin autoantibodies between patients affected by either PDAC or OPD compared to control. CONCLUSIONS: Our results do not confirm the usefulness of Ezrin autoAbs as biomarker of PDAC.

7 Article A preoperative score to predict early death after pancreatic cancer resection. 2017

Balzano, Gianpaolo / Dugnani, Erica / Crippa, Stefano / Scavini, Marina / Pasquale, Valentina / Aleotti, Francesca / Liberati, Daniela / Gandolfi, Alessandra / Belfiori, Giulio / Reni, Michele / Doglioni, Claudio / Ruffo, Giacomo / Marmorale, Cristina / Falconi, Massimo / Piemonti, Lorenzo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. · Division of General Surgery, Sacro Cuore Don Calabria Hospital, Verona, Italy. · Department of Surgery, Polytechnic University of Marche Region, Ancona, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: piemonti.lorenzo@hsr.it. ·Dig Liver Dis · Pubmed #28734776.

ABSTRACT: BACKGROUND: This study aimed to develop and validate a preoperative prognostic model for death within one year post-surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: A derivation cohort study of 296 patients who underwent surgical resection of PDAC was prospectively enrolled in an observational study. Preoperative predictors of one year mortality were used to develop a risk score which was then validated in an external cohort of 182 patients with resectable PDAC. RESULTS: Seventy-eight out of 296 patients (26%) died within the first year. Preoperative independent predictors of one year mortality were: nutritional status (Geriatric Nutritional Risk Index, OR 2.23, 1.14-4.38; p=0.02), American Society of Anaesthesiologists' score (OR 2.56, 1.1-5.98; p=0.03), abdominal or back pain at presentation (OR 2.51, 1.05-5.9; p=0.038) and non metastatic liver disease as comorbidity (OR 4.5, 1.05-19.3; p=0.043). A score ranging from 0 to 7 points was developed. In the validation cohort, the model was able to predict early mortality (OR 7.1, 3.9-12.7; p<0.0001), with a predictive ability of 53.5% (Nagelkerke R CONCLUSIONS: Our new simple risk score proved reliable in forecasting one year mortality in patients with resectable PDAC.

8 Article Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in Mouse. 2017

Dugnani, E / Pasquale, V / Liberati, D / Citro, A / Cantarelli, E / Pellegrini, S / Marra, P / Canu, T / Balzano, G / Scavini, M / Esposito, A / Doglioni, C / Piemonti, L. ·Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. ·Am J Transplant · Pubmed #28510280.

ABSTRACT: Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-Kras

9 Article Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study. 2016

Balzano, Gianpaolo / Dugnani, Erica / Gandolfi, Alessandra / Scavini, Marina / Pasquale, Valentina / Aleotti, Francesca / Liberati, Daniela / Di Terlizzi, Gaetano / Petrella, Giovanna / Reni, Michele / Doglioni, Claudio / Bosi, Emanuele / Falconi, Massimo / Piemonti, Lorenzo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center; IRCCS San Raffaele Scientific Institute, Milan, Italy. · San Raffaele Diabetes Research Institute (SR-DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. ·PLoS One · Pubmed #27814399.

ABSTRACT: AIM: To investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Prospective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery). RESULTS: Of 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06-1.99]). CONCLUSION: Preoperative recent onset DM has an impact on survival after the resection of PDAC.

10 Article Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma. 2016

Dugnani, Erica / Balzano, Gianpaolo / Pasquale, Valentina / Scavini, Marina / Aleotti, Francesca / Liberati, Daniela / Di Terlizzi, Gaetano / Gandolfi, Alessandra / Petrella, Giovanna / Reni, Michele / Doglioni, Claudio / Bosi, Emanuele / Falconi, Massimo / Piemonti, Lorenzo. ·Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. piemonti.lorenzo@hsr.it. ·Acta Diabetol · Pubmed #27552832.

ABSTRACT: AIMS: To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis. METHODS: Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression. RESULTS: Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival. CONCLUSIONS: Insulin resistance is associated with the aggressiveness of PDAC.

11 Article Diabetes associated with pancreatic ductal adenocarcinoma is just diabetes: Results of a prospective observational study in surgical patients. 2016

Dugnani, Erica / Gandolfi, Alessandra / Balzano, Gianpaolo / Scavini, Marina / Pasquale, Valentina / Aleotti, Francesca / Liberati, Daniela / Di Terlizzi, Gaetano / Petrella, Giovanna / Reni, Michele / Doglioni, Claudio / Bosi, Emanuele / Falconi, Massimo / Piemonti, Lorenzo. ·Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. · Department of Pathology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy; Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. · Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. Electronic address: piemonti.lorenzo@hsr.it. ·Pancreatology · Pubmed #27546476.

ABSTRACT: BACKGROUND: Identification of a specific diabetes signature associated to pancreatic ductal carcinoma (PDAC) could be a key to detect asymptomatic, early stage tumors. We aim to characterize the clinical signature and the pathogenetic factors of the different types of diabetes associated with PDAC, based on the time between diabetes and cancer diagnosis. METHODS: Prospective observational study on 364 PDAC patients admitted to a referral center for pancreatic disease. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. RESULTS: The prevalence of diabetes in patients was 67%. Considering 174 patients (47.8%) already having diabetes when diagnosed with PDAC (long duration, short duration, concomitant), the clinical and biochemical profile was similar to that of patients with type 2 diabetes (T2D). Diabetes was associated with known risk factors (i.e., age, sex, family history for diabetes and increased BMI) and both beta-cell dysfunction and insulin resistance were present. Considering 70 patients (19.2%) with onset of diabetes after PDAC diagnosis (early and late onset), the strongest predictor was the loss of beta-cell mass following pancreatectomy in patients with risk factors for T2D. CONCLUSION: Different types of diabetes according to the time between diabetes and PDAC diagnosis are clinical entities widely overlapping with T2D. Therefore, the success of a strategy considering diabetes onset as a marker of asymptomatic PDAC will largely depend on our ability to identify new diabetes-unrelated biomarkers of PDAC.

12 Article Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells. 2015

Bonomi, Arianna / Sordi, Valeria / Dugnani, Erica / Ceserani, Valentina / Dossena, Marta / Coccè, Valentina / Cavicchini, Loredana / Ciusani, Emilio / Bondiolotti, Gianpietro / Piovani, Giovanna / Pascucci, Luisa / Sisto, Francesca / Alessandri, Giulio / Piemonti, Lorenzo / Parati, Eugenio / Pessina, Augusto. ·Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. · Diabetes Research Institute, IRCCS S. Raffaele Scientific Institute, Milan, Italy. · Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, IRCCS Neurological Institute C. Besta, Milan, Italy. · Laboratory of Clinical Pathology and Neurogenetic Medicine, Fondazione IRCCS Neurological Institute Carlo Besta, Milan, Italy. · Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. · Biology and Genetics Division, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. · Department of Veterinary Medicine, University of Perugia, Perugia, Italy. · Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. Electronic address: augusto.pessina@unimi.it. ·Cytotherapy · Pubmed #26481416.

ABSTRACT: BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection.

13 Article Mass spectrometric analysis reveals O-methylation of pyruvate kinase from pancreatic cancer cells. 2013

Zhou, Weidong / Capello, Michela / Fredolini, Claudia / Racanicchi, Leda / Dugnani, Erica / Piemonti, Lorenzo / Liotta, Lance A / Novelli, Francesco / Petricoin, Emanuel F. ·Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA. wzhou@gmu.edu ·Anal Bioanal Chem · Pubmed #23508580.

ABSTRACT: Pyruvate kinase (PK) is an important glycolytic enzyme that catalyzes the dephosphorylation of phosphoenolpyruvate to pyruvate. Human PK isozyme M2 (PKM2), a splice variant of M1, is overexpressed in many cancer cells, and PKM2 has been investigated as a potential tumor marker for diagnostic assays and as a target for cancer therapy. To facilitate identification and characterization of PK, we studied the enzyme from pancreatic cancer cells and normal pancreatic duct cells by electrophoresis and mass spectrometry, and identified multiple O-methylated residues from PK. These findings advance our knowledge of the biochemical properties of PK and will be important in understanding its biological function in cells.