Search results for " Pancreatic ductal adenocarcinoma"
showing 10 items of 12 documents
HGF/MET Axis Induces Tumor Secretion of Tenascin-C and Promotes Stromal Rewiring in Pancreatic Cancer
2021
Simple Summary It has been previously shown that activation of the MET receptor by its ligand, the hepatocyte growth factor (HGF), modulates the tumor-stroma cross-talk in models of pancreatic cancer. We now wish to cast light on the molecular mechanisms by which this ligand/receptor pair sustains the interaction between cancer cells and the tumor microenviroment. To this end, we compared data obtained by large-scale analysis of gene expression in pancreatic cancer cells grown in the presence of HGF versus cells grown in the presence of HGF and treated with specific inhibitors of HGF/MET signaling. By clustering differentially expressed genes according to functional groups, we identified ca…
Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer
2017
Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their…
Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: Recommended schedule for expected activity…
2018
// Gemma Bruera 1, 2 , Silvia Massacese 3 , Stefania Candria 1 , Antonio Galvano 4 , Rosa Manetta 5 , Aldo Victor Giordano 5 , Sergio Carducci 5 , Alessandra Di Sibio 5 , Eugenio Ciacco 3 , Antonio Russo 4 , Enrico Ricevuto 1, 2 and on behalf of Oncology Network ASL1 Abruzzo, Italy 1 Oncology Territorial Care Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy 4 Medical Oncology Unit, Department of Surgical, Oncological and Stomatological Sciences, Univers…
Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas
2022
Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathological parameters were determined for each patient. The molecular profile was investigated using next-generation sequencing (NGS). Histologically, all tumors were hypercellular neoplasms with spindle-shaped or sarcomatoid cells. All patients showed vascular and perineural invasion. Most patients had a poor prognosis. NGS showed important similarities …
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas: a distinct entity among pancreatic tumors
2022
Aims Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach. Methods and results PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cance…
Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells
2020
A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 μM, and 0.29–12.2 μM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), elici…
An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated an…
2009
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. alpha-Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to alpha-enolase. The present work was intended to assess the ability of alpha-enolase to induce antigen-specific T cell responses. We show that alpha-enolase-pulsed dendritic cells (DC) specifically stimulate healt…
Neutrophil/lymphocyte ratio helps select metastatic pancreatic cancer patients benefitting from oxaliplatin
2016
BACKGROUND: High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA). OBJECTIVE: In the present study, we aimed at investigating the prognostic value of NLR in two homogeneous groups of chemotherapy-na've metastatic PDA patients. Patients were treated with either gemcitabine (GEM) or gemcitabine/ oxaliplatin (GEMOXA). We also assessed whether NLR could identify patients benefiting from the use of oxaliplatin. METHODS: Consecutive PDA patients treated at the Medical Oncology Unit of Tor Vergata University Hospital of Rome with either GEM or GEMOXA wer…
Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal …
2023
Pyruvate dehydrogenase kinases (PDKs) are serine/threonine kinases, that are directly involved in altered cancer cell metabolism, resulting in cancer aggressiveness and resistance. Dichloroacetic acid (DCA) is the first PDK inhibitor that has entered phase II clinical; however, several side effects associated with weak anticancer activity and excessive drug dose (100 mg/kg) have led to its limitation in clinical application. Building upon a molecular hybridization approach, a small library of 3-amino-1,2,4-triazine derivatives has been designed, synthesized, and characterized for their PDK inhibitory activity using in silico, in vitro, and in vivo assays. Biochemical screenings showed that …
Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Itali…
2022
Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and…