AB053. P024. Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma: does it have a prognostic role?

2018 ◽  
Vol 1 (1) ◽  
pp. AB053-AB053
Author(s):  
Francesca Aleotti ◽  
Ilaria Pergolini ◽  
Stefano Crippa ◽  
Michele Pagnanelli ◽  
Giulio Belfiori ◽  
...  
2015 ◽  
Vol 10 (2) ◽  
pp. 967-971 ◽  
Author(s):  
MICHELE AMMENDOLA ◽  
ROSARIO SACCO ◽  
ILARIA MARECH ◽  
GIUSEPPE SAMMARCO ◽  
VALERIA ZUCCALÀ ◽  
...  

Pancreatology ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. S84
Author(s):  
Ilaria Pergolini ◽  
Stefano Crippa ◽  
Michele Pagnanelli ◽  
Giulio Belfiori ◽  
Alessandro Pucci ◽  
...  

BJS Open ◽  
2019 ◽  
Vol 3 (5) ◽  
pp. 646-655
Author(s):  
I. Pergolini ◽  
S. Crippa ◽  
M. Pagnanelli ◽  
G. Belfiori ◽  
A. Pucci ◽  
...  

2013 ◽  
Vol 99 (4) ◽  
pp. 516-522 ◽  
Author(s):  
MinYuen Teo ◽  
Mohd Syahizul Nuhairy Mohd Sharial ◽  
Felicity McDonnell ◽  
Kevin C Conlon ◽  
Paul F Ridgway ◽  
...  

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 729-729
Author(s):  
Kenjiro Kimura ◽  
Ryota Tanaka ◽  
Ryosuke Amano ◽  
Shoji Kubo ◽  
Hiroaki Tanaka ◽  
...  

729 Background: Translational research using patient-derived tumor xenograft (PDX) model is progressing rapidly, and is also becoming widespread in pancreatic cancer research. The purpose of this study was to establish the liver transplant PDX model as artificially-created liver metastasis with cryopreserved primary pancreatic ductal adenocarcinoma(PDAC). Methods: The primary PDAC from 10 patients were cryopreserved and transplanted into NSG mice using liver pocket method. For engraftment and similarity evaluation, H&E staining and immunohistochemical staining such as Ki-67, p53, SMAD4, and MUC1 were performed. Results: Patient-derived xenograft was succeeded in 6 cases (60%), 10 mice (33.3%). Ki-67 index of primary PDAC and the interval of cryopreservation were significantly related to successful engraftment, respectively (p = 0.003, p = 0.007). Conclusions: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The factors such as Ki-67 index and the interval of cryopreservation would affect the successful establishment.


Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 113 ◽  
Author(s):  
Rita Lawlor ◽  
Nicola Veronese ◽  
Alessia Nottegar ◽  
Giuseppe Malleo ◽  
Lee Smith ◽  
...  

This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13–1.88, p = 0.004; HR, 2.65; 95% CI, 1.79–3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05–2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems.


Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1501
Author(s):  
Rahul R. Singh ◽  
Jiyan Mohammad ◽  
Megan Orr ◽  
Katie M. Reindl

Glutathione S-transferase pi-1 (GSTP1) plays an important role in regulating oxidative stress by conjugating glutathione to electrophiles. GSTP1 is overexpressed in breast, colon, lung, and prostate tumors, where it contributes to tumor progression and drug resistance; however, the role of GSTP1 in pancreatic ductal adenocarcinoma (PDAC) is not well understood. Using shRNA, we knocked down GSTP1 expression in three different PDAC cell lines and determined the effect on cell proliferation, cell cycle progression, and reactive oxygen species (ROS) levels. Our results show GSTP1 knockdown reduces PDAC cell growth, prolongs the G0/G1 phase, and elevates ROS in PDAC cells. Furthermore, GSTP1 knockdown results in the increased phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the decreased phosphorylation of extracellular signal-regulated kinase (ERK), p65, the reduced expression of specificity protein 1 (Sp1), and the increased expression of apoptosis-promoting genes. The addition of the antioxidant glutathione restored cell viability and returned protein expression levels to those found in control cells. Collectively, these data support the working hypothesis that the loss of GSTP1 elevates oxidative stress, which alters mitogen-activated protein (MAP) kinases and NF-κB signaling, and induces apoptosis. In support of these in vitro data, nude mice bearing orthotopically implanted GSTP1-knockdown PDAC cells showed an impressive reduction in the size and weight of tumors compared to the controls. Additionally, we observed reduced levels of Ki-67 and increased expression of cleaved caspase-3 in GSTP1-knockdown tumors, suggesting GSTP1 knockdown impedes proliferation and upregulates apoptosis in PDAC cells. Together, these results indicate that GSTP1 plays a significant role in PDAC cell growth and provides support for the pursuit of GSTP1 inhibitors as therapeutic agents for PDAC.


Oncotarget ◽  
2016 ◽  
Vol 7 (45) ◽  
pp. 72819-72832 ◽  
Author(s):  
Angela Diana ◽  
Lai Mun Wang ◽  
Zenobia D’Costa ◽  
Abul Azad ◽  
Michael A. Silva ◽  
...  

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