scholarly journals The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models

Oncogene ◽  
2015 ◽  
Vol 35 (7) ◽  
pp. 833-845 ◽  
Author(s):  
P L Garcia ◽  
A L Miller ◽  
K M Kreitzburg ◽  
L N Council ◽  
T L Gamblin ◽  
...  
2020 ◽  
Author(s):  
Aubrey L. Miller ◽  
Patrick L. Garcia ◽  
Tracy L. Gamblin ◽  
Rebecca B. Vance ◽  
Karina J. Yoon

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S158-S159
Author(s):  
Arthur Chevallier ◽  
Clélia Costechareyre ◽  
Loraine Jarrosson ◽  
Philippe Chalabreysse ◽  
Raphaël Bourdariat ◽  
...  

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.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 336-336
Author(s):  
Daniel F. Gaddy ◽  
Helen Lee ◽  
Nancy Paz ◽  
Shannon C. Leonard ◽  
Ashish Kalra ◽  
...  

336 Background: Nanoliposomal irinotecan (nal-IRI, MM-398) recently gained approval in combination with 5-fluorouracil/leucovorin (5-FU/LV) in post-gemcitabine metastatic pancreatic ductal adenocarcinoma (PDAC) based on the extended survival and manageable safety profile observed in the Phase 3 NAPOLI-1 trial. Preclinically, we have previously demonstrated the anti-tumor activity of nal-IRI with 5-FU and oxaliplatin, standard of care agents in first-line PDAC, and are currently investigating this combination in patients with previously untreated metastatic PDAC in a Phase 2 clinical trial (NCT02551991). Herein, we further evaluate nal-IRI as a potential backbone of first-line metastatic PDAC by assessing the preclinical anti-tumor activity of nal-IRI relative to, and in combination with, gemcitabine and nanoparticle albumin-bound-paclitaxel (nab-P). Methods: Nal-IRI tumor metabolite (CPT-11 and SN-38) levels were measured in mice treated with nal-IRI in combination with gemcitabine or nab-P. Anti-tumor activity and tolerability of nal-IRI, 5-FU, gemcitabine and nab-P monotherapies and combinations were evaluated using pancreatic cancer cell line (ASPC-1 and CFPAC-1)-derived xenograft models, as well as a panel of five patient-derived xenograft models. Results: Administration of gemcitabine or nab-P prior to or simultaneously with nal-IRI resulted in unchanged or increased nal-IRI deposition, as measured by tumor CPT-11 and SN-38 levels at 24 hours post-injection. Moreover, in both cell line-derived and patient-derived xenograft models of PDAC, nal-IRI monotherapy demonstrated comparable or improved anti-tumor activity relative to gemcitabine or nab-P monotherapies. Further, nal-IRI consistently improved tumor growth inhibition and survival when used in combination with either 5-FU, gemcitabine and/or nab-P, relative to the combination of gemcitabine plus nab-P. All treatments were well-tolerated in these preclinical models. Conclusions: These findings illustrate the compatibility and therapeutic potential of nal-IRI as a foundation of first-line PDAC combination regimens, and warrant clinical evaluation.


2021 ◽  
Author(s):  
Dan Li ◽  
Meilin Yang ◽  
Mingzhu Liang ◽  
Chaoming Mei ◽  
Yujing Lin ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC), a fatal malignant tumour, has a high postoperative recurrence rate, mainly due to the difficulty of discerning occult lesions, including those related to perineural invasion (PNI)...


2000 ◽  
Vol 15 (11) ◽  
pp. 1333-1338 ◽  
Author(s):  
Koji Uno ◽  
Takeshi Azuma ◽  
Masatsugu Nakajima ◽  
Kenjiro Yasuda ◽  
Takanobu Hayakumo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document