scholarly journals Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression

2016 ◽  
Vol 22 (5) ◽  
pp. 497-505 ◽  
Author(s):  
Hanane Laklai ◽  
Yekaterina A Miroshnikova ◽  
Michael W Pickup ◽  
Eric A Collisson ◽  
Grace E Kim ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Tissue Tension

scholarly journals Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: Implications for tumor progression and clinical outcome

Cell Cycle ◽  
2008 ◽  
Vol 7 (19) ◽  
pp. 3021-3025 ◽  
Author(s):  
Agnieszka K. Witkiewicz ◽  
Katherine Nguyen ◽  
Abhijit Dasgupta ◽  
Eugene P. Kennedy ◽  
Charles J. Yeo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Clinical Outcome ◽  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Fatty Acid Synthase ◽  
Ductal Adenocarcinoma ◽  
Caveolin 1

scholarly journals IGFBP2 promotes tumor progression by inducing alternative polarization of macrophages in pancreatic ductal adenocarcinoma through the STAT3 pathway

2021 ◽  
Vol 500 ◽  
pp. 132-146
Author(s):  
Longhao Sun ◽  
Xuebin Zhang ◽  
Qianqian Song ◽  
Liang Liu ◽  
Elizabeth Forbes ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma ◽  
Stat3 Pathway

scholarly journals Contribution of nuclear BCL10 expression to tumor progression and poor prognosis of advanced and/or metastatic pancreatic ductal adenocarcinoma by activating NF-κB-related signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sung-Hsin Kuo ◽  
Shih-Hung Yang ◽  
Ming-Feng Wei ◽  
Hsiao-Wei Lee ◽  
Yu-Wen Tien ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Cyclin B1 ◽  
Ductal Adenocarcinoma ◽  
Clinical Samples ◽  
Wild Type ◽  
Pdac Cell

Abstract Background We previously demonstrated that nuclear BCL10 translocation participates in the instigation of NF-κB in breast cancer and lymphoma cell lines. In this study, we assessed whether nuclear BCL10 translocation is clinically significant in advanced and metastatic pancreatic ductal adenocarcinoma (PDAC). Method and materials We analyzed the expression of BCL10-, cell cycle-, and NF-κB- related signaling molecules, and the DNA-binding activity of NF-κB in three PDAC cell lines (mutant KRAS lines: PANC-1 and AsPC-1; wild-type KRAS line: BxPC-3) using BCL10 short hairpin RNA (shBCL10). To assess the anti-tumor effect of BCL10 knockdown in PDAC xenograft model, PANC-1 cells treated with or without shBCL10 transfection were inoculated into the flanks of mice. We assessed the expression patterns of BCL10 and NF-κB in tumor cells in 136 patients with recurrent, advanced, and metastatic PDAC using immunohistochemical staining. Results We revealed that shBCL10 transfection caused cytoplasmic translocation of BCL10 from the nuclei, inhibited cell viability, and enhanced the cytotoxicities of gemcitabine and oxaliplatin in three PDAC cell lines. Inhibition of BCL10 differentially blocked cell cycle progression in PDAC cell lines. Arrest at G1 phase was noted in wild-type KRAS cell lines; and arrest at G2/M phase was noted in mutant KRAS cell lines. Furthermore, shBCL10 transfection downregulated the expression of phospho-CDC2, phospho-CDC25C, Cyclin B1 (PANC-1), Cyclins A, D1, and E, CDK2, and CDK4 (BxPC-3), p-IκBα, nuclear expression of BCL10, BCL3, and NF-κB (p65), and attenuated the NF-κB pathway activation and its downstream molecule, c-Myc, while inhibition of BCL10 upregulated expression of p21, and p27 in both PANC-1 and BxPC-3 cells. In a PANC-1-xenograft mouse model, inhibition of BCL10 expression also attenuated the tumor growth of PDAC. In clinical samples, nuclear BCL10 expression was closely associated with nuclear NF-κB expression (p < 0.001), and patients with nuclear BCL10 expression had the worse median overall survival than those without nuclear BCL10 expression (6.90 months versus 9.53 months, p = 0.019). Conclusion Nuclear BCL10 translocation activates NF-κB signaling and contributes to tumor progression and poor prognosis of advanced/metastatic PDAC.

Efficacy and tolerability of tremelimumab in patients with metastatic pancreatic ductal adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 470-470 ◽  
Author(s):  
Padmanee Sharma ◽  
Luc Dirix ◽  
Filip Yves Francine Leon De Vos ◽  
James Patrick Allison ◽  
Lore Decoster ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Ductal Adenocarcinoma ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Efficacy Analysis ◽  
Full Analysis ◽  
Grade 3

470 Background: Clinical activity and tolerability of the anti-CTLA-4 antibody, tremelimumab, has yet to be established in metastatic pancreatic ductal adenocarcinoma (mPDAC). In a Phase 2, multicenter, open label study (NCT02527434), tremelimumab was evaluated in pts with advanced solid tumors. We report a planned analysis of the safety and efficacy of tremelimumab monotherapy in a cohort of pts with mPDAC. Methods: Eligible pts were adults with histologically or cytologically confirmed mPDAC with tumor progression following prior standard first-line 5-FU- or gemcitabine-containing chemotherapy. Pts received tremelimumab 750 mg IV Q4W for 7 doses, followed by 750 mg Q12W for 2 doses, for up to a total of 12 mo (total 9 doses in 12 mo) or until disease progression or unacceptable toxicity. Pts were radiographically assessed Q6 wks relative to first dose. The primary endpoints were safety (evaluated by CTCAE v4.0) and objective response rate (ORR) by investigator assessments (evaluated by RECIST v1.1). Results: As of April 5, 2017, 20 mPDAC pts had received treatment and were evaluable for efficacy analysis. Median treatment duration was 1.8 mo. There were no observed objective responses (ORR 0%; 95% CI, 0.0, 16.8%). Of 20 pts, 2 were not evaluable and 18 had progressive disease (PD). Based on the full analysis set (N = 20), progression occurred in target lesions in 14 (70%), non-target lesions in 7 (35%), and new lesions in 13 (65%) pts (not mutually exclusive categories). At the time of progression, 11 (61%) pts were on treatment and 7 (39%) had discontinued treatment. Median overall survival was 4 mo (95% CI 2.83 - 5.42). Two (10%) pts were still in follow up at 12 mo after treatment initiation. Treatment-related AEs (trAEs) occurred in 14 pts (70%); grade ≥3 trAEs occurred in 6 pts (30%). Three pts (15%) discontinued therapy due to trAEs. There were no treatment-related deaths. Conclusions: Tremelimumab monotherapy did not appear to be active in mPDAC pts who had tumor progression following prior standard first-line 5-FU- or gemcitabine-containing chemotherapy. Clinical trial information: NCT02527434.

scholarly journals Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression

Immunity ◽  
2017 ◽  
Vol 47 (3) ◽  
pp. 597 ◽  
Author(s):  
Yu Zhu ◽  
John M. Herndon ◽  
Dorothy K. Sojka ◽  
Ki-Wook Kim ◽  
Brett L. Knolhoff ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma
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