scholarly journals CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

2021 ◽  
Vol 38 (4) ◽  
pp. 229-238
Author(s):  
Ji-Ping Hou ◽  
◽  
Xue-Bo Men ◽  
Lian-Ying Yang ◽  
En-Kun Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Promote Tumor Growth ◽  
Vegfr2 Signaling

scholarly journals The antitumoral activity of TLR7 ligands is corrupted by the microenvironment of pancreatic tumors

2020 ◽  
Author(s):  
Marie Rouanet ◽  
Hubert Lulka ◽  
Pierre Garcin ◽  
Martin Sramek ◽  
Delphine Pagan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Pancreatic Tumors ◽  
Antitumoral Activity ◽  
Toll Like Receptor ◽  
Immunodeficient Mice ◽  
Pancreatic Cancer Cells ◽  
Promote Tumor Growth

AbstractToll like receptors are key players in the innate immune system. Recent studies have suggested that they may impact the growth of pancreatic cancer, a disease with no cure. Among them, Toll like receptor-7 shows promise for therapy but may also promote tumor growth. Thus, we aimed to better understand the mechanism of action of Toll like receptor-7 ligands in pancreatic cancer, to open the door for clinical applications. In vitro, Toll like receptor-7 ligands strongly inhibit the proliferation and induce cell death by apoptosis of pancreatic cancer cells. In vivo, while Toll like receptor-7 agonists significantly delay the growth of aggressive tumors engrafted in immunodeficient mice, they instead surprisingly promote tumor growth and accelerate animal death in immunocompetent models. Molecular investigations revealed that Toll like receptor-7 agonists strongly increase the number of tumor-promoting macrophages to drive pancreatic tumorigenesis in immunocompetent mice. This is in stark contrast with Toll like receptor-7 ligands’ great potential to inhibit pancreatic cancer cell proliferation in vitro and tumor growth in vivo in immunosuppressed models. Collectively, our findings shine a light on the duality of action of Toll like receptor-7 agonists in experimental cancer models, and calls into question their use for pancreatic cancer therapy.

Hepatocyte Growth Factor and Macrophage-stimulating Protein “Hinge” Analogs to Treat Pancreatic Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 782-795
Author(s):  
John W. Wright ◽  
Kevin J. Church ◽  
Joseph W. Harding
Keyword(s):  
Pancreatic Cancer ◽  
Signal Transduction ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tumor Growth ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Met Receptor ◽  
Macrophage Stimulating Protein ◽  
Hepatocyte Growth

Pancreatic cancer (PC) ranks twelfth in frequency of diagnosis but is the fourth leading cause of cancer related deaths with a 5 year survival rate of less than 7 percent. This poor prognosis occurs because the early stages of PC are often asymptomatic. Over-expression of several growth factors, most notably vascular endothelial growth factor (VEGF), has been implicated in PC resulting in dysfunctional signal transduction pathways and the facilitation of tumor growth, invasion and metastasis. Hepatocyte growth factor (HGF) acts via the Met receptor and has also received research attention with ongoing efforts to develop treatments to block the Met receptor and its signal transduction pathways. Macrophage-stimulating protein (MSP), and its receptor Ron, is also recognized as important in the etiology of PC but is less well studied. Although the angiotensin II (AngII)/AT1 receptor system is best known for mediating blood pressure and body water/electrolyte balance, it also facilitates tumor vascularization and growth by stimulating the expression of VEGF. A metabolite of AngII, angiotensin IV (AngIV) has sequence homology with the “hinge regions” of HGF and MSP, key structures in the growth factor dimerization processes necessary for Met and Ron receptor activation. We have developed AngIV-based analogs designed to block dimerization of HGF and MSP and thus receptor activation. Norleual has shown promise as tested utilizing PC cell cultures. Results indicate that cell migration, invasion, and pro-survival functions were suppressed by this analog and tumor growth was significantly inhibited in an orthotopic PC mouse model.

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