Influence of Octreotide and Tamoxifen on Tumor Growth and Liver Metastasis in N-Nitrosobis(2-oxopropyl)amine-Induced Pancreatic Cancer in Syrian Hamsters

2000 ◽  
Vol 54 (2) ◽  
pp. 74-77 ◽  
Author(s):  
F.A. Wenger ◽  
M. Kilian ◽  
I. Mautsch ◽  
C.A. Jacobi ◽  
I. Schimke ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Syrian Hamsters

Effects of celebrex and zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in syrian hamsters

2001 ◽  
Vol 37 ◽  
pp. S110
Author(s):  
F.A. Wenger ◽  
M. Kilian ◽  
I. Schimke ◽  
H. Guski ◽  
C.A. Jacobi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Syrian Hamsters

Influence of Octreotide on Liver Metastasis and Hepatic Lipid Peroxidation in BOP-Induced Pancreatic Cancer in Syrian Hamsters

Pancreas ◽  
2001 ◽  
Vol 23 (3) ◽  
pp. 266-272 ◽  
Author(s):  
F. A. Wenger ◽  
M. Kilian ◽  
I. Mautsch ◽  
C. A. Jacobi ◽  
A. Steiert ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Lipid Peroxidation ◽  
Liver Metastasis ◽  
Syrian Hamsters ◽  
Hepatic Lipid ◽  
Hepatic Lipid Peroxidation

scholarly journals Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Claudia M. Kowolik ◽  
Min Lin ◽  
Jun Xie ◽  
Larry E. Overman ◽  
David A. Horne
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Cell Lines ◽  
Target Genes ◽  
Pancreatic Cancer Cell ◽  
Standard Of Care ◽  
Therapeutic Agents ◽  
Survival Times

Abstract Background Pancreatic cancer is one of the most lethal malignancies due to frequent late diagnosis, aggressive tumor growth and metastasis formation. Continuously raising incidence rates of pancreatic cancer and a lack of significant improvement in survival rates over the past 30 years highlight the need for new therapeutic agents. Thus, new therapeutic agents and strategies are urgently needed to improve the outcome for patients with pancreatic cancer. Here, we evaluated the anti-tumor activity of a new natural product-based epidithiodiketopiperazine, NT1721, against pancreatic cancer. Methods We characterized the anticancer efficacy of NT1721 in multiple pancreatic cancer cell lines in vitro and in two orthotopic models. We also compared the effects of NT1721 to clinically used hedgehog inhibitors and the standard-of-care drug, gemcitabine. The effect of NT1721 on hedgehog/GLI signaling was assessed by determining the expression of GLI and GLI target genes both in vitro and in vivo. Results NT1721 displayed IC50 values in the submicromolar range in multiple pancreatic cancer cell lines, while largely sparing normal pancreatic epithelial cells. NT1721 attenuated hedgehog/GLI signaling through downregulation of GLI1/2 transcription factors and their downstream target genes, which reduced cell proliferation and invasion in vitro and significantly decreased tumor growth and liver metastasis in two preclinical orthotopic mouse models of pancreatic cancer. Importantly, treatment with NT1721 significantly improved survival times of mice with pancreatic cancer compared to the standard-of-care drug, gemcitabine. Conclusions Favorable therapeutics properties, i.e. 10-fold lower IC50 values than clinically used hedgehog inhibitors (vismodegib, erismodegib), a 90% reduction in liver metastasis and significantly better survival times compared to the standard-of-care drug, gemcitabine, provide a rational for testing NT1721 in the clinic either as a single agent or possibly in combination with gemcitabine or other therapeutic agents in PDAC patients overexpressing GLI1/2. This could potentially result in promising new treatment options for patients suffering from this devastating disease.

scholarly journals The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lixin Ma ◽  
Bo Zhai ◽  
Huaqiang Zhu ◽  
Weidong Li ◽  
Wenjing Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Biological Behavior ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Neuropilin 1 ◽  
Cancer Tissues

Abstract Background Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear. Methods Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial–mesenchymal transition (EMT) by co-interacting the TGF-β pathway was examined. Results In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-β pathway stimulated by TGF-β ligand. Conclusions The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.

RNAi targeting EZH2 inhibits tumor growth and liver metastasis of pancreatic cancer in vivo

2010 ◽  
Vol 297 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Yangchao Chen ◽  
Dan Xie ◽  
Wing Yin Li ◽  
Chi Man Cheung ◽  
Hong Yao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Tumor Growth

scholarly journals Gemcitabine-Induced TIMP1 Attenuates Therapy Response and Promotes Tumor Growth and Liver Metastasis in Pancreatic Cancer

2017 ◽  
Vol 77 (21) ◽  
pp. 5952-5962 ◽  
Author(s):  
Zenobia D'Costa ◽  
Keaton Jones ◽  
Abul Azad ◽  
Ruud van Stiphout ◽  
Su Y. Lim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Therapy Response
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