scholarly journals Uses of the Novel Small Peptide, KTH-222, in Treating Human Pancreatic Cancer: Evaluation of Different Treatment Regimens using a Mouse Xenograft Model

2021 ◽  
Vol 36 (1) ◽  
Author(s):  
Michael R Kozlowski
Keyword(s):  
Pancreatic Cancer ◽  
Xenograft Model ◽  
Human Pancreatic Cancer ◽  
The Novel ◽  
Small Peptide ◽  
Mouse Xenograft ◽  
Treatment Regimens ◽  
Mouse Xenograft Model

scholarly journals Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer–stromal interactions in a mouse xenograft model

2016 ◽  
Vol 107 (10) ◽  
pp. 1443-1452 ◽  
Author(s):  
Masaki Yoshida ◽  
Yoshihiro Miyasaka ◽  
Kenoki Ohuchida ◽  
Takashi Okumura ◽  
Biao Zheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Xenograft Model ◽  
Calpain Inhibitor ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

scholarly journals Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis

2020 ◽  
Author(s):  
Xiaowei Fu ◽  
Xueqiang Deng ◽  
Weidong Xiao ◽  
Bo Huang ◽  
Xuan Yi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Epithelial To Mesenchymal Transition ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Pancreatic Cancer Cells ◽  
Mouse Xenograft Model ◽  
Underlying Mechanisms

Abstract BackgroundChemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown.MethodsTwo independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR, were established. Transwell assays were used to validate whether GR cells acquired EMT. qRT-PCR and western blot were performed to detect the expression levels of NEAT1, miR-506-3p, and ZEB2 in GR cells. MTT and cell apoptosis assays were conducted to evaluate the sensitivity of GR cells to gemcitabine. Rescue experiments were employed to investigate whether NEAT1 mediates drug resistance of GR cells through modulation of the miR-506-3p/ZEB2/EMT axis. Furthermore, a mouse xenograft model was established to confirm these findings.ResultsGR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Furthermore, elevated expression of NEAT1 was observed in GR cells. Downregulation of NEAT1 sensitized GR cells to gemcitabine. More importantly, we demonstrated that downregulation of NEAT1 enhanced the sensitivity of GR cells to gemcitabine by reversing the EMT process. NEAT1 regulated ZEB2 expression by sponging miR-506-3p, and the function of NEAT1 in GR cells was dependent on miR-506-3p. These findings were further confirmed in a nude mouse xenograft model.ConclusionsTaken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide a new direction for improving the chemotherapeutic effects in PC.

An engineered anti-CA19-9 cys-diabody for PET imaging of pancreas cancer and targeting of polymerized liposomal nanoparticles.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 198-198
Author(s):  
M. D. Girgis ◽  
K. McCabe ◽  
T. Olafsen ◽  
F. Bergara ◽  
V. Kenanova ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Mouse Xenograft Model ◽  
Parental Antibody ◽  
G Ratio

198 Background: Antibody-based therapeutics is a rapidly growing field. Small engineered antibody fragments, such as the cys-diabody demonstrate similar antigen affinity compared to the parental antibody but have a shorter serum half-life (4hrs) and possess the ability to be conjugated to nanoparticles. Our goal was to engineer an anti-CA19-9 cys-diabody fragment in hopes of imaging and targeting pancreatic cancer. Methods: The anti-CA19-9 cys-diabody was created by cloning the variable region of the parental antibody, engineering a C-terminus cysteine, expressing in NS0 cells followed by protein purification utilizing HPLC. Maleimide chemistry was used to conjugate the cys-diabody to PLNs through the engineered cysteine residues. Immunofluorescence and flow cytometry were used to evaluate targeting of cys-diabody and diabody conjugated PLNs to human pancreatic cancer cell lines. The cys-diabody was evaluated in a mouse xenograft model harboring CA19-9 positive (BxPC3) and negative (MiaPaca) tumors. The cys-diabody was radiolabeled with a positron emitter (I-124) and microPET/CT were performed after tail vein injection. Percent of injected dose per gram (%ID/g) of radioactivity was measured in blood and tumor to provide objective confirmation of the microPET images. Results: Immunofluorescence and flow cytometry showed specific binding of the anti-CA19-9 cys- diabody. Tumor xenograft imaging of the anti-CA19-9 cys-diabody demonstrated an average tumor:blood (%ID/g) ratio of 3.3 and positive:negative tumor ratio of 7.4. Successful conjugation of the cys-diabody to PLNs was indicated by immunofluorescence showing specific targeting of PLN-cys- diabody conjugate to human pancreatic cancer cells in vitro. Conclusions: Our results show that the anti-CA19.9 cys- diabody targets pancreatic cancer providing specific molecular imaging in tumor xenograft models. Furthermore, the PLN-cys-diabody conjugate targets human pancreatic cancer cells with the potential to deliver targeted treatment. Further studies evaluating the in vivo ability of the PLN-cys-diabody conjugate to target pancreatic cancer need to be performed. No significant financial relationships to disclose.

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