scholarly journals Active Delivery of VLPs Promotes Anti‐Tumor Activity in a Mouse Ovarian Tumor Model

Small ◽  
2020 ◽  
Vol 16 (20) ◽  
pp. 1907150 ◽  
Author(s):  
Chao Wang ◽  
Berta Esteban Fernández de Ávila ◽  
Rodolfo Mundaca‐Uribe ◽  
Miguel Angel Lopez‐Ramirez ◽  
Doris E. Ramírez‐Herrera ◽  
...  
Keyword(s):  
Ovarian Tumor ◽  
Tumor Model ◽  
Anti Tumor Activity

scholarly journals Anti-tumor activity of KNTC2 siRNA in orthotopic tumor model mice of hepatocellular carcinoma

2017 ◽  
Vol 493 (1) ◽  
pp. 800-806 ◽  
Author(s):  
Yukimasa Makita ◽  
Shumpei Murata ◽  
Yoshiki Katou ◽  
Kuniko Kikuchi ◽  
Hiroshi Uejima ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Model ◽  
Orthotopic Tumor ◽  
Orthotopic Tumor Model ◽  
Anti Tumor Activity

Abstract 3657: Phosphatidylserine-targeting antibodies enhance anti-tumor activity of a tumor vaccine in a HPV-induced tumor model

2017 ◽  
Author(s):  
Genevieve Weir ◽  
Tara Quinton ◽  
Jeff T. Hutchins ◽  
Bruce D. Freimark ◽  
Marianne Stanford
Keyword(s):  
Tumor Vaccine ◽  
Tumor Model ◽  
Anti Tumor Activity

Evaluation of PolyMPC–Dox Prodrugs in a Human Ovarian Tumor Model

2016 ◽  
Vol 13 (5) ◽  
pp. 1679-1687 ◽  
Author(s):  
Kaitlyn E. Wong ◽  
Maria C. Mora ◽  
Matthew Skinner ◽  
Samantha McRae Page ◽  
Giovanna M. Crisi ◽  
...  
Keyword(s):  
Ovarian Tumor ◽  
Tumor Model

scholarly journals Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis

2020 ◽  
Author(s):  
Qiaoming Zhi ◽  
Wei Li ◽  
Dongming Zhu ◽  
Daiwei Wan ◽  
Ye Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Model ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Biochemical Basis ◽  
Over Expression ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Anti Tumor Activity

Abstract Background The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.

scholarly journals Targeting a proteolytic neo-epitope of CUB-domain containing protein 1 in RAS-driven cancer

2021 ◽  
Author(s):  
Shion A. Lim ◽  
Jie Zhou ◽  
Alexander J. Martinko ◽  
Yung-Hua Wang ◽  
Ekaterina V. Filippova ◽  
...  
Keyword(s):  
Tumor Model ◽  
Target Cells ◽  
Drug Conjugates ◽  
Pancreatic Cancer Cells ◽  
Cub Domain ◽  
Specific Localization ◽  
Specific Regulation ◽  
Anti Tumor Activity ◽  
Disease Specific

A central challenge for any therapeutic is targeting diseased over normal cells. Proteolysis is frequently upregulated in disease and can generate proteoforms with unique neo-epitopes. We hypothesize that targeting proteolytic neo-epitopes can enable more effective and safer treatments, reflecting a conditional layer of disease-specific regulation. Here, we characterized the precise proteolytic isoforms of CUB domain containing protein 1 (CDCP1), a protein overexpressed and specifically cleaved in RAS-driven cancers. We validated that the N-terminal and C-terminal fragments of CDCP1 remain associated after proteolysis in vitro and on the surface of pancreatic cancer cells. Using a differential phage display strategy, we generated exquisitely selective recombinant antibodies that target cells harboring cleaved CDCP1 and not the full-length form using antibody-drug conjugates or a bi-specific T-cell engagers. We show tumor-specific localization and anti-tumor activity in a syngeneic pancreatic tumor model having superior safety profiles compared to a pan-CDCP1-targeting antibody. Our studies show proteolytic neo-epitopes can provide an orthogonal AND gate for disease-specific targeting.

Final results of a phase Ib study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4132-4132 ◽  
Author(s):  
Ferry Eskens ◽  
Corina N. Oldenhuis ◽  
Walter J. Loos ◽  
Brooke Esteves ◽  
Leni van Doorn ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Tumor Model ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Vascular Endothelial ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Endothelial Growth Factor ◽  
Anti Tumor Activity

4132 Background: Tivozanib is a potent, selective, oral small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 with a long half-life. A Phase I study found tivozanib's maximum tolerated dose (MTD) to be 1.5 mg/d and responses were observed in pts with colorectal cancer (CRC) and other tumors. Tivozanib has shown additive anti-tumor activity with 5-fluorouracil in a preclinical breast tumor model. FOLFOX6 is a standard chemotherapy for GI cancers. This open-label, Phase Ib study (NCT00660153) sought to determine the MTD, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and anti-tumor activity of escalating doses of tivozanib combined with a modified (m) FOLFOX6 regimen (85 mg/kg2 oxaliplatin) in pts with advanced GI tumors. Methods: Tivozanib was administered once daily in 4-week cycles (3 weeks on, 1 week off) with mFOLFOX6 administered on Days 1 and 15 of each cycle. Pts also received a single dose of tivozanib on day -5 for PK analysis. Pts were allowed to continue tivozanib following discontinuation of mFOLFOX6. Results: Twenty two pts (14:8 male:female; median age 58 years; 91% Caucasian) received tivozanib 0.5 mg (n=9), 1.0 mg (n=3), or 1.5 mg (n=10) and mFOLFOX6. Pts received a median of 5.2 (range 0.0 to 25.1) months of treatment. DLTs were observed in 2 pts on tivozanib 0.5 mg (reversible Grade [Gr] 3 diarrhea and Gr 3/4 transaminase elevations) and in 2 pts on tivozanib 1.5 mg (Gr 3 seizure and reversible Gr 3 vertigo). Other Gr 3/4 drug-related adverse events (AEs) included neutropenia, fatigue, and hypertension (n=2 each). Eight pts discontinued treatment due to AEs. The MTD for tivozanib with mFOLFOX6 was 1.5 mg. The disease control rate was 63% (<1% complete response, 27% partial response, 36% stable disease). Preliminary PK data showed no interaction between tivozanib and mFOLFOX6. Eight additional pts enrolled at the 1.5 mg dose level are currently being evaluated. Final results will be presented. Conclusions: Tivozanib can be combined at its recommended dose of 1.5 mg/day with mFOLFOX6 for pts with advanced GI tumors. The combination was tolerable and showed encouraging anti-tumor activity. A Phase II study of this combination for mCRC is ongoing.  

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