A comparison of DFO and DFO* conjugated to trastuzumab-DM1 for complexing 89Zr – In vitro stability and in vivo microPET/CT imaging studies in NOD/SCID mice with HER2-positive SK-OV-3 human ovarian cancer xenografts

2020 ◽  
Vol 84-85 ◽  
pp. 11-19 ◽  
Author(s):  
Hyungjun Cho ◽  
Noor Al-saden ◽  
Heather Lam ◽  
Juri Möbus ◽  
Raymond M. Reilly ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3939
Author(s):  
Tianqi Xu ◽  
Anzhelika Vorobyeva ◽  
Alexey Schulga ◽  
Elena Konovalova ◽  
Olga Vorontsova ◽  
...  

Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targeting component. As the EpCAM-targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1-LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM- and HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co-treatment using Ec1-LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1-LoPE was well tolerated without signs of hepatic or kidney toxicity. Co-treatment with trastuzumab and Ec1-LoPE might be a potential therapeutic strategy for HER2- and EpCAM-positive OC.


2002 ◽  
Vol 86 (10) ◽  
pp. 1652-1657 ◽  
Author(s):  
R E Aird ◽  
J Cummings ◽  
A A Ritchie ◽  
M Muir ◽  
R E Morris ◽  
...  

2012 ◽  
Vol 12 (4) ◽  
pp. 336-346 ◽  
Author(s):  
Ellie S. M. Chu ◽  
Stephen C. W. Sze ◽  
Ho P. Cheung ◽  
Qing Liu ◽  
Tzi B. Ng ◽  
...  

2013 ◽  
Vol 29 (4) ◽  
pp. 1371-1378 ◽  
Author(s):  
BEI ZHANG ◽  
XUEYA WANG ◽  
FENGFENG CAI ◽  
WEIJIE CHEN ◽  
ULI LOESCH ◽  
...  

2021 ◽  
Vol 8 (1) ◽  
pp. 141-155
Author(s):  
Enrique Ortega ◽  
Francisco J. Ballester ◽  
Alba Hernández-García ◽  
Samanta Hernández-García ◽  
M. Alejandra Guerrero-Rubio ◽  
...  

Novel Os(ii) arene complexes with a deprotonated ppy or ppy-CHO C^N ligand have been synthesized to selectively act on cancer cells as proteosynthesis inhibitors in vitro and exert antitumor activity in vivo in C. elegans models.


2018 ◽  
Vol 61 (11) ◽  
pp. 5009-5019 ◽  
Author(s):  
Betsy Marydasan ◽  
Bollapalli Madhuri ◽  
Shirisha Cherukommu ◽  
Jedy Jose ◽  
Mambattakkara Viji ◽  
...  

2016 ◽  
Vol 39 (1) ◽  
pp. 242-252 ◽  
Author(s):  
Chanjuan Li ◽  
Hongjuan Ding ◽  
Jing Tian ◽  
Lili Wu ◽  
Yun Wang ◽  
...  

Background/Aims: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. Results: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. Conclusions: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.


Sign in / Sign up

Export Citation Format

Share Document