scholarly journals Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
S. Inder ◽  
M. Bates ◽  
N. Ni Labhrai ◽  
N. McDermott ◽  
J. Schneider ◽  
...  

AbstractThe exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.

Oncotarget ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 3338-3352 ◽  
Author(s):  
Chenrui Li ◽  
Zhijun Wang ◽  
Qian Wang ◽  
Rebecca Lucinda Ka Yan Ho ◽  
Ying Huang ◽  
...  

2014 ◽  
Vol 110 (2) ◽  
pp. 348-354 ◽  
Author(s):  
Shuraila F. Zerp ◽  
Conchita Vens ◽  
Ben Floot ◽  
Marcel Verheij ◽  
Baukelien van Triest

2021 ◽  
Author(s):  
Donghui Pan ◽  
Lizhen Wang ◽  
Xinyu Wang ◽  
Junjie Yan ◽  
YuPing Xu ◽  
...  

Abstract Purpose: Radiolabeled FSH1 peptides are potential specific probes for FSHR imaging. However, moderate uptakes and fast washout from the tumors may limit its widespread use. In this study, 68Ga labeled modified FSH1 analogs was prepared and the imaging properties were determined in the prostate cancer model with or without aprotinin.Methods: NOTA-MAL-FSH4 was synthesized and labeled with 68Ga. The pharmacokinetic profile of the peptide after co-administration with aprotinin was determined through metabolism analyses and microPET imaging.Results: 68Ga-NOTA-MAL-FSH4 was successfully prepared. The IC50 value of displacement 68Ga-NOTA-MAL-FSH4 with FSH1 was 139.4±1.16 nM. The PC-3 prostate tumor was visible after administration of the 68Ga labeled tracer. In vitro RP-HPLC analysis revealed that the average percentage of intact peptide in the plasma, liver and tumor was 8.30, 9.57 and 7.06 % respectively. In presence of aprotinin, the amounts of intact peptide increased to 34.32%, 20.63 % and 15.39 % in the counterparts respectively. MicroPET imaging showed that the uptakes of PC-3 tumors at 60mins after co-administration of 100μg, 200μg or 400μg enzyme inhibitors were 2.91±0.21%ID/g, 3.89±0.16%ID/g and 9.21±0.22%ID/g respectively.Conclusion: With the aid of a serine protease inhibitor, the performance of the 68Ga labeled peptide was optimized, which may benefit further clinical application.


2001 ◽  
Vol 15 (6) ◽  
pp. 629-640 ◽  
Author(s):  
S. Bhowmick ◽  
D.J. Swanlund ◽  
J.E. Coad ◽  
L. Lulloff ◽  
M.F. Hoey ◽  
...  

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