scholarly journals Establishment of xenografts of urological cancers on chicken chorioallantoic membrane (CAM) to study metastasis

2019 ◽  
Vol 2 (3) ◽  
pp. 140-151 ◽  
Author(s):  
Junhui Hu ◽  
Moe Ishihara ◽  
Arnold I Chin ◽  
Lily Wu

Abstract Cancer of the urological system commonly occurs in the kidney, bladder, and prostate gland. The clear cell subtype of renal cell carcinoma (ccRCC) constitutes the great majority of kidney cancer. Metastatic ccRCC portends a very poor outcome with no effective treatment available. Prostate cancer is the most common cancer in males in the US. Despite recent advances in selective kinase inhibitors and immunotherapies, the rate of developing new treatment from bench to bedside is slow. A time-consuming step is at the animal drug testing stage, in which the mouse model is the gold standard. In the pursuit to streamline the in vivo cancer biology research and drug development, we explored the feasibility of the chicken chorioallantoic membrane (CAM) model to establish xenografts. The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice. We generated CAM xenografts from ccRCC, bladder and prostate cancer, with established cancer cell lines and freshly isolated patient-derived tissues, either as primary tumor cells or small pieces of tumors. The successful CAM engraftment rate from the different tumor sources is 70% or above. Using our previously established metastatic ccRCC mouse model, we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice. Taken together, CAM can serve as a valuable platform to establish new patient-derived xenografts (PDXs) to study tumor biology, thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.

2009 ◽  
Vol 181 (4S) ◽  
pp. 53-53
Author(s):  
Jean A Thomas ◽  
Susan Poulton ◽  
Tameika Phillips ◽  
Jessica C. Lloyd ◽  
Jodi Antonelli ◽  
...  

2015 ◽  
Vol 64 (7) ◽  
pp. 873-883 ◽  
Author(s):  
Vladimir Riabov ◽  
David Kim ◽  
Surmeet Chhina ◽  
Richard B. Alexander ◽  
Elena N. Klyushnenkova

2020 ◽  
Vol 21 (3) ◽  
pp. 1106 ◽  
Author(s):  
Sruthi V. Hindupur ◽  
Sebastian C. Schmid ◽  
Jana Annika Koch ◽  
Ahmed Youssef ◽  
Eva-Maria Baur ◽  
...  

The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.


2019 ◽  
Vol 40 (12) ◽  
pp. 1504-1513 ◽  
Author(s):  
Timothy O Adekoya ◽  
Nikia Smith ◽  
Temilade Aladeniyi ◽  
Joe B Blumer ◽  
Xiaoxin L Chen ◽  
...  

Abstract Prostate cancer (PCa) is a leading cause of cancer death among men, with greater prevalence of the disease among the African American population in the USA. Activator of G-protein signaling 3 (AGS3/G-protein signaling modulator 1) was shown to be overexpressed in prostate adenocarcinoma relative to the prostate gland. In this study, we investigated the correlation between AGS3 overexpression and PCa malignancy. Immunoblotting analysis and real-time quantitative-PCR showed increase in AGS3 expression in the metastatic cell lines LNCaP (~3-fold), MDA PCa 2b (~2-fold), DU 145 (~2-fold) and TRAMP-C1 (~20-fold) but not in PC3 (~1-fold), relative to control RWPE-1. Overexpression of AGS3 in PC3, LNCaP and MDA PCa 2b enhanced tumor growth. AGS3 contains seven tetratricopeptide repeats (TPR) and four G-protein regulatory (GPR) motifs. Overexpression of the TPR or the GPR motifs in PC3 cells had no effect in tumor growth. Depletion of AGS3 in the TRAMP-C1 cells (TRAMP-C1-AGS3-/-) decreased cell proliferation and delayed wound healing and tumor growth in both C57BL/6 (~3-fold) and nude mice xenografts, relative to control TRAMP-C1 cells. TRAMP-C1-AGS3-/- tumors also exhibited a marked increase (~5-fold) in both extracellular signal-regulated kinase (ERK) 1/2 and P38 mitogen-activated protein kinase (MAPK) activation, which correlated with a significant increase (~3-fold) in androgen receptor (AR) expression, relative to TRAMP-C1 xenografts. Interestingly, overexpression of AGS3 in TRAMP-C1-AGS3-/- cells inhibited ERK activation and AR overexpression as compared with control TRAMP-C1 cells. Taken together, the data indicate that the effect of AGS3 in prostate cancer development and progression is probably mediated via a MAPK/AR-dependent pathway.


The Prostate ◽  
2012 ◽  
Vol 72 (15) ◽  
pp. 1648-1658 ◽  
Author(s):  
Umesh T. Sankpal ◽  
Maen Abdelrahim ◽  
Sarah F. Connelly ◽  
Chris M. Lee ◽  
Rafael Madero-Visbal ◽  
...  

2010 ◽  
Vol 13 (4) ◽  
pp. 350-355 ◽  
Author(s):  
J A Thomas ◽  
J A Antonelli ◽  
J C Lloyd ◽  
E M Masko ◽  
S H Poulton ◽  
...  

2011 ◽  
Vol 25 ◽  
pp. S229
Author(s):  
M.S. Dulcich ◽  
R.E. Hartman ◽  
P. Gifford ◽  
C. Molinaro ◽  
X. Luo-Owen ◽  
...  

2009 ◽  
Vol 69 (18) ◽  
pp. 7466-7472 ◽  
Author(s):  
Weisheng Zhang ◽  
Joe Zhu ◽  
Clay L. Efferson ◽  
Chris Ware ◽  
Jennifer Tammam ◽  
...  

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