Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines

Author(s):  
Christopher J. Pinard ◽  
Samuel E. Hocker ◽  
Andrew C. Poon ◽  
Jordon M. Inkol ◽  
Arata Matsuyama ◽  
...  
2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander S. Hölscher ◽  
Wolfgang A. Schulz ◽  
Maria Pinkerneil ◽  
Günter Niegisch ◽  
Michèle J. Hoffmann

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15632-15632 ◽  
Author(s):  
G. Sonpavde ◽  
W. Jian ◽  
S. P. Lerner

15632 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved multinationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. Angiogenesis and plasma VEGF correlate with poor outcomes in human urothelial carcinoma. We designed a preclinical study to examine the efficacy of sunitinib malate alone and in combination with cisplatin against human urothelial carcinoma in vitro and in a murine xenograft model. Methods: The IC50 for sunitinib malate and cisplatin was determined separately against two human urothelial carcinoma cell lines (TCC-SUP and 5637). Sunitinib malate and cisplatin were also applied concurrently to determine activity of the combination. Immunohistochemical staining was performed to detect expression of VEGFR2 on the cell lines, and to measure modulation of this pathway by sunitinib by measuring phosphorylated (p)VEGFR2. Anti-tumor activity of sunitinib malate alone and in combination with cisplatin was determined in a murine xenograft model bearing 5,637 cells. Results: Both human urothelial carcinoma cell lines were found to express VEGFR2. Sunitinib malate displayed significant activity against both urothelial carcinoma cell lines in vitro at low nanomolar concentrations. Furthermore, sunitinib malate in combination with cisplatin was synergistic in vitro. We observed primarily cytostatic activity for sunitinib malate at both 20 mg/kg and 40 mg/kg orally once daily against a murine xenograft model bearing subcutaneous 5,637 cell tumors during 4 weeks of treatment. Anti-tumor activity of sunitinib malate in combination with cisplatin and correlative studies are being evaluated in the murine xenograft model. Conclusion: Sunitinib malate has anti-tumor activity against human urothelial carcinoma as a single agent and is synergistic in combination with cisplatin in vitro. Sunitinib also has significant efficacy in a murine xenograft model of human urothelial carcinoma. These results warrant further exploration of sunitinib malate as a single agent and in combination with cisplatin chemotherapy in human urothelial carcinoma. No significant financial relationships to disclose.


1999 ◽  
Vol 161 (2) ◽  
pp. 714-715 ◽  
Author(s):  
D. Makri ◽  
W.A. Schulz ◽  
M.O. Grimm ◽  
S. Clasen ◽  
H. Bojar ◽  
...  

2019 ◽  
Author(s):  
Aisha Qazi ◽  
Faith M. Thomas ◽  
Sulalita Chaki ◽  
Noah Robertson ◽  
Shovik Patel ◽  
...  

2005 ◽  
Vol 173 (4S) ◽  
pp. 206-206
Author(s):  
Fang Hong Chen ◽  
Guang Jian Zhang ◽  
Yanli Cao ◽  
Yoshiki Iwamoto ◽  
William A. See

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
J. Falke ◽  
J. Parkkinen ◽  
L. Vaahtera ◽  
C. A. Hulsbergen-van de Kaa ◽  
E. Oosterwijk ◽  
...  

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.


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