Expression of NM23-H1 and NM23-H2 in human epithelioid sarcoma cell lines of different invasive potential in vitro

1995 ◽  
Vol 121 (S1) ◽  
pp. A63-A63
Author(s):  
T. Heymer ◽  
R. Engers ◽  
C. D. Gerharz ◽  
R. Krause-Paulus ◽  
N. El-Badawy ◽  
...  
2015 ◽  
Vol 238 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Farzad Jamshidi ◽  
Ali Bashashati ◽  
Karey Shumansky ◽  
Brendan Dickson ◽  
Nalan Gokgoz ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Darina Ocadlikova ◽  
Mariangela Lecciso ◽  
Javier Martin Broto ◽  
Katia Scotlandi ◽  
Michele Cavo ◽  
...  

BackgroundHigh-grade sarcomas are a heterogeneous group of aggressive tumors arising in bone and soft tissues. After relapse, treatment options are limited. The multi-targeted receptor tyrosine kinase inhibitors (TKIs) sunitinib and inhibitor of PD-1 (anti-PD-1) nivolumab have shown antitumor activity in selected subtypes. In this study, we examine the role of TKIs and PD-1 based therapy in in vitro cocultures of sarcoma.MethodsThe human osteosarcoma (SaOS-2) and synovial sarcoma (SYO-1) cell lines were treated with sunitinib. After cell death and proliferation assessment, expression of PD-L1 was analyzed by flow cytometry. Sunitinib-treated sarcoma cells were cocultured with dendritic cells (DCs), and the phenotype of mature DCs was determined by flow cytometry. Mature DCs were cultured with autologous T cells. PD-1 expression on T cells, their proliferation, T regulatory cell (Tregs) induction and IFN-γ production, before and after nivolumab exposure, were analyzed.ResultsAlong with its anti-proliferative and direct pro-apoptotic effect on sarcoma cell lines, sunitinib prompted PD-L1 upregulation on sarcoma cells. Interestingly, sunitinib-treated sarcoma cells drive DCs to full maturation and increase their capacity to induce sarcoma-reactive T cells to produce IFN-γ. Conversely, no effect on T cell proliferation and T cell subpopulation composition was observed. Moreover, both bone and synovial sarcoma cell lines induced Tregs through DCs but sunitinib treatment completely abrogated Treg induction. Finally, sarcoma cell lines induced PD-1 upregulation on both effector T cells and Tregs when loaded into DCs, providing a rationale for using PD-1 blockade. Indeed, PD-1 blockade by nivolumab synergized with sunitinib in inducing IFN-γ-producing effector T cells.ConclusionsTaken together, our in vitro data indicate that the treatment of sarcoma cells with sunitinib can exert significant changes on immune cell subsets toward immune activation, leading to DC-based cross-priming of IFN-γ-producing effector T cells and reduced Treg induction. PD-1 blockade with nivolumab has a synergistic effect with sunitinib, supporting the use of TKI and anti-PD-1 approach in sarcomas, and perhaps in other cancers. DC-targeted drugs, including toll-like receptor 3 inhibitors and CD47 inhibitors, are under development and our preclinical model might help to better design their clinical application.


1984 ◽  
Vol 10 (7) ◽  
pp. 1005-1011 ◽  
Author(s):  
Timothy J. Kinsella ◽  
James B. Mitchell ◽  
Scott McPherson ◽  
James Miser ◽  
Timothy Triche ◽  
...  

1988 ◽  
Vol 15 (4) ◽  
pp. 937-942 ◽  
Author(s):  
Ralph R. Weichselbaum ◽  
Michael A. Beckett ◽  
Michael A. Simon ◽  
Carla McCauley ◽  
Daniel Haraf ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1553
Author(s):  
Ellie Esfandiari Nazzaro ◽  
Fahad Y. Sabei ◽  
Walter K. Vogel ◽  
Mohamad Nazari ◽  
Katelyn S. Nicholson ◽  
...  

Ewing’s sarcoma, characterized by pathognomonic t (11; 22) (q24; q12) and related chromosomal ETS family translocations, is a rare aggressive cancer of bone and soft tissue. Current protocols that include cytotoxic chemotherapeutic agents effectively treat localized disease; however, these aggressive therapies may result in treatment-related morbidities including second-site cancers in survivors. Moreover, the five-year survival rate in patients with relapsed, recurrent, or metastatic disease is less than 30%, despite intensive therapy with these cytotoxic agents. By using high-throughput phenotypic screening of small molecule libraries, we identified a previously uncharacterized compound (ML111) that inhibited in vitro proliferation of six established Ewing’s sarcoma cell lines with nanomolar potency. Proteomic studies show that ML111 treatment induced prometaphase arrest followed by rapid caspase-dependent apoptotic cell death in Ewing’s sarcoma cell lines. ML111, delivered via methoxypoly(ethylene glycol)-polycaprolactone copolymer nanoparticles, induced dose-dependent inhibition of Ewing’s sarcoma tumor growth in a murine xenograft model and invoked prometaphase arrest in vivo, consistent with in vitro data. These results suggest that ML111 represents a promising new drug lead for further preclinical studies and is a potential clinical development for the treatment of Ewing’s sarcoma.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21057-21057
Author(s):  
J. P. Diaz ◽  
S. Kehoe ◽  
D. Thapi ◽  
N. Rosales ◽  
X. Ma ◽  
...  

21057 Background: The MUC16 gene encodes the CA125 ovarian cancer antigen and may play a role in invasion. The aim of this study is to investigate the properties of MUC16 in vitro. Methods: PCR was used to create a DNA construct, MUC16–1R-GFP, containing all of the MUC 16 sequence proximal to the second cysteine loop repeat and a GFP-vector construct. SKOv-3 and T-80 cell lines were selected because they are negative for immunologically active CA125. Transfections were performed utilizing the phrGFP II C vector system. Stable transfectants were sorted for GFP by FACS and were grown as populations. The growth rate of the transfected populations were compared to vector only. Periodically the stable transfectants were analyzed by FACS for GFP and OC125 mAb. The in vitro invasive potential was examined, using a Matrigel® invasion assay. RT PCR was used to examine the effect of MUC16 constructs for a panel of invasion focused genes. Immunoblotting was performed on the 1R protein and probed for all genes that were significantly changed on RT PCR. Results: The SKOv-3 1R transfected cell lines produce measurable CA125 into the cell culture medium (4–10 U/mL) while T-80 1R cell lines did not. Analysis of the in vitro growth rate did not demonstrate any difference between the transfectant and vector only cell lines. The 1R-GFP transfected lines showed MUC16 cell surface expression by FACS analysis. Invasion assay of the MUC16 transfectants demonstrated substantially more invasive potential than vector only (SKOV-3: 36% vs. 15% invasion; T-80: 35% vs. 23% invasion). Several transcripts associated with invasion and metastasis were up-regulated 3–9 fold including CDH1, FN1, IL1B, MMP7 and MMP9. Transcripts for the tyrosine kinases SYK and HTATIP2 were down-regulated 16–20 fold respectively. Western immunoblotting confirmed the RT PCR findings. Conclusions: The1R-GFP construct did not alter the growth rate of transfectants in vitro; however; the SKOV-3 1R and T-80 1R cell line did have substantially more invasive potential than vector only. Five transcripts associated with invasion were up-regulated, and 2 transcripts for kinases were down-regulated in the transfected cell lines. These data supports an association between MUC 16 and invasive potential. No significant financial relationships to disclose.


2011 ◽  
Vol 207 (7) ◽  
pp. 417-422 ◽  
Author(s):  
Kazuhiro Yoshitani ◽  
Akira Kido ◽  
Kanya Honoki ◽  
Manabu Akahane ◽  
Hiromasa Fujii ◽  
...  

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