scholarly journals Combined BRAFV600E- and SRC-inhibition induces apoptosis, evokes an immune response and reduces tumor growth in an immunocompetent orthotopic mouse model of anaplastic thyroid cancer

Oncotarget ◽  
2014 ◽  
Vol 5 (12) ◽  
pp. 3996-4010 ◽  
Author(s):  
Pierre Vanden Borre ◽  
Viswanath Gunda ◽  
David G. McFadden ◽  
Peter M. Sadow ◽  
Shohreh Varmeh ◽  
...  
Surgery ◽  
2020 ◽  
Vol 167 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Abha Aggarwal ◽  
Zuliang Yuan ◽  
Justine A. Barletta ◽  
Jochen H. Lorch ◽  
Matthew A. Nehs

Surgery ◽  
2010 ◽  
Vol 148 (6) ◽  
pp. 1154-1162 ◽  
Author(s):  
Matthew A. Nehs ◽  
Sushruta Nagarkatti ◽  
Carmelo Nucera ◽  
Richard A. Hodin ◽  
Sareh Parangi

Surgery ◽  
2021 ◽  
Author(s):  
Bixiao Zhao ◽  
Abha Aggarwal ◽  
Jessica A. Marshall ◽  
Justine A. Barletta ◽  
Marie F. Kijewski ◽  
...  

2019 ◽  
Vol 26 (6) ◽  
pp. 551-563 ◽  
Author(s):  
Shikha Saini ◽  
Lakshmi Sripada ◽  
Kiara Tulla ◽  
Guilin Qiao ◽  
Nicholas Kunda ◽  
...  

ATC is an aggressive disease with limited therapeutic options due to drug resistance. TRAIL is an attractive anti-cancer therapy that can trigger apoptosis in a cancer cell-selective manner. However, TRAIL resistance is a major clinical obstacle for its use as a therapeutic drug. Previously, we demonstrated that MADD is a cancer cell pro-survival factor that can modulate TRAIL resistance. However, its role, if any, in overcoming TRAIL resistance in ATC is unknown. First, we characterized ATC cell lines as either TRAIL resistant, TRAIL sensitive or moderately TRAIL sensitive and evaluated MADD expression/cellular localization. We determined the effect of MADD siRNA on cellular growth and investigated its effect on TRAIL treatment. We assessed the effect of combination treatment (MADD siRNA and TRAIL) on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. The effect of combination treatment on tumor growth was assessed in vivo. We found increased levels of MADD in ATC cells relative to Nthy-ori 3-1. MADD protein localizes in the cytosol (endoplasmic reticulum and Golgi body) and membrane. MADD knockdown resulted in spontaneous cell death that was synergistically enhanced when combined with TRAIL treatment in otherwise resistant ATC cells. Combination treatment resulted in a significant reduction in MMP and enhanced generation of ROS indicating the putative mechanism of action. In an orthotopic mouse model of TRAIL-resistant ATC, treatment with MADD siRNA alone reduced tumor growth that, when combined with TRAIL, resulted in significant tumor regressions. We demonstrated the potential clinical utility of MADD knockdown in sensitizing cells to TRAIL-induced apoptosis in ATC.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3007
Author(s):  
Chen Chen ◽  
Jens Neumann ◽  
Florian Kühn ◽  
Serene M. L. Lee ◽  
Moritz Drefs ◽  
...  

Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally invasive model using murine colonoscopy. CT26 and MC38 CRC cells of different concentrations were injected into BALB/C and C57BL/6J mice, respectively. Follow-up endoscopies were performed to assign an endoscopic score to tumor growth. Gross autopsy, histologic and immuno-histochemical evaluation, and immune scoring were performed. To describe the learning curve of the procedures, a performance score was given. Local tumor growth with colorectal wall infiltration, luminal ulceration, the presence of tumor-infiltrating lymphocytes, lympho-vascular invasion, and early spontaneous lymph node, peritoneal, and hepatic metastases were observed. The tumors showed cytoplasmic immuno-staining for CK20. Compared to the MC38/C57BL/6J model, tumorigenicity and immunogenicity of the CT26/BALB/C model were higher. Tumor volume correlated with the endoscopic score. This endoscopy-guided orthotopic mouse model is easy to learn and quick to establish. It features early metastasis and enables the study of interactions with the immune system. When specific cell concentrations and cell lines are applied, controlled local tumor growth and metastasis can be achieved within short observation periods.


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 31 (7) ◽  
pp. 1284-1291 ◽  
Author(s):  
Celine J. Guigon ◽  
Laura Fozzatti ◽  
Changxue Lu ◽  
Mark C. Willingham ◽  
Sheue-yann Cheng

2014 ◽  
Vol 136 (11) ◽  
pp. 2556-2565 ◽  
Author(s):  
Dong Zhao ◽  
Xi-Dai Long ◽  
Tian-Fei Lu ◽  
Tao Wang ◽  
Wei-Wei Zhang ◽  
...  

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