Abstract A11: Using a patient-derived orthotopic xenograft (PDOX) model to screen drugs targeting renal cell carcinoma (RCC) metastasis: A personalized therapeutic strategy

Author(s):  
Jessie Gills ◽  
Ravan Moret ◽  
Xin Zhang ◽  
Ashley Richman ◽  
John Nelson ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Ling Gao ◽  
Xian Shao ◽  
Qingqing Yue ◽  
Weifei Wu ◽  
Xuejuan Yang ◽  
...  

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15084-e15084
Author(s):  
Joann Hsu ◽  
Sumanta Kumar Pal ◽  
Przemyslaw Twardowski ◽  
Courtney Carmichael ◽  
Junmi Saikia ◽  
...  

e15084 Background: Sarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. Methods: From an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, MSKCC risk criteria, and the nature of systemic therapy given. Available tissue from 11 of these patients has been identified for correlative studies to assess markers of epithelial to mesenchymal transition (EMT). Tissue will be obtained from a cohort of patients matched for age and MSKCC risk status (but lacking a sarcomatoid component) for comparison. Results: Of the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95%CI 6.9-22.0). By MSKCC status, patients with poor-risk disease had a median OS of 4.7 months, as compared to 20.1 months for patients with intermediate-risk disease (HR 0.02, 95%CI 0.003-0.15; P=0.0001). Survival in subgroups stratified by the Heng criteria will be presented at the meeting. There was no significant difference in survival in patients with sarcomatoid predominant disease (>20%) vs non-predominant disease (HR 0.62, 95%CI 0.23-1.65; P=0.34), nor was there a difference amongst patients who received targeted therapies vs non-targeted therapies (HR 1.0, 95%CI 0.61-1.40; P=0.36). Correlative analyses are ongoing, and will be presented at the meeting. Conclusions: As compared to previous retrospective series (Golshayan et al JCO 2009) and prospective trials (Haas et al Med Oncol 2011) assessing patients with sarcomatoid mRCC, the survival in our cohort was substantially prolonged. Further clinical and translational studies are needed to refine current prognostic schema for this disease, and to define the optimal therapeutic strategy.


2015 ◽  
Author(s):  
Sheng-Yu Ku ◽  
Swathi Ramakrishnan ◽  
Eric Ciamporcero ◽  
Bo Xu ◽  
Gissou Azabdaftari ◽  
...  

2012 ◽  
Vol 10 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Aline Guillot ◽  
Antonin Levy ◽  
Cécile Pacaut ◽  
Olivier Collard ◽  
Christophe Massard ◽  
...  

2016 ◽  
Author(s):  
Sebastian K. Frees ◽  
Igor Moskalev ◽  
Betty Zhou ◽  
Peter Raven ◽  
Claudia Chavez-Munoz ◽  
...  

2017 ◽  
Vol 111 ◽  
pp. 117-123 ◽  
Author(s):  
Olga Martínez-Sáez ◽  
Pablo Gajate Borau ◽  
Teresa Alonso-Gordoa ◽  
Javier Molina-Cerrillo ◽  
Enrique Grande

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Yasuhiro Inoue ◽  
Hiroshi Takahashi ◽  
Yuichiro Yokoyama ◽  
Yasuaki Iida ◽  
Katsunori Fukutake ◽  
...  

Metastatic renal cell carcinoma of the bone occurs at a high rate, and the prognosis is poor. In general, totalen blocspondylectomy is considered when there is only one vertebral metastasis and the primary disease is treated. However, palliative surgery is selected when the primary disease is not being treated or metastasis occurs to an important organ. We encountered a patient in whom lung and vertebra metastases were already present at the time of the first examination at our department and the prognosis was considered poor. However, molecular targeted therapy was markedly effective and enabled 2-stage totalen blocspondylectomy. As of one year after totalen blocspondylectomy, the condition has improved to cane gait, and surgery for lung metastasis is planned. Molecular target drugs might markedly change the current therapeutic strategy for renal cell carcinoma.


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