scholarly journals All bone metastases are not created equal: Revisiting treatment resistance in renal cell carcinoma

2021 ◽  
Vol 31 ◽  
pp. 100399
Author(s):  
Ava Brozovich ◽  
Benjamin Garmezy ◽  
Tianhong Pan ◽  
Liyun Wang ◽  
Mary C. Farach-Carson ◽  
...  
Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Tomonori Sato ◽  
Yoshihide Kawasaki ◽  
Masamitsu Maekawa ◽  
Shinya Takasaki ◽  
Kento Morozumi ◽  
...  

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.


1984 ◽  
Vol 10 (6) ◽  
pp. 380-384 ◽  
Author(s):  
U. Zwergel ◽  
W. Knopp ◽  
H.U. Braedel

2020 ◽  
Vol 49 (1) ◽  
pp. 11-17
Author(s):  
Marco Montella ◽  
Renato Franco ◽  
Gabriella Aquino ◽  
Andrea Ronchi ◽  
Federica Zito Marino ◽  
...  

2017 ◽  
Vol 15 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Sarathi Kalra ◽  
Jonathan Verma ◽  
Bradley J. Atkinson ◽  
Surena F. Matin ◽  
Christopher G. Wood ◽  
...  

Cancer ◽  
2020 ◽  
Vol 126 (S9) ◽  
pp. 2079-2085 ◽  
Author(s):  
Yi Dong ◽  
Zheng Wang ◽  
Xin Lu ◽  
Zhenjie Wu ◽  
Zongqin Zhang ◽  
...  

2020 ◽  
Vol 51 (1) ◽  
pp. 100-105
Author(s):  
Hideyuki Harada ◽  
Naoto Shikama ◽  
Hitoshi Wada ◽  
Nobue Uchida ◽  
Miwako Nozaki ◽  
...  

Abstract Purpose Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results Twenty-seven patients were included in the study. The median age was 65 (range, 50–84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0–34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2–89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.


2004 ◽  
Vol 10 (18) ◽  
pp. 6397S-6403S ◽  
Author(s):  
Allan Lipton ◽  
Alejandro Colombo-Berra ◽  
Ronald M. Bukowski ◽  
Lee Rosen ◽  
Ming Zheng ◽  
...  

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