1. |
|
|
2. |
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
- Dufies, M, et al.
(författare)
-
Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma
- 2021
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 166-
-
Tidskriftsartikel (refereegranskat)abstract
- Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
|
|
7. |
|
|
8. |
|
|
9. |
|
|
10. |
|
|
11. |
|
|
12. |
|
|
13. |
- Verhoest, G, et al.
(författare)
-
Predictive factors of chronic kidney disease stage V after partial nephrectomy in a solitary kidney : a multi-institutional study
- 2014
-
Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 32:1, s. 28.e21-28.e26
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Partial Nephrectomy (PN) in a solitary kidney is at risk of chronic kidney disease (CKD) stage V and/or haemodialysis (HD). Our objective was to determine predictive factors of CKD stage V in this population. MATERIAL & METHODS: Data from 300 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics and renal function before surgery were analyzed. Patients with and without CKD stage V (defined as MDRD<15ml/min) were compared using χ2 and Student-t tests for qualitative and quantitative variables, respectively. Predictive factors of CKD stage V were evaluated with a multivariable analysis using a Cox regression model. RESULTS: Median age and BMI were 63 years old and 26kg/m², respectively. Most of the patients (65%) were male with an anatomic solitary kidney (88.3%). Median tumor size was 4cm and 98% were malignant tumors. Median operative time, blood loss and clamping time were 180min, 350ml and 20min respectively. Renal cooling was used in 19.3% and clamping of the pedicle was performed in 61.6%. Twenty five patients (8.5%) presented post operative CKD stage V at last follow-up and 18 underwent HD (6%) post-operatively because of acute renal insufficiency. There was no difference between CKD stage V and non CKD stage V patients concerning Charlson index, operative time (180min vs 179min, p= 0.39), blood loss (475ml vs 350ml, p= 0.51), use of renal cooling and type of clamping. Patients with CKD stage V were older (70 vs 63 years old, p= 0.005), had a lower baseline renal function (clearance MDRD 41 vs. 62ml/min, p<0.0001) and an increased tumor size (p= 0.02). Complications occurred in 91 patients (30%) with 16% of minor (Clavien 1-2) and 14% of major (Clavien>2) complications, respectively. In multivariable analysis, baseline MDRD, BMI, and the occurrence of a minor complication were independent predictive factors of post operative CKD stage V. CONCLUSION: PN in a solitary kidney is at risk of post-operative CKD stage V and HD. Pre-operative altered renal function and post operative complications are the main predictive factors of permanent CKD stage V.
|
|