| 1. |
- Dabestani, Saeed, et al.
(author)
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Local treatments for metastases of renal cell carcinoma: a systematic review
- 2014
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In: The Lancet Oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 15:12, s. 549-561
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Research review (peer-reviewed)abstract
- Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.
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| 2. |
- Ekman, Mari, et al.
(author)
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Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.
- 2012
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In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 683:1-3, s. 238-245
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Journal article (peer-reviewed)abstract
- Caveolae are 50-100nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M(3) receptors and the K(ATP) channel subunit Kir6.1 are associated with human detrusor caveolae, and to pharmacologically assess the relevance of this organization for contractility. Detrusor strips were dissected and used in ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by cholesterol desorption using mβcd (methyl-β-cyclodextrin). Mβcd disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of the concentration-response curve for the muscarinic receptor agonist carbachol. The effect of mβcd was inhibited by the K(ATP) blockers glibenclamide, repaglinide and PNU-37883, and it was mimicked by the K(ATP) activator levcromakalim. Immunoelectron microscopy showed muscarinic M(3) receptors and Kir6.1 to be enriched in caveolae. In conclusion, pharmacological K(ATP) channel inhibition antagonizes the effect of caveolae disruption on muscarinic contractility in the human detrusor, and the K(ATP) channel subunit Kir6.1 co-localizes with M(3) receptors in caveolae.
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