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- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
- 2014
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
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Tidskriftsartikel (refereegranskat)abstract
- The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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- Mjörnstedt, L., et al.
(författare)
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Improved Renal Function After Early Conversion From a Calcineurin Inhibitor to Everolimus : a Randomized Trial in Kidney Transplantation
- 2012
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 12:10, s. 2744-2753
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Tidskriftsartikel (refereegranskat)abstract
- In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNI-treated controls but discontinuations and BPAR were more frequent.
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