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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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| 2. |
- Eldh, Maria, 1980, et al.
(författare)
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MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
- 2014
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Ingår i: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
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| 3. |
- Olofsson Bagge, Roger, 1978, et al.
(författare)
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Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities - Long-term follow-up of a randomised trial
- 2014
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Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 30:5, s. 295-298
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Isolated limb perfusion (ILP) is a treatment option most commonly used in the treatment of melanoma in-transit metastases of the extremities. The principle idea is to surgically isolate a region of the body and then deliver a high concentration of a chemotherapeutic agent together with hyperthermia. There have been three randomised trials exploring whether adjuvant ILP to patients with recurrent or high-risk primary melanomas increases survival; one of these trials has now been updated with a 25-year follow-up. Methods: The original study randomised 69 patients (between 1981 and 1989) with their first satellite or in-transit recurrence to either wide excision (WE group, n=36 patients) or to WE and adjuvant ILP (WE + ILP group, n=33 patients). Follow-up data 25 years later concerning survival and cause of death was retrieved from the Swedish National Cause of Death Register. Results: In the WE + ILP group there were 20 deaths (61%) due to melanoma compared with 26 deaths (72%) in the WE group (p=0.31). Median melanoma-specific survival was 95 months for WE + ILP compared to 38 months for the WE group, an almost 5 year benefit without statistical significance (p=0.24). Discussion: There is no evidence that adjuvant ILP prolongs survival in patients with high-risk or recurrent melanoma; however, the existing randomised trials are largely underpowered to detect such a difference. New studies are exploring systemic immunological effects of ILP, and a combination of regional therapy and immunotherapy may serve as a rationale for new trials using ILP in the future.
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| 4. |
- Ståhl, Ingun, 1984, et al.
(författare)
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Feasibility study of intraoperative gamma probes for determining 177Lu-octreotate activity concentration in vivo
- 2014
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Ingår i: SWE-RAYS (Swedish Radiation Research Association for Young Scientists) 3e årliga workshop, Malmö..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION 177Lu-octreotate is a good alternative for treatment of neuroendocrine tumors, with primarily kidneys as limiting organs. The development of a new treatment method using 177Lu-octreotate for liver metastases is under progress at our institute. This treatment method requires accurate activity concentrations of 177Lu-octreotate in tumor and normal tissues in vivo during surgery. Intraoperative gamma probes are mainly used for radio-guided surgery, where diagnostic radiopharmaceuticals including e.g. 99mTc or 111In are frequently used. The aim of this study was to investigate the possibility of using an intraoperative gamma probe for determining 177Lu-octreotate activity concentration in vivo. METHODS The performance of two intraoperative gamma probes was evaluated by determining the range for linear response and the spatial resolution (FWHM) at different depths using different sources containing 177Lu. To illustrate clinical conditions and further explore the ability of the gamma probes to distinguish tumor from normal tissues, measurements using various phantoms were performed. Tumor phantoms, made of agarose gel spheres (5-20 mm diameter) contained a high activity concentration of 177Lu, and were placed in a gel background containing a lower activity concentration of 177Lu, simulating tumors in a normal tissue. RESULTS A linear response (within ±10 %) was found for activities in the range of 1-30 MBq. The spatial resolution (FWHM) increased with depth (0 to 80 mm) from about 10 to 70 mm. The tumor phantom measurements showed high ratios between count rates measured over the gel spheres and the background gel, which indicates a good ability to distinguish between tumor and normal tissue. CONCLUSION The results in the present study imply that an intraoperative gamma probe could be used for measurements of activity concentration of 177Lu-octreotate in tissues in vivo.
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