| 1. |
- Keilholz, U., et al.
(författare)
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ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1435-1448
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment for brain metastases. The expert panel was divided into five working groups to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of metastatic melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 2. |
- Michielin, O., et al.
(författare)
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ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:11, s. 1449-1461
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.
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| 3. |
- Bjursten, Lars Magnus, et al.
(författare)
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Joint inflammation in rabbits induced by preformed immune complexes
- 1981
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Ingår i: International Archives of Allergy and Applied Immunology. - 0020-5915. ; 64:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- The rabbit knee joint was used to evaluate the inflammatory properties of immune complexes with different contents of antigen. Immune complexes made in vitro with antiserum from hyperimmunized rabbits and bovine serum albumin as antigen were injected into the joints. The reactivity of the individual animal was established by injection of normal rabbit serum into the contralateral joint. The number of leukocytes washed out from the joints at fixed intervals was used as a measure of the inflammatory properties of the immune complexes. With immune complexes formed at antigen excess the highest numbers of leukocytes, with a predominance of granulocytes, were found after 6 h of exposure. However, these complexes gave only weak complement activation in vitro, measured with a hemolysis assay. Complexes formed at optimal precipitation proportions gave high complement activation in vitro but only a small number of leukocytes in the joints at 6 h exposure. This finding may be explained by a rapid phagocytosis of the latter complexes while complexes formed at antigen excess are not readily phagocytized. This hypothesis is supported by the observation that higher leukocyte counts were found after shorter exposure times to complexes formed at optimal precipitation proportions than after exposure to complexes with antigen excess.
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| 4. |
- Bjursten, Lars Magnus, et al.
(författare)
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The kinetics of leucocyte migration into rabbit knee joints elicited by preformed immune complexes with different in vitro characteristics
- 1983
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Ingår i: Immunology. - 0019-2805. ; 49:2, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Immune complexes were formed in vitro with antibodies obtained from rabbits immunized with bovine serum albumin in Freund's complete (FCA) or incomplete (FIA) adjuvant. The antibodies were mixed with different amounts of antigen. Immune complexes formed at maximum precipitation proportions were efficient in complement activation, whereas immune complexes formed at antigen excess had weak complement-activating properties. When injected into rabbit knee joints, the immune complexes formed at maximum precipitation proportions with FCA or FIA antibodies caused a moderate leucocyte migration into the joints with maximum cell counts 6-8 hr after injection. Injection into the joints of immune complexes formed with FCA antibodies at antigen excess induced a pronounced leucocyte migration with maximum numbers 18 hr after injection. Immunofluorescent studies indicated that these immune complexes became associated with the leucocyte membrane, whereas immune complexes formed at maximum precipitation proportions were found in the leucocyte granulae, indicating that only the complement-activating immune complexes were efficiently eliminated.
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| 5. |
- Blomqvist, G, et al.
(författare)
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Differences in lodgement of tumour cells in muscle and liver
- 1988
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Ingår i: Clinical and Experimental Metastasis. - 1573-7276. ; 6:4, s. 285-289
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Tidskriftsartikel (refereegranskat)abstract
- Differences in the lodgement of circulating tumour cells in various organs are considered an important factor in metastatic organ selection. The present vital microscopic studies show that the pattern of intravascular arrest of tumour cells in muscle after intra-arterial injection is similar to that observed earlier, in the liver, after intraportal injection. However, parallel isotope studies on the lodgement process (at 5 min and 3 h after injection) showed that the tumour cells trapped in the muscle microvasculature were destroyed at a higher rate than in the liver. Tumour cells kept in test tubes, and thus not being subjected to the shearing forces of the circulation, had a higher survival rate than cells trapped in the muscle. The results indicate that stronger retardation forces acting on the tumour cells in muscle (arterial dissemination) than in the liver (venous dissemination) may be one mechanism behind the increased tumour cell destruction in muscle.
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| 6. |
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| 7. |
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| 8. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 9. |
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| 10. |
- Naeser, Ylva, et al.
(författare)
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TRIM study protocol - a prospective randomized multicenter Trial to assess the Role of Imaging during follow-up after radical surgery of stage IIB-C and III cutaneous malignant Melanoma
- 2020
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3years by clinical examinations only.MethodsThe TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is >1300. Patients are randomized to clinical examinations for 3years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group.DiscussionThis is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM.ResultsThe first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden.Trial registrationClinicalTrials.gov, NCT 03116412. Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412
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| 11. |
- Rosentau, A., et al.
(författare)
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A Holocene relative sea-level database for the Baltic Sea
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 266
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Tidskriftsartikel (refereegranskat)abstract
- We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5-6.5 ka BP which is consistent with the end of the final melting of the Laurentide Ice Sheet. Comparisons of RSL data with GIA predictions including global ICE-5G and ICE-6G_C ice histories show good fit with RSL data from the regions with negative tendencies, whereas in the transitional areas in the eastern Baltic, predictions for the mid-Holocene clearly overestimate the RSL and fail to recover the midHolocene RSL highstand derived from the proxy reconstructions. These results motivate improvements of ice-sheet and Earth-structure models and show the potential and benefits of the new compilation for future studies. (C) 2021 The Authors. Published by Elsevier Ltd.
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| 12. |
- Thomsen, P, et al.
(författare)
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Acute synovitis induced by preformed immune complexes
- 1986
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 15:2, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- The morphology of acute immune complex (IC) elicited synovitis in rabbit knee joints was studied, as well as IC-induced leukocyte activation in vivo and in vitro. Acute synovitis was induced by intra-articular injection of in vitro preformed, complement activating bovine serum albumin (BSA)-anti-BSA IC. Within 30 min, migration of polymorphonuclear granulocytes (PMNGs) was observed. Scanning electron microscopy showed that adhering, apparently activated leukocytes were attached to the synovial lining, often forming clusters. Phagocytosis of IC was evident, as immunoglobulins were detected within the leukocyte cytoplasm by the direct immunofluorescence technique. At the peak accumulation of PMNGs, focal erosions of the synovial lining were observed. Later, monocytes and macrophages appeared and degenerated PMNGs were found, sometimes within the cytoplasm of large macrophages. Chemiluminescence experiments showed a maximum in vitro activation of leukocytes by complement activating IC formed near optimal precipitation proportions and in slight antigen excess, whereas IC in large antigen excess gave a smaller and later response.
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| 13. |
- Thomsen, P, et al.
(författare)
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Inhibitory effect of honey bee venom on immune complex mediated leukocyte migration into rabbit knee-joints
- 1984
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Ingår i: Agents and Actions. - 0065-4299. ; 14:5-6, s. 662-666
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Tidskriftsartikel (refereegranskat)abstract
- The anti-inflammatory effect of purified honey bee venom (HBV) was studied using a recently described animal model in which preformed immune complexes were injected into rabbit knee-joints. As little as a single injection of 1.2 micrograms HBV/kg body weight subcutaneously significantly reduced the immune complex induced joint inflammation as measured by reduction in leukocyte counts in the joint fluid. This decrease was obvious 3 and 6 but not 9 hours after induction of the inflammation. There was no significant effect on leukocyte random migration, chemotactic responsiveness or phagocytosis, indicating that HBV did not interfere with normal phagocyte motility and ingestion. The modifying effects by HBV on the inflammatory response to immune complexes in vivo is most likely due to interference with other components of the inflammatory response.
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| 14. |
- van Akkooi, Alexander C. J., et al.
(författare)
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Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC)
- 2022
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Ingår i: ANNALS OF SURGICAL ONCOLOGY. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 29:6, s. 3694-3708
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Tidskriftsartikel (refereegranskat)abstract
- Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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