| 1. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Block, Mattias, 1968, et al.
(författare)
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Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis.
- 2016
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2016
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. Material and Methods. Surgical whole intestinal wall colon specimens from UC patients (n = 22) and controls (n = 10) were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. Results. Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. Conclusion. Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation.
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| 3. |
- Block, Michael, et al.
(författare)
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Research of the NUSTAR departments : SHE departments and HIM SHE section
- 2020
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Ingår i: GSI-FAIR Scientific Report 2019 : An overview of the 2019 achievements in science and technology - An overview of the 2019 achievements in science and technology. ; , s. 53-59
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The SHE departments devoted to the research of superheavy elements, operate the recoil separators SHIP and TASCA and their ancillary installations including SHIPTRAP and a laser spectroscopy setup at SHIP as well as chemistry and nuclear spectroscopy setups at TASCA. In 2019, the activities at GSI focused on the UNILAC beamtime within the FAIR Phase-0 program and on the analysis of data obtained in prior beamtimes. At HIM, the advancement of actinide sample preparation, manipulation, and characterization for various applications was most central. In addition, technical developments, for example for single-ion mass measurements, have been performed.
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| 4. |
- Cederfur, Cecilia, et al.
(författare)
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Glycoproteomic identification of galectin-3 and -8 ligands in bronchoalveolar lavage of mild asthmatics and healthy subjects.
- 2012
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Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002 .- 0304-4165. ; 1820:9, s. 1429-1436
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Galectins, a family of small carbohydrate binding proteins, have been implicated in regulation of inflammatory reactions, including asthma and fibrosis in the lungs. Galectins are found in cells of the airways and in airway secretions, but their glycoprotein ligands there have only been studied to a very limited extent. METHODS: Bronchoalveolar lavage (BAL) fluid from mild asthmatics and healthy volunteers were fractionated by affinity chromatography on the immobilized galectins. Total (10-30μg) and galectin bound (~1-10μg) protein fractions were identified, quantified and compared using shot-gun proteomics and spectral counts. RESULTS: About 175 proteins were identified in unfractionated BAL-fluid, and about 100 bound galectin-3 and 60 bound galectin-8. These included plasma glycoproteins, and typical airway proteins such as SP-A2, PIGR and SP-B. The concentration of galectin-binding proteins was 100-300 times higher than the concentration of galectins in BAL. CONCLUSION: The low relative concentration of galectins in BAL makes it likely that functional interactions with glycoproteins occur at sites rich in galectin, such as cells of the airways, rather than the extracellular fluid itself. The profile of galectin bound proteins differed between samples from asthma patients and healthy subjects and correlated with the presence of fibroblasts or eosinophils. This included appearance of a specific galectin-8-binding glycoform of haptoglobin, previously shown to be increased in serum in other inflammatory conditions. GENERAL SIGNIFICANCE: It is technically feasible to identify galectin-binding glycoproteins in low concentration patient samples such as BAL-fluid, to generate biomedically interesting results. This article is part of a Special Issue entitled Glycoproteomics.
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| 5. |
- Holmberg, Carl Jacob, et al.
(författare)
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The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
- 2022
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Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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| 6. |
- Sarmiento Pico, Luis, et al.
(författare)
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Elucidating the nature of the proton radioactivity and branching ratio on the first proton emitter discovered 53mCo
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The observation of a weak proton-emission branch in the decay of the 3174keV 53mCo isomeric state marked the discovery of proton radioactivity in atomic nuclei in 1970. Here we show, based on the partial half-lives and the decay energies of the possible proton-emission branches, that the exceptionally high angular momentum barriers, lp = 9 and lp = 7, play a key role in hindering the proton radioactivity from 53mCo, making them very challenging to observe and calculate. Indeed, experiments had to wait decades for significant advances in accelerator facilities and multi-faceted state-of-the-art decay stations to gain full access to all observables. Combining data taken with the TASISpec decay station at the Accelerator Laboratory of the University of Jyväskylä, Finland, and the ACTAR TPC device on LISE3 at GANIL, France, we measured their branching ratios as bp1 = 1.3(1)% and bp2 = 0.025(4)%. These results were compared to cutting-edge shell-model and barrier penetration calculations. This description reproduces the order of magnitude of the branching ratios and partial half-lives, despite their very small spectroscopic factors.
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| 7. |
- Såmark-Roth, Anton, et al.
(författare)
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Spectroscopy along flerovium decay chains: Discovery of 280Ds and an excited state in 282Cn
- 2021
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Ingår i: Physical Review Letters. - 1079-7114. ; 126:3
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Tidskriftsartikel (refereegranskat)abstract
- A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions 48Ca+242Pu and 48Ca+244Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to 286Fl and 288Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α-particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely 282Cn. Spectroscopy of 288Fl decay chains fixed Qα=10.06(1) MeV. In one case, a Qα=9.46(1)-MeV decay from 284Cn into 280Ds was observed, with 280Ds fissioning after only 518 μs. The impact of these findings, aggregated with existing data on decay chains of 286,288Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.
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| 8. |
- 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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