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- Mlecnik, B, et al.
(författare)
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Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I–III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I–III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10–4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.
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| 3. |
- Mlecnik, B, et al.
(författare)
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Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
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| 5. |
- Qin, Yue, et al.
(författare)
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A multi-scale map of cell structure fusing protein images and interactions
- 2021
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 600:7889, s. 536-
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Tidskriftsartikel (refereegranskat)abstract
- The cell is a multi-scale structure with modular organization across at least four orders of magnitude(1). Two central approaches for mapping this structure-protein fluorescent imaging and protein biophysical association-each generate extensive datasets, but of distinct qualities and resolutions that are typically treated separately(2,3). Here we integrate immunofluorescence images in the Human Protein Atlas(4) with affinity purifications in BioPlex(5) to create a unified hierarchical map of human cell architecture. Integration is achieved by configuring each approach as a general measure of protein distance, then calibrating the two measures using machine learning. The map, known as the multi-scale integrated cell (MuSIC 1.0), resolves 69 subcellular systems, of which approximately half are to our knowledge undocumented. Accordingly, we perform 134 additional affinity purifications and validate subunit associations for the majority of systems. The map reveals a pre-ribosomal RNA processing assembly and accessory factors, which we show govern rRNA maturation, and functional roles for SRRM1 and FAM120C in chromatin and RPS3A in splicing. By integration across scales, MuSIC increases the resolution of imaging while giving protein interactions a spatial dimension, paving the way to incorporate diverse types of data in proteome-wide cell maps.
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| 6. |
- Keegan, Kevin L., et al.
(författare)
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Towards resolving and redefining Amphipyrinae (Lepidoptera, Noctuoidea, Noctuidae) : a massively polyphyletic taxon
- 2019
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Ingår i: Systematic Entomology. - : Wiley. - 0307-6970 .- 1365-3113. ; 44:2, s. 451-464
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Tidskriftsartikel (refereegranskat)abstract
- Amphipyrinae have long been a catchall taxon for Noctuidae, with most members lacking discernible morphological synapomorphies that would allow their assignment to one of the many readily diagnosable noctuid subfamilies. Here data from seven gene regions (> 5500 bp) for more than 120 noctuid genera are used to infer a phylogeny for Amphipyrinae and related subfamilies. Sequence data for 57 amphipyrine genera – most represented by the type species of the genus – are examined. We present here the first large-scale molecular phylogenetic study of Amphipyrinae and the largest molecular phylogeny of Noctuidae to date; several proposed nomenclatural changes for well-supported results; and the identification of areas of noctuid phylogeny where greater taxon sampling and/or genomic-scale data are needed. Adult and larval morphology, along with life-history traits, for taxonomic groupings most relevant to the results are discussed. Amphipyrinae are significantly redefined; many former amphipyrines, excluded as a result of these analyses, are reassigned to other noctuid subfamily-level taxa. Four genera, Chamaeclea Grote, Heminocloa Barnes & Benjamin, Hemioslaria Barnes & Benjamin and Thurberiphaga Dyar, are transferred to the tribe Chamaecleini Keegan & Wagner tribe n. in Acontiinae. Stiriina is elevated to Stiriinae rev. stat., Grotellina is elevated to Grotellinae rev. stat. and Annaphilina is elevated to Annaphilini rev. stat. Acopa Harvey is transferred to Bryophilinae, Aleptina Dyar is transferred to Condicinae, Leucocnemis Hampson and Oxycnemis gracillinea (Grote) are transferred to Oncocnemidinae, Nacopa Barnes & Benjamin is transferred to Noctuinae and Narthecophora Smith is transferred to Stiriinae. Azenia Grote (and its subtribe Azeniina), Cropia Walker, Metaponpneumata Möschler, Sexserrata Barnes & Benjamin and Tristyla Smith are transferred to Noctuidae incertae sedis. Hemigrotella Barnes & McDunnough (formerly in subtribe Grotellina) is retained in Amphipyrinae. Argentostiria Poole and Bistica Dyar are retained in Stiriini but removed from incertae sedis position. This published work has been registered on ZooBank: http://zoobank.org/urn:lsid:zoobank.org:pub:4A140782-31BA-445A-B7BA-6EAB98ED43FA.
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| 9. |
- Hervey-Jumper, Shawn L, et al.
(författare)
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Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:11, s. 2029-2042
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Tidskriftsartikel (refereegranskat)abstract
- In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible.In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR.Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis.Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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| 10. |
- Keegan, Kevin, et al.
(författare)
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Toward a Stable Global Noctuidae (Lepidoptera) Taxonomy
- 2021
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Ingår i: Insect Systematics and Diversity. - : Oxford University Press (OUP). - 2399-3421. ; 5:3, s. 1-24
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Tidskriftsartikel (refereegranskat)abstract
- Noctuidae are one of the world's most diverse, ecologically successful, and economically important animal lineages with over 12,000 species in ∼1,150 genera. We inferred a phylogeny using eight protein-coding genes for the global fauna, greatly expanding upon previous attempts to stabilize Noctuidae higher classification by sampling 341 genera (nearly half represented by their type species) representing 70/76 widely recognized family-group taxa: 20/21 subfamilies, 32/35 tribes, and 18/20 subtribes. We evaluated 17 subfamily-level taxa in detail, discussing adult and larval morphology, life histories, and taxonomic implications of our results. We significantly alter concepts of Acontiinae, Condicinae, Eustrotiinae, Metoponiinae, and Stiriinae. Our results supported recognition of two new subfamilies: Cobubathinae Wagner & Keegan, 2021 subf. nov. and Cropiinae Keegan & Wagner, 2021 subf. nov. Other nomenclatural changes we made are as follows. We moved: 'Acontia' viridifera (Hampson, 1910), 'Azenia' virida Barnes and McDunnough, 1916, Aleptinoides, Austrazenia, Chalcoecia, Megalodes, and Trogotorna to Chamaecleini in Acontiinae; Apaustis to, and reinstated Emmelia as a valid genus in Acontiinae; Allophyes and Meganephria to Cuculliinae; 'Plagiomimicus' navia (Harvey, 1875), Airamia, Alvaradoia, Hypoperigea, Neotarache, and Mesotrosta to Condicinae; Axenus, Azenia, Metaponpneumata, Sexserrata, and Tristyla to Metoponiinae; 'Paramiana' canoa (Barnes, 1907) to Noctuinae; Aucha, Cobubatha, and Tripudia to Cobubathinae; Anycteola and Supralathosea to Oncocnemidinae; Cropia to Cropiinae; Desmoloma to Dyopsinae; Eviridemas and Gloanna to Bryophilinae; Fota and Stilbia to Stiriinae; and Copibryophila, Homolagoa, and Tyta to Noctuidae incertae sedis. We conclude with discussion of instances where current understanding of noctuid biogeography and life histories were changed by our results.
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