321 research outputs found
Prognostic information from nonmalignant and malignant lymphocytes in follicular lymphoma in relation to therapy
Follicular lymphoma is the most common indolent lymphoma. It is composed of centrocytes and centroblasts, residing in follicles that also harbour nonmalignant immune and
stroma cells. Follicular lymphoma is graded according to the World Health Organization
criteria that are based on the frequency of centroblasts. There is consensus that grades 1 and
2 are indolent, but not whether grade 3 is aggressive. Differences between grades 3A and
3B are also unclear. The nonmalignant cells in the microenvironment interact with the
tumour cells and with each other. These interactions may be important for disease outcome.
Since the introduction of the therapeutic monoclonal anti-CD20 antibody rituximab, the
prognosis of follicular lymphoma has improved. It is likely that the mechanisms of rituximab affect and involve not only CD20+ follicular lymphoma cells but also the surrounding
as well as the systemic immune cells. The aim of this thesis was to identify biological
predictors for outcome in follicular lymphoma in relation to therapy.
In paper I, using flow cytometry, we reported that higher numbers of CD8+ T cells in diagnostic lymph nodes are an independent predictor of better overall and disease-specific
survival. This finding was reproduced in paper II in which computerised quantifications of
tissue microarrays were used for a unifying multivariate model. This model showed that
many cells in the microenvironment were independently important for outcome. Higher
levels of cells positive for CD8 (cytotoxic T cells), forkhead box protein 3 (regulatory T
cells) and programmed death-1 (PD-1+ T cells) correlated with good prognosis, but higher
levels of cells positive for CD4 (helper T cells) and CD68 (macrophages) with poor. The
best predictors for poor outcome were increasing CD4/CD8 and follicular/interfollicular
CD4 ratios, suggesting that outcome is influenced by the balance between detrimental
follicular B-helper and helper2 T-cells on one hand and favourable cytotoxic and helper1 T
cells on the other. In paper III we used prospectively recorded flow cytometry analyses
from two randomised trials where all patients received single rituximab with or without
interferon-α priming. T cells in tumours (both CD4+ and CD8+) were associated with fast
and good clinical responses to rituximab, while T cells in blood (both CD4+ and CD8+)
correlated with slower but good and sustained responses, and were more important for
survival. Interferon-α abrogated the dependence on high numbers of CD8+ cells (in both
blood and tumours) for good rituximab responses. In paper IV we reviewed the follicular
lymphoma grades in 828 patients with long follow-up times, of whom 40% received
upfront rituximab. Compared with grade 1â3A patients and independently of clinical
factors, grade 3B patients showed higher mortality but outcome was improved after upfront
anthracyclines. Grade 3B patients experienced no relapses or deaths beyond five years of
follow-up. Furthermore, patients with grade 3B were different in their clinical characteristics. In the entire population, patients with grade 3A had similar outcome as those with
grade 1â2. However, in patients given upfront rituximab-containing therapy, increasing
grades of 1, 2, and 3A correlated with better overall survival and time to treatment-failure,
independently of clinical factors.
We conclude that outcome in follicular lymphoma is determined by the balance between
competing immune cells in the microenvironment and by their interactions with each other
and with the tumour cells. Rituximab and interferon-α alter the prognostic properties of the
immune cells, and also involve systemic T cells that may be very important for disease
outcome. Grade 3B, or follicular large B-cell lymphoma, is a distinct, aggressive but
curable entity. Grades 1, 2 and 3A are indolent and incurable. Increasing grades predict
better outcome with rituximab therapy. Our findings suggest a future of personalised
therapy based on biological characteristics of the patients and of the tumours
Urban trees â for better or for worse : differences in regulating and supporting ecosystem services between broadleaved and conifer trees in the urban environment
TrĂ€d har en viktig roll i att klimatanpassa stĂ€der genom att leverera ekosystemtjĂ€nster. I nordiska stĂ€der planteras mest lövtrĂ€d eftersom det historiskt funnits ett kulturellt motstĂ„nd mot barrtrĂ€d. Flera barrtrĂ€d tĂ„l dock stadens ogĂ€stvĂ€nliga stĂ„ndort och eftersom de flesta barrtrĂ€den Ă€r stĂ€dsegröna kan de leverera ekosystemtjĂ€nster Ă„ret om. I denna uppsats undersöks skillnader mellan löv- och barrtrĂ€d utifrĂ„n sex reglerande och stödjande ekosystemtjĂ€nster med hjĂ€lp av en systematisk litteraturstudie. Resultaten visar att barrtrĂ€d, som har komplexare bladstruktur, större sammanlagd bladyta och stĂ€dsegrön krona kan vara effektivare pĂ„ ekosystemtjĂ€nsterna luftrening, dagvattenhantering och vindskydd. LövtrĂ€d kan, med bredare kronor och lövfĂ€llning, vara effektivare pĂ„ temperaturreglering. Kolupptagning/kolinlagring kan anses vara likvĂ€rdiga för löv- och barrtrĂ€d och i stĂ€llet bero pĂ„ andra faktorer sĂ„som trĂ€dets biomassa, tillvĂ€xthastighet och vĂ€xtbĂ€ddsförhĂ„llanden. För biologisk mĂ„ngfald med avseende pĂ„ habitat och föda för andra organismer kunde det konstateras att löv- och barrtrĂ€d fyller olika funktioner och dĂ€rför behövs bĂ„da trĂ€dslag i staden. Lokal artsammansĂ€ttning och om trĂ€den Ă€r inhemska eller inte kan dock anses vara viktigare faktorer för denna ekosystemtjĂ€nst. Resultatet indikerar att skillnaden mellan löv- och barrtrĂ€d Ă€r större för luftrening men mindre för dagvattenhantering i det syd- och mellansvenska klimatet Ă€n vad internationell forskning visar. För svenskt klimat Ă€r det framför allt rumslig komposition som avgör skillnaden i temperaturreglering och vindskydd. TrĂ€dets förmĂ„ga att leverera de sex undersökta ekosystemtjĂ€nsterna beror pĂ„ fler faktorer sĂ„som platsen, vĂ€xtbĂ€dd, skötsel, artsammansĂ€ttning, komposition, förekomst och Ă„lder (tid) och dessa bör tas i beaktning vid trĂ€dval. Denna uppsats redogör för vilka ekosystemtjĂ€nster man kan förvĂ€ntas fĂ„ frĂ„n löv- och barrtrĂ€d i stadsmiljö och kan vĂ€gleda till ett medvetet trĂ€dval.Trees play a significant role in climate adaptation by delivering ecosystem services. Broadleaved trees are commonly planted in Nordic cities because of the historic cultural resistance towards conifers. Yet, many conifers tolerate the harsh urban environment and have potential to deliver ecosystem services all year round since most conifers are evergreen. This essay will investigate differences between broadleaved and conifer trees in six regulating and supporting ecosystem services through systematic literature studies. The results show that conifers, which have a more complex leaf structure, bigger total leaf area and evergreen canopies can be more effective at removing pollutants, managing storm water and to create wind protection. However, broadleaved trees can by being deciduous and by having broader canopies be more effective at mitigating temperature. Carbon sequestration and storage can be considered equal for broadleaved and conifer trees and depend more on other factors like biomass, growth rate and soil conditions. For biodiversity concerning habitat and food provisioning for other organisms, broadleaved and conifer trees have distinct roles and are both needed in urban areas. However, local species composition and whether the trees are native or not could be more crucial factors for this ecosystem service. The results indicate that the differences between broadleaved and conifer trees are bigger for air purification but smaller for storm water management in the climate of south and central Sweden than what international research shows. For Swedish climate, especially spatial composition decides the difference in temperature mitigation and wind protection. The treesâ capacity to deliver these ecosystem services depend on additional factors such site, soil, management, species and spatial composition, frequency and age (time) and these should be considered in tree selection. This essay covers which ecosystem services one can expect from broadleaved and conifer trees in urban areas and can guide a conscious tree selection
Third timeâs the charm? Bulgariaâs November elections and the elusive quest for a parliamentary majority
Bulgaria has held three parliamentary elections in 2021, with the latest vote taking place on 14 November alongside the first round of the countryâs presidential election. In the second round of the presidential vote, held on 21 November, incumbent President Rumen Radev was re-elected for another five-year term. Kjell Engelbrekt and Petia Kostadinova write that amid widespread frustration with the countryâs political leaders, there is now a mandate for a new government to implement real change
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