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Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
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Talita da Silva Mendes de Farias Ariclécio Cunha de Oliveira Sandra Andreotti Fernanda Gaspar do Amaral Patrícia Chimin André Ricardo Alves de Proença Francisco Leonardo Torres Leal Rogério Antonio Laurato Sertié Amanda Baron Campana Andressa Bolsoni Lopes Arnaldo Henrique de Souza José Cipolla‐Neto Fabio Bessa Lima 《Journal of pineal research》2015,58(3):251-261
Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals. 相似文献
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Rubens Souza de OLIVEIRA Lanna Jamile Corrêa da COSTA Fernanda Atanaena Gon?alves de ANDRADE Wilson UIEDA Luzia Fátima Alves MARTORELLI Ana Paula de Arruda Geraldes KATAOKA Elizabeth Salbé Travassos da ROSA Pedro Fernando da Costa VASCONCELOS Armando de Souza PEREIRA Ant?nio Ismael Barros do CARMO Marcus Emanuel Barroncas FERNANDES 《Revista do Instituto de Medicina Tropical de S?o Paulo》2015,57(6):497-503
The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005,
in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a
priority area for studies on this zoonosis. Given this, the present study provides
data on this phenomenon in an urban context, in order to assess the possible
circulation of the classic rabies virus (RABV) among bat species in Capanema, a town
in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and
dry seasons. Samples of brain tissue and blood were collected for virological and
serological survey, respectively. None of the 153 brain tissue samples analyzed
tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum
samples analyzed were seropositive. Artibeus planirostris was the most common
species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31
52.60%). Statistically, equal proportions of seropositive results were obtained in
the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly
higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95%
CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested
positive for infection, the high proportion of seropositive specimens indicates that
RABV may be widespread in this urban area. 相似文献
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Modena Débora Aparecida Oliveira Miranda Ana Carolina Godoy Grecco Clovis Liebano Richard Eloin Cordeiro Raquel Cristina Tancsik Guidi Renata Michelini 《Lasers in medical science》2020,35(4):797-806
Lasers in Medical Science - Using light sources in phototherapy has presented promising results regarding several types of facial and body skin affections for centuries. The neodymium-doped yttrium... 相似文献