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1.
Proc Natl Acad Sci U S A ; 120(8): e2205247120, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36780531

RESUMO

Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing the need for a better understanding of the disease. Herein, we analyzed the transcriptional profile of brain metastasis initiating cells (BMICs) at two distinct stages of the brain metastatic cascade-the "premetastatic" or early stage when they first colonize the brain and the established macrometastatic stage. RNA sequencing was used to obtain the transcriptional profiles of premetastatic and macrometastatic (non-premetastatic) lung, breast, and melanoma BMICs. We identified that lung, breast, and melanoma premetastatic BMICs share a common transcriptomic signature that is distinct from their non-premetastatic counterparts. Importantly, we show that premetastatic BMICs exhibit increased expression of HLA-G, which we further demonstrate functions in an HLA-G/SPAG9/STAT3 axis to promote the establishment of brain metastatic lesions. Our findings suggest that unraveling the molecular landscape of premetastatic BMICs allows for the identification of clinically relevant targets that can possibly inform the development of preventive and/or more efficacious BM therapies.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Antígenos HLA-G , Neoplasias Pulmonares , Melanoma , Adulto , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Encéfalo/patologia , Neoplasias Encefálicas/secundário , Antígenos HLA-G/genética , Pulmão/patologia , Neoplasias Pulmonares/patologia , Melanoma/patologia , Fator de Transcrição STAT3/genética , Neoplasias da Mama/patologia
2.
Can J Anaesth ; 67(4): 430-436, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31691254

RESUMO

PURPOSE: Despite an increase in the proportion of women entering the field of anesthesiology, women remain underrepresented in academic and leadership positions. Speaking at national and international conferences is an important component of academic visibility and promotion. To date, the gender representation of speakers at the Canadian Anesthesiologists' Society (CAS) annual meeting has not been examined. METHODS: We conducted a retrospective analysis of the representation of women amongst speakers at the CAS annual meeting between 2007 and 2019, inclusively. We also examined the representation of women in different subspecialty subject area symposia at each CAS annual meeting, and the gender composition of meeting symposia panels (i.e., groups of two or more speakers in a session) at the meeting. RESULTS: Overall, 28.5% (358/1,256) of speaker slots included women, similar to their representation in Canadian clinical anesthesiology over the study period (26.7%), and increasing significantly over the study period. Women were more highly represented as obstetric anesthesia speakers at the CAS annual meetings, with lower representation in cardiothoracic anesthesia, transplant anesthesia, and critical care symposia. Of the 311 meeting symposia, 146 (46%) were composed of all men speakers. CONCLUSION: The representation of women speakers at the CAS annual meeting was similar to the representation of women in the anesthesiology workforce in Canada over the study period. Gender representation varied widely by subspecialty symposia, subject area, and women were absent from nearly half of all symposia at the CAS annual meetings, which are potential areas of future investigation and intervention.


Assuntos
Anestesiologistas , Médicas , Canadá , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sociedades Médicas
3.
Can J Anaesth ; 66(5): 495-502, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30805906

RESUMO

PURPOSE: Females remain under-represented in academic anesthesiology. Our objectives were to investigate gender differences over time in the first and last authors of published articles as well as corresponding citation rates in the Canadian Journal of Anesthesia (CJA). METHODS: We conducted a cross-sectional, retrospective analysis of first and last authors' gender from editorials and original articles published in the CJA in a sample of one calendar year of each decade between 1954 to 2017. We analyzed the relationships between author gender, year of publication, article type, and number of citations. RESULTS: Out of 639 articles identified, 542 (85%) were original investigations and 97 (15%) were editorials. Where gender could be confidently identified, the majority (461/571, 81%) of first authors were male. Although there was an increase in the proportion of female first authors over time, this increase was outpaced by the overall increase in female anesthesiologists in Canada. Original articles received more citations and were more likely to have a female first author than editorial articles were. An original article with a female first author resulted in 0.34 (95% confidence interval, 0.28 to 0.39; P < 0.001) more citations per article than a male first author when adjusting for year of publication. CONCLUSIONS: Our study shows that, despite a slow increase over time, female authors are under-represented relative to male authors in the CJA and relative to the changing demographics of anesthesiologists in Canada. The reasons for this disparity are multifactorial and further research is needed to identify effective solutions.


RéSUMé: OBJECTIF: Les femmes restent sous-représentées dans le monde de l'anesthésiologie universitaire. Nos objectifs étaient d'étudier l'évolution des premiers et derniers auteurs en fonction du sexe au fil des années dans les articles publiés ainsi que les taux correspondants de citation dans le Journal canadien d'anesthésie (CJA). MéTHODES: Nous avons mené une analyse transversale rétrospective du sexe des premiers et derniers auteurs des éditoriaux et des articles originaux publiés dans le CJA dans un échantillon d'une année civile pour chaque décennie entre 1954 et 2017. Nous avons analysé les rapports entre le sexe des auteurs, l'année de publication, le type d'articles et le nombre de citations. RéSULTATS: Sur 639 articles identifiés, 542 (85 %) étaient des recherches originales et 97 (15 %) étaient des éditoriaux. Lorsque le sexe a pu être identifié avec certitude, la majorité des premiers auteurs (461/571, 81 %) étaient des hommes. Bien qu'il y ait eu une augmentation du pourcentage de femmes premières auteures au fil du temps, cette augmentation n'a pas suivi la progression du nombre global des femmes anesthésiologistes au Canada. Les articles originaux ont été cités plus souvent et ont été plus susceptibles d'avoir un premier auteur féminin que les éditoriaux. Après ajustement pour l'année de publication, un article original dont le premier auteur était une femme comptait 0,34 (intervalle de confiance à 95 %, 0,28 à 0,39; P < 0,001) fois plus de citations que lorsque le premier auteur était un homme. CONCLUSIONS: Notre étude montre que, malgré une lente augmentation avec les années, les femmes auteures sont sous-représentées par rapport à leurs collègues masculins dans le CJA et par rapport aux changements démographiques de l'anesthésiologie au Canada. Les raisons de cette disparité sont multifactorielles et d'autres recherches sont nécessaires pour trouver des solutions efficaces.


Assuntos
Anestesiologistas/estatística & dados numéricos , Anestesiologia , Autoria , Publicações Periódicas como Assunto/estatística & dados numéricos , Anestesiologistas/tendências , Canadá , Estudos Transversais , Feminino , Humanos , Masculino , Publicações Periódicas como Assunto/tendências , Estudos Retrospectivos , Fatores Sexuais
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