Refametinib, an oral MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in patients with -mutated hepatocellular carcinoma (HCC). Two phase II studies evaluated the efficacy of refametinib monotherapy and refametinib plus sorafenib in patients with-mutant unresectable or metastatic HCC. Eligible patients with mutations of cell-free circulating tumor DNA (ctDNA) determined by beads, emulsion, amplification, and magnetics technology received twice-daily refametinib 50 mg ± sorafenib 400 mg. Potential biomarkers were assessed in ctDNA via next-generation sequencing (NGS). Of 1,318 patients screened, 59 (4.4%) had a mutation, of whom 16 received refametinib and 16 received refametinib plus sorafenib. With refametinib monotherapy, the objective response rate (ORR) was 0%, the disease control rate (DCR) was 56.3%, overall survival (OS) was 5.8 months, and progression-free survival (PFS) was 1.9 months. With refametinib plus sorafenib, the ORR was 6.3%, the DCR was 43.8%, OS was 12.7 months, and PFS was 1.5 months. In both studies, time to progression was 2.8 months. Treatment-emergent toxicities included fatigue, hypertension, and acneiform rash. Twenty-seven patients had ctDNA samples available for NGS. The most frequently detected mutations were in (63.0%), (48.1%), and β-catenin (; 37.0%). Prospective testing for family mutations using ctDNA was a feasible, noninvasive approach for large-scale mutational testing in patients with HCC. A median OS of 12.7 months with refametinib plus sorafenib in this small population of-mutant patients may indicate a synergistic effect between sorafenib and refametinib-this preliminary finding should be further explored. .

RESUMO O artigo tem como objetivo apresentar o debate acerca da modernidade/colonialidade e sua crítica ao racismo epistêmico. Na análise são discutidos desde a perspectiva teórica do pensamento decolonial, os efeitos, os rastros, as estruturas persistentes da colonialidade na formação docente brasileira, e de modo especial, nos currículos de filosofia. Trata-se, ademais, de problematizar o descompasso entre as tendências acadêmicas hegemônicas de perspectiva eurocentradas, que desconsideram as determinações geopolíticas na construção do conhecimento, e os saberes e experiências de populações africanas, afrodiaspóricas, indígenas e latino-americanas. O texto argumenta, por fim, que o projeto ancorado nos valores da modernidade/colonialidade europeia opera pela subalternização e silenciamento dos conhecimentos produzidos a partir de outras matrizes corpo-políticas, invalidando-as pela via do epistemicídio. Pensar o ensino de filosofia em bases decoloniais e antirracistas exige, portanto, que se questionem as premissas ‘norteadoras’ deste projeto étnico, sexual e racialmente excludente.

Background PCNSL is a rare extranodal NHL with poor prognosis. Tumorigenesis has been associated with hyperactivation of BCR downstream and NFkB pathways. We studied the prognosis of the relative expression profile of target genes of NFkB pathway (MYC, BCL2), the essential transcriptional regulator in hematopoiesis LMO2, the checkpoint regulation pathway MGMT, the transcription factor POU2F1, the immune checkpoint gene PDCD1, and the proto‐oncogene and transcriptional repressor gene BCL6 and its proteins in PCNSL. Methods This study is a retrospective cohort study; 35 immunocompetent PCNSL‐DLBCL patients had their gene expression (RT‐qPCR) normalized to internal control gene GUSB. Results Median patient age was 62 years, median OS was 42.6 months (95% CI: 26.6–58.6), PFS was 41 months (95% CI: 19.7–62.4), and DFS was 59.2 months (95% CI 31.9–86.6). A moderate correlation was found between the gene/protein expressions of MYC (kappa = 0.596, p = .022) and of BCL2 (kappa = 0.426, p = .042). Relative gene expression of MYC ≥ 0.201 (HR 6.117; p = .003) was associated with worse 5‐year OS. Relative gene expression of MYC ≥ 0.201 (HR 3.96; p = .016) and MGMT ≥ 0.335 (HR 3.749; p = .056) was associated with worse PFS. Age > 60 years and IELSG score moderate/high were also associated with worse prognosis. Conclusions Overexpression of MYC and overexpression of MGMT were prognostic markers associated with unfavorable clinical outcomes in PCNSL.

O presente artigo busca analisar de que modo os problemas da segurança e da economia das punições passam a ser centrais no cálculo político-econômico da racionalidade neoliberal. Como propõe Michel Foucault em seu curso Nascimento da Biopolítica, de 1979, a tecnologia de governo neoliberal conceberia o aparato estatal como “efeito móvel de um regime de governamentalidades múltiplas”. É o enfoque econômico, portanto, que permitirá pôr à prova a eficácia da ação governamental, a partir da avaliação do custo-benefício das intervenções na esfera do mercado e da sociedade, conforme a proposição dos teóricos neoliberais. Essa crítica mercantil direciona-se ao que é concebido como “dispêndio” das ações econômicas do poder público, dado que o mercado se torna “uma espécie de tribunal econômico permanente em face do governo”, como sugere Foucault. Nesse cenário, no qual se ampliam as demandas punitivas, a eficiência de atuação do sistema de justiça criminal dos Estados será medida pela avaliação do mercado e da economia, tendo em vista os seus efeitos. Tratar-se-á, então, de refletir sobre o funcionamento do poder punitivo em moldes econômicos, isto é, pela via da problematização dos custos da delinquência e dos modos de torná-los o menos dispendioso possível e com a máxima eficiência.

This essay aims to reflect on the impacts of state violence upon black lives and childhoods. In the wanderings through the city of Rio de Janeiro and in the theoretical trails proposed by antiracist and decolonial thinkers, we discuss the impacts and challenges of racism in the formative and existential itineraries of racialized bodies, crossed by the public necropolitics that provides the premises of the pedagogical government of peripheral childhoods and adolescences in large Brazilian cities. From the bumping into M., 11 years old, who sells chewing gum in the surroundings of a train station in Rio de Janeiro, we problematize the vulnerabilities produced and the systematic violations of the black children’s human rights, which hinder racial justice in the country, in face of the permanent conversion of differences into inferiorized inequalities. The violence of this injustice, according to the argument developed in the text, culminates in the reinforcement of the vilification and naturalization of racial inequalities against populations historically inferiorized by the colonial wrath. It also points to the need to think about black childhoods from the territory, in order to problematize inequities and disparities that persist. We conclude, finally, that the capture and nullification of black childhoods is a State project, guided by criminalizing and stereotyping practices of subjectivation which brutalize bodies and dehumanize black lives.

RESUMO O ensaio tem por objetivo questionar as relações coloniais do saber fixadas por meio de um modelo humanista eurocentrado. Para isso, adota-se uma lente de análise centrada na crítica às categorias que reforçam o racismo epistêmico como mecanismo social determinante das relações coloniais do saber e do poder. Busca-se pensar como as resistências são organizadas diante do silenciamento dos saberes, das práticas e das narrativas de corpos racialmente designados como inferiores. Trata-se, por fim, de analisar o potencial emancipatório desse movimento de resistência, teórico e prático, produzido a partir de outras corpo-políticas do conhecimento, fruto das lutas históricas contra racismo/sexismo eurocentrados.

O ensaio objetiva discutir os pressupostos epistêmicos, políticos e culturais do currículo de filosofia, a partir da implementação da Lei 10.639/03 e da crítica endereçada ao racismo epistêmico. Discutem-se, nessa análise, desde a perspectiva teórica do pensamento decolonial, os efeitos, os rastros e as estruturas persistentes da colonialidade no ensino de filosofia e, de modo especial, nos currículos. Trata-se, ademais, de problematizar o descompasso entre as tendências acadêmicas hegemônicas de perspectiva eurocentradas, que desconsideram as determinações geopolíticas na construção do conhecimento, e os saberes e experiências de populações africanas, afrodiaspóricas, indígenas e latino-americanas. Argumenta-se, por fim, que o projeto ancorado nos valores da modernidade/colonialidade europeia opera pela subalternização e silenciamento dos conhecimentos produzidos a partir de outras matrizes corpo-políticas, invalidando-as pela via do epistemicídio. Pensar o currículo de filosofia em bases decoloniais e antirracistas exige, portanto, que se questionem as premissas norteadoras deste projeto étnico, sexual e racialmente excludente.

Nodal peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous malignancy with poor prognosis. We studied the prognostic impact of the expression profile of genes related to cell proliferation ( CCNA2 , TOP2A , and CHEK1 ), pro-inflammatory activity ( NFkB1 and IKBkB ), and angiogenesis ( VEGF1 ) in nodal PTCL outcomes, as well as the ability of this genomic panel to discriminate different histological subtypes. We investigated the relative expression of regulator genes in 63 nodal PTCL patients. CCNA2, TOP2A, CHEK1, and NF-kB1 proteins were also assessed by immunohistochemistry. The median patient age was 47 years, 57.1% were male, 34.9% were diagnosed with PTCL-NOS, 28.6% with ALK-/ALCL, 22.2% with ALK+/ALCL, and 14.3% with AITL. The proliferative genes were associated with worse 3-year OS and PFS in PTCL-NOS and better 3-year PFS in ALK-/ALCL. Expression of CCNA2≥median and overexpression of CHEK1 protein (HR 3.793; p = 0.007) were associated with worse OS for all the cohort of nodal PTCL (HR 1.418; p = 0.001). The genomic expression profile tested in this study was not able to discriminate the different subtypes of nodal PTCL, although it showed a distinct prognostic significance between PTCL-NOS and ALCL-ALK. Overexpression of the CCNA2 gene and CHEK1 protein were associated with poor prognosis in the total nodal PTCL cohort.