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Vincristine (VCR) is a classical chemotherapeutic that has been revisited to treat refractory solid tumors producing encouraging results. VCR binds to tubulin and decreases the rate of microtubule dynamics, thus triggering many cellular responses and behaviors. However, the dynamics of these responses and fates are uncharacterized. This study combined systems biology approaches with acute and long-term in vitro experiments to predict key pathways and mechanisms associated with cell fates during and after VCR treatment. Glioblastoma (GBM) cells were treated with clinically relevant doses of VCR, and interconnected cell fates were explored. A correlation matrix based on experimental cell analysis reported strong negative correlations between cell number, nuclear irregularities, senescence, or apoptosis, depending on the cells' genetic makeup and treatment regimen. P53 would be essential in all analyzed processes according to topological network analysis. Furthermore, despite the high acute sensitivity, both cell lines re-growth in the long term after a single VCR treatment, especially in those populations with high levels of autophagy. These multiple responses may also be triggered in patients' exposed tumors, which should be considered to allow the rational design of VCR protocols, including modulators of the cell fates and pathways mentioned above.

Glioblastoma (GBM) is the most aggressive and lethal among the primary brain tumors, with a low survival rate and resistance to radio and chemotherapy. The P2Y(12) is an adenosine diphosphate (ADP) purinergic chemoreceptor, found mainly in platelets. In cancer cells, its activation has been described to induce proliferation and metastasis. Bearing in mind the need to find new treatments for GBM, this study aimed to investigate the role of the P2Y(12)R in the proliferation and migration of GBM cells, as well as to evaluate the expression of this receptor in patients’ data obtained from the TCGA data bank. Here, we used the P2Y(12)R antagonist, ticagrelor, which belongs to the antiplatelet agent’s class. The different GBM cells (cell line and patient-derived cells) were treated with ticagrelor, with the agonist, ADP, or both, and the effects on cell proliferation, colony formation, ADP hydrolysis, cell cycle and death, migration, and cell adhesion were analyzed. The results showed that ticagrelor decreased the viability and the proliferation of GBM cells. P2Y(12)R antagonism also reduced colony formation and migration potentials, with alterations on the expression of metalloproteinases, and induced autophagy in GBM cells. Changes were observed at the cell cycle level, and only the U251 cell line showed a significant reduction in the ADP hydrolysis profile. TCGA data analysis showed a higher expression of P2Y(12)R in gliomas samples when compared to the other tumors. These data demonstrate the importance of the P2Y(12) receptor in gliomas development and reinforce its potential as a pharmacological target for glioma treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11302-022-09888-w.

Esse estudo reporta a presença de Henneguya sp. no sangue de Astyanax fasciatus de ambiente natural, em um córrego da sub-bacia do rio Muriaé, pertencente a bacia do rio do Paraíba do Sul de Itaperuna, estado do Rio de Janeiro, Brasil. Oito coletas foram realizadas em outubro de 2009 e setembro de 2010, com 45 dias de intervalo, em cada coleta foram capturados dez espécimes de Astyanax fasciatus dando um total de 80 lâminas de sangue. Esse estudo relata a presença de Henneguya sp. em duas espécimes coletadas em novembro de 2009. Essa baixa incidência de parasitas ocorreu porque o gênero Henneguya já foi registrado em vários órgãos de espécies do gênero Astyanax. Embora os filamentos branquiais sejam de locais com maior tropismo e alta prevalência, não foram encontrados registros na literatura de parasitas com esse gênero no sangue de peixes.