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The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p < 0.01). We modulated HA expression with 4-methylumbelliferone (4Mu) and detected an increase in sensitivity to paclitaxel (Pa). We evaluated the effect of 4Mu + chemotherapy on survival, HA metabolism, and CSC profile. The combination of 4Mu with Pa reduced the clonogenic and tumor-forming ability of CSC. Pa-induced HAS3, ABCC5, SOX2, and CD47 expression was mitigated by 4Mu. Pa + 4Mu combination significantly reduced in vivo tumor growth, enhancing animal survival and restoring the CSC profile in the TME to basal levels. Our results suggest that HA is involved in lung CSC phenotype and chemosensitivity, and its modulation by 4Mu improves treatment efficacy to inhibit tumor progression.

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Resumo Este trabalho é uma manifestação crítica a respeito do processo de admissão de pessoas privadas de liberdade (PPL) na porta de entrada das unidades prisionais do Rio de Janeiro, que passam por situações desfavoráveis, como a naturalização da invisibilidade do perfil vulnerável dos sujeitos reclusos, bem como a apresentação destes nas audiências de custódia, com parte de suas vestimentas e calçados retirados por policiais. O perfil seletivo da PPL não coincide com a população que comete delitos e crimes, pois para a privação de liberdade operam filtros socioeconômicos, políticos, raciais e culturais importantes e decisivos. Portanto, a audiência de custódia é uma política pública voltada a coibir violações e garantir direitos fundamentais. Cabe aos órgãos fiscalizadores orientar ações que identificam as violências institucionais, que não deixam marcas físicas, para que se cumpra de fato o objetivo da audiência de custódia, que é a garantia dos direitos humanos.

Abstract This work has as its object a critical statement about the admission process of people deprived of liberty (PPL) at the gateway to Rio de Janeiro, who go through unfavorable situations, such as the naturalization of the invisibility of the vulnerable profile of inmates as well as their presentation in custody hearings, with part of their clothing and shoes removed by police officers. The selective profile of PPL does not coincide with the population that commits crimes and crimes, as important and decisive socioeconomic, political, racial and cultural filters operate for deprivation of liberty. Therefore, the custody hearing is a public policy aimed at curbing violations and guaranteeing fundamental rights, which is the guarantee of human rights.

RESUMEN

This work has as its object a critical statement about the admission process of people deprived of liberty (PPL) at the gateway to Rio de Janeiro, who go through unfavorable situations, such as the naturalization of the invisibility of the vulnerable profile of inmates as well as their presentation in custody hearings, with part of their clothing and shoes removed by police officers. The selective profile of PPL does not coincide with the population that commits crimes and crimes, as important and decisive socioeconomic, political, racial and cultural filters operate for deprivation of liberty. Therefore, the custody hearing is a public policy aimed at curbing violations and guaranteeing fundamental rights, which is the guarantee of human rights.

Este trabalho é uma manifestação crítica a respeito do processo de admissão de pessoas privadas de liberdade (PPL) na porta de entrada das unidades prisionais do Rio de Janeiro, que passam por situações desfavoráveis, como a naturalização da invisibilidade do perfil vulnerável dos sujeitos reclusos, bem como a apresentação destes nas audiências de custódia, com parte de suas vestimentas e calçados retirados por policiais. O perfil seletivo da PPL não coincide com a população que comete delitos e crimes, pois para a privação de liberdade operam filtros socioeconômicos, políticos, raciais e culturais importantes e decisivos. Portanto, a audiência de custódia é uma política pública voltada a coibir violações e garantir direitos fundamentais. Cabe aos órgãos fiscalizadores orientar ações que identificam as violências institucionais, que não deixam marcas físicas, para que se cumpra de fato o objetivo da audiência de custódia, que é a garantia dos direitos humanos.

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Significance: Molecular biology techniques are being used to aid in determining the mechanisms responsible for tissue repair without scar formation. Wound healing is genetically determined, but there have been few studies that examine the genes responsible for tissue regeneration in mammals. Research using genetic mapping is extremely important for understanding the molecular mechanisms involved in the different phases of tissue regeneration. This process is complex, but an early inflammatory phase appears to influence lesion closure, and the present study demonstrates that acute inflammation loci influence tissue regeneration in mice in a positive manner. Recent Advances: Mapping studies of quantitative trait loci (QTL) have been undertaken in recent years to examine candidate genes that participate in the regeneration phenotype. Our laboratory has identified inflammation modifier QTL for wound healing. Mouse lines selected for the maximum (AIRmax) or minimum (AIRmin) acute inflammatory reactivity (AIR) have been used to study not only the tissue repair but also the impact of the genetic control of inflammation on susceptibility to autoimmune, neoplasic, and infectious diseases. Murphy Roths Large and AIRmax mice are exclusive in their complete epimorphic regeneration, although middle-aged inbred mice may also be capable of healing. Critical Issues: Inflammatory reactions have traditionally been described in the literature as negative factors in the process of skin injury closure. Inflammation is exacerbated due to the early release of mediators or the intense release of factors that cause cell proliferation after injury. The initial release of these factors as well as the clean-up of the lesion microenvironment are both crucial for following events. In addition, the activation and repression of some genes related to the regeneration phenotype may modulate lesion closure, demonstrating the significance of genetic studies to better understand the mechanisms involved in the initiation of wound repair processes. Future Directions: The pleiotropic effects of the QTL are important in the identification of the genes responsible for tissue repair processes, especially when combined with global gene expression research. Microarray analysis complements the biological information obtained in QTL mapping, making this tool essential for gene identification. This approach will allow the investigation of future targets for therapeutic wound healing treatments.