Capacidade gerencial e habilidade política dos empresários de transporte por ônibus de Belo Horizonte: mito ou realidade?

O sistema de transporte por ônibus em Belo Horizonte, comparado ao de outras capitais brasileiras, apresenta algumas particularidades, como seu elevado número de empresas e o predomínio de empresas de médio porte. Este artigo discute o processo de evolução das empresas de Belo Horizonte, destacando questões como a diferença em relação ao padrão nacional de concentração, o desenvolvimento da capacidade gerencial e da habilidade política dos transportadores mineiros, e o papel do órgão gestor nesses processos. Optou-se pelo enfoque político das organizações, privilegiando-se as relações de trabalho e de poder entre os diversos atores do sistema. Pôde-se concluir que os empresários belo-horizontinos destacam-se como articuladores na criação e no desenvolvimento de suas empresas, como pioneiros na diversificação e expansão geográfica de seus negócios e como lideranças políticas e empresariais nacionais. A partir de um processo de profissionalização e expansão no setor em Belo Horizonte, ocorreu a articulação da classe, inicialmente para fazer frente ao poder público local, expandindo-se nacionalmente. Esse processo permitiu a alavancagem e a padronização da gestão empresarial

Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells

Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.Ricardo Amorim was recipient of the fellowships SFRH/BI/51118/ 2010 and SFRH/BD/98002/2013, from Fundação para a Ciência e Tecnologia (FCT, Portugal). This study was supported by the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and co-financed by Fundo Comunitário Europeu FEDER. This work was also supported by FEDER through POFC – COMPETE and by FCT through project PEst-OE/BIA/UI4050/2014 and Helena Pereira’s fellowship (SFRH/BD/73139/2010)

MCT1 is a new prognostic biomarker and its therapeutic inhibition boosts response to temozolomide in human glioblastoma

Background: Glioblastomas (GBMs) present remarkable metabolism reprograming, in which many cells display the “Warburg effect”, with the production of high levels of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). We described previously that MCT1 is up-regulated in human GBM samples, and MCT1 inhibition decreases glioma cell viability and aggressiveness. In the present study, we aimed to unveil the role of MCT1 in GBM prognosis and to explore it as a target for GBM therapy in vivo. Methods: MCT1 activity and protein expression were inhibited by AR-C155858 and CHC compounds or stable knockdown with shRNA, respectively, to assess in vitro and in vivo the effects of MCT1 inhibition and on response of GBM to temozolomide. Survival analyses on GBM patient cohorts were performed using Cox regression and Log-rank tests. Results: High levels of MCT1 expression were revealed to be a predictor of poor prognosis in multiple cohorts of GBM patients. Functionally, in U251 GBM cells, MCT1 stable knockdown decreased glucose consumption and lactate efflux, compromising the response to the MCT1 inhibitors CHC and AR-C155858. MCT1 knockdown significantly increased the survival of orthotopic GBM intracranial mice models when compared to their control counterparts. Furthermore, MCT1 downregulation increased the sensitivity to temozolomide in vitro and in vivo, resulting in significantly longer mice survival. Conclusions: This work provides first evidence for MCT1 as a new prognostic biomarker of GBM survival and further supports MCT1 targeting, alone or in combination with classical chemotherapy, for the treatment of GBM.This work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI–Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundation for Science and Technology (FCT)–project UIDB/50026/2020 and UIDP/50026/2020 and by the projects NORTE-01-0145-FEDER-000039 and NORTE-01-0247- FEDER-045914, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by project PTDC/BTM-SAL/31142/2017 (funded by FCT) and Brazilian MCTI/CNPq No73/2013. VMG was recipient of a fellowship and BC recipient of a contract from Fundação para a Ciência e Tecnologia (FCT), Portugal, refs. SFRH/BD/51997/2012 and CEECIND/00072/2018, respectivel

Molecular impact of [C16Pyr][Amp] treatment on breast and prostate cancer cell lines

Prostate Cancer (PCa) and Breast Cancer (BCa) are the leading causes of cancer morbidity and mortality, worldwide, when diagnosed in advanced stages of the disease. Currently available therapies have limited curative effect, leading to the progression to highly aggressive hormone-resistant phenotypes. Thus, the development of new anti-tumor agents becomes imperative. Ionic liquids are organic salts with anti-neoplastic activity and have been studied in the pharmaceutical industry. Previous work of our team demonstrated that the ionic liquid [C16Pyr][Amp] has significant anti-tumor properties in PCa and BCa cell lines. However, the main cellular pathways affected were not characterized. Therefore, the aim of this work was to explore the molecular impact of [C16Pyr][Amp] treatment in order to identify relevant genes that have altered expression upon treatment and that can justify the anti-cancer effect observed in the in vitro assays.info:eu-repo/semantics/publishedVersio

Sirtuins’ deregulation in bladder cancer: SIRT7 is implicated in tumor progression through epithelial to mesenchymal transition promotion

Sirtuins are emerging players in cancer biology and other age-related disorders, and their putative role in bladder cancer (BlCa) remains elusive. Further understanding of disease biology may allow for generation of more effective pathway-based biomarkers and targeted therapies. Herein, we aimed to illuminate the role of sirtuins’ family in BlCa and evaluate their potential as disease biomarkers and therapeutic targets. SIRT1-7 transcripts and protein levels were evaluated in a series of primary BlCa and normal bladder mucosa tissues. SIRT7 knockdown was performed through lentiviral transduction in MGHU3, 5637 and J82 cells and its functional role was assessed. SIRT1, 2, 4 and 5 expression levels were significantly lower in BlCa, whereas SIRT6 and 7 were overexpressed, and these results were corroborated by TCGA cohort analysis. SIRT7 transcript levels were significantly decreased in muscle-invasive vs. papillary BlCa. In vitro studies showed that SIRT7 downregulation promoted cells migration and invasion. Accordingly, increased EMT markers expression and decreased E-Cadherin (CDH1) was observed in those BlCa cells. Moreover, increased EZH2 expression and H3K27me3 deposition in E-Cadherin promoter was found in sh-SIRT7 cells. We demonstrated that sirtuins are globally deregulated in BlCa, and specifically SIRT7 downregulation is implicated in EMT, fostering BlCa invasiveness through EZH2-CDH1 axis.This research was supported by the Research Center of the Portuguese Oncology Institute of Porto (CI-IPOP–FBGEBC-27 and PI 74-CI-IPOP-19-2016), by Fundação para a Ciência e Tecnologia (FCT) (PhD fellowships SFRH/BD/112673/2015 to S.M.-R and SFRH/BD/92786/2013 to C.S.G.; IF/00601/2012 to B.M.C.), and by Fundo Europeu de Desenvolvimento Regional (FEDER) (post-doctoral fellowships IPO/ESTIMANORTE01-0145-FEDER-000027 to V.M.-G. and COMPETE/FEDER/FCT_CI-IPOP-BPD/UID/DTP/00776/2013 to I.G.)

The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side e↵ects. Therefore, there is an urgent need for more e↵ective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays.info:eu-repo/semantics/publishedVersio

Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy

Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapyAnti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironrnental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (similar to 50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system.that offers the possibility to treat different solid tumors by intratumoral administration.Brazilian Fundação de Amparo e Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Additionally, this article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) Project PTDC/SAU-TOX/114549/2009 – FCOMP-01-0124-FEDER-016057, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersio

Experimental characterization of a microfluidic device based on passive crossflow filters for blood fractionation

The separation of red blood cells (RBCs) from blood plasma and the analysis of individual RBCs are of great importance, as they provide valuable information regarding the health of their donor. Recent developments in microfluidics and microfabrication have contributed to the fabrication of microsystems with complex features to promote the separation and analysis of RBCs. In this work, the separation capacity of a multi-step crossflow microfluidic device was evaluated by using a blood analogue fluid made by Brij L4 micelles and human RBCs separated from whole blood, suspended in a solution with hematocrits (Ht) of 0.5 and 1%. All the samples collected at the outlets of the device were experimentally analyzed and compared. The absorbance spectrum was also measured for the prepared blood samples. The results indicate that the tested blood analogue fluid has exhibited a flow behavior similar to that of blood. In addition, the optical absorbance spectrophotometry revealed that it was possible to evaluate the separation efficiency of the microfluidic device, concluding that the concentration of cells was lower at the most lateral outside outlets of the microchannel due to the cumulative effect of the multiple cross-flow filters

Volatilomics reveals potential biomarkers for identification of renal cell carcinoma: an in vitro approach

The identification of noninvasive biomarkers able to detect renal cell carcinoma (RCC) at an early stage remains an unmet clinical need. The recognition that altered metabolism is a core hallmark of cancer boosted metabolomic studies focused in the search for cancer biomarkers. The present work aims to evaluate the performance of the volatile metabolites present in the extracellular medium to discriminate RCC cell lines with distinct histological subtypes (clear cell and papillary) and metastatic potential from non-tumorigenic renal cells. Hence, volatile organic compounds (VOCs) and volatile carbonyl compounds (VCCs) were extracted by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). Multivariate and univariate analysis unveiled a panel of metabolites responsible for the separation between groups, mostly belonging to ketones, alcohols, alkanes and aldehydes classes. Some metabolites were found similarly altered for all RCC cell lines compared to non-tumorigenic cells, namely 2-ethylhexanol, tetradecane, formaldehyde, acetone (increased) and cyclohexanone and acetaldehyde (decreased). Furthermore, significantly altered levels of cyclohexanol, decanal, decane, dodecane and 4-methylbenzaldehyde were observed in all metastatic RCC cell lines when compared with the non-metastatic ones. Moreover, some alterations in the volatile composition were also observed between RCC histological subtypes. Overall, our results demonstrate the potential of volatile profiling for identification of noninvasive candidate biomarkers for early RCC diagnosis.info:eu-repo/semantics/publishedVersio