RESUMO
Dialogando com reflexão de Canclini na quarentena da Cidade do México em 2009 pela epidemia de H1N1, nosso artigo aborda as cidades de São Paulo e Rio de Janeiro para discutir desdobramentos da pandemia da Covid-19. O agravamento da crise denuncia e expõe as flagrantes desigualdades sociais fomentadas pelo modelo de gestão dos espaços urbanos que associa o político ao econômico, favorecendo a concentração de renda e limitando o acesso a recursos de toda ordem. Comunicação, vigilância, sociabilidade e cidadania são os eixos temáticos da discussão apresentada. Ao final, argumentamos sobre a urgência em constituirmos um revigorado horizonte comum de debate e ação coletiva unindo o político ao social.
In dialogue with Canclini's reflection during the quarantine of Mexico City in 2009 due to the H1N1 epidemic, our article focuses on the cities of São Paulo and Rio de Janeiro to discuss the unfolding of the Covid-19 pandemic. The worsening of the crisis denounces and exposes the flagrant social inequalities fostered by the current model of management of urban spaces that associates the political with the economic, favoring the concentration of income and limiting access to all kinds of resources. Communication, surveillance, sociability, and citizenship are interwoven in this discussion. In the end, we argue about the urgency of creating an invigorated common horizon of debate and collective action by uniting the political and the social spheres.
En diálogo con la reflexión de Canclini en la cuarentena de la Ciudad de México en 2009 debido a la epidemia de H1N1, nuestro artículo se centra en las ciudades de São Paulo y Rio de Janeiro para discutir los desarrollos de la pandemia de Covid-19. El agravamiento de la crisis denuncia y expone las flagrantes desigualdades sociales fomentadas por el modelo actual de gestión de espacios urbanos que asocia lo político con lo económico, favoreciendo la concentración de ingresos y limitando el acceso a todo tipo de recursos. Comunicación, vigilancia, sociabilidad y ciudadanía se entrelazan en esta discusión. Al final, discutimos sobre la urgencia de crear un vigorizado horizonte común de debate y acción colectiva uniendo lo político y lo social.
Assuntos
Humanos , Fatores Socioeconômicos , Cidades , Comunicação , Participação da Comunidade , Pandemias , Política , Isolamento Social , População Urbana , Quarentena , Infecções por CoronavirusRESUMO
Dialogando com reflexão de Canclini na quarentena da Cidade do México em 2009 pela epidemia de H1N1,nosso artigo aborda as cidades de São Paulo e Rio de Janeiro para discutir desdobramentos da pandemiada Covid-19. O agravamento da crise denuncia e expõe as flagrantes desigualdades sociais fomentadas pelomodelo de gestão dos espaços urbanos que associa o político ao econômico, favorecendo a concentração derenda e limitando o acesso a recursos de toda ordem. Comunicação, vigilância, sociabilidade e cidadania sãoos eixos temáticos da discussão apresentada. Ao final, argumentamos sobre a urgência em constituirmosum revigorado horizonte comum de debate e ação coletiva unindo o político ao social
Assuntos
Pandemias , Cidadania , História do Século XXI , BrasilRESUMO
BACKGROUND: Heat Shock Proteins (HSPs), a family of genes with key roles in proteostasis, have been extensively associated with cancer behaviour. However, the HSP family is quite large and many of its members have not been investigated in breast cancer (BRCA), particularly in relation with the current molecular BRCA classification. In this work, we performed a comprehensive transcriptomic study of the HSP gene family in BRCA patients from both The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts discriminating the BRCA intrinsic molecular subtypes. METHODS: We examined gene expression levels of 1097 BRCA tissue samples retrieved from TCGA and 1981 samples of METABRIC, focusing mainly on the HSP family (95 genes). Data were stratified according to the PAM50 gene expression (Luminal A, Luminal B, HER2, Basal, and Normal-like). Transcriptomic analyses include several statistical approaches: differential gene expression, hierarchical clustering and survival analysis. RESULTS: Of the 20,531 analysed genes we found that in BRCA almost 30% presented deregulated expression (19% upregulated and 10% downregulated), while of the HSP family 25% appeared deregulated (14% upregulated and 11% downregulated) (|fold change| > 2 comparing BRCA with normal breast tissues). The study revealed the existence of shared HSP genes deregulated in all subtypes of BRCA while other HSPs were deregulated in specific subtypes. Many members of the Chaperonin subfamily were found upregulated while three members (BBS10, BBS12 and CCTB6) were found downregulated. HSPC subfamily had moderate increments of transcripts levels. Various genes of the HSP70 subfamily were upregulated; meanwhile, HSPA12A and HSPA12B appeared strongly downregulated. The strongest downregulation was observed in several HSPB members except for HSPB1. DNAJ members showed heterogeneous expression pattern. We found that 23 HSP genes correlated with overall survival and three HSP-based transcriptional profiles with impact on disease outcome were recognized. CONCLUSIONS: We identified shared and specific HSP genes deregulated in BRCA subtypes. This study allowed the recognition of HSP genes not previously associated with BRCA and/or any cancer type, and the identification of three clinically relevant clusters based on HSPs expression patterns with influence on overall survival.
Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Proteínas de Choque Térmico/genética , Neoplasias da Mama/mortalidade , Estudos de Coortes , Feminino , Humanos , Modelos de Riscos ProporcionaisRESUMO
Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy. The study involved 14 patients; the pre- and post-chemotherapy paired biopsies were examined by hematoxylin and eosin staining and by immunohistochemistry. The proteins evaluated were p53, P16/INK4A, MSH2, nuclear protein transcriptional regulator 1 (NUPR1), and HSPB1 (total: HSPB1/t and phosphorylated: HSPB1/p). These proteins were selected because there is previous evidence of their relationship with drug resistance. The formation of platinum-DNA adducts was also studied. There was a great variation in the expression levels of the mentioned proteins in the pre-chemotherapy biopsies. After chemotherapy, p53 was not significantly affected by cisplatin, as well as P16/INK4A and MSH2 while nuclear NUPR1 content tended to decrease (p = 0.056). Cytoplasmic HSPB1/t expression levels decreased significantly following cisplatin therapy while nuclear HSPB1/t and HSPB1/p tended to increase. Since the most significant changes following chemotherapy appeared in the HSPB1 expression levels, the changes were confirmed by Western blot. The platinum-DNA adducts were observed in HeLa cell in apoptosis; however, in the tumor samples, the platinum-DNA adducts were observed in morphologically healthy tumor cells; these cells displayed nuclear HSPB1/p. Further mechanistic studies should be performed to reveal how HSPB1/p is related with drug resistance. When the correlations of the markers with the response to neoadjuvant chemotherapy were examined, only high pre-chemotherapy levels of cytoplasmic HSPB1/p correlated with a poor clinical and pathological response to neoadjuvant cisplatin chemotherapy (p = 0.056) suggesting that this marker could be useful opening its study in a larger number of cases.
Assuntos
Biomarcadores Tumorais/genética , Cisplatino/efeitos adversos , Proteínas de Choque Térmico HSP27/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Adutos de DNA/genética , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Proteínas de Choque Térmico , Humanos , Pessoa de Meia-Idade , Chaperonas Moleculares , Terapia Neoadjuvante/efeitos adversos , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Estudios realizados por Jairo Estrada en 1995 dieron inicio a la investigación relacionada con característi- cas antropométricas en sujetos colombianos, en la cual se tuvieron en cuenta las actividades laborales de trabajadores con las medidas personales de los mismos. Se realizó un estudio descriptivo cuyo objetivo principal fue caracterizar antropométricamente a los trabajadores de estiba de una plaza de mercado de la ciudad de Valledupar para brindar datos necesarios en el diseño de puestos de trabajo. La muestra se conformó por 98 hombres y 2 mujeres. Para el análisis estadístico de los resultados se realizaron pruebas de normalidad como (ShapiroWilk, Curtosis y asimetría) medidas de tendencia central, percentiles y una prueba de correlación de Pearson. Se encontró que existe una relación de la talla con medidas, como: altura ojo (0,697), altura alcance vertical máximo (0,667), altura codo (0, 611) y altura acromial (0,601), que fueron los índices más altos de relación encontrados durante la prueba estadística. 16 medidas no obtuvieron una distribución normal de los datos. Se concluye que la mayoría de las medidas antropométricas guardan una estrecha relación entre sí, y es esta característica de los seres humanos la que nos permite crear instrumentos de trabajo que faciliten realización de las tareas dentro de un estado de confort, estadísticamente estos datos hacen mucho mas fácil predecir las medidas de una persona solo teniendo como referencia la talla, lo que a futuro nos permitirá ajustar los puestos de trabajo según rasgos y características propias de una población especifica.
Studies done by Jairo Estrada in 1995 started the research related with anthropometric characteristics in Colombians in which the occupational activities of every worker were taken into account with personal measures of the individuals. Taking this reference as study, a research group from Universidad de Santander starts the data collecting process through a study that had as main objective to characterize anthropometrically stowage workers of a marketplace in Valledupar to provide necessary data in the job design. The research is quantitative-descriptive: the sample was 98 men and 2 women. For the result analysis, some normality tests were statistically done such as: Shapiro Wilk, Curtosis and asymmetry, measure of central tendency, percentiles and a Pearson product-moment correlation coefficient test. Therefore, there is relation between the size with the measures, as: eye height (0,697), maximum vertical range (0,667), elbow height (0,611), acromial height (0,601), that were the highest relation rates found during the statistic test, only 16 measures did not obtain a data normal distribution. Finally, it is concluded that most of the anthropometric measures have a close relation with each other and it is this feature of human beings that allows us create work instruments that facilitate to do the tasks in a comfort state. Statistically these data make much easier to predict a person measures just having as reference the size, which in the future it will allow us set jobs according to proper traits and characteristics of a specific population
Assuntos
Humanos , Antropometria , Saúde Ocupacional , Especialidade de Fisioterapia , TrabalhoRESUMO
We previously reported the association of HSPA1A and HSPB1 with high-grade astrocytomas, suggesting that these proteins might be involved in disease outcome and response to treatment. With the aim to better understand the resistance/susceptibility processes associated to temozolomide (TMZ) treatment, the current study was performed in three human malignant glioma cell lines by focusing on several levels: (a) apoptotic index and senescence, (b) DNA damage, and (c) interaction of HSPB1 with players of the DNA damage response. Three human glioma cell lines, Gli36, U87, and DBTRG, were treated with TMZ evaluating cell viability and survival, apoptosis, senescence, and comets (comet assay). The expression of HSPA (HSPA1A and HSPA8), HSPB1, O6-methylguanine-DNA methyltransferase (MGMT), MLH1, and MSH2 was determined by immunocytochemistry, immunofluorescence, and Western blot. Immunoprecipitation was used to analyze protein interaction. The cell lines exhibited differences in viability, apoptosis, and senescence after TMZ administration. We then focused on Gli36 cells (relatively unstudied) which showed very low recovery capacity following TMZ treatment, and this was related to high DNA damage levels; however, the cells maintained their viability. In these cells, MGMT, MSH2, HSPA, and HSPB1 levels increased significantly after TMZ administration. In addition, MSH2 and HSPB1 proteins appeared co-localized by confocal microscopy. This co-localization increased after TMZ treatment, and in immunoprecipitation analysis, MSH2 and HSPB1 appeared interacting. In contrast, HSPB1 did not interact with MGMT. We show in glioma cells the biological effects of TMZ and how this drug affects the expression levels of heat shock proteins (HSPs), MGMT, MSH2, and MLH1. In Gli36 cells, the results suggest that interactions between HSPB1 and MSH2, including co-nuclear localization, may be important in determining cell sensitivity to TMZ.
Assuntos
Apoptose/efeitos dos fármacos , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/análogos & derivados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos Alquilantes/farmacologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Dacarbazina/farmacologia , Glioma/patologia , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Imuno-Histoquímica , Chaperonas Moleculares , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Nucleares/metabolismo , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , TemozolomidaRESUMO
In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the same mammary mouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma. By immunohistochemistry, we have found a striking co-expression of ß-catenin and Her-2/neu in the tumor cells. The absence of Cav-1 in the tumor stroma had no effect on expression or localization of ß-catenin and Her-2/neu. Both proteins appeared co-localized at the cell surface during tumor development and progression. Since Her-2/neu activation induces MTA1, we next evaluated MTA1 in the mouse tumors. Although this protein was found in numerous nuclei, the absence of Cav-1 did not alter its expression level. In contrast, significantly more PTEN protein was noted in the tumors lacking Cav-1 in the stroma, with the protein localized mainly in the nuclei. P-Akt levels were relatively low in tumors from both Cav-1 WT and Cav-1 KO mice. There was also an increase in nuclear NHERF1 expression levels in the tumors arising from Cav-1 KO mice. The data obtained in the MMTV-neu model are consistent with a role for Cav-1 in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.
Assuntos
Caveolina 1/metabolismo , Neoplasias Mamárias Animais/metabolismo , Vírus do Tumor Mamário do Camundongo/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfoproteínas/metabolismo , Receptor ErbB-2/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , beta Catenina/metabolismo , Animais , Caveolina 1/genética , Feminino , Humanos , Imuno-Histoquímica , Células MCF-7 , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/genética , beta Catenina/genéticaRESUMO
In oligodendrogliomas, 1p loss of heterozygosity (LOH) is a predictor of good prognosis and treatment response. In contrast, in uveal melanomas, LOH of chromosome 3 has been linked to poor prognosis and downregulation of Hsp27. In the present study, we have analyzed the expression of heat-shock proteins (Hsps) to characterize subtypes of gliomas and their histopathologic features and to correlate with other molecular markers including LOH of 1p. Biopsies from patients with primary gliomas (n = 65) were analyzed by immunohistochemistry, chromogenic in situ hybridization and fluorescent in situ hybridization and methylation-specific PCR (MSP). Elevated Hsp27 and total Hsp70 expression levels were associated with high-grade astrocytomas (p = 0.0001 and p = 0.01, respectively). In grade III oligodendrogliomas, the Hsp27 levels were significantly higher (p = 0.03). Low O6-methylguanine-DNA methyltransferase (MGMT) expression was associated with grade II astrocytomas. Elevated ß-catenin expression was associated with grade III/IV astrocytomas (p = 0.003); p53 (+) tumors were more frequently found in grade III/IV astrocytomas (p = 0,001). LOH on 1p was associated with oligodendroglial tumours. In addition, a higher Hsp27 expression correlated with LOH of 1p (p = 0.017); this was also tested in two glioma cell lines. MSP was successful in only six samples. No significant correlations were found for the other markers. In conclusion, in oligodendroglial tumors, Hsp27 appeared as a surrogate marker of LOH of 1p which could also help to predict the disease prognosis. In gliomas, p53, Hsp27, Hsp70, MGMT, and ß-catenin correlated with histopathological characteristics, suggesting that these markers could predict the disease outcome and the response to treatments.
Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Perda de Heterozigosidade , Oligodendroglioma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Cromossomos Humanos Par 1 , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Oligodendroglioma/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem , beta Catenina/metabolismoRESUMO
Heat shock proteins (Hsp) are molecular chaperones with the capability to interact with a wide range of other proteins and are thus often found coupled with other heat shock and non-heat shock proteins. This can be an advantage to study specific interactions between a chaperone and other proteins and to generate an antitumoral immune response. In this chapter, we present two protocols to isolate Hsp. One involves column chromatography with hydroxyapatite and the other employs immunoprecipitation with antibodies coupled to magnetic beads. In both cases, we specifically want to isolate Hsp coupled with other proteins and use the Hsp complexes as intermediaries to present the coupled peptides/proteins to the immune system, or to explore the associations of a particular Hsp with other proteins.
Assuntos
Cromatografia de Afinidade/métodos , Proteínas de Choque Térmico/isolamento & purificação , Imunoprecipitação/métodos , Materiais Biocompatíveis , Linhagem Celular Tumoral , Durapatita , Proteínas de Choque Térmico/química , Humanos , Domínios e Motivos de Interação entre ProteínasRESUMO
The heat shock proteins (HSP) constitute a superfamily of chaperone proteins present in all cells and in all cell compartments, operating in a complex interplay with synergistic/overlapping multiplicity of functions, even though the common effect is cell protection. Several reasons explain the need for investigating HSP in prostate cancer: (1) these molecules function as chaperones of tumorigenesis accompanying the emergence of prostate cancer cells, (2) they appear as useful molecular markers associated with disease aggressiveness and with resistance to anticancer therapies including hormone therapy, radiotherapy, chemotherapy and hyperthermia, and (3) they can be used as targets for therapies. The latter can be accomplished by: (i) interrupting the interaction of HSP (mainly HSPC1) with various client proteins that are protected from degradation when chaperoned by the HSP; (ii) using the chaperone and adjuvant capabilities of certain HSP to present antigenic peptides to the immune system, so this system can recognise the prostate tumour cells as foreign to mount an effective antitumoral response; and (iii) using treatment planning models taking into account the HSP expression levels to obtain more effective therapies. In summary, the study of the HSP during tumorigenesis as well as during cancer progression, and the inclusion of treatment designs targeting HSP combined with other treatment modalities, should improve prostate cancer survival in the near future.