The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities / 神经科学通报·英文版

Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.

Research Progress of Long Non-Coding RNA in Hematological Tumors --Review / 中国实验血液学杂志

Long non-coding RNA (lncRNA) is a hot topic in the field of researching tumor pathogenesis, and the importance in hematologic malignancies has been gradually being elucidated. LncRNA not only regulates hematological tumorigenesis and progression through affecting various biological processes such as cell proliferation, differentiation, pluripotency and apoptosis; moreover, abnormal expression and mutation of lncRNA are closely related to drug resistance and prognosis. Thus lncRNA can be used as novel biomarker and potential therapeutic target for hematological tumors. In this review, we will focus on the latest progress of lncRNA in hematological tumors to provide new ideas for the clinical diagnosis, prognostic evaluation together with research and development of target drugs for hematologic malignancies.

Improved antimutagenic effect of Pyrostegia venusta (Ker Gawl. ) Miers nanostructured extract in liposome and polymeric nanoparticle

Abstract Pyrostegia venusta (Ker Gawl.) Miers, popularly known as "Cipó-de São-João", has been used in traditional medicine for its therapeutic properties. Nanotechnology is able to enhance the pharmacological activity of plant extracts. In this context, liposomes and polymeric nanoparticles containing P. venusta ethanolic extract were developed and then physico-chemically characterized to evaluate the mutagenic/antimutagenic effects of P. venusta. In addition, transaminases and serum creatinine were biochemically analyzed for liver and renal damage, respectively. The micronucleus test was performed with male Swiss mice treated orally for 15 consecutive days with free extracts and nanostructured with P. venusta, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg/kg) on the 15th day of treatment. Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. There was a significant reduction in the frequency of MNPCE (LPEPV = 183% and NPEPV = 114%, p < 0.001), indicating antimutagenic potential of the nanostructured extracts with P. venusta. The groups treated with only nanostructured extract did not show an increase in MNPCE frequency, and biochemical analyzes showed no significant difference between treatments. The liposomes and polymeric nanoparticles containing Pyrostegia venusta ethanolic extract showed biological potential in preventing the first step of carcinogenesis under the experimental conditions

Asociación entre los niveles elevados de ácidos biliares y cáncer digestivo / Association between high bile acid levels and digestive cancer

Introducción: Los ácidos biliares en condiciones no fisiológicas se consideran agentes inflamatorio-carcinógenos endógenos que originan alteraciones en membranas plasmáticas, mitocondrias, el ADN, los genes y, la apoptosis de las células epiteliales. Objetivo: Describir la asociación entre los niveles elevados de ácidos biliares en la luz intestinal y la secuencia inflamación-cáncer, expresados como lesiones inflamatorias, premalignas y malignas del tracto digestivo. Métodos: Revisión sistemática y crítica de las evidencias sobre los mecanismos biomoleculares asociados a niveles altos de ácidos biliares en la luz intestinal y la secuencia inflamación-carcinogénesis, en bases de datos como PubMed, Medline, SciELO, LILACS y Elsevier, publicados entre 2015-2020, que establecen el fundamento teórico y metabolómico de dicha secuencia. Resultados: Los ácidos biliares tienen una acción tóxica en la secuencia inflamación-cáncer del tracto digestivo, al perderse el control de su homeostasis o la integridad anatomo-funcional del sistema hepato-vesículo-bilio-intestinal. Conclusiones: Los mecanismos celulares y biomoleculares desencadenados por los niveles altos de ácidos biliares contextualizan la génesis del proceso secuencial inflamación-cáncer y su interacción con los factores de riesgo clásicos, genéticos y epigenéticos reconocidos como un nuevo paradigma fisiopatológico del cáncer digestivo(AU)

Introduction: In non-physiological conditions, bile acids (BA) are considered to be endogenous inflammatory-carcinogenic agents causing alterations in plasma membranes, mitochondria, DNA, genes and epithelial cell apoptosis. Objective: Describe the association between high bile acid levels in the intestinal lumen and the inflammation-cancer sequence, expressed as inflammatory premalignant and malignant lesions of the digestive tract. Methods: A systematic critical review was conducted of the evidence about biomolecular mechanisms associated to high bile acid levels in the intestinal lumen and the inflammation-carcinogenesis sequence published in the databases PubMed, Medline, SciELO, LILACS and Elsevier in the period 2015-2020, laying the theoretical and metabolomic foundations of that sequence. Results: Bile acids display toxic activity in the inflammation-cancer sequence of the digestive tract, since control is lost of its homeostasis or the anatomical-functional integrity of the hepato-vesicular-biliary-intestinal system. Conclusions: The cellular and biomolecular mechanisms triggered by high bile acid levels provide a context for the genesis of the inflammation-cancer sequential process and its interaction with the classic, genetic and epigenetic risk factors recognized as a new pathophysiological paradigm of digestive cancer(AU)

BMI-1 expression increases in oral leukoplakias and correlates with cell proliferation

Abstract Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC.

Vías de señalización celular implicadas en la carcinogénesis cervical / Cellular Signaling Pathways Involved in Cervical Carcinogenesis

RESUMEN Introducción: El Virus de Papiloma Humano se considera un factor clave en el desarrollo de lesiones cérvico uterinas. No obstante, la infección per se no es suficiente para desarrollar todos los eventos carcinogénicos, de manera que estos podrían estar regulados por vías de señalización celular. Las señales transmitidas hacia el interior de la célula, se producen a través de cascadas de señalización, en las que intervienen numerosas proteínas que ganan y/o pierden su actividad biológica, regulando así el metabolismo, la transcripción y traducción de genes. Objetivo: Proveer información actualizada sobre las vías de señalización TLRs, Wnt/ß-catenina y PI3K/Akt implicadas en la carcinogénesis cervical. Métodos: Se realizó una revisión de la literatura especializada mediante artículos originales y revisiones publicadas en bases de datos pertenecientes a los sitios web PubMed, Google Scholar, EBSCO y NCBI, en idiomas español e inglés. Resultados: Se constató que la vía TLR juega un rol clave en el combate a virus, bacterias y otras infecciones, además de poseer actividad inmune antitumoral. La vía Wnt/ß-catenina participa en varios procesos biológicos como la diferenciación, migración y adhesión celular, mientras que, PI3K/Akt está relacionada con el crecimiento, la motilidad y la supervivencia celular. Conclusiones: La activación o desregulación de algunos componentes de estas vías están implicadas en la proliferación incontrolada de células tumorales, evento importante en la carcinogénesis cervical(AU)

ABSTRACT Introduction: Human papillomavirus is considered a key factor in the development of uterine cervical lesions. However, infection per se is not enough to develop all carcinogenic events, so that these could be regulated by cell signaling pathways. The signals transmitted into the cell are produced through signaling cascades, which involve numerous proteins that gain and, or lose their biological activity, thus regulating the metabolism, transcription and translation of genes. Objective: To provide updated information on TLRs, Wnt / ß-catenin and PI3K / Akt signaling pathways involved in cervical carcinogenesis. Methods: A review of specialized literature was carried out through original articles and reviews published in PubMed, Google Scholar, EBSCO databases and NCBI websites, in Spanish and English languages. Results: TLR pathway was found to play a key role in the fight against viruses, bacteria and other infections, as well as having antitumor immune activity. The Wnt / ß-catenin pathway participates in several biological processes such as cell differentiation, migration and adhesion, while PI3K / Akt is related to cell growth, motility and survival. Conclusions: The activation or deregulation of some components of these pathways are involved in uncontrolled proliferation of tumor cells, an important event in cervical carcinogenesis(AU)

Efeito quimiopreventivo da Beta-ionona na hepatocarcinogênese associada à fibrose hepática / Chemopreventive effect of Beta-ionone in hepatocarcinogenesis associated with hepatic fibrosis

O carcinoma hepatocelular (HCC) é a neoplasia primária mais frequente que acomete o fígado, a quarta principal causa de morte relacionada ao câncer e apresenta mau prognóstico. A fibrose hepática está presente em grande parte dos casos de HCC e é um dos principais fatores de risco para esta afecção. Segundo estudos prévios do grupo, a ß-ionona (BI), presente em uvas e aromatizantes de vinho, apresenta potencial quimiopreventivo na hepatocarcinogênese principalmente por reduzir o número e tamanho de lesão pré neoplásica (LPN) e inibir a proliferação celular. No entanto, até o presente não foram identificados na literatura estudos que investigaram o efeito deste isoprenóide no processo fibrótico e na hepatocarcinogênese a ele associada. Desta forma, este estudo pretendeu investigar o potencial efeito quimiopreventivo da BI na hepatocarcinogênese associada à fibrose hepática. Para tanto, ratos machos Wistar foram tratados com óleo de milho (OM) [0,25 ml / 100 g de peso corporal (p.c.); Grupo de OM] ou BI (16mg / 100g p.c.; Grupo BI) durante 18 semanas. A partir da 2ª semana, todos os animais receberam uma dose intraperitoneal de dietilnitrosamina (DEN - 50 mg / Kg p.c.) uma vez por semana até a 16ª semana. Os animais foram eutanasiados em diferentes períodos do protocolo experimental: na 10a semana (grupos OMP1 e BIP1), na 14a semana (grupos OMP2 e BIP2) e na 18ª semana (grupos OMP3 e BIP3). O isoprenóide demonstrou, de maneira inédita na literatura, inibir o desenvolvimento da fibrose hepática em diferentes estágios da hepatocarcinogênese (pontos 1, 2 e 3) por reduzir (p < 0,05) a porcentagem de área marcada para picrosirius. Além disso, BI reduziu a porcentagem de área positiva para α- SMA (p < 0,05) e as concentrações de hidroxiprolina (p < 0,05) no ponto 2. Foi observada ação quimiopreventiva da BI nas fases iniciais da hepatocarcinogênese (pontos 1 e 2) mesmo em modelo associada a fibrose por reduzir (p < 0,05) o número e porcentagem de área do corte ocupada por LPN GSTP positivas. Este efeito não foi observado em fase mais avançada da hepatocarcinogênese (ponto 3). Corroborando este dado não foram observadas diferenças em relação ao número de tumores (p>=0,05) avaliados por imageamento e por análise histopatológica. No entanto, quando comparados ao seu controle (OMP3), os animais do grupo BIP3 apresentaram menor mortalidade e menor incidência (p < 0,05) de HCC high, considerado um tipo mais agressivo de HCC, sugerindo que este composto possa atuar na agressividade das células tumorais. O grupo BIP2 demonstrou ainda menor proliferação celular (p < 0,05) quando comparado ao grupo OMP2. Assim foram avaliadas as vias de proliferação celular PI3K/AKT e MAPK/ERK, bem como as proteínas p21 e p53, relacionadas a progressão do ciclo celular. Não foram observadas(p≥0,05) alterações nestas vias por parte do isoprenóide. O presente estudo demonstrou ação protetora da BI no desenvolvimento de fibrose, bem como na hepatocarcinogênese a ela associada. Contudo, são necessárias análises complementares para elucidar mecanismos pelos quais a BI atua na carcinigênese hepática associada à fibrose

Hepatocellular carcinoma (HCC) is the primary liver cancer, the fourth leading cause of death related to cancer and presents a poor prognosis. Hepatic fibrosis is present in most cases of HCC and represents one of the main risk factors for this condition. According to previous studies of the group, ß-ionone (BI), present in grapes and wine flavorings, has a potential chemopreventive in hepatocarcinogenesis mainly by reducing the number and size of preneoplastic lesions (LPN) and inhibiting cell proliferation. However, to date, no studies have been identified in the literature that investigated the effect of this isoprenoid on the fibrotic process and in its association with hepatocarcinogenesis. Thus, this study aimed to investigate the potential chemopreventive effect of BI in hepatocarcinogenesis associated with hepatic fibrosis. Male Wistar rats were treated with corn oil (OM) [0.25 ml / 100 g body weight (b.w.); OM] or BI group (16mg / 100g b.w; BI group) for 18 weeks. From week 2, all animals received an intraperitoneal dose of diethylnitrosamine (DEN - 50 mg / kg b.w.) once in a week until week 16. The animals were euthanized at different periods of the experimental protocol: at week 10 (groups OMP1 and BIP1), at week 14 (groups OMP2 and BIP2) and week 18 (groups OMP3 and BIP3). The isoprenoid, for the first time in the literature, shown to inhibit the development of liver fibrosis at different stages of hepatocarcinogenesis (points 1, 2 and 3) by reducing (p <0.05) the percentage of the area labeled for picrosirius. Also, BI reduced the percentage of α-SMA positive area (p <0.05) and hydroxyproline concentrations (p <0.05) at point 2. BI chemopreventive action was observed in the early stages of hepatocarcinogenesis (point 1 and 2) even in a model associated with fibrosis for reducing (p <0.05) the number and percentage of the liver section area occupied by GSTP positive LPN. This effect was not observed at a later stage of hepatocarcinogenesis (point 3). Corroborating this data, no differences were observed regarding the number of tumors (p>=0.05) evaluated by imaging and histopathological analysis. However, when compared to its control (OMP3), animals from the BIP3 group had lower mortality and lower incidence (p<0.05) of HCC high, considered a more aggressive type of HCC, suggesting that this compound may act in aggressiveness of tumor cells. The BIP2 group also showed lower cell proliferation (p <0.05) when compared to the OMP2 group. Thus, PI3K / AKT and MAPK / ERK cell proliferation pathways were evaluated, as well as p21 and p53 proteins, related to cell cycle progression. No changes were observed in these pathways by the isoprenoid (p≥0.05). The present study demonstrated the protective action of BI in the development of fibrosis, as well as its association with hepatocarcinogenesis. However, further analysis is needed to elucidate mechanisms by which BI acts on fibrosis-associated liver carcinogenesis

Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer. METHODS: In the present study, 200 individuals were separated into three groups: (i) 72 women constituting the control group who were selected according to rigorous and well-established criteria; (ii) 56 patients with benign breast tumors; and (iii) 72 patients with malignant breast cancers of different clinical stages. The miR-195 and let-7a expression levels in serum were evaluated by real-time PCR. The results were assessed alone and in combination, and the analysis included an estimation of sensitivity and specificity in ROC curves. RESULTS: Compared with the benign and control groups, both microRNAs were downregulated in the malignant breast cancer patient group. Compared with the malignant group, the combination of both biomarkers in the control and benign groups showed good sensitivity and specificity in the serum with AUCs of 0.75 and 0.72, respectively. The biomarker combination for the control group versus the malignant group exhibited a better sensitivity and specificity than for the benign group versus the malignant group. CONCLUSION: These findings support the evidence that the analysis of miR-195 and let-7a can be used as a non-invasive biomarker for breast cancer detection.

Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine

Abstract Purpose: To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Methods: Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. Results: On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0.045). No inflammatory cells, dysplasia or abnormalities were observed. Staining with Alcian blue revealed a substantial reduction of goblet cells and mucins in the colon segment (Groups A and B). Conclusion: The administration of L-lysine to rats accelerated the development of transitional metaplasia in the epithelium of the colon segment in cystoplasty.

Nuevas evidencias del uso de la metformina en el tratamiento del cáncer / New evidence of the use of metformin in the treatment of cancer

La metformina es una biguanida ampliamente usada en el tratamiento de la diabetes mellitus tipo 2. Evidencias recientes proponen nuevos usos para esta vieja droga. El cáncer, que constituye un problema de salud mundial, se desarrolla con más frecuencia y peor pronóstico en los pacientes con diabetes tipo 2. Sin embargo, se ha comprobado que cuando estos son tratados con metformina presentan menor incidencia, complicaciones y mortalidad por cáncer. Por tal motivo, durante casi una década, se llevaron a cabo numerosas investigaciones epidemiológicas, básicas, preclínicas y ensayos clínicos, para fundamentar las evidencias del efecto protector y antitumoral de este medicamento. En tal sentido, se encontró que posee efectos antineoplásicos, por mecanismos sensibilizadores de la insulina, y otros, como que son pro-apoptóticos, que alteran el desarrollo de la célula madre cancerosa e interfieren con la carcinogénesis. Esto ha abierto una amplia gama de aplicaciones de la metformina en la terapéutica del cáncer, que abarcan desde los efectos preventivos, hasta las coadyuvantes de los tratamientos estándares(AU)

Metformin is a widely used biguanide in the treatment of type 2 diabetes mellitus. Recent evidence indicates new uses for this old drug. Cancer is a worldwide health problem that develops more frequently in type 2 diabetic people with worse prognosis. However, it has been demonstrated that when they are treated with metformin, the incidence, complications and mortality rates are lower. For these reasons, a number of epidemiological, basic, preclinical research studies as well as clinical assays have been conducted for almost a decade in order to substantiate evidence from the protective and antitumor effect of this drug. It was found that it has some antineoplastic effects due to insulin sensitizing mechanisms and other pro-apoptotic ones that impair the cancer stem cell development and interfere in carcinogenesis. This has shown a wide range of applications of metformin in the treatment of cancer including the preventive and coadjuvant effects of the conventional treatments(AU)

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Muertes por accidente de motocicleta y su asociación con variables relacionadas a la reproducción social en un estado del noreste brasileño / Deaths due to motorcycle accidents and their association with variables related to social reproduction in a northeastern Brazilian state

El objetivo de este artículo es identificar el comportamiento de las muertes por accidentes de motocicleta y las variables relacionadas con la teoría de la reproducción social de Samaja, para el período 2000-2005 en el estado de Pernambuco, Brasil. Se realizó un estudio ecológico con abordaje caso-control. La unidad de análisis fue el municipio. Los casos fueron definidos considerando el 20% de los municipios con los mayores coeficientes bayesianos empíricos locales de mortalidad por accidentes de motocicleta y los controles, como el 40% de los municipios con menores coeficientes de mortalidad por accidentes de motocicleta. Los municipios con mayor probabilidad de altos coeficientes de mortalidad por accidentes de motocicleta mostraron factores de crecimiento poblacional altos, así como de crecimiento de la flota de vehículos, bajas densidades demográficas, bajo PBI per cápita, y más de 20 motocicletas por mil habitantes. Se concluye que las variables relacionadas a las macropolíticas mostraron una mayor fuerza para explicar las probabilidades de defunciones por accidentes de motocicleta.

The objective of this article was to identify the association between motorcycle deaths and variables related to Samaja's theory of social reproduction in the period 2000-2005 in the state of Pernambuco. An ecological, case-control study was carried out, with municipalities as the unit of analysis. Cases were defined as the 20% of municipalities with the highest local empirical Bayesian coefficients for mortality due to motorcycle accidents, and controls as the 40% with the lowest coefficients. The municipalities with the greatest chances of high coefficients for mortality due to motorcycle accidents showed high population growth factors and increases in the total fleet of motorcycles, with low population densities, low GDP per capita, and more than 20 motorcycles per thousand inhabitants. We conclude that the variables related to macro-policies proved to have greater force in explaining higher chances of motorcycle death.

O papel da inflamação na carcinogênese induzida pelo HPV / The role of inflammation in HPV carcinogenesis

A inflamação é uma estratégia de defesa inata que evoluiu nos organismos superiores, contra agentes invasores externos e moléculas nocivas. Estudos recentes mostram que a inflamação opera como um sistema muito mais complexo do que se imaginava antes, em termos moleculares, envolvendo diversos processos na sua iniciação, regulação e resolução. Na última década, tornou-se evidente que a inflamação crônica está fortemente associada com câncer, desempenhando um papel importante na tumorigênese. Uma das causas de inflamação crônica são as infecções persistentes por agentes patogênicos virais, com destaque para o papilomavírus humano (HPV). A ligação entre a inflamação crônica decorrente da infecção persistente por agentes infecciosos e o câncer está atualmente sendo apontada como um dos mecanismos-chave para o controle do surgimento de novos casos de carcinomas. Por esse motivo, consultamos os bancos de dados eletrônicos PubMed/Medline, Lilacs, Embase e SciELO, sem restrição linguística, à procura de artigos que abordassem avanços recentes sobre os mecanismos envolvidos na inflamação, sua participação no processo de carcinogênese, com ênfase na correlação entre inflamação e o desenvolvimento do câncer associado ao HPV, os quais foram incluídos na presente revisão.(AU)

Inflammation is an innate defense strategy that evolved in higher organisms against external invaders and harmful molecules. Recent studies show that inflammation operates as a much more complex system than imagined before, in molecular terms, involving many processes in its initiation, regulation and resolution. In the very last decade, it has become evident that chronic inflammation is strongly associated with cancer and plays an important role in tumorigenesis. One of the causes of chronic inflammation are persistent infections by viral pathogens, particularly human papillomavirus (HPV). The link between chronic inflammation resulting from persistent infection by infectious agents and cancer is currently being suggested as a key mechanism for controlling the appearance of new cases of carcinoma. Therefore, we consult electronic databases such as PubMed/Medline, Lilacs, Embase and SciELO, without language restriction, looking for papers discussing recent advances on the mechanisms involved in inflammation, their participation in the process of carcinogenesis, with emphasis on the correlation between inflammation and the development of cancer associated with HPV, which were included in this review.(AU)

Cancer stem cells - the current status of an old concept: literature review and clinical approaches

As regards their morphology and biology, tumours consist of heterogeneous cell populations. The cancer stem cell (CSC) hypothesis assumes that a tumour is hierarchically organized and not all of the cells are equally capable of generating descendants, similarly to normal tissue. The only cells being able to self-renew and produce a heterogeneous tumour cell population are cancer stem cells. CSCs probably derive from normal stem cells, although progenitor cells may be taken into consideration as the source of cancer stem cells. CSCs reside in the niche defined as the microenvironment formed by stromal cells, vasculature and extracellular matrix. The CSC assays include FACS sorting, xenotransplantation to immunodeficient mice (SCID), incubation with Hoechst 33342 dye, cell culture in non-adherent conditions, cell culture with bromodeoxyuridine. CSCs have certain properties that make them resistant to anticancer therapy, which suggests they may be the target for potential therapeutic strategies.