RESUMO

Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17ß-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.

Assuntos

Laurencia , MicroRNAs , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Camundongos , Animais , Laurencia/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/patologia , MicroRNAs/genética , Camundongos Transgênicos , Carcinogênese , Papillomaviridae/genética

RESUMO

Introducción: La disfagia resulta de varios mecanismos fisiopatológicos donde sus síntomas no son estáticos ni homogéneos en las personas, especialmente cuando existe disfagia orofaríngea neurogénica. Objetivo: Conocer la percepción y comportamiento en el tiempo de síntomas de disfagia mediante el instrumento Eating Assessment Tool-10 (EAT-10) en pacientes con disfagia orofaríngea neurogénica, con el fin de visualizar la dinámica clínica de esta forma de disfagia. Metodología: Estudio observacional tipo cohorte en pacientes con disfagia orofaríngea neurogénica de causas neurológicas y neuromusculares, con seguimiento a tres y seis meses y diligenciamiento del EAT-10 al momento basal, tercer y sexto mes. Resultados: Un total de 90 personas con evaluación basal, de las cuales el 56,7 % (51/90) lograron seguimiento al tercer mes y 25,6 % (23/90) al sexto mes. Los síntomas de disfagia con mayor autopercepción en los tres momentos fueron la dificultad para tragar sólidos, sensación de comida pegada en garganta y tos al comer. La odinofagia no fue un síntoma habitualmente percibido. La puntuación total del EAT-10 estuvo entre 16,61 ± 9 y 18,1 ± 9,5 puntos en general. En pacientes con seguimiento completo se observó variación en la autopercepción para tragar líquidos y pastillas. Se observó variación del puntaje al ajustarlo por recepción de terapias. Discusión: Las enfermedades neurológicas y neuromusculares impactan directamente la deglución con gravedad entre leve a profunda, donde la autopercepción de síntomas deglutorios es dinámica, pero con síntomas cardinales de disfagia orofaríngea en el tiempo. Conclusiones: El reconocimiento y seguimiento de síntomas de disfagia deben ser aspectos usuales en la atención de pacientes con enfermedades neurológicas y neuromusculares.

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Introduction: Dysphagia results from several pathophysiological mechanisms where its symptoms are not static or homogeneous in people, especially when there is neurogenic oropharyngeal dysphagia. Objective: To know the perception and behavior over time of symptoms of dysphagia using the Eating Assessment Tool-10 (EAT-10) in patients with neurogenic oropharyngeal dysphagia to visualize the clinical dynamics of this form of dysphagia. Methodology: Observational cohort study in patients with neurogenic oropharyngeal dysphagia of neurological and neuromuscular causes with, follow-up at three and six months, and completion of the EAT-10 at baseline, third and sixth month. Results: A total of 90 people with baseline evaluation were included, of whom 56.7% (51/90) achieved follow-up at the third month and 25.6% (23/90) at the sixth month. Symptoms of dysphagia with greater self-perception at all three moments were difficulty swallowing solids, sensation of food stuck in the throat and coughing when eating. Odynophagia was not a commonly perceived symptom. The total score of the EAT-10 was between 16.61±9 and 18.1±9.5 points in general. In patients with complete follow-up, variation in self-perception of swallowing liquids and pills was observed. Variation of the score when adjusting for the reception of therapies. Discussion: Neurological and neuromuscular diseases directly impact swallowing with mild to profound severity, where self-perception of swallowing symptoms is dynamic, but with cardinal symptoms of oropharyngeal dysphagia over time. Conclusions: The recognition and monitoring of dysphagia symptoms should be usual aspects in the care of patients with neurological and neuromuscular diseases.

RESUMO

Introducción: la disfagia es un trastorno de la deglución, el cual es habitualmente desatendido por profesionales de la salud, en especial la disfagia orofaríngea neurogénica, que es capaz de producir varios síntomas, signos y complicaciones secundarias en los pacientes. Objetivo: realizar una caracterización clínica incluyendo percepción de síntomas de disfagia en pacientes con disfagia orofaríngea neurogénica de causas neurológicas y neuromusculares en Antioquia, Colombia entre los años 2019 y 2021. Metodología: estudio transversal realizado en 80 pacientes con disfagia orofaríngea neurogénica confirmada a través de la herramienta Eating Assessment Tool-10, evaluación clínica y/o resultados de video fluoroscopia de la deglución. Resultados: 71 pacientes presentaron causas neurológicas centrales. La enfermedad cerebrovascular y la enfermedad de Parkinson fueron las etiologías más frecuentes. Solo 18% de los pacientes con causas neurológicas y 33% con causas neuromusculares reportaron tolerancia a todas las consistencias de alimentos. Mediana de 16 puntos en cuanto a autopercepción de síntomas de disfagia mediante el instrumento Eating Assessment Tool-10, con puntuaciones más altas en pacientes con presencia de gastrostomía, antecedente de neumonía, odinofagia y alteración en la oclusión mandibular al examen físico. En los pacientes con causas neurológicas hubo mayor presencia de signos motores linguales y apraxias orofaciales. Conclusión: existen características clínicas como sensación de comida pegada, dificultad para tragar alimentos sólidos, tos y ahogo al tragar, que son útiles en el reconocimiento de casos de disfagia orofaríngea, y apoyan que esta genera más síntomas que signos al examen físico en pacientes con condiciones neurológicas y neuromusculares.

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Introduction: dysphagia is a swallowing disorder that is usually neglected by health professionals, especially neurogenic oropharyngeal dysphagia, which can produce various symptoms, signs and secondary complications in patients. Objective: to perform a clinical characterization, including perception of dysphagia symptoms, in patients with neurogenic oropharyngeal dysphagia of neurological and neuromuscular causes in Antioquia, Colombia between 2019 and 2021. Methodology: cross-sectional study conducted in 80 patients with neurogenic oropharyngeal dysphagia confirmed through the Eating Assessment Tool-10, clinical assessment and/ or video fluoroscopy results of swallowing. Results: 71 patients presented central neurological causes. Cerebrovascular disease and Parkinson's disease were the most frequent etiologies. Only 18% of patients with neurological causes and 33% with neuromuscular causes reported tolerance to all food consistencies. Median of 16 points in terms of self-perception of dysphagia symptoms using the Eating Assessment Tool-10, with higher scores in patients with gastrostomy, a history of pneumonia, odynophagia, and abnormal mandibular occlusion on physical examination. In patients with neurological causes, there was a greater presence of lingual motor signs and orofacial apraxia. Conclusion: there are clinical characteristics such as a sensation of stuck food, difficulty swallowing solid foods, coughing, and choking when swallowing, which are useful in recognizing cases of oropharyngeal dysphagia, and support that this generates more symptoms than signs on physical examination in patients with neurological and neuromuscular conditions.

Assuntos

Humanos , Masculino , Feminino , Transtornos de Deglutição , Sinais e Sintomas , Doenças do Sistema Nervoso , Manifestações Neurológicas , Doenças Neuromusculares

RESUMO

Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets.

RESUMO

Infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC), but viral infection alone does not guarantee the development of this malignancy. Indeed, deficiencies of dietary micronutrients could favor cervical cancer development in individuals that harbor HR-HPV infections. The status of retinoid levels, natural and synthetic derivatives of vitamin A, is important in maintaining cellular differentiation of the cervical epithelium. Moreover, many studies show a link between deficient intake of retinoids or alteration of the retinoid receptors and CC development. In spite of this, the effect of vitamin A deficiency (VAD) in presence of HR-HPV oncoproteins on cervical carcinogenesis in vivo has not been reported. Transgenic mice expressing E6 or E7 oncoproteins (K14E6 or K14E7 mice, respectively) were used to evaluate the possible role of VAD in the development of malignant cervical lesions. The survival of the mice in VAD condition was studied, and histopathological analysis and immunohistochemical detection of molecular cancer markers such as the tumor suppressor retinoic acid receptor beta (RARß), proliferating cell nuclear antigen (PCNA), cleaved caspase 3, and the tumor suppressor protein p16INK4A (inhibitor of CDK4) were performed. Our results show that K14E6/VAD mice showed moderate cervical dysplasia; notably, K14E7/VAD mice developed severe cervical dysplasia and cervical in situ carcinoma at an early age. VAD synergizes with HPV16E7 oncoprotein expression favoring cervical carcinogenesis in vivo.

Assuntos

Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Deficiência de Vitamina A/complicações , Animais , Colo do Útero/metabolismo , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Transgênicos , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Deficiência de Vitamina A/genética , Deficiência de Vitamina A/metabolismo , Deficiência de Vitamina A/patologia

RESUMO

The high-risk human papillomavirus (HR-HPV) E7 oncoprotein appears to be a major determinant for cell immortalization and transformation altering critical processes such as cell proliferation, apoptosis, and immune response. This oncoprotein plays an essential role in cervical carcinogenesis, but other cofactors such as long-term use of hormonal contraceptives are necessary to modulate the risk of cervical cancer (CC). The role of HR-HPVs in the alteration of microRNA (miRNA) levels in persistent viral infections currently remains unclear. The aim of this study was to evaluate the miR-34a and miR-15b expression levels in the murine HPV16K14E7 (K14E7) transgenic model after chronic estrogen (E2) treatment and their involvement in CC. Interestingly, results showed that, although miR-34a expression is elevated by the HPVE7 oncogene, this expression was downregulated in the presence of both the E7 oncoprotein and chronic E2 in cervical carcinoma. On the other hand, miR-15b expression was upregulated along cervical carcinogenesis mainly by the effect of E2. These different changes in the expression levels of miR-34a and miR-15b along cervical carcinogenesis conduced to low apoptosis levels, high cell proliferation and finally, to cancerous cervical tissue development. In this work, we also determined the relative mRNA expression of Cyclin E2 (Ccne2), Cyclin A2 (Ccna2), and B cell lymphoma 2 (Bcl-2) (target genes of miR-34a and miR-15b); Sirtuin 1 (Sirt1), Cmyc, and Bax (miR-34a target genes); and p21/WAF1 (mir15b target gene) and the H-ras oncogene. Given the modifications in the expression levels of miR-34a and miR-15b during the development of cervical cancer, it will be useful to carry out further investigation to confirm them as molecular biomarkers of cancer.

Assuntos

MicroRNAs , Neoplasias do Colo do Útero , Animais , Proliferação de Células , Colo do Útero , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , MicroRNAs/genética , Neoplasias do Colo do Útero/genética

RESUMO

Circulating biological markers, such as miRNAs, hold the greatest possibilities to complement tissue biopsy and clinical diagnostic tests. The objective of this study was to evaluate the relative abundance of three circulating miRNAs in serum from 17 HPV16-positive patients with early cervical lesions known as Low-Grade Squamous Intraepithelial Lesions (LSILs). The expression of circulating microRNAs miR-15b, miR-34a and miR-218 in patients with LSILs was compared to 23 HPV-negative individuals showing normal cervical epithelium (healthy women) and 23 Squamous Cell Carcinoma (SCC) samples. The expression levels of miR-15b remained unchanged while those of miRNAs 34a and 218 were relatively high in serum obtained from LSIL patients in comparison with healthy women (results were statistically significant with a p of < 0.01 or < 0.001). According to previous findings, miR-15b was overexpressed and miRNAs 34a and 218 were underexpressed in serum from SCC patients. Additionally, the mRNA expression levels of some selected gene targets were determined [Cyclin D1 (CCND1), Cyclin E1 (CCNE1), B-cell lymphoma 2 (Bcl-2) and MutS homolog 2 (MSH-2)]. All serum results correlated with tissue samples from the same patients. We propose that circulating microRNAs can be valuable as molecular markers for the early follow-up of cervical carcinogenesis risk.

Assuntos

MicroRNA Circulante/sangue , MicroRNAs/sangue , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Colo do Útero/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/sangue , Adulto Jovem , Displasia do Colo do Útero/sangue

RESUMO

OBJECTIVE: This work aimed to determine if cataractous changes associated with EMT occurring in the K14E6 mice lenses are associated with TGF-ß and Wnt/ß-catenin signaling activation. MATERIALS AND METHODS: Cataracts of K14E6 mice were analysed histologically; and components of TGF-ß and Wnt/ß-catenin signaling were evaluated by Western blot, RT-qPCR, in situ RT-PCR, IHC, or IF technics. Metalloproteinases involved in EMT were also assayed using zymography. The endogenous stabilisation of Smad7 protein was also assessed using an HDAC inhibitor. RESULTS: The K14E6 mice, which displayed binocular cataracts in 100% of the animals, exhibited loss of tissue organisation, cortical liquefaction, and an increase in the number of hyperproliferative-nucleated cells with mesenchymal-like characteristics in the lenses. Changes in lenses' cell morphology were due to actin filaments reorganisation, activation of TGF-ß and Wnt/ß-catenin pathways, and the accumulation of MTA1 protein. Finally, the stabilisation of Smad7 protein diminishes cell proliferation, as well as MTA1 protein levels. CONCLUSION: The HPV16-E6 oncoprotein induces EMT in transgenic mice cataracts. The molecular mechanism may involve TGF-ß and Wnt/ß-catenin pathways, suggesting that the K14E6 transgenic mouse could be a useful model for the study or treatment of EMT-induced cataracts.

Assuntos

Catarata/metabolismo , Transição Epitelial-Mesenquimal , Papillomavirus Humano 16/metabolismo , Proteínas Oncogênicas Virais/biossíntese , Proteínas Repressoras/biossíntese , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt , Animais , Catarata/genética , Catarata/patologia , Modelos Animais de Doenças , Papillomavirus Humano 16/genética , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta/genética

RESUMO

Los dientes supernumerarios en la región del tercer molar inferior sonpoco frecuentes. Cuando se presentan en posición distal se les denominadistomolares o distodens. Algunos autores los denominan cuarto molar; ésta denominación es la menos aceptada, ya que el cuarto molarno forma parte de la fórmula dental permanente, sino que es un dientesupernumerario. Cuando éste se presenta paralelo a los molares, en lacara externa o interna de la mandíbula, se denomina paramolar. El manejo quirúrgico suele ser complejo y requiere consideraciones especiales. Presentamos dos casos de dientes supernumerarios en la región del tercer molar: distomolar y paramolar; describimos su diagnóstico, etiología y la técnica quirúrgica empleada.

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Supernumerary teeth in the lower third-molar region are rare. When these are located in the region posterior to the third molar, they are known as ®distomolars¼ or ®distodens¼. Some authors refer to them as ®fourth molars¼, a term that is somewhat less accepted due to the fact that the fourth molar is not part of the permanent dentition, but rather a supernumerary tooth. When a distomolar occurs parallel to the molars, either on the outer or inner surface of the jaw, it is known as a ®paramolar¼. Surgical management is often complex and requires special considerations. We report two cases of supernumerary teeth in the third-molar region, one distomolar and one paramolar, and describe their diagnosis, etiology, and the surgical technique employed.

Assuntos

Humanos , Masculino , Adulto , Adulto Jovem , Dente Supranumerário/cirurgia , Dente Supranumerário/etiologia , Dente Serotino/anormalidades , Unidade Hospitalar de Odontologia , Dente Supranumerário/diagnóstico , Extração Dentária/métodos , México , Osteotomia/métodos , Retalhos Cirúrgicos

RESUMO

The role of p53 as modulator of OxPhos and glycolysis was analyzed in HeLa-L (cells containing negligible p53 protein levels) and HeLa-H (p53-overexpressing) human cervix cancer cells under normoxia and hypoxia. In normoxia, functional p53, mitochondrial enzyme contents, mitochondrial electrical potential (ΔΨm) and OxPhos flux increased in HeLa-H vs. HeLa-L cells; whereas their glycolytic enzyme contents and glycolysis flux were unchanged. OxPhos provided more than 70% of the cellular ATP and proliferation was abolished by anti-mitochondrial drugs in HeLa-H cells. In hypoxia, both cell proliferations were suppressed, but HeLa-H cells exhibited a significant decrease in OxPhos protein contents, ΔΨm and OxPhos flux. Although glycolytic function was also diminished vs. HeLa-L cells in hypoxia, glycolysis provided more than 60% of cellular ATP in HeLa-H cells. The energy metabolism phenotype of HeLa-H cells was reverted to that of HeLa-L cells by incubating with pifithrin-α, a p53-inhibitor. In normoxia, the energy metabolism phenotype of breast cancer MCF-7 cells was similar to that of HeLa-H cells, whereas p53shRNAMCF-7 cells resembled the HeLa-L cell phenotype. In hypoxia, autophagy proteins and lysosomes contents increased 2-5 times in HeLa-H cells suggesting mitophagy activation. These results indicated that under normoxia p53 up-regulated OxPhos without affecting glycolysis, whereas under hypoxia, p53 down-regulated both OxPhos (severely) and glycolysis (weakly). These p53 effects appeared mediated by the formation of p53-HIF-1α complexes. Therefore, p53 exerts a dual and contrasting regulatory role on cancer energy metabolism, depending on the O2level.

Assuntos

Neoplasias da Mama/metabolismo , Metabolismo Energético , Proteína Supressora de Tumor p53/fisiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias da Mama/patologia , Divisão Celular , Hipóxia Celular , Feminino , Células HeLa , Humanos , Células MCF-7 , Neoplasias do Colo do Útero/patologia

RESUMO

High-risk human papillomaviruses (HR-HPVs) are the causative agents of cervical cancer, and they are also associated with a subset of head and neck squamous cell carcinomas. In addition, HPVs have also been postulated in the development of non-melanoma skin cancers (NMSC). In these cancers, the oncogene E6 is best known for its ability to inactivate the tumor suppressor p53 protein. Interestingly, in transgenic mice for HPV16 E6 (K14E6), it was reported that E6 alone induced epithelial hyperplasia and delay in differentiation in skin epidermis independently of p53 inactivation. Transforming growth factor ß (TGFß) is an important regulator of cell growth/differentiation and apoptosis, and this pathway is often lost during tumorigenesis. Ultraviolet radiation B (UVB) exposure activates diverse cellular responses, including DNA damage and apoptosis. In this study, we investigated whether the E6 oncogene alone or in combination with UVB dysregulate some components of the TGFß pathway in the epidermis of K14E6 mice. We used 8-day-old K14E6 and non-transgenic mice irradiated and unirradiated with a single dose of UVB. We found that the E6 oncogene and UVB irradiation impair the TGFß pathway in epidermis of K14E6 mice by downregulation of the TGFß type II receptor (TßRII). This loss of TßRII prevents downstream activation of Smad2 and target genes as p15, an important regulator of cell cycle progression. In summary, the TGFß signalling in cells of the epidermis is downregulated in our mouse model by both the E6 oncoprotein and the UVB irradiation.

Assuntos

Epiderme/efeitos da radiação , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/efeitos da radiação , Raios Ultravioleta , Animais , Apoptose/efeitos da radiação , Dano ao DNA/efeitos da radiação , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Regulação para Baixo/genética , Regulação para Baixo/efeitos da radiação , Epiderme/metabolismo , Epiderme/patologia , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/metabolismo , Fosforilação , Proteínas Repressoras/metabolismo , Proteína Smad2 , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/efeitos da radiação

RESUMO

To gain insights into the antitumor mechanisms of resveratrol (RES), we carried out a DNA microarray analysis in the breast cancer cell line MCF-7 to study the global gene expression profile induced by RES treatment. The mRNA expression level of 19 734 well-characterized human genes from MCF-7 cells was determined using Affymetrix microarrays under two different RES treatments: 150 µmol/l (IC(50)) and 250 µmol/l during 48 h. A total of 1211 genes were found to have altered mRNA expression levels of two-fold or more in the 150 µmol/l RES-treated group (518 upregulated and 693 downregulated genes). However, 2412 genes were found to have altered expression levels of two-fold or more in the 250 µmol/l RES-treated group (651 genes upregulated and 1761 downregulated). Under both conditions of RES treatment, several genes of mismatch repair, DNA replication, homologous recombination (HR), and cell cycle were strongly inhibited. Consistently, we found decreased protein levels of the MRN complex (MRE11-NBS1-RAD50), an important complex of the HR DNA repair pathway. The ability to inhibit the expression of DNA repair genes by RES could help to overcome drug resistance commonly shown by transformed cells and to provide a solid basis for carrying out clinical trials with RES, alone or in combination with other agents, to enhance treatment efficacy, reduce toxicity, and overcome chemoresistance. Remarkably, after RES treatment, we found a decrease in NBS1 and MRE11 protein levels, two major proteins involved in HR, which suggests that RES could be used to sensitize cancer cells to cell death in combination with anticancer drugs.

Assuntos

Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Regulação para Baixo/efeitos dos fármacos , Estilbenos/farmacologia , Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/fisiologia , Feminino , Humanos , Resveratrol

RESUMO

La infección persistente por el virus del papiloma humano de alto riesgo (HR-HPV) está relacionada con la aparición de cáncer cervical (CC), una de las principales causas de mortalidad por cáncer en todo el mundo. La infección se produce en la zona de transformación, la región más sensible del cérvix a estrógenos y retinoides. El CC afecta a un bajo porcentaje de mujeres infectadas por HR-HPV y tarda en desarrollarse hasta décadas después de la infección, lo que sugiere que el HR-HPV es necesario pero no suficiente para causar CC. Otros factores son necesarios para la progresión desde la infección por HR-HPV hasta el cáncer, como por ejemplo: uso de anticonceptivos orales por largos períodos, fumar, partos múltiples, falta de micronutrientes, particularmente una dieta baja en retinoides, los cuales alteran la diferenciación epitelial, el crecimiento celular y la apoptosis de las células malignas. La detección precoz del HR-HPV y el manejo de lesiones precancerosas, aunado a un conocimiento detallado de factores de riesgo adicionales, puede ser una estrategia para prevenir esta enfermedad. La presente revisión se enfoca en explicar el efecto de los estrógenos, la deficiencia de retinoides y el HR-HPV en la aparición del CC. Dichos cofactores pueden actuar en conjunto para inducir transformación neoplásica en el epitelio escamoso del cérvix, promoviendo un segundo evento genético o epigenético que lleve a la aparición del CC.

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ersistent infection with high-risk human papillomaviruses (HR-HPVs) is involved in cervical cancer (CC),a major cause of cancer mortality worldwide. Infection occurs primarily at the transformation zone (TZ),the most estrogen- and retinoid-sensitive region of the cervix. Development of CC affects a small per-centage of HR-HPV-infected women and often takes decades after infection, suggesting that HR-HPVis a necessary but not sufficient cause of CC. Thus, other cofactors are necessary for progression fromcervical HR-HPV infection to cancer such as long-term use of hormonal contraceptives, multiparity, smo-king, as well as micronutrient depletion and in particular retinoid deficiency, which alters epithelial diffe-rentiation, cellular growth and apoptosis of malignant cells. Therefore, early detection of HR-HPV andmanagement of precancerous lesions together with a profound understanding of additional risk factorscould be a strategy to avoid this disease. In this review we focus on the synergic effect of estrogens,retinoid deficiency and HR-HPVs in the development of CC. These risk factors may act in concert to indu-ce neoplastic transformation in the squamous epithelium of the cervix, setting the stage for secondarygenetic or epigenetic events leading to cervical cancer.

Assuntos

Estrogênios , Infecções por Papillomavirus , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Retinoides

RESUMO

La infección persistente por el virus del papiloma humano de alto riesgo (HR-HPV) está relacionada con la aparición de cáncer cervical (CC), una de las principales causas de mortalidad por cáncer en todo el mundo. La infección se produce en la zona de transformación, la región más sensible del cérvix a estrógenos y retinoides. El CC afecta a un bajo porcentaje de mujeres infectadas por HR-HPV y tarda en desarrollarse hasta décadas después de la infección, lo que sugiere que el HR-HPV es necesario pero no suficiente para causar CC. Otros factores son necesarios para la progresión desde la infección por HR-HPV hasta el cáncer, como por ejemplo: uso de anticonceptivos orales por largos períodos, fumar, partos múltiples, falta de micronutrientes, particularmente una dieta baja en retinoides, los cuales alteran la diferenciación epitelial, el crecimiento celular y la apoptosis de las células malignas. La detección precoz del HR-HPV y el manejo de lesiones precancerosas, aunado a un conocimiento detallado de factores de riesgo adicionales, puede ser una estrategia para prevenir esta enfermedad. La presente revisión se enfoca en explicar el efecto de los estrógenos, la deficiencia de retinoides y el HR-HPV en la aparición del CC. Dichos cofactores pueden actuar en conjunto para inducir transformación neoplásica en el epitelio escamoso del cérvix, promoviendo un segundo evento genético o epigenético que lleve a la aparición del CC. (AU)

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ersistent infection with high-risk human papillomaviruses (HR-HPVs) is involved in cervical cancer (CC),a major cause of cancer mortality worldwide. Infection occurs primarily at the transformation zone (TZ),the most estrogen- and retinoid-sensitive region of the cervix. Development of CC affects a small per-centage of HR-HPV-infected women and often takes decades after infection, suggesting that HR-HPVis a necessary but not sufficient cause of CC. Thus, other cofactors are necessary for progression fromcervical HR-HPV infection to cancer such as long-term use of hormonal contraceptives, multiparity, smo-king, as well as micronutrient depletion and in particular retinoid deficiency, which alters epithelial diffe-rentiation, cellular growth and apoptosis of malignant cells. Therefore, early detection of HR-HPV andmanagement of precancerous lesions together with a profound understanding of additional risk factorscould be a strategy to avoid this disease. In this review we focus on the synergic effect of estrogens,retinoid deficiency and HR-HPVs in the development of CC. These risk factors may act in concert to indu-ce neoplastic transformation in the squamous epithelium of the cervix, setting the stage for secondarygenetic or epigenetic events leading to cervical cancer.(AU)

Assuntos

Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/prevenção & controle , Retinoides , Estrogênios , Infecções por Papillomavirus

RESUMO

Objetivo: Determinar la prevalencia de vaginitis y vaginosis bacteriana en el personal policial de la provincia de Ica, Perú. Material y métodos: Se realizó un estudio de tipo descriptivo y transversal, en personal policial de la provincia de Ica constituida por 80 mujeres. Resultados: Al evaluar las características macroscópicas de la secreción vaginal se encontró, en relación al tipo: 48,8% blanquecina, 23,8% amarillo verdosa, 12,5% blanco grisáceo y 15% amarillento; en cuanto a la cantidad: 58,8% fue regular, 23.8% y escasa; con respecto a la consistencia: 41,3% espumosa, 31,3% homogénea-adherente y grumosa 27,5%. Al evaluar el olor, 42,5% tenía olor normal, 40% maloliente. Mediante coloración Gram se halló gran negativos: una cruz en el 45%, dos cruces en 42,5%;gran positivos: una cruz en 41.3%, dos cruces en 26.3% y ninguno en 32.5%; lactobacilos: una cruz en 27.5%, dos cruces en 55; Mediante coloración Giemsa se halló positividad en 77,5% de las muestras estudiadas. En el 27,5% de las mujeres se halló Trichomona vaginalis en la secreción vaginal, en 12,5% Gardenella y en 11,2% Candida sp. Conclusiones: La prevalencia de vaginitis es 38,75% y la prevalencia de vaginosis bacteriana fue 12,50%.

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Objective: To determine the prevalence of vaginitis and bacterial vaginosis in female police personnel in the city of Ica. Materials and Methods: A descriptive-transversal investigation in the city of Ica in 80 female police was made. Results: In 27.50% Trichomona vaginalis in vaginal discharge was found, in 12.50% Gardenella and in 11.25% Candidasp. At macroscopic characteristics of vaginal discharge were found these types: 48.8% white, 23.80% greenish yellow, 12.5% grayish white and 15.0% off-white yellowish; in terms of amount: 58.8% regular, low in 23.8% and abundant at 17.5%; about the consistency: 41.3% foam, 31.3% homogeneous, adherent and 27.5% lumpy. In assessing the odor: 42.5% normal, 40.0% malodorous and 17.5% smelled fishy. Gram staining found Gram negatives: a cross in 45.0%, two crosses in 42.5% and 12.5% none, Gram positives: a cross at 41.3%, two crosses in 26.3% and 32.5% none, lactobacilli: a cross in 27.5%, two crosses in 55.0% and 17.5% none. By Giemsa stainingwas found positive in 77.5% of the samples. Conclusions: The prevalence of vaginitis is 38.75% and the prevalence of bacterial vaginosis is 12.50%.

Assuntos

Humanos , Feminino , Candidíase , Polícia , Vaginite por Trichomonas , Vaginite/epidemiologia , Vaginose Bacteriana/epidemiologia , Epidemiologia Descritiva , Estudos Retrospectivos , Estudos Observacionais como Assunto , Peru

RESUMO

BACKGROUND: Prevention providers wonder whether benefits achieved in the original, researcher-led, efficacy trials of interventions are replicated when the intervention is delivered in real-world settings by their agency's staff. METHODS: A replication study was conducted at 2 public sexually transmitted disease (STD) clinics (New York City and San Juan, PR). Using a controlled trial design, intervention (VOICES/VOCES) and comparison conditions (regular clinic services) were assigned in alternating 4-week blocks. Trained agency staff delivered the intervention. Effectiveness was assessed for incident STDs, redemption of coupons for condoms at neighborhood location after the visit, and improved knowledge and attitudes about STDs and condoms. RESULTS: A total of 3365 patients were recruited, completed the protocol, and followed through STD surveillance systems for an average of 17 months. Of 397 with an incident infection, 226 (13.4%) were among those enrolled during comparison blocks; 171 were among those in the intervention condition (10.2%). Controlling for site and gender, participants enrolled during intervention blocks were significantly less likely to have an incident STD reported to the surveillance system (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96). Intervention block participants scored higher on scales of STD knowledge (4.89 vs. 3.87, P < 0.001) and condom knowledge, attitude, and efficacy (10.98 vs. 9.16, P < 0.001). More of those exposed to VOICES/VOCES redeemed condoms (P < 0.05). Positive effects were more consistent in New York, which may be related to fidelity of implementation. CONCLUSIONS: A packaged human immunodeficiency virus prevention intervention can be delivered by agencies, with benefits similar to those achieved in the research setting.

Assuntos

Atenção à Saúde , Infecções por HIV/prevenção & controle , Promoção da Saúde , Avaliação de Programas e Projetos de Saúde , Infecções Sexualmente Transmissíveis/prevenção & controle , Adolescente , Adulto , Idoso , Instituições de Assistência Ambulatorial , Centers for Disease Control and Prevention, U.S. , Preservativos/estatística & dados numéricos , Difusão de Inovações , Feminino , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Porto Rico/epidemiologia , Comportamento de Redução do Risco , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem

Assuntos

Síndrome da Imunodeficiência Adquirida/patologia , Doenças da Vulva/patologia , Candidíase/patologia , Condiloma Acuminado/patologia , Feminino , Herpes Simples/patologia , Humanos , Molusco Contagioso/patologia , Sarcoma de Kaposi/patologia , Tuberculose Cutânea/patologia

RESUMO

SHORT SUMMARY: Syphilis cases were reviewed to see if reported stages met the Centers for Disease Control and Prevention case definition. Classification was excellent for primary and secondary and good for late latent, but half of early latent and unknown duration were misclassified. New surveillance definitions are suggested, comments requested. BACKGROUND: Uncertainty when staging latent syphilis should lead clinicians to call it late latent (requires more treatment) and disease investigators to call it early latent (priority for partner investigation). Accurate surveillance requires consistent case definitions. OBJECTIVE: Assess validity of reported syphilis stages. METHODS: Record reviews in 6 jurisdictions to determine if reported cases met the Centers for Disease Control and Prevention case definitions. RESULTS: Nine hundred seventy-three records from 6 jurisdictions in 2002 showed excellent agreement for reported primary (94.0%) and secondary (95.4%), good agreement for late latent (80.2%), and poor agreement for early latent (48.4%) and unknown duration (49.7%). Unknown duration (age < or =35 and nontreponemal test titer > or =32) was often misinterpreted to mean "not known." Early latent (within the past year, documented: seroconversion, fourfold titer increase, symptoms, or contact with an independently documented early syphilis case) was often misinterpreted to include patients with risky behavior, young age, or high nontreponemal test titers. CONCLUSIONS: The unknown duration stage should be dropped. Surveillance of latent syphilis would be more consistent if cases were reported as having high or low titers on nontreponemal test. Alternative approaches are solicited from readers.

Assuntos

Avaliação de Resultados em Cuidados de Saúde , Vigilância da População , Sorodiagnóstico da Sífilis/normas , Sífilis Latente/epidemiologia , Sífilis Latente/prevenção & controle , Adulto , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Masculino , Auditoria Médica , Prontuários Médicos , Penicilina G Benzatina/administração & dosagem , Porto Rico/epidemiologia , Estudos Retrospectivos , Sorodiagnóstico da Sífilis/estatística & dados numéricos , Sífilis Latente/sangue , Sífilis Latente/classificação , Estados Unidos/epidemiologia

RESUMO

La hemorragia aguda de vías digestivas altas es una de las emergencias más frecuentes en los servicios de urgencias. Su mortalidad promedio es del 10 por ciento. La etiología más común continúa siendo la úlcera péptica, representando casi la mitad de los casos. La restauración del volumen intravascular y la estabilización de la presión arterial son la primera prioridad del manejo más que identificar la causa del sangrado. En un 70-80 por ciento de los casos el sangrado se detiene espontáneamente. La endoscopia debe realizarse luego de la reanimación inicial y lograda la estabilidad, en diversas técnicas de hemostasis endoscópica. Respecto al tratamiento farmacológico, no hay datos convincentes para soportar el uso de antagonistas de receptores IL. Aunque algunos resultados son contradictorios, los inhibidores de la bomba de protones han demostrado su utilidad, sin embargo un beneficio claro en la mortalidad no se ha demostrado. Los beta-bloqueadores disminuyen la tasa de resangrado por várices esofágicas. Los pacientes con resangrado después de una fase inicial de estabilización requieren una nueva endoscopia para confirmarlo y tratarlo, en caso fallido deben ser llevados a cirugía. Se revisan los aspectos relacionados al diagnóstico, pronóstico y tratamiento, este último según grados de evidencia y se propone un algoritmo de diagnóstico y toma de decisiones

Assuntos

Hemorragia Gastrointestinal

RESUMO

Las bacteremias y sepsis por catéter constituyen una importante fuente de morbimortalidad en los pacientes hospitalizados, especialmente en las unidades de cuidados intensivos, donde son una de las tres más frecuentes infecciones nosocomiales, después de la neumonía asociada a la ventilación mecánica y las infecciones intra-abdominales siguiendo trauma o cirugía. Esas potenciales consecuencias negativas oscurecen los beneficios de monitoria y manejo obtenidos con su uso. Un meta-análisis promedió la mortalidad en 3 por ciento. La colonización interna y extema de la superficie del catéter constituye la más importante vía del proceso de infección. El estándar de oro para su diagnóstico es aún controversial; el cultivo semicuantitativo de la punta del catéter utilizando la técnica de Maki es el procedimiento más usado a pesar de sensibilidad y especificidad subóptimas, demostrado por meta-análisis. La evidencia soporta como medidas preventivas con nivel I las siguientes tres: heparina profiláctica, evitar el cambio rutinario del catéter usando guía y los catéteres impregnados con clorhexidina-sulfadiazina de plata. El conocimiento adecuado de las medidas con eficacia comprobada para evitar dichas infecciones es necesario como punto de partida para prevenirlas. Se revisan la epidemiología, patogénesis, el diagnóstico, tratamiento y la literatura con aproximación crítica basada en la evidencia respecto alas medidas de prevención

Assuntos

Cateterismo , Sepse