RESUMO
OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.
Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Absorciometria de Fóton , Idoso , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Receptor alfa de Estrogênio/genética , Feminino , Frequência do Gene , Haplótipos , Humanos , Modelos Lineares , Desequilíbrio de Ligação , México , Pessoa de Meia-Idade , Ossos Pélvicos/patologiaRESUMO
Objetivo: Demostrar la utilidad de la ecografía Doppler en la detección de la invasión vesical en el percretismo placentario. Materiales y métodos: Se evaluó por ecografía, desde noviembre de 2011 hasta mayo de 2013, a 21 pacientes de entre 20 y 44 anos que tenían diagnóstico quirúrgico e histopatológico de acretismo placentario (AP). Se consideró invasión vesical a la presencia de estructuras vasculares parietales en la evaluación Doppler color, mientras que se estableció como probable invasión a la presencia de otros hallazgos ecográficos sin senal Doppler. Resultados: De las 21 pacientes con acretismo placentario, 7 presentaron afectación vesical en el examen histopatológico: 5 tuvieron diagnóstico e informe ecográfico de invasión vesical (por la detección de estructuras vasculares en la evaluación Doppler color) y en las 2 restantes se planteó una probable afectación. De las 14 pacientes sin afectación vesical en el resultado histopatológico, hubo 7 con informes normales en la ecografía y 7 con resultados probables. Conclusión: La ecografía Doppler es un método muy útil para la detección de la invasión vesical en el percretismo placentario. Esta se observa con una vascularización parietal positiva en el Doppler color.(AU)
Purpose: To demonstrate the usefulness of Doppler ultrasound in the detection of bladder invasion in cases of placenta percreta. Materials and methods: Twenty-one patients, aged 20-44 years old, with surgery and histopathological diagnosis of placenta accreta were tested with ultrasound between November 2011 and May 2013. We considered bladder invasion the presence of hypervascularity detected with Doppler ultrasound, and probable invasion the presence of signs in gray-scale ultrasound, without Doppler color. Results: From the 21 patients included in the study with placenta accreta, 7 had bladder invasion in the histopathological study. Out of these seven, five had been reported to have bladder invasion because of the presence of hypervascularity detected with Doppler ultrasound, and the 2 remaining were reported as probably affected. Regarding the other 14, 7 were reported as normal in the ultrasound, and 7 as probable. Conclusion: Doppler ultrasound is a very reliable method to detect bladder invasion in placenta percreta, seen as hipervascularity of the uterine-bladder interface in the Doppler color exam.(AU)
RESUMO
Objetivo: Demostrar la utilidad de la ecografía Doppler en la detección de la invasión vesical en el percretismo placentario. Materiales y métodos: Se evaluó por ecografía, desde noviembre de 2011 hasta mayo de 2013, a 21 pacientes de entre 20 y 44 anos que tenían diagnóstico quirúrgico e histopatológico de acretismo placentario (AP). Se consideró invasión vesical a la presencia de estructuras vasculares parietales en la evaluación Doppler color, mientras que se estableció como probable invasión a la presencia de otros hallazgos ecográficos sin senal Doppler. Resultados: De las 21 pacientes con acretismo placentario, 7 presentaron afectación vesical en el examen histopatológico: 5 tuvieron diagnóstico e informe ecográfico de invasión vesical (por la detección de estructuras vasculares en la evaluación Doppler color) y en las 2 restantes se planteó una probable afectación. De las 14 pacientes sin afectación vesical en el resultado histopatológico, hubo 7 con informes normales en la ecografía y 7 con resultados probables. Conclusión: La ecografía Doppler es un método muy útil para la detección de la invasión vesical en el percretismo placentario. Esta se observa con una vascularización parietal positiva en el Doppler color.
Purpose: To demonstrate the usefulness of Doppler ultrasound in the detection of bladder invasion in cases of placenta percreta. Materials and methods: Twenty-one patients, aged 20-44 years old, with surgery and histopathological diagnosis of placenta accreta were tested with ultrasound between November 2011 and May 2013. We considered bladder invasion the presence of hypervascularity detected with Doppler ultrasound, and probable invasion the presence of signs in gray-scale ultrasound, without Doppler color. Results: From the 21 patients included in the study with placenta accreta, 7 had bladder invasion in the histopathological study. Out of these seven, five had been reported to have bladder invasion because of the presence of hypervascularity detected with Doppler ultrasound, and the 2 remaining were reported as probably affected. Regarding the other 14, 7 were reported as normal in the ultrasound, and 7 as probable. Conclusion: Doppler ultrasound is a very reliable method to detect bladder invasion in placenta percreta, seen as hipervascularity of the uterine-bladder interface in the Doppler color exam.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Adulto Jovem , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/cirurgia , Placenta Acreta/patologia , Ultrassonografia DopplerRESUMO
Cytomegalovirus (CMV) infection is one of the most common complications among kidney transplant recipients; two approaches preventing this complication are currently available: universal prophylaxis (UP) and pre-emptive therapy (PT). Despite some differences, similar effectiveness and safety have been proven in several studies for both strategies. However, Spinner et al compared both treatments in 115 renal transplant recipients showing deaths were more likely to occur in patients who received UP. Most of these deaths (2/4 cases) occurred because malignancies developed. This finding is paradoxical because CMV is considered a potentially oncogenic virus and, therefore, UP (a longer therapy compared with the PT) should not be linked with the emergence of a greater number of tumors. New evidence suggests that changes in host immune response triggered by CMV infection may have a mitigating effect on the development of tumors. It is now known CMV infection produces a clonal expansion of gamma delta T lymphocytes which can elicit an aggressive response against neoplastic cells. Currently, UP is the therapy most frequently used in Colombian transplant centers; however, doses administered vary depending on several clinical and laboratory factors. There are no clinical cohorts treated with PT. Reviewing the impact of different length dosing schemes is important for creating an immune response affecting malignancy development in kidney transplant recipients.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/metabolismo , Transplante de Rim/métodos , Neoplasias/etiologia , Colômbia , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Humanos , Sistema Imunitário , Transplante de Rim/efeitos adversos , Neoplasias/complicações , Resultado do Tratamento , Valganciclovir , Carga ViralRESUMO
BCL3 is a putative proto-oncogene deregulated in haematopoieitic and solid tumours. It has been suggested that its oncogenic effects could be mediated, at least in part, by inducing proliferation and inhibiting cell death. To provide more insight into the mediators of these effects, we used an unbiased approach to analyse the mRNA expression changes after knocking-down BCL3 using specific shRNAs. One hundred eighty genes were up-regulated and sixtynine genes were down-regulated after knocking down BCL3. Function analyses showed enrichment in genes associated with cellular growth and proliferation, cell death and gene expression. We found that STAT3, an important oncogene in human cancer, was the central node of one of the most significant networks. We validated STAT3 as a bona fide target of BCL3 by additional interference RNA and in silico analyses of previously reported lymphoma patients.
Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias do Colo do Útero/genética , Proteína 3 do Linfoma de Células B , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Células HeLa , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/genética , Proteínas/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Fatores de Transcrição/genética , Regulação para Cima , Neoplasias do Colo do Útero/metabolismoRESUMO
Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.
Assuntos
Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Ciclina D1/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Umbeliferonas/farmacologia , Biotransformação , Divisão Celular , Relação Dose-Resposta a Droga , Humanos , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
Integrins are receptors that mediate cell adhesion and the formation of signaling complex. Changes in the expression of integrins are required during the following steps in the generation of metastases: a) angiogenesis; b) detachment from the primary tumor; c) tumor cell-platelet interaction; d) adhesion to vascular endothelium and e) proliferation. There is a correlation between invasive capability and changes in the expression of some proteins that are clustered in focal adhesion sites, as FAK, CD82, CD9 or CD63. Both, integrin blocking (using antibodies or RGD containing peptides), as well as induced changes in the expression of integrin-associated molecules, are able to inhibit formation of metastases. Discovery and characterization of molecules that regulate the adhesive capability of tumor cells, will lead to development of antimetastasic therapies. In the search of tumor dissemination inhibitors, integrins and some integrin-associated molecules are important pharmacological targets.