RESUMEN
BACKGROUND Survival in rectal cancer remains unchanged despite improved treatment modalities. Molecular biology may hold the key to new strategies. Gene expression abnormalities need identification in tumour specimens to identify targets for therapy. The impact of neoadjuvant therapy on induced gene expression changes needs to be assessed to distinguish the intrinsic tumour-specific changes from those changes that may be induced by neoadjuvant therapy. METHODS Gene expression changes were examined in 21 rectal tumours plus matched normal mucosa and cells exposed to 5-FU and gamma radiation, using DNA membrane arrays. These arrays contained 100 genes in common cancer pathways. The most commonly up-regulated gene, c-FOS, was quantified using real-time PCR. RESULTS c-FOS was the most commonly up-regulated gene, occurring in 7 of 21 samples (33%), all samples having a greater than 2-fold increase. SERPINE-1 was the second most commonly up-regulated gene with 6 of 21 samples showing up-regulation (29%). There was no clear correlation between up-regulation of c-FOS or SERPINE-1 and clinico-pathological data. Neither c-FOS nor SERPINE-1 gene expression was induced by 5-FU treatment or gamma irradiation in vitro, but MUC 18 was up-regulated by 5-FU treatment. This suggests that FOS and SERPINE-1 expression changes are specific to the tumour and will not arise as artefacts of neoadjuvant therapy. CONCLUSION The study suggests that c-FOS and SERPINE-1 may have important but as yet unclear roles in the tumour biology of rectal cancer but probably only represent a small part of the complex molecular biology of rectal cancer.
Asunto(s)
Biomarcadores de Tumor/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Regulación Neoplásica de la Expresión Génica , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/farmacología , Estudios de Casos y Controles , Femenino , Fluorouracilo/farmacología , Rayos gamma , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Invasividad Neoplásica , Estadificación de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Inhibidor 1 de Activador Plasminogénico/genética , Pronóstico , Proteínas Proto-Oncogénicas c-fos/genética , ARN Mensajero/genética , Neoplasias del Recto/terapia , Recto/metabolismo , Recto/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
Interest in estimating HIV-1 incidence using specimens obtained as part of cross-sectional surveys has led to the development of new methods to detect recent HIV-1 infection through the testing of a single anti-HIV-positive specimen. These assays are based on quantitative and qualitative differences in anti-HIV-1 antibodies between recent and long-standing infections. An ongoing vaccine preparedness study enrolled female sex workers in the Dominican Republic. Specimens from women found to be HIV positive at baseline were tested for recent HIV-1 infection using the detuned assay, avidity index, and BED-CEIA assay. An unweighted kappa statistic in pairwise comparisons was used to estimate the correlation of recent HIV-1 infection detection by the three methods. Nineteen (3.9%) of 482 women were positive for HIV-1 infection. The incidence of HIV infection was 1.4% [95% confidence interval (CI): 0.2, 5.3], 0.9%(95% CI: 0.1, 4.4), and 1.0%(95% CI: 0.1, 4.4) using detuned assay, avidity index, and BED-CEIA techniques, respectively. The overall agreement between both detuned assay and avidity index and detuned assay and BED-CEIA was 94%(kappa = 0.8, 95% CI; 0.3, 1.0). The correlation was highest between BED-CEIA and avidity index methods (100%; kappa = 1.0). All three methods performed similarly in detecting recent HIV-1 infection in this region dominated by clade B HIV-1 infection. Although incidence estimates were slightly higher using the detuned assay method, they were not significantly different. These assays may be of value in both clinical research and practice. The utility of individual assays for recent infection detection will depend upon operating characteristics, HIV-1 subtype limitations, and selection of appropriate assay cutoff values.
Asunto(s)
Serodiagnóstico del SIDA/métodos , Infecciones por VIH/diagnóstico , VIH-1 , Inmunoensayo/métodos , Trabajo Sexual , Adulto , Estudios de Cohortes , Estudios Transversales , República Dominicana/epidemiología , Femenino , Infecciones por VIH/epidemiología , Humanos , IncidenciaRESUMEN
OBJECTIVE: To validate a method for salivary testing for HIV infection in children older than 12 months. METHODS: Oral fluid samples were collected via sponge foam swabs from children born to HIV-positive mothers and were tested for antibodies to HIV-1 and HIV-2 with an IgG antibody capture enzyme-linked immunosorbent assay and a modified Western blot for confirmation. In each child serum antibody status was the standard used to validate the salivary antibody test. RESULTS: We obtained 331 oral fluid samples from children born to HIV-positive mothers. The specificity and sensitivity of salivary testing compared with results on sera were both 100% (297 of 297 (95% confidence interval 98.8 to 100%) and 34 of 34 (95% confidence interval 89.7 to 100%), respectively). Compliance in the study population increased from 91% to 97% when mothers were offered the opportunity to provide oral fluid from their children instead of blood specimens. CONCLUSION: Salivary testing provides an accurate and acceptable noninvasive method for assessing the HIV infection status of children born to infected mothers by using IgG antibody capture enzyme-linked immunosorbent assay alone with a strategy of duplicate retesting of reactive specimens.