ABSTRACT
Objetivo: La introducción del Antígeno Prostático Específico (APE) como herramienta de uso masivo en la detección precoz de cáncer prostático (CaP), parece ser al menos parcialmente responsable de la disminución en la mortalidad observada en el último tiempo. Sin embargo, el APE tiene una baja especificidad como marcador de cáncer, especialmente en el rango de 4 a 10 ng/ml donde existe una alta sobreposición con otras patologías de mayor prevalencia como por ejemplo, Hiperplasia Prostática Benigna (HPB). Es por esto, que existe una búsqueda constante de nuevos marcadores. Nuestro objetivo fue caracterizar el perfil de expresión génica del CaP utilizando microarray. Material y métodos: Doce casos de CaP con PSA <10 ng/ml y 4 casos con PSA >10 ng/ml fueron seleccionados prospectivamente para análisis de microarray para 96 genes característicos de tejido prostático. Los análisis se efectuaron por el método de Hierarchical Clustering y se realizó Transcripción Reversa y Reacción de Polimerasa en Cadena para confirmar la información obtenida mediante microarray. Además, se evaluó la presencia en sangre periférica de los genes sobre-expresados en tejido y que pudieran ser marcadores sistémicos de CaP. Resultados: Se definieron 13 genes basándose en su alta expresión, los cuales se agruparon en NCOA4/NDRG1, LDHA/LIM/GSTP1 y KLK2/KLK4 y estos con CALR y CSTB. Los genes SPARCL1, KLK3(PSA), ARSDR1 y ACPP se ordenaron en ramas independientes. El gen ACPP (fosfatasa ácida prostática) fue el más independientemente sobreexpresado. Realizamos RT-PCR para ACPP en 15 tumores primarios y sangre periférica observando señal positiva en 10 (71 por ciento) de 14 casos analizados. Conclusiones: Nuestros resultados indican que el gen ACPP se encuentra sobreexpresado a nivel molecular en tumor primario y sangre periférica, convirtiéndolo en un potencial marcador de CaP con niveles de PSA <10 ng/ml.
Objective: The introduction of prostate specific antigen (PSA) as a screening tool for early detection of prostate cancer (CaP), seems to take a role in being responsible for the decreasing of mortality observed in the last time. Nevertheless, the APE has a low specificity like cancer marker, especially in the rank from 4 to 10 ng/ml where a high superposition with other pathologies of greater prevalence like Benign Prostate Hiperplasia (HPB) exists. This is why there is a constant research for new markers. Our objective was to characterize the gene expression profile of prostate using microarray. Material and Methods: Twelve cases of CaP with PSA <10 ng/ml and 4 cases with PSA >10 ng/ml were prospectively selected for microarray analysis for 96 genes characteristic of prostate tissue. The analysis was performed by the method of Hierarchical Clustering and performed reverse transcription polymerase chain reaction to confirm the information obtained by microarray. We assessed the presence in peripheral blood of over-expressed genes in tissue that could become in systemic markers of PC. Results: We identified 13 genes based on their high expression, which were grouped into NCOA4/NDRG1, LDHA/LIM/GSTP1 and KLK2/KLK4 and those with CALR and CSTB. Genes SPARCL1, KLK3 (PSA) and ACPP ARSDR1 were ordered in separate branches. The ACPP gene (prostatic acid phosphatase) was overexpressed more independently. We RT-PCR for ACPP in 15 primary tumors and peripheral blood positive signal observed in 10 (71per cent) of 14 cases analyzed. Conclusions: Our results indicate that the ACPP gene is overexpressed in a molecular level in primary tumor and peripheral blood, making it a potential marker for prostate cancer with PSA levels <10 ng/ml.
Subject(s)
Humans , Carcinoma/genetics , Prostatic Neoplasms/genetics , Gene Expression , Biomarkers, Tumor , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Background: Cervical cancer is the third cause of cancer death among Chilean women, affecting mainly women from low socioeconomic status. Aim: To determine main risk factors (RF) including human papilomavirus (HPV) types associated with abnormal cervical cytology (Atypical Squamous Cells of Undetermined Significance or ASCUS) among Chilean women from low socioeconomic status in Santiago, Chile. Material and Methods: A random population based sample of616 women from La Pintana (a low-income district in Santiago) participated in 2001 in a HPV prevalence study and were re-evaluated in 2006 through a risk factors questionnaire, Papanicolaou test and DNA detection for HPV. The Papanicolaou test was analyzed in Santiago and HPV analysis (PCR_GP5+/GP6+) was conducted in Vrije University, Amsterdam. Cases included 42 women with cervical lesions and controls included 574 women with normal cytology during the period 2001-2006. Logistic regression with uni and multivariate analysis was performed to identify RF for cervical lesions. Results: During the study period, there was a significant increase in the proportion of single women, from 8.3 to 14.8 percent (p < 0.05), of women with 3 or more sexual partners from 8.9 to 13.3 and of women high risk HPV, from 9.1 to 14.3 percent. The proportion of abnormal Papanicolaou tests remained stable (3.08 and 3.9 percent > ASCUS). High risk HPV was the most significant factor associated with cervical lesions (odds ratio (OR) = 9.695 percent> confidence intervals (CI) = 4.4-21.1) followed by oral contraceptive use (OR = 2.58 95 percent> CI= 1.2-5.7). Among women infected by high risk HPV, the use of oral contraceptives was a risk factor while compliance with screening was protective for cervical lesions. Conclusions: From 2001 to 2006, there was an increase in the proportion of women with high-risk HPV infections.
Subject(s)
Adult , Female , Humans , Papillomavirus Infections/epidemiology , Uterine Cervical Diseases/epidemiology , Vaginal Smears , Chile/epidemiology , Epidemiologic Methods , Papillomavirus Infections/pathology , Socioeconomic Factors , Uterine Cervical Diseases/pathology , Uterine Cervical Diseases/virologyABSTRACT
Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type of tumor is not preceded by precancerous changes and is associated with early-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchicalclustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%),followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA1 and younger age (<45 years old), and the second by hypermethylation of p14 and p16 genes, male predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA1 associated with young age suggests a role in early-onset gastric carcinoma.
Subject(s)
Female , Humans , Male , Middle Aged , DNA Methylation/genetics , DNA, Neoplasm/genetics , Genes, BRCA1 , Stomach Neoplasms/genetics , Cluster Analysis , CpG Islands/genetics , Early Diagnosis , Gastric Mucosa/pathology , Immunohistochemistry , Polymerase Chain Reaction , Precancerous Conditions/genetics , Promoter Regions, Genetic/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathologyABSTRACT
Background: Infection of the Fallopian tubes (FT) by Neisseria gonorrhoeae (Ngo) can lead to acute salpingitis, an inflammatory condition resulting in damage primarily to the ciliated cells, with loss of ciliary activity and sloughing of the cells from the epithelium. Recently, we have shown that Ngo infection induced apoptosis in FT epithelium cells by a TNF-alpha dependent mechanism that could contribute to the cell and tissue damage observed in gonococcal salpingitis. Aim: To investigate the apoptosis-related genes expressed during apoptosis induction in cultured FT epithelial cells infected in vitro by Ngo. Materials and Methods: In the current study, we used cDNA macroarrays and real time PCR to identify and determine the expression levels of apoptosis related genes during the in vitro gonococci infection of FT epithelial cells. Results: Significant apoptosis was induced following infection with Ngo. Macroarray analysis identified the expression of multiple genes of the TNF receptor family (TNFRSF1B, -4, -6, -10A, -10B and -10D) and the Bcl-2 family (BAK1, BAX, BLK, HRK and MCL-1) without differences between controls and infected cells. This lack of difference was confirmed by RT-PCR of BAX, Bcl-2, TNFRS1A (TNFR-I) and TNFRSF1B (TNFR-II). Conclusion: Several genes related to apoptosis are expressed in primary cultures of epithelial cells of the human Fallopian tube. Infection with Ngo induces apoptosis without changes in the pattern of gene expression of several apoptosis-related genes. Results strongly suggest that Ngo regulates apoptosis in the FT by post-transcriptional mechanisms that need to be further addressed.