RESUMEN
A frequently recommended systemic therapy for breast cancer involves a combination of anthracyclines and taxanes, however, approximately 30% of patients experience recurrence. We aimed to investigate the mechanisms of resistance to anthracycline-paclitaxel based treatment by analyzing gene expression patterns in tumor samples collected during surgery and subsequent therapeutic responses. A database of 187 patients with information about relapse-free survival (RFS) allowed the analysis of 10,017 genes. Patients were divided into responders and nonresponders based on whether relapse occurred within sixty months. The expression of each gene was compared between the two groups using the Mann-Whitney U-test, with a statistical significance set at p <0.05 and fold change (FC) ≥1.44. We identified 51 up-regulated genes among nonresponders, primarily associated with inflammatory processes and the innate immune response. The high expression of SLC7A5, encoding an amino acid transporter, was linked to worse overall survival (p = 2.3E-10), with elevated expression in tumors (p = 2.94E-20), and further increase in metastases (p = 1.33E-10). Our results emphasize the significance of tumor microenvironment and metabolism in therapy resistance. These findings may allow better patient classification and identification of relevant treatment targets.
RESUMEN
The HSD11B1 gene encodes the type 1 isoform of the 11-ß-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , Síndrome del Ovario Poliquístico/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adulto , Femenino , Estudios de Asociación Genética , Haplotipos , Humanos , Adulto JovenRESUMEN
Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort.
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Perfilación de la Expresión Génica , Neoplasias Ováricas/genética , Anciano , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Ovario/anatomía & histología , Ovario/metabolismo , Ovario/patología , Receptores de Estrógenos/genética , Receptores de Progesterona/genética , Tetraspaninas/genética , gamma-Sinucleína/genética , Proteínas tau/genéticaRESUMEN
OBJECTIVES: The aim of this study was to present our results of the sonographic measurement of the fetal iliac angle during the first and second trimesters of pregnancy. METHODS: A total of 2168 fetal iliac angle measurements were performed in a transverse section of the fetal pelvis. The iliac angle measurements were compared in fetuses with trisomy 21 (n = 52) and fetuses with normal karyotype (n = 1980). The sensitivity, specificity, positive predictive value, negative predictive value and false positive rate in trisomy 21 fetuses were compared for multiple cut-off value. Statistical significance for measurements was estimated for trisomy 21. RESULTS: A total of 2064 fetuses had adequate images for satisfactory measurement of the iliac wing angle and 1831 patients asked for a genetic invasive procedure. Of the fetuses with chromosomal aberrations, only the fetuses with trisomy 21 were included in the investigation. The risk of trisomy 21 in our population was 1 of 39. In the euploid fetuses, the mean iliac wing angle was 63.72°. The mean iliac wing angle in the fetuses with trisomy 21 was 90.32°, significantly higher than those seen in fetuses with normal karyotype. CONCLUSION: The proven larger iliac wing angle in neonates with Down syndrome can be demonstrated sonographically during the pregnancy, especially in the first and second trimesters. This marker may be useful in prenatal screening or exclusion of trisomy 21.
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Pesos y Medidas Corporales/métodos , Arteria Ilíaca/diagnóstico por imagen , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Ultrasonografía Prenatal , Adolescente , Adulto , Estudios de Casos y Controles , Síndrome de Down/diagnóstico por imagen , Femenino , Feto/anatomía & histología , Edad Gestacional , Humanos , Arteria Ilíaca/anatomía & histología , Recién Nacido , Persona de Mediana Edad , Embarazo , Primer Trimestre del Embarazo/fisiología , Segundo Trimestre del Embarazo/fisiología , Curva ROC , Sensibilidad y Especificidad , Adulto JovenRESUMEN
PURPOSE: Fibroids may cause infertility and recurrent pregnancy loss. Studies have analysed the reproductive results after myomectomy according to the size, location and number of fibroids removed, but data are insufficient about comparison of opening the uterine cavity or not during surgery. MATERIALS AND METHODS: Two hundred twenty-nine abdominal myomectomies with the indication of infertility and/or recurrent pregnancy loss were analysed retrospectively. The main purpose was to compare postoperative pregnancy, delivery and miscarriage rates according to either the uterine cavity was opened or not during the surgery. As a secondary outcome postoperative pregnancy rates were assessed by location, size and number of fibroids. RESULTS: There was no significant difference in reproductive results according to either the uterine cavity was opened or remained closed. Preoperative location, size and number of fibroids did not influence significantly the postoperative pregnancy rates. CONCLUSION: Opening the uterine cavity does not impair postoperative pregnancy rates. Preoperative location, size and number of fibroids do not influence postoperative reproductive results.
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Leiomioma/cirugía , Resultado del Embarazo , Neoplasias Uterinas/cirugía , Adulto , Femenino , Humanos , Leiomioma/patología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Uterinas/patologíaRESUMEN
OBJECTIVE: The aim of our study was to determine the effect of abnormal implantation on uterine circulation and to evaluate whether the assessment of uterinal blood flow can provide additional information for the diagnosis of tubal pregnancies. METHODS: Forty-nine patients with ectopic pregnancy were examined by transvaginal color Doppler immediately before surgery. Resistance and pulsatility indices of blood flow in the uterine and tubal arteries were measured. RESULTS: The blood flow parameters of the uterine and tubal arteries did not change with gestational age. There was a significant increase in blood flow on the side with the tubal gestation. Differences between sides were higher in the tubal arteries than in the main uterine arteries and showed no dependence on gestational age. CONCLUSION: The abnormal implantation and tubal trophoblast invasion in ectopic pregnancy (EP) can cause more marked blood flow changes in the adjacent supplying vessels than in the main uterine arteries.