Fernando Arias

PURPOSE: microRNAs (miRNA) are small RNAs that function as post-transcriptional regulators of gene expression. Recent evidence has shown that some miRNAs can act as oncogenes or tumor suppressors. This study was conducted to evaluate the potential association of miRNA expression with clinical outcome in patients with gastric cancer. EXPERIMENTAL DESIGN: Expression of 250 human mature miRNAs was measured by real-time PCR on paraffin-embedded tumor samples of 21 patients with gastric cancer stage III uniformly treated with surgical resection followed by chemoradiation. We identified the miRNAs correlated with disease-free and overall survival times, and the results were evaluated including 24 other patients. In vitro cell proliferation and radiosensitivity studies were done to support clinical data. RESULTS: The results revealed that down-regulation of miR-451 was associated with worse prognosis. miR-451 was detected by in situ hybridization in epithelial cells and showed decreased expression in gastric and colorectal cancer versus nontumoral tissues. Overexpression of miR-451 in gastric and colorectal cancer cells reduced cell proliferation and increased sensitivity to radiotherapy. Microarray and bioinformatic analysis identified the novel oncogene macrophage migration inhibitory factor (MIF) as a potential target of miR-451. In fact, overexpression of miR-451 down-regulated mRNA and protein levels of MIF and decreased expression of reporter genes with MIF target sequences. Moreover, we found a significant inverse correlation between miR-451 and MIF expression in tumoral gastric biopsies. CONCLUSIONS: These findings support the role of miR-451 as a regulator of cancer proliferation and open new perspectives for the development of effective therapies for chemoradioresistant cancers.

A population of 489 low birth weight infants was studied to identify specific subgroups with high neonatal morbidity and mortality. It was found that 134 (27.4%) of these infants were born at term but were small for gestational age. The other 355 were preterm and contributed most of the mortality and morbidity of the overall population. There was no significant difference in morbidity and mortality between preterm small and appropriate for gestational age infants. The etiologic analyses show that premature rupture of the fetal membranes and maternal-fetal problems are more frequent causes of low birth weight than preterm labor and that they cause significantly more severe neonatal morbidity. It is concluded that only by developing means to improve the outcome of patients with premature rupture of the membranes and maternal-fetal problems will it be possible to decrease significantly the unacceptably high mortality and morbidity of low birth weight infants.

The purpose of this study was to examine the relationship among adverse pregnancy outcome, the presence of thrombotic lesions in the placenta, and the frequency and type of laboratory abnormalities consistent with the presence of a thrombophilic state. A retrospective cohort study was designed to determine the frequency of laboratory abnormalities consistent with thrombophilia among patients with thrombotic lesions of the placenta and adverse pregnancy outcome. The workup for a thrombophilic state included anticardiolipin antibodies, lupus anticoagulant, protein C and antithrombin III activities, protein S total and free, activated protein C resistance ratio, and Factor V Leiden mutation. Thrombotic lesions were identified by histopathologic examination of the placenta. Thirteen patients met the study criteria over an 11-month period. Seven patients were heterozygous for Factor V Leiden mutation (53.8%). Protein S deficiency was found in three cases (23.0%), and no hemostatic abnormality was detected in three cases (23.0%). Mothers with an adverse pregnancy outcome and thrombotic lesions of the placenta often have laboratory abnormalities indicative of a thrombophilic state. We propose that thrombophilia leading to thrombosis in the maternal and/or fetal circulations is a significant mechanism of disease during pregnancy.