One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance.Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines. To identify specific candidate genes under miRNA regulation, we assembled “in silico” miRNAs and mRNAs sequences by using ten different algorithms followed by qRT-PCR validation. Functional assays of site-directed mutagenesis and luciferase activity, miRNAs precursor overexpression, silencing by antago-miR and cell viability were performed to confirm their specificity in gene regulation. Results were further explored in 187 primary samples obtained from ovarian tumors and controls.Results: We identified 4 candidates, miR-7, miR-132, miR-335 and miR-148a, which deregulation seems to be a common event in the development of resistance to cisplatin in both tumor types. miR-7 presented specific methylation in resistant cell lines, and was associated with poorer prognosis in ovarian cancer patients. Our experimental results strongly support the direct regulation of MAFG through miR-7 and their involvement in the development of CDDP resistance in human tumor cells.Conclusion: The basal methylation status of miR-7 before treatment may be a potential clinical epigenetic biomarker, predictor of the chemotherapy outcome to CDDP in ovarian cancer patients. To the best of our knowledge, this is the first report linking the regulation of MAFG by miRNA-7 and its role in chemotherapy response to CDDP. Furthermore, this data highlights the possible role of MAFG as a novel therapeutic target for platinum resistant tumors.
Hemoperitoneum during pregnancy is a rare but potentially lethal clinical condition. Improvements in antenatal and intrapartum care, especially in surgical and anesthetic techniques, have reduced maternal mortality; perinatal mortality remains very high (31%). Treatment is based on the systemic correction of hypovolemia and immediate surgery via laparotomy or laparoscopy in cases in the first trimester of pregnancy for hemostatic purposes. Sometimes, hysterectomy is needed. A 35-year-old Asiatic primigravid woman at 37 weeks' gestation with otherwise uneventful pregnancy came to the hospital referring abrupt-onset lumbar and abdominal pain. A bleeding uterine superficial varicocele of about 7 cm was found on the left uterine horn during Caesarean section. Interventional radiologic embolization of both uterine arteries was successfully performed. Posterior evolution of the patient was favorable. Percutaneous vascular embolization of the uterine arteries is an effective alternative treatment for many obstetrical and gynecological causes of bleeding. The main advantage of this technique is the low rate of serious complications and the preservation of reproductive function. To our knowledge, this is the first case of spontaneous intrapartum hemoperitoneum treated with this technique. An early diagnosis and a rapid indication of this therapeutic option are essential. Hemodynamic stability is needed to decide this conservative management.
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