ABSTRACT
LEVEL OF EVIDENCE: Level IV.
Subject(s)
Forearm Injuries , Fracture Fixation, Intramedullary , Fractures, Bone , Radius Fractures , Ulna Fractures , Bone Nails , Child , Forearm , Forearm Injuries/surgery , Fracture Fixation, Intramedullary/adverse effects , Fractures, Bone/etiology , Humans , Radius Fractures/diagnostic imaging , Radius Fractures/etiology , Radius Fractures/surgery , Retrospective Studies , Risk Factors , Treatment Outcome , Ulna Fractures/diagnostic imaging , Ulna Fractures/etiology , Ulna Fractures/surgeryABSTRACT
Ovarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.
Subject(s)
Biomarkers, Tumor/metabolism , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Ovarian Neoplasms/pathology , RNA, Long Noncoding/genetics , STAT3 Transcription Factor/metabolism , Animals , Antineoplastic Agents/pharmacology , Apoptosis , Biomarkers, Tumor/genetics , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Female , Humans , Mice , Mice, Nude , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Prognosis , STAT3 Transcription Factor/genetics , Signal Transduction , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
The spontaneous rupture of an unscarred uterus at 28 gestational weeks is an extremely rare event, particularly when associated with an intact amniotic sac extrusion and fetal leg entrapment, which has not been previously reported. A 27-year-old primigravid woman was referred to our department, due to perpetual abdominal pain, at 28 weeks and 5 days of gestation. The patient, G3p0, had previously undergone two induced abortions. At the time of admission, abdominal ultrasonography suggested a defect in the left uterine horn. An emergency laparotomy was subsequently performed and revealed an intact amniotic sac extrusion and fetal leg entrapment. Considering the risk of placental abruption, and the possibility of a secondary rupture if the gestation was not terminated, an emergency Cesarean section was recommended. Uterine rupture may be suspected whenever a patient complains of durative abdominal pain at 28 weeks and 5 days of gestation, even in the absence of an intra-abdominal hemorrhage or vaginal bleeding.
ABSTRACT
Cisplatin is a common chemotherapeutic agent against ovarian cancer; however, drug resistance is a major limiting factor for its use in clinical treatment. The underlying mechanisms of cisplatin resistance in ovarian cancer have not yet been fully elucidated. Thus, this study aimed to elucidate some of the mechanisms responsible for resistance to cisplatin in ovarian cancer. The results demonstrated that the cisplatinresistant human ovarian cancer cell lines, SKOV3/DDP and A2780/DDP, exhibited higher autophagy levels than the control ovarian cancer cell lines, SKOV3 and A2780. Moreover, autophagy inhibition by 3methyladenine or shRNA against autophagyrelated gene (ATG)5 potentiated the cytotoxicity induced by cisplatin, whereas autophagy induction by rapamycin (Rapa) increased cell survival. Exposure to cisplatin induced an upregulation in the expression of thioredoxinrelated protein of 14 kDa (TRP14). Furthermore, TRP14 knockdown or overexpression decreased or increased the autophagy response and cisplatin resistance, and this effect was reversed by treatment with Rapa or ATG5 knockdown. The findings of this study also suggested that TRP14 induced autophagy and chemoresistance via the 5'AMPactivated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. Importantly, the data from a tissue array revealed a positive association between TRP14 and Beclin1 in human ovarian cancer and marginal tissues. These findings have identified, for the first time, to the best of our knowledge, that TRP14 induces autophagy and consequently cisplatin resistance in ovarian cancer cells via the AMPK/mTOR/p70S6K signaling pathway. This in turn renders TRP14 as a potential predictor or target in ovarian cancer therapy.
