BackgroundUnderstanding carboplatin resistance in ovarian cancer is critical for the improvement of patients’ lives. Multipotent mesenchymal stem cells or an aggravated epithelial to mesenchymal transition phenotype of a cancer are integrally involved in pathways conferring chemo-resistance. Long non-coding RNA HOTAIR (HOX transcript antisense intergenic RNA) is involved in mesenchymal stem cell fate and cancer biology.MethodsWe analyzed HOTAIR expression and associated surrogate DNA methylation (DNAme) in 134 primary ovarian cancer cases (63 received carboplatin, 55 received cisplatin and 16 no chemotherapy). We validated our findings by HOTAIR expression and DNAme analysis in a multicentre setting of five additional sets, encompassing 946 ovarian cancers. Chemo-sensitivity has been assessed in cell culture experiments.ResultsHOTAIR expression was significantly associated with poor survival in carboplatin-treated patients with adjusted hazard ratios for death of 3.64 (95 % confidence interval [CI] 1.78–7.42; P < 0.001) in the discovery and 1.63 (95 % CI 1.04–2.56; P = 0.032) in the validation set. This effect was not seen in patients who did not receive carboplatin (0.97 [95 % CI 0.52–1.80; P = 0.932]). HOTAIR expression or its surrogate DNAme signature predicted poor outcome in all additional sets of carboplatin-treated ovarian cancer patients while HOTAIR expressors responded preferentially to cisplatin (multivariate interaction P = 0.008).ConclusionsNon-coding RNA HOTAIR or its more stable DNAme surrogate may indicate the presence of a subset of cells which confer resistance to carboplatin and can serve as (1) a marker to personalise treatment and (2) a novel target to overcome carboplatin resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0233-4) contains supplementary material, which is available to authorized users.
Background Vascular injury is a very rare complication following arthroscopic knee surgery. This is the first report of pseudoaneurysm at the saphenous branch of the descending genicular artery complicating semitendinosus tendon harvest in arthroscopic anterior cruciate ligament reconstruction. Case presentation A 19-year-old male had developed large ecchymosis, focal swelling and tenderness around his posteromedial knee after an arthroscopic anterior cruciate ligament reconstruction. Compartment syndrome of the lower leg and deep vein thrombosis were ruled out. A pseudoaneurysm formation was confirmed through an angiography and coil embolization was performed. At one year follow up, the patient reported improved functional outcome with good stability of the knee. However, mild paresthesia over the posteromedial calf was noted due to the compression injury of the saphenous nerve by the hematoma. Conclusions The pseudoaneurysm was presumed to result from accidental vascular injury while dissecting the accessory bands of the semitendinosus and was successfully treated by coil embolization. Care must be taken to section the expansions of the hamstring tendon, especially when the patient presents with underlying coagulopathy or vascular disease.
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