RESUMEN
Background Context: Spinal fusion surgery is a common treatment for lumbar degenerative diseases and has been associated with the long-term complication of adjacent segment disease (ASD). In recent years, the "topping-off" technique has emerged as a new surgical method, combining spinal fusion with a hybrid stabilization device (HSD) or interspinous process device (IPD) proximal to the fused vertebrae. Methods: A literature search using the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science databases identified eligible studies comparing topping-off implant(s) with spinal fusion surgery for lumbar degenerative diseases. Risk of bias was assessed using the Cochrane RoB 2.0 tool for randomized controlled trials and the Newcastle-Ottawa scale for retrospective studies. Each outcome was analyzed using the statistical Confidence in NMA (CINeMA) 1.9.0 software. Results: 17 RCTs and retrospective studies that included 1255 participants and five interventions were identified. The topping-off implants device for intervertebral assisted motion (DIAM; OR = 0.235, p < 0.001), Dynesys (OR = 0.413, p < 0.001), and Coflex (OR = 0.417, p < 0.01) significantly lowered the incidence of radiographic adjacent segment degeneration (RASDeg) compared with spinal fusion surgery alone. Spinal fusion supplemented with DIAM significantly reduced the incidence of clinical adjacent segment disease (CASD) (OR = 0.358, p = 0.032). Conclusions: Spinal fusion supplemented with DIAM substantially reduced the incidence of radiographic and clinical adjacent segment disease. No significant difference was observed between the treatment comparators for reoperation due to ASD and back pain relief score.
RESUMEN
Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells. The two cell lines had similar upstream JAK/STAT1 signaling and IDO1 mRNA stability. However, using a series of breast cancer cell lines, IFNγ stimulated IDO1 protein expression and enzymatic activity only in ER-, not ER+, cell lines. Treatment with 5-aza-deoxycytidine reversed the suppression of IDO1 expression in MCF7 cells, suggesting that DNA methylation was potentially involved in IDO1 induction. By analyzing several breast cancer datasets, we discovered subtype-specific mRNA and promoter methylation differences in IDO1, with TNBC/basal subtypes exhibiting lower methylation/higher expression and ER+/luminal subtypes exhibiting higher methylation/lower expression. We confirmed this trend of IDO1 methylation by bisulfite pyrosequencing breast cancer cell lines and an independent cohort of primary breast tumors. Taken together, these findings suggest that IDO1 promoter methylation regulates anti-immune responses in breast cancer subtypes and could be used as a predictive biomarker for IDO1 inhibitor-based immunotherapy. Cancer Immunol Res; 5(4); 330-44. ©2017 AACR.