TET2 启动子甲基化和 TET2 蛋白在儿童后颅窝室管膜瘤中的表达。
- 作者列表："Pierscianek D","Teuber-Hanselmann S","Ahmadipour Y","Darkwah Oppong M","Unteroberdörster M","Müller O","Jabbarli R","Sure U","Zhu Y","El Hindy N
Pediatric posterior fossa ependymoma (PF) is one of the most common brain tumors in children. Recently, two subtypes of PF were identified. PF-A has a dismal prognosis and shows a hypermethylation phenotype, whereas PF-B shows a great genomic instability. The ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene (TET2) has been linked to the regulation of DNA methylation. We analyzed TET2 promotor methylation and protein expression to assess the role of TET2 in PF. Medical records of all PF cases treated in our institution between 1993 and 2015 were evaluated regarding tumor histology, grade, tumor location, gender, age, tumor recurrence, distant metastasis, survival and time to progression. Subsequently, we analyzed TET2 promotor methylation using methylation-specific polymerase chain reaction. TET2 protein expression was assessed using immunohistochemistry. Low TET2 expression was detected in seven of 17 cases. There was an association between low TET2 expression and tumor recurrence (P = 0.049). A TET2 promotor methylation was detected in five of 10 cases. There was no association between the TET2 promotor methylation with recurrence, tumor grade or gender. TET2 promotor methylation and low TET2 expression was detected in a subgroup of PF. Our data show an association between low TET2 expression and tumor recurrence in PF.
小儿后颅窝室管膜瘤 (PF) 是儿童最常见的脑肿瘤之一。最近发现了 PF 的两种亚型。PF-A 预后不佳，表现出高甲基化表型，而 PF-B 表现出很大的基因组不稳定性。十一易位甲基胞嘧啶双加氧酶 2 (TET2) 基因 (TET2) 与 DNA 甲基化的调控有关。我们分析了 TET2 启动子甲基化和蛋白表达，以评估 TET2 在 PF 中的作用。对 2015 和 1993年在本机构治疗的所有 PF 病例的病历进行了肿瘤组织学、分级、肿瘤部位、性别、年龄、肿瘤复发、远处转移、生存期和进展时间的评价。随后，我们使用甲基化特异性聚合酶链反应分析 TET2 启动子甲基化。使用免疫组织化学评估 TET2 蛋白表达。17 例中 7 例检测到 TET2 低表达。TET2 低表达与肿瘤复发有相关性 (P = 0.049)。10 例中有 5 例检测到 TET2 启动子甲基化。TET2 启动子甲基化与复发、肿瘤分级或性别之间无相关性。在 PF 亚组中检测到 TET2 启动子甲基化和 TET2 低表达。我们的数据显示了 PF 中 TET2 低表达与肿瘤复发之间的相关性。
METHODS::Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.
METHODS:The aim of the present study was to explore the possible mechanisms of phosphatase and tensin homolog (PTEN) in the pathogenesis of Burkitt's lymphoma, and provide novel information that can be used in the targeted treatment of this disease. PTEN lentiviral overexpression vector and short‑hairpin PTEN silencing vectors were constructed. The effect of PTEN on the growth and proliferation of CA46 and RAJI cells was analyzed using a Cell Counting Kit‑8 assay. Apoptosis was detected by Hoechst 33342 and propidium iodide double staining. Flow cytometry was used to analyze the cell cycle. A Transwell chamber was used to detect cell migration and invasion abilities. Western blot analysis was used to detect related protein changes. The mechanism of the effect of PTEN on the biological characteristics of Burkitt's lymphoma cells was subsequently analyzed. The results revealed that PTEN inhibited the proliferation of CA46 and RAJI cells by downregulating the expression of p‑AKT, It was indicated that the upregulation of proapoptotic proteins (including Bad and Bax) induced apoptosis, regulated cyclin (including P53, P21, CDK4, CDK6, cyclin D3 and cyclin H) to inhibit cell cycle progression, and mediated epithelial‑mesenchymal transition‑like cell markers (including E‑cadherin, N‑cadherin, β‑catenin, TCF‑8, vimentin, Slug and Snail) to inhibit cell migration and invasion. In conclusion, the tumor‑suppressor gene PTEN inhibited the phosphoinositide 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibited the proliferation and migration of Burkitt's lymphoma cells, induced apoptosis and cell cycle arrest, thus playing a crucial role in the pathogenesis of Burkitt's lymphoma.
METHODS:Melatonin (Mel) has been shown to involve in many essential cell functions via modulating many signaling pathways. We for the first time investigated that Mel exerted anti-tumor activities in Hodgkin lymphoma (HL) via inhibiting cell proliferation and promoting cell apoptosis. Further study revealed that Mel treatment increased expression of LC3-II and decreased p62 proteins with the enhanced production of autolysosome, indicating it induced activation of autophagy. Nevertheless, Mel treatment together with autophagy inhibitors 3-MA or CQ exacerbated the damage effect of Mel in HL cells, which means autophagy plays a protective role in this process. Furthermore, we found Mel treatment increased the expression of G protein-coupled receptors MT2 and retinoic acid-related orphan receptors (RORs), eg. RORA, RORB and RORC. While RORC has the highest increase in Mel treated HL cells. In addition, RORC overexpression induced autophagy activation. Therefore, Mel showed tumor-suppressive role due to an increased level of RORC induced autophagy in HL.