Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naïve patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.     

Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival

Journal of Neuro-Oncology - Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT)...     

营养风险与腹膜后肿瘤患者住院时间的相关性研究

目的 探讨营养风险与腹膜后肿瘤患者住院时间的相关性。方法 采用回顾性研究，选取2012年1月至2018年12月四川大学华西医院血管外科新入院腹膜后肿瘤患者60例，采用营养风险筛查表评估患者营养风险，收集患者体质指数、围术期血红蛋白和白蛋白水平、住院天数、术后恶心呕吐发生情况、术后排气、排便时间和首次进食时间。采用单因素分析比较不同患者住院时间，采用多重线性逐步回归分析患者住院时间的影响因素。结果 纳入的60例腹膜后肿瘤患者中，40例患者（66.7%）术前存在营养风险，52例患者（86.7%）术后存在营养风险；单因素分析显示，患者术前、术后营养风险 （术前P<0.001，术后P=0.043）、术前白蛋白 （P=0.019）、术后血红蛋白 （P=0.019）、术后白蛋白（P=0.025） 水平以及术后恶心呕吐 （P=0.001） 均会影响患者的住院时间；患者住院时间与围术期营养风险筛查工具评分、术后首次进食时间、术后排气时间和排便时间具有相关性，且相关性强（r=0.759~0.770； P<0.01）；多因素分析显示术前营养风险是腹膜后肿瘤患者住院时间的重要预测因素（β=0.399）。结论 术前营养风险是腹膜后肿瘤患者住院时间的预测因子。     

小檗碱通过影响糖原结构调节肝糖代谢研究

目的探讨小檗碱调节糖原代谢的机制及对糖原结构的影响。方法采用自发型糖尿病模型db/db小鼠作为疾病模型鼠,考察小檗碱对db/db小鼠血糖水平的影响;提取小鼠的肝糖原进行体积排阻色谱(SEC)和透射电镜(TEM)分析,考察小檗碱对db/db小鼠肝糖原的结构影响,并探讨其影响机制。结果小檗碱可以显著性降低db/db小鼠的空腹血糖,降低db/db小鼠血清胰岛素水平;改善db/db小鼠肝糖原的结构不稳定性;降低db/db小鼠肝组织中糖原磷酸化酶(GP)、糖原脱分支酶(GDBE)和环磷酸腺苷(cAMP)表达水平,降低血清胰高血糖素水平。结论小檗碱可以调控cAMP/GP信号通路,改善db/db小鼠的肝糖原结构,修复受损糖原结构,这可能是其调节肝糖代谢,改善糖尿病症状的机制之一。     

Basic fibroblast growth factor promotes doxorubicin resistance in chondrosarcoma cells by affecting XRCC5 expression

Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future.     

风池穴不同刺法对椎动脉型颈椎病的临床疗效评价

目的:探究风池穴不同刺法对椎动脉型颈椎病的临床疗效。方法:选择2018年4月—2019年1月北京中医药大学东直门医院针灸科门诊就诊的84例椎动脉型颈椎病患者作为研究对象,分为观察组43例、对照组41例。观察组采用短刺法针刺风池穴治疗,对照组采用平补平泻法针刺风池穴治疗,1个疗程后比较两组患者的ESCV、颈椎病症状分级量化表评分以及TCD相关指标,TCD指标观察基底动脉和双侧椎动脉的平均血流速度(Vm)、收缩期血流速度峰值(Vs)、血管搏动指数(PI)和血管阻力指数(RI)的变化。结果:治疗前后两组ESCV、颈椎病症状分级量化表评分比较,差异有统计学意义(P<0.05),且椎动脉、基底动脉的Vs、Vm较治疗前明显减慢,且观察组治疗效果优于对照组(P<0.05)。结论:针刺风池穴治疗椎动脉型颈椎病临床效果显著,且短刺法优于平补平泻法。     

GPER-induced signaling is essential for the survival of breast cancer stem cells

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER⁻/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.