Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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RPV‐modified epirubicin and dioscin co‐delivery liposomes suppress non‐small cell lung cancer growth by limiting nutrition supply

Chemotherapy for non‐small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self‐adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV‐modified epirubicin and dioscin co‐delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM‐related and angiogenesis‐related proteins in vitro. Furthermore, when tested in vivo, the targeted co‐delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV‐modified epirubicin and dioscin co‐delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.     

基于中医传承辅助平台分析高血压病阴阳两虚证的用药规律

目的分析治疗高血压病阴阳两虚证的方药特征信息,探索组方用药规律,挖掘有效的药物组合及新处方。方法检索相关数据库并查阅资料,收集关于高血压病阴阳两虚证的文献和医案,筛选治疗该病证的方剂。基于中医传承辅助平台(V 2. 5)建立方药特征数据库,并通过关联规则分析法、改进互信息法、熵层次聚类等方法,对处方用药进行数据分析。结果筛选出关于高血压病阴阳两虚证的组方179首,中药190味,使用频次最高的三味中药为熟地黄、茯苓、山药,并获得核心药物组合24个,新处方12个。结论通过此研究,明确了本病的用药规律,得出滋阴助阳、补益肾气为治疗高血压病阴阳两虚证的主要方法,对本病的临床治疗及组方用药具有重要价值。     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

"肺炎1号"治疗新型冠状病毒肺炎451例多中心临床研究

目的:观察“肺炎1号”治疗新型冠状病毒肺炎的临床疗效。方法:选取2020年2月17日至2020年3月15日湖北省中医院、监利县中医院、蕲春县人民医院、潜江市中医院、洪湖市中医医院、阳新县中医医院、浠水县中医院、大冶市中医医院、汉川市人民医院、武昌方舱医院收治的新型冠状病毒肺炎患者451例,采用“肺炎1号”联合西医常规治疗,观察“肺炎1号”对新型冠状病毒肺炎患者的临床症状、舌象、实验室检查结果及肺部CT情况。结果:共纳入451例患者,其中轻型21例,普通型378例,重型46例,危重型6例。疑似病例6例(1.33%),临床诊断病例168例(37.25%),确诊病例277例(61.42%)。治疗后与治疗前比较,患者发热、咳嗽、乏力主要症状发生率显著降低(P<0.05);恶寒、鼻塞、流涕、打喷嚏、咽部痒、咽痛、呼吸困难、胸闷、肌肉酸痛或关节疼痛、头晕头痛、纳差、恶心呕吐、腹胀、大便稀溏症状发生率显著改善(P<0.05);白细胞计数、中性粒细胞绝对值变化差异无统计学意义(P>0.05);淋巴细胞绝对值明显升高,差异有统计学意义(P<0.05);C反应蛋白、降钙素原明显降低,差异有统计学意义(P<0.05)。退热时间3(1～3.25)d。229例患者舌质由红或绛逐渐转为淡红,好转率为75.58%;177例患者白腻苔、厚腻苔、黄腻苔明显变薄,好转率为65.31%。新型冠状病毒核酸转阴时间为8(5,11)d。415例(92.02%)肺部CT明显好转,主要表现在病灶面积减小,变薄变淡。达到出院标准430例,临床治愈率95.34%;好转15例;无效3例;死亡3例(0.67%)。治疗过程中,未见明显不良反应,临床应用安全。结论:“肺炎1号”结合西医常规治疗对新型冠状病毒肺炎有较好的治疗作用,能够快速稳定病情,阻断轻型、普通型向重型、危重型转化;明显改善患者临床症状;较好促进肺部炎性反应吸收;使用安全可靠。     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。     

胃癌组织中WISP1和Ki67的表达及其临床病理意义

目的:探讨胃癌组织中WISP1和Ki67蛋白的表达及其临床病理意义。方法:收集中国医科大学附属第一医院肿瘤外科手术切除的胃癌组织标本87例及其配对非癌（距癌灶边缘>5 cm取材）胃黏膜组织80例，采用免疫组织化学方法检测WISP1和Ki67蛋白在胃癌组织及其配对正常胃黏膜组织中的表达。结果:胃癌组织中WISP1的阳性表达率为81.61%（71/87），显著高于非癌胃黏膜组织阳性表达率12.50%（10/80）。WISP1蛋白表达，在低分化腺癌中的阳性表达较中（P=0.000）、高（P=0.032)分化管状腺癌显著增高，弥漫型胃癌显著高于肠型胃癌（P=0.000），在肿瘤直径>5 cm的胃癌组织中显著高于肿瘤直径≤5 cm的胃癌组织（P=0.010），在伴有淋巴结转移的胃原发灶癌组织中较无淋巴结转移组增高（P=0.025）。Ki67蛋白表达与进展期胃癌患者肿瘤浸润深度（P=0.043）和淋巴结转移（P=0.027）相关。WISP1阳性表达与Ki67表达呈正相关（rk=0.240，P=0.026）。结论:WISP1在胃癌组织中表达显著上调，联合检测胃癌组织中WISP1和Ki67蛋白的表达，可更好的预测淋巴结转移情况，为胃癌患者预后评价提供参考。     

LPS对骨肉瘤细胞迁移、侵袭及TLR4/HOTAIR通路的影响

目的探讨脂多糖(LPS)对骨肉瘤细胞迁移和侵袭的影响及其潜在的作用机制。方法将人MG-63骨肉瘤细胞随机分为2组:对照组和LPS组。LPS组细胞用10 g/ml的LPS干预24 h,对照组用生理盐水干预。ELISA检测干预后培养基中促炎因子的水平,Transwell实验检测细胞迁移和侵袭能力,Western Blot检测相关蛋白的表达。结果与对照组相比,LPS组培养基中促炎因子TNF-α、IL-1和IL-6的释放水平均显著增高(P<0.05),LPS组迁移细胞数和侵袭细胞数均显著增高(P<0.05),LPS组中E-cadherin的表达显著降低(P<0.05),而N-cadherin、α-SMA、波形蛋白、TLR4和HOTAIR的表达均显著增高(P<0.05)。结论LPS诱导的肿瘤微环境可促进骨肉瘤细胞的迁移和侵袭,其机制与TLR4/HOTAIR途径介导的EMT过程的发生有密切关系。     

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.