上调miR-145表达抑制卵巢癌HO8910细胞侵袭、迁移及促进TβR-Ⅱ蛋白表达北大核心

目的:探究微小RNA-145(microRNA-145,miR-145)对卵巢癌(ovarian cancer, OC)HO8910细胞侵袭、迁移及TβR-Ⅱ蛋白水平的影响。方法:将某大学研究实验室细胞库提供的OC细胞HO8910分为ZW组(无转染HO8910细胞)、ZN组(转染miR-145-NC)、YJ组(转染miR-145 mimics)。采用qRT-PCR、MTT、Hoechst33258荧光染色、Transwell小室、细胞划痕、Western blot检测miR-145、转化生长因子βⅡ型受体(transforming growth factorβtypeⅡreceptor, TβR-Ⅱ)表达、细胞活力、凋亡、侵袭、迁移能力以及TβR-Ⅱ蛋白量。结果:YJ组HO8910细胞中miR-145的表达量最高,提示转染成功。YJ组TβR-Ⅱ表达量较其他两组对比明显提高(P<0.05),ZW组、ZN组miR-145、TβR-ⅡmRNA表达水平无明显差异(P>0.05);培养48、72、96 h, YJ组细胞活力较ZW组、ZN组比较明显减弱(P<0.05),随着时间的延续,培养96 h三组细胞活力均优于48、72 h(P<0.05);YJ组与ZW组、ZN组对比细胞凋亡率明显提高(P<0.05);ZW组HO8910细胞荧光强度最弱,细胞凋亡率最低,ZW组与ZN组对比无明显差异(P>0.05);三组细胞侵袭、迁移数量相比差异较大(P<0.05),其中YJ组侵袭、迁移数量少于其他两组(均P<0.05),ZN组与ZW组的细胞侵袭、迁移数量无明显差异(P> 0.05);YJ组TβR-Ⅱ蛋白表达量与ZU组、ZN组对比明显升高(P<0.05),YJ组转化生长因子-β(transforming growth factorβ,TGF-β)蛋白表达量与其他两组对比均降低(P<0.05),ZW组TGF-β、TβR-Ⅱ蛋白表达量与ZN组对比差异较小(P> 0.05)。结论:通过上调miR-145对抑制OC细胞迁移、侵袭等生物活性发挥积极作用,分析原因可能与靶向调控TβR-Ⅱ蛋白相关。     

鼻咽癌患者血清中miR-141-3p和miR-155-3p的表达水平及其临床意义北大核心

目的:探讨鼻咽癌患者血清中miR-141-3p及miR-155-3p的表达水平及临床意义。方法:选取2017年01月至2020年09月我院收治的95例鼻咽癌患者和45例健康对照组作为研究对象,采用实时荧光定量PCR法检测miR-141-3p及miR-155-3p表达水平。应用受试者工作特征(receiver operating characteristic, ROC)曲线分析血清中miR-141-3p及miR-155-3p表达水平对鼻咽癌的诊断价值。Pearson相关分析分析鼻咽癌患者血清中miR-141-3p与miR-155-3p表达水平的相关性。结果:鼻咽癌组血清中miR-141-3p(3.25±1.28 vs 0.64±0.17)及miR-155-3p(1.47±0.83 vs 0.35±0.08)表达水平均明显高于对照组(P均<0.001)。鼻咽癌患者血清中miR-141-3p及miR-155-3p表达水平升高与临床分期高、分化程度低、淋巴结转移及远处转移相关(P均<0.001)。ROC曲线显示,血清中miR-141-3p及miR-155-3p表达水平诊断鼻咽癌的最佳截断值分别为2.18、0.97,两项联合诊断鼻咽癌的曲线下面积(0.940,95%CI:0.877~0.998)最大,其敏感度和特异度为97.0%和86.2%。相关分析显示,鼻咽癌患者血清中miR-141-3p与miR-155-3p表达水平呈正相关(r=0.853,P<0.001)。结论:鼻咽癌患者血清中miR-141-3p及miR-155-3p表达水平明显升高,有望作为鼻咽癌诊断的潜在标志物。     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间，但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效，但因为少见驱动基因突变的肺癌患者本身样本量少，开展大规模临床随机对照试验尚存在一定的困难，目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述，以期在一定程度上为临床工作提供一些依据和参考。     

Transcervical approach with endoscopic assistance for surgical treatment of patient with irreducible atlantoaxial dislocation: a case report

We demonstrate the case of a surgery in a patient with irreducible atlantoaxial dislocation (IrAAD) after C2 fracture. The challenges of this case were the flexed head in a forced position, impossibility of neck extension, and revision operation after posterior occipito-cervical fixation. The patient underwent the following surgeries: 1. A ventral release of C1-C2 using transcervical endoscopy; 2. Removal of occipito-cervical system and fibrous block resection in the posterior surfaces of the C1-C2; 3. Reducing of AAD and odontoid screw fixation; 4. Posterior C1-C2-C3 screw fixation. Ankylosing of C1-C2 and C2-C3-C4 fusion was verified by computed tomography scan. There was an improvement in patient status as observed by the increase of the SF-36 scale scores.The use of endoscopic transcervical approach is a good alternative to the transoral approach. Comparative studies of these methods should be performed regarding the choice of an optimal method of decompression in cases of IrAAD.     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

肺癌是世界上发病率最高的癌症之一，且尚无二线进展后的标准治疗方案，而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点，小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路，抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验，且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）获批治疗晚期非小细胞肺癌，本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状，归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分别与化疗、表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs、免疫治疗、放疗等联合）]治疗非小细胞肺癌的疗效与安全性研究，同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等，并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望，同时为肺癌后续的精准治疗及个体化治疗提供新的思路。