Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (a) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (b) the transformation of exosomes into potential DDSs.     

宫颈癌免疫治疗的耐药机制及应对措施

宫颈癌严重威胁全球女性的生命健康，晚期宫颈癌治疗手段有限，5年生存率不到20%，是妇科肿瘤的巨大挑战。免疫治疗是晚期宫颈癌患者的重要治疗手段之一，包括免疫检查点抑制剂、治疗性疫苗和过继性T细胞免疫疗法等，但免疫治疗耐药性使部分患者无应答而效果不佳。因此，迫切需要深入研究和探讨免疫耐药的机制从而改善耐药，现归纳总结了近年有关宫颈癌中免疫耐药机制的相关研究，主要分为肿瘤内在因素和外在免疫环境改变等因素，并介绍针对免疫耐药提出的应对措施及进展。     

NRP-1单克隆抗体对乳腺癌裸鼠移植瘤生长的影响

 目的 探讨NRP-1单克隆抗体（NRP-1 MAb）的特异性，以及不同剂量的NRP-1 MAb治疗乳腺癌裸鼠移植瘤的疗效。方法 Western blot和共聚焦免疫荧光法检测NRP-1 MAb是否识别MCF7细胞上NRP-1蛋白。将MCF7细胞接种于BALB/c裸鼠皮下建立乳腺癌细胞移植瘤模型，并进行瘤组织传代。传代的肿瘤体积生长至300~500 mm3时，随机分为对照组、NRP-1 MAb低剂量组、中剂量组和高剂量组，每组6只，给药7次。观察荷瘤裸鼠一般状况，测量瘤体大小及裸鼠体重。实验结束时剥离瘤体称重，提取组织蛋白，Western blot检测组织中VEGF蛋白和NRP-1蛋白的表达量。结果 NRP-1MAb成功识别MCF7细胞上的NRP-1蛋白；NRP-1 MAb能够有效抑制MCF7细胞裸鼠移植瘤的生长，低剂量组（1 mg/kg）抑瘤率为47.01%，中剂量组（5 mg/kg）抑瘤率为65.70%，高剂量组（10 mg/kg）抑瘤率为69.19%。。结论 NRP-1 MAb能够识别并有效结合MCF7细胞膜上的NRP-1蛋白，且可抑制MCF7细胞移植瘤的生长，NRP-1 MAb抑制移植瘤的增长可能与下调NRP-1和VEGF表达有关。     

穴位贴敷联合风咳汤治疗感染后咳嗽的临床研究

目的:探究风咳汤联合穴位贴敷治疗感染后咳嗽的临床疗效,以期丰富治疗方法,为治疗感染后咳嗽提供科学依据。方法:选取2017年1月至2018年1月南京市中西医结合医院收治的感染后咳嗽患者88例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组44例。对照组予常规治疗,观察组在对照组基础上加用风咳汤联合穴位贴敷治疗,均治疗2周。观察比较2组患者采用不同方法治疗前、后中医证候积分、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、诱导痰上清液中P物质(SP)含量水平变化情况。治疗过程中收集不良反应资料,结束治疗后比较2组疗效。结果:1)2组患者完成治疗方案后,中医症候积分较治疗前均显著下降,观察组显著优于对照组,差异有统计学意义(P<0.05);2)治疗后2组患者IL-8、TNF-α、SP含量均较治疗前显著下降,且观察组优于对照组,差异有统计学意义(P<0.05);3)观察组患者临床控制率、总有效率明显高于对照组,差异有统计学意义(P<0.05)。4)2组患者ALT、AST、CCr、BUN水平和不良反应发生率比较,差异无统计学意义(P>0.05)。结论:风咳汤联合穴位贴敷治疗感染后咳嗽能提高疗效,降低炎性反应水平,改善症状和生命质量。     

非小细胞肺癌顺铂耐药相关基因生物信息学研究

目的：通过分析非小细胞肺癌顺铂敏感株及耐药株的基因芯片表达数据，筛选差异基因及关键通路，构建蛋白相互作用网络，探讨关键集群功能。方法:从GEO数据库获得基因芯片表达数据，利用GEO2R工具筛选差异基因，通过STRING数据库和Cytoscape软件构建蛋白相互作用网络，经DAVID富集得到相关特征基因与信号通路信息。结果：通过芯片分析共获得481个差异表达基因，相比于敏感细胞株，顺铂获得性耐药细胞株中有418个上调基因和63个下调基因。差异基因功能主要富集在piRNA代谢、DNA甲基化修饰、细胞有丝分裂及细胞周期进程等信号通路。蛋白复合物预测得到主要功能集群6个，分别与细胞趋化性、细胞角化性、piRNA代谢过程、细胞因子受体相互作用、细胞因子分泌调节及染色质沉默相关生物进程相关。结论:本研究利用生物信息学方法，发现顺铂耐药细胞株特征基因及信号通路，其中SAA1、KRT5、TDRD9、BCL2A1、CSF1R和HIST1H1A等显著上调基因及其功能集团可能是非小细胞肺癌顺铂耐药的潜在分子机制，为临床精准治疗提供新的理论依据。     

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.     

免疫编辑诱导的免疫治疗耐药

近年来，免疫治疗在多种恶性肿瘤治疗中取得突破性进展，为肿瘤患者带来明显生存获益。然而，免疫系统在识别和杀伤肿瘤细胞的同时，出现免疫编辑诱导，导致大多数患者对免疫治疗具有先天或后天的耐药性。肿瘤免疫编辑是免疫系统抑制或促进肿瘤发生发展的过程，肿瘤的发生发展经历了免疫消除、免疫平衡和免疫逃逸三个阶段。在整个过程中，肿瘤的免疫原性被编辑，并获得使疾病进展的各种免疫抑制机制，致使肿瘤细胞逃避免疫系统的监测，导致肿瘤细胞免疫逃逸产生耐药。因此，揭示肿瘤免疫治疗耐药机制及克服耐药至关重要。本文主要从肿瘤免疫编辑过程背后的机制对肿瘤免疫治疗耐药作一具体阐述，为临床中克服免疫耐药取得更好疗效提供参考。