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.     

盐霉素对鼻咽癌CNE-2细胞放射敏感性的影响

目的:体外实验研究盐霉素对鼻咽癌CNE-2细胞放射敏感性的影响。方法:通过CCK-8法检测盐霉素作用后鼻咽癌CNE-2细胞的增殖情况。利用克隆集落形成实验观察鼻咽癌细胞成活情况，单击多靶模型拟合剂量存活曲线，计算放射增敏指数（SER）；Chou-Talalay数学模型绘制联合指数（CI）曲线，判断盐霉素和放射的作用关系。利用γ-H2AX焦点形成检测DNA分子损伤情况。结果:盐霉素能够抑制鼻咽癌细胞的增殖，并且具有明显的时间和剂量依赖性；盐霉素作用鼻咽癌细胞的IC50值在24 h时为17.81 μmol/L，48 h时为3.98 μmol/L。根据单击多靶模型拟合细胞的存活曲线，可知在鼻咽癌细胞CNE-2中盐霉素浓度为0.1 μmol/L和0.5 μmol/L时SER分别为1.19和1.21，均大于1.0，表明盐霉素对鼻咽癌细胞具有明显的放射增敏作用。制作联合指数（CI）曲线，可知在盐霉素浓度为0.1 μmol/L时，放射剂量为2 Gy时，CI值≈1，盐霉素和放射对CNE-2的作用接近相加作用，放射剂量为4、6、8 Gy时，CI值均＜1，二者为协同作用；在盐霉素浓度为0.5 μmol/L时，放射剂量为2、4、6、8 Gy时，CI值均＜1，二者均为协同作用。相对于照射组，盐霉素+照射组能增加DNA损伤数目。结论:盐霉素能提高鼻咽癌细胞的放射敏感性，为一种潜在的放射增敏药物。     

基于MRI动态图像观察吞咽时器官动度对头颈部肿瘤调强放疗靶区影响

目的 利用MRI技术连续采集头颈部肿瘤患者吞咽时图像,观察并测量软腭、舌、喉的运动规律及最大活动度。方法 随机选取2018年7月-10月在中国医学科学院肿瘤医院接受调强放疗的原发头颈部恶性肿瘤20例患者,其中男17例、女3例,中位年龄58.5岁(28~78岁)。20例患者中鼻咽癌7例,口腔癌3例,口咽癌5例,下咽癌3例,鼻腔鼻旁窦2例。根据AJCC第八版分期Ⅰ-Ⅱ期患者2例,Ⅲ期8例,Ⅳ期10例。结果 吞咽时软腭向上移动移动距离为(1.06±0.31) cm且服从正态分布,向后移动距离为(0.83±0.24) cm且近似正态分布。舌体向后移动距离为(0.77±0.22) cm,且服从正态分布。含压舌板行图像采集患者舌上移位移为0,无压舌板患者舌体中位上移距离为1.23 cm (0.59~1.41 cm)。喉向上移动距离为(1.14±0.22) cm且服从正态分布,向前移动的中位距离为0.4 cm (0.27~0.90 cm)。结论 吞咽运动有可能发生于头颈部肿瘤患者放疗过程中,并引起大体肿瘤体积(GTV)及周围正常组织移动;因此在制定放疗计划时应注意GTV至PGTV的个体化外放距离,以保证肿瘤处方剂量。     

Comparison of microtransplantation,chemotherapy and allogeneic transplantation in post-remission therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia

Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) have poor prognosis, and the efficacy of chemotherapy plus tyrosine kinase inhibitors (TKIs) followed by mismatched donor stem cell infusion (microtransplantation, MST) has not been determined. We retrospectively summarized 45 patients including 11 undergoing MST with TKIs, 17 receiving allogeneic transplant and 17 undergoing chemotherapy with TKIs. Improved 4-year overall survival rate was observed in the MST group (91%) compared with either transplant group (31%, P = .005) or chemotherapy group (36%, P = .013). The MST group also had higher 2-year and 4-year leukemia-free survival rates (91% and 72%, respectively) compared with either transplant group (33%, P = .005 and 33%, P = .021, respectively) or chemotherapy group (41%, P = .017 and 31%, P = .023, respectively). 2-year and 4-year cumulative incidences of hematologic relapse were lower in the MST group (9% and 28%, respectively) compared with those in the chemotherapy group (56%, P = .025 and 67%, P = .034, respectively). In patients undergoing MST, donor microchimerism was detected (1.07 × 10^-5 to 6.6 × 10^-4 copies from 9 to 1499 days) in 7 patients, and donor/patient-derived HLA*0201/2402⁺WT1⁺CD8⁺ T cells were found from 0.05% to 0.67% in 6 patients. MST may provide a favorable treatment for patients with Ph⁺ ALL.     

Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder

Idiopathic rapid eye movement sleep behavior disorder(iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients(male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls(male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume(GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital(approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry(ISRCTN18238599).     

Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry and Database-Driven Automatic Peak Annotation for the Rapid Profiling and Characterization of the Multicomponents from Stephaniae Tetrandrae Radix (Fang-Ji)

Quality control of traditional Chinese medicine (TCM) begins with elucidation of its chemical basis. The root of Stephania tetrandra, Stephaniae Tetrandrae radix (STR; Fang-Ji), has long been utilized as an antirheumatic, analgesic, and diuretic TCM. Powerful analytical strategies that would enable a multicomponent characterization of STR are still lacking. In the present study, we established a rapid, reliable, and enhanced profiling approach, using ultra?high performance liquid chromatography coupled with ion mobility/quadrupole time?of?flight mass spectrometry (MS) and automatic peak annotation facilitated by computational matching of an in?house library. This approach was used to characterize the multicomponents of STR. Good chromatographic separation was achieved within 17 min on a reversed-phase BEH C18 column eluted with acetonitrile/0.1% ammonium hydroxide in water, whereas data?independent high?definition MSE in the positive mode was applied to acquire the MS2 data using a Vion? IM?QTOF instrument, which, in theory, could cover all the profiled precursor ions. To overcome the interference of three predominant peaks, a knockout strategy was utilized by automated valve switching. An in?house library of 163 compounds was established and incorporated into the UNIFI? platform. By applying this method, we could identify or tentatively characterize 76 alkaloidsfrom the methanolic extract of STR, including 14 aporphine?type, four morphine?type, 48 bisbenzylisoquinoline?type, seven tetrahydroprotoberberine?type, one protopine?type, one benzylisoquinoline?type, and one other. For each component, four?dimensional information, such as retention time, collision cross-section, high-accuracy MS1, and high-accuracy MS2 data, was utilized to achieve the systematic multicomponent characterization of STR.     

黄酮类化合物及其纳米制剂在肿瘤防治中的研究进展

传统的肿瘤治疗方法依然存在肿瘤组织可及性差和药物不良反应普遍的问题。黄酮类化合物已被证实对多种类型肿瘤有效，但其安全性和作用部位特异性尚未被评估。然而，膳食黄酮类化合物因溶解度小、代谢快、口服吸收差等特点限制了其在体内抗肿瘤活性的发挥。此外，黄酮类化合物在某些情况下还能通过生物转化等作用与药物相互作用而影响生物利用度。纳米载体因可改变药物的药动学和药效学特征而被设计用于靶向药物传递，提高难溶性药物的生物利用度，将大分子传递到细胞内的作用位点，同时还能减少药物不良反应。体内、外研究均表明，纳米类黄酮制剂，特别是槲皮素、柚皮素、芹菜素、儿茶素和非瑟酮等在多种肿瘤的预防和治疗方面具有潜在作用，但其临床应用价值仍有待阐明。本文就纳米类黄酮制剂在提高生物利用度、肿瘤治疗效果和安全性方面的作用展开综述，为肿瘤治疗药物的开发利用提供新思路。     

Long Noncoding RNA WEE2-AS1 Plays an Oncogenic Role in Glioblastoma by Functioning as a Molecular Sponge for MicroRNA-520f-3p

The long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) plays an oncogenic role in hepatocellular carcinoma and triple negative breast cancer progression. In this study, we investigated the expression and roles of WEE2-AS1 in glioblastoma (GBM). Furthermore, the molecular mechanisms behind the oncogenic actions of WEE2-AS1 in GBM cells were explored in detail. WEE2-AS1 expression was detected using quantitative real-time polymerase chain reaction. The roles of WEE2-AS1 in GBM cells were evaluated by the cell counting kit-8 assay, flow cytometric analysis, Transwell cell migration and invasion assays, and tumor xenograft experiments. WEE2-AS1 expression was evidently enhanced in GBM tissues and cell lines compared with their normal counterparts. An increased level of WEE2-AS1 was correlated with the average tumor diameter, Karnofsky Performance Scale score, and shorter overall survival among GBM patients. Functionally, depleted WEE2-AS1 attenuated GBM cell proliferation, migration, and invasion in vitro, promoted cell apoptosis, and impaired tumor growth in vivo. Mechanistically, WEE2-AS1 functioned as a molecular sponge for microRNA- 520f-3p (miR-520f-3p) and consequently increased specificity protein 1 (SP1) expression in GBM cells. A series of recovery experiments revealed that the inhibition of miR-520f-3p and upregulation of SP1 could partially abrogate the influences of WEE2-AS1 downregulation on GBM cells. In conclusion, WEE2-AS1 can adsorb miR-520f-3p to increase endogenous SP1 expression, thereby facilitating the malignancy of GBM. Therefore, targeting the WEE2-AS1–miR-520f-3p–SP1 pathway might be a promising therapy for the management of GBM in the future.