Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

携带同源重组修复相关基因突变的消化道肿瘤的临床特点

目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene，HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者，79例患者进行了血液标本HRR检测，53例患者进行了组织标本HRR检测，40例患者同时行血液和组织的HRR基因检测，收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例（12.6%）有临床意义HRR突变，在53例患者组织标本检测中发现9例（17.0%）有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例（10.0%）、ATM突变3例（7.5%）、BRCA1突变2例（5.0%）。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例（76.9%）、APC突变5例（38.5%）、PIK3CA突变4例（30.8%）。40例患者中13例患者血液和/或组织中有临床意义HRR突变，27例患者血液和组织中均无任何临床意义HRR突变且两组相比，有临床意义HRR突变组肿瘤突变负荷（tumor mutational burden，TMB）为6.17(2.24～11.52)，而未携带HRR突变组TMB为0.4(0～3.75)，差异有统计学意义（P＜0.05）。40例患者组织检测中7例HRR有临床意义的突变，33例无HRR突变，血液检测中10例HRR有临床意义的突变，30例无HRR突变，一致性检验的Kappa值为0.333（P=0.031）。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高，血液和组织检测HRR突变有较好的一致性。     

What is the Potential Interplay between Microbiome and Tumor Microenvironment in Oral Squamous Cell Carcinomas?

Oral cancer, with an around 50% mortality rate, is one of the most common malignancies world-wide. It is often detected in advanced or terminal stage and has a poor prognosis, although substantial progress in cancer management. Microbiome has become an increasingly recognized factor that may contribute to the cancerous development. Oral microbiological population comprising more than 700 bacterial species, varies since saliva and different habitats of oral cavity. A shift of composition of oral microbiome from usual condition to functional inflammation to pathological state has been discovered amongst patients with premalignant disorders and oral carcinoma, with evidence suggesting the tumor microenvironment (TME) could strongly exacerbate the influence of oral microorganisms. The complex interactions taking place in either cancer formation or progression have been evaluated in several publications, however given their results’ heterogeneity, a review is needed to correctly untangle the potential correlation in this group of pro-carcinogenesis. In this review, we briefly summarize our current knowledge of the role of oral microbiome, focusing on its potential crosstalk with TME in oral squamous cell carcinomas (OSCC) more precisely, and pave the way for manipulating oral microbiome to deal with OSCC in the future.     

Segmentation of CT Lung Images Using FCM with Active Contour and CNN Classifier

Objective: Lung cancer is one of the unsafe diseases for human which reduces the patient life time. Generally, most of the lung cancers are identified after it has been spread into the lung parts and moreover it is difficult to find the lung cancer at the early stage. It requires radiologist and special doctors to find the tumoral tissue of the lung cancer. For this reason, the recommended work helps to segment the tumoral tissue of CT lung image in an effective way. Methods:  The research work uses hybrid segmentation technique to separate the lung cancer cells to diagnose the lung tumour. It is a technique which combines active contour along with Fuzzy c means to diagnose the tumoral tissue. Further the segmented portion was trained by Convolutional Neural Network (CNN) in order to classify the segmented region as normal or abnormal. Results: The evaluation of the proposed method was done by analyzing the results of test image with the ground truth image. Finally, the results of the implemented technique provided good accuracy, Peak signal to noise ratio (PSNR), Mean Square Error (MSE) value. In future the other techniques can be utilized to improve the details before segmentation. The proposed work provides 96.67 % accuracy. Conclusion: Hybrid segmentation technique involves several steps like preprocessing, binarization, thresholding, segmentation and feature extraction using GLCM.     

外泌体在肿瘤细胞与TAMs之间相互作用中“桥梁”和调控作用的研究进展北大核心

外泌体是一类直径为30~100 nm的圆盘囊泡,其内包含许多组分,诸如复杂RNA和蛋白质等,主要参与细胞间的信号转导。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中普遍存在的巨噬细胞,通过对肿瘤生长、免疫逃逸、侵袭和转移、耐药性等多方面的作用影响肿瘤进程。外泌体在肿瘤相关巨噬细胞的招募、极化及抗肿瘤免疫调控等方面发挥着重要的调节功能。同时,TAMs以外泌体为媒介作用于肿瘤细胞,从而构成了外泌体、TAMs与肿瘤细胞之间相互作用的调控通路。综上所述,本文旨在阐明肿瘤细胞与TAMs之间,以外泌体为“桥梁”相互影响的潜在机制,以及靶向肿瘤细胞和TAMs来源的外泌体在恶性肿瘤治疗中的展望。     

PSMA-CAR-CIK转基因细胞体外杀伤三种前列腺癌细胞株效率的研究北大核心

目的:本研究通过检测前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)-肿瘤特异性嵌合抗原受体(chimeric antigen receptor,CAR)-细胞因子诱导的杀伤细胞(cytokine induced killer cell,CIK)转基因细胞杀伤三种前列腺癌细胞株的效率,鉴定其用于后期治疗前列腺癌的可行性。方法:通过已经构建的二代PSMA-CAR慢病毒表达载体转染CIK细胞,构建PSMA-CAR-CIK转基因细胞;通过CCK8法检测CIK细胞及PSMA-CAR-CIK转基因细胞杀伤三种前列腺癌细胞株PC3、LNCaP、DU145的效率及效靶比。结果:转基因PSMA-CAR-CIK细胞构建成功;3 h~3.5 h为检测效应细胞对靶细胞细胞毒活性时与CCK8试剂孵育的最佳时间;两种效应细胞均在效靶比为10∶1、15∶1、20∶1时,杀伤率逐步增高,无统计学意义(P>0.05),但与其它组相比差异显著(P<0.05)。结论:两种效应细胞对于前列腺癌细胞的杀伤,只要效靶比达到10∶1的比例,就能起到一个较好的杀瘤效果,并且随着效应细胞的增加,其抗肿瘤能力逐步加强;转基因PSMA-CAR-CIK细胞的构建为CAR技术治疗前列腺癌的临床应用奠定了基础。     

Geographic Characteristics of Various Cancers in Yogyakarta Province,Indonesia: A Spatial Analysis at the Community Level

Background: Cancer remains a significant public health problem in Indonesia and worldwide. Yogyakarta Province has the largest number of cancer cases in Indonesia. Maps of the distribution of cancer cases are useful tools for stratification of cancer risk and for selective prevention strategies. The aim of this study was to determine the spatial distribution of cancer cases in Yogyakarta Province. Methods: Cancer patient data registered by the Yogyakarta Provincial Health Office during 2019-2020 were analysed in this study (n=9,933). To evaluate cancer pattern distributions, ArcGIS 10.2 and Excel 2016 software were used. Results: The mean participant age (± standard deviation) was 55.08 ± 15.46 years, and 79.40% were female. Breast and cervical cancer were the most frequently diagnosed, and the majority of patients were located in Sleman district. The incidence of all cancer types varied by county-level. The majority of cancer patients lived below the poverty line. Cancer screening rates were low, and screening was limited to breast and cervical cancer. Conclusion: Various types of cancers were identified in Yogyakarta, Indonesia; of them, breast and cervical cancer predominated. Most of the cancer patients were from Sleman district and economically poor areas. Geospatial techniques are useful for identifying environmental factors related to cancer and improving cancer control strategies and resource allocation.     

hsacirc0006867在结直肠癌组织中的表达及其临床意义北大核心

目的:探讨环状RNA hsa_circ_0006867在结直肠癌中的表达及其与临床病理因素的关系。方法:全转录组测序筛选结直肠癌中特异circRNAs表达谱,挑选出差异表达显著的hsa_circ_0006867,qRT-PCR检测54例结直肠癌组织及癌旁组织中hsa_circ_0006867表达情况,分析其表达水平与结直肠癌临床病理特征的相关性,ROC曲线分析hsa_circ_0006867在结直肠癌中的诊断价值。结果:测序获得circRNAs在结直肠癌中的差异表达谱,qRT-PCR验证hsa_circ_0006867在结直肠癌中表达下调(P<0.05)。其表达水平与肿瘤分化程度和远处转移有关(P<0.05)。ROC曲线显示hsa_circ_0006867诊断结直肠癌AUC为0.851(95%CI:0.775~0.927),当截断值为0.0146时,敏感度为88.46%(95%CI:0.770~0.946),特异度为73.08%(95%CI:0.598~0.832),差异具有统计学意义(P<0.001)。结论:hsa_circ_0006867在结直肠癌中表达下调,与相关临床病理特征密切联系,可作为潜在结直肠癌临床诊断指标。     

Effect of Replacement of Wharton Acellular Jelly With FBS on the Expression of Megakaryocyte Linear Markers in Hematopoietic Stem Cells CD34+

Objective: Animal environments for the growth of stem cells cause the transmission of some diseases and immune problems for the recipient. Accordingly, replacing these environments with healthy environments, at least with human resources, is essential.  One of the media that can be used as an alternative to animal serums is Wharton acellular jelly (AWJ).  Therefore, in this study, we intend to replace FBS with Wharton jelly and investigate its effect on the expression of megakaryocyte-related genes and markers in stem cells. Materials and Methods: In this study, cord blood-derived CD34 positive HSCs were cultured and expanded in the presence of cytokines including SCF, TPO, and FLT3-L. Then, the culture of expanded CD34 positive HSCs was performed in two groups: 1) IMDM culture medium containing 10% FBS and 100 ng / ml thrombopoietin cytokine 2) IMDM culture medium containing 10% AWJ, 100 ng / ml thrombopoietin cytokine.  Finally, CD41 expressing cells were analyzed with the flow cytometry method. The genes related to megakaryocyte lineage including FLI1 and GATA2 were also evaluated using the RT-PCR technique.  Results: The expression of CD41, a specific marker of megakaryocyte lineage in culture medium containing Wharton acellular jelly was increased compared to the FBS group. Additionally, the expression of GATA2 and FLI1 genes was significantly increased related to the control group. Conclusion: This study provided evidence of differentiation of CD34 positive hematopoietic stem cells from umbilical cord blood to megakaryocytes in a culture medium containing AWJ.     

阿克替苷通过激活血红素加氧酶-1抑制H_(2)O_(2)诱导的视网膜神经节细胞氧化损伤北大核心

目的研究阿克替苷对视网膜神经节细胞(RGC-5)的保护作用及其机制。方法将RGC-5细胞分为对照组、H_(2)O_(2)组、阿克替苷+H_(2)O_(2)组(1μmol·L^(-1)、10μmol·L^(-1)、30μmol·L^(-1)阿克替苷分别预处理细胞2 h),MTT法检测各组细胞活力;后续实验阿克替苷+H_(2)O_(2)组选择阿克替苷30μmol·L^(-1)作为治疗浓度,荧光探针H2DCF-DA检测活性氧(ROS)产生和罗丹明123检测线粒体膜电位,Western blot检测各组细胞中Bcl-2、Bcl-2/Bax、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。机制研究中首先用不同浓度阿克替苷单独处理RGC-5细胞24 h,Western blot检测血红素加氧酶-1(HO-1)蛋白表达水平,进一步锌原卟啉(ZnPP)预处理RGC-5细胞1 h,而后30μmol·L^(-1)阿克替苷单独预处理后与200μmol·L^(-1)H_(2)O_(2)共孵育24 h,通过MTT法测定细胞活力。结果与对照组相比,H_(2)O_(2)组中细胞活力明显降低(P<0.01)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组中10μmol·L^(-1)、30μmol·L^(-1)阿克替苷预处理可显著提高细胞活力(P<0.05、P<0.01)。与对照组相比,H_(2)O_(2)组RGC-5细胞ROS生成明显增加,线料体膜电位显著降低,同时Bcl-2/Bax比值降低和Caspase-3蛋白相对表达量增加(均为P<0.05)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组RGC-5细胞ROS生成减少,线粒体膜电位增加,Bcl-2/Bax比值提高,Caspase-3蛋白相对表达量减少(均为P<0.05)。与阿克替苷未处理组相比,阿克替苷剂量依赖性诱导HO-1蛋白的表达,与阿克替苷+H_(2)O_(2)组相比,加入ZnPP后细胞活力降低(P<0.01),说明HO-1抑制剂ZnPP降低了阿克替苷对H_(2)O_(2)损伤的抑制作用。结论阿克替苷能够通过上调HO-1表达抑制H_(2)O_(2)诱导的RGC-5氧化应激损伤。