环状RNA作为肿瘤标志物及其在肿瘤放疗中应用的研究进展

放疗是肿瘤综合治疗的重要手段之一,但放疗抵抗是影响肿瘤患者放疗疗效及预后的一大难题。由于肿瘤细胞放疗抵抗的机制十分复杂,所以至今还未找到特别有效的调控放疗敏感性的开关分子。环状RNA（circRNA）是一类通过反式剪接使得 3' 末端与 5' 末端共价结合的闭合circRNA分子,具有丰度高、结构稳定和特异性强等特征。circRNA参与肿瘤的发生、发展、侵袭和转移等过程,可以作为新型肿瘤分子标志物和潜在的治疗靶点。此外,circRNA在受照后的肿瘤细胞中存在差异性表达,并可作为微小RNA（miRNA）的海绵,调控与肿瘤放疗抵抗相关的miRNA及其下游信号通路,使其有望成为攻克肿瘤放疗抵抗的突破口。笔者综述了circRNA作为新型肿瘤标志物及其在肿瘤放疗中应用的研究进展。     

胰腺癌生物标志物的研究进展

胰腺癌（pancreatic cancer,PC）患者生存期的中位数低于1年,在诊断时即为不可救治者超过96％。2002年全世界有约227000人死于该病,病死率为98％。该病的病死率高,很大程度上是因为患者在诊断时已处晚期阶段。     

环状RNA在DNA损伤修复中作用的研究进展

环状RNA（CircRNA）是一类由外显子、内含子或基因间区经反向剪接形成的非编码RNA,具有种类丰富、序列保守、结构稳定和细胞组织特异性等特点。CircRNA在多种恶性肿瘤中处于失调状态,其可通过调节放化疗后细胞DNA双链断裂的损伤修复功能,使肿瘤细胞发生增殖失控、远处转移和凋亡受阻等一系列不良反应,进而影响治疗效果和预后。笔者综述了CircRNA的分子生物学特性及其在DNA损伤修复（特别是DNA双链断裂损伤修复）中发挥的作用,并对CircRNA在肿瘤患者的治疗、预后和减轻放化疗产生的不良反应等方面可能发挥的作用进行展望。     

胰腺癌的影像学诊断

目的 :探讨胰腺癌的早期影像学诊断。方法 :回顾性分析了自 1995 - 0 1～ 1999- 12月经影像学诊断 ,手术或穿刺病理证实的胰腺癌 16 8例。结果 :胰头颈部癌 15 2例 ,胰体癌 12例 ,胰尾癌 4例。 期 8例 , 期 88例 , 期 72例。误诊 2 9例 ,其中超声误诊 2 0例 ,CT误诊 6例 ,MRI误诊 3例。结论 :CT的薄层动态增强扫描和 MRI的 STIR序列对早期胰腺癌的诊断有较大帮助 ;在 B超或 CT定位下细针穿刺活检或行 ERCP检查有助于诊断和鉴别诊断 ;MRCP和 MRA在诊断和判定临床分期及能否施行根治切除有很好的预测价值     

胰腺癌早期诊断

胰腺癌约占全身肿瘤的1％～3％,占消化道肿瘤的8％～10％,其起病隐匿、病情进展快、恶性程度高,在因癌死亡的病例中占第4位。近几年,胰腺癌发病率明显增高。在美国胰腺癌每年新发病例约28000人,为消化道肿瘤死亡原因的第2位。在英国,胰腺癌的发病率在近30年内亦升高3倍。在     

环状RNA与糖尿病微血管病变相关性的研究进展

糖尿病微血管病变是糖尿病常见的慢性并发症。环状RNA(circRNA)在多种疾病的发生、发展中有着重要作用。研究发现circRNA与糖尿病微血管病变密切相关,是糖尿病视网膜病变(DR)、糖尿病肾病(DKD)和糖尿病周围神经病变(DPN)发生、发展的重要调控分子,有可能用于糖尿病微血管病变的诊断,也有望成为治疗DR、DKD和DPN的分子工具。因此,该文就circRNA在糖尿病微血管病变的作用作一综述。     

胰腺癌的CT诊断

目的：探讨胰腺癌的ＣＴ特征、诊断与鉴别诊断。材料和方法：分析５５例（男３９例，女１６例）胰腺癌患者的临床和ＣＴ表现。年龄最大７８岁，最小２８岁，平均５７．７岁。其中胰头部癌３８例（６９．０９％），体部１２例（２１．８２％），尾部５例（９．０９％）。ＣＴ扫描以１０ｍｍ层厚与间隔，自隔顶扫至钩突下缘，胰腺部则取５ｍｍ层厚与间隔。并作冠状面及矢状面重建。结果：５５例中仅２０例手术切除。平均生存期为５～８月。ＣＴ表现为胰腺局部分叶状肿块（５０／５５）；平扫时与周围胰腺组织呈等密度或略低密度：增强后强化不明显，甚至低于正常胰腺组织；胰周组织浸润（２０／５５）；血管受侵（３７／５５）；远处转移（１７／５５）；继发性囊肿（４／５５）。３８例胰头癌ＣＴ中可见胰体、尾萎缩（３４／３８）；胰管扩张（２４／３８）；梗阻性胆管扩张（肝内胆管＋总阻管扩张１５例；单纯肝内胆管扩张４例）。结论：熟悉胰腺癌的特征性与非特征性表现，多数病例可被确诊，但对临床预后无帮助。     

血清MicroRNA-122作为脓毒症诊断特异性标志物的研究

目的观察脓毒症患者血清中miRNA-122的表达量在病程中的动态变化情况,并探讨其与脓毒症严重程度的关系。方法选择52例脓毒症患者,其中一般脓毒症23例,重症脓毒症29例,23例健康人作为对照。采用荧光定量PCR(qRT-PCR)检测研究对象在入组第1,3,5,7,10,14天血清中miRNA-122表达量,并记录患者的基本临床信息。结果在脓毒症患者入组后14d的病程中,52例脓毒症患者和23例健康人群血清中的miRNA-122表达量在每个时间点比较,前者均比后者显著下降(P<0.01)。用入组第1天的miRNA表达量做ROC诊断分析得出,miRNA-122诊断脓毒症的特异性是95.7%,敏感性是53.8%。重症脓毒症组的血清miRNA-122表达量水平高于一般脓毒症组,并且在各个观测时间点两组表达量具有统计学差异(P<0.01)。结论血清中miRNA-122可能作为脓毒症诊断的特异性标志物,具有潜在的临床价值,并且miRNA-122在预警脓毒症患者疾病严重程度方面具有积极的临床意义。     

基于GEO数据库胃癌差异表达环状RNA及其功能与通路研究

目的利用GEO数据库胃癌环状RNA(circRNA)表达谱数据,探讨胃癌差异表达circRNA及其富集的通路和参与的功能。方法首先在GEO数据库查询并下载胃癌circRNA表达谱数据,选择符合条件的3个数据集,分别为GSE78092、 GSE100170、GSE83521,对circRNA的命名进行整合和统一,在R.3.5.0环境下应用Limma包筛选差异表达circRNA,过滤条件为校正P<0.05,log2FC绝对值>1。然后,利用聚类分析热图筛选在正常组织和癌组织中区分度最佳的circRNA进行深入研究,分析其潜在作用的GO功能和KEGG通路。结果在整合数据中共发现13个差异表达circRNA,对其表达水平和组织样本进行聚类分析发现,hsa_circ_0009172、hsa_circ_0006089在正常组织和胃癌组织中差异表达最为明显。GO功能和KEGG通路发现hsa_circ_0009172可能在细胞粘附分子结合、转录因子活性等GO功能存在富集,可能通过P53信号通路发挥抑癌作用;而hsa_circ_0006089可能发挥钙粘蛋白结合、翻译调节活性等GO功能,可能通过癌症的转录失调信号通路、轴突引导信号通路发挥促癌作用。结论综合GEO公共数据库胃癌circRNA表达谱芯片数据,使样本量相对充足,筛选胃癌组织与正常组织间差异表达circRNA并进行深入研究是可行的,为胃癌相关circRNA的基础研究提供有意义的参考,将来可能为胃癌的个体化治疗提供分子标志物及治疗靶点。     

环状RNA在非酒精性脂肪肝中作用机制的研究进展

随着肥胖、糖尿病、高血压、高脂血症在全球的流行,非酒精性脂肪肝已经成为全球第一大慢性肝病,其作用机制复杂,至今仍未达成共识。但近年来研究发现,基因调控在其发生发展过程中起着重要作用。环状RNA具有稳定性、广泛性、保守性及组织特异性等性质,在基因表达调控中发挥重要作用。因此,研究非酒精性脂肪肝发生发展过程中环状RNA的调控作用有助于了解其发病机制并推动其临床治疗的进展。     

Hypoxia as a biomarker for radioresistant cancer stem cells

Purpose:?The use of nuclear/radiation devices against the civilian population is now a realistic scenario. Haematopoietic syndrome is the primary therapeutic challenge in the case of whole body acute exposure over 2 Grays (Gy) whereas burns and combined injuries would be frequently observed in myelo-suppressed patients. Optimisation of scoring and treatments are important goals to achieve.

Conclusion:?The European Response Category (RC) concept represents an attempt to integratively assess haematological/extrahematological radiation-induced lesions. Based on the frequently observed heterogeneity of bone marrow damage in accidental/intentional irradiations, the stimulation of residual stem cells using granulocyte Colony-stimulating factor remains the therapeutic standard after exposure to less than the lethal dose 50 % (Haematopoietic[H] score 3-H3). Allogeneic stem cell transplantation is indicated in case of medullary eradication (Haematopoietic score 4-H4) whereas extramedullary toxicity may determine the outcome. Especially in case of numerous casualties exhibiting acute radiation sydrome, the administration of survival factor combinations remains questionable, at least as a palliative treatment. In addition pleiotropic cytokines injection such as erythropoietin and keratinocyte growth factor and grafting multipotent mesenchymal stem cells – from underexposed bone marrow areas or fat tissues – could be proposed to prevent multiple organ failure syndrome development. Multi-disciplinary teams should be prepared to manage such patients.     

Radiomics signature as a new biomarker for preoperative prediction of neoadjuvant chemoradiotherapy response in locally advanced rectal cancer

PURPOSEWhether radiomics methods are useful in prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) is unclear. This study aimed to investigate multiple magnetic resonance imaging (MRI) sequence-based radiomics methods in evaluating therapeutic response to nCRT in patients with locally advanced rectal cancer (LARC).METHODSThis retrospective study enrolled patients with LARC (06/2014–08/2017) and divided them into nCRT-sensitive and nCRT-resistant groups according to postoperative tumor regression grading results. Radiomics features from preoperative MRI were extracted, followed by dimension reduction using the minimum redundancy maximum relevance filter. Three machine-learning classifiers and an ensemble classifier were used for therapeutic response prediction. Radiomics nomogram incorporating clinical parameters were constructed using logistic regression. The receiver operating characteristic (ROC), decision curves analysis (DCA) and calibration curves were also plotted to evaluate the prediction performance.RESULTSThe machine learning classifiers showed good prediction performance for therapeutic responses in LARC patients (n=189). The ROC curve showed satisfying performance (area under the curve [AUC], 0.830; specificity, 0.794; sensitivity, 0.815) in the validation group. The radiomics signature included 30 imaging features derived from axial T1-weighted imaging with contrast and sagittal T2-weighted imaging and exhibited good predictive power for nCRT. A radiomics nomogram integrating carcinoembryonic antigen levels and tumor diameter showed excellent performance with an AUC of 0.949 (95% confidence interval, 0.892–0.997; specificity, 0.909; sensitivity, 0.879) in the validation group. DCA confirmed the clinical usefulness of the nomogram model.CONCLUSIONThe radiomics method using multiple MRI sequences can be used to achieve individualized prediction of nCRT in patients with LARC before treatment.

Colorectal cancer is one of the most common malignancies. It ranks fourth for morbidity and third for mortality among malignant tumors, among which the proportion of rectal cancer with poor prognosis is over 60% (1, 2). Neoadjuvant therapy, combined with total mesorectal excision, has become a common strategy for rectal cancer (3). Response to neoadjuvant chemoradiotherapy (nCRT) is a marker of good prognosis in patients with locally advanced rectal cancer (LARC) (4). Tumor regression grading (TRG) is a reliable biomarker for evaluating the efficacy of nCRT (5, 6). TRG reflects the treatment effect of nCRT by evaluating fibrosis and the ratio of residual tumor cells (4). The accurate nCRT evaluation can only be achieved by postoperative histopathological TRG (3, 4), and there is still no technology that can noninvasively evaluate the therapeutic response.Magnetic resonance imaging (MRI) is commonly used in the diagnosis, preoperative staging, and therapeutic efficacy evaluation of rectal cancer. Prediction of the efficacy of nCRT by MRI has been rarely reported, partly due to the heterogeneity of the tumor combined with the prevalence of fibrosis and edema of lesions and surrounding tissue after nCRT. Over the recent years, a magnetic resonance TRG system was proposed for the evaluation of nCRT efficacy by using MRI and evaluating residual tumor and fibrosis. Nevertheless, the magnetic resonance TRG method has a low predictive value for pathological TRG and poor consistency, which hinders its clinical applications (7, 8).In recent years, radiomics has drawn increasing attention in oncology. Radiomics features selected from medical images have shown to be highly associated with the diagnosis and prognosis of cancers, and even with gene expression patterns (9). Studies highlighted the value of radiomics approaches in determining tumor status, preoperative staging, and efficacy evaluation (9, 10). Nevertheless, the application of the radiomics methods in evaluating therapeutic responses to nCRT is limited (11).Accordingly, the aim of the present study was to establish an nCRT prediction model based on multiple MRI sequences combined with tumor anatomy and biological characteristics so as to achieve a comprehensive preliminary prediction of nCRT efficacy for rectal cancer before treatment, to provide an essential basis for the rational formulation of clinical diagnosis and treatment decisions, and to avoid unnecessary exposure to radiotherapy and chemotherapy and the related risks such as toxicity and delayed definitive surgery.     

CXCR4 as biomarker for radioresistant cancer stem cells

Abstract

Purpose: Radioresistance of cancer cells remains a fundamental barrier for maximum efficient radiotherapy. Tumor heterogeneity and the existence of distinct cell subpopulations exhibiting different genotypes and biological behaviors raise difficulties to eradicate all tumorigenic cells. Recent evidence indicates that a distinct population of tumor cells, called cancer stem cells (CSC), is involved in tumor initiation and recurrence and is a putative cause of tumor radioresistance. There is an urgent need to identify the intrinsic molecular mechanisms regulating the generation and maintenance of resistance to radiotherapy, especially within the CSC subset. The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. The interaction of CXCR4 with its ligand, the chemokine C-X-C motif ligand 12 (CXCL12), plays an important role in modulating the tumor microenvironment, angiogenesis and CSC niche. Moreover, the therapeutic inhibition of the CXCR4/CXCL12 signaling pathway is sensitizing the malignant cells to conventional anti-cancer therapy.

Content: Within this review we are summarizing the role of the CXCR4/CXCL12 axis in the modulation of CSC properties, the regulation of the tumor microenvironment in response to irradiation, therapy resistance and tumor relapse.

Conclusion: In light of recent findings, the inhibition of the CXCR4/CXCL12 signaling pathway is a promising therapeutic option to refine radiotherapy.     

Impact of new diagnostic imaging methods on pancreatic angiography.

The results of 100 consecutive pancreatic arteriograms performed in concert with a combination of other diagnostic procedures (gray scale ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography) were evaluated to determine the value of angiography in diagnosis and management of patients with known or suspected pancreatic disease. Angiography was found to be valuable for diagnosis in 68% (68/100) of cases and was considered helpful for management in 81% (57/70) of patients with pancreatic neoplasm, pancreatitis, or a nonpancreatic abnormality.