磁性纳米粒在肝癌靶向治疗中的研究进展

磁性纳米粒子作为一种优良的靶向治疗载体,目前已广泛运用于基础医学及临床领域,其中涉及影像学诊断、临床治疗等方面。本文介绍了磁性纳米粒治疗肝癌的基本靶向机制、不同表面修饰后的纳米粒的靶向治疗机制,以及以纳米粒靶向性质为基础的化疗、热疗、免疫治疗、基因治疗等治疗方案。认为磁性纳米粒靶向治疗肝癌有着广阔的临床应用前景。     

Epigenetics and pancreatic cancer:Pathophysiology and novel treatment aspects

An improvement in pancreatic cancer treatment represents an urgent medical goal.Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades.Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations,such as mutations of K-ras,and especially epigenetic dysregulation of tumor-associated genes,such as silencing of the tumor suppressor p16ink4a,are hallmarks of pancreatic cancer.Here,we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation,histone acetylation or miRNA(microRNA)expression,and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition,morphological pattern formation,or cancer stem cell regulation during carcinogenesis from PanIN(pancreatic intraepithelial lesions)to invasive cancer and resistance development.Epigenetic drugs,such as DNA methyltransferases or histone deactylase inhibitors,have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development.Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.     

Novel approaches to the development of targeted therapeutic agents for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic multisystem disease in which various cell types and immunological pathways are dysregulated. Current therapies for SLE are based mainly on the use of non-specific immunosuppressive drugs that cause serious side effects. There is, therefore, an unmet need for novel therapeutic means with improved efficacy and lower toxicity. Based on recent better understanding of the pathogenesis of SLE, targeted biological therapies are under different stages of development. The latter include B-cell targeted treatments, agents directed against the B lymphocyte stimulator (BLyS), inhibitors of T cell activation as well as cytokine blocking means. Out of the latter, Belimumab was the first drug approved by the FDA for the treatment of SLE patients. In addition to the non-antigen specific agents that may affect the normal immune system as well, SLE-specific therapeutic means are under development. These are synthetic peptides (e.g. pConsensus, nucleosomal peptides, P140 and hCDR1) that are sequences of conserved regions of molecules involved in the pathogenesis of lupus. The peptides are tolerogenic T-cell epitopes that immunomodulate only cell types and pathways that play a role in the pathogenesis of SLE without interfering with normal immune functions. Two of the peptides (P140 and hCDR1) were tested in clinical trials and were reported to be safe and well tolerated. Thus, synthetic peptides are attractive potential means for the specific treatment of lupus patients. In this review we discuss the various biological treatments that have been developed for lupus with a special focus on the tolerogenic peptides.     

利用目标基因测序技术发现马方综合征FBN1新突变

目的:建立目标基因捕获结合第二代测序技术,对马方综合征(Marfan syndrome,MFS)患者的原纤维蛋白-1(fibrillin-1,FBN1)基因进行突变筛查,探讨MFS与FBN1基因突变的关系。方法:提取5例MFS患者外周血全基因组DNA,利用GenCap目标基因捕获技术(北京迈基诺公司),设计FBN1的65个外显子区域特异性捕获探针,与基因组DNA文库进行杂交,将目标基因组区域的DNA片段进行富集后,再利用illumina hiseq2000第二代测序仪进行测序,通过数据分析,确定突变位点,用Sanger测序法对突变位点进行验证。结果:设计合成的目标基因特异性捕获探针可有效地捕捉并富集基因组DNA的目标靶片段。5例患者目标区域平均测序深度为173.85~280.73,97.10%~98.00%目标区域4×覆盖度。经过数据分析及Sanger测序验证,发现1个新的无义突变c.5968 CT(p.Gln1990X)。结论:本研究所建立的GenCap目标基因捕获技术结合illumina hiseq2000第二代测序技术成功的发现了FBN1的新突变。该方法快速而有效,可以使我们对MFS分子病因学有更好的认识。     

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.     

Updated developments on molecular imaging and therapeutic strategies directed against necrosis

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.     

目标性救治措施救治重症手足口病的临床效果分析

目的：探讨目标性救治措施救治重症手足口病（ HFMD）患儿的临床效果。方法对2012年在该院住院的138例重症手足口病患儿（研究组）采用目标性救治。同时将该院2010年未进行目标性救治（均按国家诊疗规范救治）的152例患儿作为对照组进行回顾性对比分析。结果研究组的病情加重率低于对照组（P＜0.01）,但两组的抢救成功率和病死率比较差异无统计学意义（P均＞0.05）;研究组的症状消失时间和住院时间均短于对照组（ P＜0.05或＜0.01）;研究组的高血糖和神经系统后遗症发生率均低于对照组（ P均＜0.01）。结论目标性救治措施为重症HFMD的救治提供了系统性、可操作性的救治方案,可显著缩短临床症状消失时间和住院时间,降低高血糖和神经系统后遗症的发生率,改善预后。