软骨样脊索瘤的超微病理对比研究

目的：探讨软骨样脊索瘤的超微病理特点,为阐明此肿瘤的来源提供线索。方法：结合光镜、免疫组化及临床资料,对3例软骨样脊索瘤和4例普通的脊索瘤进行了超微结构对比观察。结果：1．在软骨样脊索瘤的软骨样区域,胞膜游离,形成棘突和微绒毛样突起;在非软骨样区域,瘤细胞排列紧密,粗面内质网发达。2．普通的脊索瘤,一些瘤细胞粗面内质网扩张、融合,挤压瘤细胞核至一侧。结论：1．软骨样脊索瘤出现了两个不同分化的层面,既有分化原始的类似胚胎脊索的瘤组织,又有分化高的软骨样区域,而普通的脊索瘤仅有单一的分化层面。2．软骨样脊索瘤的瘤细胞属同一起源,即胎儿的脊索残余。3,瘤组织的黏液性间质成分是由瘤细胞的粗面内质网合成的。液滴状细胞是部分瘤细胞由于粗面内质网高度扩张而成。     

ALA联合小剂量HPD激光光动力学治疗皮肤肿瘤临床研究

目的:局部外敷ALA和静脉注射小剂量HPD联合用药后进行激光光敏诊断和光动力学治疗,探讨这种联合用药光动力学疗法治疗皮肤恶性肿瘤的疗效.并与常规HPD-PDT及激光气化肿瘤合并ALA-PDT治疗作临床疗效对比.方法:30例患者,45处皮肤损害.采用ALA-PDT与小剂量HPD-PDT联合的方案进行治疗.光敏药物剂量:8%ALA 霜剂外敷,1.5mg/kg HPD静脉用药,波长630nm半导体激光照射(功率密度250mW/cm~2,照射时间20分钟/光斑).同时在PDT治疗过程中,及以后的随访中均以激光光敏诊断技术指导治疗及判断避光时间.并与常规HPD(5mg/kg)-PDT治疗皮肤恶性肿瘤43例及三周前激光气化肿瘤加20%ALA霜剂外敷光动力学治疗29例作疗效比较.结果:ALA联合小剂量HPD激光光动力学治疗组,除一例鳞癌II级患者及一例恶性黑色素瘤患者出现复发外,其余患者对联合治疗的效果均佳,随访6～24月,均获得了痊愈,近期痊愈率93.33%,显效率6.67%,皮肤避光时间减少到10～14天.HPD-PDT治疗皮肤恶性肿瘤组43例,40例达近期痊愈,近期痊愈率91.43%,3例显效,显效率8.57%(显效3例,2例为色素型基底细胞癌, 1例为直肠癌肛周复发).激光气化肿瘤加ALA-PDT治疗组29例,26例一次治疗痊愈,近期痊愈率89.66%,3例显效,显效率10.34%(显效3例,2例鳞癌II级经二次治疗痊愈,1例汗管癌7周复发改用手术治疗).结论:1.ALA联合小剂量HPD的光动力学疗法对于诊断和治疗皮肤恶性肿瘤有较佳的疗效.两种光敏剂的联合使用,使皮肤避光时间由原来常规剂量HPD-PDT所必需的4～5周缩短到2周左右,并改善了ALA-PDT作用深度浅(2mm)的弊端.2.光敏诊断是一种简便、快捷、灵敏、非创伤性的肿瘤诊断方法,对于提高肿瘤的早期诊断率有很大意义,又能作为判断避光时间的辅助手段.3.光动力学治疗是一种对肿瘤组织杀伤具有高度选择性的微创技术,病人对整个治疗过程的耐受性好,更适合于年老体弱或对皮肤美观有特殊需求的患者.     

Obesity Has a Systemic Effect on Immune Cells in Naïve and Cancer-Bearing Mice

Obesity is a major risk factor for developing cancer, with obesity-induced immune changes and inflammation in breast (BC) and colorectal cancer (CRC) providing a potential link between the two. This study investigates systemic effects of obesity on adaptive and innate immune cells in healthy and tumour-bearing mice. Immune cells from lean and obese mice were phenotyped prior to implantation of either BC (C57mg and EO771.LMB) or CRC (MC38) cells as tumour models. Tumour growth rate, tumour-infiltrating lymphocytes (TIL) and peripheral blood immune cell populations were compared between obese and lean mice. In vitro studies showed that naïve obese mice had higher levels of myeloid cells in the bone marrow and bone marrow-derived dendritic cells expressed lower levels of activation markers compared to cells from their lean counterparts. In the tumour setting, BC tumours grew faster in obese mice than in lean mice and lower numbers of TILs as well as higher frequency of exhausted T cells were observed. Data from peripheral blood showed lower levels of myeloid cells in tumour-bearing obese mice. This study highlights that systemic changes to the immune system are relevant for tumour burden and provides a potential mechanism behind the effects of obesity on cancer development and progression in patients.     

肿瘤磁热疗用产热材料的研究现状及评价

鉴于总结和评价已开发产热材料对今后正确选择磁热疗用材料进行有效治疗人体肿瘤有现实意义,系统综述了近2年各产热材料的最新研究,并引入评价因子以比较不同磁场条件下各材料的产热能力.经比较,产热能力较好的材料分别为羟基磷灰石包覆的Fe_3O_4/γ-Fe_2O_3、Fe_3O_4包覆的Fe、聚乙烯亚胺包覆的MnFe_2O_4及金属Co,其中铁氧化物已有人体临床实验的研究,可预见合理包覆的铁氧化物在人体肿瘤磁热疗中的应用前景.     

Selenium-Substituted Hydroxyapatite/Biodegradable Polymer/Pamidronate Combined Scaffold for the Therapy of Bone Tumour

The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and contained an active substance—bisphosphonate. For this purpose, a series of biodegradable polyesters were synthesized through a ring-opening polymerization of ε-caprolactone or d,l-lactide in the presence of 2-hydroxyethyl methacrylate (HEMA) or hyperbranched 2,2-bis(hydroxymethyl)propionic acid polyester-16-hydroxyl (bis-MPA) initiators, substances often used in the synthesis of medical materials. The polymers were obtained with a high yield and a number-average molecular weight up to 45,300 (g/mol). The combined scaffolds were then manufactured by a direct compression of pre-synthesized hydroxyapatite doped with selenite or selenate ions, obtained polymer and pamidronate as a model drug. It was found that the kinetic release of the drug from the scaffolds tested in vitro under physiological conditions is strongly dependent on the physicochemical properties and average molecular weight of the polymers. Furthermore, there was good correlation with the hydrolytic biodegradation results of the scaffolds fabricated without drug. The preliminary findings suggest that the fabricated combined scaffolds could be effectively used for the sustained delivery of bioactive molecules at bone defect sites.     

~(99m)Tc标记生长抑素类似物KE108的制备及生物学评价

为了探讨生长抑素类似物~(99m)Tc-HYNIC-KE108用于生长抑素受体阳性肿瘤显像的可行性,本研究设计合成了新型的生长抑素类似物HYNIC-KE108,并进行~(99m)Tc标记,优化标记条件,测定标记物的脂水分配系数和体外稳定性,研究其在正常小鼠及荷瘤鼠体内的生物分布。在优化条件下,~(99m)TcHYNIC-KE108的标记率90%,经Waters Oasis HLB小柱纯化后,放化纯度98%,标记物的脂水分配系数logP为0.43±0.02(n=3),体外稳定性良好。标记物在正常小鼠体内血液清除快,主要通过肾脏代谢,在胃、肺和肝脏中放射性摄取相对较高。荷瘤鼠体内分布结果表明,标记物注入体内4h时在肿瘤中的放射性摄取为(1.14±0.91)%ID·g-1,肿瘤与血、肌肉、心脏的放射性摄取比(T/NT)为1.78、8.14、3.35。本工作为进一步研究~(99m)Tc标记的KE108作为生长抑素受体阳性肿瘤显像剂提供了实验依据。     

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.     

Aspartic acid 50 and tyrosine 108 are essential for receptor binding and cytotoxic activity of tumour necrosis factor beta (lymphotoxin)

Single amino acid substitutions were generated in predictedhydrophilic loop regions of the human tumour necrosis factorbeta (TNF-ß) molecule, and the mutant proteins wereexpressed in Escherichia coli and purified. Mutants with singleamino acid changes at either of two distinct loop regions, atpositions aspartic acid 50 or tyrosine 108, were found to havegreatly reduced receptor binding and cytotoxic activity. Thesetwo regions in TNF-ß correspond to known loop regionswhere mutations also result in loss of biological activity ofTNF–, a related cytokine which shares the same cellularreceptors with TNF-ß. The two distinct loops at positions31-34 and 84-89 in the known three-dimensional structure ofTNF- (equivalent to positions 46–50 and 105–110respectively in TNF-ß), lie on opposite sides of theTNF- monomer. When the TNF-a monomer forms a trimer, the twoloops, each from a different subunit of the trimer, come togetherand lie in a cleft between adjacent subunits. Together, thesefindings suggest that a TNF receptor binds to a cleft betweensubunits via surface loops at amino acid residues 31–34and 84–89 in TNF–, and similarly via surface loopsincluding amino acids aspartic acid 50 and tyrosine 108 in TNF–ß.     

Modelling glioma progression,mass effect and intracranial pressure in patient anatomy

Increased intracranial pressure is the source of most critical symptoms in patients with glioma, and often the main cause of death. Clinical interventions could benefit from non-invasive estimates of the pressure distribution in the patient''s parenchyma provided by computational models. However, existing glioma models do not simulate the pressure distribution and they rely on a large number of model parameters, which complicates their calibration from available patient data. Here we present a novel model for glioma growth, pressure distribution and corresponding brain deformation. The distinct feature of our approach is that the pressure is directly derived from tumour dynamics and patient-specific anatomy, providing non-invasive insights into the patient''s state. The model predictions allow estimation of critical conditions such as intracranial hypertension, brain midline shift or neurological and cognitive impairments. A diffuse-domain formalism is employed to allow for efficient numerical implementation of the model in the patient-specific brain anatomy. The model is tested on synthetic and clinical cases. To facilitate clinical deployment, a high-performance computing implementation of the model has been publicly released.