肿瘤相关抗原Tn及其低聚体的合成

目的:展示肿瘤相关抗原Tn及其低聚体合成的进展。方法:查阅国内外文献,概括肿瘤相关抗原Tn及其低聚体合成的方法。结果:肿瘤相关抗原Tn是由糖基供体与保护丝氨酸(苏氨酸)缩合,去保护基后而得,Tn抗原低聚体通过Tn的逐步缩合或直接缩合而得。结论:肿瘤相关抗原Tn及其低聚体的合成是肿瘤疫苗研究中的一个热点。     

急性淋巴细胞白血病细胞肿瘤相关糖抗原前体的丁酰化改造

目的 探讨急性淋巴细胞白血病细胞肿瘤相关糖抗原前体的丁酰化改造。方法采用化学方法合成新前体N-丁酰甘露糖胺。结果核磁共振氢谱证明新前体为N-丁酰甘露糖胺。结论通过新前体N-丁酰甘露糖胺的合成,实现对急性淋巴细胞白血病细胞肿瘤相关糖抗原前体的丁酰化改造,为进一步通过细胞生物工程方法合成免疫原性显著增强的新肿瘤相关糖抗原N-丁酰唾液酸、解决ALL患者免疫治疗时免疫耐受问题打下了基础。     

肿瘤相关疫苗的合成

随着人们对肿瘤相关糖抗原分子特征的深入认识，近年来开始开化学合成方法进行癌疫苗的设计。这种癌疫苗的优点是结构简单、易制取、易表征、易处理。本文重点对肿瘤相关糖抗原（Ｔｎ、ｓＴｎ抗原）的合成、半合成（Ｔｎ、ｓＴｎ）疫苗的制备及全合成的Ｔｎ疫苗的制备进行论述。     

肝癌抗原的表达

目前,肿瘤抗原可分为以下几类：（1）组织特异性分化抗原;（2）基码的抗原;（3）不同剪切造成的变异体抗原;（4）CT抗原（cancer-testis antigen）。其中,CT抗原被认为是肿瘤特异性的抗原,因为这一类抗原在多种肿瘤组织中表达,而在睾丸、卵巢和胎盘除外的正常组织中无表达,所以也是最有希望应用于免疫治疗的一类抗原。     

T-Synthase及Tn、s-Tn抗原在上皮性卵巢癌中的表达及其临床意义

目的探讨T-Synthase及Tn、s-Tn抗原在上皮性卵巢癌中的表达及其临床意义。方法选取西京医院从2012年1月~2014年1月获得的30例上皮性卵巢癌和5例正常卵巢组织标本,应用免疫组化SABC法检测比较标本中T-Synthase及Tn、s-Tn抗原的表达情况。结果 T-Synthase在正常卵巢组织中的表达阳性率为100.00%,而在上皮性卵巢癌组织中只有6.67%,2组间比较差异有统计学意义(P<0.05)。Tn抗原在正常卵巢组织中的表达阳性率为20.00%,而在上皮性卵巢癌组织中有83.33%,2组间比较差异有统计学意义(P<0.05)。s-Tn抗原在正常卵巢组织中的表达阳性率为20.00%,而在上皮性卵巢癌组织中有96.67%,2组间比较差异有统计学意义(P<0.05)。结论 T-Synthase活性降低使Tn、s-Tn在卵巢癌组织中存在异常表达,T-Synthase、Tn、s-Tn肿瘤相关抗原在卵巢癌的发生和发展中起着重要作用。     

甾体激素人工抗原合成概况

目的介绍运用免疫学方法分析甾体激素时,人工抗原合成的设计及合成方法、合成的影响因素、与载体蛋白偶联方法及最佳结合比的研究概况。方法查阅国内外文献资料,整理、归纳甾体激素化合物人工抗原合成的研究情况。结果与结论甾体激素合成是小分子药物免疫学检测的基础,将直接影响抗体的特异性和亲和性,对建立甾体激素化合物灵敏、简便、快速的、超微量的免疫检测法非常关键。     

蛋白质组技术鉴定肿瘤相关抗原的研究进展

随着人类基因组测序的完成和蛋白质组技术的发展,采用蛋白质组技术筛选肿瘤相关抗原是近来发展的一种有效、简单的筛选肿瘤抗原的方法。基于蛋白质组技术肿瘤相关抗原的鉴定主要包括两步:一是利用血清学蛋白质组技术筛选自身抗原,二是鉴定目的分子。在多种肿瘤中已经采用该方法鉴定了一些肿瘤抗原,并在肿瘤的诊断、治疗以及预后发挥重要作用。本文主要介绍了基于蛋白质组技术鉴定的肿瘤相关抗原和鉴定抗原的表达情况以及与疾病关系的分析。     

H_2受体拮抗剂Bisfentidine

本品是继Mifentidine(已进入Ⅱ期临床研究)之后开发的选择性H_2受体拮抗剂。不同于Mifentidine的是在咪唑环的2位上引入了一个甲基。合成本品的合成方法有两种:1.由化合物Ⅰ与Ⅱ在乙醇内缩合而得;2.由化合物Ⅰ与Ⅲ在乙醇内反应,所得化合物Ⅳ在水中经异丙胺处理而得[EP131973;GB2149393]。     

肿瘤标志物与卵巢癌的相关性研究

目的 探讨血清肿瘤相关抗原CA125、CA19-9、癌胚抗原（CEA）联合检测对卵巢癌诊断的诊断价值.方法 正常健康对照组30例.患病组30例,相同条件下,均同时检测血清CA125、CA19-9、CEA.结果 患病组血清CA125、CA19-9、CEA与正常健康对照组比较,差异有统计学意义（P＜0.05）.患病组血清肿瘤相关抗原CA125、CA19-9、CEA单独检测时的阳性检出率分别为79.2%、47.9%、31.3%,联合检测肿瘤相关抗原CA125、CA19-9检测率提高89.1%,三者联合检测检出率为92.5%.结论 联合检测肿瘤相关抗原CA125、CA19-9和CEA三项指标可以大大提高卵巢癌诊断率.     

糖类抗原诊断卵巢癌的研究进展

单克隆抗体技术的广泛应用,为确定肿瘤相关抗原、肿瘤生物学的研究、肿瘤的诊断、预后和治疗具有广泛价值。糖类抗原作为肿瘤标志在临床上具有重要意义,本文对糖类抗原诊断卵巢癌的研究进展作一综述。一、糖类抗原的特征(一)细胞碳水化合物:细胞碳水化合物一般分为糖蛋白和糖脂,两者构成糖结合物。糖蛋白既是细胞的分泌产物又是膜的组成部分,而糖脂一般     

银曲软胶囊制备工艺研究

目的 通过实验,确定银曲软胶囊的制备工艺.方法 选定指标,设计处方,确定囊壳和内容物的最佳处方工艺.结果 囊皮最佳处方为明胶∶甘油:聚乙二醇(PEG)600∶水∶可可壳色素∶二氧化钛=100∶40∶5∶ 100∶0.2∶ 1.5;内容物最佳处方为主药∶大豆油∶PEG600∶CMC-Na∶1,2-丙二醇∶大豆卵磷脂∶水=54∶15∶10∶1∶8∶5∶7.结论 所确定的处方工艺稳定可靠,重复性好,适合工业生产.     

Anti-inflammatory compounds of plant origin. Part II. modulation of pro-inflammatory cytokines, chemokines and adhesion molecules

It has been widely shown that many plant-derived compounds present significant anti-inflammatory effects. For this reason, they represent potential molecules for the development of new drugs, especially designed for the treatment and/or control of chronic inflammatory states such as rheumatism, asthma, inflammatory bowel diseases, atherosclerosis, etc. This review focuses on the naturally-occurring compounds with anti-inflammatory properties and attempts to correlate their actions with the modulation of cytokines and associated intracellular signalling pathways; it continues the review published in the November, 2003 issue of Planta Medica. Abbreviations. AP-1:activator protein-1 CCR1:chemokine receptor 1 CINC-1:cytokine-induced neutrophil chemoattractant 1 COX:cyclooxygenase EGCG:(-)-epigallocatechin gallate ELAM-1:endothelial-leukocyte adhesion molecule-1 ERK:extracellular signal-regulated kinase GRO:growth-related oncogene HUVEC:human umbilical vein endothelial cells ICAM-1:intercellular adhesion molecule-1 IFN:interferon IL:interleukin iNOS:inducible nitric oxide synthase IRA:the natural interleukin receptor activation JAK:janus kinase JNK:c-Jun NH2-terminal kinase LPS:lipopolysaccharide MAPK:mitogen-activated protein kinases MCP:monocyte chemotactic protein MHC:major histocompatibility complex MIP:macrophage inflammatory protein MMP:matrix metalloproteinases MPO:myeloperoxidase NF-kappaBnuclear factor kappa B NO:nitric oxide PAF:platelet aggregation factor PGEE:prostaglandin PK:protein kinase PMA/TPA:phorbol myristate acetate RANTES:regulated upon activation normal T-cell expressed and secreted TGF-beta:transforming growth factor-beta TNFalpha:tumour necrosis factor VCAM-1:vascular cell adhesion molecule-1     

不同配比头孢呋辛/三唑巴坦的体外抗菌活性研究

目的 评价不同配比头孢呋辛/三唑巴坦(CXM/TB)的体外抗菌活性.方法 采用平皿琼脂二倍稀释法测定不同配比CXM/TB对1436株临床分离致病菌的最低抑菌浓度(MIC).结果 不同配比CXM/TB(1:1、2:1、3:1、4:1、8:1和16:1)对1436株临床分离菌具有广谱抗菌作用,CXM/TB 1:1、2:1、3:1的抗菌活性相近,稍强于CXM/TB 4:1、8:1、16:1.不同配比CXM/TB对1109株产β-内酰胺酶菌株中的金葡菌、表皮葡萄球菌、大肠埃希菌、肺炎克雷伯菌、醋酸钙不动杆菌、普通变形菌、奇异变形菌、雷氏普罗威登斯菌、摩氏摩根菌、阴沟肠杆菌、产气肠杆菌、异型柠檬酸杆菌和黏质沙雷菌的MIC_(90)值分别为CXM的1/4～1/32,对产ESBLs大肠埃希菌、肺炎克雷伯菌的MIC_(90)值分别为CXM的1/8～1/16,但对产β-内酰胺酶的铜绿假单胞菌、假单胞菌属(除铜绿假单胞菌)的MIC_(90)值与CXM相近;对不产β-内酰胺酶的金葡菌、表皮葡萄球菌、化脓链球菌、肺炎链球菌、流感嗜血菌、副流感嗜血菌的抗菌活性与CXM相近.不同配比CXM/TB对612株产酶耐药临床分离菌中的金葡菌、表皮葡萄球菌、大肠埃希菌、肺炎克雷伯菌、醋酸钙不动杆菌、普通变形菌、奇异变形菌、产气肠杆菌的MIC_(90)分别为CXM的1/8～1/64.不同配比CXM/TB对MRSA、MRSE、粪肠球菌、假单胞菌属的抗菌活性差.结论 不同配比CXM/TB均有较强的体外抗菌活性,CXM/TB 1:1、2:1、3:1的抗菌活性相近,稍优于CXM/TB 4:1、8:1、16:1,TB增强了CXM抗产β-内酰胺酶细菌的活性.     

高效液相色谱法测定盐酸喹那普利片含量

目的：采用高效液相色谱法测定盐酸喹那普利片的含量。方法：采用C18色谱柱，甲醇：水：磷酸：二乙胺(160：40：0.13：0.16)为流动相，紫外检测波长为215nm。结果：平均回收率为99．60％，RSD=0．12％符合要求。结论：本方法切实可行。     

Clinical translation of immunoliposomes for cancer therapy: recent perspectives

Introduction: Liposomes have been extensively investigated as drug delivery vehicles. Immunoliposomes (ILs) are antibody-conjugated liposomes designed to selectively target antigen-expressing cells. ILs can be used to deliver drugs to tumor cells for improving efficacy and reducing toxicity. In addition, ILs can be used in immunoassays, immunotherapy, and imaging. Although there has been extensive coverage on ILs in the literature, only a limited number of clinical trials have been reported and no IL drug has been approved by the FDA.

Areas covered: Factors to consider in developing ILs are discussed, including the choice of antibody or antibody fragment, the formulation of liposomes, and the conjugation chemistry. In addition, challenges and opportunities in clinical development of ILs are discussed. The purpose of this review is to provide an overview on the state of the art of ILs and to discuss potential future developments.

Expert opinion: IL research has had a lengthy history and numerous preclinical studies have yielded encouraging results. However, there are a number of obstacles to clinical translation of ILs. Given the unique capabilities of ILs, its potential for clinical application is underexplored. There is great potential for expanded role for ILs in the clinic and further efforts to this end are warranted.

Abbreviations: Ab: antibody; ADCs: antibody-drug conjugates; API: active pharmaceutical ingredient; ADCC: antibody-dependent cellular cytotoxicity; CR: complete remission; cGMP: current good manufacturing practice; DSPE: distearoyl phosphatidylethanolamine; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPR: enhanced permeability and retention; Fc: fragment crystalline; Tf: transferrin; HACA: human-anti-chimeric antibody; HAHA: human-anti-human antibody; HAMA: human-anti-mouse antibody; HER2: human epidermal growth factor 2; IL: immunoliposome; LNPs: lipid nanoparticles; MRI: magnetic resonance imaging; MTD: maximum tolerated dose; PEG: polyethylene glycol; PET: positron emission tomography; PR: partial response; PSMA: prostate-specific membrane antigen; scFv: single-chain variable fragment; SPECT: single photon emission computed tomography; TTR: transthyretin     

Lavender oil inhibits immediate-type allergic reaction in mice and rats

We studied the effects of lavender oil on mast cell-mediated immediate-type allergic reactions in mice and rats. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 in mice by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) also inhibited concentration-dependently the histamine release from the peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, lavender oil (1:1000, 1:100, 1:10, 1:0) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from peritoneal mast cells. These results indicate that lavender oil inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in-vivo and in-vitro.     

Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in rat liver.

The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased the contents of 1-palmitoyl-2-docosahexaenoyl (16:0-22:6), 1-stearoyl-2-arachidonoyl (18:0-20:4), and 1-stearoyl-2-linoleoyl (18:0-18:2) PC; the drug did not change the content of 1-palmitoyl-2-arachidonoyl (16:0-20:4) PC. The mechanism underlying these changes has been investigated with regard to the in vivo formation of the molecular species of PC by: (i) de novo synthesis, (ii) reacylation, and (iii) methylation of phosphatidylethanolamine (PE). We found that (i) the incorporation of [3H]glycerol, which was injected intravenously, into 16:0-18:1 diacylglycerol (DG) and 16:0-18:1 PC was increased markedly by clofibric acid feeding without changing the substrate specificity of CDP-choline:DG cholinephosphotransferase, (ii) the in vivo formation of 16:0-18:1 and 16:0-20:4 PC from 1-16:0-[3H]glycerophosphocholine (GPC), which was injected intraportally, was increased markedly by clofibric acid feeding, and (iii) the incorporation of [14C]ethanolamine, which was injected intravenously into 16:0-22:6, 18:0-22:6, and 18:0-20:4 PC, was decreased by clofibric acid feeding; the extent of the decrease in 16:0-20:4 PC was less than that of 18:0-20:4 PC. It was concluded, therefore, that (i) clofibric acid selectively increased the content and proportion of 16:0-18:1 PC by enhancing both the CDP-choline pathway and the remodeling of the pre-existing PC molecule, and (ii) the drug kept the content of 16:0-20:4 PC unchanged by stimulating the remodeling of the pre-existing PC molecule, whereas the formation of other more long chain, polyunsaturated molecular species, such as 16:0-22:6, 18:0-22:6, and 18:0-20:4, was decreased owing to the suppression of PE methylation.     

Report on intrauterine drug exposure during second trimester of pregnancy in a heroin-associated death

A 17-year-old girl was found dead in a public toilet with fresh needle puncture marks. She was 18-20 weeks pregnant with a male fetus. Drug screening of her blood and urine indicated recent heroin use. Chronic drug use was confirmed by hair analysis. Amniotic fluid as well as fetal and maternal tissues and body fluids were analyzed by GC/MS and HPLC. All the fetal specimens were investigated, and the following levels of drugs were found: 6-monoacetyl-morphine (blood: 152 ng/g; amniotic fluid: 128 ng/g; brain: 140 ng/g; lung: 110 ng/g; liver: 2 ng/g; kidney: 40 ng/g), morphine (blood: 1360 ng/g; amniotic fluid: 604 ng/g; brain: 710 ng/g; lung: 1030 ng/g; liver: 2060 ng/g; kidney: 1100 ng/g), codeine (blood: 70 ng/g; brain: 60 ng/g; lung: 60 ng/g; liver: 90 ng/g; kidney: 70 ng/g), and morphine-3-glucuronide (amniotic fluid: 209 ng/g; brain: 170 ng/g; lung: 325 ng/g; kidney: 231 ng/g). Morphine-6-glucuronide was present in the maternal circulation but could not be detected in the fetal circulation.     

Identification and estimation of partially linear censored regression models with unknown heteroscedasticity

In this paper, we introduce a new identification and estimation strategy for partially linear regression models with a general form of unknown heteroscedasticity, that is, and , where ε is independent of and the functional forms of both and are left unspecified. We show that in such a model, β₀ and can be exactly identified while can be identified up to scale as long as permits sufficient nonlinearity in X. A two‐stage estimation procedure motivated by the identification strategy is described and its large sample properties are formally established. Moreover, our strategy is flexible enough to allow for both fixed and random censoring in the dependent variable. Simulation results show that the proposed estimator performs reasonably well in finite samples.