BACKGROUND & AIMS: :The interactions between nerve fibres from para- and orthosympathetic ganglia and adreno-cortical and -medullary cells were studied in joint cultures using explanted guinea-pig ciliary and sympathetic chain ganglia and enzyme-dispersed rat adrenal gland cells. Nerve fibres from both para- and orthosympathetic ganglia made only transitory contact with cortical cells, but consistently formed associations with isolated chromaffin cells which lasted for up to 10 days. Contacts between axons and chromaffin cells often showed particularly large varicosities and frequently withstood severe tests of durability from pulls of the fibre or the cell or both. By correlating phase contrast and catecholamine histochemistry (Falck-Hillarp method) it was shown that sympathetic fibres forming long-lasting contacts with chromaffin cells were adrenergic. The functional implications of the ability of autonomic nerves to distinguish between adreno-cortical and -medullary cells and the lack of specificity shown by the para- and orthosympathetic neurons during formation of long-lasting associations with chromaffin cells are discussed.

背景与目标： : 使用外植的豚鼠睫状和交感链神经节以及酶分散的大鼠肾上腺细胞，在联合培养物中研究了来自对侧和正交感神经节的神经纤维与肾上腺皮质和髓质细胞之间的相互作用。来自副神经节和正交感神经节的神经纤维仅与皮质细胞短暂接触，但始终与分离的嗜铬细胞形成关联，持续长达10天。轴突和嗜铬细胞之间的接触通常显示出特别大的静脉曲张，并且经常经受住纤维或细胞或两者的拉力对耐久性的严格测试。通过关联相衬和儿茶酚胺组织化学 (Falck-Hillarp方法)，表明与嗜铬细胞形成持久接触的交感神经纤维是肾上腺素能的。讨论了自主神经区分肾上腺皮质细胞和髓质细胞的能力的功能含义，以及在与嗜铬细胞形成长期关联的过程中，副神经和直系神经神经元表现出的缺乏特异性。

BACKGROUND & AIMS: :Rabbits of allotype a1a3 were injected on days 0, 2, and 4 with mixtures containing equal amounts of pigeon erythrocytes (Prbc) coupled to para-azobenzenearsonate (AA) and to para-azobenzene-N-trimethylammonium (TMA). On day 6, the allotypes of antibody from plaque-forming cells (PFC) of the blood were determined by observing the inhibition of plaque formation by anti-allotype sera. Anti-AA PFC appeared to consist for the most part of cells making antibody of allotype a1 since 65% of them were inhibited by anti-a1 serum and only 8% by anti-a3. Anti-TMA PFC, on the other hand, appeared to consist mostly of cells making antibody of allotype a3, since less than 1% of them were inhibited by anti-a1 but 47% by anti-a3. Antibody allotype for spleen PFC was also determined on day 6 and was similar to that found for blood PFC. Anti-AA PFC were inhibited 74% by anti-a1 serum and 15% by anti-a3 whereas anti-TMA PFC were inhibited 19% by anti-a1 and 43% by anti-a3. Serum hemolysin specific for AA hapten from a1a3 animals was also strongly inhibited by anti-a1 serum but not by anti-a3 whereas the converse was true for hemolysin against TMA hapten. The a1a3 rabbits, in whcih the anti-AA was restricted to allotype a1, were mated to produced homozygous a3a3 animals. When the PFC and serum antibodies of these a3a3 offspring were examined by specific inhibition, the anti-AA activity was found to be of allotype a3 rather than being a-negative. The number of anti-AA PFC in the blood of a3a3 rabbits was lower than that in blood of a1a3 or a1a1 animals. In addition, the TMA hapten appeared to inhibit the response to the AA hapten. Thus a1a3 rabbits immunized with AA-Prbc alone had 14-fold more anti-AA PFC or 18-fold higher anti-AA hemolysin titer than a3a3 animals immunized with both AA-Prbc and TMA-Prbc. Our results are discussed in relation to various explanations which have been offered for an imbalance of allotypes in a given antibody.

背景与目标： : 在第0、2和4天，向同种异体a1a3兔子注射含有等量的鸽子红细胞 (Prbc) 的混合物，该混合物与对偶氮苯硬脂酸酯 (AA) 和对偶氮苯-N-三甲基铵 (TMA) 偶联。在第6天，通过观察抗异体血清对斑块形成的抑制作用，确定了来自血液中斑块形成细胞 (PFC) 的抗体的同种异型。抗AA PFC似乎由大部分细胞组成，产生同种异型a1抗体，因为其中65% 被anti-a1血清抑制，仅被anti-a3 8%。另一方面，抗TMA PFC似乎主要由产生同种异体a3抗体的细胞组成，因为其中少于1% 的细胞被anti-a1抑制，但47% 被anti-a3抑制。脾脏PFC的抗体同种异型也在第6天测定，与血液PFC相似。抗AA PFC 74% 被anti-a1血清抑制，15% 被anti-a3抑制，而抗TMA PFC 19% 被anti-a1抑制，43% 被anti-a3抑制。来自a1a3动物的AA半抗原特异性血清溶血素也被anti-a1血清强烈抑制，但未被anti-a3抑制，而针对TMA半抗原的溶血素则相反。将抗AA仅限于同种异型a1的a1a3兔交配产生纯合的a3a3动物。当通过特异性抑制检查这些a3a3后代的PFC和血清抗体时，发现抗AA活性是同种异体a3，而不是a阴性。a3a3兔血液中抗AA PFC的数量低于a1a3或a1a1动物的血液。此外，TMA半抗原似乎抑制了对AA半抗原的反应。因此，仅用aa-prbc免疫的a1a3兔的抗AA PFC或抗AA溶血素滴度比用aa-prbc和tma-prbc免疫的a3a3动物高14倍。我们讨论了有关给定抗体中同种异体失衡的各种解释的结果。

BACKGROUND & AIMS: PURPOSE:The Radiation Therapy Oncolology Group (RTOG) 0116 trial was designed to test the ability of Amifostine to reduce the toxicity of combined chemotherapy with extended-field radiotherapy and brachytherapy (Part 2), after first determining the toxicity rate for the regimen without Amifostine (Part 1). This manuscript reports the results of Part 1. METHODS AND MATERIALS:Eligibility included patients with cervical carcinoma and high common iliac or para-aortic metastasis. Patients received extended-field radiotherapy to 45 Gy (1.8 Gy/fraction) with intracavitary irradiation. The final point A dose was 85 Gy LDR equivalent. Use of HDR was allowed. The positive para-aortic and high common iliac nodes were boosted to 54 to 59.4 Gy. Cisplatin (40 mg/m(2)) was delivered weekly during external beam and once with brachytherapy. The primary endpoint of Part 1 was acute Grade 3/4 toxicity, excluding Grade 3 leukopenia. RESULTS:A total of 26 eligible patients were entered between August 1, 2000, and December 3, 2003. Of these, 21 had para-aortic metastasis (15 also had high common iliac involvement), and 5 had high common iliac involvement only. The median follow-up was 17.1 months (range, 1.8-38.6 months) for all patients and 21.7 months (range, 11.4-38.6 months) for alive patients. The acute Grade 3/4 toxicity rate, excluding Grade 3 leukopenia was 81%. Late Grade 3/4 toxicity was 40%. Eight patients underwent surgery for complications. Sixteen (62%) patients had a complete response for both local and nodal disease. The complete local response was 92%, the complete overall nodal response rate was 62% and the regional and para-aortic nodal response rates were 60% and 71% respectively. Estimated disease-free and overall survival at 18 months are 46% and 60%. CONCLUSIONS:Extended field and intracavitary irradiation with cisplatin for para-aortic or high common iliac metastasis from cervical cancer is associated with significant acute and late toxicity.

背景与目标：

BACKGROUND & AIMS: :A series of ethacrynic acid analogues, lacking the α,β-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, Hs578Ts(i)8 as well as of human prostate cancer cells, C4-2B. These cell lines provide a good model system to study migration and invasion, since they represent metastatic cancer. Our studies show that ethacrynic acid analogues with methyl substituents at the aromatic ring demonstrate no inhibitory effect on the migration of both cancer cell lines, whereas a precursor in the synthesis of these ethacrynic acid analogues (II-1, a para-acylated m-cresol) is an excellent inhibitor of the migration of both cancer cell lines.

背景与目标： : 合成了一系列缺乏 α，β-不饱和羰基单元的乙酸类似物，随后评估了其抑制人乳腺癌细胞Hs578Ts(i)8以及人前列腺癌细胞迁移的能力，C4-2B。这些细胞系为研究迁移和侵袭提供了良好的模型系统，因为它们代表了转移性癌症。我们的研究表明，在芳环上具有甲基取代基的乙炔酸类似物对两种癌细胞系的迁移均无抑制作用，而这些乙炔酸类似物的合成前体 (II-1，对酰化的间甲酚) 是两种癌细胞系迁移的出色抑制剂。

BACKGROUND & AIMS: :We present here the results concerning the antibacterial properties evaluation of para-guanidinoethylcalix[4]arene, compared with its constitutive monomer, the para-guanidinoethylphenol, and hexamidine (Hexomédine), an antiseptic from the diamidine family widely used in therapeutic, chosen as a reference in this study for its resemblance in terms of functional groups. Antibacterial activities of those three compounds were evaluated by microdilution methods, in Mueller Hinton broth, onto 5 bacterial strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 & ATCC 29213 and Enterococcus faecalis ATCC 29212, according to CA-SFM and CLSI (formerly NCCLS) approved standards. In parallel, the effects of these three compounds on MRC-5 eukaryotic cell viability were evaluated with MTT assay. The results obtained here confirm a lack of activity for the monomer compound (MIC> or =512 mg/l) and a real antibacterial activity for the calixarene, comparable to hexamidine. This activity is expressed, both on Gram+and Gram- bacteria (MIC=4 mg/l for E. coli, 8 mg/l on both S. aureus strains) and at a lesser degree on E. faecalis and P. aeruginosa (MIC=32 mg/l). Similarly, both compounds, monomer and calixarene, slightly induce any modification on MRC-5 cells viability, and this until 168 h of treatment for concentrations reaching 10(-4) mol/L while hexamidine demonstrates a significant and increasing effect during the time of experiment and this for 100 to 1000 times lower concentrations. Thus, this study tends to confirm the significance of the organization of the para-guanidinoethylphenol monomer into its cyclic calixarenic tetramer for the gain of an antibacterial activity, similar to a widely used antiseptic one.

背景与目标： : 我们在这里介绍了有关对胍基乙基杯 [4] 芳烃的抗菌性能评估的结果，与其组成性单体，对胍基乙基苯酚和六胺 (Hexomédine) (一种来自二胺家族的防腐剂) 进行了比较，广泛用于治疗，由于其在官能团方面的相似之处，因此在本研究中被选为参考。根据ca-sfm和CLSI (原NCCLS) 批准的标准，通过微稀释方法在Mueller Hinton肉汤中对5种细菌菌株: 大肠杆菌ATCC 25922，铜绿假单胞菌ATCC 27853，金黄色葡萄球菌ATCC 25923和ATCC 29213和粪肠球菌ATCC 29212进行抗菌活性评估。同时，用MTT测定法评估这三种化合物对MRC-5真核细胞活力的影响。此处获得的结果证实了单体化合物缺乏活性 (MIC> 或 = 512 mg/l) 和杯芳烃的实际抗菌活性，与六胺定相当。这种活性在革兰氏细菌和革兰氏细菌上都有表达 (大肠杆菌的MIC = 4 mg/l，两种金黄色葡萄球菌菌株的MIC = 8 mg/l)，在粪肠球菌和铜绿假单胞菌 (MIC = 32 mg/l)。类似地，单体和杯芳烃这两种化合物轻微地诱导对MRC-5细胞活力的任何修饰，这直到浓度达到10(-4) mol/L的处理168小时，而在实验期间，六胺定显示出显著且增加的效果，这对于100到1000倍的低浓度。因此，这项研究倾向于证实将对位胍基乙基酚单体组织成其环状杯烯四聚体以获得抗菌活性的重要性，类似于广泛使用的防腐剂。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to determine the prognostic value of lymph node ratio (LNR) in women with 2018 International Federation of Gynecology and Obstetrics stage IIIC cervical cancer. METHODS:In this retrospective dual-institutional study, a total of 185 node-positive cervical cancer patients who had undergone radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy were included. All of the patients received adjuvant chemoradiation after surgery. LNR was defined as the ratio of positive lymph nodes (LNs) to the total number of LNs removed. The patients were categorized into 2 groups according to LNR; LNR <0.05 and LNR ≥0.05. The prognostic value of LNR was evaluated with univariate log-rank tests and multivariate Cox regression models. RESULTS:A total of 138 patients (74.6%) had stage IIIC1 disease and 47 (25.4%) patients had stage IIIC2 disease. With a median follow-up period of 45.5 months (range 3-135 months), the 5-year disease-free survival (DFS) rate was 62.5% whereas the 5-year overall survival (OS) rate was 70.4% for the entire study population. The 5-year DFS rates for LNR <0.05 and LNR ≥0.05 were 78.2%, and 48.4%, respectively (p<0.001). Additionally, the 5-year OS rates for LNR <0.05 and LNR ≥0.05 were 80.6%, and 61.2%, respectively (p=0.007). On multivariate analysis, LNR ≥0.05 was associated with a worse DFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.15-3.90; p=0.015) and OS (HR=1.95; 95% CI=1.01-3.77; p=0.046) in women with stage IIIC cervical cancer. CONCLUSIONS:LNR ≥0.05 seems to be an independent prognostic factor for decreased DFS and OS in stage IIIC cervical carcinoma.

背景与目标：

BACKGROUND & AIMS: :Transient junctional rhythm late after para-Hisian accessory pathway cryoablation occurred in two patients. Cryoablation was delivered using the 8 mm tip Freezor MAX™ catheter (Cryocath Technologies Inc., Montreal, Canada), 2 mm distal to the largest His potential. Transient symptomatic junctional rhythm occurred after 1 week. This benign, self-limiting rhythm is possibly caused by reversible cryoinjury to the His bundle periphery.

背景与目标： : 两名患者发生了副Hisian辅助途径冷冻消融后晚期的短暂连接节律。使用8毫米尖端Freezor MAX进行冷冻消融™导管 (Cryocath Technologies Inc.，加拿大蒙特利尔)，2毫米最大的潜力。1周后出现短暂症状性交界节律。这种良性的，自限性的节律可能是由His束周围的可逆冷冻损伤引起的。

BACKGROUND & AIMS: :The rubber particle is a special organelle in which natural rubber is synthesised and stored in the laticifers of Hevea brasiliensis. To better understand the biological functions of rubber particles and to identify the candidate rubber biosynthesis-related proteins, a comprehensive proteome analysis was performed on H. brasiliensis rubber particles using shotgun tandem mass spectrometry profiling approaches-resulting in a thorough report on the rubber particle proteins. A total of 186 rubber particle proteins were identified, with a range in relative molecular mass of 3.9-194.2 kDa and in isoelectric point values of 4.0-11.2. The rubber particle proteins were analysed for gene ontology and could be categorised into eight major groups according to their functions: including rubber biosynthesis, stress- or defence-related responses, protein processing and folding, signal transduction and cellular transport. In addition to well-known rubber biosynthesis-related proteins such as rubber elongation factor (REF), small rubber particle protein (SRPP) and cis-prenyl transferase (CPT), many proteins were firstly identified to be on the rubber particles, including cyclophilin, phospholipase D, cytochrome P450, small GTP-binding protein, clathrin, eukaryotic translation initiation factor, annexin, ABC transporter, translationally controlled tumour protein, ubiquitin-conjugating enzymes, and several homologues of REF, SRPP and CPT. A procedure of multiple reaction monitoring was established for further protein validation. This comprehensive proteome data of rubber particles would facilitate investigation into molecular mechanisms of biogenesis, self-homeostasis and rubber biosynthesis of the rubber particle, and might serve as valuable biomarkers in molecular breeding studies of H. brasiliensis and other alternative rubber-producing species.

背景与目标： : 橡胶颗粒是一种特殊的细胞器，其中天然橡胶被合成并存储在巴西橡胶树的胶乳中。为了更好地了解橡胶颗粒的生物学功能并鉴定与橡胶生物合成相关的候选蛋白，使用shot弹枪串联质谱分析方法对巴西橡胶颗粒进行了全面的蛋白质组分析，从而获得了有关橡胶颗粒蛋白的全面报告。总共鉴定了186种橡胶颗粒蛋白，其相对分子质量范围为3.9-194.2 kDa，等电点值为4.0-11.2。对橡胶颗粒蛋白进行了基因本体论分析，并根据其功能可分为八大类: 包括橡胶生物合成，应激或防御相关反应，蛋白质加工和折叠，信号转导和细胞转运。除了众所周知的橡胶生物合成相关蛋白如橡胶伸长因子 (REF) 、小橡胶颗粒蛋白 (SRPP) 和顺异戊二烯基转移酶 (CPT) 外，许多蛋白质首先被鉴定为在橡胶颗粒上，包括亲环素、磷脂酶D、细胞色素P450、小GTP结合蛋白，网格蛋白，真核翻译起始因子，膜联蛋白，ABC转运蛋白，翻译控制的肿瘤蛋白，泛素结合酶以及REF，SRPP和CPT的几种同源物。建立了多反应监测程序，以进一步进行蛋白质验证。橡胶颗粒的蛋白质组数据将有助于研究橡胶颗粒的生物发生，自我平衡和橡胶生物合成的分子机制，并可能在巴西H. brasiliensis和其他替代橡胶生产物种的分子育种研究中用作有价值的生物标志物。

BACKGROUND & AIMS: :The aim of this study was to investigate the feasibility and safety of laparoscopic radical parametrectomy and pelvic and para-aortic lymphadenectomy after previous supracervical or extrafascial hysterectomy. This is a prospective study of six patients with vaginal or cervical stump carcinoma after previous supracervical or extrafascial hysterectomy. The technique of radical parametrectomy with pelvic and para-aortic lymphadenectomy as used for open surgical cases for years was performed laparoscopically. The average operating time was 180 min, the estimated average blood loss was 220 mL, and the duration of hospitalization was 11.8 days. There was no intraoperative or postoperative complication. Laparoscopic radical parametrectomy with pelvic and para-aortic lymphadenectomy for cervical or vaginal stump carcinoma can be successfully and safely accomplished.

背景与目标： : 这项研究的目的是研究先前的脊柱上或筋膜外子宫切除术后腹腔镜根治性切除术以及盆腔和主动脉旁淋巴结切除术的可行性和安全性。这是一项前瞻性研究，对6例先前的宫颈上或筋膜外子宫切除术后的阴道或宫颈残端癌患者进行了研究。腹腔镜下进行了多年开放手术病例的盆腔和主动脉旁淋巴结切除术根治性副视网膜切除术技术。平均手术时间为180 min，估计平均失血量为220 mL，住院时间为11.8天。术中或术后无并发症。腹腔镜根治性副视网膜切除术联合盆腔和主动脉旁淋巴结清扫术治疗宫颈或阴道残端癌可以成功，安全地完成。

BACKGROUND & AIMS: :The aim of this study was to investigate if p-chloroamphetamine (PCA), which is neurotoxic to serotonin (5-HT) nerve terminals, was able to induce, like 3,4-methylenedioxymethamphetamine, a region-specific regulation of 5-HT1A receptor mRNA expression. The effect of PCA on the expression of 5-HT7 receptors, which share some pharmacological properties with 5-HT1A receptors, was comparatively studied. PCA (2 x 5 mg/kg) produced a lasting depletion of 5-HT content in the rat frontal cortex and hippocampus. In the hippocampus, the maximal 5-HT depletion was found on day 21 (-70%), whereas in the cortex, the highest 5-HT depletion was found on day 14 (-73%), with a partial but significant recovery on day 21. At the latter time point, 5-HT1A receptor mRNA expression was increased by 80% in the cortex and decreased by 50% in the hippocampus. The 5-HT1A receptor mRNA expression was also enhanced after exposure to PCA of rat cortical but not of hippocampal primary cultures. In regard to 5-HT7 receptor mRNA expression, the most remarkable change after PCA was the great increase (+200%) in the brain-stem. Binding studies to 5-HT1A receptors matched the changes in receptor mRNA expression. Gel shift assays revealed enhanced nuclear protein binding to the KB sequence with use of cortical but not hippocampal extracts of PCA-treated rats. Overall, the data show region-specific changes in 5-HT receptor-type expression that may not be entirely dependent on the neurotoxic effect of PCA on 5-HT terminals.

背景与目标： : 这项研究的目的是研究对5-羟色胺 (5-HT) 神经末梢具有神经毒性的对氯苯丙胺 (PCA) 是否能够像3,4-亚甲二氧甲基苯丙胺一样诱导5-HT1A受体mRNA表达。比较研究了PCA对5-HT7受体表达的影响，该受体与5-HT1A受体具有某些药理特性。PCA (2x5 mg/kg) 在大鼠额叶皮层和海马中持续消耗5-HT含量。在海马中，最大的5-HT耗竭在第21天 (-70%) 发现，而在皮质中，最高的5-HT耗竭在第14天 (-73%) 发现，在第21天部分但显着恢复。在后一个时间点，5-HT1A受体mRNA的表达在皮层中80% 增加，而在海马中50% 减少。暴露于大鼠皮质的PCA而不是海马原代培养物后，5-HT1A受体mRNA的表达也得到了增强。关于5-HT7受体mRNA表达，PCA后最显着的变化是脑干中的显着增加 (200%)。与5-HT1A受体的结合研究与受体mRNA表达的变化相匹配。凝胶位移测定显示，使用PCA处理的大鼠的皮质而不是海马提取物，核蛋白与KB序列的结合增强。总体而言，数据显示5-HT受体类型表达的区域特异性变化可能不完全取决于PCA对5-HT末端的神经毒性作用。

BACKGROUND & AIMS: :An 8-yr-old female child presented with acute onset of severe pain in the lower limbs and difficulty in walking. Spine MRI showed hyperintense signals on T2 weighted images at T2-T3 level, which was intramedullary in location. The patient was operated and histopathology reported as neuroepithelial cyst. Spinal intramedullary neuroepithelial cysts are rare. Spinal cord compression due to the cyst is very uncommon and because of its rarity the present case is being reported. The clinical features, embryogenesis and literature were reviewed briefly.

背景与目标： : 一名8岁的女童出现下肢剧烈疼痛和行走困难的急性发作。脊柱MRI在T2-T3水平的T2加权图像上显示出高强度信号，该信号位于髓内。患者手术，组织病理学报告为神经上皮囊肿。脊髓髓内神经上皮囊肿很少见。由于囊肿引起的脊髓压迫非常罕见，并且由于其稀有性，目前正在报道这种情况。简要回顾了临床特征，胚胎发生和文献。

BACKGROUND & AIMS: :Syntheses of various bis-ortho-alkoxy-para-piperazineanilino-pyrimidines and -triazines of KRCA-0008 analogs are described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2,4-pyrimidine analog (2) seems to be most potent in both biochemical and cellular assay in this study, however it shows inferior mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less potent or inactive to ALK wt., and this observation is explained with their molecular modeling compared to KRCA-0008.

背景与目标： : 描述了KRCA-0008类似物的各种双邻位烷氧基-对哌嗪苯胺基嘧啶和三嗪的合成，并讨论了它们与间变性淋巴瘤激酶 (ALK) 的构效关系。在这项研究中，5-三氟甲基-2,4-嘧啶类似物 (2) 在生化和细胞测定中似乎最有效，但是它显示出克唑替尼的小鼠异种移植活性较差，可能是由于其PK参数次优。KRCA-0008的4,6-二取代嘧啶和2,4-二取代三嗪衍生物对alkwt.的效力较低或无活性，并且与KRCA-0008相比，用它们的分子模型解释了这一观察结果。

BACKGROUND & AIMS: :Manganese (Mn) is an essential metal for biological systems; however, occupational or clinical exposure to high levels of Mn can produce a neurological disorder called manganism. Oxidative stress and neuroinflammation play major roles in the Mn-induced neurodegeneration leading to dysfunction of the basal ganglia. We investigated the toxic effects of MnCl2 in an immortalized rat brain endothelial cell line (RBE4) and the protective effects of the radical scavenging aminosalicylic acids, 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-PAS). Mn cytotoxicity was determined with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) activity. A significant decrease in MTT reduction concomitant with increased LDH release was noted in RBE4 cells exposed for 24 h to MnCl2 (600 and 800 μM; p < 0.0001). Our results establish that compared to 4-PAS, 5-ASA has greater efficacy in protecting RBE4 cells from Mn-induced neurotoxicity after preexposure to MnCl2 800 μM (p < 0.0001).

背景与目标： 锰 (Mn) 是生物系统必不可少的金属; 但是，职业或临床暴露于高水平的Mn会产生称为manganism的神经系统疾病。氧化应激和神经炎症在Mn诱导的神经变性导致基底神经节功能障碍中起主要作用。我们研究了MnCl2在永生化大鼠脑内皮细胞系 (RBE4) 中的毒性作用以及自由基清除氨基水杨酸，5-氨基水杨酸 (5-ASA) 和4-氨基水杨酸 (4-PAS) 的保护作用。用3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四唑 (MTT) 还原和乳酸脱氢酶 (LDH) 活性测定Mn的细胞毒性。在暴露于MnCl2 (600和800 μ m; P  <  0.0001) 24小时的RBE4细胞中，MTT减少与LDH释放增加同时显著降低。我们的结果表明，与4-PAS相比，5-ASA在预先暴露于800 μ m (p  <  0.0001) 后保护RBE4细胞免受Mn诱导的神经毒性方面具有更大的功效。

BACKGROUND & AIMS: BACKGROUND:Patients with cervical cancer who had negative para-aortic lymph nodes (PALNs) identified by pretreatment surgical staging were compared with patients who had only radiographic exclusion of PALN metastases before they received treatment with pelvic radiation and brachytherapy (RT) plus cisplatin (C)-based chemotherapy. METHODS:Patients who participated in 1 of 3 Phase III Gynecologic Oncology Group (GOG) trials (GOG 85, GOG 120, and GOG 165) and who were assigned randomly to receive either RT plus C or RT plus C combined with 5-fluorouracil with or without hydroxyurea comprised this retrospective analysis. Patients who had negative PALN status determined by surgical sampling (mandatory in GOG 85 and GOG 120 and optional in GOG 165) were compared with patients who had negative PALN status determined radiographically (GOG 165). RESULTS:Five hundred fifty-five patients underwent surgical PALN sampling (the S group), and 130 patients underwent radiographic evaluation only (the R group). Age, race, histology, and tumor grade were similar. Patients in the R group had better performance status (P < .01), less advanced stage (P = .023), and smaller tumor size (P = .004) compared with patients in the S group, although patients with stage III and IV disease in the S group had better 4-year progression-free survival (48.9% vs 36.3%) and overall survival (54.3% vs 40%) compared with patients in the R group. In multivariate analysis, the R group was associated independently with a poorer prognosis compared with the S group (for disease progression: hazard ratio [HR], 1.35, 95% confidence interval [95% CI], 1.01-1.81; for death: HR, 1.46, 95% CI, 1.08-1.99). CONCLUSIONS:Surgical exclusion (compared with radiographic exclusion) of positive PALNs in patients with cervical cancer who received chemoradiation (RT plus C-based chemotherapy) had a significant prognostic impact.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Locally advanced gastric cancer with extensive regional and/or para-aortic lymph node (PAN) metastases is typically unresectable and associated with poor outcomes. This study investigated the safety and efficacy of S-1 plus cisplatin followed by extended surgery with PAN dissection for gastric cancer with extensive lymph node metastasis. METHODS:Patients with gastric cancer with bulky lymph node metastasis along the coeliac artery and its branches and/or PAN metastasis received two or three 28-day cycles of S-1 plus cisplatin, followed by gastrectomy with D2 plus PAN dissection. The primary endpoint was the percentage of complete resections with clear margins in the primary tumour (R0 resection). A target sample size of 50 with one-sided α of 0.105 and β of approximately 0.2 corresponded to an expected R0 rate of 65 per cent and a threshold of 50 per cent. RESULTS:Between February 2005 and June 2007, 53 patients were enrolled, of whom 51 were eligible. The R0 resection rate was 82 per cent. Clinical and pathological response rates were 65 and 51 per cent respectively. The 3- and 5-year overall survival rates were 59 and 53 per cent respectively. During chemotherapy, grade 3/4 neutropenia occurred in 19 per cent and grade 3/4 non-haematological adverse events in 15.4 per cent. The incidence of grade 3/4 adverse events related to surgery was 12 per cent. There were no reoperations or treatment-related deaths. CONCLUSION:For locally advanced gastric cancer with extensive lymph node metastasis, 4-weekly S-1 plus cisplatin followed by surgery including PAN dissection was safe and effective for some patients. Further investigation of this treatment strategy is warranted.

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