Decreased Cerebrospinal Fluid Glutamine Levels in Patients with Benign Brain Tumors

Abstract: CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with non-cerebral tumors, and a reference group of 24 patients. The mean ± SD levels in the benign tumor group (424 ± 124 μ M ) were significantly lower (p < 0.0004) than those in the reference group (642 ± 195 μ M ). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 ± 210 μ M ) or noncerebral tumor group (599 ± 127 μ M ) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter.     

Patho- and immunobiology of malignant mesothelioma: characterisation of tumour infiltrating leucocytes and cytokine production in a murine model

Malignant mesothelioma (MM) is an aggressive, uniformly fatal serosal tumour, usually associated with asbestos exposure, for which there currently is no effective treatment. In order to gain insight into the mechanism(s) whereby MM might escape immune surveillance, a murine model for MM was used (a) to characterise the tumour-infiltrating lymphocytes (TIL) and macrophages (TIM) phenotypically, (b) to examine systemic immune recognition of MM, and (c) to examine the possible influence of tumour-derived cytokines on systemic and local pathobiological manifestations of MM. A profound down-regulation of lymphocyte surface markers, known to be infolved in T cell activation, was found in TIL. Likewise, although TIM were present in large numbers, their expression of MHC class II antigen and integrins was weak or absent, suggestive of altered functional activity. Significant amounts of cytokines, in particular transforming growth factor , interleukin-6 (IL-6), IL-1 and tumour necrosis factor were produced during the course of MM tumour development-directly by the MM cells and/or indirectly in response to tumour growth. These factors may contribute both to derangement of antitumour effector mechanisms and to the clinical and pathological manifestations of the disease.     

核仁组成区蛋白在软组织肿瘤及瘤样病变中的表达与意义

应用胶银技术,对软组织肿瘤特别是纤维源性肿瘤核仁组成区蛋白进行了定量研究。在软组织一些恶性肿瘤中,以血管肉瘤、横纹肌肉瘤核仁组成区蛋白均值最高,并以此排列了它们的恶性度顺序。在纤维源性肿瘤中,纤维瘤、瘤样纤维组织增生、纤维肉瘤及其亚类核仁组成区蛋白均值有显著与高度显著性差异(P<0.05、P<0.001),其中随访的34例纤维肉瘤患者,具有高核仁组成区蛋白均值(≥5)与低核仁组成区蛋白均值(<5)的5年生存率分别是20％和53％(P<0.05)。因此,作者认为核仁组成区蛋白定量在判定软组织肿瘤的恶性度、鉴别其良恶性及预测患者预后中均有一定实用价值。     

原发性子宫大B细胞淋巴瘤一例报告及文献复习

摘要 目的：总结原发性子宫恶性淋巴瘤的临床表现、影像及病理学特点,以期提高对原发性子宫恶性淋巴瘤的认识及诊治水平。方法：通过PubMed、万方、维普、中国知网数据库检索2001年1月至2019年12月报道的原发性子宫恶性淋巴瘤的文献,结合首都医科大学附属北京妇产医院收治的1例原发性子宫大B细胞淋巴瘤的病例资料,对此类患者临床表现、影像及病理学特点、治疗方案及预后进行总结。结果：患者女,64岁,发现盆腔肿物半月伴有绝经后阴道流血,盆腔CT提示：宫体与宫颈局部巨大团块状软组织密度灶,宫底及宫体上段可见内膜。宫腔镜下组织活检病理：（宫内物）符合低分化恶性肿瘤,结合免疫组化结果,诊断原发性子宫大B细胞淋巴瘤。行开腹全子宫及双侧附件、大网膜及腹膜后淋巴结清扫术,术后接受CHOP方案化疗六程,现治疗后随访17月,未发现复发。结论：原发性子宫恶性淋巴瘤极少见,组织学上以大B 细胞淋巴瘤为主,临床表现缺乏特异性。最终需要结合免疫组化确诊。该疾病恶性程度高,治疗上以根治性手术联合化疗为主,预后较差。     

Yeast and cancer cells – common principles in lipid metabolism

One of the paradigms in cancer pathogenesis is the requirement of a cell to undergo transformation from respiration to aerobic glycolysis – the Warburg effect – to become malignant. The demands of a rapidly proliferating cell for carbon metabolites for the synthesis of biomass, energy and redox equivalents, are fundamentally different from the requirements of a differentiated, quiescent cell, but it remains open whether this metabolic switch is a cause or a consequence of malignant transformation. One of the major requirements is the synthesis of lipids for membrane formation to allow for cell proliferation, cell cycle progression and cytokinesis. Enzymes involved in lipid metabolism were indeed found to play a major role in cancer cell proliferation, and most of these enzymes are conserved in the yeast, Saccharomyces cerevisiae. Most notably, cancer cell physiology and metabolic fluxes are very similar to those in the fermenting and rapidly proliferating yeast. Both types of cells display highly active pathways for the synthesis of fatty acids and their incorporation into complex lipids, and imbalances in synthesis or turnover of lipids affect growth and viability of both yeast and cancer cells. Thus, understanding lipid metabolism in S. cerevisiae during cell cycle progression and cell proliferation may complement recent efforts to understand the importance and fundamental regulatory mechanisms of these pathways in cancer.     

血清CA153、TK1、TSGF联合检测对乳腺癌诊断的价值

目的：探讨细胞表面糖蛋白（CA153）、胸苷激酶（TKl）、肿瘤生长因子（TSGF）等联合检测在乳腺癌诊断中的应用价值。方法：73例确诊为乳腺癌患者的血清标本作为实验组;66例乳腺良性疾病（包括乳腺纤维瘤、囊肿、增生等）及50例健康人群血清标本作为对照组。采用电化学发光法检测血清CAl53,免疫化学发光法检测TKl,化学显示法检测TSGF的表达。结果：血清CAl53、TKl及TSGF对乳腺癌的敏感性分别为54．8％、53．4％及79．5％,特异性分别为87．9％、81．8％及83．3％;血清CAl53、TKl、TSGF联合检测乳腺癌的敏感性为89．0％,特异性为92．4％。结论：与单项指标检测相比,多个指标联合检测提高了对乳腺癌早期诊断的敏感性．同时又有较好的特异性．有助于良、恶乳腺疾病的鉴别．具有一定的临床应用价值．     

N-terminal and Central Segments of the Type 1 Ryanodine Receptor Mediate Its Interaction with FK506-binding Proteins

We used site-directed labeling of the type 1 ryanodine receptor (RyR1) and fluorescence resonance energy transfer (FRET) measurements to map RyR1 sequence elements forming the binding site of the 12-kDa binding protein for the immunosuppressant drug, FK506. This protein, FKBP12, promotes the RyR1 closed state, thereby inhibiting Ca²⁺ leakage in resting muscle. Although FKBP12 function is well established, its binding determinants within the RyR1 protein sequence remain unresolved. To identify these sequence determinants using FRET, we created five single-Cys FKBP variants labeled with Alexa Fluor 488 (denoted D-FKBP) and then targeted these D-FKBPs to full-length RyR1 constructs containing decahistidine (His₁₀) “tags” placed within N-terminal (amino acid residues 76–619) or central (residues 2157–2777) regions of RyR1. The FRET acceptor Cy3NTA bound specifically and saturably to these His tags, allowing distance analysis of FRET measured from each D-FKBP variant to Cy3NTA bound to each His tag. Results indicate that D-FKBP binds proximal to both N-terminal and central domains of RyR1, thus suggesting that the FKBP binding site is composed of determinants from both regions. These findings further imply that the RyR1 N-terminal and central domains are proximal to one another, a core premise of the domain-switch hypothesis of RyR function. We observed FRET from GFP fused at position 620 within the N-terminal domain to central domain His-tagged sites, thus further supporting this hypothesis. Taken together, these results support the conclusion that N-terminal and central domain elements are closely apposed near the FKBP binding site within the RyR1 three-dimensional structure.     

模拟微重力对恶性胶质瘤细胞U87 影响的实验研究

目的:探讨模拟微重力(Modeled microgravity,MMG)对恶性胶质瘤细胞U87形态、生长增殖、基质金属蛋白酶-2、-9(Matrix metalloproteinase 2,MMP-2、Matrix metalloproteinase 9,MMP-9)及神经胶质酸性蛋白(Glial fibrillary acidic protein,GFAP)表达的影响。方法:常规培养U87细胞,传代培养3代后分为两组,正常重力组(Normal gravity,NG组)及模拟微重力干预组(Modeled microgravity,MMG组),相应条件下培养24 h,48 h和72 h。倒置显微镜观察U87细胞形态改变,细胞计数法及四甲基偶氮唑盐微量酶反应比色法(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT法)检测模拟微重力干预和干预后U87细胞生长增殖情况;Western Blot检测不同培养时间后胶质瘤细胞U87 MMP-2、MMP-9及GFAP蛋白的表达情况。结果:模拟微重力条件下培养72 h后,U87细胞轮廓不规则,边缘圆钝,触角变少;模拟微重力条件下,U87细胞生长速度明显减慢,并且经模拟微重力干预48 h和72 h后的胶质瘤细胞经传代再培养,其增殖率也明显低于正常重力组;同时,U87细胞MMP-2及MMP-9蛋白表达水平与模拟微重力处理时间呈时间依赖性下降,而GFAP蛋白表达水平则呈时间依赖性升高。结论:模拟微重力影响U87细胞的形态、生长及表型。     

苦参注射液与恩度联合顺铂对肺癌恶性胸腔积液患者血清炎症因子水平的影响

目的:探讨苦参注射液与恩度分别联合顺铂对肺癌恶性胸腔积液患者血清炎症因子水平影响。方法:收集我院以非小细胞肺癌合并恶性胸腔积液患者68例,按照就诊先后顺序分为实验组和对照组。对照组予恩度联合顺铂化疗,实验组予苦参注射液联合顺铂化疗。于患者治疗前后进行CD8~+、IL-2检测,KPS评分,并进行生活质量评价及胸腔积液疗效评价比较,以及药物不良反应评价。结果:1治疗后实验组CD8~+下降、IL-2均上升(P0.05);2治疗后实验组KPS评分较对照组明显上升(P0.05);3实验组患者生活质量评价明显好于对照组,胸腔积液疗效优于对照组(P0.05)。结论:苦参注射液联合顺铂较恩度联合顺铂对肺癌合并恶性胸腔积液患者CD8~+T淋巴细胞及IL-2水平有更明显调节作用,且安全性更佳,对肺癌合并恶性胸腔积有显著临床疗效,对提高患者生活质量、延长患者生存期有重要意义。     

右美托咪定对老年恶性肿瘤全麻手术患者术后细胞免疫功能、认知功能及炎症因子水平的影响

目的:探讨右美托咪定对老年恶性肿瘤全麻手术患者术后细胞免疫功能、认知功能及炎症因子水平的影响。方法:选取2017年2月～2019年6月期间到我院择期行手术治疗的老年恶性肿瘤患者119例,根据随机数字表法将患者分为对照组(n=59)和研究组(n=60),研究组麻醉中输注右美托咪定,对照组麻醉中输注同容量等速率的生理盐水,比较两组患者围术期指标、细胞免疫功能、不良反应、炎症因子指标、简易智力状态量表(MMSE)评分。结果:两组患者术后第3 d的CD4~+/CD8~+、CD3~+、CD4~+较术前下降,CD8~+较术前升高(P0.05);研究组术后第3 d的CD4~+/CD8~+、CD3~+、CD4~+高于对照组,CD8~+则低于对照组(P0.05)。两组术后第3 d的血清高迁移率族蛋白1(HMGBl)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平均升高,但研究组低于对照组(P0.05)。两组手术时间、术中出血量、麻醉时间比较无差异(P0.05)。两组患者术前、术后第1 d、术后第3 d的MMSE评分呈先下降后升高趋势(P0.05),且研究组术后第1 d、第3 d的MMSE评分高于对照组(P0.05)。两组不良反应发生率比较无统计学差异(P0.05)。结论:老年恶性肿瘤全麻手术患者术中输注右美托咪定,可减轻细胞免疫抑制及炎症反应,对术后早期的认知功能下降有一定预防作用。