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.     

异源PDGF-A链表达对CHO细胞生长和转化的作用

用DNA磷酸钙盐沉淀方法把含人PDGF(血小板衍生生长因子)A链cDNA的表达质粒pSV_2neo-A转染CHO细胞(中国仓鼠卵巢细胞),然后经G 418(400-800 μg/ml)筛选分离20个转染细胞株。选出其中At_1和Aot7细胞株所进行的实验结果表明,这些细胞的形态和生长行为均发生明显的变化,PDGF-A链mRNA的表达水平比CHO细胞明显增高,胞质有强阳性的PDGF荧光反应,显示有PDGF样蛋白的合成。这些细胞不但生长速率加快,有高密度持续生长的特性,而且能在软琼脂培基上形成大集落和在裸鼠体内接种形成纤维肉瘤,提示外源PDGF-A链基因的表达有使CHO细胞生长失控和发生细胞恶性转化的作用。     

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。     

压力-应激对大鼠心肌细胞Cx43蛋白表达及心肌纤维化的影响

目的:探讨压力-应激对大鼠心肌细胞间隙连接蛋白-43(Cx43)蛋白表达及心肌纤维化的影响。方法:将20只雄性SD大鼠随机分为正常对照组(n=10)和模型组(n=10),对照组正常饲养,模型组给予不可预测性复合应激结合孤养建立压力-应激大鼠模型。监测两组大鼠的体重变化,并通过组织形态学方法,探讨压力-应激对大鼠心肌细胞Cx43蛋白表达及心肌纤维化的影响。结果:在为期42天的造模过程中,从应激第7天开始,模型组大鼠体重明显低于对照组,差异有统计学意义(P<0.001)。且模型组体重增长缓慢,体重增长百分比明显低于对照组,差异有统计学意义(P<0.001)。与对照组相比,模型组大鼠组织HE染色可见心肌细胞排列紊乱,横纹消失,细胞间隙增大,部分肌纤维断裂、溶解,Masson染色可见心肌间质纤维化,胶原纤维增生、排列紊乱。心肌细胞免疫组化染色可见模型组Cx43蛋白表达明显下降(平均光密度值为0.0110±0.0028),与对照组相比(平均光密度值为0.0268±0.0025),差异具有统计学意义(t=-13.081,P<0.001)。结论:过度疲劳导致猝死的发生可能与Cx43蛋白表达水平的下降引起的恶性心律失常有关。     

妇科盆腔恶性肿瘤血常规检测结果分析

目的:了解妇科盆腔恶性肿瘤血常规变化及其临床意义。方法:以无锡市人民医院2018年1月～2019年3月收治的90例妇科盆腔恶性肿瘤患者作为病例组,同期住院的243例确诊为盆腔良性病变或妊娠状态的患者作为良性对照组,选取同期717名接受体检的成年女性作为健康对照组,对三组研究对象的血常规指标进行回顾性分析。结果:与健康对照组比较,良性对照组和病例组患者的嗜酸性粒细胞百分比(EO)、嗜酸性粒细胞计数(EO#)、红细胞压积(HCT)、血红蛋白水平(HGB)、淋巴细胞百分比(LY)、淋巴细胞计数(LY#)、红细胞平均血红蛋白浓度(MCHC)、血小板分布宽度(PDW)、红细胞计数(RBC)水平降低,单核细胞计数(MO#)、血小板平均体积(MPV)、中性粒细胞百分比(NE)、中性粒细胞计数(NE#)、红细胞分布宽度(RDW)、白细胞计数(WBC)水平升高;病例组患者EO、EO#、LY、LY#、MO#、MPV水平低于良性对照组,HCT、HBG、MCHC、PDW、NE、NE#、RDW水平高于良性对照组,同时,病例组患者的红细胞平均血红蛋白含量(MCH)、红细胞平均体积(MCV)水平高于健康对照组,健康对照组的MCH、MCV水平高于良性对照组,良性对照组患者的单核细胞百分比(MO)、血小板压积(PCT)水平高于健康对照组,健康对照组的MO、PCT水平高于病例组,差异均有统计学意义(P0.05)。Logistic多元回归分析结果显示,LY#、MO#、MCHC、RDW、MCH、MCV与盆腔恶性肿瘤的发生具有相关性(P0.05)。ROC曲线分析结果显示,在各项血常规指标中,MCV诊断妇产科盆腔恶性肿瘤的曲线下面积(AUC)最高,为0.683。结论:盆腔恶性肿瘤患者的血常规指标与良性病变患者和健康人群均存在差异,部分指标与恶性肿瘤的发生具有独立相关性。     

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.