Thymic Function and Output of Recent Thymic Emigrant T Cells During Intracranial Glioma Progression

One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naïve T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4⁺CD8⁺ (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8⁺ RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.     

An endogastric capsule for measuring tumor markers in gastric juice: an evaluation of the safety and efficacy of a new diagnostic tool.

BACKGROUND: In gastric juice, high levels of the carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9) have been found to correlate with precancerous lesions and gastric cancer. So far, sampling of gastric juice has required upper endoscopy. In place of this invasive procedure, we investigated a new tool for the quantitation of tumor markers in gastric juice. MATERIALS AND METHODS: The study population consisted of healthy controls and consecutive subjects with suspected gastric cancer or dyspepsia/epigastric distress. Patients were asked to swallow a small gelatine capsule (14 mm in length and 5 mm in diameter) containing a pierced plastic cover and surrounding a piece of absorbent paper. The capsule was left in the gastric cavity for 60 min to allow saturation of the absorbent paper with gastric juice. A 45-50 cm length of nylon thread connected to the inner capsule was used to remove the device from the gastric cavity. After processing the absorbent paper for radioimmunoassay, CEA and CA 19-9 levels were correlated to the findings of upper endoscopy and biopsies of gastric mucosa or suspected lesions. RESULTS: The endogastric capsule did not cause any side-effects and 62 participants were fully compliant to the procedure. Assessable gastric juice samples were taken from 23 patients with gastric cancer, 15 patients with intestinal metaplasia or dysplasia, 12 patients with gastritis and 12 controls without gastric diseases. In the 12 samples of gastric juice from control patients, mean values of CEA and CA 19-9 were 1.1 +/- 0.9 ng/ml and 16 +/- 7.5 ng/ml, respectively. The mean levels of both markers were found to increase according to the severity of gastric lesions and in patients with cancer, mean CEA and CA 19-9 levels were 513 +/- 627 ng/ml and 545 +/- 510 ng/ml, respectively. Patients with precancerous lesions and cancer showed higher levels of CEA and CA 19-9 than patients with normal findings or gastritis (P <0.001). CONCLUSIONS: The endogastric capsule is a simple, non-invasive tool for the measurement of CEA and CA 19-9 levels in gastric juice. These values may discriminate between normal or minor pathologic changes and precancerous lesions or carcinomas. Further investigations are warranted, since this may represent a new method for gastric cancer screening.     

99mTcN(NOEt)2与99mTc-MIBI在肿瘤模型显像中的对比研究

目的　探讨99mTc 氮 二 (N 乙基 N 乙氧基二硫代氨基甲酸盐 ) [99mTcN (NOEt) 2 ]应用于肿瘤诊断的可能性并与99mTc 甲氧基异丁基异腈(99mTc MIBI)肿瘤模型显像进行比较。方法　制备99mTcN (NOEt) 2 ,用上行薄层色谱法测定放化纯。各取 4只移植性艾氏腹水癌小鼠分别尾静脉注射99mTc MIBI或99mTcN(NOEt) 2 ,30min、2h、4h后进行全身后位静态显像。利用感兴趣区技术 ,分别计算不同时相肿瘤与头部 (T/H)、胸部 (T/C)、及健侧肢体对称部位 (T/L)的放射性比值。 4h后处死99mTcN (NOEt) 2 显像组小鼠 4只 ,取血并剥离脏器组织及肿瘤组织 ,称重 ,测量放射性计数 ,计算肿瘤与各脏器放射性比值。结果　99mTcN (NOEt) 2 室温下 4h保持稳定。99mTcN (NOEt) 2 选择性地有效的聚集于肿瘤组织。除腹部外其它组织靶 /非靶比值较高 ,注射2h后T/L比值达最高 ,为 4.87。99mTcN (NOEt) 2 显像组与99mTc MIBI显像组比较T/L比值差异有显著性 (P <0 .0 1)。体外测量肿瘤与血、肌肉、肺等脏器的单位重量放射性比值较高 ,与肝、小肠等腹部脏器的单位重量放射性比值较低。结论　在移植性艾氏腹水癌小鼠模型中99mTcN (NOEt) 2 从血液中清除很快 ,肿瘤摄取率高 ,有一定的滞留量 ,靶与非靶比值高 ,图像质量明显优于99mTc MIBI肿瘤     

肝癌门静脉癌栓多排螺旋CT三维成像

目的 探讨门静脉癌栓多排螺旋CT3D成像的临床意义。方法 收集了57例门静脉3D成像,6例正常,5例肝硬化门脉高压,42例肝癌门静脉癌栓,4例肝门部淋巴结肿大患者,所有病例来源于肝脏常规双期扫描。对比剂按1.5-2ml/kg,对比剂注射流率2.5-3ml/s,门脉期延迟时间60-70s。对肝癌形成的42例门静脉癌栓进行轴位和3D成像观察,并行两组对照。结果 根据癌栓不同部位分为门脉左支(13例)、右支(20例)、主干(9例)3种类型。3D成像与轴位之间对显示门静脉癌栓没有差异性(P>0.05),但3D对显示主干栓塞形成的侧支循环优于轴位。结论 门静脉癌栓多排螺旋CT3D成像可较好地多方位显示癌栓部位及癌栓类型,CT3D成像和轴位结合可更好地对门静脉癌栓作出判断,以进一步指导临床对治疗方案的选择。     

多种siRNA的抗肿瘤作用研究

目的研究短干扰RNA(short interfering RNA,siRNA)的抗肿瘤作用.方法采用MTT法检测siR-NA的生长抑制作用,H&E染色法观察细胞形态变化,TUNEL标记法检测核DNA断裂,Western Blot法分析蛋白表达水平变化和流式细胞法检测细胞周期分布变化.结果siRNA-Bcl2,siRNA-MDM2,siRNA-CDK2和siRNA-HRas可以明显抑制人乳腺癌MCF-7等肿瘤细胞的生长;siRNA-MDM2和siRNA-Bcl2可以引起MCF-7细胞染色质凝集;siRNA-Bcl2,siRNA-MDM2,siRNA-CDK2和siRNA-HRas均可以明显降低靶基因的表达水平,同时诱导MCF-7细胞发生染色体DNA断裂;siRNA-MDM2还可以导致MCF-7细胞发生G1期阻滞.结论siRNA可以明显抑制肿瘤细胞的生长,降低靶基因的表达水平,并诱导肿瘤细胞凋亡和周期阻滞,提示siRNA可能发展成为一类高效特异的新型抗肿瘤药物.     

MTT肿瘤药敏试验中培养基的选择

目的考察RPMI1640双琼脂培养基(R)对肿瘤细胞培养的选择性,选择适合的MTT法培养基。方法用R和肿瘤细胞选择性培养基(completeassaymedium,CAM)分别进行乳腺、肠、胃癌的MTT药敏试验。结果所试的3个癌种、20个药品总体来说在两种培养基中抑制率无统计学差异(P>0.05),单个药敏在乳腺癌中长春新碱、长春地辛和吡柔比星的CAM培养抑制率大于R培养(P<0.05),在肠、胃癌中无统计学差异。结论R培养肿瘤细胞的选择性和CAM相当,但鉴于R抑制成纤维细胞能力相对比CAM弱,R可能更适合含纤维细胞较少的癌种。     

雷公藤内酯醇对大鼠脑局灶性缺血再灌注后脑组织肿瘤坏死因子-α含量变化的影响

目的　观察雷公藤内酯醇 (TL)是否通过降低脑组织内肿瘤坏死因子 (TNF α)含量而减少白细胞浸润 ,从而改善局灶性脑缺血再灌注所致的神经功能缺失。方法　大鼠ipTL 0 .2或 0 .4mg·kg- 1·d- 1,连续 4d。d 4给药前行右侧大脑中动脉缺血 1h再灌注 2 4h。行为观察行大鼠神经功能缺损评分 ;放射免疫法检测缺血再灌注侧大脑皮层TNF α含量。病理切片观察缺血再灌注侧脑微血管内附壁中性粒细胞计数。结果　与损伤模型组比较 ,TL处理组大脑皮质TNF α含量明显减少 ,神经功能受损程度明显改善。脑微血管内附壁中性粒细胞计数明显减少。结论　TL有抑制缺血再灌注脑组织内TNF α生成 ,降低其含量的作用 ,从而抑制白细胞浸润 ,改善受损的神经功能     

三氧化二砷诱导人肿瘤细胞凋亡和G2＋M期阻滞但引起人永 …

目的　研究 As2 O3引起肿瘤细胞凋亡和对细胞周期的影响。方法　采用 DNA凝胶电泳 ,流式细胞仪分析、RT- PCR和 Western免疫印迹等技术检测细胞凋亡的发生。结果　由 As2 O3诱导的人肺腺癌 GL C- 82、胃腺癌 MGC- 80 3和 SGC- 790 1、食管癌 Ec10 9、宫颈癌 He L a细胞凋亡前 ,细胞阻滞在 G2 M期 ,上述细胞均表现为对c- myc基因的下行调节 ;但在导致永生化人宫颈上皮 HCE16 /3细胞凋亡之前 ,细胞却被阻滞在 G1期 ,对 c- m yc基因表达无影响。结论　 As2 O3引起细胞凋亡与细胞周期阻滞有关 ,在肿瘤细胞和前恶变的 HCE16 /3细胞中阻滞的时期不同 ,这可能与 c- myc基因表达的改变与否有关     

ONCOPROTEINS AND TUMOR SUPPRESSOR PROTEINS IN CONGENITAL SACROCOCCYGEAL TERATOMAS

Congenital sacrococcygeal teratoma SCT is the most common germ cell tumor of infancy and childhood with a female preponderance. Most SCTs are diagnosed at birth, are benign, and consist of fully differentiated, mature tissues. Tumorigenesis of SCTs remains poorly understood. Almost nothing is known about possible oncogene activation or tumor suppressor inactivation in these rare tumors. We describe the presence of various oncoproteins and tumor suppressor proteins in eight cases of congenital SCT. The following oncogenes were examined: ras family c-H-, c-N-, and c-K-ras , early genes fos, jun , and tumor suppressor genes p53 and nm23-H-1 . There was no relationship between the intensity of expression of these oncoproteins and tumor suppressor genes and the following parameters: tumor size, age, and survival of the patients. We did not observe any difference, however, between the expression of the examined oncogenes and tumor suppressor genes nm23 and p53 in immature and mature teratomas. Our findings suggest that the ras family of oncogenes, fos and jun oncogenes, and nm23 and p53 tumor suppressor genes are present in congenital SCT, indicating a possible role in genesis and development of these tumors.