Oxygenated and reoxygenated tumors show better local control in radiation therapy for cervical cancer

The presence of hypoxic cells is one of the major factors affecting resistance against radiation therapy. In the clinical setting, little information exists as to the relationship between intratumoral oxygen partial pressure (pO(2)) and outcome. This study involved 30 consecutive patients with cervical cancer, who were treated with a combination of external and high-dose rate intracavitary irradiation. The pO(2) was measured before radiation therapy and at 9 Gy, using a needle-type polarographic oxygen electrode. The mean intratumoral pO(2) before radiation therapy was 17.3 +/- 10.8 mm Hg. The 3-year local control rates of patients with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg before radiation therapy were 52% and 100%, respectively, representing a significant difference (P= 0.035). At 9 Gy, mean intratumoral pO(2) was 23.6 +/- 9.1 mm Hg, a significant increase compared to the value before radiation therapy (P= 0.006). The 3-year local control rates of tumors with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg at 9 Gy were 35% and 93%, respectively, representing a significant difference (P= 0.001). The significantly better local control for oxygenated tumors at 9 Gy as well as before radiation therapy indicated that the oxygen effect and reoxygenation by radiation played an important role in local control in radiation therapy for cervical cancer.     

Histamine differentially interacts with tumor necrosis factor-α and thrombin in endothelial tissue factor induction: the role of c-Jun NH2-terminal kinase

BACKGROUND: Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes. OBJECTIVES: This study examined the effect of histamine on tumor necrosis factor-alpha- (TNF-alpha-) vs. thrombin-induced endothelial TF expression. METHODS AND RESULTS: Histamine (10(-8)-10(-5) mol L-1), TNF-alpha (5 ng mL-1), and thrombin (1 U mL-1) induced TF expression in human endothelial cells. Although TF expression by TNF-alpha and thrombin was identical, histamine augmented TNF-alpha-induced expression 7.0-fold, but thrombin-induced expression only 2.6-fold. Similar responses occurred with TF activity. The H1-receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine-induced p38 activation preceded a weak second activation to both TNF-alpha and thrombin. Histamine-induced c-Jun NH2-terminal kinase (JNK) activation was followed by a strong second activation to TNF-alpha, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF-alpha by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF-alpha- and thrombin-induced vascular cell adhesion molecule 1 (VCAM-1) expression to a similar extent. Consistent with this observation, VCAM-1 induction to TNF-alpha and thrombin was mediated by p38, but not by JNK. CONCLUSIONS: Histamine differentially augments TNF-alpha- vs. thrombin-induced TF expression and activity, which is mediated by the H1-receptor, occurs at the mRNA level, and is related to differential JNK activation.     

Total and free tissue factor pathway inhibitor in pregnancy hypertension.

OBJECTIVE: To clarify the role played by tissue factor pathway inhibitor (TFPI) in pregnancy hypertension. METHODS: Using enzyme-linked immunosorbent assays, hemostatic measurements were obtained for women with pre-eclampsia (n=51), nonproteinuric hypertension of pregnancy (n=62), postpartum pre-eclampsia 24 h after childbirth (n=31), and no hypertension (healthy pregnant controls, n=100). RESULTS: There was a significant increase in circulating free TFPI levels in women with pre-eclampsia (9.7+/-6.2 ng/mL) or nonproteinuric hypertension of pregnancy (8.3+/-5.3 ng/mL) compared with healthy controls (5.3+/-2.1 ng/mL). In women with pre-eclampsia the levels remained elevated after placental delivery (10.6+/-4.0 ng/mL). Free protein S levels were significantly higher in women with pre-eclampsia (40.0%+/-10.7%), nonproteinuric hypertension of pregnancy (37.1%+/-12.5%), or postpartum pre-eclampsia (39.3%+/-9.1%) than in healthy pregnant controls (32.2%+/-8.5%). CONCLUSION: Increased levels of the physiologically active free forms of TFPI and free protein S, 2 coagulation inhibitors, may protect women with pregnancy-induced hypertension from the risks of hemostatic activation.     

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.     

Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity

The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3).     

植入式心律转复除颤患者的护理及随访

目的总结植入式心律转复除颤器(ICD)安置术的护理。方法2001年7月~2004年6月给予13例ICD患者进行了护理及随访。结果术后有2例患者出现心律失常“风暴”,经处理后未再出现心室颤动。随访患者1~4年,均存活,未发生晕厥等并发症。结论术前重视患者的心理护理,术后密切观察病情,积极预防心律失常“风暴”,并做好ICD健康教育,是ICD手术成功的重要护理措施。     

反义骨调素寡核苷酸对肾小管上皮细胞骨调素mRNA表达及其胶原凝胶黏附能力的影响

【目的】观察反义骨调素(OPN)寡核苷酸(AS-ODN)对大鼠肾小管上皮细胞(NRK52E)骨调素mRNA表达及黏附能力的影响;比较AS-ODN的游离形式和经阳离子脂质体(DOTAP)包裹形式的反义抑制效果。【方法】用荧光显微镜观察荧光素标记的AS-ODN在细胞中的分布;将寡核苷酸处理NRK52E细胞48h,用TRIzol试剂提取细胞总RNA;用RNA斑点杂交和RT-PCR检测OPNmRNA的表达;将ODN/DOTAP复合物处理的细胞置于胶原凝胶表面,计算细胞的黏附率。【结果】AS-ODN能转移进入胞核中;AS-ODN处理的细胞OPNmRNA表达水平均较低(P<0.05),而顺义或错义寡核苷酸处理的细胞OPNmRNA水平较高,即使30μmol/L浓度也无抑制作用;游离AS-ODN最低抑制浓度为3.75μmol/L,而AS-ODN浓度为0.5μmol/L的AS-ODN/DOTAP复合物具有良好抑制作用;AS-ODN处理的细胞黏附率降低,而顺义或错义寡核苷酸处理的细胞黏附能力较强。【结论】反义骨调素寡核苷酸能特异地抑制大鼠肾小管上皮细胞OPNmRNA表达和黏附胶原凝胶能力;阳离子脂质体能促进AS-ODN的反义抑制作用。     

阿米福汀对同步放化疗杀伤肺癌细胞作用的影响

目的　探讨阿米福汀在多烯紫杉醇和同步放射治疗非小细胞肺癌过程中对肺癌组织细胞是否有保护作用。方法　使用MTT方法评价在多烯紫杉醇和同步照射 (10Gy)体外培养的SPC A1肺癌细胞过程中 ,阿米福汀对SPC A1肺癌细胞的影响 ;以Lewis肺癌荷瘤鼠模型评价在多烯紫杉醇同步放射 (10Gy)在体Lewis肺癌过程中 ,阿米福汀对Lewis肺癌的影响。结果　体外实验表明同步放化疗加阿米福汀组和同步放化疗组的吸光度分别相当于对照组的 2 2 .8%和 2 4 .4 % ,两组之间比较 ,经过t检验P >0 .0 5。体内实验表明 ,同步放化疗加阿米福汀组和同步放化疗组在实验观察的 2 0d内 ,相同时间点两组动物的肿瘤体积差异无统计学意义。结论　在多烯紫杉醇和放疗同步治疗肺癌过程中 ,阿米福汀无论是对离体还是在体的肿瘤细胞没有保护作用 ,多烯紫杉醇和同步放射治疗肺癌的疗效不会因为使用阿米福汀而减弱     

BDNF基因修饰神经干细胞移植后大鼠脊髓损伤移植处的基因表达变化

目的：了解脑源性神经营养因子（Brain-derived neurotrophic factor,BDNF）基因修饰神经干细胞移植到大鼠脊髓损伤处后的基因表达变化，为脊髓损伤修复提供基础研究资料。方法：大鼠随机分为4组：正常对照组，手术对照组，神经干细胞（Neural stem cells,NSCs）移植组，BDNF－NSCs移植组，各组分4个时相点（7d、1个月、2个月、3个月），利用细胞移植、X-gal组化、免疫组化、原位杂交等方法，观察了移植处细胞的标记基因（LacZ）表达和BDNF、胶质纤维酸性蛋白（GFAP）、神经丝－200（NF－200）的表达。结果：大鼠脊髓损伤移植处细胞中，有标记基因阳性细胞，BDNF强烈表达，尤其是BDNF－NSCs移植组的移植后1周和1个月时。各组各时相点均有GFAP和NF－200免疫反应阳性细胞和纤维。结论：BDNF基因修饰神经干细胞能在脊髓损伤移植处存活，强烈表达BDNF，BDNF基因修饰神经干细胞可以作为脊髓损伤修复的移植材料。     

聚对苯撑乙炔的合成及光谱性能-共轭主链被间位苯环阻隔

报道了一种阻隔型聚对幕撑乙炔((PPE)的合成与电致发光特性，合成的模型小分子证明，在聚对苯撑乙炔(PPV)主链引入间位幕环，可阻隔PPV的有效共轭长度，改变其发光颜色，研究了电致发光暑件ITO／m-PPE／Al的电致发光特性。