初次吸毒者与复吸者戒毒期间生活质量比较

目的:了解包头市初次吸毒者与复吸者戒毒期间的生活质量。方法:用QOL-DA2.0量表对戒毒人员的生活质量进行调查。结果:初次吸毒者与复吸者各纬度进行t检验显示躯体功能纬度(t=10.51)、心理功能纬度(t=5.94)、症状及毒副作用纬度(t=6.41)、社会功能纬度(t=10.47)和总分(t=10.48)均有统计学意义(P<0.001),表明戒毒期间初次吸毒者的生活质量高于复吸者。结论:在戒毒期间初次吸毒者的生活质量较复吸者易改善。     

DIFF33H参与TRAIL诱导的人Jurkat T淋巴细胞白血病细胞凋亡调控

目的：研究DIFF33H在人T淋巴细胞白血病细胞Jurkat凋亡中的表达规律及其生物学功能。方法：采用PCR扩增DIFF33H cDNA，Northern blot分析DIFF33H的mRNA表达，MTT法测定细胞凋亡。结果：在重组可溶性TRAIL诱导的人T淋巴细胞白血病细胞Jurkat凋亡过程中，DIFF33H mRNA的表达水平随着Jurkat细胞的凋亡而下降，并对重组可溶性TRAIL的作用具有浓度和时间的依赖性。在抗肿瘤药物5-FU诱导肿瘤细胞凋亡过程中，DIFF33H的mRNA表达水平也显著下降。结论：DIFF33H参与人T淋巴细胞白血病细胞Jurkat凋亡的调控。     

5-氟尿嘧啶缓释剂瘤内注射治疗胰腺癌的实验研究

目的:观察5FU缓释剂瘤内注射对裸鼠胰腺癌肿瘤细胞的影响,探讨其作用机制。方法:体外培养胰腺癌细胞株PC3,以2×106个细胞分别接种于70只裸鼠。4周后挑选肿瘤大小一致的裸鼠60只,随机分成5组,即静脉NS对照组、5FU静注组(10mg/kg)、基质植入组、5FU缓释剂(4mg/kg)植入组及5FU缓释剂(1mg/kg)植入组。于治疗前及治疗后14d内测量肿瘤大小,计算肿瘤生长速度;观察组织学变化和细胞分裂指数;免疫组化法测定bcl2和Bax的蛋白表达水平;采用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测凋亡指数(AI)。结果:5FU缓释剂瘤内注射组裸鼠移植瘤生长速度减慢(P<0.05),最终瘤重小于其他各组(P<0.05);细胞分裂指数亦均低于其他各组(P<0.05)。5FU缓释剂瘤内注射组肿瘤组织中炎症反应和血管内膜增厚程度明显高于其他各组(P<0.05)。5FU缓释剂瘤内注射组荷瘤裸鼠的bcl2基因蛋白表达明显低于其他各组,而Bax基因的蛋白表达明显高于其他各组,其肿瘤细胞的AI明显高于其他各组(P<0.05)。结论:5FU缓释剂瘤内注射可明显抑制裸鼠胰腺癌瘤体的生长,其作用机制与药物在肿瘤组织中引起的炎症反应和血管内膜增厚等因素有关,并可能与诱导肿瘤细胞的凋亡有关。     

亚叶酸钙加氟尿嘧啶联合奥沙利铂治疗晚期胃癌26例

目的 :探讨亚叶酸钙加氟尿嘧啶 (5 Fu)持续 72h滴注联合奥沙利铂治疗晚期 /转移性胃癌的临床疗效和毒副作用。方法 :共入选 2 6例。治疗方案为 :在每周期的d1,静脉滴注奥沙利铂 130mg·m-2 ;d1～d3静脉滴注亚叶酸钙 2 0 0mg·m-2 ·d-1;在d1静脉滴注亚叶酸钙结束后 ,静脉注射 5 Fu 0 .75 g ,然后静脉滴注 5 Fu 3.0g·m-2 ,持续 72h(d1～d3)。 4周为 1个周期 ,每例患者至少应用 2个周期。结果 :2 6例晚期胃癌患者获CR 2例 ,PR9例 ,有效率 4 2 .3%。毒副作用主要为骨髓抑制、口腔黏膜炎、腹泻 ,无严重神经损害。结论 :此方法治疗晚期 /转移性胃癌疗效好 ,安全性高。     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的：研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应，并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较。方法：经病理确诊的晚期大肠癌83例分为以下两组：治疗组行奥沙利铂(oxalipatin)130mg／m^2静脉滴注，第1天给药：氟尿嘧啶(5-FU)425mg／m^2静脉滴注，第1-5天给药；亚叶酸钙(CF)100mg／m^2静脉滴注，第1～5天给药；每3周重复。对照组行氟尿嘧啶(5-FU)42h5mg／m^2静脉滴注,第1～5天给药；亚叶酸钙(CF)100mg／m^2。静脉滴注，第1-5天给药；每3周重复。每例患者至少完成两个周期。结果：治疗组有效率为46．5％，常见的毒性反应为神经毒性；对照组有效率为17．5％，与治疗组差别有统计学意义，未见神经毒性，其他毒性与治疗组无统计学差异。结论：奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好，毒副反应较轻，疗效高于氟尿嘧啶加亚叶酸钙方案。     

姜黄素与氟尿嘧啶抗人结肠癌细胞株HT-29增殖的协调作用研究

目的:检测姜黄素能否增强氟尿嘧啶(fluorouracil,FU)抗结肠癌细胞的增殖作用,并探讨其与环氧合酶-2(cyclooxygenase-2,COX-2)蛋白表达的关系。方法:应用中位效应原理和联合作用指数法来定量姜黄素与FU的联合作用。应用Westernblot分析联合应用两种药物之后对于COX-2蛋白表达的影响。结果:姜黄素和FU的半数生长抑制率(IC50)分别为15.9±1.96和17.3±1.85μmol/L。当姜黄素与FU联合应用时,在较高的作用水平可以定量地观察到对HT-29细胞的协同抑制作用。并且这种协同作用随COX-2蛋白表达水平下调。结论:姜黄素可以增强FU的化学治疗效果,在结肠癌的临床治疗方面联合应用这两种药物可能具有实际意义。     

Modulation of multidrug resistance by andrographolid in a HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line

OBJECTIVE To develop an HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line and to elucidate the effect of Andrographolid (AG), an extract from Andrographis paniculate, a medicinal herb on the HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line. METHODS An HCT‐8 colorectal cancer cell line was used and a high concentration of 5‐Fluorouracid (5‐FU) was introduced at the beginning to induce drug resistance, then the concentration of 5‐FU was increased in gradients. Approximately 7 months later, the cells grew stably in 2.0 µg/mL of 5‐FU, and the cell line was named HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line. The resistant index of HCT‐8/5‐FU cells to 5‐FU, adriamycin (ADM), cisplatin (DDP) was checked by MTT test, and a growth curve was drawn. The morphological changes were observed by both light and electron microscope. The function of P‐170 was detected by rhodamine staining. After the application of AG and co‐administration of 5‐FU, ADM and DDP, the growth curves and inhibition rate as well as apoptosis rate of HCT‐8/5‐FU at different concentrations of AG were evaluated by MTT and flow cytometry. Rhodamine staining was used to investigate the possible mechanism involved by AG. RESULTS The resistance index of HCT‐8/5‐FU to 5‐FU was 16.6, and a cross‐resistance to ADM and DDP was noticed. Compared with parental cells, HCT‐8/5‐FU cell's growth rate did not change significantly but the cell's morphology was remarkably changed as compared with parental cells. Overexpression of P‐170 by HCT‐8/5‐FU cell was indicated through rhodamine staining. AG at a low concentration showed weak inhibitory effect on HCT‐8/5‐FU. However, a remarkable inhibitory and apoptosis rate was shown when AG was co‐administered with 5‐FU, ADM and DDP, respectively. Interestingly AG alone could not induce apoptosis and change the cell cycles. AG might affect the expression of P‐170, which was indicated by rhodamine staining. CONCLUSIONS The HCT‐8/5‐FU multidrug‐resistant colorectal cancer cell line has been successfully developed and because it has cross‐resistance to 5‐FU, ADM and DDP, it might serve as an ideal multidrug resistance (MDR) model for colorectal cancer research. The mechanism of HCT‐8/5‐FU resistance to chemotherapeutic agents might be related to the overexpression of P‐170. Low concentrations of AG alone have no significant inhibition on HCT‐8/5‐FU and fail to induce apoptosis and to change cell cycles. AG might act as a chemosensitizer when co‐administered with 5‐FU, ADM and DDP, and the mechanism of reversal modulation of multidrug resistance by AG in the HCT‐8/5‐FU resistant cell line might be related to its downregulation of overexpression of P‐170.     

Combinational treatment of 5‐fluorouracil and casticin induces apoptosis in mouse leukemia WEHI‐3 cells in vitro

Leukemia is one of the major diseases causing cancer‐related deaths in the young population, and its cure rate is unsatisfying with side effects on patients. Fluorouracil (5‐FU) is currently used as an anticancer drug for leukemia patients. Casticin, a natural polymethoxyflavone, exerts anticancer activity against many human cancer cell lines in vitro, but no other reports show 5‐FU combined with casticin increased the mouse leukemia cell apoptosis in vitro. Herein, the antileukemia activity of 5‐FU combined with casticin in WEHI‐3 mouse leukemia cells was investigated in vitro. Treatment of two‐drug combination had a higher decrease in cell viability and a higher increase in apoptotic cell death, the level of DNA condensation, and the length of comet tail than that of 5‐FU or casticin treatment alone in WEHI‐3 cells. In addition, the two‐drug combination has a greater production rate of reactive oxygen species but a lower level of Ca²⁺ release and mitochondrial membrane potential (ΔΨ_m) than that of 5‐FU alone. Combined drugs also induced higher caspase‐3 and caspase‐8 activities than that of casticin alone and higher caspase‐9 activity than that of 5‐FU or casticin alone at 48 hours treatment. Furthermore, 5‐FU combined with casticin has a higher expression of Cu/Zn superoxide dismutase (SOD [Cu/Zn]) and lower catalase than that of 5‐FU or casticin treatment alone. The combined treatment has higher levels of Bax, Endo G, and cytochrome C of proapoptotic proteins than that of casticin alone and induced lower levels of B‐cell lymphoma 2 (BCL‐2) and BCL‐X of antiapoptotic proteins than that of 5‐FU or casticin only. Furthermore, the combined treatment had a higher expression of cleaved poly (ADP‐ribose) polymerase (PARP) than that of casticin only. Based on these findings, we may suggest that 5‐FU combined with casticin treatment increased apoptotic cell death in WEHI‐3 mouse leukemia cells that may undergo mitochondria and caspases signaling pathways in vitro.     

Echocardiographic evolution of pulmonary artery pressure after acute pulmonary embolism. Results from IPER registry

Aims

The aim of the study is to describe the course of the echocardiographically measured pulmonary artery systolic pressure (PAsP) in a series of patients included in the Italian Pulmonary Embolism Registry (IPER).

Methods

Patients with confirmed PE received an echo-Doppler evaluation within 24 hours from hospital admission and after one year. Pulmonary hypertension (PH) was considered “likely” , “possible” or “unlikely” with a right ventricular-right atrial (RV-RA) pressure gradient > 45 mm Hg, between 32 and 45 mm Hg and ≤ 31 mm Hg and no additional echocardiographic variables suggestive of PH, respectively.

Results

We studied 286 patients (169 females and 117 males, mean age 67 ± 15; mean follow-up 387 ± 45 days): 240 had a baseline tricuspid regurgitation (TR) and a RV-RA gradient of variable degree. PH was considered likely, unlikely and possible in 97, 93 and 50 patients respectively. At FU echocardiography, 6 patients (2.1%) had a likely PH and all of them were part of the group of 97 patients with a baseline likely PH; 24 patients (8.4%) had a possible PH, and 67% of them had an initial likely PH. No patients with a baseline unlikely PH or without TR developed a follow-up PH (both likely or possible). The probability to show a likely PH at FU echocardiography for patients with a baseline RV-RA gradient > 45 mm Hg was 6.2%, while the probability not to have a likely PH for patients with a baseline RV-RA gradient ≤ 45 mm Hg was 100%.

Conclusion

In our study population of patients with acute PE, we observed that those presenting with a baseline echocardiographic RV-RA pressure gradient ≤ 45 mm Hg were completely free from a likely PH after 1-year.