新型内皮素受体拮抗剂ETP-508对实验性大鼠肺纤维化的干预作用

目的：研究新型内皮素受体拮抗剂ETP-508对实验性大鼠肺纤维化的干预作用,并探讨其机制．方法：实验分为4组：博莱霉素组、ETP-508组、地塞米松组和正常对照组．博莱霉素组、ETP-508组和地塞米松组均给以博莱霉素（5mg／kg）气管内注射复制大鼠肺纤维化模型,正常对照组给以气管内注射等量生理盐水替代．ETP-508组和地塞米松组造模开始后次日又分别给以腹腔注射ETP-508（100μg／kg）和地塞米松（1mg／kg）,隔日1次．博莱霉素组和正常对照组以等量生理盐水替代．造模后第28日处死所有大鼠,测定肺组织ET-1和羟脯氨酸含量,并进行组织病理学观察．结果：博莱霉素组肺组织内羟脯氨酸明显高于正常对照组,病理为肺纤维化改变．博莱霉素组的ET-1水平高于正常对照组和地塞米松组,差异有统计学意义（P〈0．01）;ETP-508组ET-1水平均高于上述各组,与博莱霉素组（P〈0．05）,正常对照组和地塞米松组比较（P〈0．01）有统计学意义;地塞米松组与正常对照组比较,无统计学意义（P〉0．05）．结论：ETP-508对肺纤维化的形成有一定的干预作用,其机制可能通过拮抗ET-1与内皮素受体结合的作用有关．     

三七总皂甙对实验性肺纤维化大鼠病理变化和转化生长因子-β1表达的影响

目的研究博莱霉素（BLM）所致大鼠肺纤维化的病理形态学变化和三七总皂甙（PNS）的干预作用及其机制。方法通过气管内注入BLM复制动物肺纤维化模型,于造模后第2天各治疗组开始每天给药,于给药后第7,14,28天分别随机处死一批大鼠,取肺组织行HE染色,用免疫组织化学方法检测肺组织中TGF-β1的表达,并测定肺组织中羟脯氨酸（HYP）含量。结果PNS能抑制实验性肺纤维化大鼠肺组织中胶原沉积及TGF-β1的异常升高,减轻其肺部的病理损害。结论PNS对BLM诱导产生的肺纤维化有一定的抑制作用。     

Antitumour effect of electrochemotherapy with bleomycin on human prostate cancer xenograft

OBJECTIVE

To investigate the antitumour effect of electroporation (EP), a drug delivery system that has been shown to be effective synergistically with antitumour drugs, with bleomycin on the growth of prostate cancer xenografts in nude mice.

MATERIALS AND METHODS

PC‐3 cells were implanted subcutaneously into nude mice. After determination of the optimal conditions of electric pulse voltage and bleomycin dose, tumour growth in mice treated with EP plus bleomycin was compared with that in mice receiving EP alone, bleomycin alone or no treatment. In all four groups, apoptosis in the tumours was assessed.

RESULTS

There was a significant reduction in tumour growth in mice that received EP with bleomycin. Apoptotic cells in tumours at 24 h after treatment with EP plus bleomycin showed a significant difference compared with the other three groups, but not at 12 h after treatment.

CONCLUSIONS

These results indicate the possibility that EP with bleomycin could be effective as an ablation therapy for prostate cancer, especially androgen‐independent cancer.     

G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis

Dose-intensity of chemotherapy is important in the treatment of Hodgkin lymphoma (HL) and granulocyte-colony stimulating factor (G-CSF) is commonly used to maintain it. We reviewed all newly diagnosed HL patients who were treated at our institution between 1996 and 2005. Fifty-nine patients received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose reductions, treatment delays, and without G-CSF, regardless of absolute neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was 0.925 x 10(9)/l, and was <0.5 x 10(9)/l on 26% of treatment days. Median normalised ABVD dose-intensity was 99.1% (range, 93-100%) and median cycle duration was 28.2 d. Incidence of bleomycin lung toxicity was 1.6%, 0.44% treatments were complicated by febrile neutropenia, and no secondary malignancies have occurred (median follow-up 48 months; range, 11-130 months). Five-year event-free (EFS) and overall survival (OS) were 92.9% and 97.4% respectively. Furthermore, the 5-year EFS and OS (87.4% and 94.1% respectively) for advanced stage patients compared favourably with a similar ABVD patient group who received routine prophylactic G-CSF (n = 23) with EFS 80.0% and OS 91.3% (P = 0.46 and 0.67 respectively). Our experience suggests that ABVD may be safely and effectively administered at >99% dose-intensity without G-CSF support, regardless of the ANC.     

恶性心包积液的内科治疗进展

恶性心包积液是晚期癌症患者常见并发症之一,已严重影响病人的生活质量和生存期,近年来许多临床医师对恶性心包积液的内科治疗做了大量研究,如腔内化疗、生物反应调节剂、博莱霉素、热疗等,其近期疗效均较好,不良反应轻。     

争光霉素复合物中两种新组份的研究

从争光霉素产生菌轮枝链霉菌平阳新变种（Ｓｔｒｅｐｔｏｍｙｃｅｓｖｅｒｔｉｃｉｌｌｕｓｖａｒ．Ｐｉｎｇｙａｎ－ｇｅｎｓｉｓｎ．ｓｐ．）的发酵产物争光霉素复合物中分离得到了二种新组份Ｚ－９０１和Ｚ－９０２，通过ＵＶ、ＩＲ、ＣＤ、ＦＡＢＭＳ、１Ｈ－ＮＭＲ、１３Ｃ－ＮＭＲ、１３Ｃ－１ＨＣＯＳＹ等光谱测定，确定了它们的结构，证明它们是二个新的化合物，分别称为ＤｅｐｙｒｕｖａｍｉｄｅＢＬＭＡ５（Ｚ－９０１）和Ｄｅａｍｉｄｅ－Ｄｅｐｙｒｕｖａ－ｍｉｄｅＢＬＭＡ５（Ｚ－９０２）。     

Uncatalyzed microwave deuterium exchange labeling of bleomycin A2

Bleomycin sulfate in D₂O was deuterated using microwave irradiation under catalyst free conditions. Following the removal of labile deuterium and purification, bleomycin A₂ with mass M + 1 to M + 7 was obtained. Successful selective uncatalyzed microwave deuterium exchange reactions on examples from the following classes of heterocycles are also described: imidazole, thiazole, indole, purine, and quinazoline. The described method was used as a test for non‐labile active protons. Copyright © 2004 John Wiley & Sons, Ltd.     

Sonographically guided small-bore chest tubes and sonographic monitoring for rapid sclerotherapy of recurrent malignant pleural effusions.

OBJECTIVE: To evaluate the role of sonographically guided small-bore chest catheters and sonographically based monitoring of fluid evacuation in rapid sclerotherapy of malignant pleural effusions. METHODS: In 50 patients with recurrent malignant pleural effusions, a 9F catheter was inserted into the pleural space under sonographic guidance. When sonography documented complete fluid evacuation, bleomycin (0.75 mg/kg) was injected via the tube. Fluid drainage was monitored for 12 hours; if fluid output was less than 100 mL, the pleural catheter was removed; otherwise, a second dose of bleomycin was administered after 24 hours. If loculations or fluid reaccumulations due to tube malfunctioning were detected, they were evacuated by sonographically guided thoracentesis, and bleomycin (1.5 mg/100 mL of fluid) was injected through the thoracentesis needle. All patients were monitored for fluid recurrence with thoracic sonography. RESULTS: Twenty-nine patients received 1 dose of bleomycin, and 21 received 2 doses. In 11 patients with residual loculations, sonographically guided thoracentesis was performed, and bleomycin was injected into the loculations. In 29 patients, pleurodesis was completed within 24 hours; in 21, it was completed within 48 hours. The 30-day response was 84%; the long-term response was 60%. No complications or serious side effects were observed. CONCLUSIONS: Rapid pleurodesis can be accomplished within 24 to 48 hours, with good short- and long-term responses. Thoracic sonography plays a pivotal role. It guides placement of the pleural catheter and is valuable in the monitoring of fluid evacuation for determining the right time for sclerosing agent administration and in the detection and treatment of loculations or residual pleural fluid due to tube malfunctioning.     

平阳霉素碘油乳剂动脉内栓塞治疗原发性大肝癌初探

目的回顾性评价平阳霉素碘油乳剂（PLE）经肝动脉化疗栓塞治疗原发性大肝癌的安全性、技术成功率及临床疗效，以期提高患者生活质量及生存率。方法对20例原发性大肝癌患者实施超选择性肿瘤滋养动脉PLE栓塞治疗。随机抽取前期用丝裂霉素碘油乳剂（MLE）治疗的24例原发性大肝癌患者作为对照组，比较两组病例治疗后肿瘤大小、肿瘤血管的改变及生存率等变化。结果研究组较对照组术后肿瘤缩小更明显（X^2=7．51，P〈O．05），甲胎蛋白水平下降显著（X^2=8.290，P〈0．05）。研究组6、12、24、36个月生存率分别为95％（19／20）、70％（14／20）、30％（6／20）和20％（4／20），对照组6、12、24、36个月生存率分别为80％（19／24）、54％（13／24）、21％（5／24）和13％（3／24），两组生存率比较，差异有统计学意义。结论PLE超选择性肿瘤滋养动脉栓塞治疗原发性大肝癌安全，治疗效果明显，其疗效明显优于MLE栓塞治疗。