Establishment of human osteosarcoma cell lines with high metastatic potential to lungs and their utilities for therapeutic studies on metastatic osteosarcoma

Relevant animal models for metastasis of osteosarcoma is needed to understand the biology and to develop the treatment modality of metastasis of human osteosarcoma. Therefore, we screened six human osteosarcoma cell lines for metastatic ability in nude mice. The HuO9 cell line was identified as being metastatic to the lung after intravenous injection. We established two sublines, HuO9-M112 and HuO9-M132, with high metastatic potential to the lung from the parental HuO9 cells by in vivo selection. There were no differences between these two sublines and the parental cells in the growth rate in vitro and the tumorigenicity after subcutaneous injection in nude mice, however, mice injected with the metastatic sublines became moribund earlier than mice injected with the parental HuO9 cells did. Thus, adriamycin (ADR) and recombinant interleukin-12 (IL-12) were administered to mice injected with the HuO9-M112 subline to suppress experimental lung metastases. Production of lung colonies was significantly suppressed and the prognoses of mice were significantly improved by both ADR and IL-12 treatments. These results indicate that both ADR and IL-12 are effective agents against pulmonary metastatic osteosarcoma, and that these sublines are useful for studies on the biological behavior and treatment of pulmonary metastatic osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.     

细胞凋亡在阿霉素大鼠肾病模型中的作用

目的：探讨细胞凋亡在阿霉素肾病中的作用及其机制。方法：将30只体重250－300g的Wistar雄性大白鼠随机分为3组,给模型组和SOD组一次性尾静脉注射阿霉素7．0mg/kg,SOD组于注射阿霉素30min后,每天尾静脉注射超氧化物歧化酶（SOD)1．8mg/kg,对照组注射等量生理盐水,于实验第7天,第14天,第28天分别用代谢笼留取24h尿液,测定尿蛋白,第28天末处死动物,取贤皮质做常规病理检查,电镜检查,并用原位末端标记法检测肾小球,肾小管细胞凋亡情况,肾皮质匀浆丙二醛（MDA）及谷胱甘肽过氧化物酶（GSH－Px)水平分别用硫代巴比妥酸比色法,还原型谷胱甘肽消耗法测定。结果：模型组肾小球,肾小管细胞凋亡数及肾皮质MDA水平明显高于对照组（P＜0．01）,GSH－Px水平则明显低于对照组（P＜0．01）,SOD组肾小球,肾小管,细胞凋亡数及肾皮质MDA水平明显低于模型组（P＜0．01）,GSH－Px水平则明显高于模型组（P＜0．01）,结论：阿霉素肾病鼠发病与病鼠肾小球,肾小管细胞亡有密切关系,而病鼠肾小球,肾小管细胞凋亡与氧自由基（OFR）有关。     

阿霉素注射神经干治疗原发性三叉神经痛

对 6 8例原发性三叉神经痛患者施行阿霉素神经干注射治疗。全部病例均在术后 2周内三叉神经痛症状消失 ,其中 6 3.2 %在术后 2 4h内痛疼消失 ;2 8.9%在术后 1周内疼痛消失 ;7.9%在术后 2周内疼痛消失。随访结果显示 ,3年内复发率为 10 .3% ,3～ 5年复发率为 15 .4%。该方法具有复发率低、疗效肯定、安全、微创等特点。     

茯苓对阴虚水肿模型大鼠及其热象的影响

目的 观察茯苓对阴虚水肿模型大鼠的影响,研究茯苓利水作用特点及机制,并评价茯苓对阴虚水肿所表现出热象的影响。方法 尾iv阿霉素联合ig甲状腺片复制阴虚水肿模型大鼠,给予茯苓水煎液或六味地黄丸干预4周,观察大鼠水肿情况和一般生长状态,检测24 h尿量和尿蛋白,测量肛温,进行冷热板实验计算热板停留时间比;检测血清总蛋白（total cholesterol,TP）、白蛋白（albumin,Alb）、尿素氮（blood urea nitrogen,BUN）、肌酐（creatinine,Cr）、环磷酸腺苷（cyclic adenosine monophosphate,c AMP）、环磷酸鸟苷（cyclic guanosine monophosphate,c GMP）水平;测定肾组织超氧化物歧化酶（superoxide dismutase,SOD）活性及活性氧（reactive oxygen species,ROS）、丙二醛（malondialdehyde,MDA）水平;苏木素-伊红（HE）染色观察肾组织病理变化;Western blotting检测肾脏组织Klotho和棕色脂肪组织中解偶联蛋白1...     

Toxicity of magnetic albumin microspheres bearing adriamycin

Magnetic albumin microspheres entrappingadriamycin ( ADM- MAM) is a novel chemothera-peutic compound with site- specific drug delivery,which was exploited and developed in 1 970 's[1] .However,there wasno detailinformation indexed onits toxicity[2 ] . In recentyears,we studied the toxici-ty of the compounds macroscopically and microscopi-cally and also gotits value of LD50 .1　METHODSAND RESULTSBased on the method previously reported[1] ,thecompound of ADM- MAM was synthesized[14 ]…     

生脉注射液对阿霉素致心脏损伤保护作用的实验研究

用Wister大鼠模型研究生脉注射液对阿霉素致心脏损伤的保护作用。结果：使用生脉注射液比单纯使用阿霉素,血清SOD活性升高,MDA、GOT、LDH、HBDH、LDH1／LDH2比值及心肌病理计分下降。表明;生脉注射液对阿霉素导致的心脏损伤具有保护作用,其机理与其清除氧自由基,保护SOD活性有关。     

丹参及生脉液对阿霉素所致大鼠肾小球硬化的实验性治疗作用

观察丹参及生脉液对阿霉素所致 Ｓ Ｄ 大鼠肾小球硬化实验性治疗作用。摘除大鼠左肾７ ｄ 后,尾静脉注射阿霉素（６ ｍ ｇ·ｋｇ － １） 。隔日腹腔注射丹参及生脉液,８ 周后处死大鼠。观察血红蛋白（ Ｈｂ） 、血尿素氮（ Ｂ Ｕ Ｎ） 、胆固醇（ Ｃｈ） 及２４ ｈ 尿蛋白含量; Ｅ Ｌ Ｉ Ｓ Ａ 法测定肾皮质Ⅳ型胶原（ Ⅳｃｏｌ ．） 及层粘连蛋白（ Ｌ Ｎ） ;用免疫组化法,计算机图象分析肾小球系膜区Ⅳｃｏｌ ．及 Ｌ Ｎ 含量。结果显示：模型丹参及模型生脉液组肾皮质、肾小球系膜区Ⅳｃｏｌ．及 Ｌ Ｎ 含量明显低于模型对照组（ Ｐ ＜ ０ ．０５） ,高于正常对照组（ Ｐ ＜ ０ ．０１） 。提示丹参及生脉液能减轻阿霉素所致肾小球硬化的程度。     

Osteoclastome-like giant cell thyroid carcinoma controlled by intensive radiation and adriamycin,in a patient with meningioma and multiple myeloma treated by radiation and cytoxan

The eighth case of osteoclastome-like giant cell carcinoma of the thyroid, and the first one to be treated with adriamycin in addition to surgery and radiation, is reported. This rare variant of anaplastic thryoid carcinoma appeared in a patient operated on for meningioma and treated for multiple myeloma with cranial radiation and chronic administration of cytoxan.     

含诺维本的联合化疗对47例中晚期肺癌的近期疗效

目的：探讨含诺维本的联合化疗治疗中晚期肺癌的近期疗效及毒副反应。方法：应用以诺维本为主，与顺铂及阿霉素联合治疗47例中晚期肺癌有效率及毒副反应。结果：47例中晚期肺癌总有效率为48．9％。其中非小细胞肺癌有效率为56．8％（肺鳞癌为57．8％，肺腺癌为55．6％），小细胞肺癌有效率为20％.两组差异显著（P＜0．05），而鳞癌和腺癌疗效无明显差别（P＞0．05）。本方案毒副反应主要是骨髓抑制、神经毒性，胃肠道反应则较少。结果提示含有诺维本的联合化疗不仅对非小细胞肺癌有较好疗效，且毒副反应较轻。结论：含有诺维本的联合化疗，是一个值得临床更深入研究及应用的治疗非小细胞肺癌方案。     

抑制生存传导路径可增加肿瘤细胞化疗敏感性

目的：研究抑制磷酸酰肌醇3激酶(PI3K)／Akt生存传导路径是否可增加肿瘤细胞对一些化疗药物的敏感性。方法：采用Akt亚型特异抑制剂结合多柔比星(阿霉素ADM)或喜树碱治疗各种肿瘤细胞系；检测细胞凋亡蛋白激酶3活性，来定量评估细胞凋亡程度；免疫沉淀 Werstern印迹法测定药物对磷酸化各类Akt亚型的抑制作用。结果：①各类Akt亚型抑制剂可阻断Akt1或Akt2蛋白序列上的第308位点苏氨酸(pAkt^308)和第473位点丝氨酸(pAkt^473)磷酸化，并表现出相应的Akt亚型抑制特异性；②单独抑制某一类Akt亚型并不足以增加肿瘤细胞对化疗药物的敏感性，只有同时抑制Akt1和Akt2才能增敏药物对肿瘤细胞的杀灭效应；③药物的增敏效应可能和肿瘤细胞内源性PTEN脱磷酸酶的表达有一定的关联。结论：临床应用化疗结合PI3K／Akt生存传导路径抑制剂应选择具有阻断2种Akt亚型功能的药物以达到最大的肿瘤杀灭效应。