制首乌总多糖对贫血小鼠造血祖细胞增殖的影响

目的观察制首乌总多糖(PPS)对放化疗所致骨髓抑制贫血小鼠造血祖细胞增殖的影响。方法建立骨髓抑制贫血小鼠模型,采用造血祖细胞培养技术,观察PPS体内ip给药和细胞培养直接用药对造血祖细胞增殖和骨髓有核细胞(BMC)数目的影响。结果体内用药能显著增加BMC数目,提高BFU-E、CFU-E和CFU-Meg集落数产率(P<0.01),能增加CFU-GM集落数产率(P<0.05);在一定浓度下,体外直接用药,能增加CFU-Meg集落数产率(P<0.01)。结论PPS能通过间接作用促进红系和粒系祖细胞的增殖,能通过间接和直接作用刺激巨核系祖细胞的增殖。     

奈达铂（Nedaplatin）在大鼠体内的肾毒性和骨髓抑制的时辰毒理学研究

目的:以大鼠为实验对象,通过测定给药时间与奈达铂(Nedaplatin)诱发的肾毒性和骨髓抑制的关系,研究铂(Pt)衍生物奈达铂的时辰毒理.方法:于8:00或20:00通过尾静脉给S-D大鼠(n=8)注射奈达铂(5 mg/kg体重)或空白溶媒,给药间隔为7天.定期采血、采尿测定血清肌苷清除率和周边血中的中性粒细胞.最后一次给药后24小时,处死动物,采集肾脏和大腿骨用于Pt浓度测定和组织学检查.共给药6次.结果:20:00给药组的体重抑制明显高于8:00给药组,实验结束时,两实验组均有2只动物死亡.奈达铂诱发的骨髓抑制没有明显的给药时间相关性,但20:00给药组的肾毒性明显大于8:00给药组.肌苷清除率和肾组织损伤积分均与肾皮质中n的含量有很好的相关性.结论:奈达铂诱发的肾毒性和药物在组织中的蓄积与给药时间有很好的相关性,提示该类药物在临床使用过程中应注意给药时间的选择.     

重组人粒细胞集落刺激因子治疗乳腺癌术后化疗后骨髓抑制的疗效

目的 观察重组人粒细胞集落刺激因子治疗乳腺癌术后化疗后骨髓抑制的临床疗效。方法 将63例乳腺癌术后化疗后骨髓抑制患者按入院的先后顺序分为2组：治疗组（32例）和对照组（31例）。2组化疗前24 h均给予地塞米松片7.5 mg口服,2次·d^-1,连续3 d。化疗前30 min给予盐酸昂丹司琼8 mg加入0.9%氯化钠注射液100 mL中静脉滴注。在此基础上,治疗组化疗48 h后开始给予重组人粒细胞集落刺激因子治疗。观察2组白细胞减少、中性粒细胞数减少、血小板减少、血红蛋白减少及中性粒细胞减少性发热发生率的情况。结果 治疗组血小板减少、血红蛋白减少发生率与对照组比较差异均无统计学意义（0.0%、43.8%比0.0%、45.2%,均P＞0.05）;治疗组白细胞减少、中性粒细胞数减少和中性粒细胞减少性发热发生率均较对照组明显降低（68.8%、59.4%、65.6%比96.8%、93.5%、83.9%,均P＜0.05）。结论 重组人粒细胞集落刺激因子治疗乳腺癌术后化疗后骨髓抑制,能有效控制肿瘤术后化疗后骨髓抑制的发生,减少感染机会,能保障化疗的顺利进行。     

Reassembling of albumin-bound paclitaxel mitigates myelosuppression and improves its antitumoral efficacy via neutrophil-mediated targeting drug delivery

Albumin-bound paclitaxel (abPTX) has been widely used in cancer treatment. However, dose-related side effects, such as myelosuppression, restrict its clinical application. Cell-based targeting drug delivery is a promising way to mitigate systematic side-effects and improve antitumoral efficacy. In this study, we demonstrated that reassembled abPTX could be engulfed by neutrophils in vivo and delivered to tumor site, thus improving therapeutic efficacy and mitigating myelosuppression. First, in vitro analysis confirmed that reassembling of abPTX formed uniform and stable serum albumin nanoparticles (NP-abPTX) with size of 107.5 ± 2.29 nm and reserved the ability to kill tumor cells. Second, we found that NP-abPTX could be engulfed by activated neutrophil in vitro and in vivo but do not affect neutrophils’ function, such as chemotaxis and activation. In a murine tumor model, we further proved that local radiotherapy (RT) induced inflammation activated peripheral neutrophils to capture venous infused NP-abPTX and carry them into tumor tissue. As compared to abPTX, infusion of NP-abPTX dramatically enhanced inhibition of tumor growth treated by local RT and mitigated hematotoxicity. Therefore, our study demonstrated a novel strategy to mitigate side-effects and to improve tumor killing efficacy of abPTX through neutrophil-mediated targeting drug delivery.     

加味龟鹿二仙汤时辰用药调节乳腺癌化疗后骨髓造血功能的临床研究

目的:探讨加味龟鹿二仙汤及时辰用药方案在防治乳腺癌化疗后骨髓抑制方面的作用。方法:共纳入乳腺癌术后患者120例,随机分为3组,其中西药对照组36例(化疗后予利血生、鲨肝醇、V itB4服用);中药(加味龟鹿二仙汤)不拘时口服组43例;中药时辰用药组(加味龟鹿二仙汤组酉时服用)41例。结果:经统计学分析,中药不拘时口服组与时辰用药组在减轻乳腺癌化疗后血液学毒性方面(白细胞、血红蛋白、血小板减少方面)均优于西药对照组(P=0.000),而在白细胞数减少方面,中药时辰用药组尚优于中药不拘时服用组(P=0.035)。此外,中药组相比于西药对照组,可以明显减少集落细胞刺激因子粒生素的使用量(P<0.01)。结论:补肾中药加味龟鹿二仙汤能明显改善乳腺癌患者化疗后骨髓造血功能,尤以按时辰用药(酉时服用)效果为著。     

当归补血汤不同剂型及配伍对骨髓抑制小鼠造血调控的实验研究

 目的本实验通过比较当归补血汤煎剂及颗粒剂对骨髓抑制小鼠造血机能调控的影响来比较它们之间的疗效差异。旨在为中药颗粒剂的疗效提供实验室依据。方法本实验用高效液相色谱仪检测了当归补血汤不同制剂中阿魏酸、黄芪甲苷的含量差异;采用造血祖细胞培养术、外周血像计数法、ELISA等方法对造血祖细胞集落数、外周血像的变化及造血微环境中EPO,TPO,G-CSF的变化进行检测。结果当归补血汤煎剂、颗粒剂能通过平衡骨髓微环境中EPO,TPO,GM-CSF的表达;促进骨髓造血细胞从G_{0/G1期进入G2/M期和S期;促进造血祖细胞增殖,从而提高骨髓抑制小鼠外周血像和骨髓像。结论当归补血汤煎剂、颗粒剂均能改善骨髓抑制小鼠的造血机能,其中配方颗粒剂疗效较为突出。}     

Efficacy and tolerability of lower-dose topotecan in recurrent ovarian cancer: a retrospective case review

Topotecan (1.5 mg/m(2)/day for 5 consecutive days of a 21-day cycle) is an established recurrent ovarian cancer treatment, but myelosuppression can be dose limiting. This study evaluates the activity and tolerability of low-dose topotecan in our clinical experience. Case records were reviewed for patients with recurrent ovarian cancer in first through third relapse. Eligible patients had received > or =2 cycles of < or =1.25 mg/m(2) topotecan. Adverse events were evaluated using laboratory and clinical evaluation data. Twenty-seven eligible patients, most with advanced disease, received a total of 209 cycles (median, six cycles). Grade 3 or 4 hematologic toxicities during 184 cycles in 24 assessed patients were neutropenia, leukopenia, thrombocytopenia, and anemia in 35%, 28%, 36%, and 11% of cycles, and 21, 19, 16, and 10 patients, respectively. Only four grade 4 toxicities occurred: anemia (one) and thrombocytopenia (three). Myelosuppression was reversible, noncumulative, and manageable. Moreover, nonhematologic toxicity was generally mild to moderate, and the only two grade 3 events were constipation and deep vein thrombosis. Low-dose topotecan was active in this setting. Lower-dose topotecan is generally well tolerated and active in patients with pretreated ovarian cancer. Prospective clinical trials of low-dose topotecan in recurrent ovarian cancer are warranted.     

Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for refractory neuroblastoma

BACKGROUND: (131)I Metaiodobenzylguanidine ((131)I-MIBG) is an effective targeted radiotherapeutic for neuroblastoma with response rates greater than 30% in refractory disease. Toxicity is mainly limited to myelosuppression. The aim of this study was to determine the response rate and hematologic toxicity of multiple infusions of (131)I-MIBG. PROCEDURE: Patients received two to four infusions of (131)I-MIBG at activity levels of 3-19 mCi/kg per infusion. Criteria for subsequent infusions were neutrophil recovery without stem cell support and lack of disease progression after the first infusion. RESULTS: Sixty-two infusions were administered to 28 patients, with 24 patients receiving two infusions, two patients receiving three infusions, and two patients receiving four infusions. All patients were heavily pre-treated, including 16 with prior myeloablative therapy. Eleven patients (39%) had overall disease response to multiple therapies, including eight patients with measurable responses to each of two or three infusions, and three with a partial response (PR) after the first infusion and stable disease after the second. The main toxicity was myelosuppression, with 78% and 82% of patients requiring platelet transfusion support after the first and second infusion, respectively, while only 50% had grade 4 neutropenia, usually transient. Thirteen patients did not recover platelet transfusion independence after their final MIBG infusion; stem cell support was given in ten patients. CONCLUSIONS: Multiple therapies with (131)I-MIBG achieved increasing responses, but hematologic toxicity, especially to platelets, was dose limiting. More effective therapy might be given using consecutive doses in rapid succession with early stem cell support.     

口服甲氨蝶呤引起腹痛、腹泻及骨髓抑制

1名72岁女性类风湿关节炎患者，口服甲氨蝶呤2．5mg，2次／d，1周后出现腹痛，腹泻，遂停药并服用诺氟沙星、小檗碱，但症状未缓解。入院后血常规检查显示WBC 1．6×10^9／L，RBC2．7×10^12／L，Hb86g／L，PLT 51×10^9／L，给予粒细胞集落刺激因子、左氧氟沙星等治疗，但外周全血细胞进行性下降，大便由水样便转为黏液血便，皮肤出现瘀点及瘀斑。给予肌内注射亚叶酸钙15mg，3次／d。入院第4天，患者WBC0．5×10^9／L，Hb73/L，PLT11×10^9／L。给予静脉输注血小板、压积红细胞，继续行补液、止血、抗感染等治疗。1周后，患者腹痛、腹泻症状缓解，复查血常规：WBC4．9×10^9／L，Hb76g／L，PLT70×10^9／L。2年后随访，血常规正常。