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.     

精元康胶囊对化疗致骨髓抑制小鼠骨髓细胞Bcl-2,Bax mRNA表达水平的影响

目的:通过观察精元康胶囊对骨髓细胞Bcl-2,Bax mRNA表达水平的影响,以深入探讨该药的作用机制。方法:实时荧光定量PCR检测骨髓抑制模型小鼠骨髓细胞表达Bcl-2,Bax mRNA的情况。结果:Bcl-2 mRNA的表达水平精元康胶囊组最高,Bax mRNA的表达水平精元康胶囊组最低,与模型组比较有显著差异,与空白组比较无明显差异。结论:精元康胶囊能升高抗凋亡基因Bcl-2的表达,同时降低促凋亡基因Bax的表达,对骨髓细胞凋亡相关通路产生影响,可能是精元康胶囊对化疗致骨髓抑制影响的重要机制。     

增免抑瘤颗粒剂干预卵巢癌大剂量化疗后免疫及骨髓抑制的实验研究

目的探讨增免抑瘤颗粒剂对卵巢癌SKOV3荷瘤小鼠顺铂（DDP）化疗后免疫及骨髓抑制的改善情况。方法建立卵巢癌SKOV3荷瘤小鼠模型,测定小鼠单次腹腔注射DDP的LD50。取40只造模成功的荷瘤鼠,随机分为DDP组、ZMYL高、中、低剂量合并DDP组,每组10只,各组均予DDP LD50值单次腹腔注射。注射后次日开始灌胃给药,ZMYL高、中、低剂量组的给药剂量分别为24.0g/kg、12.0g/kg、6.0g/kg,DDP组灌以等量的0.9%NaC l溶液,共干预8天。观察荷瘤小鼠存活时间、存活率、脾脏指数及骨髓DNA含量、血常规等指标变化情况,应用荧光标记的单克隆抗体染色结合流式细胞仪测定外周血T淋巴细胞亚群比例。结果①DDP腹腔注射LD50为16.36 mg/kg,95%可信限为13.22mg/k-20.39 mg/kg。②各组生存时间以及存活率差异均无统计学意义（P〉0.05）。③与DDP组比较,各剂量ZMYL＋DDP组均可提高荷瘤小鼠脾脏指数,中高剂量组还可提高骨髓DNA含量,差异均有统计学意义（P〈0.05）。④与DDP组比较,各剂量ZMYL＋DDP组均可提高荷瘤小鼠外周血中白细胞数,差异均有统计学意义（P〈0.05）。⑤与DDP组比较,各剂量ZMYL＋DDP组的CD3、CD4、CD8及CD4/CD8差异无统计学意义（P〉0.05）。结论 ZMYL对顺铂大剂量化疗引起的荷瘤小鼠外周血白细胞减少及骨髓DNA含量、脾脏指数的降低有明显的升高作用,能调节机体紊乱的免疫功能,改善骨髓抑制。     

温肾升白方防治乳腺癌术后化疗致骨髓抑制的临床观察

目的:探讨中药温肾升白方在防治乳腺癌术后化疗所致骨髓抑制方面的作用。方法:共纳入乳腺癌术后患者120例,按随机数字表分为治疗组与对照组,每组各60例。在术后化疗期间,治疗组予服用温肾升白方,对照组口服利可君片。检测患者血常规并分析骨髓抑制的分度,记录应用集落刺激因子情况。结果:前两疗程化疗后两组白细胞计数无统计学差异(P0.05);第三疗程后治疗组白细胞下降程度明显较对照组减轻(P0.05),且集落刺激因子使用量明显减少(P0.05)。两组在血红蛋白、血小板下降方面无明显差异(P0.05),也无肝肾功能异常表现。结论:温肾升白方能明显减轻乳腺癌患者化疗后骨髓抑制的毒副反应,减少集落细胞刺激因子的使用量。     

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.     

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.