补肾解毒方对恶性肿瘤化疗中骨髓抑制的影响

目的:探讨补肾解毒方对恶性肿瘤化疗中骨髓抑制的影响。方法:选择恶性肿瘤化疗患者152例为研究对象,以随机数字表法分组,分为观察组与对照组,各76例。对照组单纯接受常规化疗,观察组在常规化疗基础上口服补肾解毒中药复方制剂。对比两组患者两个化疗疗程完成率及第1疗程中血象情况。结果:观察组两个化疗疗程完成率为97.37%,显著高于对照组的84.21%(P<0.05);第1疗程化疗后1周、3周时,观察组各血象指标均高于对照组,差异有统计学意义(P<0.05)。结论:补肾解毒方可减轻恶性肿瘤化疗患者骨髓抑制,有助于骨髓造血功能恢复,提高化疗耐受性和成功率,值得临床推广。     

鬼臼乙叉甙(VP-16)治疗急性白血病

16例急性白血病患者接受鬼臼乙叉甙(VP-16)、阿糖胞苷(Ara-C)的治疗。10例为初治的M_4或M_5患者。5例有效,其中4例为CR,1例PR。另外6例是难治性白血病,包括1例慢粒急变,1例M_6(红-单细胞性),4例第一次或第二次复发者。他们之中仅三例获PR。鬼臼乙叉甙的副作用是骨髓抑制。     

In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

Imatinib mesylate (IM) is used to treat chronic myeloid leukemia (CML) because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM). The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM), using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM) reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells) increased. At higher concentrations (15 µM), the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control). Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G₀/G₁ phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.     

紫杉醇类化疗药物导致骨髓抑制的中医药防治进展

紫杉醇类化疗药物易出现骨髓抑制不良反应,常导致患者不能按时、足量完成既定化疗方案,而中医药对其骨髓抑制不良反应有独到的认识和疗效。现从对紫杉醇所致骨髓抑制的中医认识、临床常用药物、单味药物研究、经方验方、中成药及外治法等方面系统总结了近年中医药改善紫杉醇类化疗药物所致骨髓抑制的研究,为治疗骨髓抑制的不良反应提供中医论治思路。     

多西紫杉醇联合吡柔比星化疗治疗乳腺癌的效果及复发情况观察

目的观察多西紫杉醇联合吡柔比星化疗在乳腺癌患者治疗中的效果,及对不良反应发生率的影响。方法选取乳腺癌患者为研究对象,并根据其化疗药物的不同分为对照组和观察组,对照组给予紫杉醇联合吡柔比星进行化疗,观察组给予多西紫杉醇联合吡柔比星进行化疗。观察2组患者的治疗效果、不良反应发生率和复发率,比较2组患者治疗前后肿瘤标志物水平的差异。结果观察组治疗有效率为97. 50%,明显高于对照组的80. 00%,差异有统计学意义(χ^2=6. 135,P=0. 013)。2组患者治疗前肿瘤标志物水平无差别,治疗后,观察组患者的CEA、CA125、CA153水平低于对照组(t=11. 432、18. 876、3. 703,P <0. 001)。2组患者骨髓抑制、恶心呕吐、脱发、中性粒细胞减少、肝功能损害等不良反应发生率无差别(χ^2=0. 238,P=0. 626)。对照组1年复发率较观察组高,但差异无统计学意义(χ^2=1. 053,P=0. 305)。结论多西紫杉醇联合吡柔比星化疗对乳腺癌患者的化疗效果较好,且不会增加骨髓抑制等不良反应发生率,具有良好的应用价值。     

利可君在放射性核素内照射治疗疾病中预防骨髓抑制作用

放射性核素靶向治疗是治疗恶性肿瘤及其他一些常见疾病的重要手段之一,但也有可能由于电离辐射生物效应同时造成骨髓抑制副反应.临床解决骨髓抑制的主要方法为口服或注射升白药物,最为常见的口服用药为利可君,化学性质独特,具有稳定升高白细胞水平以及一定的抗癌作用.在131Ⅰ治疗甲亢、甲状腺功能自主毒性腺瘤和大剂量131Ⅰ治疗甲癌术后残留、局部复发或远处转移的患者配合使用利可君可有效预防骨髓抑制或提高白细胞水平.     

辐射导致长期骨髓抑制的研究进展

随着接受放疗患者生存期的延长,患者发生长期骨髓抑制的概率也大幅提高。长期骨髓抑制在临床中常被忽略,随着时间延长患者病情会逐渐加重,生活质量降低。许多长期骨髓抑制患者会形成再生障碍性贫血或者骨髓增生异常综合征,严重者可引发死亡。研究资料表明,活性氧和丝裂原活化蛋白激酶p38（P38MAPK）通路在辐射诱导长期骨髓抑制中占主要作用。笔者总结了辐射导致的长期骨髓抑制的相关研究,指出了今后的研究方向。     

The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor.

The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy. The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60%. In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses. It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%). The administration of antibiotics was required for about 7 days to patients with febrile episodes. Sepsis was experienced in five courses, in which the neutrophils were all zero. All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.     

索拉非尼联合干扰素治疗肾细胞癌致Ⅳ度骨髓抑制一例

患者女,64岁.2007年3月因自扪及左腰腹部巨大包块2月余来我院泌尿外科就诊,胸腹部CT示双肺多发结节,左肾占位,左侧胸腔积液.于3月9日行左肾切除术.术后病理示,左肾透明细胞癌伴坏死,癌组织穿透肾包膜达周围脂肪组织,癌细胞穿透肾盂黏膜.患者被诊断为左肾透明细胞癌pT4NxcM1 Ⅳ期(双肺).3月底患者开始出现胸闷,活动后加重,夜间可平卧,咳嗽较明显,但无咳痰、咯血、胸痛等不适,KPS评分为70分.入我科治疗.     

Effect of the Cdk-inhibitor roscovitine on mouse hematopoietic progenitors in vivo and in vitro

Myelosuppression is one the most frequent side effects of chemotherapy. New agents that more selectively target cancer cells have been developed in attempt to improve the effects and to decrease the side effects of cancer treatment. Roscovitine is a purine analogue and cyclin-dependent kinase inhibitor. Several studies have shown its cytotoxic effect in cancer cell lines in vitro and in xenograft models in vivo. In this study, we investigated the effect of roscovitine on hematopoietic progenitors in vitro and in vivo in mice. The clonogenic capacity of hematopoietic progenitors was studied using burst-forming unit-erythroid (BFU-E), colony-forming unit granulocyte, macrophage (CFU-GM) and colony-forming unit granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM). In vitro, bone marrow cells were exposed to roscovitine (25–250 μM) in Iscove’s modified Dulbecco’s media for 4 h or to roscovitine (1–100 μM) in MethoCult media for 12 days. No effect on colony formation was observed after exposure to roscovitine for 4 h; however, concentration- and cell type-dependent effects were observed after 12 days. Roscovitine in concentration of 100 μM inhibited the growth of all types of colonies, while lower concentrations have shown differential effect on hematopoietic progenitors. The most sensitive were CFU-GEMM, followed by BFU-E and then CFU-GM. In vivo, mice were treated with single dose of roscovitine (50, 100 or 250 mg/kg) and the effect on bone marrow was studied on day 1, 3, 6, 9 or 12 after the treatment. In the second part of experiment, the mice were treated with roscovitine 350 mg/kg/day divided into two daily doses for 4 days. The bone marrow was examined on day 1 and 5 after the last dose of roscovitine. On day 1, BFU-E decreased to less than 50% of the controls (P = 0.019). No decrease in BFU-E formation was observed on day 5. No significant effect was observed on CFU-GM and CFU-GEMM growth after the treatment with multiple doses of roscovitine. Single doses of roscovitine or dimethylsulfoxide did not affect the colony formation. We also studied the distribution of roscovitine to the bone marrow after a dose of 50 mg/kg was administered intraperitoneally. Only 1.5% of the drug was detected in the bone marrow. Thus, the roscovitine effect on hematopoietic progenitors in bone marrow in vivo is only transient. One reason may be that only a small fraction of roscovitine reaches the bone marrow. Another explanation may be the short half-life observed for roscovitine that might not allow enough cell exposure to the drug. However, the toxicity of roscovitine to hematopoietic progenitors in vitro is within the same exposure range as cytotoxicity to cancer cells. Thus, precaution should be taken in clinical trials, especially when combinations with myelosuppressive cytostatics are used. Hairong Song and Marina Vita contributed equally to this work.