多西他赛和表柔比星联合用于乳腺癌化疗的用药顺序对疗效的影响

目的 探讨在乳腺癌新辅助治疗中多西他赛和表柔比星联用时的用药顺序对化疗效果的影响。方法 回顾性分析2010—2014年我院先使用表柔比星再使用多西他赛(对照组,34例)及先使用多西他赛后使用表柔比星(观察组,58例)的乳腺癌病历,评价行3个疗程后的近期疗效。结果 对照组近期有效率61.76%,生存获益85.29%;观察组近期有效率74.13%,生存获益91.37%。结论 临床在乳腺癌的新辅助治疗过程中,宜采用先使用紫杉烷类药物后使用蒽环类药物的给药次序。     

表柔比星诱导小鼠药物心肌病模型的建立及清醒状态下超声评价该模型的研究

目的建立表柔比星诱导的小鼠心肌病模型并探讨高频率超声心动图对其检测的可行性。方法按电脑随机数字表法随机将70只小鼠分为对照组和给药组各35只．两组各以第3、4、5天为超声检测时间点。给药组腹腔注射10mg／kg表柔比星,对照组注射同容量0．9％氯化钠溶液。每天监测心率,第3、4、5天超声心动图测量左心室舒张末期内径、收缩末期内径（LVEDD、LVESD）、左心室短轴缩短率（FS）、每分钟心输出量（CO）。第5天处死小鼠,取心肌组织行心肌病理学评价。结果与对照组相比,给药组小鼠心率呈下降趋势,第4天、第5天心率显著下降,差异有统计学意义（P〈0．05）。与基础状态比较,给药组小鼠第4天每分钟心输出量明显下降,差异有统计学意义[（11．8±2．7）mL／minm（7．6±2．2）mL／min,P〈0．05];第5天左心室舒张末期内径减少（P〈0．01）而左心室收缩末期内径无明显变化;第5天左心室短轴缩短率明显下降,差异有统计学意义（P〈0．05）。第5天给药组小鼠组织学评分中位数为2．5。与对照组相比,第5天小鼠心脏重量明显减轻,差异有统计学意义（P〈0．05）。第5天电镜检查显示给药组小鼠心肌细胞内水肿、线粒体肿胀、部分肌纤维断裂。结论通过腹腔注射表柔比星,短时间内能在小鼠诱导出药物心肌病模型。小鼠清醒状态下高频率超声能成功评价该模型。     

Tamoxifen induces resistance to activated protein C

Introduction

The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.

Materials and Methods

Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.

Results

APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.

Conclusions

This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors.     

生脉注射液对乳腺癌表柔比星多程化疗心脏毒性的作用

目的探析生脉注射液对乳腺癌表柔比星多程化疗心脏毒性的作用。方法选取2015年1月至2019年8月在我院接受化疗的60例乳腺癌患者,将其随机分为对照组(n=30)与观察组(n=30)。对照组患者给予AC方案(表柔比星+多西他赛)化疗,观察组患者在对照组基础上给予生脉注射液。比较两组患者临床疗效、心电图异常率、心肌酶谱指标及不良反应发生情况。结果对照组临床总缓解率为33.33%,观察组为53.33%,两组临床总缓解率比较,差异无统计学意义(P>0.05)。对照组心电图异常率为30.00%,观察组为16.67%,两组心电图异常率比较,差异无统计学意义(P>0.05)。治疗后,对照组CK、CKMB、cTnT水平显著升高,观察组cTnT水平显著升高,且观察组CK、CKMB、cTnT水平显著低于对照组(P<0.05)。观察组不良反应总发生率为16.67%,显著低于对照组的46.67%(P<0.05)。结论在乳腺癌表柔比星多程化疗中应用生脉注射液,能够显著减轻心脏毒性,且不良反应发生率较低,值得临床进一步应用与借鉴。     

活性炭-表阿霉素混悬液对乳腺癌腋窝淋巴结转移的治疗作用

目的评价活性炭微粒-表阿霉素(Epi-CH)混悬液对乳腺癌腋窝淋巴结清扫和转移灶化疗的改进作用。方法60例II-III期乳腺癌病人随机分为两组,治疗组40例术前72h于瘤床或肿瘤周围腺体注射Epi-CH混悬液10mg,对照组20例注射表阿霉素水溶液10mg,术后清点腋窝淋巴结总数和黑染淋巴结数并计算腋窝淋巴结清除率。用高效液相色谱法检测治疗组黑染和未黑染淋巴结中表阿霉素的含量。光镜观察淋巴结组织变性坏死改变。结果治疗组平均每例清除淋巴结比对照组多4.04个(P<0.01)。治疗组中腋窝淋巴结的黑染率为86.9%(565/650);直径≤1.0cm淋巴结黑染率明显高于直径﹥1.0cm淋巴结黑染率(P<0.01);黑染淋巴结癌转移率与未黑染淋巴结转移率无显著性差异(P>0.05)。治疗组黑染淋巴结中表阿霉素的含量是未黑染淋巴结含量的14.3倍(P<0.01)。黑染淋巴结内癌细胞有明显的变性坏死改变。结论Epi-CH混悬液能增加手术清除的腋淋巴结数目,显著增加并维持表阿霉素在局部淋巴结中的高浓度。     

Changes in Cellular Immunity during Chemotherapy for Primary Breast Cancer with Anthracycline Regimens

Abstract

Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3+CD4+), T-cytotoxic cells (CD3+CD8+), B-cells (CD19+CD20+) and NK cells (CD16+/CD56+CD3-) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.     

Small Cell Bronchogenic Carcinoma: a Cyclical Alternating Combination of Epirubicin plus Cisplatin and Cyclophosphamide plus Etoposide

Summary

Forty-seven patients with advanced small-cell bronchogenic carcinoma (SCLC) were treated with a combination of epirubicin (4-EPIDX) (60 mg/m² i.v.) and cisplatin (CDDP) (50 mg/m² i.v.) on day 1, alternated with cyclophosphamide (CTX) (800 mg/m² i.v.) day 1 and etoposide (VP16) (120 mg/m² i.v.) on days 21-23. Four patients (9%) obtained a complete remission and 27 (57%) a partial remission with an overall remission rate of 66%. The median duration of response was 37 weeks (range 13-150) and the median duration of survival was 43 weeks (range 10-150). No severe bone marrow depression was noted. The other side-effects were of a mild grade.