剂量密集型蒽环序贯紫杉醇脂质体与蒽环序贯多西紫杉醇在局部晚期HER-2阴性乳腺癌新辅助化疗中的疗效及安全性比较

摘   要 背景与目的：剂量密集型的新辅助化疗在局部晚期乳腺癌中使用越来越广泛。但在剂量密集型的新辅助化疗方案中,使用紫杉醇脂质体的研究较少。本研究探讨剂量密集型蒽环序贯紫杉醇脂质体对比蒽环序贯多西紫杉醇在局部晚期HER-2阴性乳腺癌新辅助化疗中的安全性和疗效。 方法：回顾性分析2017年1月—2018年12月可手术的局部晚期HER-2阴性的女性乳腺癌患者资料。该研究人群均行8周期新辅助化疗,其中196例采用蒽环序贯多西紫杉醇方案（多西紫杉醇组）,48例采用剂量密集型蒽环序贯紫杉醇脂质体方案（紫杉醇脂质体组）。采用倾向性评分匹配（PSM）方法,按照1:1匹配两组基线特征差异后,比较两组患者病理完全缓解（pCR）与临床疗效情况以及不良事件发生率。 结果：通过1:1 PSM匹配后,两组各48例患者。两组间pCR率无统计学意义（22.9% vs. 18.8%,P>0.05）;多西紫杉醇组客观缓解率（ORR）93.7%、疾病控制率（DCR）100.0%,紫杉醇脂质体组ORR与DCR均为100.0%,组间差异无统计学意义（P>0.05）。多西紫杉醇组III~IV度白细胞及中性粒细胞减少症的发生率以及III~IV度恶心、呕吐、乏力和口腔黏膜炎发生率均高于紫杉醇脂质体化疗组（均P<0.05）,两组其他毒副反应的发生率比较,均无统计学意义（均P>0.05）。 结论：在局部晚期HER-2阴性乳腺癌新辅助化疗中,蒽环序贯多西紫杉醇与剂量密集型蒽环序贯紫杉醇脂质体的疗效相当。紫杉醇脂质体化疗组毒副反应明显优于多西紫杉醇化疗组。紫杉醇脂质体可作为HER-2阴性乳腺癌新辅助化疗方案中紫杉醇类药物的优选。     

十全大补汤对结直肠癌术后化疗患者减毒增效及免疫功能的影响

目的:探讨十全大补汤对结直肠癌术后化疗患者减毒增效及免疫功能的影响。方法:选取2015年2月至2016年3月洛阳市第二中医院收治的结直肠癌患者98例,随机分为对照组(n=49)与观察组(n=49)。对照组患者采用FOLFOX4化疗方案进行化疗,观察组在对照组基础上应用十全大补汤治疗。比较2组治疗前后临床症状、外周血T淋巴细胞亚群(CD3~+、CD4~+、CD8~+)的变化及不良反应,并评价2组临床疗效。结果:观察组治疗有效率为81.63%(40/49),高于对照组61.22%(30/49),差异有统计学意义(P0.05);治疗后观察组CD3~+、CD4~+均上升,中医症候积分均下降,且观察组上述观察指标均优于对照组,差异有统计学意义(P0.05);观察组白细胞减少、胃肠道不适、脱发、恶心呕吐发生率均低于对照组,差异有统计学意义(P0.05)。结论:对结直肠癌术后化疗患者采用十全大补汤,可显著提高临床疗效,缓解临床症状,减少化疗所致的不良反应,增强患者免疫功能,促进身体恢复,具有临床推广意义。     

Decision of adjuvant chemotherapy in intermediate risk luminal breast cancer patients: A prospective multicenter trial assessing the clinical and psychological impact of EndoPredict® (EpClin) use (UCBG 2–14)

PurposeGenomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in “intermediate” clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients.MethodsThis multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes.ResultsOne third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2–42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2–34.8]) and added in 15 (7.5% [3.8–11.2]. 6 changes (8%) were based on patients’ decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p < 10⁻⁷ and 0.00022 respectively), while stable in other situations. At 1-year, all patients had returned to the baseline anxiety and distress levels (mean anxiety 51.5, +/− SD = 2.5 [max. 80], mean distress 3±1 [max. 10]).ConclusionsEndoPredict ® (EpClin) is clinically useful in deciding whether or not to administer adjuvant chemotherapy in patients with intermediate risk. A single-step decision is preferable since adding chemotherapy at a later stage increases anxiety and distress.     

多西他赛联合内分泌疗法治疗转移性激素敏感性前列腺癌的疗效研究

目的探讨多西他赛联合内分泌疗法治疗转移性激素敏感性前列腺癌的临床疗效。方法回顾性分析长海医院2004年1月至2018年7月收治的497例转移性激素敏感性前列腺癌患者的病例资料。患者确诊年龄为(72.1±8.7)岁。治疗前中位PSA为100.0(42.3~999.0)ng/ml。TNM临床分期分别为:T2期213例(42.9%)、T3期160例(32.2%)、T4期124例(24.9%);N0期319例(64.2%)、N1期144例(29.0%)、Nx期34例(6.8%);M0期100例(20.1%)、M1a期51例(10.3%)、M1b期332例(66.8%),M1c期9例(1.8%)、Mx期5例(1.0%)。穿刺Gleason评分≤7分146例(29.4%)、8分103例(20.7%)、≥9分248例(49.9%)。根据治疗方式分为2组,采用单独内分泌治疗(单独治疗组)459例,多西他赛联合内分泌治疗(联合治疗组)38例。采用倾向评分匹配方法,卡钳值设置为0.02,对两组数据实行1∶1匹配。共37对匹配成功,匹配后两组的年龄(P=0.102)、PSA(P=0.713)、T分期(P=0.113)、N分期(P=0.226)、M分期(P=0.514)、Gleason评分(P=0.612)、肿瘤负荷(P=0.812)比较差异均无统计学意义。采用log-rank和Breslow-wilcoxon检验比较两组的无进展生存期和肿瘤特异性生存期。绘制两组患者年龄、临床TNM分期、Gleason评分、肿瘤负荷及是否接受过姑息性电切手术等各亚组生存情况的森林图,并针对高肿瘤负荷亚组比较两组间的无进展生存期差异。结果匹配后单独治疗组和联合治疗组的中位随访时间分别为22.6个月和13.7个月;发生去势抵抗的患者例数分别为23例和17例;死亡患者例数分别为3例和6例。单独治疗组和联合治疗组患者进展为去势抵抗的中位时间差异无统计学意义(10.3个月与16.5个月,P>0.05);平均前列腺癌特异性生存期分别为21.9个月和14.8个月,但均未达到中位生存期,且差异无统计学意义(P>0.05)。高肿瘤负荷亚组中,联合治疗组的中位无进展生存期明显优于单独治疗组(10.6个月与7.2个月,P=0.044),但低肿瘤负荷亚组中两组平均无进展生存期分别为10.5个月和12.6个月,均未达到中位生存期,且差异无统计学意义(P>0.05)。结论多西他赛联合内分泌治疗可以延长高肿瘤负荷激素敏感性前列腺癌患者的无进展生存期,但低肿瘤负荷患者无明显获益。     

miR-24对肺癌A549细胞化疗敏感性的影响

目的:探究微小RNA(miR)-24对肺癌细胞A549化疗敏感性的影响及可能的作用机制。方法:Real-time PCR实验检测肺腺癌细胞系A549及肺腺癌耐药细胞株A549/DDP中miR-24的表达情况。转染miR-24抑制序列(miR-24 inhibitor)下调A549/DDP细胞中的miR-24后,采用CCK-8法检测细胞活力,流式细胞术检测细胞凋亡,Western blot检测Bcl-2、Bax、cleaved caspase-3、cleaved caspase-9、细胞色素C(Cyt C)、磷酸化细胞外信号调节激酶(p-ERK)和P53的蛋白水平。双荧光素酶报告基因实验预测及验证miR-24可能的靶基因。结果:耐药细胞株A549/DDP中miR-24的表达水平明显高于A549细胞(P0.05)。miR-24 inhibitor可诱导肺腺癌耐药细胞株A549/DDP的凋亡,增加细胞对顺铂的敏感性;此外还可下调Bcl-2/Bax比值,同时上调P53、p-ERK、cleaved caspase-9、cleaved caspase-3及Cyt C的蛋白水平。而应用ERK特异性抑制剂U0126可部分恢复miR-24 inhibitor转染的细胞活力。生物信息学分析显示p53是miR-24的可能作用靶点基因,在A549/DDP细胞中共转染miR-24 inhibitor和P53 siRNA可部分逆转miR-24 inhibitor对细胞活力的影响。结论:下调肺腺癌耐药细胞株A549/DDP中miR-24的表达可增加细胞对顺铂的敏感性,其机制可能与靶向p53基因同时激活ERK/P53信号通路后促进细胞经线粒体途径的凋亡有关。     

Knockdown of PINCH-1 protein sensitizes the estrogen positive breast cancer cells to chemotherapy induced apoptosis

Introduction

PINCH-1 is a ubiquitously expressed protein belonging to the focal adhesion protein group which has a role in cell survival, spreading, adhesion and migration. It has been implicated in pathogenesis of several cancers. In the present study we aimed to investigate the role of this protein in estrogen positive and negative breast cancer subtypes.

A double-blind,crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy

Background Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. Patients and methods In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 μg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1–23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 μg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. Results Patients in the granisetron 10 and 40 μg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. Conclusion We conclude that granisetron 10 and 40 μg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.