多西他赛联合氟尿嘧啶、顺铂方案与多西他赛联合氟尿嘧啶、洛铂方案治疗胃癌的疗效比较

目的:比较多西他赛联合氟尿嘧啶、顺铂方案与多西他赛联合氟尿嘧啶、洛铂方案治疗晚期不可手术胃癌患者的疗效和不良反应。方法:回顾性分析2015年2月至2018年6月126例晚期不可手术的胃癌患者。洛铂组55例:多西他赛+氟尿嘧啶+洛铂，顺铂组71例:多西他赛+氟尿嘧啶+顺铂。洛铂组和顺铂组均21天为一个疗程，连续治疗四个疗程。结果:洛铂组患者客观有效率为50.91%，顺铂组为35.21%，差异无统计学意义（P＞0.05）。洛铂组患者疾病控制率达到83.64%，顺铂组为67.61%，差异有统计学意义（P＜0.05）。洛铂组患者在恶心、呕吐、白细胞减少和四肢麻木方面发生率明显低于顺铂组，差异有统计学意义（P＜0.05）。洛铂组患者血小板减少发生率高于顺铂组，差异有统计学意义（P＜0.05）。洛铂组患者严重不良反应的发生率为21.82%，顺铂组为39.44%，差异具有统计学意义（P＜0.05）。结论:将多西他赛联合氟尿嘧啶、顺铂方案中的顺铂以洛铂替代，取得了更好的疾病控制率，而患者的不良反应更轻，严重不良反应的发生率也更低，值得临床进一步研究。     

Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

E-钙黏蛋白在人非小细胞肺癌细胞多西他赛耐药中的作用

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)A549、H1299、H358、H441多西他赛（docetaxel，DTX）耐药细胞株与上皮间质转化（epithelial-mesenchymal transition,EMT）的关系，并初步研究逆转E-cadherin的表达对NSCLC细胞多西他赛耐药性的影响。方法:应用Real-time PCR 和Western blot 方法检测上皮间质转化相关标志物E-cadherin、Vimentin、N-cadherin、Snail在亲本细胞和多西他赛耐药细胞之间的表达差异；应用慢病毒载体介导构建稳定表达E-cadherin的NSCLC多西他赛耐药细胞；MTS法检测NSCLC细胞多西他赛耐药特性。结果:与A549、H1299、H358、H441四株亲本细胞相比，多西他赛耐药细胞（A549DTX，H1299DTX，H358DTX，H441DTX）形态呈长梭形，呈上皮间质转化（EMT）样改变。多西他赛耐药细胞中E-cadherin表达下调，Vimentin、N-cadherin、Snail表达上调。成功构建了过表达E-cadherin的NSCLC多西他赛耐药细胞。过表达E-cadherin细胞株细胞形态与空载对照细胞株以及亲本耐药细胞株相比呈间质上皮转化(MET)样改变。MTS结果显示四种不同E-cadherin过表达的NSCLC多西他赛耐药细胞对多西他赛的敏感性均强于其亲本耐药细胞和空载对照细胞。结论:NSCLC多西他赛耐药细胞发生EMT样改变，上调E-cadherin能增加NSCLC多西他赛耐药细胞对多西他赛的敏感性。     

恩度联合多西他赛序贯腹腔灌注治疗胃癌伴恶性腹水的临床观察

目的:回顾性分析恩度联合多西他赛序贯腹腔灌注治疗胃癌伴恶性腹水的疗效及不良反应。方法:收集72例胃癌伴腹水患者，曾接受过二线及以上方案化疗，观察组35例，采用恩度45 mg联合多西他赛35 mg/m2 d1，d5序贯腹腔灌注1周期；对照组37例，采用多西他赛35 mg/m2 d1，d5腹腔灌注1周期，统计患者腹水控制有效率、KPS改善率、腹水控制时间及不良反应。结果:治疗组中腹水控制有效率71.43%；对照组中腹水控制有效率48.65%，P=0.049，两组具有统计学差异；治疗组中KPS改善率77.14%，对照组中KPS改善率54.05%，P=0.04，两组具有统计学差异；观察组中腹水控制时间8~90天，中位控制时间44天，对照组中腹水控制时间5~66天，中位控制时间28天，两组控制时间比较，P=0.048，具有统计学差异；III级以上不良反应发生率低，无治疗相关性死亡，两组不良反应比较，P>0.05，无统计学差异。结论:恩度联合多西他赛序贯腹腔灌注治疗体力状况（performance status,PS）评分较差的胃癌伴恶性腹水患者，腹水控制较好，能明显提高患者生活质量，未见明显不良反应。     

Preoperative intra-arterial chemotherapy with docetaxel,cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma

The objectives of this study were to evaluate survival in 141 patients with stage II–IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.     

TH1902, a new docetaxel-peptide conjugate for the treatment of sortilin-positive triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of cancers which lacks the expression and/or amplification of targetable biomarkers (ie, estrogen receptor, progestrogen receptor, and human epidermal growth factor receptor 2), and is often associated with the worse disease-specific outcomes than other breast cancer subtypes. Here, we report that high expression of the sortilin (SORT1) receptor correlates with the decreased survival in TNBC patients, and more importantly in those bearing lymph node metastases. By exploiting SORT1 function in ligand internalization, a new anticancer treatment strategy was designed to target SORT1-positive TNBC-derived cells both in vitro and in two in vivo tumor xenografts models. A peptide (TH19P01), which requires SORT1 for internalization and to which many anticancer drugs could be conjugated, was developed. In vitro, while the TH19P01 peptide itself did not exert any antiproliferative or apoptotic effects, the docetaxel-TH19P01 conjugate (TH1902) exerted potent antiproliferative and antimigratory activities when tested on TNBC-derived MDA-MB-231 cells. TH1902 triggered faster and more potent apoptotic cell death than did unconjugated docetaxel. The apoptotic and antimigratory effects of TH1902 were both reversed by two SORT1 ligands, neurotensin and progranulin, and on siRNA-mediated silencing of SORT1. TH1902 also altered microtubule polymerization and triggered the downregulation of the anti-apoptotic Bcl-xL biomarker. In vivo, both i.p. and i.v. administrations of TH1902 led to greater tumor regression in two MDA-MB-231 and HCC-70 murine xenograft models than did docetaxel, without inducing neutropenia. Altogether, the data demonstrates the high in vivo efficacy and safety of TH1902 against TNBC through a SORT1 receptor-mediated mechanism. This property allows for selective treatment of SORT1-positive TNBC and makes TH1902 a promising avenue for personalized therapy with the potential of improving the therapeutic window of cytotoxic anticancer drugs such as docetaxel.     

Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.     

阿帕替尼治疗晚期非小细胞肺癌疗效与安全性的Meta分析

目的 系统评价阿帕替尼对比紫杉醇/多西他赛治疗晚期非小细胞肺癌（NSCLC）的疗效与安全性,为临床用药提供参考。方法 计算机检索从建库至2019年8月中国知网、维普网、万方数据库、PubMed及Cochrane Library数据库,对符合纳入标准的随机对照试验进行质量评价,用RevMan 5.3软件进行Meta分析。结果 共纳入9篇文献,均为随机对照试验,合计637例患者。Meta分析结果显示：阿帕替尼组客观缓解率高于紫杉醇/多西他赛组［O=1.77（95% CI：1.15,2.72）］,疾病控制率高于紫杉醇/多西他赛组［O=2.15（95% CI：1.42,3.24）］,KPS评分高于紫杉醇组［均数差=6.84（95% CI：4.84,8.84）］,骨髓抑制发生情况低于紫杉醇/多西他赛组［R=0.39（95% CI：0.26,0.57）］,胃肠道不良反应发生情况低于紫杉醇/多西他赛组［R=0.50（95% CI：0.33,0.76）］。结论 阿帕替尼对比紫杉醇/多西他赛治疗晚期NSCLC能提高客观缓解率及疾病控制率,健康状况和生活质量更佳,骨髓抑制及胃肠道不良反应发生率较低。     

醋酸阿比特龙联合强的松治疗去势抵抗型前列腺癌的疗效分析

目的 分析去势抵抗型前列腺癌(castration resistant prostate cancer,CRPC)患者接受醋酸阿比特龙(abiraterone acetate,AA)联合强的松(prednisone,P)治疗的疗效及安全性,为后续治疗提供经验。方法 筛选2018年7月至2021年4月首都医科大学附属北京朝阳医院泌尿外科共计46例CRPC患者,选择使用AA+P治疗,最后共计37例患者纳入研究。分析37例患者的基本资料,参照前列腺特异抗原(prostate specific antigen,PSA)工作组2(PSA Working Group 2, PSAWG2)标准计算PSA缓解率,按照实体瘤的疗效评价(response evaluation criteria in solid tumors,RECIST)标准评估患者治疗期间的影像学结果,同时分析行多西他赛化疗、PSA闪烁现象以及基线PSA水平、肿瘤T分期、Gleason评分等指标对AA+P治疗的PSA缓解率的影响差异。结果 37例CRPC患者接受AA+P治疗,中位随访时间9.7个月。在接受AA+P初始,有5例患者发生了PSA闪烁现象,其PSA达峰再次下降至基线水平以下的中位时间为3.0(2.0,4.5)个月。37例患者PSA总体缓解率为59.5%,其中13例患者达到缓解后又发生了PSA复发,其中位复发时间为7.0个月。参照RECIST标准,37例CRPC患者中,有7例患者发生了影像学进展,而5例有明确的影像学缓解。6例达到PSA缓解后出现复发的患者将强的松转换为地塞米松,其中2例PSA再次缓解,PSA缓解率为33.3%。化疗失败后接受AA+P的患者PSA缓解低于未行化疗的患者(20.0% vs 65.6%,P=0.076)。此外,有PSA闪烁现象的PSA缓解率低于无此现象的患者(20.0% vs 65.6%,P=0.076)。醋酸阿比特龙的总体耐受性较好,药物不良反应少。结论 CRPC患者口服醋酸阿比特龙联合强的松疗效确切,安全性高,对于不愿意选择或不能耐受化疗的患者,有较高的PSA缓解率。PSA闪烁现象在AA治疗过程中并不少见,这部分患者达到PSA缓解的比例较低。PSA缓解后的中位复发时间为7.0个月,部分PSA进展患者用地塞米松替换强的松可重新达到PSA缓解,可恢复对阿比特龙治疗的敏感性。