诺维本为主的联合方案治疗晚期乳腺癌

目的　观察以诺维本为主的联合方案治疗晚期难治性乳腺癌的疗效。方法　应用诺维本为主的联合方案治疗晚期难治性乳腺癌28例。结果　28例病人有效率为53．2％，毒副反应主要为骨髓抑制。结论　以诺维本为主的联合方案治疗晚期难治性乳腺癌的疗效较好且大多数病人均能耐受。     

Selective targeting and degradation of doxorubicin-loaded folate-functionalized DNA nanocages

Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors. Functionalized DNA nanocages are highly stable, not cytotoxic and can be efficiently loaded with the chemotherapeutic agent doxorubicin. After entry into cells, doxorubicin-loaded nanoparticles are confined in vesicular structures, indicating that DNA nanocages traffic through the endocytic pathway. Doxorubicin release from loaded DNA cages, facilitated by low pH of endocytic vesicles, induces toxic pathways that, besides selectively killing folate receptor-positive cancer cells, leads to cage degradation avoiding nanoparticles accumulation inside cells.     

A stochastic population pharmacodynamic model of QAP14 in the treatment of lung metastases of 4T1 breast cancer

Cancer metastasis is a process with multi-step complexity and apparent randomness. In this study, we aimed to establish a stochastic mathematical model to describe the random process of cancer metastasis and predict the drug effect of QAP14 on metastasis in a mouse model. The data of lung metastases on the 22^nd day after cancer cell implantation with or without the treatment of QAP14, a new chemical compound, were collected in 4T1 breast cancer BALB/c mice. Based on the exponential growth of the primary tumor and metastatic loci, a joint distribution model of metastasis size and number was developed. Disease progression of metastasis and preclinical efficacy of QAP14 were modeled. Parameters M and m representing maximum and minimum of metastasis volume were 3.24 and 0.0184 mm³, respectively. The metastasis growth rate γ and metastasis promotion time ρ were estimated and fixed to be 0.0216 d^–1 and 7.8 d, respectively. The efficacy of QAP14 acted on metastasis promotion time and metastasis growth rate constant in an exponential term, and the effect parameter Effect_ρ and Effect_γ were 16.6 and 0.327 g/mg, respectively. In the present study, we comprehensively characterized the random process of lung metastasis and efficacy of QAP14 in 4T1 breast cancer mice, which might provide a useful reference for the establishment of a clinical population model of cancer metastasis.     

CXCR4在"人源性"乳腺癌骨转移小鼠模型中的表达及其意义

目的 探讨趋化因子受体CXCR4在"人源性"乳腺癌骨转移小鼠模型转移骨中的表达对判断乳腺癌预后的价值.方法 建立"人源性"乳腺癌骨转移小鼠模型,SCID雌性小鼠50只随机分为实验组(n=30)与对照组(n=20).实验组小鼠背部皮下植入人骨,4周后将移植骨成活鼠随机均分A,B,C亚组,分别注射MD-MBA-231干细胞亚群1×105个/只,1×106个/只及MD-MBA-231人乳腺癌亲代细胞1×106个/只.D组鼠(阳性对照组,未植入人骨)注射MD-MBA-231人乳腺癌亲代细胞1×106个/只;E组鼠(阴性对照组,植人人骨)注射生理盐水.第8周处死所有小鼠,取人骨、鼠骨组织.用免疫组化及实时定量PCR法检测其中CXCR4的表达,并进行定量和相关性分析.结果 在小鼠模型中B组骨转移率最高(77.8%,P＜0.05).B组中人骨转移灶CXCR4抗原表达高于C、D组骨中的表达(P＜0.05);B组CXCR4 mRNA表达水平是C组8.4倍、D组28.4倍.结论 CXCR4的表达与乳腺癌发生、转移密切相关;推测其可作为判断乳腺癌患者一个有价值的预后指标.     

紫杉醇联合阿霉素治疗晚期乳腺癌临床观察与护理

目的观察紫杉醇联合阿霉素治疗晚期乳腺癌的效果,并探讨护理措施。方法 68例晚期乳腺癌患者随机分为观察组和对照组各34例,观察组采用紫杉醇联合阿霉素治疗,对照组采用阿霉素联合环磷酰胺治疗,观察2组疗效。结果观察组总有效率为50.0%,高于对照组的23.5%,差异有统计学意义（P〈0.05）。结论紫杉醇联合阿霉素治疗晚期乳腺癌,结合有效护理,效果明显。     

局部动脉灌注化疗在乳腺癌新辅助化疗中的应用

目的局部动脉灌注化疗(LACE)具有肿瘤局部药物浓度高、全身副作用少的特点,术前LACE可显著改变乳腺癌患者肿瘤局部病灶的组织学形态。本文旨在探讨术前LACE作为乳腺癌新辅助化疗的临床应用效果。方法对95例不同期别的乳腺癌病人手术前采用MA(FM—丝裂霉素,A—阿霉素,F—5-氟尿嘧啶)方案行LACE,对比化疗前后局部病灶形态学改变。同时比较同期10例周围静脉化疗病人的局部病灶形态学改变。结果95例行LACE乳腺癌病人组化疗前后局部病灶有效率为95.7%,周围静脉化疗病人组为40%。前者明显优于后者。结论局部动脉灌注化疗是新辅助化疗的有效方法,极具临床应用前景。     

CXCR4在乳腺癌组织中的表达及其临床意义

目的检测乳腺癌组织中趋化因子受体4(CXCR4)的表达情况,分析其与乳腺癌各临床病理学指标之间的关系,探讨CXCR4的临床意义。方法运用免疫组织化学的方法,检测了乳腺癌组织中CXCR4的表达情况。结果 CXCR4在乳腺癌组织中的阳性表达率为26.0%。乳腺癌CXCR4的表达水平与患者肿瘤的大小、组织学类型、ER、PR、Her-2/neu表达、淋巴结转移等密切相关(P<0.05)。结论乳腺癌细胞表达CXCR4可能与乳腺癌恶性生物学行为相关。CXCR4是乳腺癌诊断和治疗的分子靶点,检测CXCR4可望用于评估乳腺癌患者预后。     

乳腺癌化疗药物耐药性的机制浅析

恶性肿瘤对化疗药物产生耐药是困扰各种肿瘤治疗的共同难题,同样在乳腺癌的治疗中,这也是导致化疗失败的重要原因。化疗药物耐药性的产生涉及一系列的机制,包括药泵表达增加,βⅢ微管蛋白亚型过度表达,TopoⅡ水平下降,抑癌基因突变,解毒作用增强等。只有充分了解其相关机制,才能指导临床,合理用药,降低耐药的发生率,并有效推动基因组学的广泛应用,研发出不同作用机制的抗肿瘤药物,改善乳腺癌和其他恶性疾病的治疗现状。     

Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ~ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism.     

紫杉醇联合米托蒽醌治疗难治性晚期乳腺癌的临床研究

目的 评价紫杉醇联合米托蒽醌治疗难治性晚期乳腺癌疗效。方法 １２例晚期乳腺癌患术后复发转移,接受常规方案治疗失败后改用ＴＭｘ方案化疗：第１ｄ紫杉醇１３５ｍｇ／ｍ＾２,静脉滴注４ｈ;第２ｄ米托蒽辊８ｍｇ／ｍ＾２,静脉滴注３０ｍｉｎ。每４周重复疗程。结果 完全缓解（ＣＲ）２例（１６．７％）,部分缓解（ＰＲ）７例５８．３％。毒副反应主要有白细胞下降。结论 ＴＭｘ方案是治疗难治性晚期乳腺癌疗效较高的方案     

乳腺癌组织中HER-2的表达及其药物治疗策略

目的 探讨乳腺癌组织中HER-2的表达与患者组织学类型、TNM分期、腋窝淋巴结转移、ER和PR间的关系,及HER-2过度表达乳腺癌的药物治疗策略.方法 用免疫组织化SP法检测311例乳腺癌组织HER-2的表达.结果 1、HER-2阳性表达87例(占27.97%).2、HER-2的表达与组织学类型、TNM分期无关(P值分别为0.157和0.256).3、HER-2阳性表达与腋窝淋巴结转移、ER和PR表达降低有关(P值分别为0.032,0.014和0.026).结论 乳腺癌患者HER-2过表达提示预后不良,检测该指标可为化疗、内分泌、靶向治疗提供依据.     

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand–receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.     

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood–brain barrier (BBB) and blood–tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a “Y-shaped” peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.     

Discovery of ARF1-targeting inhibitor demethylzeylasteral as a potential agent against breast cancer

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保乳手术与全乳切除治疗T1N0期乳腺癌的疗效对比分析

目的对比分析保乳手术与全乳切除治疗T1N0期乳腺癌的临床疗效。方法将本院收治的220例T1N0期乳腺癌患者临床资料进行回顾性分析,分为对照组和治疗组,其中对照组行全乳切除手术,治疗组行保乳手术治疗。观察患者的评价外观优良率、局部复发率、生存率等指标。结果治疗组患者评价外观优良率为94.55%,而5年内局部复发率和生存率两组患者相当,无显著差异。结论早期乳腺癌患者行保乳手术治疗,在保证临床疗效的基础上保留乳房,显著提高外观优良率,是值得推广的常规术式。     

多柔比星纳米递药系统在三阴性乳腺癌靶向治疗中的应用

三阴性乳腺癌为高度恶性肿瘤。多柔比星是三阴性乳腺癌的常规化疗药物,该药药理作用是通过嵌入DNA碱基对之间,干扰基因转录,抑制mRNA和DNA合成。常规给药方式对正常组织损伤严重。多柔比星纳米递药系统借助肿瘤酸性微环境实现缓控释效应,多柔比星与肿瘤细胞的组织相容性增加,对正常组织影响较小。该系统有效抑制和杀灭肿瘤细胞,明显减轻正常细胞的细胞毒性。本文综述了近年来多柔比星靶向纳米递药系统的应用,以期开拓三阴性乳腺癌的的靶向治疗新视野。     

新辅助化疗或放疗对乳腺癌组织乳腺癌特异性基因1表达水平变化研究

目的检测乳腺癌特异性基因1（BCSG1）在放、化疗前后乳腺癌组织中mRNA的表达差异,并以此来探讨BCSG1在乳腺癌治疗中的意义。方法应用逆转录-聚合酶链反应检测40例化疗前后的乳腺癌组织以及30例放疗前后乳腺癌组织的BCSG1 mRNA表达。结果化疗组40例乳腺癌组织中有33例表达BCSG1,放疗组30例乳腺癌组织有26例BCSG1 mRNA表达,并且放疗前后和化疗前后BCSG1表达比较,差异有统计学意义（P〈0．05）。结论放疗以及化疗对乳腺癌的BCSG1 mRNA表达水平有明显的影响,BC—SG1可以作为乳腺癌治疗疗效评价指标之一。