多西他赛对乳腺癌患者糖代谢的影响

目的 探讨多西他赛对乳腺癌患者糖代谢的影响.方法 124例经术后病理证实的女性乳腺癌患者术后均接受含多西他赛方案化疗,化疗前均已排除血糖异常及糖尿病,观察每周期化疗前后血糖及糖化血红蛋白变化.结果 全部124例患者均按计划完成6周期化疗.化疗后有11例(8.87％)空腹血糖升高,24例(19.35％)糖耐量减低;其中诊断为2型糖尿病者8例(6.45％),一过性血糖增高5例(4.03％).结论 乳腺癌接受含多西他赛方案化疗后可能引起血糖增高、糖耐量减低,甚至2型糖尿病,化疗期间应密切监测血糖及糖化血红蛋白水平,及时干预治疗.     

miR-374过表达增强人乳腺癌细胞对多西他赛的耐药性

目的:观察miR-374过表达对人乳腺癌MDA-MB-231细胞docetaxel(多西他赛)耐药性的影响。方法:qPCR检测miR-374过表达细胞MDA-MB-231-miR-374和对照细胞MDA-MB-231-Cherry中miR-374的相对含量;采用不同浓度的多西他赛处理细胞72小时后,MTT检测细胞的活性。在终浓度为3.2nmol/L的多西他赛处理下,用平板克隆实验检测MDA-MB-231-Cherry和MDA-MB-231-miR-374细胞的增殖能力。流式细胞术检测细胞周期和凋亡。结果:与MDA-MB-231-Cherry细胞相比,miR-374过表达细胞MDA-MB-231-miR-374中miR-374的相对表达量明显增高;MDA-MB-231-miR-374细胞的耐药性和克隆形成能力明显增强(P<0.05)。细胞凋亡率明显降低,G0/G1期细胞减少,S期细胞增加,G2/M期细胞增加。结论:miR-374过表达可明显增强乳腺癌细胞株MDA-MB-231对多西他赛的耐药性。     

miR-221增强乳腺癌细胞对多西他赛的耐药性

目的:探究miR-221在人乳腺癌细胞T47D和MCF-7多西他赛(docetaxel)耐药性中的作用及机制。方法:qPCR检测多西他赛处理乳腺癌细胞T47D和MCF-7不同时间点,细胞中miR-221含量的变化;qPCR和Western blot检测miR-221 mimics的转染效率。用阴性对照（NC）或miR-221 mimics转染细胞,不同浓度的多西他赛刺激细胞72小时后,MTT法检测细胞对多西他赛的耐药性;PI和Annexin V双染法检测miR-221 过表达对T47D和MCF-7细胞凋亡的影响;qPCR和Western blot检测靶蛋白p27的表达。结果:在T47D和MCD-7中多西他赛刺激明显促进miR-221的表达量升高;miR-221在细胞内可以发挥生物学效应,降低靶蛋白p27的表达;且过表达miR-221明显增强T47D和MCF-7对多西他赛的耐药性,降低其凋亡率。结论:miR-221过表达可明显增强T47D和MCF-7细胞对多西他赛的耐药性。     

多西他赛对复发转移性乳腺癌免疫功能的影响

目的：探讨多西他赛化疗前、化疗2周期评价疗效时复发转移性乳腺癌（MBC）患者外周血淋巴细胞亚群比率的变化及影响因素。方法应用流式细胞仪检测34例行多西他赛一线化疗的复发MBC患者化疗前、化疗2周期评价疗效时外周血淋巴细胞亚群[CD3+T淋巴细胞、CD3+/CD4+T淋巴细胞、CD3+/CD8+T淋巴细胞、CD3－/CD16+56+自然杀伤细胞（NK）、CD3+/CD16+56+T淋巴细胞、CD19+B淋巴细胞、CD4+/CD25+调节性T细胞（Treg细胞）、CD8+/CD28－T淋巴细胞和CD8+/CD28+T淋巴细胞]比率,并进一步分析患者临床病理因素对于外周血淋巴细胞亚群变化的影响。结果34例患者化疗后CD3+总T淋巴细胞、CD3+/CD4+T淋巴细胞及CD19+B淋巴细胞比率均较化疗前下降（P=0.002、0.044、0.006）,下降平均比率分别为2.2%、4.7%、3.1%。中位年龄﹥54岁的患者CD19+B淋巴细胞下降比率较中位年龄≤54岁的患者小（P=0.031）;中位OS﹥3.6个月的患者CD3+总T淋巴细胞下降比率较中位OS≤33.6个月的患者小（P=0.038）。结论多西他赛化疗后MBC患者外周血总T、B淋巴细胞比率下降,免疫功能降低,而相对保留较好的T淋巴细胞免疫功能的患者可能有更好的生存获益。     

吡柔比星和环磷酰胺联合多西他赛对乳腺癌的临床疗效观察

目的探讨吡柔比星和环磷酰胺联合多西他赛对进展期乳腺癌的临床疗效。方法Ⅱ~Ⅲ期择期手术乳腺癌患者116例,随机分为两组,每组58例。TAC组采用吡柔比星和环磷酰胺联合多西他赛治疗方案,CAF组采用吡柔比星和环磷酰胺联合氟尿嘧啶治疗方案,对比分析两组患者的临床疗效和不良反应。结果化疗结束后,与CAF组相比,TAC组患者的KPS得分、病理完全缓解率和总有效率有统计学意义(P<0.05)。TAC组和CAF组的腋窝淋巴结转阴率分别为35.6%和22.7%,差异有统计学意义(P<0.05)。不良反应中,两组白细胞减少率、粒细胞减少率、脱发发生率比较,差异均有统计学意义(P<0.05);而血小板减少率、恶心呕吐发生率、心脏毒性发生率比较,差异均无统计学意义(P>0.05)。结论 TAC方案可作为乳腺癌手术患者的新辅助化疗方案,疗效较好。     

miR-520a-3p靶向ABCG2增强乳腺癌细胞对多西他赛敏感性的机制研究

目的:研究miR-520a-3p对乳腺癌细胞多西他赛敏感性的影响,并探索潜在的分子机制。方法:收集2015年4月至2017年10月在我院乳腺外科确诊的45例乳腺癌标本,实时荧光定量PCR法检测乳腺癌组织中miR-520a-3p的表达水平。分析miR-520a-3p与乳腺癌化疗耐受和肿瘤生物学特征的相关性。采用实时荧光定量PCR检测乳腺癌细胞MCF-7、MCF-7/Doc和MDA-MB-231中miR-520a-3p和三磷酸腺苷结合盒转运蛋白（ABCG2）mRNA的表达,采用蛋白质免疫印迹实验检测ABCG2的表达。转染miR-520a-3p mimic后,采用细胞毒性实验观察乳腺癌细胞对多西他赛敏感性的变化。采用实时荧光定量PCR和蛋白质免疫印迹实验观察miR-520a-3p升高后,ABCG2 mRNA和蛋白的表达变化。进一步采用双荧光素酶活性实验验证miR-520a-3p对ABCG2的靶向作用。结果:化疗耐药组新辅助化疗后肿瘤原发部位的miR-520a-3p表达水平明显降低（P＜0.05）,同时相关性分析发现,miR-520a-3p低表达与高TNM分期（III期）和淋巴结转移相关（P＜0.05）。miR-520a-3p在MCF-7/Doc和MDA-MB-231细胞中表达较在MCF-7细胞中下降（P＜0.05）,而ABCG2的表达水平则明显升高（P均<0.05）。上调miR-520a-3p后,MCF-7和MCF-7/Doc细胞对多西他赛的敏感性增强（P＜0.05）,而ABCG2在mRNA和蛋白水平的表达均下降（P＜0.05）。双荧光素酶报告基因结果则证实ABCG2是miR-520a-3p的靶基因。结论:miR-520a-3p可逆转MCF-7/Doc对多西他赛的耐药性,这一作用可能与负调控肿瘤耐药相关蛋白ABCG2的表达从而抑制药物外排有关。     

国产多西他赛为主的联合化疗治疗转移性乳腺癌

 目的 观察国产多西他赛为主的联合化疗治疗转移性乳腺癌的疗效、毒副反应和临床受益反应（Clinical　benefit　response，CBR），并以进口多西他赛作对照。方法 A组30例转移性乳腺癌患者，既往未采用蒽环类药物治疗的14例采用国产多西他赛联合阿霉素治疗（A1组），既往蒽环类药物治疗失败的16例采用国产多西他赛联合卡培他滨治疗（A2组）；B组25例转移性乳腺癌患者作对照，其中未采用蒽环类药物治疗的11例采用进口多西他赛联合阿霉素治疗（BI组），既往蒽环类药物治疗失败的14例采用进口多西他赛联合卡培他滨治疗（B2组）；3周为1个周期，2周期评价疗效，记录毒副反应。结果 A组有效率（CR＋PR）66．7％，肿瘤控制率（CR＋PR＋SD）93．3％。毒副反应主要为骨髓抑制和脱发，可耐受，无治疗相关性死亡。CBR评价有效者73．3％；B组有效率68％，肿瘤控制率92％。毒副反应与A组相似。CBR评价有效者72％。结论 国产多西他赛为主的联合化疗治疗转移性乳腺癌有较好的疗效，毒副反应可耐受，临床受益反应良好，与进口多西他赛的疗效和不良反应相似。     

多西他赛联合表阿霉素治疗乳腺癌的疗效观察

目的 探讨多西他赛联合表阿霉素治疗乳腺癌的临床疗效和毒副反应.方法 将60例乳腺癌患者随机分为观察组和对照组,每组30例.观察组给予多西他赛联合表阿霉素治疗,对照组给予表阿霉素治疗,比较观察2组患者的临床疗效和毒副反应.结果 观察组和对照组的总有效率分别为96.67％和76.67％,观察组疗效明显优于对照组(P＜0.05);主要毒副反应为骨髓抑制、消化道反应,观察组发生率明显低于对照组(P＜0.05).结论 多西他赛联合表阿霉素治疗乳腺癌疗效显著,毒副反应可耐受.     

多西他赛为主的联合方案治疗晚期乳腺癌临床研究

目的观察多西他赛为主的联合化疗方案治疗晚期乳腺癌的疗效及毒副反应。方法共有46例晚期乳腺癌病人接受治疗。初次化疗者及既往未使用过葸环类者24例,接受多西他赛加吡柔吡星方案化疗,吡柔吡星40mg／m^2,静脉冲入,d1,多西他赛75mg／m^2,静脉滴注1h,d2;既往使用过葸环类治疗失败者22例,接受多西他赛加顺铂方案化疗,多西他赛75mg／m^2,静脉滴注1h,d1,顺铂25-30mg／m^2,静脉滴注,d2-d5。至少化疗2个周期以后评价疗效,按WHO标准进行评价。结果46例CR3例,PR21例,SD13例,PD9例,有效率52．2％（24／46）,毒性反应主要为骨髓抑制和脱发。结论多西他赛为主化疗方案治疗晚期乳腺癌疗效确切,毒性反应能耐受。     

多西他赛治疗晚期乳腺癌的临床研究

目的 观察国产多西他赛注射液对一线治疗后失败的晚期乳腺癌患者的临床疗效及毒副反应,并对安全性进行评估。方法 以国产多西他赛对44例既往治疗后进展的乳腺癌患者进行70mg／m^2静脉滴注,每3周1次,单药治疗。试验中不预防使用粒细胞集落刺激因子。用世界卫生组织（WHO）的疗效及抗肿瘤药急性及亚急性毒性反应分度标准评价疗效及毒性,用卡式评分评价身体状况变化。结果 在41例可评价疗效的患者中,4例达到完全缓解,14例部分缓解,有效率达43．9％,临床获益率85．4％。不良反应主要表现为Ⅲ、Ⅳ度白细胞下降（42．9％）、脱发（7．1％）和消化道反应（4．8％）。未出现水钠潴留。结论 使用多西他赛注射液治疗化疗后进展的晚期乳腺癌患者,疗效显著,耐受性良好,可作为该类患者的治疗选择。     

miR-204对乳腺癌MCF-7细胞增殖及凋亡的影响

目的 探讨miR-204在人乳腺癌组织及MCF-7细胞中的表达水平及其对乳腺癌细胞增殖及凋亡的影响。方法 提取癌症和肿瘤基因组图谱（the cancer genome atlas,TCGA）数据库中浸润性乳腺癌的miR-204相关数据进行汇总,转染miR-204过表达病毒,筛选稳定转染细胞株并通过RT-qPCR检测转染率,MTT法检测过表达miR-204后乳腺癌MCF-7细胞的增殖情况,流式细胞仪检测细胞凋亡情况。 结果 miR-204在浸润性乳腺癌组织中的表达水平较癌旁组织明显下调（P＜0.001）,且与淋巴结转移和远处转移相关（P＜0.05）。过表达miR-204能够抑制乳腺癌MCF-7细胞的增殖能力（P＜0.05）;miR-204上调后,细胞凋亡率达到（34.7±1.9）%,细胞凋亡能力明显增强（P＜0.001）。结论 miR-204可抑制乳腺癌细胞增殖并介导细胞凋亡。     

miR-203a通过靶向抑制CDK6调控膀胱癌细胞增殖及放射敏感性

目的:探讨miR-203a在膀胱癌(BC)细胞系(RT-112、T24、5637、UM-UC-3细胞)中的表达及对细胞增殖及放射敏感性的影响。方法:将miR-203a mimics、miR-203a inhibitor、CDK6 siRNA、CDK6表达质粒及相应阴性对照(NC)转染入BC细胞中。实时荧光定量PCR检测...     

MiR-144 suppresses proliferation,invasion, and migration of breast cancer cells through inhibiting CEP55

Objective: The study aimed to investigate the molecular mechanism of miR-144 and CEP55 as well as the influence of their interaction on the cell proliferation, migration, invasion, cell cycle and cell apoptosis in breast cancer.

Methods: In this study, The Cancer Genome Atlas (TCGA, https://tcga-data.nci.nih.gov/) database was used for microarray analysis. The expressions of miR-144 and CEP55 in 40 adjacent tissues and 36 tumor tissues were examined by western blot, qRT-PCR and immunohistochemistry. The target relationship between miR-144 and CEP55 was predicted and confirmed by TargetScan and luciferase reporter assay. The cell proliferation, cell cycle and cell apoptosis in different groups were detected by MTT and flow cytometry assays, while wound healing and transwell assays were used for the cell migration and invasion tests. The regulatory effects of miR-144 and CEP55 on breast tumor were verified through nude mouse model in vivo experiment.

Results: MiR-144 was down-regulated in breast cancerous tissues and cells, whereas CEP55 expression was up-regulated in breast cancerous tissues. Moreover, there existed a target relationship between miR-144 and CEP55 and negative correlation on their expressions. MiR-144 could down-regulate CEP55 expression, thereby inhibiting proliferation, invasion, migration, retarding cell cycle and accelerating cell apoptosis. MiR-144 could inhibit cell progression through down-regulating CEP55 in vivo.

Conclusion: MiR-144 suppressed cell proliferation, migration, invasion and induced cell cycle arrest and cell apoptosis by repressing CEP55. This might provide a promising therapy for clinical treatment.     

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study

Purpose: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. Methods: Forty-eight (median age 54 years, range 26–77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0–2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m² for 90 min and docetaxel infusion 80 mg/m² for 90 min, repeated once every 3 weeks. Results: Twenty-five (52.08%, 95% confidence interval [CI] 37.95–66.21) patients showed responses: 3 complete (6.25%, 95% CI 0–13.05) and 22 (45.83%, 95% CI 31.74–59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. Conclusion: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.     

miR-340对乳腺癌MDA-MB231细胞增殖和凋亡的影响

背景与目的：既往研究表明,微小RNA-340(miR-340)能负性调控多种肿瘤的进展,但其在乳腺癌细胞增殖和凋亡中的研究较少,本研究旨在探讨miR-340对乳腺癌MDA-MB231细胞增殖和凋亡的作用。方法：利用脂质体LipofectamineTM2000将pre-miR-340或anti-miR-340瞬时转染至乳腺癌MDA-MB231细胞,通过RT-PCR检测miR-340 mRNA的水平,蛋白质印迹法(Western blot)检测cleaved-caspase-3蛋白的表达,MTT比色法检测细胞增殖的抑制情况,流式细胞仪检测细胞凋亡。结果：Pre-miR-340增加了MDA-MB231细胞中miR-340表达,同时增加cleaved-caspase-3蛋白表达、抑制MDA-MB231细胞增殖并促进其凋亡。而anti-miR-340抑制了MDAMB231细胞中miR-340表达,并且抑制cleaved-caspase-3蛋白表达,促进了MDA-MB231细胞增殖,抑制了MDAMB231细胞的凋亡。结论：miR-340转染后能上调MDA-MB231细胞中cleaved-caspase-3蛋白的表达从而抑制细胞增殖,促进其凋亡。     

多西紫杉醇联合米托蒽醌治疗晚期乳腺癌

目的:评定多的紫杉醇联合米托蒽醌治疗晚期乳腺癌临床疗效及不良反应。方法:52例病人均有病理学诊断及可评价客观指标。采用多西紫杉醇75mg/m~2d1,静脉滴注1小时,用多西紫杉醇前1天口服地塞米松10mg,连续3天。米托蒽酿14mg/m~2d1化疗。21～30天为1周期,2周期评价疗效。结果:52例病人可评价疗效和不良反应。CR 6例,PR 32例,NC 10例,PD 4例,有效率73.08％,不良反应主要为白细胞减少Ⅲ度占32.69％,Ⅳ度占25.00％;脱发Ⅱ度占44.23％,Ⅲ度占21.15％;腹泻Ⅱ度占32.69％,Ⅲ度占21.15％。结论:多西紫杉醇联合米托蒽醌治疗晚期乳腺癌有效率较高,不良反应可以耐受。     

MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b

Background

The metastasis-associated gene 1 (MTA1) has been identified as one critical regulator of tumor metastasis. Previously, we identified miR-125b as a downregualted miRNA in non-small cell lung cancer (NSCLC) cell line upon MTA1 depletion. However, the role of miR-125b and MTA1 in the regulation of NSCLC metastasis remains unclear.

Methods

Stable MTA1 knockdown NSCLC cell lines 95D and SPC-A-1 were established by transfection with MTA1 shRNA. The effects of MTA1 depletion on the expression of miR-125b and cell migration and invasion were examined by real-time PCR, wound healing and matrigel invasion assay.

Results

MTA1 knockdown led to the upregulation of miR-125b level in NSCLC cells. Furthermore, MTA1 knockdown reduced while miR-125b inhibitor enhanced cell migration and invasion of NSCLC cells. Notably, miR-125b inhibitor antagonized MTA1 siRNA induced inhibition of cell migration and invasion.

Conclusion

MTA1 and miR-125b have antagonistic effects on the migration and invasion of NSCLC cells. The newly identified MTA1-miR-125b axis will help further elucidate the molecular mechanism of NSCLC progression and suggest that ectopic expression of miR-125b is a potentially new therapeutic regimen against NSCLC metastasis.     

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.     

MicroRNA-125a influences breast cancer stem cells by targeting leukemia inhibitory factor receptor which regulates the hippo signaling pathway

Cancer stem cells (CSC) are the main driving force behind cancer initiation and progression. The molecular mechanisms that regulate CSC properties are poorly understood. MicroRNAs (miRNAs) play a significant role in normal and cancer tissues. Here, we show that miRNA-125a indirectly regulates TAZ, an effector molecule in the Hippo pathway, through the leukemia inhibitory factor receptor (LIFR). The miR-125a→LIFR axis affected the homeostasis of nonmalignant and malignant breast epithelial stem cells through the Hippo signaling pathway. Inhibition of miR-125a in breast cancer cells led to a significant reduction in the CSC pool. In contrast, enhanced expression of miR-125a in nonmalignant breast epithelial cells resulted in significant expansion of the stem cell pool. Gain of function and loss of function of LIFR directly correlated with the inhibition and overexpression of miR-125a, respectively. Modulation of miR-125a led to a change in the activity of TAZ and its subcellular localization. We further demonstrated that miR-125a influenced stem cells by regulating Hippo signaling through LIFR in human primary breast cancer cells confirming the data obtained from established cell lines. We suggest that miR-125a could be a potential target against CSCs that maybe used along with the existing conventional therapies.     

Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.