改良乳腺癌根治术联合表柔比星治疗乳腺癌的疗效及对血清抵抗素、脂联素水平的影响

目的:探究改良乳腺癌根治术联合表柔比星治疗乳腺癌的疗效及对血清抵抗素、脂联素水平的影响.方法:收集2019年1月～2020年1月我院确诊为乳腺癌的60例患者资料,使用随机数字法将患者分为对照组、观察组,每组30例.两组患者均接受改良乳腺癌根治术,对照组患者在此基础上接受阿霉素、环磷酰胺、5-氟尿嘧啶治疗,观察组接受表;...     

提高表柔比星质量与生产水平的研究

柔红霉素产生菌S．Coeruleorubidus经N^ 、Co^60理化诱变剂选育后,获得的高产菌株经发酵罐应用后,其发酵产率分别提高25．8％、17．6％,累计净增利润超亿元,经分离收集的活性生物精品制成表柔比星,纯度提高4％,杂质比例下降2倍以上,收率提高50％,符合最新国际权威药典标准,产品畅销世界。     

消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌患者免疫功能、生活质量及血清肿瘤标志物的影响

摘要 目的：探讨消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌（TNBC）患者免疫功能、生活质量及血清肿瘤标志物的影响。方法：选取TNBC患者89例,按照随机数字表法分为对照组和研究组,对照组（n=44）患者给予表柔比星新辅助化疗治疗,研究组（n=45）患者给予消癌平注射液联合表柔比星新辅助化疗。对比两组疗效、免疫功能、生活质量、血清肿瘤标志物及不良反应。结果：研究组治疗12周后的临床总有效率为91.11%（41/45）,高于对照组的63.64%（28/44）（P<0.05）。两组治疗12周后健康调查简表（SF-36）量表各维度评分升高,且研究组较对照组高（P<0.05）。两组治疗12周后CD4+CD25+Treg、Th17/ Treg均降低,且研究组较对照组低（P<0.05）,Th17升高,且研究组较对照组高（P<0.05）。两组治疗12周后癌胚抗原（CEA）、糖类抗原199（CA199）、糖类抗原125（CA125）均降低,且研究组较对照组低（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：消癌平注射液联合表柔比星新辅助化疗治疗TNBC,具有确切的治疗效果,可降低血清肿瘤标志物水平,改善患者免疫功能和生活质量。     

不同手术方式联合新辅助化疗治疗乳腺癌患者的临床疗效对比

目的:探究不同手术方式联合新辅助化疗治疗乳腺癌患者的临床疗效。方法:选择2012年1月~2014年1月我院收治的80例乳腺癌患者为研究对象。综合考虑患者自主意愿、身体条件、经济状况,将80例乳腺癌患者分为A组(23例)和B组(57例)。两组患者均给予EC(表柔比星+环磷酰胺)方案新辅助化疗,在此基础上A组接受保乳术,B组接受改良根治术。比较两组患者临床疗效、乳房美容效果、生活质量、心理状态。结果:A组患者的住院时间、拔管时间均显著短于B组(P0.05),术中出血量、HAMA、HRSD评分、术后并发症的发生率明显低于B组(P0.05),乳房美容效果明显优于B组(P0.05),QLQ-BR23评分显著高于B组(P0.05)。两组患者随访期间的2年生存率、复发率比较差异均无统计学意义(P0.05)。结论:保乳术联合表柔比星新辅助化疗治疗乳腺癌的临床效果显著,可减少术后并发症,提高乳房美观度和患者的生活质量。     

胃癌SGC7901 表柔比星耐药细胞亚系的建立与耐药机制研究

目的:建立人胃癌SGC7901表柔比星耐药细胞系,探讨其对表柔比星的耐药机制。方法:采用逐步增加表柔比星浓度,间歇作用体外诱导法,建立人胃癌SGC7901表柔比星耐药细胞亚系SGC7901/EPI。用MTT法测定药物敏感性;流式细胞仪检测其药物排除能力和凋亡抵抗能力等生物学指标的改变,western blot检测相关蛋白的表达。结果:经过12个月建成人胃癌SGC7901表柔比星耐药细胞系SGC7901/EPI,其对表柔比星明显耐药,且对其他多种抗癌药具有不同程度的交叉耐药性,阿霉素蓄积潴留实验显示SGC7901/EPI的阿霉素含量明显低于亲本细胞,Western blot显示MRP1的表达上调;SGC7901/EPI凋亡抵抗能力明显上升,Bcl-2表达比亲本细胞增高,而Bax的表达下调。结论:SGC7901/EPI细胞具有多药耐药表型,其可能通过MRP1的上调增加药物排出和上调Bcl-2/Bax的比值促进凋亡抵抗等机制产生耐药。该胃癌多药耐药细胞亚系为进一步研究胃癌耐药机制及逆转方法奠定基础。     

TURis-Bt术前膀胱灌注表柔比星治疗NMIUC的临床疗效观察

目的:探讨TURis-Bt术前膀胱灌注表柔比星治疗非肌层浸润性膀胱癌(NMIUC)的临床疗效。方法:选取2008年9月至2012年1月潍坊市中医院和上海交通大学附属第一人民医院泌尿外科收治的76例NMIUC患者,并将其随机分为观察组(TURis-Bt术前膀胱灌注表柔比星+术后常规灌注组)41例和对照组(TURis-Bt术后常规表柔比星膀胱灌注组)35例。灌注前将50mg表柔比星溶解于50ml 5%葡萄糖注射液,术前膀胱保留灌注30分钟后膀胱镜观察肿瘤组织及周围膀胱粘膜染色情况,将表柔比星橙染的膀胱粘膜活检并行TURis-Bt;对照组取瘤旁2 cm处及其他部位膀胱粘膜多点活检。比较两组的原位癌(CIS)、非典型性增生及腺性膀胱炎等病变检出率和术后肿瘤的复发率。结果:观察组患者瘤旁膀胱粘膜橙染56处,其中7处病理证实为膀胱原位癌、5处为非典型性增生、11处为腺性膀胱炎;对照组患者膀胱原位癌1处、非典型性增生3处、腺性膀胱炎2处,两组病变阳性率分别为41.1%(23/56)和13.4%(17/127),差异有显著统计学意义(P0.01)。观察组与对照组术后2年内肿瘤复发率分别为10.3%(4/39)和35.3%(12/34),差异有统计学意义(P0.05)。结论:TURis-Bt术前膀胱灌注表柔比星能提高NMIUC病变的早期检出率并降低肿瘤术后复发率。     

多柔比星脂质体在晚期乳腺癌治疗的疗效和安全性分析

摘要 目的：探讨在既往使用过蒽环类药物的晚期乳腺癌患者中再使用多柔比星脂质体的临床疗效及毒副作用相关性分析。方法：回顾性分析2019年5月至2021年1月就诊于本院的79例使用含多柔比星脂质体方案治疗晚期乳腺癌患者的临床资料,并对晚期乳腺癌患者多柔比星脂质体再使用与初使用的临床疗效、影响因素及不良反应进行相关性分析。结果：79例患者中,有65例患者可以进行疗效评估,其中客观缓解率（ORR）为13.85%,疾病控制率（DCR）为63.08%,在HER-2阳性晚期乳腺癌中,抗Her-2 治疗联合多柔比星脂质体,ORR为20.00%,DCR为75.00%,中位无疾病进展生存时间（PFS）为3.23个月。最常见不良反应为骨髓抑制、手足综合征、口腔黏膜炎。结论：含多柔比星脂质体化疗辅助治疗晚期乳腺癌可获得较好疗效,抗HER-2治疗联合多柔比星脂质体对HER-2阳性晚期乳腺癌的疗效及安全性均较佳。     

龙葵碱通过抑制Med19表达增加多柔比星耐药乳腺癌细胞对多柔比星的敏感性

目的 探讨龙葵碱（solanine）对乳腺癌细胞多柔比星耐药性的影响及其机制。方法 选用乳腺癌细胞MCF-7细胞和对阿霉素（adriamycin,ADM）或多柔比星耐药的乳腺癌细胞MCF-7/ADR细胞,转染pcDAN-Med19过表达中介体19(mediator 19,Med19),应用CCK-8法检测细胞增殖水平,qRT-PCR和Western blot检测细胞中Med19和凋亡相关Bcl-2、Bax及Cleaved-Caspase-3表达水平,TUNEL染色和流式细胞术分析细胞凋亡水平。结果 龙葵碱显著降低MCF-7/ADM细胞活力。Med19高表达于MCF-7/ADM细胞,龙葵碱显著抑制MCF-7/ADM细胞中Med19表达,龙葵碱对多柔比星处理的MCF-7/ADM细胞活力的降低、凋亡的促进、凋亡相关蛋白Bax和Cleaved-Caspase-3水平的上调及Bcl-2水平的下调可被过表达Med19明显抑制。结论 龙葵碱通过抑制Med19表达而降低乳腺癌细胞MCF-7/ADM对多柔比星的耐药性。     

药物联合新辅助化疗(ET)对三阴乳腺癌患者生存状态的改善及其疗效评价

目的:观察表柔比星和多西紫杉醇联合新辅助化疗(ET)对三阴乳腺癌患者生存状态的改善及其疗效,评价该化疗方案在三阴乳腺癌的化疗中加入紫杉类化疗药物的可行性。方法:收集我院2011年1月至2011年12月收治的300例乳腺癌患者,将患者随机分为两组,研究组及对照组,每组各150例。对照组采用单纯表柔比星,研究组采用新辅助化疗的方案(ET方案),随访12个月,统计两组临床疗效并进行评价。结果:研究组完全缓解率(92.00%)明显高于对照组的78.00%,疾病无缓解率(1.33%)及疾病恶化率(0%)明显低于对照组的14.00%及1.33%,差异具有统计学意义(P0.01)。随访期间,对照组患者68例(45.3%)复发或转移,而研究组患者35例(23.3%)出现复发或远处转移,两者比较,差异显著(P0.001)。结论:在三阴乳腺癌的化疗中加入紫杉类化疗药物是可行的,效果显著。     

选择性环氧化酶-2抑制剂对乳腺癌细胞的化疗增敏作用

目的:观察选择性环氧化酶-2(COX-2)的抑制剂塞来昔布对表柔比星抗乳腺癌MCF-7细胞增殖和诱导凋亡作用以及探讨其机制.方法:应用四甲基偶氮唑蓝(MTT)比色法分析塞来昔布联用表柔比星对MCF-7细胞的生长抑制作用,流式细胞术检测细胞的凋亡,western blotting检测凋亡相关蛋白Bcl-2、Bax、caspase-3的表达.结果:10μmol/l的cxlecoxib和10μg/l表柔比星联用细胞抑制率和早期凋亡率均显著增高,并引起caspase-3上调及裂解激活,bcl-2下调,bax则变化不大.结论:塞来昔布对表柔比星抗乳腺癌MCF-7细胞有协同作用,其诱导凋亡与caspase-3激活和Bcl-2表达下调有关.     

Prise en charge du cancer du sein,avancées et perspectives

Breast cancer treatment has developed rapidly for the last 15 years, promoted by a better understanding of tumour growth biology. Targeted therapies have been rapidly expending: immunotherapy, targeted chemotherapy, endocrine therapy efficacy enhanced by mTOR inhibitors. Changes of molecular profiling tumours during the illness need to perform regularly biopsies and to adapt drugs. This article will focus on a high-level overview of main advances across systemic treatment.     

UCH-L1在乳腺癌中的表达及其与转移关系的研究

目的研究泛素羧基末端水解酶L1(UCH-L1)与磷酸化p38(p-p38)在乳腺癌组织、细胞系中的表达情况、两种蛋白的表达与临床病理特征的关系以及UCH-L1与乳腺癌侵袭转移的关系。方法用免疫组织化学方法检测乳腺癌组织中UCH-L1与p-p38蛋白的表达情况,用Western Blot方法检测乳腺癌组织以及细胞系中UCH-L1与p-p38蛋白的表达情况。应用UCH-L1特异性抑制剂作用于乳腺癌高侵袭高转移细胞系MDA-MB-435s后,用Western Blot观察UCH-L1与p-p38蛋白表达改变的情况,用Transwell实验检测MDA-MB-435s细胞侵袭潜能的改变。结果 UCH-L1和p-p38蛋白在乳腺浸润性导管癌中的表达高于其在癌旁正常乳腺组织中的表达(P=0.012,P=0.001),二者呈正相关(r=0.397,P=0.000),并与乳腺癌的TNM分期(P=0.017,P=0.010)、淋巴结转移情况(P=0.033,P=0.021)相关。乳腺上皮细胞系MCF-10A、乳腺癌低侵袭低转移细胞系MCF-7和乳腺癌高侵袭高转移细胞系MDA-MB-435s中两种蛋白表达水平呈递增趋势(P均<0.05)。UCH-L1特异性抑制剂可以浓度依赖性地下调MDA-MB-435s细胞系中p-p38蛋白的表达水平(P均<0.05),并能抑制乳腺癌细胞的侵袭转移潜能。结论 UCH-L1、p-p38过表达与乳腺癌的TMN分期、淋巴结转移有关。UCH-L1可能通过上调p-p38介导乳腺癌转移。     

吉西他滨联合化疗方案治疗复发转移性乳腺癌的临床疗效观察

目的:观察吉西他滨与顺铂联合以及吉西他滨与紫杉醇联合治疗复发转移性乳腺癌的疗效和不良反应。方法:本研究收集65例女性乳腺癌术后复发转移的患者作为研究对象。随机分成两组,分别应用吉西他滨与顺铂(GP方案组)、吉西他滨与紫杉醇(GT方案组)联合进行治疗。GP方案组患者有30例,第1天、第8天用吉西他滨800mg~1000mg/m2溶于0.9%的100mL生理盐水中静脉滴注;第1天~第3天,21天重复用顺铂30mg/m2溶于0.9%的250mL生理盐水中静脉滴注;GT方案组患者有35例,吉西他滨的使用方法与GP方案组相同,第2天,21重复用紫杉醇135mg/m2溶于0.9%的500mL生理盐水中静脉滴注。对化疗时产生的不良反应进行对症处理。结果 :GP方案组化疗有效率为46.67%,疾病控制率为70.00%;GT方案组化疗有效率为42.86%,疾病控制率为68.57%,两组比较差异均无统计学意义(P0.05)。GT组脱发的发生率为62.86%,明显高于GP组的10.00%(P0.001),其他不良反应在两组之间差异无统计学意义(P0.05)。结论:GP方案和GT方案在治疗复发转移性乳腺癌有较好的疗效,不良反应较轻,可作为复方转移性乳腺的一种化疗方案。     

胃癌患者HER2、VEGF、HIF-1a mRNA的表达与临床特点及预后的关系

目的:探讨胃癌患者血清中人表皮生长因子受体-2 (Human epithelial growth factor receptor 2, HER2)HER-2、血管内皮生长因子(Vascular endothelial growth factor,VEGF)、低氧诱导因子-1α(hypoxia inducible factor-1, HIF-1α) mRNA水平与其临床特征及预后的关系。方法:选取我院2015年7月至2016年7月治疗的50例胃癌患者作为研究对象,采用荧光定量PCR检测血清中HER-2、VEGF、HIF-1α mRNA水平,探讨其与胃癌患者临床特点的关系,采用COX回归模型探讨HER-2、VEGF、HIF-1α mRNA表达与胃癌临床预后的关系。结果:胃癌组患者血清中HER2、VEGF、HIF-1α mRNA水平明显高于对照组患者,年龄越高、分化程度越低、临床分期晚、伴有淋巴结转移的胃癌患者血清中HER2、VEGF、HIF-1α mRNA水平明显高与相对应的患者,HER-2(P=0.04)、VEGF(P=0.03)、HIF-1α(P=0.04)是胃癌患者预后不良的独立危险因素。结论:胃癌组织中HER-2、VEGF、HIF-1α mRNA表达水平与胃癌恶性程度密切相关,是胃癌患者预后不良的独立危险因素     

Role of a metastatic suppressor gene KAI1/CD82 in the diagnosis and prognosis of breast cancer

Globally, breast cancer is the most common type of cancer in females and is one of the leading causes of cancer death in women. The advancement in the targeted therapies and the slight understanding of the molecular cascades of the disease have led to small improvement in the rate of survival of breast cancer patients. However, metastasis and resistance to the current drugs still remain as challenges in the management of breast cancer patients. Metastasis, potentially, leads to failure of the available treatment, and thereby, makes the research on metastatic suppressors a high priority. Tumor metastasis suppressors are several genes and their protein products that have the capability of arresting the metastatic process without affecting the tumor formation. The metastasis suppressors KAI1 (also known as CD82) has been found to inhibit tumor metastasis in various types of solid cancers, including breast cancer. KAI1 was identified as a metastasis suppressor that inhibits the process of metastasis by regulating several mechanisms, including cell motility and invasion, induction of cell senescence, cell–cell adhesion and apoptosis. KAI1 is a member of tetraspanin membrane protein family. It interacts with other tetraspanins, chemokines and integrins to control diverse signaling pathways, which are crucial for protein trafficking and intracellular communication. It follows that better understanding of the molecular events of such genes is needed to develop prognostic biomarkers, and to identify specific therapies for breast cancer patients. This review aims to discuss the role of KAI1/CD82 as a prognosticator in breast cancer.     

Specific expression of the human voltage-gated proton channel Hv1 in highly metastatic breast cancer cells, promotes tumor progression and metastasis

The newly discovered human voltage-gated proton channel Hv1 is essential for proton transfer, which contains a voltage sensor domain (VSD) without a pore domain. We report here for the first time that Hv1 is specifically expressed in the highly metastatic human breast tumor tissues, but not in poorly metastatic breast cancer tissues, detected by immunohistochemistry. Meanwhile, real-time RT-PCR and immunocytochemistry showed that the expression levels of Hv1 have significant differences among breast cancer cell lines, MCF-7, MDA-MB-231, MDA-MB-468, MDA-MB-453, T-47D and SK-BR-3, in which Hv1 is expressed at a high level in highly metastatic human breast cancer cell line MDA-MB-231, but at a very low level in poorly metastatic human breast cancer cell line MCF-7. Inhibition of Hv1 expression in the highly metastatic MDA-MB-231 cells by small interfering RNA (siRNA) significantly decreases the invasion and migration of the cells. The intracellular pH of MDA-MB-231 cells down-regulated Hv1 expression by siRNA is obviously decreased compared with MDA-MB-231 with the scrambled siRNA. The expression of matrix metalloproteinase-2 and gelatinase activity in MDA-MB-231 cells suppressed Hv1 by siRNA were reduced. Our results strongly suggest that Hv1 regulates breast cancer intracellular pH and exacerbates the migratory ability of metastatic cells.     

CCN6: a novel method of aTAKing cancer

It is well-established that the expression of CCN family of matricellular proteins is altered in essentially all cancers and, hence, targeting these proteins may be a novel therapeutic approach to treating these diseases. For example, CCN6 (WISP3) is downregulated in aggressive breast cancers, and this phenomenon appears to result in the tumor survival by promoting Akt phosphorylation. In a recent report by Pal et al. (Cancer Res 72(18):4818-4828, 2012), CCN6 knockdown was shown to promote BMP4-mediated activation of the Smad-independent TAK1 and p38 kinases. CCN6 expression was inversely associated with BMP4 and phospho-p38 levels in 69 % of invasive breast carcinomas. TAK1 inhibition has been previously shown to decrease tumor progression in preclinical models of TAK1-dependent cancers. These data are consistent with the idea that CCN6 may represent a novel therapeutic approach, as compared to attacking TAK1 directly, to selectively target breast cancers.     

Mouse models for breast cancer metastasis

Metastasis of cancer cells is the main cause of death in most breast cancer patients. Although markers for early diagnosis and drugs that limit the spread of cancer to other organs have been developed, it is difficult to prevent the relapse of breast cancer. Recent research has highlighted the importance of tumor environment in which communication between tumor cells and the body system occurs. Emerging data have suggested that animal models are a good system to investigate this communication. Therefore, studies with mouse models have been developed as a reasonable method for a systemic approach to understand breast cancer metastasis. In this review, we summarize mouse models of breast cancer and their applications to the study of human breast cancers, and discuss limitation of model system and advanced techniques to overcome it.