ER/PR阳性和阴性乳腺癌的定量蛋白质组学和生物信息学比较研究

目的:建立雌/孕激素受体(ER/PR)阴性和阳性乳腺癌的蛋白质表达谱,寻找ER/PR阴性和阳性乳腺癌中差异表达蛋白,为乳腺癌患者提供新的预后预测指标和治疗新靶点。方法:应用蛋白质组学i TRAQ技术建立ER/PR阳性和阴性乳腺癌的蛋白质差异表达谱,鉴定两组乳腺癌的差异表达蛋白,对部分差异表达蛋白进行生物信息学分析,包括蛋白功能注释和分类GO分析和KEGG通路分析。结果:应用i TRAQ蛋白质组学技术对乳腺癌组织进行了蛋白组学分析,鉴定出ER/PR阳性和阴性组间有差异表达的蛋白4999种,以ER/PR阳性:ER/PR阴性≥3为上调标准,确定ER/PR阳性组上调蛋白101种。以ER/PR阳性:ER/PR阴性≤0.5为下调标准,ER/PR阳性组下调蛋白122种。GO分析结果显示ER/PR受体阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞定位较为复杂,并且在上调蛋白和下调蛋白上存在分布差异。KEGG通路分析发现部分差异表达蛋白涉及201条信号通路。结论:ER/PR阳性和阴性乳腺癌间存在差异表达蛋白,这些蛋白涉及复杂的分子功能、生物过程和信号通路。     

乳腺癌分子分型的研究进展

乳腺癌是目前世界上女性最为常见的恶性肿瘤之一。随着个体化的乳腺癌的化疗、内分泌治疗和靶向治疗的广泛使用,乳腺癌的分子分型检测也因此得到高度重视和广泛使用。2013年St.Gallen国际乳腺癌会议上重新定义了乳腺癌的分子分型标准,使Luminal A型和Luminal B型乳腺癌的比例有所改变,导致原本分类为Luminal A型的部分患者重新分类为Luminal B型而使Luminal B型患者数量有所增加。人上皮生长因子受体-2(human epidermalgrowth factor receptor-2,HER2)型乳腺癌的靶向药物曲妥珠单抗与其他化疗药物的联合应用及不同时间应用的治疗效果有了进一步研究。雄激素受体(Androgen Receptor,AR)认为可用于常规评估三阴性乳腺癌,除此之外,三阴性乳腺癌的小亚型的分型也为三阴性乳腺癌的个体化治疗提供了新的思路。尽管乳腺癌分子分型方面已取得一定进展,并获得国际同行间的认可,给乳腺癌患者的治疗和预后复发预测提供了重要依据,但目前所有的分子标记物仍不能够满足治疗需求使其临床实用性仍旧具有局限性,因此还期待更多更深入的研究。     

超声刀与普通电刀手术治疗乳腺癌的临床效果比较

目的:研究超声刀与普通电刀手术治疗乳腺癌的临床效果,为乳腺癌的临床诊治提供参考。方法:选取2012年1月至2014年10月我院收治的112例乳腺癌患者为研究对象,将其分为研究组和对照组,分别给予超声刀与普通电刀手术治疗。对两组患者的手术时间、术中出血量、伤口愈合时间、住院时间、住院费用、相关不良反应发生率进行观察和比较。结果:研究组患者的手术时间、术中出血量、伤口愈合时间等三项指标均明显优于对照组,差异有统计学意义(P0.05);相较于对照组,研究组患者的住院时间更短,住院费用更少,差异有统计学意义(P0.05);研究组患者的皮下积液、游离皮瓣坏死、术后出血和术中损伤等不良反应发生率均低于对照组,但组间数据比较,术后出血发生率差异有统计学意义(P0.05)。结论:超声刀手术治疗乳腺癌的临床效果较好,是临床治疗乳腺癌的理想方式之一。     

35 岁以下年轻乳腺癌患者的临床特征及预后因素分析

目的:探讨年轻乳腺癌患者的临床病理特点及影响其预后的相关因素。方法:选取潍坊市人民医院2005年11月至2011年11月收治的年龄不高于35岁的137例年轻乳腺癌患者的临床资料,其中共有116例入组,初步分析年轻乳腺癌患者的临床病理特征及对预后产生的影响。结果:116例患者中位随访时间为46.0个月。3年OS和PFS为94.6%和79.1%。单因素、多因素分析结果显示淋巴结转移情况和Ki67水平与预后的显著相关(P0.05),淋巴结转数目、Ki67水平与预后呈负相关。结论:年轻乳腺癌患者的生物学行为、病理及预后较为特殊。淋巴结转移情况、Ki67水平是影响预后的关键因素。     

乳腺MRI 与乳腺X线在导管原位癌临床诊断中应用的比较研究

目的:探讨乳腺MRI与乳腺X线检查在导管原位癌(DCIS)诊断中的应用价值。方法:选择2012年5月至2014年9月在我院接受诊治的乳腺DCIS患者52例(58个病灶)为研究对象,对所有患者进行乳腺MRI及X线检查,以病理检查结果作为金标准,比较乳腺MRI及X线检查在导管原位癌(DCIS)诊断中的应用价值。结果:58个病灶中,乳腺MRI共检查出阳性54例,阴性4例,其中误诊或漏诊4例;乳腺X线共检查出阳性49例,阴性9例,其中误诊或漏诊11例。乳腺MRI检查的灵敏度和准确度均显著高于乳腺X线,差异有统计学意义(P0.05)。此外,乳腺MRI检查的特异度、阳性预测值及阴性预测值均分别高于乳腺X线,但差异无统计学意义(P0.05)。结论:乳腺MRI检查对DCIS的诊断价值较高,具有广泛的应用前景,但亦存在少数误诊或漏诊。     

人巨细胞病毒感染与乳腺癌关系的研究进展

人巨细胞病毒(human cytomegalovirus,HCMV)是β疱疹病毒家族成员,全世界70%以上人口感染过该病毒。HCMV通常以潜伏感染形式存在于宿主体内,并产生了逃避宿主免疫系统识别和清除等多种能力,可通过表达HCMV基因及蛋白发挥肿瘤调节作用,干扰细胞代谢过程,促进肿瘤的发生和发展。乳腺癌是女性最常见的恶性肿瘤之一,而HCMV在非肿瘤和乳腺癌患者乳腺上皮细胞中的阳性检出率较高,同时有研究表明晚期暴露于HCMV可引起乳腺癌。近期新型抗HCMV药物对乳腺癌靶向治疗的临床有效性也再次提示,HCMV可能与乳腺癌的发生和发展密切相关。本文主要综述了HCMV的致癌潜能及其与乳腺癌发生和发展的潜在关联。     

保乳手术联合放射治疗84例乳腺癌患者临床疗效观察

目的:观察保乳手术联合放射治疗乳腺癌患者临床疗效。方法:选取我院收治的乳腺癌患者84例,均采取保乳手术联合放射治疗,观察临床疗效。结果:所有患者手术均获得成功,84例乳腺癌患者均在出院后进行随访,平均随访时间(2.1±0.4)年,各项检查未发现复发迹象。在放疗的期间内,乳房出现刺痛、发痒的不适患者20例,皮肤色素沉着、红斑的患者37例,在治疗后发生湿性脱皮患者10例,放射性食管炎患者8例;在放疗结束1个月,出现反射性肺炎患者2例。手术及放疗后,患者乳房的美容效果中优秀患者49例,良好患者29例,较差患者6例;行肿瘤扩大切除术患者优秀率高于行象限切除术患者,差异有统计学意义(P0.05)。结论:保乳手术联合放疗可保证治疗效果,同时降低并发症的发生,有利于美观,是一种优秀的乳腺癌治疗方法。     

Unintended irradiation of internal mammary chain – Is that enough?

Aim

To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed.

Background

The dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions.

Materials and methods

One hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques.

Results

The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), and breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy, and 18.67 Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). Mean doses to IMC were greater in patients with T3–T4 tumors when compared with more initial stages (≤T2) (p = 0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1 Gy × node negative: 17.8 Gy, p = 0.0017).

Conclusions

The moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy.     

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin

Context: Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics.

Objective: Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study.

Materials and methods: Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of doxorubicin (DOX) vis–a-vis enhanced antitumor activity.

Results: The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH ～5, compared to physiological pH ～7.4. SLpH-HA was evaluated for their cytotoxicity potential on CD44 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5?μM, respectively, after 48?h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the DOX-loaded HA-targeted pH-sensitive liposomes was also verified in a tumor xenograft mouse model.

Discussion: DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction. The major side-effect of conventional DOX formulation, i.e. cardiotoxicity was also estimated by measuring serum enzyme levels of LDH and CPK and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44.

Conclusion: Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.