The value of assessing cell proliferation in breast cancer

Using three methods to measure cell proliferation, namely DNA cell cycle; anti-proliferating cell monoclonal antibody (MAb) (Ki67, P145) analysis by flow cytometry; and the histological silver (argyrophilic) staining technique to visualize nuclear-organizing regions (AgNOR), twenty-two paired samples of primary breast tumour and axillary lymph node were analysed. The results showed variable levels of correlation between the methods used for the tumour group (r = 0.915, P <0.001 for Ki677 versus P145; r = 0.42, P <0.005 for percentage S/G2/M-phase versus P145; r = 0.16, P <0.5 for percentage S/G2/M-phase versus AgNOR; r = 0.400, P < 0.1 for Ki67 versus AgNOR). The lymph-node group showed slightly poorer correlations, yet involved nodes showed a consistently higher level of proliferation than non-involved nodes by all methods used. Overall, MAb binding of Ki67 or P145 was seen to be a good indicator of cycling cells, detecting G1-phase cells in addition to S/G2/M-phase cells indentified by the other methods used. However, no advantage was found over the usual DNA flow cytometric analysis of cells, which had clear prognostic value. AgNOR scores were found to be able to discriminate between diploid and aneuploid; and dividing and non-dividing cells, but areas of score overlap limited the application of this technique to that of a positive discriminator only.     

乳腺癌前哨淋巴结不同检测方法效果研究

目的 :研究染色法、同位素法、联合法3种不同检测方法对乳腺癌前哨淋巴结检测的影响。方法:选取2007年9月²013年11月在我院就诊的早期女性乳腺癌患者为研究对象,将患者随机分为3组,蓝染料组、核素组、联合组。比较各组乳腺癌前哨淋巴结活检的成功率、准确率及假阴性率。结果 :与单纯使用染料的方法相比,联合法的假阴性率显著性降低,差异有统计学意义。与单用染料组及核素组相比,联合法发现的SLN数较多,但无统计学差异。结论:联合应用染料及同位素示踪较单一方法更能提高前哨淋巴结检测的成功率,降低假阴性率。     

基于单细胞代谢组学的他莫昔芬抗乳腺癌作用机制研究

雌激素受体阳性型是乳腺癌最常见的亚型,以他莫昔芬为代表的内分泌治疗是针对该亚型乳腺癌患者的主要治疗手段。然而,乳腺癌是一种高度异质性的疾病,部分患者在接受他莫昔芬治疗后仍然面临复发的风险。本研究利用单细胞流式质谱装置,考察他莫昔芬作用下MCF-7细胞代谢产物的变化情况。结果表明,在正、负离子模式下分别鉴定到576、480种代谢物,在对照组和他莫昔芬给药组的细胞中分别鉴定到811、776种代谢物。其中,在负离子模式下检测到的代谢物能够实现他莫昔芬给药前后MCF-7细胞的显著区分。在他莫昔芬作用下,MCF-7细胞中共有28种代谢物含量上调,59种代谢物含量下调,主要影响氨基酸代谢、核苷酸代谢等代谢通路。本研究利用基于质谱的单细胞代谢组学技术考察他莫昔芬对乳腺癌细胞产生的代谢变化,从单细胞代谢组学角度阐明他莫昔芬抗雌激素受体阳性型乳腺癌的作用机制,可为研究其他药物的作用机制提供参考。     

应用新型荧光定量PCR技术检测FGFR2基因SNP

目的:探讨一种目前较为新颖的通过Rotor Gene-3000荧光定量PCR仪进行Tm-shifting荧光定量PCR扩增测定单核苷酸多态性(SNP)的可行性。方法:以913份乳腺肿物患者成纤维细胞生长因子受体2(FGFR2)基因rs2981582位点(T→C)作为研究对象,用荧光染料SYBR GreenI标记DNA,并在设计引物时在所研究基因的特异性引物5’末端连接上不同长度的尾,使不同基因型标本的PCR融解曲线的高峰出现在不同位置,最终可通过对PCR融解曲线的分析进行SNP分型测定。结果:纯合子C/C基因型融解曲线峰出现在≤84.60C处,特殊情况下稍向右偏移,但不超过85.10C,峰型较尖。纯合子T/T基因型融解曲线峰出现在≥87.50C处,特殊情况下稍向左偏移,但不小于870C,峰型较尖。杂合子T/C基因型融解曲线峰出现在前两者之间,峰型较平。结论:实验结果表明,用本方法检测大批量人群标本的SNP结果符合遗传平衡定律,且操作简便,检测耗时短,结果特异且费用较为低廉,适合于进行大规模样品的SNP快速测定。     

The potentials of MS-based subproteomic approaches in medical science: the case of lysosomes and breast cancer

Because of the great number of women who are diagnosed with breast cancer each year, and though this disease presents the lowest mortality rate among cancers, breast cancer remains a major public health problem. As for any cancer, the tumorigenic and metastatic processes are still hardly understood, and the biochemical markers that allow either a precise monitoring of the disease or the classification of the numerous forms of breast cancer remain too scarce. Therefore, great hopes are put on the development of high-throughput genomic and proteomic technologies. Such comprehensive techniques should help in understanding the processes and in defining steps of the disease by depicting specific genes or protein profiles. Because techniques dedicated to the current proteomic challenges are continuously improving, the probability of the discovery of new potential protein biomarkers is rapidly increasing. In addition, the identification of such markers should be eased by lowering the sample complexity; e.g., by sample fractionation, either according to specific physico-chemical properties of the proteins, or by focusing on definite subcellular compartments. In particular, proteins of the lysosomal compartment have been shown to be prone to alterations in their localization, expression, or post-translational modifications (PTMs) during the cancer process. Some of them, such as the aspartic protease cathepsin D (CatD), have even been proven as participating actively in the disease progression. The present review aims at giving an overview of the implication of the lysosome in breast cancer, and at showing how subproteomics and the constantly refining MS-based proteomic techniques may help in making breast cancer research progress, and thus, hopefully, in improving disease treatment.     

乳腺癌伽玛刀换源机器人运动学仿真研究

乳腺癌伽玛刀是一种新研制的治疗乳腺癌的放射性治疗设备,针对利用工业机器人更换乳腺癌伽玛刀放射源的实际要求,根据机器人的结构特点,建立机器人D-H连杆坐标系和机器人运动学方程,并对机器人运动学正问题和逆问题进行分析,利用MATLAB编程求解机器人运动学逆解,分析了机器人更换乳腺癌伽玛刀放射源的工作过程,规划了机器人换源运动轨迹,在COSMOSMotion中仿真机器人换源的运动过程,分析了机器人关节的运动曲线,为研究真实的换源情况提供技术支持。     

Centred contact density functions for the statistical analysis of random sets A stereological study on benign and malignant glandular tissue using image analysis

Real structures investigated in the material and biological sciences, such as minerals or tissues, can often be reduced to two phases. In a stochastic approach, the components of such binary structures may be considered as the union of grains — random sets implanted with their centres at random points — and their complementary space, which is called the pore space. The simplest stochastic germ-grain model is the Boolean model of random sets, which we use here instrumentally as a null model (reference model) for comparison with our biological material. After a brief review of basic properties of the Boolean model and related statistical methods, we introduce centred contact density functions as a new approach. Empirical contact density functions are estimated from the empirical contact distribution functions with an image analyser by dilation of the grain phase. Theoretical contact density functions are then predicted from a set of image parameters, under the assumption that the Boolean model holds. A centred contact density function is the difference between the estimated and the predicted contact density function. Apart from a random error term, centred contact density functions amount to zero irrespective of the area fraction of the grain phase, when the germ-grain model is Boolean. As a section of a spatial Boolean model is a planar Boolean model, the method is also applicable in stereological studies where digitized images are obtained from sections of a three-dimensional structure. Centred contact density functions were determined for mastopathic tissue as compared to mammary cancer, and for tumour-free prostatic tissue as compared to prostatic cancer. For each category of specimens, twenty cases with 10 images each were analysed. Benign and malignant glandular tissue of the aforementioned types deviates significantly from the Boolean model. Centred contact density functions show that malignant transformation is connected with profound geometric remodelling of the pore space.