Fine-Needle Aspirates CYFRA 21-1 is a Useful Tumor Marker for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients

Introduction

To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.

Methods

US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.

Results

Among the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).

Conclusion

Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.     

Sec62 Protein Mediates Membrane Insertion and Orientation of Moderately Hydrophobic Signal Anchor Proteins in the Endoplasmic Reticulum (ER)

Nascent chains are known to be targeted to the endoplasmic reticulum membrane either by a signal recognition particle (SRP)-dependent co-translational or by an SRP-independent post-translational translocation route depending on signal sequences. Using a set of model and cellular proteins carrying an N-terminal signal anchor sequence of controlled hydrophobicity and yeast mutant strains defective in SRP or Sec62 function, the hydrophobicity-dependent targeting efficiency and targeting pathway preference were systematically evaluated. Our results suggest that an SRP-dependent co-translational and an SRP-independent post-translational translocation are not mutually exclusive for signal anchor proteins and that moderately hydrophobic ones require both SRP and Sec62 for proper targeting and translocation to the endoplasmic reticulum. Further, defect in Sec62 selectively reduced signal sequences inserted in an N_in-C_out (type II) membrane topology, implying an undiscovered role of Sec62 in regulating the orientation of the signal sequence in an early stage of translocation.     

Macrophage migration inhibitory factor (MIF) interacts with Bim and inhibits Bim-mediated apoptosis

The pro-apoptotic Bcl-2 family member Bim acts as a sensor for apoptotic stimuli and initiates apoptosis through the mitochondrial pathway. To identify novel regulators of Bim, we employed the yeast two-hybrid system and isolated the human gene encoding macrophage migration inhibitory factor (MIF), a ubiquitously expressed proinflammatory mediator that has also been implicated in cell proliferation, the cell cycle and carcinogenesis. The interaction between MIF and Bim was confirmed by both in vitro and in vivo protein interaction assays. Intriguingly, protein complexes between MIF and the three major Bim isoforms (BimEL/BimL/BimS) could be detected in HEK293 and K562 cells, especially in cells undergoing apoptosis. Moreover, exogenous expression of MIF partially inhibited Bim-induced apoptosis in HEK293 cells. SiRNA-mediated knockdown of MIF increased apoptosis in K562 cells exposed to the chemical oxidant diamide. Endogenous MIF may regulate the pro-apoptotic activity of Bim and inhibit the release of cytochrome c from mitochondria.     

Water Striders:The Biomechanics of Water Locomotion and Functional Morphology of the Hydrophobic Surface(Insecta:Hemiptera-Heteroptera)

Water striders are insects living on the water surface, over which they can move very quickly and rarely get wetted. We measured the force of free walking in water striders, using a hair attached to their backs and a 3D strain gauge. The error was calculated by comparing force and data derived from geometry and was estimated as 13%. Females on average were stronger (1.32 mN) than males (0.87 mN), however, the ratio of force to weight was not significantly different. Compared with other lighter species, Aquarius paludum seems stronger, but the ratio of force to weight is actually lower. A. paludum applies about 0.3 mN·cm-1 to 0.4 mN·cm-1 with its mid-legs, thus avoiding penetrating the surface tension layer while propelling itself rapidly over the water surface.We also investigated the external morphology with SEM. The body is covered by effectively two layers of macro-and micro-hairs, which renders them hydrophobic. The setae are long (40 um-60 um) and stiff, being responsible for waterproofing, and the microtrichia are much smaller (<10 um), slender, and flexible, holding a bubble over the body when submerged.     

Ergasiophygophytes and xenophytes of East Asiatic origin in Adjaria a stimulus to new terminology,especially for ergasiophygophytes

Studies of the Adjarian flora resulted in a detailed classification of the ergasiophygophytes, based mainly on the degree of their naturalization: (1) The ephemeroergasiophygophytes display unstable naturalization both in artificial and natural habitats, and disappear after only a few growing seasons. (2) The deuteroergasiophygophtes show stable naturalization in anthropogenic habitats. (3) The protoergasiophygophytes are distinguished by uncertain stability of naturalization in natural habitats, and, if firmly naturalized on a certain spot, they lack any tendency to further spreading. (4) The autergasiophygophytes tend to spread in natural habitats. (5) The aggressive ergasiophygophytes transform natural vegetation in new plant communities, and can become dominant species in these communities. New terms, viz. emphemeroxenophytes, protoneophytes, non-aggressive neophytes, slightly aggressive neophytes, and postneophytes with vegetative reproduction have also been introduced to express diverse features of the xenophytes.     

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

The rise of CuI‐catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in‐house preparation of a set of five Fmoc azido amino acids: β‐azido l ‐alanine and d ‐alanine, γ‐azido l ‐homoalanine, δ‐azido l ‐ornithine and ω‐azido l ‐lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user‐friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2‐(1H‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses. Experimental procedures and/or analytical data for compounds 3 – 5 , 20 , 25 , 26 , 30 and 43 – 47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.     

ShRNA knock‐down of CXCR7 inhibits tumour invasion and metastasis in hepatocellular carcinoma after transcatheter arterial chemoembolization

To investigate the effects of lentiviral vector‐mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7‐shRNA, negative control (NC) and blank groups. The qRT‐PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP‐2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7‐shRNA + TACE, CXCR7‐shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP‐2, vascular endothelial growth factor (VEGF) and intratumoral CD31‐positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP‐2 were decreased in the CXCR7‐shRNA group. The cell proliferation and invasion rates of the CXCR7‐shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7‐shRNA + TACE group increased continuously. The CXCR7‐shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7‐shRNA + TACE and CXCR7‐shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP‐2, VEGF and CD31‐positive vessel count. CXCR7‐shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP‐2 and VEGF.     

小球藻热水提取物功能成分的活性跟踪分离

本研究旨在以自由基清除作用和促巨噬细胞增殖作用为导向,对小球藻热水提取物(CPE)的分离纯化产物进行活性跟踪,以确定CPE的主要功能成分。采用高压热水提取、Sevag除蛋白、乙醇沉淀和超滤的方法得到CPE粗多糖,然后通过DEAE52离子交换层析柱和Sephadex G-100对CPE粗多糖组分进一步分离纯化。研究结果表明,通过上述方法对CPE进行分离纯化,得到3种高活性成分PS-1-4-2、PS-1-3-2和PS-2-3-3,经凝胶渗透色谱GPC分析得知其分子质量分别为3.97×10~4 Da、2.28×10~4 Da和4.1×10~3 Da。活性跟踪结果表明,CPE能够清除自由基并促进巨噬细胞Ana-1细胞生长,主要是由于其多种活性组分共同发挥作用,清除自由基作用的功能成分主要集中于PS-1-3、PS-1-4、PS-2-3和PS-2-4,促Ana-1细胞增殖作用的功能成分主要集中于PS-1-3、PS-1-4和PS-2-3。本研究确立了CPE主要功能成分的活性筛选手段,并获得3种新型功能成分,可用于指导小球藻高附加值产品的开发,从而进一步推动微藻能源的产业化进程,实现"高附加值微藻产品、微藻能源与微藻固碳"一体化的示范作用。     

皂苷类药物的制剂研究进展

皂苷类药物普遍分子量比较大,水溶性好,但不易透过细胞膜难以被人体吸收,因此口服制剂体内生物利用度较低.近年来对单体皂苷及总皂苷类药物制剂方面的研究越来越多,随着新型的给药系统和新辅料的出现,皂苷类药物在体内的生物利用度大大提高.本文主要介绍以单体皂苷或总皂苷活性部位为主药的制剂研究进展,以期为该类成分的进一步研究提供思路.