Functionality of insect‐cell‐derived colorectal cancer vaccine candidate protein EpCAM‐Fc in human dendritic cells

The baculovirus–insect cell expression system is widely used to produce recombinant proteins for various biomedical applications. Our previous study demonstrated that EpCAM, a colorectal cancer vaccine candidate protein, can be expressed in the baculovirus–insect cell expression system. However, its functionality (the ability to elicit an immune response), which is important for its possible use as a colorectal cancer vaccine for immunotherapy, still needed to be confirmed. In this study, we examined the ability of recombinant EpCAM to induce maturation of immature dendritic cells (DCs) derived from CD34⁺ cells isolated from human umbilical cord blood. We demonstrated that EpCAM induces the expression of four DC maturation markers: CD80, CD83, CD86 and MHC II. These results suggest that EpCAM produced in the baculovirus–insect cell expression system is functional in terms of its ability to trigger maturation of human DCs.     

Optical quantitative pathology of cervical intraepithelial neoplasia in human tissues using spatial frequency analysis

An optical quantitative histological method in human tissues using spatial frequencies is demonstrated. Optical spatial frequency spectra from different stages of human Cervical Intraepithelial Neoplasia (CIN) tissue are evaluated as a potential quantitative pathological tool. The degree of randomness of tissue structures from normal to different stages of CIN tissue can be recognized by spatial frequency analysis. The standard deviation, σ of human normal and CIN tissue, is obtained by assuming the spatial frequency spectra as a Gaussian distribution. A support vector machine classifier (SVM) is trained in the subspace of σ. Twenty‐eight normal and CIN samples of varying grades are examined and compared with current diagnostic outcomes. Our results suggest that an excellent accuracy for diagnostic purposes can be achieved. This approach offers a simple, efficient and objective way to supplement histopathology in recognizing alterations from normal to different stages of cervical pre‐cancer, which are reflected by spatial information contained within the aperiodic and random structures of the different types of tissue. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody,is associated with inhibition of tumor angiogenesis

Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.     

分化抑制因子-1在大肠癌中的表达及临床意义

目的:研究分化抑制因子-1(Id-1)在人大肠癌组织中的表达及其与临床病理特征的关系。方法:应用免疫组织化学方法(SP法)检测Id-1在56例大肠癌组织及56例远癌肠黏膜中的表达水平,并分析其与临床病理特征的关系。结果:在大肠癌组织中Id-1的过表达率为80.4%,在远癌肠粘膜中过表达率为12.5%,两组比较差异有统计学意义(P0.01)。Id-1过表达与大肠癌Dukes分期及淋巴结转移有关(P0.05),而与患者年龄、性别、肿瘤组织分化程度无关(P0.05)。结论:Id-1过表达可能参与大肠癌演进,Id-1可作为判断大肠癌恶性程度和预后的指标。     

Subtyping borderline nuclear changes: is it of value in predicting high-grade cervical intraepithelial neoplasia on histology?

The aim was to determine the association between the subtypes of borderline nuclear changes (BNC) in cervical smears and high-grade cervical intraepithelial neoplasia (HCIN). BNC was reported in 23236 smears received in our laboratory over a 7-year period, 3278 patients were referred for colposcopy. Analysis was restricted to 2007 cases, which fitted the criteria of: (1). consistent subtyping of borderline change and (2). cervical histology result within 12 months of the last abnormal smear. BNC was reported in six categories and correlated with histology. Atypia bordering on dyskaryosis, atypical metaplastic cells and endocervical atypia, were associated with HCIN in 25%, 25.4% and 23.8% of cases, respectively. Dyskeratosis and koilocytotic atypia were associated with HCIN in 19.2% and 13.7% of cases, respectively. Some subtypes of borderline change are more frequently associated with HCIN. The difference is not sufficient to dictate clinical management.     

NCK is critical for the development of deleted in colorectal cancer (DCC) sensitive spinal circuits

As our understanding of motor circuit function increases, our need to understand how circuits form to ensure proper function becomes increasingly important. Recently, deleted in colorectal cancer (DCC) has been shown to be important in the development of spinal circuits necessary for gait. Importantly, humans with mutation in DCC show mirror movement disorders pointing to the significance of DCC in the development of spinal circuits for coordinated movement. Although DCC binds a number of ligands, the intracellular signaling cascade leading to the aberrant spinal circuits remains unknown. Here, we show that the non‐catalytic region of tyrosine kinase adaptor (NCK) proteins 1 and 2 are distributed in the developing spinal cord. Using dissociated dorsal spinal neuron cultures we show that NCK proteins are necessary for the outgrowth and growth cone architecture of DCC^+ve dorsal spinal neurons. Consistent with a role for NCK in DCC signaling, we show that loss of NCK proteins leads to a reduction in the thickness of TAG1^+ve commissural bundles in the floor plate and loss of DCC mRNA in vivo. We suggest that DCC signaling functions through NCK1 and NCK2 and that both proteins are necessary for the establishment of normal spinal circuits necessary for gait.