Highlights • Tissue and Liquid Biopsy can be combined in the provision of personalized therapy. • We discuss the clinical applications of cfDNA as a Liquid Biopsy. • We highlight the potential of ...tumor-educated platelets and tumor-related RNA. • An overview of the various and newly developed ctDNA analysis platforms.
Over the last decades, advances in the knowledge of immunology have led to the identification of immune checkpoints, reinvigorating cancer immunotherapy. Although normally restricted to activated T ...and B cells, constitutive expression of CD70 in tumor cells has been described. Moreover, CD70 is implicated in tumor cell and regulatory T cell survival through interaction with its ligand, CD27. In this review, we summarize the targetable expression patterns of CD70 in a wide range of malignancies and the promising mechanism of anti-CD70 therapy in stimulating the anti-tumor immune response. In addition, we will discuss clinical data and future combination strategies.
Considering the important side effects of conventional microtubule targeting agents, more and more research focuses on regulatory proteins for the development of mitosis‐specific agents. Polo‐like ...kinase 1 (Plk1), a master regulator of several cell cycle events, has arisen as an intriguing target in this research field. The observed overexpression of Plk1 in a broad range of human malignancies has given rise to the development of several potent and specific small molecule inhibitors targeting the kinase. In this review, we focus on volasertib (BI6727), the lead agent in category of Plk1 inhibitors at the moment. Numerous preclinical experiments have demonstrated that BI6727 is highly active across a variety of carcinoma cell lines, and the inhibitor has been reported to induce tumor regression in several xenograft models. Moreover, volasertib has shown clinical efficacy in multiple tumor types. As a result, Food and Drug Administration (FDA) has recently awarded volasertib the Breakthrough Therapy status after significant benefit was observed in acute myeloid leukemia (AML) patients treated with the Plk1 inhibitor. Here, we discuss both preclinical and clinical data available for volasertib administered as monotherapy or in combination with other anticancer therapies in a broad range of tumor types.
Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still ...lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as mediators for cell to cell communication because of the regulatory functions of their content. High levels of exosomes are found in several body fluids from cancer patients and could be a potential source of non-invasive biomarkers. In this review, we summarize the diagnostic and prognostic utility of exosomal miRNAs in prostate cancer.
Molecular characterisation of single circulating tumour cells (CTCs) holds considerable promise for predictive biomarker assessment and to explore CTC heterogeneity. We evaluate a new method, the ...DEPArray system, that allows the dielectrophoretic manipulation and isolation of single and 100% purified groups of CTCs from pre-enriched blood samples and explore the feasibility of their molecular characterisation.
Samples containing known numbers of two cell populations were used to assess cell loss during sample loading. Cultured breast cancer cells were isolated from spiked blood samples using CellSearch CTC and Profile kits. Single tumour cells and groups of up to 10 tumour cells were recovered with the DEPArray system and subjected to transcriptional and mutation analysis.
On average, 40% cell loss was observed when loading samples to the DEPArray system. Expected mutations in clinically relevant markers could be obtained for 60% of single recovered tumour cells and all groups of tumour cells. Reliable gene expression profiles were obtained from single cells and groups of up to 10 cells for 2 out of 3 spiked breast cancer cell lines.
We describe a semiautomated workflow for the isolation of small groups of 1 to 10 tumour cells from whole blood samples and provide proof of principle for the feasibility of their comprehensive molecular characterisation.
The use of Building Information Modeling (BIM) for existing buildings based on point clouds is increasing. Standardized geometric quality assessment of the BIMs is needed to make them more reliable ...and thus reusable for future users. First, available literature on the subject is studied. Next, an initial proposal for a standardized geometric quality assessment is presented. Finally, this method is tested and evaluated with a case study. The number of specifications on BIM relating to existing buildings is limited. The Levels of Accuracy (LOA) specification of the USIBD provides definitions and suggestions regarding geometric model accuracy, but lacks a standardized assessment method. A deviation analysis is found to be dependent on (1) the used mathematical model, (2) the density of the point clouds and (3) the order of comparison. Results of the analysis can be graphical and numerical. An analysis on macro (building) and micro (BIM object) scale is necessary. On macro scale, the complete model is compared to the original point cloud and vice versa to get an overview of the general model quality. The graphical results show occluded zones and non-modeled objects respectively. Colored point clouds are derived from this analysis and integrated in the BIM. On micro scale, the relevant surface parts are extracted per BIM object and compared to the complete point cloud. Occluded zones are extracted based on a maximum deviation. What remains is classified according to the LOA specification. The numerical results are integrated in the BIM with the use of object parameters.
Today's construction industry relies heavily on high-performing building information modelling (BIM) systems. By deploying the Industry Foundation Classes (IFC) as a description language, these ...systems offer building information in a widely interoperable format, so that several applications are able to infer extra information. For a certain functionality, IFC shows limitations however. Existing semantic web technology may be able to overcome these limitations, thereby enabling a range of significant improvements and possibilities for automation in building design and construction. This paper gives a short overview of the functionality of IFC as a language, compared to the functionality of languages deployed in the semantic web domain. The improvements generated by deploying semantic web languages are briefly discussed, after which a concrete implementation approach is presented for a semantic rule checking environment for building design and construction. An implemented test case for acoustic performance checking illustrates the improvements of such an environment compared to traditionally deployed approaches in rule checking.
► The Industry Foundation Classes are often combined with procedural code. ► This procedural basis limits building performance checking implementations. ► Logic-based semantic web languages might address these limitations. ► Combining IFC with semantic web technologies appears thus more appropriate. ► A test case for acoustic performance checking briefly illustrates the possibilities.
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