Next-generation diagnostic pathology / 中华病理学杂志

With the technological progresses and applications of human genome sequencing, bioinformatics analysis and data mining, and molecular pathology and artificial intelligence-assisted pathological diagnosis, the development of clinical medicine is moving towards the era of precision diagnosis and treatment. In the context of this era, the traditional diagnostic pathology is facing unprecedented opportunities and challenges in our history and is striving towards the "next-generation diagnostic pathology" (NGDP). NGDP is based on histomorphology and clinical data, and characterized by the combination of molecular detection and bioinformatics analysis, intelligent sampling and process quality control, intelligent diagnosis and remote consultation, lesion visualization and "non-invasive" pathology as well as other innovative cutting edge interdisciplinary technologies. The NGDP reports will include the results from multi-omics and cross-scale integrated diagnosis for final diagnosis. NGDP will also be applied for predicting disease progression and outcomes, and determining optional therapeutics as well as assessing treatment responses, so that a novel "golden standard" of disease diagnosis can be established. In the near fature, it is necessary to stimulate the innovative vitality of pathology disciplines, accelerate the maturity and application for NGDP, update the theory and technical system of pathology, and perform its important applicable role in the prevention, diagnosis, treatment of diseases so that the futher development of clinical medicine will be promoted and the strategy for maintenance of being healthy in China will be served.

Contribution of cancer stem cells to tumor vasculogenic mimicry

Vasculogenic mimicry (VM), a newly-defined pattern of tumor blood supply, provides a special passage without endothelial cells and is conspicuously different from angiogenesis and vasculogenesis. The biological features of the tumor cells that form VM remain unknown. Cancer stem cells (CSCs) are believed to be tumor-initiating cells, capable of self-renewal and multipotent differentiation, which resemble normal stem cells in phenotype and function. Recently CSCs have been shown to contribute to VM formation as well as angiogenesis. These findings challenge the previous understanding of the cellular basis of VM formation. In this review, we present evidence for participation of CSCs in VM formation. We also discuss the potential mechanisms and possible interaction of CSCs with various elements in tumor microenvironment niche. Based on the importance of VM in tumor progression, it constitutes a novel therapeutic target for cancer.

Activation of CXCR4 in human glioma stem cells promotes tumor angiogenesis / 中华病理学杂志

<p><b>OBJECTIVE</b>To isolate, culture and identify glioma stem cells from human malignant glioma cell line U87, and investigate the changes of pro-angiogenic factors production by glioma stem cells followed by activation of CXCR4 and observe their tumorigenesis as well as the expression of vascular endothelial growth factor when implanted into nude mice.</p><p><b>METHODS</b>The ratio of CD133 positive cells was detected by flow cytometry. Magnetic separation of CD133 positive cells was carried out on the magnetic cell sorting system (MACS). Expression of nestin, glial fibrillary acidic protein (GFAP) and CXCR4 on tumorspheres was detected by indirect immunofluorescence under confocal laser scanning microscopy. The functional activation of CXCR4 was assessed by calcium mobilization experiments. ELISA was used to detect the production of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in conditioned medium. Glioma stem cells were implanted into nude mice to assess their tumorigenesis ability and the expression of VEGF.</p><p><b>RESULTS</b>The ratio of CD133 positive cells with stem cell property was 0.5% in U87 cells. Activation of CXCR4 on glioma stem cells induced calcium mobilization and increased VEGF and IL-8 protein secretion. CD133 positive cells secreted more VEGF and IL-8 than their negative counterparts in vitro. Tumors derived from CD133 positive cells grew more rapidly and expressed elevated level of VEGF than their negative counterparts.</p><p><b>CONCLUSIONS</b>There are a small fraction of glioma stem cells in human glioblastoma cell line U87. Expressing functional CXCR4 and secreting more pro-angiogenic factors may be involved in tumor angiogenesis mediated by glioma stem cells.</p>

Effect of nordy on FPR function of malignant human glioma cell line U87 / 药学学报

Nordy is a synthesized chrial compound. To investigate the effects of nordy (25 - 100 micromol x L(-1)) on the function of formylpeptide receptor (FPR) of malignant human glioma cells, human glioblastoma cell line U87 was used to detect its proliferation, migration, calcium mobilization, vascular endothelial growth factor (VEGF) mRNA and protein levels after activation of FPR by its agonist N-formyl-methionyl-leucyl-phenylalanine (fMLF). Cell proliferation, migration ability, VEGF mRNA, VEGF protein and calcium mobilization were evaluated by cell counting, chemotaxis assay, RT-PCR, ELISA and spectrometry. Nordy (50 - 100 micromol x L(-1)) potently inhibited the proliferation, migration and calcium mobilization of U87 cells induced by fMLF (P < 0.05). Moreover, 100 micromol x L(-1) nordy showed a significantly impaired VEGF mRNA expression and protein secretion induced by fMLF (P < 0.05). Nordy could inhibit FPR functioning in glioma cell proliferation, migration and angiogenesis, which might be a possible mechanism of its anti-cancer effects.