Project description:CTCs in cancer patients are thought to be responsible for metastasis. Currently, there is no ex vivo model that can isolate this group of cells. We have developed an ex vivo 4D lung cancer model that forms perfusable tumor nodules and form CTCs. Gene array analyses show 2504 differentially expressed genes when comparing CTCs from the 4D model seeded with A549 cells to the same cells grown on a petri dish (2D). We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, human lung cancer cell line, grown on petri dish (2D) and same cells circulating as tumor cells in our ex vivo model (4D/CTC).
Project description:Tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently we developed an ex vivo lung cancer model (4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown on petri dish (2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown on petri dish (2D) and matrigel (3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2954 genes differentially expressed between 2D and 4D. Gene Ontology (GO) analysis showed up-regulation of several genes associated with extracellular matrix, polarity, and cell fate and development. Moreover, expression array analysis of 2D versus 3D showed 269 genes that were most differentially expressed, with only 35 genes (13%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (versus 2D) correlated significantly with poor survival in patients with lung cancer (n=1492), while the expression signature of 3D versus 2D correlated with better survival in lung cancer patients. Since patients with larger tumors tend to have worse survival, the ex vivo 4D model may offer additional features over the 3D model, to better mimic of natural progression of tumor growth in lung cancer patients. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, human lung cancer cell line, grown on petri dish (2D) and same cells grown in the matrix of our ex vivo model (4D).
Project description:Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated NET-1 siRNA nanoparticles system to conduct targeted gene therapy of HCC xenograft in vivo with the aid of sonodynamic therapy (SDT). Then, a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in this study. The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 61 proteins up-regulated and the expression of 17 proteins were significantly down-regulated. Of the differentially expressed proteins, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein-protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein-protein interactions happened after the NET-1 gene has been silenced. Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC.
Project description:4D printing, integrating the temporal dimension into 3D printing, offers transformative potential for bone implants. Yet its application to metallic materials is constrained by the scarcity of suitable alloys and the requirement for harsh external stimuli to trigger shape change. Here, we introduce 4D printed metallic metamaterials (4DMM) driven by controlled biodegradation. The 4DMM combine biodegradable constraints (e.g., Mg or Zn) with biometals of higher corrosion potential (e.g., Ti). Upon electrochemical degradation of the constraint, the metamaterials recover their original geometry—via stretching, bending, or expansion—generating programmable recoil forces tuned through structural design parameters. When developed as scaffolds for bone implants, 4DMM exhibit excellent cytocompatibility and, in vivo, promote superior bone regeneration through the synergistic effects of bioactivity and mechanical stimulation. This strategy establishes a new paradigm in 4D metal printing via metamaterial design, enabling bioactive, self-restoring implants with broad applicability across biomedical engineering.
Project description:MicroRNAs (miRNAs) are aberrant expressed in hepatocellular carcinoma (HCC) tissue and play a central role in diverse biological processes. We conducted a genome-wide miRNAs screening in 10 pairs of HCC tumor and adjacent non-tumor tissues to test the hypothesis that dysregulation of miRNAs in HCC tumor tissue are partially due to aberrant methylation in relevant miRNAs host genes. Taqman low density arrays were used to examine miRNA profiles in paired HCC tissues, and quantitative RT-PCR was used to validate candidate miRNAs for both discovery and validation sets. A cross-sectional study was conducted in 10 HCC tumor tissues and 10 adjacent non-tumor tissues in Columbia University Medical Center (CUMC), which is approved by the Institutional Review Board.
Project description:We analyzed the proteome of tumor and matched non-tumor biopsies from 51 treatment-naive Hepatocellular carcinoma (HCC) patients by DIA (SWATH). Thereby we aim to find subgroups of patients characterized by specific pathway activation. Furthermore, we aim to find novel factors involved in HCC development and novel biomarkers.
Project description:Overexpression of human epidermal growth factor receptor 2 (HER-2) occurs in 20% of all breast cancer subtypes, those that present the worst prognostic outcome through a very invasive and aggressive tumour. HCC-1954 (HER-2+) is a highly invasive, metastatic cell line whereas MCF-7 is mildly aggressive and non-invasive. We investigated membrane proteins from both cell lines that could have a pivotal biological significance in the metastatic process. Membrane protein enrichment for HCC-1954 and MCF-7 proteomic analysis was performed. The samples were analysed on a two-dimensional liquid chromatography coupled to mass spectrometry (2-D-SCX/RP-LCMS system) and the protein expression was quantified by MSE method. High abundance membrane proteins were confirmed by western blot, immunofluorescence, and flow cytometry. Protein interaction prediction and correlations with TCGA patient’s data were conducted by bioinformatic analysis. The comparison between HCC-1954 and MCF-7 membrane proteins revealed that proteins involved in cytoskeleton organization, such as HER-2, β-1 integrin, E-cadherin and CD166 (ALCAM) were more abundant in HCC-1954. The Cancer Genome Atlas (TCGA) analysis showed a trend toward a positive correlation between HER-2 and β-1 integrin in HER-2+ breast cancer patients. Differences in protein profile and abundance reflect distinctive capabilities for motility and invasiveness between cell lines. HCC-1954 could be an excellent model to study β1 integrin and epithelial–mesenchymal transition (EMT) involvement in trastuzumab resistance mechanisms.