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:Investigation of the Types and Expression Levels of Target Proteins Regulated by the Transcription Factor NapR Following Its Overexpression in Intracellular BCG vaccine
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:We have developed a 4D lung cancer model that forms perfusable tumor nodules. We determined if the model could be modified to mimic metastasis. We modified the 4D lung cancer model by seeding H1299 cells via the trachea only to the left lobes of the acellular lung matrix. The model was modified so that the tumor cells can reach the right lobes of the acellular lung matrix only through the pulmonary artery as circulating tumor cells (CTC). We determined the gene expressions of the primary tumor, CTCs, and metastatic lesions using the Human OneArray chip. All cell lines formed a primary tumor in the left lobe of the ex vivo 4D lung cancer model. The CTCs were identified in the media and increased over time. The CTC gene signature predicted poor survival in lung cancer patients. A unique set of genes were significantly expressed in CTC compared to the primary tumor and metastatic lesion. The 4D lung cancer model can isolate tumor cells in three phases of tumor progression. This 4D lung cancer model may mimic the biology of lung cancer metastasis and may be used to determine its mechanism and potential therapy in the future.
Project description:The ovarian tissues of 3 mice aged 3 months in the control group and the hyperhomocysteinemia group were selected for advanced 4D Laber-free quantitative proteomic analysis. According to 4D Laber-free quantitative proteomics analysis, we successfully quantified 56,611 peptides and identified 5,764 quantifiable proteins. Principal component analysis (PCA) highlights the extraordinary quantitative repeatability between biological replicas. Subsequently, we screened for differentially expressed proteins (DEPs) (P <0.05, multiple change (FC) >1.5). The results showed that there were 317 up-regulated and 113 down-regulated proteins.