ABSTRACT: Detecting metastatic tumors after γ-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules
Project description:Microarray analysis in the mouse metastatic tumor after ɣ-irradiation(ɣ-IR): non-irradiated primary tumor vs. radiated primary tumor vs. metastatic tumor after ɣ-irradiation Metastatic tumors in C6-L (rat glioma cells ) xenografted mice were studied after local treatment with fractionated γ-IR. To accurately detect the metastatic nodules after γ-IR, we observed the effect of γ-IR on distant metastatic tumor growth. Metastatic nodules after γ-IR indicated extensive colonization of C6-L cells in the lungs within 6 weeks after γ-IR. Identified and described the molecular events occurring after γ-IR through gene expression profiling to elucidate genetic changes (differentially expressed genes between the γ-IR primary tumors vs. non-γ-IR primary tumors and metastatic lung nodules vs. γ-IR primary tumors). We investigated the change of gene expression profile in the γ-IR primary tumors vs. non-γ-IR primary tumors and metastatic lung nodules vs. γ-IR primary tumors in rat glioma (C6-L cell) xenograft model.
Project description:Microarray analysis in the mouse metastatic tumor after ɣ-irradiation(ɣ-IR): non-irradiated primary tumor vs. radiated primary tumor vs. metastatic tumor after ɣ-irradiation Metastatic tumors in C6-L (rat glioma cells ) xenografted mice were studied after local treatment with fractionated γ-IR. To accurately detect the metastatic nodules after γ-IR, we observed the effect of γ-IR on distant metastatic tumor growth. Metastatic nodules after γ-IR indicated extensive colonization of C6-L cells in the lungs within 6 weeks after γ-IR. Identified and described the molecular events occurring after γ-IR through gene expression profiling to elucidate genetic changes (differentially expressed genes between the γ-IR primary tumors vs. non-γ-IR primary tumors and metastatic lung nodules vs. γ-IR primary tumors).
Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray A highly metastatic mouse squamous cell carcinoma NR-S1 was implanted into the hind leg of synergetic C3H/HeNrs mice and irradiated with 5 Gy of carbon ion beam. 8 Gy of gamma ray was used as a reference beam. At 2 weeks after the irradiation, the lung tissue was sampled. In order to collect samples of primary tumors, the tumors were implanted in other mice and irradiated in the same manner, and the primary tumors were collected at 1 week after the irradiation. The tumor cells of the primary and metastatic tumors were collected by laser microdissection, and oligonucleotide microarray analysis of the irradiated primary tumors and the metastatic tumors were all performed in comparison to the non-irradiated primary tumor by two-color methods.
Project description:Analysis of LBNF1 rat testes from controls, containing both somatic and all germ cell types and from irradiated rats in which all cells germ cells except type A spermatgogonia are eliminated. Results provide insight into distinguishing germ and somatic cell genes and identification of somatic cell genes that are upregulated after irradiation.
Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray
Project description:Preclinical lung cancer models frequently fail to predict clinical outcomes due to their limited ability to replicate the complex tumor microenvironment and metastatic processes seen in patients. In this study, we establish and characterize a clinically relevant orthotopic lung cancer model in mice, offering a substantial advancement over conventional subcutaneous models. Using thoracotomy-based injection of luciferase-expressing lung adenocarcinoma cells, we consistently generate single, well-defined nodules within the lung parenchyma that closely mimic human primary tumors. Longitudinal monitoring with bioluminescence imaging and computed tomography enables accurate spatial and volumetric assessment of tumor progression, with tumor size correlating with the initial cell dose.	
Comparative analyses demonstrate that orthotopic tumors exhibit enhanced vascularization, proliferation, and reduced hypoxic and stress markers (HIF-1α, γH2AX, p16, p21), alongside elevated Cyclin D1 expression-features reflecting a more physiologically relevant tumor environment. Importantly, orthotopic tumors display an enriched and organized immune infiltration, including enriched CD4⺠and CD8⺠T cells and dendritic cells, forming immune niches not present in subcutaneous models. 	
To model metastasis, we isolate and culture circulating tumor cells (CTCs) from orthotopic tumor-bearing mice. Intracardiac injection of these CTCs leads to organ-specific metastases (e.g., liver, brain, bone), recapitulating clinical dissemination patterns. Transcriptomic and proteomic profiling of metastatic sublines reveals both conserved pro-metastatic programs-including chemokine signaling, EMT, and immune evasion-and niche-specific adaptations, particularly in bone metastases.	
This orthotopic model offers enhanced translational relevance for evaluating therapies and dissecting metastatic progression in lung cancer.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes