Project description:To determine the effects of photothermal therapy on regulatory genes and molecular pathways of mouse triple negative breast cancer cells (4T1 cells), we studied the RNA sequences of 4T1 cells treated with medium (control), MoS2 NPs and MoS2 NPs + NIR (808 nm).
Project description:Comparative analysis of the transcriptome of primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18), primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR) or lung metastasis foci from 4T1-SCR tumor-bearing mice (4T1-SCR MTTS). Three experimental conditions, 4T1-C18, 4T1-SCR and 4T1-SCR MTTS. Biological replicates: 4 4T1-C18, 4 4T1-SCR, 4 4T1-SCR MTTS independently grown in different mice. 2 days-old tumors and 30 days old lung foci. One replicate per array. All microarrays were processed the same day
Project description:We have reported that intra-tumoral treatment with 1V270, a phospholipid-conjugated TLR7 agonist,induces local expansion an systemic dispersion of oligoclonal tumor-specific T cells by TCR repertoire analysis using next generation RNAseq methodology. Here, we examined whether systemic 1V270 therapy also induced oligoclonal expansion of tumor-specific T cells. Two groups of BALB/c mice (n=4/group) were i.p. treated with 1V270,a phospholipid-conjugated TLR7 agonist. One cohort of mice was i.v. injected with 4T1-GLF cells (2×104) on day 0. Another cohort did not receive i.v. tumor injection (no tumor-exposed mice). 4T1 cells were orthotopically inoculated on day 21. To examine clonal specificity of tumor-specific T cells, CD8+ cells were isolated from the spleens and the tumor infiltrating lymphocytes of secondarily challenged tumors after initial 1V270 therapy. The TCR repertoires were assessed by next generation RNA sequencing of both TCRαand TCR β genes.
Project description:Comparative analysis of the transcriptome of primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a siRNA against murine SPARC (4T1-C18), primary tumors generated from 4T1 cells transduced with a lentiviral vector expressing a scramble sequence (4T1-SCR) or lung metastasis foci from 4T1-SCR tumor-bearing mice (4T1-SCR MTTS).
Project description:Investigation of whole genome gene expression level changes in mouse 4T1 mammary tumors expressing Cebpb shRNA, compared to 4T1 tumors expressing control shRNA. Analysis of mouse 4T1 mammary tumors expressing Cebpb shRNA compared to control shRNA are further described in Johansson & Berg et al 2012. A 10 chip study using total RNA recovered from five separate 4T1 tumors expressing Cebpb shRNA and five separate 4T1 tumors expressing control shRNA. All tumors were surgically removed after subcutaneous implantation in syngeneic BALB/c mice two weeks earlier. Each chip measures the expression level of 44,170 genes from Mus Musculus with fourteen 24-mer probe pairs (PM/MM) per gene, with three-fold technical redundancy.
Project description:we present an aggregation-induced emission (AIE) - bacteria hybrid bionic robot to address the above issues. This bionic robot is composed of a multifunctional AIE molecule, INX-2 and Escherichia coli Nissle 1917 (EcN), i.e. EcN@INX-2. The robot is characterized by NIR-II fluorescence emission with efficient photodynamic and photothermal effects and tumor targeting, which was realized by INX-2 and EcN respectively, EcN@INX-2 achieved in vivo multimodal imaging and therapy of the tumors through multiple mechanisms including the activation of anti-tumor immunity, photodynamic and photothermal therapy in CT26 tumor-bearing female mice.
Project description:The efficacy of photodynamic therapy for treating premalignant and malignant tumors is often limited by the emerging resistant tumor cells. We have developed experimental model systems to study the mechanisms associated with resistance to photodynamic therapy induced by structurally similar photosensitizers (two novel porphyrin-based photosensitizers and temoporfin) in mouse mammary carcinoma cell line 4T1. Photodynamic therapy resistant clones were obtained in vitro by exposure to constant photosensitizer concentration and irradiation with increasing light doses.
Project description:Purpose: To understand the underlying mechanisms of oncolytic virus therapy in breast cancer. Methods: The primary tumors of 4T1 in BALB/C mice were exstracted and analyzed by RNA-seq. Results: In consistent with previous studies, we found some anti-tumor factors were up-regulated. Interestingly, several immunosupressive genes were activited. Conclusion: Our study identified the intercellular and intracellular factors restricting the optimized oHSV efficacy and supported the rationally designed triple therapy for clinical translation.
Project description:Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGFβ hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer. Mice bearing established 4T1 mouse mammary carcinoma treated with pan-isoform specific TGFβ neutralizing antibody, 1D11, showed significantly improved control of the irradiated tumor and non-irradiated metastases, but no effect in the absence of RT. Notably, whole tumor transcriptional analysis demonstrated the selective upregulation of genes associated with immune-mediated rejection only in tumors of mice treated with RT+TGFβ blockade. Mice treated with RT+TGFβ blockade exhibited cross-priming of CD8+ T cells producing IFNγ in response to three tumor-specific antigens in tumor-draining lymph nodes, which was not evident for single modality treatment. Analysis of the immune infiltrate in mouse tumors showed a significant increase in CD4+ and CD8+ T cells only in mice treated with the combination of RT+TGFβ blockade. Depletion of CD4+ or CD8+ T cells abrogated the therapeutic benefit of RT+TGFβ blockade. These data identify TGFβ as a master inhibitor of the ability of RT to generate an in situ tumor vaccine, which supports testing inhibition of TGFβ during radiotherapy to promote therapeutically effective anti-tumor immunity. We used genome-wide microarray to depict main biological processes responsibles for the therapeutic benefit of the combination ofTGF-beta blockade and local radiotherapy. To gain a more comprehensice protrait of the effects of RT and TGFbeta blockade on gene expressionin tumors, we collected 4T1 tumors 4 days after completion of RT. Three tumors from each group were then subjected to RNA extraction and hybridization on affymetrix array.
Project description:4T1 mouse mammary carcinoma cells have an autocrine FGFR active loop leading to constitutive activation of downstream signaling pathways. We found that FGFR inhibitors have a strong effect on 4T1 tumors in-vivo. We used microarray to understand the contribution of FGFR signaling to the tumor formation upon TKI258 treatment. 4T1 cells were injected in the 4th mammary gland of Balb/C mice. After 7 days, daily treatment with TKI258 or water was performed for 14 days. At the end of the experiment, the RNA were extracted from three individual tumors per condition and hybridized on Affimetrix microarrays.