Project description:RNAi-mediated silencing of Rab5 and the consequent loss of endosomes in the mouse liver caused severe metabolic defects such as hypoglycemia, hepatomegaly, hypercholesterolemia, hyperlipidemia and glycogen accumulation. Gene expression in mice liver after knockdown of Rab5 has been performed the Mouse Genome 430 2.0 microarrays to identify biological processes and pathways affected by Rab5. The mice received either PBS or lipid nanoparticles (LNPs) loaded with siRNAs agains Rab5all or Luciferase control at 1.5 mg/kg via tail vein injection. At 5 day post injection mice were sacrificed using cervical dislocation and liver tissue was harvested, snap frozen in liquid nitrogen for RNA isolation; Gene expression studies were performed applying the Mouse Genome 430 2.0 microarrays.
Project description:We used here the presence of disseminated tumors cells (DTC) in the bone marrow for defining early metastasized breast cancer patients. By comparing expression profiles of early metastasized primary breast tumors with non-metastasized tumors, we found candidate metastasis suppressor genes that were further validated in other published breast cancer data.
Project description:Background: Immune checkpoint inhibitors combined with antiangiogenic therapy has become the standard of care for advanced hepatocellular carcinoma, albeit with limited therapeutic benefit. Our previous studies demonstrated the immunomodulatory and antitumor effects of polyIC, a synthetic double-stranded RNA. Here, we compared the efficacy of anti-programmed death ligand 1 (?PD-L1) plus polyIC versus ?PD-L1 plus anti-vascular endothelial growth factor (?VEGF) in primary liver tumor models.Conclusion: This preclinical study identifies polyIC as a better enhancer of ?PD-L1 efficacy than ?VEGF in liver cancer, providing a novel strategy for improving immunotherapy outcomes. Further clinical investigation is warranted.
Project description:This study aimed to explore the mechanism of Astragalus Polysaccharide loaded chitosan / pectin nanoparticles (APS CS / Pt NPs) in preventing the malignant transformation of liver fibrosis to liver cancer by regulating the gut liver axis, improving the structure of intestinal flora, reducing lipid accumulation, and regulating the nf- κ B signaling pathway.
Project description:To further study the transcriptome of Caco-2 human colon epithelial-like cells after exposure to S-nitrosoglutathione (GSNO, 1.4 μM), or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO) we investigate whole genome microarray to identify genes regulates by exposure or not to GSNO (1.4 μM) or Eudragit RL PO polymeric nanoparticles (NP-ERL, 50 μg/mL) or GSNO loaded nanoparticles (NP-GSNO, 50 μg/mL corresponding to (1.4 μM GSNO).
Project description:Perotein corona is formed surrouding interface of nanopsrticles upon administered in biological fluids. The quality of protein corona is recognized as the crucial factor for in vivo fate of the administered nanoparticles. In this project, Cas9 ribnonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) capable of robust gene knockout of hepatic genes of interest after single intravenous injection were developed. Compared with short interfering RNA (siRNA)-loaded LNPs, RNP-loaded LNPs showed different morphology, biodistribution, and mechanism of hepatic acccumulation. Therefore, proteome analysis of the corona proteins on the RNP and siRNA-loaded LNPs were performed to elucidate the impact of payloads on nano-bio interactions.
Project description:To further study the transcriptome of THP-1 human monocytes after exposure to S-Nitrosoglutathione (GSNO), we investigate whole genome microarray expression to identify genes regulated by exposure or not to GSNO. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 50 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of GSNO-loaded ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 200 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 200 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 24 h to 50 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of GSNO-loaded ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 24 h to 50 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 50 ug / mL of empty polymeric Eudragit RL nanoparticles (empty ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 50 ug / mL of empty ENP. To further study the transcriptome of THP-1 human monocytes after exposure for 4 h to 200 ug / mL of S-Nitrosoglutathione-loaded polymeric Eudragit RL nanoparticles (GSNO-loaded ENP), we investigate whole genome microarray expression to identify genes regulated by exposure or not to 200 ug / mL of GSNO-loaded ENP.
Project description:Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease with a 5 year overall survival rate of 11%. In order to better understand and characterized PDAC we have performed RNAseq on 289 primary and metastatic PDAC tumors collected at our center. Nucleic acids (RNA and DNA) were extracted from formalin fixed paraffin embeded FFPE tumor tissue with tumor enriched regions identified by pathologic analysis. RNA sequencing and resulting gene expression data was then used to study biologic differences in primary PDAC tumors that metastasized to either the liver or to the lung but not liver based on clinical data review. A novel gene expression signature was identified for liver vs lung avid metastatic properties. Samples in the entire cohort were then scored based on this gene signature. Pathway analysis revealed that samples high for this signature (as well as liver cohort patient samples) were enriched for pathways involved in ongoing replication stress response, and this was associated with poorer patient outcome.
