Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with chronic hepatitis B virus (HBV) infection being a major contributor to its development. Despite this, effective treatment for HBV-associated HCC remains a significant challenge. In this study, we combined the strengths of vesicular stomatitis virus (VSV) and therapeutic vaccines to propose a novel strategy for treating HBV-related liver cancer. We engineered an oncolytic virus that delivers hepatitis B surface antigen (HBsAg) and the IL-15 cytokine directly to tumor cells, thereby enhancing immune activation and promoting tumor cell destruction. As the tumor cells die, they release additional virus particles, spreading HBsAg and IL-15 expression to neighboring tumor cells. This approach demonstrated promising efficacy in multiple HBV-positive HCC mouse models.
Project description:Analysis of whole transcriptome gene expression in 6 groups of liver samples in mice: HCC induced by high-LET radiation, HCC induced by low-LET radiation, spontaneous HCC, non-tumor liver irradiated with high-LET radiation, non-tumor liver irradiated with low-LET radiation, normal liver without radiation.
Project description:To investigate the inhibitory effect of K458R mutation of HNF4A on HCC, we established Huh-7 xenografts treated with Ad-GFP, Ad-HNF4A or Ad-K458R. We then performed gene expression profiling analysis using data obtained from RNA-seq of three groups of Huh-7 xenografts treated with adenovirus.
Project description:This study looked for signals produced in UV-B irradiated leaves, and possibly induced in shielded leaves, that modulate physiological responses in maize. Transcriptome and proteomics profiling tracked changes in exposed and shielded organs. Metabolic profiling was examined for signaling molecules. Exposure of just the top leaf substantially alters the transcriptome of both irradiated and shielded organs, with greater changes as an additional 1-2 leaves are irradiated. Transcriptome, proteome and metabolome changes are UV-B regulated in shielded organs. Early steps in signal transduction and possible signal molecules are identified utilizing a time course experiment. Keywords: UVB, maize, leaves, ears Compared irradiated leaves in a time course, irradiated leaves versus shielded leaves, and shielded ears on plants with irradiated leaves. Also compared different number of leaves being irradiated. Spike-in controls were included.
Project description:BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a high mortality rate due to the lack of effective treatments and drugs. Arsenic trioxide (As2O3, ATO, arsenious acid), which has been proved to successfully treat acute promyelocytic leukemia (APL), was recently reported to show therapeutic potential in solid tumors including liver cancer. Although the mechanistic effects of ATO in APL are established, its anticancer mechanism of action in HCC is still unclear. METHODS: We established an HCC subcutaneous xenograft and intrahepatic metastasis mouse model. In CSC models, tumorspheres and the flow cytometry analysis of CSC markers together with limiting dilution and serial transplantation were used. We compared mRNA expression profiles of the ATO-treated and control cells with mRNA microarray. The expression of target molecule or a clinical correlation was analyzed by immunohistochemistry staining in tissues from ATO-treated mouse and 76 HCC patients. We generated five stable minichromosome maintenance protein 7 (MCM7)-knockdown and two stable MCM7-overexpression HCC cell lines. The chromatin immunoprecipitation (ChIP) assays, immunoprecipitation (IP) assays, the dual luciferase reporter assays, a green biarsenical labeling reagent (FlAsH-EDT2) and a “competing endogenous RNA” (ceRNA) analysis were used. RESULTS: ATO could inhibit the liver tumor-initiating capacity and distant metastasis and prolongs survival in mice. We then screened and found that ATO downregulates the overexpression of MCM7 which is correlated with the progression and prognosis in HCC patients. Knockdown of MCM7 expression recapitulates the inhibition function of ATO on self-renewal of cancer stem cells (CSCs), while overexpression of MCM7 abolishes the inhibition function of ATO on tumorsphere formation. Most importantly, we revealed that ATO directly binds to the MCM7 protein and disturbs the interaction between serum response factor (SRF) and MCM7, resulting in downregulation of MCM7 transcription. A ceRNA analysis also indicated the alterations of endogenous MCM7-associated gene networks involved in stemness-related signaling pathways and cell differentiation. CONCLUSIONS: Here, for the first time, we report that ATO inhibits liver CSCs through blocking the interaction between SRF/MCM7 and suppressing MCM7 autoregulation activity.
Project description:Gene expression was analyzed and compared of normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC cells. The results provide valuable information about the gene expression alterations during the chronic process of liver cancer development. HCC in age-matched male mice were induced by DEN injection. Normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC were freshly isolated and RNA extracted.
Project description:Hepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600,000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, β-catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths We used microarrays to detail the global programme of gene expression profiles of cirrhosis and tumor liver samples. 15 cirrhosis and 15 HCC samples were collected with informed constent of each patient. Surgically resected tissues were snap frozen in liquid nitrogen and stored at -80C, and subjected to RNA extraction. Histology slides were prepared for all samples and scored by an experienced scientist. For the tumor samples, tissues were resected from inside the tumor, while tissues were resected from adjacent tissue sorrounding the tumor for non-tumor samples.