Project description:The aim of this study was to investigate the inhibitory effect of TSU68, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRβ) and fibroblast growth factor receptor 1 (FGFR1), on colon cancer liver metastasis and to test the hypothesis that TSU68 modulates the microenvironment in the liver before the formation of metastasis. Experiment Overall Design: The human colon cancer TK-4 was implanted orthotopically into cecal walls of 6-week-old male BALB/c nu/nu mice (Clea Japan, Tokyo, Japan). The animals were treated with TSU68 (400 mg/kg/day, twice-daily, p.o.) or vehicle from 7 days after orthotopic implantation. After one week of drug administration, livers were removed and total RNA was extracted. Experiment Overall Design: We established four different groups of mice; non-tumor-bearing and treated with vehicle alone (NT-Co), non-tumor-bearing and treated with TSU68 (NT-TSU), tumor-bearing and treated with vehicle (T-Co), and tumor-bearing and treated with TSU68 (T-TSU). NT-Co, T-Co and T-TSU group were applied to microarray analysis.
Project description:To characterize the immune landscape of colorectal tumors, we analysed the immune tumor microenvironment cells from mice bearing orthotopic tumors using single cell transcriptomics.
Project description:Validation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer. Microarray analysis was performed on intrahepatic cholangiocarcinomas formed at 10, 15, and 25 days after bile duct inoculation of neu-transformed rat cholangiocytes (BDEneu cells) into rat liver and on peritoneal metastases at the 25 day time period, compared with non-cancerous right liver lobe from the same animals. Experiment Overall Design: Tumors were collected at 10, 15, 25 days post inoculation from biological triplicates (different rats innoculated simultaneously). Also, biological triplicates of metastatic tumors (Mets) at day 25 were analyzed. Biological triplicates of paired normal right liver lobe (RLL) from the same animals from which tumors/mets were obtained were also analyzed in this study. Thus, a total of 9 rats were used for this study.
Project description:Total RNA was isolated from normal C57BL/6 mouse pancreas, PANC02-H7, and UN-KC-6141 tumors from tumor-bearing mice. The RNA was used for RNA-Seq. The gene expression profiles between normal mouse pancreas and orthotopic pancreatic tumors were compared, and differentially expressed genes were identified.
Project description:The aim of this study was to identify the transcriptomic response 6 hours after the MRT irradiation, in normal brain tissue (11 samples) and in glioma tissue (11 samples), in rat. The orthotopic tumor-bearing rats were either treated with MRT radiation (six MRT-tumors), or untreated (five No irradiated tumors). The contralateral half hemisphere without tumor received the MRT treatment for six rats (6 MRT-Contralateral samples) and no irradiation for five rats (5 Untreated contralateral samples). Six hours after treatment, the tumors and their controlateral regions were resected and analysed for transcriptomic response.
Project description:The spontaneous pulmonary metastasis model of human uterine sarcoma was established using GFP-expressed MES-SA cells. Several sublines with different metastatic potentials were generated by in vivo passaging. We used microarrays to identify the metastatic-related genes using the orthotopic tumors with different metastatic potentials. Orthotopic transplanted uterine sarcoma were observed after 3 weeks post-transplantation and the xenografted tumor reached about 2000 mm3 in additional 3 weeks. After 6 weeks post-transplantation, the animals were sacrificed under isoflurane anesthesia, and the tumors were resected. The GFP-positive regions were collected using Leica MZ10F fluorescent stereomicroscope. This study compared the gene expression profiling between the orthotopic tumors with high (H)- and low (L)-metastatic potentials.
Project description:We treated FVBN/J mice bearing orthotopic KI tumors with vehicle or CA-4948 for two weeks and performed bulk RNASeq to assess transcriptomic changes in the tumor
Project description:Metastasis is a major factor for mortality in patients with hepatocellular carcinoma (HCC). Thus, there is a need for predictive biomarker(s) for detecting the tipping point before metastasis, so as to prevent further deterioration. To discover early warning signals of pulmonary metastasis in HCC, we analysed time-series gene expression data in the spontaneous pulmonary metastasis mouse HCCLM3-RFP model with our novel dynamic network biomarker (DNB) method. To simulate tumour growth and metastasis in patient livers, we used the spontaneous pulmonary metastasis mouse model, HCCLM3-RFP, which involves the orthotopic transplanted human HCCLM3 cell line labelled with a stable fluorescent protein.We observed that, hepatic tumours in orthotopic xenograft HCCLM3-RFP mice grew gradually from the second to the fifth week after orthotopic implantation in the primary liver tissue, whereas spontaneous pulmonary metastasis occurredonly at the last time point (the fifth week after orthotopic implantation).Thus, we chose the second, third, fourth, and fifth weeks after orthotopic implantation as observation points to collect liver tumours of five orthotopic xenograft mice at each time point and to assess the whole-genome expression.