Project description:we aim to compare the difference of chemotherapy responses between FOLFOX-resistant and wild type colorectal cancer cells for suggesting novel treatment targets.
Project description:To find candidate circRNAs and to unravel their molecular functions during colorectal cancer progression and during LDM topotecan chemotherapy, we utilized a xenograft mouse model based on the HT29.hCG.Luc colorectal cancer cell line (referred to as HT29) implanted into SCID mice. HT29 cells were injected into the spleen and primary tumors developed. Three mice served as control group while two mice served as LDM topotecan treated group. After another 4-6 weeks, liver metastasis can be detected and resected for further investigation. For a global view on gene expression changes, we performed rRNA-depletion RNA-Seq from HT29 cells, primary tumors and liver metastases.
Project description:To find candidate circRNAs and to unravel their molecular functions during colorectal cancer progression and during LDM topotecan chemotherapy, we utilized a xenograft mouse model based on the HT29.hCG.Luc colorectal cancer cell line (referred to as HT29) implanted into SCID mice. HT29 cells were injected into the spleen and primary tumors developed. Three mice served as control group while two mice served as LDM topotecan treated group. After another 4-6 weeks, liver metastasis can be detected and resected for further investigation. For a global view on miRNA changes, we performed miRNA-Seq from HT29 cells, primary tumors and liver metastases from control mice (C-PT and C-LM) and liver metastases from treated mice (T-LM).
Project description:We studied the impact of a combination of chemotherapy and PD-1 immune checkpoint blockade on tumor progression in the PyMT mammary carcinoma mouse model compared to each treatment as monotherapy. To gain insight into the reasons underlying improved efficacy of combined chemoimmunotherapy, whole transcriptome profiling of tumors of mice receiving either a control antibody, anti-PD-1 antibody, doxorubicin chemotherapy + a control antibody or doxorubicin chemotherapy + anti-PD-1 antibody was performed via next generation mRNA sequencing, in triplicates, on a NextSeq 550 high-throughput bench top sequencer.
Project description:To measure global gene expression in primary metastatic colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. Samples from primary metastatic colorectal cancer patients were collected. The effects of chemotherapy were evaluated.
Project description:The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 39 patients with metastatic colorectal carcinoma
Project description:Background: Capecitabine-based adjuvant chemotherapy is the first-line treatment for patients with colorectal cancer (CRC). Although this therapy generally reduces the incidence of CRC recurrence and mortality, it can cause various chemotherapy-related adverse events (CRAEs), one of the most frequent of which is hand-foot syndrome (HFS). Most of the currently available HFS prediction markers focus on the pharmacokinetic parameters of drugs or their metabolites, yet our understanding of the biomolecular mechanism of HFS remains limited. Methods: We conducted an integrated multi-omics analysis of 63 Chinese patients with colorectal cancer (CRC) who had chemotherapy related adcerse effect (CRAE) records during adjuvant chemotherapy. The metabolomic profiles for each of plasma, urine, and colorectal tissue as well as profiles for colorectal-tissue transcriptomics and genome methylation were analyzed based on samples collected before and during surgery. Results: Susceptibility to HFS was found to be associated with profibrotic changes in several aspects of cellular biochemistry and physiology, characterized by reduced nucleotide salvage (indicating potential tissue damage, elevated spermine release, increased M2 macrophage polarization, and hypermethylation of genes for collagen formation. All these aspects were found to promote fibrosis, even before patients received chemotherapeutic drugs or developed any HFS symptoms. Additionally, we developed and validated relevant biomarkers with reasonably good discrimination performance and a high AUROC (area under the receiver operating characteristic curve) value, i.e., from 0.848 to 1.000. Conclusions: Our results demonstrate that a profibrotic phenotype characterized by multi-omics variation in colorectal tissue, plasma, and urine is closely related to the susceptibility to chemotherapy-induced HFS. Our findings provide a better understanding of the molecular mechanism underlying HFS.
Project description:Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear if drug efficacy data obtained from xenograft models translate into clinically-relevant treatment modalities. In this study, we have generated a panel of 28 patient-derived colorectal cancer explants (PDCCEs), an extension of our previous work, by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice. A comprehensive histological and molecular evaluation of PDCCEs and their corresponding patient tumor demonstrates that PDCCEs maintain histological features and global biology through multiple passages. Furthermore, we demonstrate that in vivo sensitivity of PDCCEs to oxaliplatin can predict patient outcomes. Our findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and can serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with CRC. 28 human primary colorectal and 37 mouse derived colorectal explant tumors
Project description:Colorectal Cancer (CRC) is one of most common cancers in the world and a main treatment in postoperative chemotherapy is oxaliplatin and fluorouracil (FOLFOX), But the effect is different among CRC patients. In this study, LC-MS/MS strategy was used to profile the plasma proteome in FOLFOX benefit and futile group. As a result, a panel of plasma proteins by machine learning from our data was verified for a possible prediction tool in postdiagnosis.