Translational Cancer Research

• The animal experiment is an important bridge between cell experiment and clinical experiment.
• Under certain conditions, the occurrence and development of animal diseases are similar to that of human beings, and animals have similar anatomy, physiology and heredity to human beings.
• Animal models are often used to study human diseases.
• In cancer research, the use of animal models can help us understand the genetic basis of cancer and the role of specific genes and gene mutations in the occurrence and development of cancer, which also facilitates the development and testing of drugs.
• Differential Gene Expression Detect genes are differentially expressed between two or more samples (t-test, F-test).
• Bevacizumab in combination with PDL1 has shown some success for the treatment of hepatocellular carcinoma and renal cancer.
• Antiangiogenic therapy has focused on targeting the VEGF-VEGF receptor signaling axis and has included a neutralizing antibody to VEGF (Bevacizumab), decoy receptor for VEGF (Aflibercept), tyrosine kinase inhibitor (Sorafenib), and antibody that blocks VEGF binding its receptor (Ramucirumab).
• Successful integration of antiangiogenic therapy into the clinic will likely require combination with other agents or approaches.
• Microarray analyses are performed using Bioconductor R packages Like affy and limma.
• Microarray data analysis is the final step in reading and processing data produced by a microarray chip.
• Samples undergo various processes including purification and Scanning using the microchip, which then produces a large amount of data that requires processing via computer software.
• The main goal is to remove the systematic bias in the data as completely as possible, while preserving the variation in gene expression that occurs because of biologically relevant changes in transcription.
• As a single agent, most patients either do not respond to antiangiogenic therapy or develop resistance.
• Moderated t-statistic from limma package, Uses empirical Bayes to estimate a posterior variance of the gene with the information borrow from all genes.
• Limma package, Ebayes: borrow information from ensemble of genes, a good strategy for small sample project, superior to t-test.
• RNASeq analysis starts with the conversion of RNA into cDNA.
• Promising preclinical studies have shown potential for the use of chimeric antigen receptor natural killer cells, liver stellate cells and fibroblasts.
• While therapeutically targeting the tumor microenvironment is an attractive strategy for the treatment of cancer, existing FDA-approved treatments have limited efficacy.
• As we continue to understand how the tumor microenvironment contributes to tumorigenesis, new therapeutic targets and strategies will be identified.
• Two commonly used classification methods of cancer animal models are based on different modeling methods and different species.
• Innate immunity is a non-specific defense mechanism that comes into play within hours of a foreign antigen entering the body.
• Single-cell RNA-sequencing (scRNA) allows us to understand cellular differences in expression, making it directly applicable to the studies of cell heterogeneity, cell population and subpopulation identification.
• Gene expression profiling allows us to examine gene expression patterns between various conditions, treatments, and timepoints, but is limiting when understanding gene expression patterns within the cell.
• Persistent inflammation due to chronic infection is a common mechanism underlying tumor formation in several types of cancer, including colorectal, hepatocellular and cervical cancer.
• To overcome a hypoxic and acidic microenvironment, the tumor microenvironment coordinates a program that promotes angiogenesis to restore oxygen and nutrient supply and remove metabolic waste.
• Tumors become infiltrated with diverse adaptive and innate immune cells that can perform both pro- and anti-tumorigenic functions.
• Adaptive immunity is activated by exposure to specific antigens and uses an immunological memory to ‘evaluate’ the threat and enhance immune responses.
• Immune cells fall into two categories: adaptive immune cells and innate immune cells.
• The composition of the tumor microenvironment varies between tumor types, but hallmark features include immune cells, stromal cells, blood vessels, and extracellular matrix.
• An expanding literature on the tumor microenvironment has identified new targets within it for therapeutic intervention.
• Immune cells are critical components of the tumor microenvironment, and depending on the context, a dichotomy exists in the relationship between immune cells and the tumor microenvironment: immune cells can either suppress tumor growth or promote it.
• Early in tumor growth, a dynamic and reciprocal relationship develops between cancer cells and components of the tumor microenvironment that supports cancer cell survival, local invasion and metastatic dissemination.
• Tumor cells stimulate significant molecular, cellular and physical changes within their host tissues to support tumor growth and progression.
• A tumor is not simply a group of cancer cells, but a heterogeneous collection of infiltrating and resident host cells, secreted factors and extracellular matrix.
• T cells, B cells and natural killer (NK) cells belong to the adaptive immune response.
• The tumor microenvironment is not just a silent bystander, but an active promoter of cancer progression.
• Genetically Modified Mouse Models (GEMM) are mouse models that have had their genomes altered for the purpose of studying gene functions.
• Macrophages are critical components of the innate immune system that modulate immune responses through pathogen phagocytosis and antigen presentation.
• Such tertiary lymphoid structures allow close association between T and B cells, and are a positive prognostic marker in breast cancer, melanoma and ovarian cancer.
• Tumor-infiltrating B cells are important in the formation of 'tertiary lymphoid structures', which are ectopic lymphoid structures formed within the tumor microenvironment.