| Summary: | 碩士 === 國立臺灣大學 === 醫學工程學研究所 === 99 === Strategies of treatments on cancers evolve with the understanding of their epidemiology and biology. Traditional chemotherapies not only kill cancers, but also do harms to normal tissues. To selectively treat on cancer, target therapies can deliver drugs to the biomarkers over expressed on cancer cells through a specific antibody binding. Because of the polymorphism of genetic phenotype, markers of tumors are quite different even though they grow in the same organ. With this blind spot of chemotherapy, treatments on cancers can further induce the genetic mutation. Therefore, treating cancers with markers just on themselves is not enough. Recently, people start to search markers necessary for the development of tumors. Candidate targets could be the critical ligands or secondary messengers on the transduction pathways among tumor cells, extracellular matrices, blood vessels, and immune cells. Through the blocking of tumor-associated signal transduction in the microenvironment, such pathway-targeting therapy can arrest the tumor growth and prevent tumor metastasis. Therefore, the understanding of the interaction between tumors with surrounding microenvironment in vivo is an important first step and basis for pathway-targeting cancer therapy.
In this thesis, we develop a small animal nonlinear microscopic imaging platform for in vivo, high-resolution, long-term, consecutive observation on tumor microenvironments. It was achieved with the least invasive femtosecond Cr:forsterite laser and a laser scanning microscope. Through this unique platform, we can in vivo investigate three major contexts of tumor microenvironments with sub-micron spatial resolution, that is, the remodeling of collagens, the trafficking of immune cells, and the permeability of neovasculatures. We anticipate thus developed platform with ongoing developments in molecular probes can be a powerful tool to reveal spatial-temporal dynamics of molecular pathways in tumor microenvironments, enhance our understanding of tumor biology, and trigger new therapeutic approaches.
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