The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and... Show moreThe aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic and macroscopic level. Because we believe optical imaging in particular represents a technology that has unique potential to exploit further our knowledge in preclinical research. First, we imaged breast tumors and their metastases using combinations of four NIR fluorescent probes that possess different optical imaging properties. Then, we studied two different NIR fluorescent probes, PSVue and a heat shock protein-90 alkylator (NIR fluorescent conjugate of GSAO), which can be used to non-invasively imaging cell death with different optical modules in a mouse model of traumatic brain injury. Next, we employed the NIR fluorescently tagged GSAO as a biomarker for monitoring breast cancer cell death after chemotherapy. Moreover, we provides a general discussion about the advantages and the challenging that the state-of-art optical imaging is facing and shares some future prospective. This thesis ends with a summary that outlined the major findings of studies described in different chapters and explored the clinical implications. Show less
Immunotherapy and chemotherapy are major strategies in current cancer treatments. In the first half of this thesis, a new way of antigen cross-presentation from apoptotic cells to APCs, mediated by... Show moreImmunotherapy and chemotherapy are major strategies in current cancer treatments. In the first half of this thesis, a new way of antigen cross-presentation from apoptotic cells to APCs, mediated by gap junctions, is described. And potential anti-tumor applications of gap junction mediated antigen cross-presentation are discussed in the context of the current knowledge. In the second half of this thesis, an unexpected novel mechanism of action__selective induction of histone eviction__is described, which could explain the long standing clinical observation that anthracycline members, like doxorubicin, daunorubicin and aclarubicin, are efficient but with long term side-effects such as cardiotoxicity Show less