Pancreatic cancer (PC) is a challenging cancer to treat, with a 5 year survival of < 13% in the United States. This is attributed to multiple histologic subtypes, extensive desmoplastic reactions, resistance to chemotherapy, profound immunosuppression and crosstalk between tumor, immune and stromal cells in the microenvironment. Alternative modalities are needed to treat this aggressive tumor. Our laboratory has shown that targeting polyamines using a polyamine blockade therapy (PBT), which is a combination of Difluoromethylornithine (polyamine synthesis inhibitor) and Trimer44NMe (polyamine transport inhibitor), is effective against PC. In the present study, we used a KPC genetic model of PC, as it mimics human tumors from spontaneous tumor conception to metastasis. Despite tumor heterogeneity, PBT improved outcomes in KPC mice. Histopathology revealed decreased tumor size, variable decrease in tumor weights, and significant stromal alterations. Stromal alterations were driven by reduced collagen deposition. PBT was found to variably inhibit markers associated with cancer-associated fibroblasts and activated pancreatic stellate cells, which are key producers of collagen. Also, M1 macrophage associated markers were upregulated in the microenvironment. To elucidate the effect of PBT on cells known to contribute to the immunosuppressive environment in PC, we treated bone marrow-derived myeloid derived suppressor cells (MDSC). We found using flow cytometry that PBT inhibited the abundance of PMN (polymorphonuclear)-MDSC phenotype. Finally, RNA sequencing revealed that PBT inhibited genes involved in chemotaxis and inflammation associated with MDSC biology. Collectively, this work provides the basis for feasibility and utility of testing PBT in larger cohorts of the KPC model.

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This thesis is a part of the research work for Azelio TES.POD (Thermal energy storage. power on demand). It is a patented thermal energy storage system developed by Swedish cleantech company Azelio AB. The objective of this thesis work to find an alternative charging technology system that can be validated to be efficient and safe in operation for the charging of TES.POD. Induction heating technology is chosen as an alternative charging solution. Derived design steps to implement induction heater as a charging unit then selection of PCM container compatible with induction heater. Later simulating to evaluate total flux path in Finite Element Method Magnetics (FEMM) simulation tool which proposes the electrical results. The electrical performance of the induction heater indicates almost 9% higher electrical losses than the charging mechanism of the existing TES.POD design. However, from a safety standpoint, the alternate charging approach appears to be safer in operation than the existing system. Additionally, it reflects better intuitiveness from a manufacturing viewpoint.