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Lootera full movie in hindi hd download hd 1080p.PROJECT SUMMARY (Project 2) No successful therapy exists to date for the treatment of sarcoma, a rare and fatal malignant tumor that occurs in soft tissue and bone. In the past decade, we identified focal adhesion kinase (FAK) as a promising therapeutic target for sarcoma. However, the development of small molecules and other forms of targeting FAK therapy have been disappointing for the treatment of sarcoma. Thus, we hypothesize that a new class of biologic therapies targeting FAK inhibit tumor growth through a unique mechanism of tumor cell death. We have also identified a novel mechanism by which cancer cells defend their self-renewal capacity. Specifically, we have shown that FAK activation can reprogram tumor cells to acquire a stem cell-like phenotype that is protected from death. Thus, we conclude that cancers that rely on FAK to resist death have a stem cell-like phenotype. These discoveries provide new opportunities to target FAK and to develop a new generation of highly effective biologic therapies for the treatment of sarcoma and other cancers. We will test our hypothesis in the following aims: 1) Determine how FAK plays a role in regulating tumor stem cell-like phenotypes, and 2) Determine how FAK drives stemness and mediates resistance to death. In aim 1, we will determine the clinical relevance of FAK for cancer stem cell-like phenotypes. In aim 2, we will identify the mechanisms by which FAK protects stemness and mediates resistance to death. In this aim, we will develop new FAK inhibitors that target unique domains of FAK required for stemness and for the survival of tumor cells. We will optimize the FAK inhibitors and define the mechanism of action of FAK inhibitors in sarcoma cell cultures and a syngeneic mouse model of FAK-dependent sarcoma. In aim 3, we will determine the effect of preventing FAK activation on sarcoma cell stemness and the resistance to death. In this aim, we will define the role of FAK in the induction of stemness and the resistance to death using the optimized FAK inhibitors. Together, these aims will provide a unique paradigm for the targeting of cancer stemness and for the development of new biologic therapies for the treatment of sarcoma and other cancers.Human gamma-glutamyltranspeptidase: isolation of a new 0b46394aab