Examination of the engraftment of exogenous mesenchymal stem cells in ovarian tumors and their potential use as delivery vehicles for therapeutic genes

Interactions between neoplastic cells and the host stroma play a role in both tumor cell migration and proliferation. Stromal cells provide structural support for malignant cells, modulate the tumor microenvironment, and influence phenotypic behavior as well as the aggressiveness of the malignancy. In response, the tumor provides growth factors, cytokines, and cellular signals that continually initiate new stromal reactions and recruit new cells into the microenvironment to further support tumor growth. Since growing tumors recruit local cells, as well as supplemental cells from the circulation, such as fibroblasts and endothelial precursors, the question arises if it would be possible to access circulating stromal cells to modify the tumor microenvironment for therapeutic benefits. One such cell type, mesenchymal stem cells (MSC), could theoretically be engrafted into stroma. MSC are pluripotent cells that have been shown to form stromal elements such as myofibroblasts, perivascular tissues and connective tissues. Several reports have demonstrated that MSC can incorporate into sites of wound healing and tissue repair, due to active tissue remodeling and local paracrine factors, and given the similarity between wound healing and the carcinoma induced stromal response one can hypothesize that MSC have the potential to be recruited to sites of tumor development. In addition, gene-modified MSC could be used as cellular vehicles to deliver gene products into tumors. My results indicate that MSC home to and participate in tumor stroma formation in ovarian tumor xenografts in mice. Additionally, once homed to tumor beds, MSC proliferate rapidly and integrate. My studies aim at understanding the fate of MSC in the tumor microenvironment, as well as utilizing them for cellular delivery of therapeutic genes into the stroma of ovarian carcinomas. ^

K-Ag age of volcanites from underwater rises of the Sea of Okhotsk and the Sea of Japan

New K-Ar datings of Meso-Cenozoic volcanites from the Sea of Japan and the Sea of Okhotsk were obtained. They enabled to reason age of different volcanic complexes. Basalts from volcanic edifices of the Sea of Japan Basin were determined as Middle Miocene - Pliocene (13.1-4.5 Ma) in age, which correlates well with geological evolution of the Sea of Japan. New datings for basalts from the continental slope of the South Primorye (11.1 Ma) confirm their age being similar to volcanites from Neogene basalt plateaus of the South Primorye; they are very similar not only in age but also in mineral and chemical compositions. Datings for rocks from the andesite series of the Northern Yamato Rise (24.7, 21.5 Ma) show that they are coeval with volcanites of the trachyandesite complex; this allows to combine them into one Oligocene - Early Miocene complex. In the Sea of Okhotsk datings of volcanite samples from three complexes were obtained: Cretaceous, Paleogene, and Pliocene-Pleistocene. Cretaceous magmatic rocks make part of basements of large rises in the Sea of Okhotsk, and Paleogene and Pliocene - Pleistocene complexes illustrate stages of Cenozoic tectono-magmatic activation of the region.