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1.
Int J Cancer ; 137(6): 1330-40, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-25735931

ABSTRACT

Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.


Subject(s)
Endoplasmic Reticulum Stress/genetics , Epithelial-Mesenchymal Transition/genetics , Membrane Proteins/genetics , Ovarian Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Animals , Cell Line, Tumor , Female , Genes, Tumor Suppressor/physiology , Heterografts , Humans , Mice , Mice, Inbred NOD , Mice, SCID
2.
Biomacromolecules ; 16(4): 1146-56, 2015 Apr 13.
Article in English | MEDLINE | ID: mdl-25728457

ABSTRACT

The ability to tailor mechanical properties and architecture is crucial in creating macroporous hydrogel scaffolds for tissue engineering. In the present work, a technique for the modification of the pore size and stiffness of acrylamide-based cryogels is demonstrated via the regulation of an electron beam irradiation dose. The samples were characterized by equilibrium swelling measurements, light and scanning electron microscopy, mercury porosimetry, Brunauer-Emmett-Teller surface area analysis, and stiffness measurements. Their properties were compared to cryogels prepared by a standard redox-initiated radical polymerization. A (125)I radiolabeled azidopentanoyl-GGGRGDSGGGY-NH2 peptide was bound to the surface to determine the concentration of the adhesive sites available for biomimetic modification. The functionality of the prepared substrates was evaluated by in vitro cultivation of adipose-derived stem cells. Moreover, the feasibility of preparing layered cryogels was demonstrated. This may be the key to the future preparation of complex hydrogel-based scaffolds to mimic the extracellular microenvironment in a wide range of applications.


Subject(s)
Cryogels/chemical synthesis , Polymerization , Porosity , Adipocytes/drug effects , Cryogels/pharmacology , Electrons , Humans
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