Project description:To examine potential mechanisms underlying resistance to anti-VEGF antibody (AVA) therapy, we used mouse models to identify tumors that demonstrated growth subsequent to a period of initial response. Specifically, we established orthotopic mouse models of ovarian cancer designed to develop adaptive resistance after treatment with an AVA. To examine potential mechanisms underlying resistance to anti-VEGF antibody (AVA) therapy, we used mouse models to identify tumors that demonstrated growth subsequent to a period of initial response. Specifically, we established orthotopic mouse models of ovarian cancer designed to develop adaptive resistance after treatment with an AVA.
Project description:Cancer associated fibroblasts (CAFs) have been shown to plays crucial roles in cancer progression. Although increasing evidence demonstrates that CAFs have important roles in modulating the aggressive phenotypes of cancer cells, their effects on the tumor vasculature remain underexplored. We co-cultured TIME human microvascular endothelial cells (MECs) with either primary human ovarian CAFs or normal ovarian fibroblasts (NFs) to evaluate the effects of CAFs on phenotypes of endothelial cells.
Project description:For this project N-glycosylated peptides were extracted from tissue of a mouse model for ovarian cancer tissue and matched control mice. The extracted N-glycosites were analyzed by LC-MSMS
Project description:CDCP1 and PLAGL2 have been shown to act as oncogenes in several cancer types but little is known about the molecular signalling underlying these processes in ovarian cancer cells. In this study we aim to find the downstream signalling upon their individual silencing in the human ovarian cancer cell line SKOV3. We used microarrays to detail the global programme of gene expression underlying CDCP1 and PLAGL2 signalling in the human ovarian cancer cell line SKOV3
Project description:Ovarian cancer is the most lethal gynecological malignancy, because its early detection is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. Despite a large number of proteomic studies of biological fluids from ovarian cancer patients, only a few biomarkers are used in clinical practice. Low molecular weight endogenous peptides more easily diffuse across endothelial barriers and can be more relevant biomarker candidates. In this current study, detailed peptidomic analysis of 26 ovarian cancer and 15 non-cancer samples of biological fluids (ascites and sera) were performed using TripleTOF 5600+ mass-spectrometer.
Project description:In a mouse model of ovarian cancer, we have established that prolonged exposure to 17β-estradiol (E2) accelerates tumour onset and increases the incidence of morphologically dysplastic ovarian surface epithelium (OSE). OSE cell proliferation and morphology are tightly regulated by the asymmetrical distribution of polarity proteins that provide positional cues for surface localization and growth inhibition. We hypothesized that E2 causes OSE dysplasia by inhibiting a tumour suppressor gene called Disabled-2 (Dab2). Dab2 is critical in mediating the polarized distribution of cell surface proteins and is highly expressed in normal OSE, but is absent in the majority of ovarian cancers. In this study, Dab2 is shown to be suppressed by E2 and we investigated the possibility that this occurs through E2 up-regulation of microRNAs. microRNA microarray analysis comparing control vs. E2 treated mouse ovarian cancer cells (MASE) was used to identify candidate miRNAs that have a seeding sequence capable of targeting the 3-prime untranslated region (3’UTR) of both human and mouse Dab2 transcript.