{"title":"OVARIAN CANCER SUICIDE GENE THERAPY WITH GENETICALLY ENGINEERED, TRANSGENICALLY EXPRESSED, INTRACELLULAR scFv ANTIBODIES AGAINST ANTI-OXIDATIVE ENZYMES.","authors":"Marek Malecki, Raf Malecki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ovarian cancer is the leading cause of death among all gynecological cancers. Some women choose bilateral oophorectomy as means of cancer prevention. In most patients, by the time this cancer is diagnosed, it has already metastasized. Treatment involves oophorectomy followed by radiation, chemo-, and immuno-therapies. However, oopherectomy results in infertility and fails to eliminate all cancer cells. Radiation and chemotherapy cause severe side effects and may lead to genetic mutations in DNA of the ova.The ultimate goal of this project is development of a therapy which would target a therapeutic gene specific to ovarian cancer cells causing their apoptosis, but which would leave ova and other cells unharmed.Herein, we report the proof of concept for such a therapy, in which genetically engineered single chain variable fragment (scFv) antibodies against HER2/ neu, RON, and NK1R, guide the delivery of the therapeutic transgenes into the cancer cells of the ovaries. Under ovary specific promoters (OSP), the transgene expression generates the intracellular scFv antibodies, which quench cell antioxidative enzymes, thus raising levels of reactive oxygen species (ROS), inflicting oxidative stress, activating apoptotic signaling pathways, and causing cancer cell deaths.</p>","PeriodicalId":89714,"journal":{"name":"Proceedings of the South Dakota Academy of Science","volume":"87 ","pages":"249-260"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520127/pdf/nihms375151.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31126825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HER2/NEU GENE EXPRESSION PRODUCTS EVALUATED WITH SUPERPARAMAGNETIC, GENETICALLY ENGINEERED ANTIBODIES.","authors":"Marek Malecki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Her2/neu is a protooncogene often amplified and overexpressed in ovary and breast cancer cells. HER2/neu receptors - HER2/neu gene expression products stimulate signal transduction pathways leading to increased cell proliferation. The level of its expression is associated with cancer malignancy. Therefore, HER2/neu is an important indicator of cancer malignancy, as well as, a target for antibody guided cancer therapies. The main objective of this work was to develop molecular probes, which would report levels of HER2/neu gene expression and anatomical distribution of its products in vivo. Magnetic resonance imaging (MRI) is particularly suitable for this endeavor, as it offers not only the best spatial resolution from all in vivo imaging modalities currently available, but also the topographic reference for location of these probes within anatomy of the human body. Superparamagnetic single chain variable fragment (scFv) antibodies targeting HER2/neu receptors were genetically engineered. They warranted high labeling specificity and affinity revealed with EDXSI, as well as, induced significant changes in relaxivity detected with NMR. This study demonstrated a proof of concept for using superparamagnetic scFvs in diagnostic evaluation of levels of gene expression products with NMR and MRI for planning receptor targeted therapies.</p>","PeriodicalId":89714,"journal":{"name":"Proceedings of the South Dakota Academy of Science","volume":"86 ","pages":"297-308"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535833/pdf/nihms-416339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40213616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}