ATTITUDES TOWARD AND UTILIZATION OF NON-INVASIVE PRENATAL TESTING FOR CHROMOSOME ANEUPLOIDY AMONG OB/GYNS

Prenatal diagnosis is traditionally made via invasive procedures such as amniocentesis and chorionic villus sampling (CVS). However, both procedures carry a risk of complications, including miscarriage. Many groups have spent years searching for a way to diagnose a chromosome aneuploidy without putting the fetus or the mother at risk for complications. Non-invasive prenatal testing (NIPT) for chromosome aneuploidy became commercially available in the fall of 2011, with detection rates similar to those of invasive procedures for the common autosomal aneuploidies (Palomaki et al., 2011; Ashoor et al. 2012; Bianchi et al. 2012). Eventually NIPT may become the diagnostic standard of care and reduce invasive procedure-related losses (Palomaki et al., 2011). The integration of NIPT into clinical practice has potential to revolutionize prenatal diagnosis; however, it also raises some crucial issues for practitioners. Now that the test is clinically available, no studies have looked at the physicians that will be ordering the testing or referring patients to practitioners who do. This study aimed to evaluate the attitudes of OB/GYN’s and how they are incorporating the test into clinical practice. Our study shows that most physicians are offering this new, non-invasive technology to their patients, and that their practices were congruent with the literature and available professional society opinions. Those physicians who do not offer NIPT to their patients would like more literature on the topic as well as instructive guidelines from their professional societies. Additionally, this study shows that the practices and attitudes of MFMs and OBs differ. Our population feels that the incorporation of NIPT will change their practices by lowering the amount of invasive procedures, possibly replacing maternal serum screening, and that it will simplify prenatal diagnosis. However, those physicians who do not offer NIPT to their patients are not quite sure how the test will affect their clinical practice. From this study we are able to glean how physicians are incorporating this new technology into their practice and how they feel about the addition to their repertoire of tests. This knowledge gives insight as to how to best move forward with the quickly changing field of prenatal diagnosis.

CHEMOSENSITIZATION OF HEPATOCELLULAR CARCINOMA TO GEMCITABINE BY NON-INVASIVE RADIOFREQUENCY FIELD-INDUCED HYPERTHERMIA

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage through late S/ G2 phase of cell cycle in comparison to cells treated with gemcitabine alone. This coincides with inhibition of resolution of γH2AX foci. Our findings also demonstrate that thermal sensitization of human hepatocellular carcinoma cell lines to gemcitabine is mediated through an Mre11-dependent homologous recombination repair pathway. Combination of non-invasive radiofrequency field-induced hyperthermia and gemcitabine was superior to either therapy alone (p