Trials and Tribulations of Humanizing Mice for Cancer Research

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow us to study the effects of NPS therapy on the human tumor and the human immune system, albeit not without trials and tribulations. Here we show that mice engrafted with human cord blood CD34+ hematopoietic stem cells (hCD34+ HSC) lack consistency in expansion and chimerism, or variety of immune cell types. Unfortunately, mice that developed the human immune system rejected the human tumors without treatment, while mice that rejected the immune system developed the human tumors. Therefore, we had mice with human immune systems and no tumor to treat, and mice with tumors to treat yet no immune system to study. In non-humanized mice, NPS induced complete tumor death in the patient derived mammary cancer xenograft (PDX) model, but not in the MDA-MB-231 VIM-RFP mammary cancer cell-derived xenograft (CDX) model. The absence of NPS elimination of the CDX is the only known NPS cancer failure and requires further study.https://digitalcommons.odu.edu/gradposters2021_gradschool/1000/thumbnail.jp

Pregnancy in a Patient with Idiopathic Pulmonary Fibrosis: A Case Report

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive restrictive lung disease. Data on the impact of pregnancy on IPF and maternal outcome is extremely limited. We present the case of a 35-year-old woman, gravida 1 para 0 with familial IPF with no oxygen requirement prior to pregnancy. The patient demonstrated significant deterioration in her lung function beginning at 22 weeks' gestation and underwent hospitalization at 272/7 weeks gestation due to acute on chronic hypoxic respiratory failure, ultimately requiring delivery at 28 weeks' gestation. The patient has not regained her baseline pulmonary function and remains oxygen dependent at 5 months postpartum. Based on limited available data, significant maternal morbidity and mortality is reported for women with IPF who become pregnant. Key Points Pregnancy outcomes in IPF are more severe than chronic interstitial lung disease due to connective tissue disorders. Deterioration in lung function amongst pregnant women with IPF occurs predominantly in the late second trimester, and lung function does not appear to recover postpartum. Significant maternal morbidity and mortality (40% at 1 year postpartum) is reported for women with IPF who become pregnant