Medical Sciences Commons^™

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …

Identifying Predictors For Inflammation-Induced Preterm Birth: A Murine Study, Tzu Ning Liu Bs, Jose Galaz Md, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Introduction: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. A large proportion of preterm deliveries is affected by intra-amniotic inflammation, which can occur in the presence (intra-amniotic infection) or absence (sterile intra-amniotic inflammation) of microbes. Studies have shown an association between intra-amniotic inflammation, cervical shortening, and changes in the cervicovaginal microbiome. However, their causal relationships are unknown. This study aims to determine the causality of intra-amniotic inflammation, cervical shortening, and cervicovaginal microbiome alterations.

Methods: Pregnant C57BL/6 dams received an ultrasound-guided intra-amniotic injection of an endotoxin lipopolysaccharide (LPS) or the alarmin interleukin-1 alpha (IL-1 alpha) on 16.5 …

The Safety Of Covid-19 Vaccines In Pregnancy, Lauren Zacharias

Capstone Showcase

SARS-CoV-2 has caused over 800,000 deaths in the United States since it was first detected here in 2020. Despite there being 3 available COVID-19 vaccines in the US, and recommendations by the CDC and countless other public health agencies that any potential risks are outweighed by the benefit of the vaccines, only 31% of pregnant women in the US are vaccinated against COVID-19 due to unfounded claims by an anti-vaccination movement that COVID mRNA vaccines cause infertility. This presentation explores where these claims originated, why they are untrue, the risks of COVID-19 infections in pregnancy, and the potential benefits of …