Unique model of chronic hypoxia in fetal lambs demonstrates abnormal contrast-enhanced ultrasound brain perfusion.

Background: Children with congenital heart disease (CHD) demonstrate long-term neurodevelopmental impairments. We investigated contrast-enhanced ultrasound (CEUS) cerebral perfusion in a fetal animal model exposed to sub-physiologic oxygen at equivalent levels observed in human fetuses with CHD.

Methods: Fifteen fetal lambs [hypoxic animals (n = 9) and normoxic controls (n = 6)] maintained in an extrauterine environment underwent periodic brain CEUS.

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer.

Although the development of immunotherapies has been revolutionary in the treatment of several cancers, many cancer types remain unresponsive to immune-based treatment and are largely managed by chemotherapy drugs. However, chemotherapeutics are not infallible and are frequently rendered ineffective as resistance develops from prolonged exposure. Recent investigations have indicated that some chemotherapy drugs have additional functions beyond their normative cytotoxic capacity and are in fact immune-modifying agents.

Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.

Pancreatic cancer is a lethal disease, harboring a five-year overall survival rate of only 13%. Current treatment approaches thus require modulation, with attention shifting towards liberating the stalled efficacy of immunotherapies. Select chemotherapy drugs which possess inherent immune-modifying behaviors could revitalize immune activity against pancreatic tumors and potentiate immunotherapeutic success.

Identifying potential imaging markers for diffusion property changes in a mouse model of amyotrophic lateral sclerosis: Application of the continuous time random walk model to ultrahigh b-value diffusion-weighted MR images of spinal cord tissue.

Diffusion MRI (dMRI) explores tissue microstructures by analyzing diffusion-weighted signal decay measured at different b-values. While relatively low b-values are used for most dMRI models, high b-value diffusion-weighted imaging (DWI) techniques have gained interest given that the non-Gaussian water diffusion behavior observed at high b-values can yield potentially valuable information. In this study, we investigated anomalous diffusion behaviors associated with degeneration of spinal cord tissue using a continuous time random walk (CTRW) model for DWI data acquired across an extensive range of ultrahigh b-values.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI.

Contrast-enhanced subharmonic aided pressure estimation for assessment of intracranial pressure in vivo.

Background: Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored.

Objective: The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs.

The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer.

The histone deacetylase (HDAC) inhibitor vorinostat, used with gemcitabine and other therapies, has been effective in treatment of experimental models of pancreatic cancer. In this study, we demonstrated that M344, an HDAC inhibitor, is efficacious against pancreatic cancer in vitro and in vivo, alone or with gemcitabine. By 24 hours post-treatment, M344 augments the population of pancreatic cancer cells in G1, and at a later time point (48 hours) it increases apoptosis.

Immune checkpoint blockade in pancreatic cancer: Trudging through the immune desert.

Pancreatic cancer (PC) has exceptionally high mortality due to ineffective treatment strategies. Immunotherapy, which mobilizes the immune system to fight against cancer, has been proven successful in multiple cancers; however, its application in PC has met with limited success. In this review, we articulated that the pancreatic tumor microenvironment is immuno-suppressive with extensive infiltration by M2-macrophages and myeloid-derived suppressive cells but low numbers of cytotoxic T-cells.

Tailoring Our Approach in Response to the SARS-CoV-2 Pandemic and Transcending Science Outreach Modalities for Native American Students in a Cancer Research Education Program.

In response to the SARS-CoV-2 pandemic, a cancer research education program at the University of Nebraska Medical Center designed for Native American middle school, high school and undergraduate students adapted activities to be delivered online. There are considerable challenges to adapting in-person science programming to online delivery that can impact overall effectiveness. These challenges are further exacerbated when the cognate student population also faces significant disparities in health, wealth, and educational outcomes.

Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia.

Background: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH.

Methods: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity.

The fetal lamb model of congenital diaphragmatic hernia shows altered cerebral perfusion using contrast enhanced ultrasound.

Background: Neurodevelopmental impairment is common in survivors of congenital diaphragmatic hernia (CDH). Altered cerebral perfusion in utero may contribute to abnormal brain development in CDH patients.

Methods: 5 fetal lambs with surgical left-CDH and 5 controls underwent transuterine cranial Doppler and contrast enhanced ultrasound (CEUS).

Major histocompatibility complex class I molecule expression by pancreatic cancer cells is regulated by activation and inhibition of the epidermal growth factor receptor.

Pancreatic cancer is one of the deadliest neoplasms, with a dismal 5-year survival rate of only 10%. The ability of pancreatic cancer cells to evade the immune system hinders an anti-tumor response and contributes to the poor survival rate. Downregulation of major histocompatibility complex (MHC) class I cell-surface expression can aid in immune evasion by preventing endogenous tumor antigens from being presented to cytotoxic T cells.

The EXTrauterine Environment for Neonatal Development: Present and Future.

Despite advances in clinical care and modest improvement in mortality rates for extreme prematurity, morbidity remains a significant challenge. The ideal environment to support prematurity would be fluidic and rely on natural fetal circulation to mimic the natural fetal amniotic environment, yet such an environment has been unsuccessful in long-term support until recently. Our group has succeeded in developing such a support system to foster fetal growth in the premature lamb model that shows promise for clinical translation.

Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency.

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.

Duramycin radiosensitization of MCA-RH 7777 hepatoma cells through the elevation of reactive oxygen species.

Objective: The objective of this study is to explore the radiosensitization effects of duramycin against the liver cancer hepatoma cells and relationship to reactive oxygen species (ROS) generation.

Materials And Methods: MCA-RH 7777 cells were treated with various combinations of duramycin concentrations and radiation doses. After the treatment, cell viabilities were determined by a cell proliferation assay; intracellular ROS levels were detected with the flow cytometric method.

Amyloid Precursor-like Protein 2 Expression Increases during Pancreatic Cancer Development and Shortens the Survival of a Spontaneous Mouse Model of Pancreatic Cancer.

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed.

The role of tumor heterogeneity in immune-tumor interactions.

The development of cancer stems from genetic instability and changes in genomic sequences, and hence, the heterogeneity exhibited by tumors is integral to the nature of cancer itself. Tumor heterogeneity can be further altered by factors that are not cancer cell intrinsic, i.e.

Development and Validation of Sorafenib-eluting Microspheres to Enhance Therapeutic Efficacy of Transcatheter Arterial Chemoembolization in a Rat Model of Hepatocellular Carcinoma.

Purpose: To validate the therapeutic efficacy of sorafenib-eluting embolic microspheres (SOR-EMs) used in combination with transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC) in a preclinical animal model.

Materials And Methods: SOR-EMs were prepared with poly(d,l-lactide--glycolide), iron oxide nanoparticles, and sorafenib. The morphology of the prepared SOR-EMs was confirmed by using optical microscopy.

Tumor Frameshift Mutation Proportion Predicts Response to Immunotherapy in Mismatch Repair-Deficient Prostate Cancer.

Background: Genomic biomarkers that predict response to anti-PD1 therapy in prostate cancer are needed. Frameshift mutations are predicted to generate more neoantigens than missense mutations; therefore, we hypothesized that the number or proportion of tumor frameshift mutations would correlate with response to anti-PD1 therapy in prostate cancer.

Methods: To enrich for response to anti-PD1 therapy, we assembled a multicenter cohort of 65 men with mismatch repair-deficient (dMMR) prostate cancer.

Correlation and Agreement of Yttrium-90 Positron Emission Tomography/Computed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model.

Purpose: To demonstrate a stronger correlation and agreement of yttrium-90 (Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization.

Materials And Methods: Hepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors.

Localized and triggered release of oxaliplatin for the treatment of colorectal liver metastasis.

The aim of this study was to develop and evaluate a liposome formulation that deliver oxaliplatin under magnetic field stimulus in high concentration to alleviate the off-target effects in a rat model of colorectal liver metastases (CRLM). Hybrid liposome-magnetic nanoparticles loaded with Cy5.5 dye and oxaliplatin (L-NIR- FeO/OX) were synthesized by using thermal decomposition method.

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures.

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures.

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation.

Extreme prematurity remains a major cause of neonatal mortality and severe long-term morbidity. Current neonatal care is associated with significant morbidity due to iatrogenic injury and developmental immaturity of extreme premature infants. A more physiologic approach, replacing placental function and providing a womb-like environment, is the foundational principle of artificial placenta (AP) and womb (AW) technology.

Yttrium-90 Portal Vein Radioembolization in Sprague-Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver.

Purpose: Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass Y microspheres (Y90 PVE) in Sprague-Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy.