Effective Treatment of Disseminated Prostate Cancer Using CD46-Targeted 225Ac Therapy.

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has limited treatment options and a poor prognosis. Recently, PSMA-targeted alpha particle therapy agents using Actinium-225 (225Ac) have shown promising results for prostate cancer treatment, but a significant fraction of patients with advanced mCRPC demonstrate loss of PSMA expression. We have previously reported that PSMA-null and PSMA-positive tumors can be detected and treated effectively with CD46-targeted radiopharmaceuticals.

PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer.

The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery.

3D small-scale dosimetry and tumor control of Ac radiopharmaceuticals for prostate cancer.

Radiopharmaceutical therapy using -emitting Ac is an emerging treatment for patients with advanced metastatic cancers. Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with -sensitive detection devices can measure radioactivity distributions at 20-40 resolution, but anatomical characterization is typically limited to 2D.

Vein distensibility is superior to vein diameter for predicting unassisted maturation of arteriovenous fistulae.

Background: A mature arteriovenous fistula (AVF) is the preferred hemodialysis access owing to its durability and lower risk of complications. Various factors have been implicated as predictors for maturation, including vein diameter and access type. Vein distensibility, which refers to the ability of the vein to dilate in response to changes in blood flow and pressure, has been proposed as a potential predictor for maturation, but its utility remains poorly studied.

Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized.

Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes.

Objective: There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAAs in order to identify novel biomarkers of disease.

Toward endovascular treatment of type A aortic dissection with smaller landing zones and more patient eligibility.

Objective: Type A or ascending aortic dissection is an acute life-threatening condition with high morbidity and mortality. Open surgery remains the standard of care. The development of minimally invasive endografts for type A aortic dissection (TAAD) will require a detailed understanding of the dissection and aortic root anatomy to determine patient eligibility and optimal device specifications.

Impact of the coronavirus disease 2019 pandemic on an academic vascular practice and a multidisciplinary limb preservation program.

With the aggressive resource conservation necessary to face the coronavirus disease 2019 pandemic, vascular surgeons have faced unique challenges in managing the health of their high-risk patients. An early analysis of patient outcomes after pandemic-related practice changes suggested that patients with chronic limb threatening ischemia have been presenting with more severe foot infections and are more likely to require major limb amputation compared with 6 months previously. As our society and health care system adapt to the new changes required in the post-coronavirus disease 2019 era, it is critical that we pay special attention to the most vulnerable subsets of patients with vascular disease, particularly those with chronic limb threatening ischemia and limited access to care.

Circulating exosomes from patients with peripheral artery disease influence vascular cell migration and contain distinct microRNA cargo.

Objective: Peripheral artery disease (PAD) is a chronic condition characterized by inflammation. Emerging literature suggests that circulating exosomes and their microRNA (miRNA) contents may influence atherosclerosis and vascular remodeling. We hypothesize that circulating exosomes in patients with PAD directly modulate vascular cell phenotype and contain proinflammatory miRNAs.

Natural history of acute pediatric iliofemoral artery thrombosis treated with anticoagulation.

Objective: Acute iliofemoral artery thrombosis (IFAT) can occur in critically ill neonates and infants who require indwelling arterial cannulas for monitoring or as a consequence of cardiac catheterization. Guidelines suggest treatment with anticoagulation, but evidence supporting the optimal duration of therapy and the role of surveillance ultrasound is limited. The objectives of this study were to characterize the kinetics of thrombus resolution and to define an appropriate duration of anticoagulation and interval for surveillance ultrasound.

Functional outcomes of arteriovenous fistulas recruited with regional anesthesia.

Objective: Regional anesthesia (RA)-induced vasodilation increases the proportion of patients with vein anatomy suitable for arteriovenous fistula (AVF) creation. The functional outcomes of AVFs created with veins initially small for size on preoperative duplex ultrasound mapping (≤2.4 mm) that are recruited under RA have not been clearly defined.

Infrarenal aortic repair with or without false lumen intentional placement of endografts for hybrid management of complex aortic dissection.

Objective: Aortic dissection (AD) often involves the infrarenal aorta. We review our experience with open infrarenal aortic repair with or without false lumen intentional placement (FLIP) of endografts in the proximal dissected aorta as part of a hybrid strategy to treat complex AD.

Methods: A prospectively maintained database of patients undergoing intervention for AD was reviewed.

Contemporary outcomes after venography-guided treatment of patients with May-Thurner syndrome.

Objective: Patients with May-Thurner syndrome (MTS) present with a spectrum of findings ranging from mild left leg edema to extensive iliofemoral deep venous thrombosis (DVT). Whereas asymptomatic left common iliac vein (LCIV) compression can be seen in a high proportion of normal individuals on axial imaging, the percentage of these persons with symptomatic compression is small, and debate exists about the optimal clinical and diagnostic criteria to treat these lesions in patients with symptomatic venous disease. We evaluated our approach to venography-guided therapy for individuals with symptomatic LCIV compression and report the outcomes.

Hybrid treatment of aortic arch aneurysms.

The advent of thoracic aortic endovascular stent-grafting has drastically changed the management of thoracic aneurysms. In 1991, Volodos and colleagues performed the first hybrid aortic arch repair. The case involved an arch debranching with placement of an endograft in a patient with a previous repair for an aortic coarctation.

Drosha regulates hMSCs cell cycle progression through a miRNA independent mechanism.

Recently we demonstrated that the miRNA regulate human mesenchymal stem cells (hMSCs) differentiation. To determine the role of the miRNA pathway in hMSCs proliferation, Drosha and Dicer knockdown hMSCs were generated using a lentiviral based tetracycline inducible shRNA. hMSCs with reduced Drosha expression had a significantly reduced proliferation rate, while hMSCs with reduced Dicer expression displayed a proliferation rate similar to untransduced cells.

Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic.

Recent reports have indicated that mesenchymal stromal cells (MSCs) from bone marrow have a potential in vascular remodeling and angiogenesis. Here, we report a unique phenomenon that under serum-deprived conditions MSCs survive and replicate. Secretome analysis of MSCs grown under serum-deprived conditions (SD-MSCs) identified a significant upregulation of prosurvival and angiogenic factors including VEGF-A, ANGPTs, IGF-1, and HGF.

Activation of autophagy in mesenchymal stem cells provides tumor stromal support.

Recent studies have implicated multipotential mesenchymal stem cells (MSCs) as an aid to breast cancer cell proliferation and metastasis, partly as a result of the MSCs secretome. As the tumor gets beyond 2 mm in diameter, the stromal cells could undergo starvation due to the lack of sufficient nutrients in solid tumor microenvironment. In this study, we investigated the survival mechanisms used by stressed stromal cells in breast cancers.

Human mesenchymal stromal cells (MSCs) reduce neointimal hyperplasia in a mouse model of flow-restriction by transient suppression of anti-inflammatory cytokines.

Aim: Mesenchymal stromal cells from human bone marrow (hMSCs) were observed to produce therapeutic benefits in some models for cardiac and vascular injuries but their mode of action was not defined. We tested the effects of hMSCs in models for restricted vascular flow.

Methods: We made model for restricted vascular flow produced by permanent ligation of a carotid artery and injected hMSCs to clarify the effects of hMSCs to vascular lesions.

Epigenetic reprogramming of IGF1 and leptin genes by serum deprivation in multipotential mesenchymal stromal cells.

Recent studies on the therapeutic effect of multipotential mesenchymal stem cells (MSCs) in various models of injury have shown that paracrine factors secreted by MSCs are responsible for tissue repair with very little engraftment. In this study we tested the hypothesis that MSCs under stress undergo epigenetic modifications that direct secretion of paracrine factors responsible for tissue repair. Microarray assays of MSCs that had been deprived of serum (SD-MSCs), to induce stress, demonstrated an increase in the expression of several angiogenic, prosurvival, and antiapoptotic factors, including insulin-like growth factor 1 (IGF1) and leptin.

Human multipotent stromal cells from bone marrow and microRNA: regulation of differentiation and leukemia inhibitory factor expression.

We observed that microRNAs (miRNAs) that regulate differentiation in a variety of simpler systems also regulate differentiation of human multipotent stromal cells (hMSCs) from bone marrow. Differentiation of hMSCs into osteoblasts and adipocytes was inhibited by using lentiviruses expressing shRNAs to decrease expression of Dicer and Drosha, two enzymes that process early transcripts to miRNA. Expression analysis of miRNAs during hMSC differentiation identified 19 miRNAs that were up-regulated during osteogenic differentiation and 20 during adipogenic differentiation, 11 of which were commonly up-regulated in both osteogenic and adipogenic differentiation.

CREB phosphorylation and c-Fos expression in the hippocampus of rats during acquisition and recall of a socially transmitted food preference.

In the present study, phosphorylation of cAMP-response element binding protein (pCREB) and expression of c-Fos were measured in the dorsal and ventral hippocampus, as well as in a control region, the retrosplenial cortex, of rats following acquisition and recall of a socially transmitted food preference (STFP). Behavioral analyses revealed that STFP-trained rats showed a stronger preference for the demonstrated food than did rats in social-control or odor-control conditions. Rats in a social + odor control condition displayed an intermediate preference that was not significantly different from either STFP-trained rats or the social- or odor-controls.