Medical Sciences Commons^™

Β-Aminopropionitrile-Induced Aortic Aneurysm And Dissection In Mice, Hisashi Sawada, Zachary A. Beckner, Sohei Ito, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

The mechanistic basis for the formation of aortic aneurysms and dissection needs to be elucidated to facilitate the development of effective medications. β-Aminopropionitrile administration in mice has been used frequently to study the pathologic features and mechanisms of aortic aneurysm and dissection. This mouse model mimics several facets of the pathology of human aortic aneurysms and dissection, although many variables exist in the experimental design and protocols that must be resolved to determine its application to the human disease. In the present brief review, we have introduced the development of this mouse model and provided insights into understanding its pathologic …

No Effect Of Hypercholesterolemia On Elastase-Induced Experimental Abdominal Aortic Aneurysm Progression, Toru Ikezoe, Takahiro Shoji, Jia Guo, Fanru Shen, Hong S. Lu, Alan Daugherty, Masao Nunokawa, Hiroshi Kubota, Masaaki Miyata, Baohui Xu, Ronald L. Dalman

Saha Cardiovascular Research Center Faculty Publications

Objective: Epidemiological studies link hyperlipidemia with increased risk for abdominal aortic aneurysms (AAAs). However, the influence of lipid-lowering drugs statins on prevalence and progression of clinical and experimental AAAs varies between reports, engendering controversy on the association of hyperlipidemia with AAA disease. This study investigated the impact of hypercholesterolemia on elastase-induced experimental AAAs in mice. Methods: Both spontaneous (targeted deletion of apolipoprotein E) and induced mouse hypercholesterolemia models were employed. In male wild type (WT) C57BL/6J mice, hypercholesterolemia was induced via intraperitoneal injection of an adeno-associated virus (AAV) encoding a gain-of-function proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) followed by …

Pi3k/Mtor Dual Inhibitor Pf-04691502 Is A Schedule-Dependent Radiosensitizer For Gastroenteropancreatic Neuroendocrine Tumors, Zeta Chow, Jeremy Johnson, Aman Chauhan, Tadahide Izumi, Michael Cavnar, Heidi L. Weiss, Courtney M. Townsend Jr., Lowell B. Anthony, Carrigan Wasilchenko, Matthew L. Melton, Jörg Schrader, B. Mark Evers, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up …

Role Of Ampk And Akt In Triple Negative Breast Cancer Lung Colonization, Jeremy Johnson, Zeta Chow, Eun Young Lee, Heidi L. Weiss, B. Mark Evers, Piotr G. Rychahou

Pathology and Laboratory Medicine Faculty Publications

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …

Method Of Predicting Obesity Comprising Measuring Neurotensin, B. Mark Evers, Jing Li, Paul Dobner, Olle Melander

Surgery Faculty Patents

The presently disclosed subject matter relates to a method for predicting increased risk of obesity on a non-obese subject. More particularly, the presently disclosed subject matter relates to a method of predicting increased risk of obesity in a non-obese subject by determining a level of neurotensin expression in a biological sample from the subject and comparing the level of neurotensin expression in the sample with a control level. The presently disclosed subject matter further relates to a method of preventing and/or treating obesity in a subject in need thereof by administering to the subject an effective amount of an agent …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

In-Hospital Mortality And Post-Surgical Complications Among Cancer Patients With Metabolic Syndrome, Tomi Akinyemiju, Swati Sakhuja, Neomi Vin-Raviv

Epidemiology and Environmental Health Faculty Publications

Background

Metabolic syndrome (MetS) is an important etiologic and prognostic factor for cancer, but few studies have assessed hospitalization outcomes among patients with both conditions.

Methods

Data was obtained from the Healthcare Cost and Utilization project Nationwide Inpatient Sample (HCUP-NIS). Study variables were assessed using ICD-9 codes on adults aged 40 years and over admitted to a US hospital between 2007 and 2011 with primary diagnosis of either breast, colorectal, or prostate cancer. We examined in-hospital mortality, post-surgical complications, and discharge disposition among cancer patients with MetS and compared with non-MetS patients.

Results

Hospitalized breast (OR: 0.31, 95% CI: 0.20–0.46), …

Effect Of Social Support And Marital Status On Perceived Surgical Effectiveness And 30-Day Hospital Readmission, Owoicho Adogwa, Aladine A. Elsamadicy, Victoria D. Vuong, Ankit I. Mehta, Raul A. Vasquez, Joseph Cheng, Carlos A. Bagley, Isaac O. Karikari

Neurosurgery Faculty Publications

Study Design: Retrospective cohort review.

Objective: To determine whether higher levels of social support are associated with improved surgical outcomes after elective spine surgery.

Methods: The medical records of 430 patients (married, n = 313; divorced/separated/widowed, n = 71; single, n = 46) undergoing elective spine surgery at a major academic medical center were reviewed. Patients were categorized by their marital status at the time of surgery. Patient demographics, comorbidities, and postoperative complication rates were collected. All patients had prospectively collected outcomes measures and a minimum of 1-year follow-up. Patient reported outcomes instruments (Oswestry Disability Index, Short Form-36, and visual …