The University of Nebraska Medical Center is a public center of health science research, patient care, and education located in Omaha, Nebraska.Founded as a private medical college in 1880, UNMC became part of the University of Nebraska System in 1902. Rapidly expanding in the early 20th century, the university founded a hospital, dental college, pharmacy college, and a graduate college of medicine. One of Omaha's top employers, UNMC has an endowment valued at $641 million and an economic impact of $3.8 billion.In 2014, UNMC was ranked 6th in the United States by U.S. News & World Report. Wikipedia.
News Article | April 17, 2017
New patients who have sleep apnea in Aurora, CO, can now see Dr. Mark Braasch for leading sleep apnea treatment, with or without a referral. Sleep apnea is often left untreated because patients are not familiar with common symptoms of the condition, which can include daytime sleepiness, morning headaches and chronic snoring. Dr. Braasch seeks to raise awareness of sleep apnea in Aurora, CO, and provides leading care for those who have the condition. Unfortunately, sleep apnea is commonly left undiagnosed, simply because those who have it rarely realize they do. The condition is characterized by symptoms that mainly occur during sleep, including snoring and shallow breathing that can prevent those affected from entering into a deep, restful sleep. In addition to nighttime symptoms, sleep apnea is also characterized by chronic daytime sleepiness, an inability to focus and morning headaches. If left untreated, the condition can not only reduce the patient’s daily quality of life, but can also increase the risk of heart attack, diabetes, high blood pressure and other physical problems. Depending on the type of sleep apnea an individual is experiencing, Dr. Braasch may recommend a variety of treatment options. In some cases, the patient may simply need to make some healthy lifestyle changes to greatly improve their quality of sleep. In other cases, oral devices may be recommended to change the position of the mouth during sleep and prevent apnea symptoms. In the most severe cases, surgery may also be recommended. Patients who have issues with snoring, daily fatigue and other common symptoms of sleep apnea in Aurora, CO, are invited to schedule an appointment with Dr. Braasch. Consultations can be reserved by calling 720-325-2460. Meadow Hills Dental is a family and cosmetic dental practice offering personalized dental care for patients in Aurora, Colorado. Dr. Mark Braasch graduated from the University of Nebraska Medical Center in 2004 and earned his post doctorate fellowship from Las Vegas Institute. Dr. Braasch is a member of the American Academy of Sleep Medicine (AASM) and was voted Best Dentist in Omaha, Nebraska. Meadow Hills Dental offers a variety of dental services such as general dentistry, orthodontics, TMD treatments, cosmetics, and medical devices for sleep apnea. To learn more about Meadow Hills Dental and their services, visit their website at http://www.meadowhillsdental.com or call 720-325-2460 to schedule an appointment.
Vose J.M.,University of Nebraska Medical Center
American Journal of Hematology | Year: 2013
Disease Overview: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood, and bone marrow with a short remission duration to standard therapies and a median overall survival of 4-5 years. Diagnosis: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t(11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX-11 or a low Ki-67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma. Risk Stratification: The Mantle Cell Lymphoma International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki-67 proliferative index if available. The median overall survival (OS) for the low risk group was not reached (5-year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group. Risk-Adapted Therapy: For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytarabine containing regimen±autologous stem cell transplantation should be considered. For older MCL patients with intermediate or high risk MIPI, combination chemotherapy with R-CHOP, R-Bendamustine, or a clinical trial should be considered. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor) or lenalidamide (anti-angiogenesis) are approved agents. Clinical trials with Ibruitinib (Bruton's Tyrosine Kinase inhibitor) or Idelalisib (PI3K inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. © 2013 Wiley Periodicals, Inc.
Talmadge J.E.,University of Nebraska Medical Center |
Gabrilovich D.I.,Wistar Institute
Nature Reviews Cancer | Year: 2013
Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies have revealed that this hyperplasia is associated with populations of multipotent progenitor cells that have been identified as myeloid-derived suppressor cells (MDSCs). The study of MDSCs has provided a wealth of information regarding tumour pathobiology, has extended our understanding of neoplastic progression and has modified our approaches to immune adjuvant therapy. In this Timeline article, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs and the host macroenvironment. © 2013 Macmillan Publishers Limited. All rights reserved.
Fey P.D.,University of Nebraska Medical Center
Current Opinion in Microbiology | Year: 2010
It is well accepted that bacterial pathogens growing in a biofilm are recalcitrant to the action of most antibiotics and are resistant to the innate immune system. New treatment modalities are greatly warranted to effectively eradicate these infections. However, bacteria growing in a biofilm are metabolically unique in comparison to the bacteria growing in a planktonic state. Unfortunately, most antibiotics have been developed to inhibit the growth of bacteria in a planktonic mode of growth. This review focuses on the metabolism and physiology of biofilm growth with special emphasis on staphylococci. Future treatment options should include targeting unique metabolic niches found within bacterial biofilms in addition to the enzymes or compounds that inhibit biofilm accumulation molecules and/or interact with quorum sensing and intercellular bacterial communication. © 2010.
Talmadge J.E.,University of Nebraska Medical Center
Seminars in Cancer Biology | Year: 2011
The infiltration of tumors and their metastases by hematopoietic cells can contribute both positively and negatively to tumor growth, invasion, and patient outcomes. These differing outcomes are associated with both tumor heterogeneity and the diversity of leukocytes infiltrating neoplastic lesions. Tumors infiltration by histiocytes (macrophages and dendritic cells (DCs)) is associated with poor clinical outcomes, although infiltration by a subset of DCs is related to improved outcomes. T-cell infiltration of tumors and metastases are surrogates for positive outcomes, although subset analysis suggests that not all infiltrating T-cells have this potential. Overall, tumor infiltration by CD8+ T-cells is associated with a positive outcome, while the frequency of infiltrating CD4+ cells may be a negative predictor. In addition to tumor infiltration by macrophages and T-cells, recent studies have shown that myeloid-derived suppressor cells (MDSCs), also infiltrate tumors, inhibiting T-cell and DC number and function and facilitate tumor growth, angiogenesis, and metastasis. In summary, hematopoietic cell infiltration of tumors can regulate tumor progression and provide a useful diagnostic surrogate. Further, strategies focused on the manipulation of cellular infiltration via cellular, gene and molecular immunotherapies have the potential to provide a novel target for adjuvant therapy. © 2010 Elsevier Ltd.
Shukla V.,University of Nebraska Medical Center
Blood | Year: 2013
Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator of B-cell development and function. A recent genome-wide single-nucleotide polymorphism (SNP) association study identified IRF4 as a major susceptibility gene in chronic lymphocytic leukemia (CLL). Although the SNPs located in the IRF4 gene were linked to a downregulation of IRF4 in CLL patients, whether a low level of IRF4 is critical for CLL development remains unclear. In rodents, CLL cells are derived from B1 cells whose population is dramatically expanded in immunoglobulin heavy chain Vh11 knock-in mice. We bred a Vh11 knock-in allele into IRF4-deficient mice (IRF4(-/-)Vh11). Here, we report that IRF4(-/-)Vh11 mice develop spontaneous early-onset CLL with 100% penetrance. Further analysis shows that IRF4(-/-)Vh11 CLL cells proliferate predominantly in spleen and express high levels of Mcl-1. IRF4(-/-)Vh11 CLL cells are resistant to apoptosis but reconstitution of IRF4 expression in the IRF4(-/-)Vh11 CLL cells inhibits their survival. Thus, our study demonstrates for the first time a causal relationship between low levels of IRF4 and the development of CLL. Moreover, our findings establish IRF4(-/-)Vh11 mice as a novel mouse model of CLL that not only is valuable for dissecting molecular pathogenesis of CLL but could also be used for therapeutic purposes.
Verma V.,University of Nebraska Medical Center
Nature Reviews Clinical Oncology | Year: 2015
Owing to the institution of annual low-dose CT for lung cancer screening in the USA, the presumed increase in detection of early stage lung cancers elicits many questions about so-called 'grey areas' of the management of this disease that have been inadequately addressed to date. Herein, important and potentially difficult ambiguous cases that oncologists might come across are discussed. © 2015 Macmillan Publishers Limited.
Liu C.,University of Nebraska Medical Center
Blood | Year: 2013
Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.
Lockridge O.,University of Nebraska Medical Center
Pharmacology and Therapeutics | Year: 2015
Phase I clinical trials have shown that pure human butyrylcholinesterase (BChE) is safe when administered to humans. A potential therapeutic use of BChE is for prevention of nerve agent toxicity. A recombinant mutant of BChE that rapidly inactivates cocaine is being developed as a treatment to help recovering cocaine addicts avoid relapse into drug taking. These clinical applications rely on knowledge of the structure, stability, and properties of BChE, information that is reviewed here. Gene therapy with a vector that sustains expression for a year from a single injection is a promising method for delivering therapeutic quantities of BChE. © 2014 Elsevier Inc.. All rights reserved.
Geng L.,University of Nebraska Medical Center
Oncogene | Year: 2014
Metastasis causes most deaths from colon cancer yet mechanistic understanding and therapeutic options remain limited. Here we show that expression of microRNA (miR)-192 is inversely correlated with metastatic potential of colon cancer cells. Ectopic expression of miR-192 sensitizes colon cancer cells to growth factor deprivation stress-induced apoptosis, whereas inhibition of miR-192 confers resistance. Overexpression of miR-192 inhibits metastatic colonization to the liver in an orthotopic mouse model of colon cancer. Alterations associated with the metastatic phenotype in the primary tumors include increased apoptosis, decreased proliferation and angiogenesis. Further studies indicate that miR-192 downregulates expression of Bcl-2, Zeb2 and VEGFA in vitro and in vivo, which is responsible for enhanced apoptosis, increased expression of E-cadherin and decreased angiogenesis in vivo, respectively. Finally, studies performed on human colonic adenocarcinoma show that expression of miR-192 is significantly reduced in neoplastic cells as compared with normal colonic epithelium. Importantly, there is a significant decrease in miR-192 expression in stage IV tumors when compared with stage I or II lesions. These findings indicate that miR-192 has an important role in colon cancer development and progression. Our studies underscore the clinical relevance and prognostic significance of miR-192 expression in colon cancer. Therefore, a major implication of our studies is that restoration of miR-192 expression or antagonism of its target genes (Bcl-2, Zeb2 or VEGFA) may have considerable therapeutic potential for anti-metastatic therapy in patients with colon cancer.