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Search Results: 1 - 10 of 427237 matches for " Diana M. Lee "
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Treatment Patterns and Clinical Characteristics of Patients with Advanced Basal Cell Carcinoma in the Community Oncology Setting  [PDF]
Mark S. Walker, Lee S. Schwartzberg, Diana M. Chen, D. Devi Ramanan, Arthur C. Houts, Carolina Reyes
Journal of Cancer Therapy (JCT) , 2013, DOI: 10.4236/jct.2013.46A1004
Abstract:

Advanced basal cell carcinoma (aBCC) includes metastatic and locally advanced BCC that is inoperable (or with surgery contraindicated). We describe patient characteristics and treatment history for aBCC cases from community oncology. Nine cases of aBCC were found within the ACORN Data Warehouse, a community oncology database of >180,000 cancer patients. Data were summarized descriptively. Three illustrative case histories are presented. Patients were predominantly Caucasian (8/9), male (6/9), and over 60 (6/9). Four had metastatic disease; five had aBCC without metastasis. Five had a history of treatment for early stage BCC, including surgery (5/5), radiation (1/5), and none had chemotherapy. Those with history of early stage BCC had periods of apparent lack of follow-up and treatment. One had chemotherapy for aBCC (platinum based with radiation) and eight had radiation without chemotherapy. Patients had multiple comorbid serious medical conditions. Six were deceased, but only one was documented to have aBCC as cause of death. Advanced BCC is rare in community oncology settings. There appear to be gaps in the care and follow-up of patients with initial early stage BCC. More data and larger samples are needed from multi-specialty databases such as dermatology and head and neck surgery.

A diverse portfolio of novel drug discovery efforts for Alzheimer's disease: Meeting report from the 11th International Conference on Alzheimer's Drug Discovery, 27-28 September 2010, Jersey City, NJ, USA
Linda H Lee, Diana W Shineman, Howard M Fillit
Alzheimer's Research & Therapy , 2010, DOI: 10.1186/alzrt57
Abstract: Given the escalating worldwide socioeconomic burden of Alzheimer's disease (AD), there is a strong impetus for better therapeutics. Currently, there are approved symptomatic drugs but very few disease-modifying agents capable of slowing down or reversing disease progression.As the Alzheimer's Drug Discovery Foundation (ADDF) executive director Howard Fillit (ADDF, New York, NY, USA) pointed out in his opening remarks, major issues include the difficulty in drugging central nervous system targets and the predictability of AD animal models. Preclinical trials have so far demonstrated hundreds of 'cures', yet the track record for translating these treatments to the human disease is lackluster, as evidenced by the recent spate of high-profile failures.An overarching theme of the conference was disease prevention and early treatment before AD manifests significant cognitive decline, when it is probably too late to reverse the substantial neural pathology. To create preventative treatments, however, we first need accurate and reliable biomarker diagnostics to identify prodromal AD (mild cognitive impairment and even earlier).As Holly Soares (Bristol-Myers Squibb, New York, NY, USA) pointed out, biomarkers are also critical for patient selection and monitoring treatment efficacy in AD clinical trials. The Alzheimer's Disease Neuroimaging Initiate has proposed cerebrospinal fluid amyloid-β (Aβ) levels and amyloid positron emission tomography imaging as good biomarkers for early detection. Dawn Matthews (Abiant, Inc., Grayslake, IL, USA) expanded on the use of neuroimaging techniques as diagnostic tools. For example, fluorodeoxyglucose positron emission tomography imaging can sensitively detect changes in various brain regions, even in pre-mild cognitive impairment, and follows cognitive decline in AD. Quality control in data acquisition, processing, and analysis is critical, however, for the successful use of neuroimaging methods as diagnostics.In addition to neuroimaging a
Interferon signaling patterns in peripheral blood lymphocytes may predict clinical outcome after high-dose interferon therapy in melanoma patients
Diana L Simons, Gerald Lee, John M Kirkwood, Peter P Lee
Journal of Translational Medicine , 2011, DOI: 10.1186/1479-5876-9-52
Abstract: PBL from 14 melanoma patients harvested on Day 0 and Day 29 of neoadjuvant HDI induction therapy were analyzed using phosflow to assess their interferon signaling patterns through IFN-α induced phosphorylation of STAT1-Y701.Patients who had a clinical response to HDI showed a lower PBL interferon signaling capacity than non-responders at baseline (Day 0). Additionally, clinical responders and patients with good long-term outcome showed a significant increase in their PBL interferon signaling from Day 0 to Day 29 compared to clinical non-responders and patients that developed metastatic disease. The differences in STAT1 activation from pre- to post- HDI treatment could distinguish between patients who were inclined to have a favorable or unfavorable outcome.While the sample size is small, these results suggest that interferon signaling patterns in PBL correlate with clinical responses and may predict clinical outcome after HDI in patients with melanoma. A larger confirmatory study is warranted, which may yield a novel approach to select patients for HDI therapy.High-dose Interferon (HDI) therapy produces a clinical response and achieves relapse-free survival in 20-33% of patients with operable high risk or metastatic melanoma [1-9]. However, patients may develop significant side effects frequently necessitating dose reduction or discontinuation of therapy. Therefore, approaches to select patients for initiation and/or maintenance on HDI therapy would be very useful.While interferon has been shown to induce anti-tumor effects such as anti-proliferative, anti-vascular [10] and pro-apoptotic effects [11], it has also been suggested that HDI therapy mediates its effects through modulating the immune response [12]. Indeed development of autoimmunity [13] and a certain serum cytokine profile [14] have been shown to correlate with clinical responses in HDI adjuvant treated melanoma patients. Nonetheless, the mechanism of HDI's immunomodulatory roles is unclear and it is unc
The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America
Bruce Y. Lee ,Kristina M. Bacon,Diana L. Connor,Alyssa M. Willig,Rachel R. Bailey
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000916
Abstract: Background Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is the leading etiology of non-ischemic heart disease worldwide, with Latin America bearing the majority of the burden. This substantial burden and the limitations of current interventions have motivated efforts to develop a vaccine against T. cruzi. Methodology/Principal Findings We constructed a decision analytic Markov computer simulation model to assess the potential economic value of a T. cruzi vaccine in Latin America from the societal perspective. Each simulation run calculated the incremental cost-effectiveness ratio (ICER), or the cost per disability-adjusted life year (DALY) avoided, of vaccination. Sensitivity analyses evaluated the impact of varying key model parameters such as vaccine cost (range: $0.50–$200), vaccine efficacy (range: 25%–75%), the cost of acute-phase drug treatment (range: $10–$150 to account for variations in acute-phase treatment regimens), and risk of infection (range: 1%–20%). Additional analyses determined the incremental cost of vaccinating an individual and the cost per averted congestive heart failure case. Vaccination was considered highly cost-effective when the ICER was ≤1 times the GDP/capita, still cost-effective when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective when the ICER was >3 times the GDP/capita. Our results showed vaccination to be very cost-effective and often economically dominant (i.e., saving costs as well providing health benefits) for a wide range of scenarios, e.g., even when risk of infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an individual could likely provide net cost savings that rise substantially as risk of infection or vaccine efficacy increase. Conclusions/Significance Results indicate that a T. cruzi vaccine could provide substantial economic benefit, depending on the cost of the vaccine, and support continued efforts to develop a human vaccine.
Sorting Live Stem Cells Based on Sox2 mRNA Expression
Hans M. Larsson, Seung Tae Lee, Marta Roccio, Diana Velluto, Matthias P. Lutolf, Peter Frey, Jeffrey A. Hubbell
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049874
Abstract: While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB+SSEA1+ cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB+ cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB? cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner.
Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects
Diana M. Lee, Kenneth W. Jackson, Nicholas Knowlton, Joshua Wages, Petar Alaupovic, Ola Samuelsson, Aso Saeed, Michael Centola, Per-Ola Attman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022360
Abstract: The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol. In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls.
Systematic review: comparative effectiveness of adjunctive devices in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention of native vessels
Diana M Sobieraj, C Michael White, Jeffrey Kluger, Vanita Tongbram, Jennifer Colby, Wendy T Chen, Sagar S Makanji, Soyon Lee, Ajibade Ashaye, Craig I Coleman
BMC Cardiovascular Disorders , 2011, DOI: 10.1186/1471-2261-11-74
Abstract: We conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov webcite, abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus.37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment.Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none a
Offshore Wind Power for Marine Conservation  [PDF]
Linus Hammar, Diana Perry, Martin Gullstr?m
Open Journal of Marine Science (OJMS) , 2016, DOI: 10.4236/ojms.2016.61007
Abstract: The seas of northern Europe are strongly affected by human activities and there is a great need for improved marine conservation. The same region is also the current hotspot for offshore wind power development. Wind farms can have negative environmental impacts during construction, but during the operational phase many organisms are attracted to the foundations and thereby may also find refuge from fisheries. Given the recent implementation of marine spatial planning in Europe and elsewhere, this is a critical time to address potential compatibility and synergies between marine conservation and wind power. This review concludes that offshore wind farms can be at least as effective as existing marine protected areas in terms of creating refuges for benthic habitats, benthos, fish and marine mammals. The degree of advantage for these organisms depends on the location of the wind farm and the level of imposed fishing restriction. Under certain conditions wind farms may even be more efficient means of conservation than ordinary marine protected areas. However, offshore wind farms can be negative for several species of seabirds, essentially as occupying preferred feeding or wintering grounds. In areas important to these seabirds wind farms may not comply with conservation. The results bring important messages to marine spatial planning as some but not all wind farms can be spatially combined with, and even synergistic to, marine conservation.
Aberrant Expression of Interleukin-1β and Inflammasome Activation in Human Malignant Gliomas
Leonid Tarassishin, Diana Casper, Sunhee C. Lee
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0103432
Abstract: Objective Glioblastoma is the most frequent and malignant form of primary brain tumor with grave prognosis. Mounting evidence supports that chronic inflammation (such as chronic overactivation of IL-1 system) is a crucial event in carcinogenesis and tumor progression. IL-1 also is an important cytokine with species-dependent regulations and roles in CNS cell activation. While much attention is paid to specific anti-tumor immunity, little is known about the role of chronic inflammation/innate immunity in glioma pathogenesis. In this study, we examined whether human astrocytic cells (including malignant gliomas) can produce IL-1 and its role in glioma progression. Methods We used a combination of cell culture, real-time PCR, ELISA, western blot, immunocytochemistry, siRNA and plasmid transfection, micro-RNA analysis, angiogenesis (tube formation) assay, and neurotoxicity assay. Results Glioblastoma cells produced large quantities of IL-1 when activated, resembling macrophages/microglia. The activation signal was provided by IL-1 but not the pathogenic components LPS or poly IC. Glioblastoma cells were highly sensitive to IL-1 stimulation, suggesting its relevance in vivo. In human astrocytes, IL-1β mRNA was not translated to protein. Plasmid transfection also failed to produce IL-1 protein, suggesting active repression. Suppression of microRNAs that can target IL-1α/β did not induce IL-1 protein. Glioblastoma IL-1β processing occurred by the NLRP3 inflammasome, and ATP and nigericin increased IL-1β processing by upregulating NLRP3 expression, similar to macrophages. RNAi of annexin A2, a protein strongly implicated in glioma progression, prevented IL-1 induction, demonstrating its new role in innate immune activation. IL-1 also activated Stat3, a transcription factor crucial in glioma progression. IL-1 activated glioblastoma-conditioned media enhanced angiogenesis and neurotoxicity. Conclusions Our results demonstrate unique, species-dependent immune activation mechanisms involving human astrocytes and astrogliomas. Specifically, the ability to produce IL-1 by glioblastoma cells may confer them a mesenchymal phenotype including increased migratory capacity, unique gene signature and proinflammatory signaling.
A Spectral Graph Approach to Discovering Genetic Ancestry
Ann B. Lee,Diana Luca,Kathryn Roeder
Statistics , 2009,
Abstract: Mapping human genetic variation is fundamentally interesting in fields such as anthropology and forensic inference. At the same time patterns of genetic diversity confound efforts to determine the genetic basis of complex disease. Due to technological advances it is now possible to measure hundreds of thousands of genetic variants per individual across the genome. Principal component analysis (PCA) is routinely used to summarize the genetic similarity between subjects. The eigenvectors are interpreted as dimensions of ancestry. We build on this idea using a spectral graph approach. In the process we draw on connections between multidimensional scaling and spectral kernel methods. Our approach, based on a spectral embedding derived from the normalized Laplacian of a graph, can produce more meaningful delineation of ancestry than by using PCA. The method is stable to outliers and can more easily incorporate different similarity measures of genetic data than PCA. We illustrate a new algorithm for genetic clustering and association analysis on a large, genetically heterogeneous sample.
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