bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosolic Phospholipase A2: Targeting Cancer through the Tumor Vasculature
Authors: Linkous Amanda , Geng Ling , Lyshchik Andrej , Hallahan Dennis E. , Yazlovitskaya Eugenia M. 
Published: February 2009

Abstract
Purpose: In vascular endothelial cells, low doses of ionizing radiation trigger the immediate activation of cytosolic phospholipase A2 (cPLA2). This event initiates prosurvival signaling that could be responsible for radioresistance of tumor vasculature. Thus, the development of radiosensitizers targeting these survival pathways may enhance tumor response to radiation therapy. Arachidonyltrifluoromethyl Ketone (AACOCF3), a specific cPLA2 inhibitor, was studied as a potential radiosensitizer.
Experimental Design: Vascular endothelial cells (3B11 and MPMEC) and lung tumor cells (LLC and H460) were treated with 1 μmol/L AACOCF3 for 30 minutes prior to irradiation. Treatment response was evaluated by clonogenic survival, activation of extracellular signal-regulated kinase 1/2 (ERK1/2), tubule formation, and migration assays. For in vivo experiments, mice with LLC or H460 tumors in the hind limbs were treated for 5 consecutive days with 10 mg/kg AACOCF3 administered daily 30 minutes prior to irradiation. Treatment response was assessed by tumor growth delay, Power Doppler Sonography, and immunohistochemistry.
Results: In cell culture experiments, inhibition of cPLA2 with AACOCF3 prevented radiation-induced activation of ERK1/2 and decreased clonogenic survival of irradiated vascular endothelial cells but not the lung tumor cells. Treatment with AACOCF3 also attenuated tubule formation and migration in irradiated vascular endothelial cells. In both tumor mouse models, treatment with AACOCF3 prior to irradiation significantly suppressed tumor growth and decreased overall tumor blood flow and vascularity. Increased apoptosis in both tumor cells and tumor vascular endothelium was determined as a possible mechanism of the observed effect.
Conclusion: These findings identify cPLA2 as a novel molecular target for tumor sensitization to radiation therapy through the tumor vasculature.
Evidence of Systemic Th2-Driven Chronic Inflammation in Patients with Metastatic Melanoma
Authors: Nevala Wendy K. , Vachon Celine M. , Leontovich Alexey A. , Scott Christopher G. , Thompson Michael A. , Markovic Svetomir N. ,   for the Melanoma Study Group of the Mayo Clinic Cancer Center
Published: February 2009

AbstractPurpose: Immunotherapeutic modalities are commonly used for treatment of patients with melanoma. The therapeutic success in preclinical models has not yielded the expected clinical results. To understand this discrepancy, we attempted to define immune homeostasis of 209 patients with melanoma across stages of disease relative to normal controls.Experimental Design: Peripheral blood mononuclear cells (PBMC) and plasma were collected from patients and healthy donors. PBMC were analyzed for frequencies of natural killer, dendritic, and T cells and their functional status. Matched plasma samples were analyzed for the concentrations of 27 cytokines, chemokines, and growth factors. RNA was isolated from 24 metastatic melanoma tumor biopsies and profiled by microarray analysis.Results: The frequency of natural killer, T, and dendritic cells in patients does not significantly change across stages of melanoma. However, plasma concentrations of Th2 cytokines [interleukin (IL)-4, IL-5, IL-10, and IL-13] in tumor-bearing patients were significantly higher than those with resected melanoma. Expression array analysis of metastatic melanoma revealed that the malignant melanocytes were not the source of the Th2 cytokines but did highly up-regulate vascular endothelial growth factor (VEGF) transcripts, consistent with plasma VEGF concentrations. In vitro VEGF exposure of normal PBMC lead to repolarization from Th1 to Th2 emulating the state of metastatic melanoma.Conclusions: Patients with metastatic melanoma exist in a state of Th2-mediated “chronic inflammation” as a result of at least VEGF overproduction by malignant tumors. These data support prior observations regarding the effect of VEGF on immune cell function and suggests consideration of VEGF inhibitors in future cancer immunotherapy clinical studies in metastatic melanoma.
Pilot Study on Light Dosimetry Variables for Photodynamic Therapy of Barrett's Esophagus with High-Grade Dysplasia
Authors: Gill Kanwar R.S. , Wolfsen Herbert C. , Preyer Norris W. , Scott Marquitta V. , Gross Seth A. , Wallace Michael B. , Jones Linda R. 
Published: February 2009

Abstract
Purpose: Photodynamic therapy (PDT) is used to treat Barrett's esophagus with high-grade dysplasia and mucosal carcinoma. Outcomes are variable with some patients having persistent disease, whereas others develop strictures. The aims of this study were (a) to compare porfimer sodium tissue uptake, light dose, and esophageal thickness with clinical outcomes and (b) to determine the selectivity of porfimer sodium uptake in diseased and normal epithelium.
Experimental Design: Forty-eight hours after porfimer sodium infusion, patients underwent mucosal biopsy for quantification of the porfimer sodium. Laser light was delivered at 48 hours and again 24 or 48 hours later. Porfimer sodium was extracted from the biopsy samples and quantified using fluorescence spectroscopy. The enhanced photodynamic dose was determined as [porfimer sodium content * light dose/esophageal thickness]. PDT efficacy was determined 6 to 8 weeks later based on persistence or complete ablation of dysplasia or carcinoma.
Results: Mean porfimer sodium content of 6.2 mg/kg (range, 2.6-11.2 mg/kg) and mean total light dose of 278 J/cm (range, 225-360 J/cm) resulted in a complete treatment. Mean porfimer sodium tissue content of 3.9 mg/kg (range, 2.1-8.1 mg/kg) and mean total light dose of 268 J/cm (range, 250-350 J/cm) resulted in an incomplete treatment. The total esophageal thickness (range, 1.7-6.0 mm) and enhanced photodynamic dose were correlated with treatment outcome.
Conclusions: Esophageal thickness is the strongest predictor of treatment outcome. The porfimer sodium content of Barrett's and normal tissue is not significantly different. “Photodynamic dose” for esophageal PDT should incorporate the esophageal thickness.
Palettes of Vaccines and Immunostimulatory Monoclonal Antibodies for Combination
Authors: Melero Ignacio , Martinez-Forero Ivan , Dubrot Juan , Suarez Natalia , Palazón Asis , Chen Lieping 
Published: February 2009

AbstractVarious monoclonal antibodies (mAb) target immune system molecules to enhance immunity by costimulating T cells (i.e., CD137, OX40, CD40, GITR) or interfering in coinhibitory signals (i.e., CTLA-4, PD-1). These powerful agents can be guided by cancer vaccines to enhance immunity against tumor but not self tissues. Clinically powerful therapeutic synergies are at hand.
Identification of novel small-molecule compounds that inhibit the proproliferative Krüppel-like factor 5 in colorectal cancer cells by high-throughput screening
Authors: Bialkowska Agnieszka B. , Du Yuhong , Fu Haian , Yang Vincent W. 
Published: February 2009

Abstract
Colorectal cancer is one of the leading causes of cancer mortality and morbidity worldwide. Previous studies indicate that the zinc finger-containing transcription factor Krüppel-like factor 5 (KLF5) positively regulates proliferation of intestinal epithelial cells and colorectal cancer cells. Importantly, inhibition of KLF5 expression in intestinal epithelial cells and colorectal cancer cells by pharmacologic or genetic means reduces their rate of proliferation. To identify additional and novel small molecules that inhibit KLF5 expression and thus colorectal cancer proliferation, we developed a reporter assay using colorectal cancer cell line (DLD-1) that stably expressed a luciferase reporter gene directed by 1,959 bp of the human KLF5 promoter upstream of the ATG start codon and performed a cell-based high-throughput screen with the Library of Pharmacologically Active Compounds that contains 1,280 biologically active compounds. The screen identified 8 potential inhibitors and 6 potential activators of the KLF5 promoter. Three potential inhibitors, wortmannin, AG17, and AG879, were further evaluated by secondary analyses. All three significantly reduced both KLF5 promoter-luciferase activity and protein level in DLD-1 cells in a dose- and time-dependent manner when compared with controls. They also significantly reduced the rate of proliferation of DLD-1 and two other colorectal cancer cell lines, HCT116 and HT29. Our results show the principle of using high-throughput screening to identify small-molecule compounds that modulate KLF5 activity and consequently inhibit colorectal cancer proliferation. [Mol Cancer Ther 2009;8(3):563–70]
Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2
Authors: Feng Siting , Tang Qizhu , Sun Meng , Chun Jae Yeon , Evans Christopher P. , Gao Allen C. 
Published: February 2009

Abstract
The standard treatment for advanced, androgen-responsive prostate cancer is androgen deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually progresses to an androgen-refractory stage. The mechanism underlying bicalutamide resistance in the course of prostate cancer progression is incompletely understood. However, interleukin-6 (IL-6) plays a critical role in the development and progression of CRPC. Herein, we explored an association between IL-6 and bicalutamide resistance. To study this, series of lower and higher passages of LNCaP cell sublines generated by long-term exposure to IL-6 were used. The cells from higher passages of LNCaP treated with IL-6 developed resistance to bicalutamide treatment compared with parental LNCaP cells. The levels of transcriptional intermediary factor 2 (TIF2) in IL-6-treated LNCaP cells were found to be significantly higher than parental LNCaP cells. Down-regulation of TIF2 expression via short hairpin RNA in IL-6-treated LNCaP cells sensitized these cells to bicalutamide treatment, whereas overexpression of TIF2 in the parental LNCaP cells increased resistance to bicalutamide. Furthermore, overexpression of IL-6 attenuated bicalutamide-mediated blockage of androgen-induced androgen receptor nuclear translocation and recruitment. These results show that overexpression of IL-6 increases the resistance of prostate cancer cells to bicalutamide via TIF2. Overexpression of IL-6 not only plays an important role in prostate cancer progression but also contributes to bicalutamide resistance. Our studies suggest that bicalutamide-IL-6-targeted adjunctive therapy may lead to a more effective intervention than bicalutamide alone. [Mol Cancer Ther 2009;8(3):665–71]
Effects of Pressure on Collision, Coalescence, and Breakup of Raindrops. Part II: Parameterization and Spectra Evolution at 50 and 100 kPa
Authors: List Roland , Nissen R. , Fung C. 
Published: February 2009

Abstract
Fragment size distributions, experimentally obtained for six drop pairs colliding at 50 kPa, are parameterized similarly to the 100-kPa drop pair experiments by Low and List. This information is then introduced into a box model to allow assessment of the spectra evolution and a comparison of the two datasets taken at the two pressures. The differences in breakup patterns include the following: The contributions to mass transfer by breakup and coalescence are very similar at the two pressures, with larger values at lower pressure; the overall mass evolution is not particularly sensitive to pressure; and disk breakup plays an “erratic” role. The situation for the number concentration, however, is totally different and develops gradually. At 50 kPa there is also no three-peak equilibrium developing as for 100 kPa. The times to reach equilibrium are ∼12 h. Note that the box model does not include accretion of cloud droplets—which may well be more important than growth by accretion of fragments.
Application of the new parameterization is not beneficial for low rain rates, but it is strongly recommended for large rain rates (&gt;50 mm h−1).
Soil Moisture Impacts on Convective Margins
Authors: Lintner Benjamin R. , Neelin J. David 
Published: February 2009

Abstract
An idealized prototype for the location of the margins of tropical land region convection zones is extended to incorporate the effects of soil moisture and associated evaporation. The effect of evaporation, integrated over the inflow trajectory into the convection zone, is realized nonlocally where the atmosphere becomes favorable to deep convection. This integrated effect produces “hot spots” of land surface–atmosphere coupling downstream of soil moisture conditions. Overall, soil moisture increases the variability of the convective margin, although how it does so is nontrivial. In particular, there is an asymmetry in displacements of the convective margin between anomalous inflow and outflow conditions that is absent when soil moisture is not included. Furthermore, the simple cases presented here illustrate how margin sensitivity depends strongly on the interplay of factors, including net top-of-the-atmosphere radiative heating, the statistics of inflow wind, and the convective parameterization.
Two-Way Particle-Tracking Model for Specifying Sources of Drifting Objects: Application to the East China Sea Shelf
Authors: Isobe Atsuhiko , Kako Shin’ichiro , Chang Pil-Hun , Matsuno Takeshi 
Published: February 2009

Abstract
The two-way Lagrangian particle-tracking model (PTM) is proposed for specifying sources of objects drifting with random-walk processes on the sea surface. First, to determine object source candidates, modeled particles are released from the point (hereafter, “receptor”) where an observer finds the objects using a backward-in-time PTM with modeled ocean currents of which directions are reversed in sign. Second, the modeled particles are released from these source candidates in a forward-in-time PTM using ocean currents originally computed in hydrographic models. Third, the source candidates are considered to be reliable at a 5% significance level if the observed receptor is located inside the ellipse whose center is the mean position of the modeled particles at the time when the observer found the objects and whose axis length is twice the standard deviation computed using all modeled particle positions. The two-way PTM experiments are carried out in a realistic hydrographic model over the East China Sea shelf for the period from June through August 2004. Statistically significant sources are well specified close to the true source because 58%–90% of source candidates are rejected in the experiments.
Convective Contribution to the Genesis of Hurricane Ophelia (2005)
Authors: Houze Robert A. , Lee Wen-Chau , Bell Michael M. 
Published: February 2009

AbstractThe convection occurring in the tropical depression that became Hurricane Ophelia (2005) was investigated just prior to tropical storm formation. Doppler radar showed a deep, wide, intense convective cell of a type that has been previously thought to occur in intensifying tropical depressions but has not heretofore been documented in detail. The updraft of the cell was 10 km wide, 17 km deep, had updrafts of 10–20 m s−1 throughout its mid- to upper levels, and contained a cyclonic vorticity maximum. The massive convective updraft was maintained by strong positive buoyancy, which was maximum at about the 10-km level, probably aided by latent heat of freezing. Evaporative cooling and precipitation drag occurred in the rain shower of the cell but were insufficient to produce a strong downdraft or gust front outflow to force the updraft. The convective updraft was fed by a layer of strong inflow that was several kilometers deep. Wind-induced turbulence, just above the ocean surface, enriched the equivalent potential temperature of the boundary layer of the inflow air, thus creating an unstable layer with little convective inhibition. This air was raised to its level of free convection when it encountered the denser air in the rainy core of the convection. The updraft motion and latent heat release in the intense cell generated potential vorticity throughout the low to midlevels, and contained a cyclonic vortex at the midlevels. Vorticity generated throughout the depth of the low to midtroposphere within convective updraft cells was subsequently incorporated into a stratiform region attached to the region of active convective cells. The vorticity perturbations at the low to midlevels in convective cells and their attached stratiform regions were available to be axisymmetrized into the larger-scale intensifying depression vortex.
Development of a Diabetes Education Program for Youth With Type 2 Diabetes
Authors: Grey Margaret , Schreiner Barbara , Pyle Laura 
Published: February 2009

Purpose The purpose of this article is to present the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TOD2AY) study and a description of the implementation of the standard diabetes education (SDE) program. Methods A total of 218 participants (one third of the eventual sample of 750) were initially enrolled in the study. To date, the mean age of participants was 14.3 + 2.1 years, with 63% being female. Families of study participants were largely low or middle income (more than half report family income <$35000) and about three-quarters were minority. Results More than three-quarters (79%) of families achieved full mastery of the entire SDE program. Mastery required on average 5.5 + 1.3 sessions. In addition, 62% of the families were able to achieve mastery of the session topic in a single visit. Conclusions In summary, the TOD2AY study SDE program fills the need for effective, engaging materials for youth and their families to use in mastering essential type 2 diabetes skills and knowledge.
Are Children With Type 1 Diabetes Consuming a Healthful Diet?
Authors: Rovner Alisha J. , Nansel Tonja R. 
Published: February 2009

Purpose The purpose of this study is to review the literature on usual dietary intake in children with type 1 diabetes (T1D) and to discuss approaches to promote dietary change with potential efficacy. Methods Search strategies included a MEDLINE search for English-language articles that estimated usual dietary intake in children with T1D and a screening of the reference lists from original studies. The keywords used were diet, dietary intake, nutrition, type 1 diabetes, children, adolescents, and youth. Studies were included if they were observational, contained a sample of children with T1D, and estimated usual dietary intake. Results Nine studies fulfilled the criteria (6 US, 3 European). Of the 4 studies with a control group, 3 reported that both total fat and saturated fat intake were higher in the children with T1D. Six studies examined the percent of total calories from saturated fat; mean intake ranged from 11 to 15%, exceeding ADA recommendations (< 7%). Fruit, vegetable, and fiber intakes were low among children with T1D. No prior studies have addressed dietary change in this population. The behavior-change literature suggests that nutrition education alone is unlikely to be adequate, but that incorporation of behavioral approaches offers potential efficacy in promoting healthful dietary change. Conclusions Children with T1D are not meeting dietary guidelines, and in some areas their diets are less healthful than children without diabetes. As these dietary behaviors may affect the risk of long-term complications, the incorporation of behavioral approaches promoting healthy eating into routine clinical practice is warranted.
A Pilot Study of Diabetes Education via Telemedicine in a Rural Underserved Community—Opportunities and Challenges
Authors: Balamurugan Appathurai , Hall-Barrow Julie , Blevins Mary Alice , Brech Detri , Phillips Martha , Holley Elizabeth , Bittle Kim 
Published: February 2009

Purpose Telemedicine technology may offer an avenue to implement diabetes self-management education (DSME) for people with diabetes in underserved rural communities. The continuous quality improvement process was used to identify the problem, collect and analyze data, and develop and implement a DSME program via telemedicine (DSME-T) in an underserved rural community. Methods A pilot study was conducted in 2006, implementing a DSME-T utilizing facilities at the University of Arkansas for Medical Sciences and a rural community hospital in Arkansas (Ozark Health, Inc). A total of 38 people were enrolled to receive DSME-T. Participant knowledge, self-efficacy, and self-care practices were assessed before participants began the education program and after they had completed it. Also, select clinical measures (glycosylated hemoglobin, lipid profile, and urine microalbumin) were collected. Results A total of 66% of participants (n = 25) completed the DSME-T program. A significantly greater proportion of participants demonstrated improved knowledge (39% vs 83%; P = .012), endorsed greater self-efficacy (54% vs 86%; P = .016), and reported more frequent self-care practices to manage their diabetes at the conclusion of the study period. Conclusions The results of this pilot study suggest that DSME-T may offer opportunities for DSME among rural residents with diabetes. Plans are in place to explore the possibility of sustaining and expanding the program to other underserved rural communities.
Universal Design in Diabetes Care An Idea Whose Time Has Come
Authors: Williams Ann S. 
Published: February 2009

Purpose The purpose of this article is to introduce diabetes educators to the emerging concept of universal design (UD): the design of products, environments, and services to be used by persons with a wide range of abilities, without needing adaptation or specialized design. Method Drawing from the use of the term universal design in a variety of types of writing, this article covers the definition of UD, the contrast of average-person design with UD, principles of UD, and implications for diabetes self-management education (DSME). Summary Implications for DSME are (1) diabetes consumer medical devices (such as blood glucose meters and insulin pumps) can be designed using UD principles, with a goal of successful use by the largest number of persons possible, and (2) diabetes educators can use UD principles in the design of diabetes education programs to reach the largest number of learners possible without the need for special accommodations. Conclusions Adoption of UD principles by designers of diabetes medical devices could benefit persons with disabilities, increase the potential market for the manufacturer, and have unexpected benefits for people of average abilities. Adoption of UD principles for DSME programs would not require a paradigm change because diabetes educators already do many activities that could contribute to UD of an education program. By replacing average-person design of DSME programs with UD, diabetes educators can promote full participation in DSME for individuals with the wide range of abilities normally present in target populations without the need for added adaptations or specialized design.