bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B25: Porous silicon microparticles exhibit immunomodulatory effects leading to suppression of tumor growth.
Authors: Meraz Ismail M. , Williams Laura , Yang Marie , Lavelle Edward C. , Serda Rita E. 
Published: August 2014

Abstract
Nanoparticles, such as polymeric delivery platforms, can exhibit intrinsic immunostimulant properties, dependent on size, charge, surface modification, and composition. To function as effective adjuvants, a balance between immunostimulatory properties and biocompatibility is essential. We have demonstrated that porous silicon (pSi) microparticles are effective delivery vehicles, with uptake by target cell populations. A peritonitis mouse model was used to access early innate immune responses 24 hours following administration of pSi microparticles. C57BL/6 mice were injected intraperitoneally with microparticles of various shapes and sizes and cytokine production and cell infiltration were assessed. pSi microparticles were found to have proinflammatory effects. The microparticles induced significant leukocyte infiltration into the site of injection and elevated IL-1β levels in lavage fluid.
As cancer progresses, immune responses become more tolerant and cancer cells become more refractory to chemotherapies. Select chemotherapeutics, including cyclophosphamide, doxorubicin, and paclitaxel, have immunodulatory effects. Based on the immunopotentiating effects of pSi microparticles, and the ability of monophosphoryl lipid A (MPL) adsorbed pSi microparticles to activate antigen presenting cells, we sought to potentiate the doxorubicin-mediated immune response through co-delivery of MPL-pSi microparticles. When tumors in mice bearing intramammary 4T1-luc breast tumors reached a volume of 100 mm3, mice were injected with doxorubicin loaded liposomes (5 mg/kg) and MPL-pSi microparticles (5x108 microparticles; 10 µg MPL equivalent) by means of tail vein injection. Tumor growth was monitored by calipher measurements and luciferase expression using the IVIS Imaging System 200. While MPL-pSi microparticle-treated mice exhibited reduced tumor growth, mice receiving MPL-pSi microparticles and doxorubicin-loaded liposomes exhibited arrest of tumor growth. Thus pSi microparticles are an attractive immunopotentiating platform, with applications for both drug and antigen delivery.
Citation Format: Ismail M. Meraz, Laura Williams, Marie Yang, Edward C. Lavelle, Rita E. Serda. Porous silicon microparticles exhibit immunomodulatory effects leading to suppression of tumor growth. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B25.
Abstract B57: A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity.
Authors: Smith Annalise R. , Lopez Darlah , Andreansky Samita 
Published: August 2014

Abstract
Recent research involving chemotherapeutic drugs such as anthracyclines have aided in redefining the definition of apoptosis from a form of cell death that is immunologically silent to the one that can activate an anti-cancer immune response. This form of apoptosis has been characterized as immunogenic cell death (ICD) and possess certain hallmarks such as the cell surface expression of heat shock proteins (HSPs) including HSP70 and HSP90 as well as ER-stress mediated pre-apoptotic expression of the ER chaperone calreticulin (CRT). One of the mechanisms by which ICD occurs is linked to the induction of an unfolded protein response (UPR) due to prolonged chemotherapeutic stress on cancer cells. Our research focuses on the development of Withaferin A (WA), a steroidal lactone derived from the Indian ayurvedic medicinal plant Withania somnifera as a chemoimmunotherapeutic agent. The benefit of using natural plant derived products is their low toxicity, multimodal action and potential ability to enhance the immune system. We initially screened the effect of Withaferin A by microarray analysis on breast cancer cells. WA induced significant alteration of 1160 genes (p-value 0.005). A pathway analysis determined that WA induces a robust heat shock response through up-regulation of several genes related to this pathway including response to unfolded proteins. The gene expression data was confirmed by the induction of intracellular HSP70, HSP40 as well as the UPR marker Bip78 by western blot. Furthermore we are able to demonstrate that WA treatment results in the translocation of known immunogenic HSPs HSP70, CRT and gp96 to the cell surface of several cancer cell lines. Additionally, WA treatment results in the induction of apoptosis and these WA mediated apoptotic cells can confer immunological protection against re-challenge with live tumor cells in vivo. Our long-term goal is to elucidate the anti-tumor immunomodulatory mechanisms of WA.
Funded by: American Cancer Society (S.A.)
Citation Format: Annalise R. Smith, Darlah Lopez, Samita Andreansky. A natural plant-derived compound, Withaferin A, exploits the stress pathway to induce antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B57.
Abstract IA21: Using viruses to advance T cell therapy for malignancy.
Authors: Yanagisawa Miyuki , Ngo Minhtran , Rooney Cliona M. , Leen Ann Marie , Vera Juan , Heslop Helen E. , Brenner Malcolm K. 
Published: August 2014

Abstract
Virus-specific T cells effectively prevent and treat viral diseases after stem cell transplantation and have produced complete remissions (CRs) in patients with EBV-positive malignancy outside the transplant setting. The success of EBV-specific T cells is thought to be due to the strong viral antigens expressed by these tumors and the vaccine effect of endogenous EBV.
We tested if this endogenous viral vaccine effect could be exploited for the treatment of non-viral malignancy by engrafting chimeric antigen receptors specific for the disialoganglioside,GD2 (GD2.CAR) on EBV-specific T cells and comparing their in vivo expansion with that of GD2.CAR-engrafted CD3-activated T cells (ATCs) in patients with relapsed neuroblastoma. Transgenic EBV-CTLs were detected at higher levels than GD2.CAR-ATCs and 6 of 8 patients without disease at infusion remain tumor-free, while 6 of 11 with disease had tumor responses including 3 CRs. However the expected increase in frequency of EBV-specific T cells in patient blood was not observed, perhaps because EBV was well-controlled in these patients.1,2
To improve this vaccine effect, we looked to VZV, for which a potent, but safe commercially-available vaccine exists. We identified five VZV antigens that we predicted would be presented to the immune system early after infection, generated overlapping peptide libraries (pepmixes) for each and used them to stimulate T- cells from both naturally-infected and vaccinated individuals. T cells expanded in vitro and were antigen-specific as measured on day 9 using γ-IFN ELIspot analysis. T cells specific for all five antigens increased in frequency in response to VZV vaccination. VZV-specific T cells transduced with a GD2.CAR retained their ability to respond to VZV antigens and acquired the ability to eliminate GD2+ tumor cells.
Ultimately, we plan to combine GD2.CAR-engrafted, VZV-specific T cells with VZV vaccination for the treatment of patients with relapsed GD2+ tumors.
References:
1 Pule et al. Nat Med. 2008 Nov;14(11):1264-70
2 Louis et al. Blood. 2011 Dec 1;118(23):6050-6
Citation Format: Miyuki Yanagisawa, Minhtran Ngo, Cliona M. Rooney, Ann Marie Leen, Juan Vera, Helen E. Heslop, Malcolm K. Brenner. Using viruses to advance T cell therapy for malignancy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA21.
The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis
Authors: Lucas Jared M. , Heinlein Cynthia , Kim Tom , Hernandez Susana A. , Malik Muzdah S. , True Lawrence D. , Morrissey Colm , Corey Eva , Montgomery Bruce , Mostaghel Elahe , Clegg Nigel , Coleman Ilsa , Brown Christopher M. , Schneider Eric L. , Craik Charles , Simon Julian A. , Bedalov Antonio , Nelson Peter S. 
Published: August 2014

Abstract
TMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries, we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal transition phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.
Significance: The vast majority of prostate cancer deaths are due to metastasis. Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through mechanisms involving the HGF–c-MET axis. Therapeutic approaches directed toward inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in patients with prostate cancer. Cancer Discov; 4(11); 1310–25. ©2014 AACR.
See related commentary by Rubin, p. 1262
This article is highlighted in the In This Issue feature, p. 1243
A genomewide study of body mass index and its genetic correlation with thromboembolic risk
Authors: Pena Geórgia , Ziyatdinov Andrey , Buil Alfonso , López Sonia , Fontcuberta Jordi , Soria José Manuel , Souto Juan Carlos 
Published: August 2014

SummaryThrombosis and obesity are complex epidemiologically associated diseases. The mechanism of this association is not yet understood. It was the objective of this study to identify genetic components of body mass index (BMI) and their possible role in the risk of thromboembolic disease. With the self-reported BMI of 397 individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the genetic correlation with the risk of thrombosis. Subjects were genotyped for an autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate and bivariate multipoint linkage analyses were performed. The heritability for BMI was 0.31 (p= 2.9×10–5). Thromboembolic disease (including venous and arterial) and BMI had a significant genetic correlation (ρG= 0.54, p= 0.005). Two linkage signals for BMI were obtained, one at 13q34 (LOD= 3.36, p= 0.0004) and other at 2q34, highly suggestive of linkage (LOD= 1.95). Bivariate linkage analysis with BMI and thrombosis risk also showed a significant signal at 13q34 (LOD= 3), indicating that this locus influences at the same time normal variation in the BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy with both phenotypes, contains two candidate genes, which may explain our linkage pleiotropic signal and deserve further investigation as possible risk factors for obesity and thrombosis.
Optimizing the Probability of Flying in High Ice Water Content Conditions in the Tropics Using a Regional-Scale Climatology of Convective Cell Properties
Authors: Protat A. , Rauniyar S. , Kumar V. V. , Strapp J. W. 
Published: August 2014

AbstractIn this paper, statistical properties of rainfall are derived from 14 years of Tropical Rainfall Measuring Mission data to optimize the use of flight hours for the upcoming High Altitude Ice Crystals (HAIC)/High Ice Water Content (HIWC) program. This program aims to investigate the convective processes responsible for the generation of the high ice water content that has been recognized as a threat to civil aviation. The probability that convective cells are conducive to HIWC is also further investigated using three years of C-band polarimetric radar data. Further insights into the variability of convective rainfall and favorable conditions for HIWC are also gained using two different methods to characterize the large-scale atmospheric conditions around Darwin, Australia (the Madden–Julian oscillation and the Darwin atmospheric regimes), and the underlying surface type (oceanic vs continental). The main results from the climatology relevant to flight-plan decision making are (i) convective cells conducive to HIWC should be found close to Darwin, (ii) at least 90% of convective cells are conducive to HIWC at 10- and 12-km flight levels, (iii) multiple flights per day in favorable large-scale conditions will be needed so as to utilize the 150 project flight hours, (iv) the largest numbers of HIWC radar pixels are found around 0300 and 1500 local time, and (v) to fulfill the requirement to fly 90 h in oceanic convection and 60 h in or around continental convection, a minimum “acceptable” size of the convective area has been derived and should serve as a guideline for flight-decision purposes.
Uncertainties of GPM DPR Rain Estimates Caused by DSD Parameterizations
Authors: Liao Liang , Meneghini Robert , Tokay Ali 
Published: August 2014

AbstractA framework based on measured raindrop size distribution (DSD) data has been developed to assess uncertainties in DSD models employed in Ku- and Ka-band dual-wavelength radar retrievals. In this study, the rain rates and attenuation coefficients from DSD parameters derived by dual-wavelength algorithms are compared with those directly obtained from measured DSD spectra. The impact of the DSD gamma parameterizations on rain estimation from the Global Precipitation Measurement mission (GPM) Dual-Frequency Precipitation Radar (DPR) is examined for the cases of a fixed shape factor μ as well as for a constrained μ—that is, a μ–Λ relation (a relationship between the shape parameter and slope parameter Λ of the gamma DSD)—by using 11 Particle Size and Velocity (Parsivel) disdrometer measurements with a total number of about 50 000 one-minute spectra that were collected during the Iowa Flood Studies (IFloodS) experiment. It is found that the DPR-like dual-wavelength techniques provide fairly accurate estimates of rain rate and attenuation if a fixed-μ gamma DSD model is used, with the value of μ ranging from 3 to 6. Comparison of the results reveals that the retrieval errors from the μ–Λ relations are generally small, with biases of less than ±10%, and are comparable to the results from a fixed-μ gamma model with μ equal to 3 and 6. The DSD evaluation procedure is also applied to retrievals in which a lognormal DSD model is used.
Regional differences in statistical geometry of endothelial dense granules in human extremity veins
Authors: Gősi G , Nádasy GL , Raffai G , Fehér E , Szeberin Z , Monos E , Acsády G 
Published: August 2014

Objectives Leg and arm human veins are exposed to different gravitational stresses. We investigated if there is difference in the amount and geometry of secretory vesicles in their endothelium. Methods Superficial small vein segments were removed during vascular operations for electromicroscopic analysis. Vesicular area/total endothelial cross-sectional area was determined by computer-based morphometry. Long and short axes of granule cross sections were measured by image analyzing software. Results Vesicular density in all samples was 2.26 ± 0.34%. There was no significant difference between the vesicular densities of upper extremity and leg. The shape of the vesicles was more frequently elongated in leg than in arm sections ( p < 0.01). Conclusions The density of the vesicles does not depend on vascular region or orthostatic load. Ellipticity of these granules is significantly different in areas exposed to different gravitational stresses. This might contribute to the differences of thrombotic and hemodynamic properties of leg and upper body veins.
Electrophysiological correlates of alcohol- and non-alcohol-related stimuli processing in binge drinkers: A follow-up study
Authors: Petit Géraldine , Kornreich Charles , Dan Bernard , Verbanck Paul , Campanella Salvatore 
Published: August 2014

Background: The continuation of binge drinking is associated with the development of neurocognitive brain abnormalities similar to those observed in patients with alcohol dependence. Alcohol cue reactivity constitutes a risk marker for alcohol dependence. Through event-related potentials (ERPs), we aimed to examine its potential presence as well as its evolution over time in binge drinkers in a one-year period. Methods: ERPs were recorded during a visual oddball task in which controls ( n=15) and binge drinkers ( n=15) had to detect infrequent deviant stimuli (related or unrelated to alcohol) among frequent standard stimuli. The test was performed twice with a one-year interval in order to explore the long-lasting influence of drinking habits. Results: Contrary to the controls, binge drinkers showed significantly reduced amplitudes of the P1 component for both alcohol and non-alcohol-related cues and of the P3 component only for neutral cues in the second assessment compared with the first. Conclusion: The continuation of binge drinking over one year is associated with the development of brain functional abnormalities (indexed by the P1 component) as well as a higher reactivity to alcohol-related stimuli and/or a decreased reactivity to non-alcohol-related stimuli (indexed by the P3 component).
Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a Community Hospital Cancer Center
Authors: Daniel Divya , Waddell Aubrey 
Published: August 2014

Objective Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. Design Retrospective study of patients receiving their first cycle of chemotherapy. Patients A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. Data Data were collected retrospectively from patient chemotherapy dispensing folders. Results In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. Conclusion Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis.
Incidence of Deep Venous Thrombosis After Tibial Tubercle Osteotomy
Authors: Tanaka Miho J. , Munch Jacqueline L. , Slater Alissa J. , Nguyen Joseph T. , Shubin Stein Beth E. 
Published: August 2014

Background: Tibial tubercle osteotomy (TTO) is performed in a predominantly young and often female population due to the prevalence of patellofemoral disorders in this group. While considered a procedure that falls within the realm of sports surgeries, the procedure can carry significant morbidity, including infection, fracture, and deep vein thrombosis (DVT). The incidence of postoperative DVT in this population has not been described in the literature, although it has been mentioned anecdotally, and current guidelines do not address the issue of DVT prophylaxis in postoperative TTO patients. Purpose: To describe the incidence of DVT after TTO and identify any predisposing factors. Study Design: Case series; Level of evidence, 4. Methods: Subjects who had undergone TTO by the senior author from 2002 to 2013 were identified, and a retrospective chart review was performed. Those who presented with symptomatic DVT confirmed with ultrasonography were reported. Demographic data, as well as potential risk factors such as body mass index, family history of bleeding/clotting disorders, duration of the nonweightbearing period, total tourniquet time, use of contraceptive medication, smoking status, and use of anticoagulants, were collected from the chart and analyzed for correlation with development of DVT. Results: A total of 156 patients were included in this study. Six patients were found to have developed symptomatic DVT during the first 6 weeks after surgery. The mean age at the time of surgery in the DVT group was 34.94 ± 6.57 years, compared with 26.26 ± 10.20 years in the non-DVT group ( P = .04). Due to the small number of patients with positive findings, there was no statistically significant correlation between the development of DVT and factors such as nonweightbearing duration, tourniquet time, or the use of contraceptives. Conclusion: The incidence of postoperative DVT in arthroscopic and sports procedures has been thought to be low. This case series reported a rate of 3.8% with symptomatic DVT after TTO, and patients diagnosed with DVT were significantly older than unaffected patients. It is anticipated that the actual rate including asymptomatic DVT would be higher, as only 60% of patients with DVT are symptomatic. More studies are needed to define the actual incidence in this population. Given the number of common risk factors in this population, including nonweightbearing duration and the use of oral contraceptive pills, future studies may show the advantage of chemical prophylaxis for DVT in this group.