bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-415: Polymorphisms in nucleotide excision repair genes and endometrial cancer risk
Authors: Doherty Jennifer A. , Weiss Noel S. , Fish Sherianne , Loomis Melissa M. , Rossing Mary A. , Chen Chu 
Published: February 2011

Abstract
The increased risk of endometrial cancer associated with unopposed exogenous estrogens and high levels of endogenous estrogens (as are present in obesity) has been hypothesized to result, at least in part, via two possible mechanisms: 1) increased cellular proliferation, and 2) through the production of estrogen metabolites, which can result in DNA damage by directly binding to DNA and forming bulky DNA adducts, and/or indirectly through the production of reactive oxygen species. Thus, interindividual variation in the ability to repair such damage might influence a woman's risk of endometrial cancer. To test this hypothesis, we examined whether the presence of the minor alleles in 64 tag SNPs in the nucleotide excision repair genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, LIG1, XPA, and XPC was associated with risk of endometrial cancer in a population-based case-control study in Washington State, with 726 cases ages 50-74 years diagnosed between 1994-2005, and 736 controls frequency-matched to the cases by age. The analyses were restricted to non-Hispanic white women. Most of the genotypes that we investigated were not associated with endometrial cancer risk. However, the presence of the rs4150386 C allele (ERCC5), the rs3730865 C allele (LIG1), and the rs3731127 T allele (XPC) was associated with risk, with respective age-adjusted per-allele odds ratios (ORs) and 95% confidence intervals (CIs) of 0.68 (0.53-0.87), 1.50 (1.05-2.14) and 1.52 (1.10-2.10). The association between rs4150386 and endometrial cancer risk was considerably stronger among obese women (body mass index (BMI)≥30 kg/m2: per-C-allele OR=0.40, 95% CI 0.24-0.65) compared to women with BMI&lt;30 kg/m2 (per-C-allele OR=0.86, 95% CI 0.64-1.14), while the association with rs3730865 was stronger among lighter versus heavier weight women (per-C-allele ORs and 95% CIs were: 1.69, 95% CI 1.12-2.56 for BMI&lt;30 kg/m2, and 1.15, 95% CI 0.55-2.42 for BMI≥30 kg/m2). The association with rs3731127 did not vary by BMI, and the altered risk associated with the minor alleles of the three SNPs did not vary by use of long-term unopposed estrogens. Because of the multiple redundancies in DNA repair pathways and the large number of possible associations examined, there is the potential for false positive findings, both overall and in BMI subgroups. Any conclusions regarding the influence of NER genotypes on risk of endometrial cancer await the results of additional studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-415.
Abstract LB-425: Design of ß-cyclodextrin-curcumin self-assembly: A new approach for enhanced curcumin delivery and therapeutic efficacy in prostate cancer cells
Authors: Yallapu Murali M. , Jaggi Meena , Chauhan Subhash C. 
Published: February 2011

Abstract
Curcumin (CUR), a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, has shown a wide range of biological applications including cancer prevention and treatment. However, low water solubility, poor pharmacokinetics and suboptimal tumor uptake, greatly hamper its anti-cancer efficacy. This study was designed to develop a novel ß-cyclodextrin-curcumin (CD-CUR) self-assembly approach for sustained release and improved curcumin delivery in prostate cancer cells. Cyclodextrin-curcumin self-assemblies were prepared by solvent evaporation technique. The formation of self-assemblies was evaluated by Fourier Transform Infra-red (FTIR), Differential Scanning Calorimetry (DSC), Thermo-gravimetric Analysis (TGA), Scanning and Transmission Electron Microscopic (SEM/TEM) analyses. Intracellular uptake of these self-assemblies was evaluated by Flow cytometry and immunofluorescence microscopy analyses. Therapeutic efficacy of these self-assemblies was determined by cell proliferation and colony formation assays using C4-2, DU145, LNCaP and PC3 prostate cancer cells. The effect of CD-CUR formulation on apoptosis related proteins was determined by immunoblotting. Physico-chemical characterization analyses confirm the formation of CD-CUR self-assemblies, which demonstrated excellent stability and solubility in physiological solutions and showed enhanced intracellular uptake in cells. Additionally, CD-CUR formulation has exhibited an improved therapeutic efficacy and enhanced PARP cleavage in prostate cancer cells compared to free curcumin. In conclusion, CD-CUR self-assemblies enhance intracellular delivery of active curcumin in prostate cancer cells and improved its therapeutic efficacy. This study suggests that CD-CUR self-assembly may be a useful nanoscale formulation for improved curcumin delivery in prostate cancer cells. Tumor specific antibody targeted CD-CUR formulation can further improve the in vivo delivery of curcumin in prostate tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-425.
Abstract LB-68: Comparative analysis of the miRNome in tumors and plasma from colorectal cancer patients
Authors: Nielsen Søren J. , Jacobsen Nana , Fog Jacob U. , Willenbrock Hanni , Baker Adam , Ørntoft Torben F. , Nielsen Hans J. , Andersen Claus L. , Møller Søren 
Published: February 2011

Abstract
MicroRNAs (miRNAs) constitute a recently discovered class of small cellular RNAs (typically 21-23 nt) that function as post-transcriptional regulators of gene expression through binding of miRNA target sequences in mRNA 3′ untranslated regions (UTRs). Current estimates indicate that at least one third of the cellular transcriptome is regulated by miRNAs, and that each miRNA has the potential to regulate hundreds of different mRNAs. As a consequence, miRNAs have been proposed to be master regulators of cellular state. This hypothesis has been borne out by a large number of studies demonstrating a causal link between miRNA dys-regulation and numerous disease states, including a diverse array of human cancers. Furthermore, the high relative stability of miRNA in common clinical source materials (e.g. FFPE blocks, plasma, urine, saliva, etc.) and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNA quantification as a promising new tool for a wide range of diagnostic applications.
To facilitate discovery and clinical transfer of miRNA-based diagnostic markers, we developed a genome-wide LNA™-based miRNA q-rt-PCR platform with unparalleled sensitivity and robustness. The platform uses a universal RT system and thus allows high-throughput profiling of miRNAs from important clinical sources without the need for pre-amplification. Using this system, we profiled samples relevant to colorectal cancer: tumor samples from colorectal cancer patients, normal adjacent tissue (NAT) from the same patients, plasma from the same patients from blood drawn on the day before surgery, and plasma from matched healthy volunteers. Both principal component analysis and unsupervised hierarchical clustering of the most variable miRNAs accurately classified tumor samples away from the set of NAT samples, suggesting that the single most important distinguishing factor between the two sets of samples is related to neoplastic transformation. We also define miRNAs that are differentially expressed in the plasma of healthy volunteers versus colorectal cancer patients and we will present an analysis of the overlap between differentially expressed miRNAs in plasma and tissue.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-68.
Abstract LB-70: In vitro anti-cancer activity of PF-04691502, a potent dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) in a panel of human breast cancer cell lines
Authors: Britten Carolyn D. , Chow Lucy , Conklin Dylan , Kalous Ondrej , Desai Amrita , Ginther Charles , Dering Judy , Christensen James , Milham Robert , Slamon Dennis J. , Finn Richard S. 
Published: February 2011

Abstract
Introduction: Activating mutations in the PIK3CA gene (encoding for the P110 catalytic subunit of PI3K) are found in more than 25% of human breast cancers [Saal LH Cancer Res 2005]. PF-04691502 is a potent orally-available ATP-competitive and reversible dual inhibitor of PI3K and mTOR. This study evaluates the anti-proliferative and cytotoxic activity of PF-04691502 across a large panel of breast cancer cell lines that recapitulate the clinical spectrum of the disease.
Methods: Over 40 human breast cancer cell lines were exposed in vitro to PF-0469102 over 9 concentrations to generate dose-response curves. These assays were performed over a 6-day incubation period using direct cell counts. The ability of PF-04691502 to inhibit proliferation and induce cell death was calculated using IC50 and LD50 values, respectively. PI3K mutation status was available from public databases. In addition, baseline gene expression profiles were generated using the Agilent platform. A subset of breast cancer cell lines with varying levels of sensitivity to the compound were incubated with PF-04691502 concentrations ranging from 10 to 1000 nM, and processed for Western blotting.
Results: Twenty-two cell lines had IC50 values &lt; 100 nM, with a trend towards increased sensitivity to PF-04691502 in breast cancer cell lines harboring PIK3CA mutations, and in those belonging to the luminal subtype. Lethality (LD50 &lt; 1 M) was observed in 10 out of 12 breast cancer cell lines harboring PI3KCA mutations, and was prevalent in cell lines of luminal subtype. Inhibition of the downstream target pAKT was observed.
Conclusions: PF-04691502 has anti-cancer activity across a spectrum of breast cancer cell lines, and demonstrates lethality against a subset of cell lines. A first-in-human phase I trial of PF-04691502 is ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-70.
Abstract LB-93: The epigenetic basis of the tumorigenic action of retinoic acid
Authors: Rossetti Stefano , Ren MingQiang , Somenzi Giulia , Tagliavacca Luigina , Sacchi Nicoletta 
Published: February 2011

Abstract
Preformed vitamin A, or Retinol, is found in animal foods, such as liver and whole milk, and in some fortified food products. Carotenoids, such as beta-carotene from fruit and vegetables, are also efficiently converted into Retinol. Retinol, once converted into its bioactive form, retinoic acid (RA), plays a major role in cell division, cell death, and cell differentiation. We found that RA can exert a double-edged action: it can either inhibit, or promote, tumorigenesis according to the functional status of one of its receptors, the RA receptor alpha (RARA). Further, we found that RA, through RARA, controls a network of tumor suppressor genes governing cell death, cell proliferation, cell differentiation, migration, and invasion. Finally, we observed that concomitant with epigenetic silencing of the tumor suppressor gene network, due to loss/functional inhibition of RARA, RA exerts a clear tumor-promoting action, raising the question as to whether dietary sources of RA, or RA precursors, can also promote tumorigenesis in cells with an impaired RARA. Using an isogenic breast cancer cell model (T47D), comprising two clonal cell lines, one with a functional RARA-regulated gene network (T47DLXC5) and one without functional RARA (T47DDNC8) (Ren et al., MCB, 2006), we generated subcutaneous xenograft tumors in athymic female nude mice. A 6-week diet with either RA (5 or 10 mg/kg) or Retinol (50 mg/kg) induced an opposite effect on xenograft tumor growth. T47DDNC8 xenograft tumors were stimulated to grow and metastasize to distant sites by RA/Retinol, while T47DLXC5 xenograft tumors were growth-inhibited by RA/Retinol, and did not invade.
In breast cancer RARA function is often impaired due to a variety of upstream causes, including faulty RA transport by CRABP2 onto RARA and/or loss of Estrogen Receptor alpha (ERA), a pivotal RARA transcriptional regulator. Early detection of epigenetic silencing of tumor suppressor genes of the RARA network can be used to prevent tumorigenic effects of dietary sources of RA on breast tumorigenesis.
This work was funded by R01 CA127614 (NS), PRIN 2007 (LT, SR).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-93.
Sunnybrook and House‐Brackmann Systems in 5397 Facial Gradings
Authors: Kanerva Mervi , Jonsson Lars , Berg Thomas , Axelsson Sara , Stjernquist‐Desatnik Anna , Engström Mats , Pitkäranta Anne 
Published: February 2011

ObjectivesTo study the correlation between Sunnybrook and House‐Brackmann facial grading systems at different time points during the course of peripheral facial palsy.Study DesignProspective multicenter trial.SettingSeventeen otorhinolaryngological centers.Subjects and MethodsData are part of the Scandinavian Bell’s palsy study. The facial function of 1920 patients with peripheral facial palsy was assessed 5397 times with both Sunnybrook and House‐Brackmann (H‐B) facial grading systems. Grading was done at initial visit, at days 11 to 17 of palsy onset, and at 1 month, 2 months, 3 months, 6 months, and 12 months. Statistical evaluation was by Spearman correlation coefficient and box plot analysis.ResultsSpearman correlation coefficient varied from −0.81 to −0.96, with the weakest correlation found at initial visit. Box plot analysis for all assessments revealed that Sunnybrook scores were widely spread over different H‐B grades. With 50% of the results closest to the median, Sunnybrook composite scores varied in H‐B grades as follows: H‐B I, 100; H‐B II, 71 to 90; H‐B III, 43 to 62; H‐B IV, 26 to 43; H‐B V, 13 to 25; and H‐B VI, 5 to 14.ConclusionGradings correlated better in follow‐up assessments than at initial visit. As shown by the wide overlap of the grading results, subjective grading systems are only approximate. However, a conversion table for Sunnybrook and H‐B gradings was obtained and is included in the article. It can be used for further development of facial grading systems.
Thyroid Alar Cartilage Graft Laryngotracheal Reconstruction in Adults
Authors: Cui Pengcheng , Gao Pengfei , Luo Jiasheng , Ruan Yanyan 
Published: February 2011

ObjectiveTo assess the outcomes of laryngotracheal reconstruction using thyroid alar cartilage grafting in adult patients with laryngotracheal stenosis.Study DesignCase series with chart review.SettingTertiary university hospital.Subjects and MethodsTwelve adults who underwent thyroid alar cartilage graft laryngotracheal reconstruction from April 1997 to April 2009 for laryngotracheal stenosis were analyzed. The mean age of the study population was 29 years. Using the Myer‐Cotton grading system, 3 patients had grade II stenosis, 7 had grade III, and 2 had grade IV. Seven of the 12 patients had subglottic stenosis, 3 had tracheal stenosis, and 2 had subglottic and upper tracheal stenosis.ResultsNine of 12 (75%) patients were decannulated. Of the patients in whom laryngotracheal reconstruction failed, 2 had grade IV stenosis and 1 had severe grade III stenosis with a long segment of stenotic tissue. The postoperative complications were hematoma of the left laryngeal ventricle at the donor site in 1 patient, granulation tissues in the supraglottic and suprastomal region and at the graft site in 4 patients, and neck wound infection in 1 patient. Ossification of the thyroid alar cartilage was observed in 2 patients. A T‐tube remained in situ for 6 to 18 months.ConclusionLaryngotracheal reconstruction with thyroid alar cartilage graft could be a viable alternative for the treatment of laryngotracheal stenosis in adults. However, it should be used only in cases of limited and minor subglottic or tracheal stenosis.
Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium
Authors: Pidala Joseph , Kurland Brenda , Chai Xiaoyu , Majhail Navneet , Weisdorf Daniel J. , Pavletic Steven , Cutler Corey , Jacobsohn David , Palmer Jeanne , Arai Sally , Jagasia Madan , Lee Stephanie J. 
Published: February 2011

Abstract
Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT.
Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation
Authors: Jo Stephanie Y. , Granowicz Eric M. , Maillard Ivan , Thomas Dafydd , Hess Jay L. 
Published: February 2011

AbstractDisruptor of telomeric silencing 1-like (Dot1l) is a histone 3 lysine 79 methyltransferase. Studies of constitutive Dot1l knockout mice show that Dot1l is essential for embryonic development and prenatal hematopoiesis. DOT1L also interacts with translocation partners of Mixed Lineage Leukemia (MLL) gene, which is commonly translocated in human leukemia. However, the requirement of Dot1l in postnatal hematopoiesis and leukemogenesis of MLL translocation proteins has not been conclusively shown. With a conditional Dot1l knockout mouse model, we examined the consequences of Dot1l loss in postnatal hematopoiesis and MLL translocation leukemia. Deletion of Dot1l led to pancytopenia and failure of hematopoietic homeostasis, and Dot1l-deficient cells minimally reconstituted recipient bone marrow in competitive transplantation experiments. In addition, MLL-AF9 cells required Dot1l for oncogenic transformation, whereas cells with other leukemic oncogenes, such as Hoxa9/Meis1 and E2A-HLF, did not. These findings illustrate a crucial role of Dot1l in normal hematopoiesis and leukemogenesis of specific oncogenes.
Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α
Authors: Wang Zhongyan , Bishop Eric P , Burke Peter A 
Published: February 2011

AbstractBackgroundHepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.ResultsThe expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).ConclusionThe results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.
Discovery of barley miRNAs through deep sequencing of short reads
Authors: Schreiber Andreas W , Shi Bu-Jun , Huang Chun-Yuan , Langridge Peter , Baumann Ute 
Published: February 2011

Abstract

Background
MicroRNAs are important components of the regulatory network of biological systems and thousands have been discovered in both animals and plants. Systematic investigations performed in species with sequenced genomes such as Arabidopsis, rice, poplar and Brachypodium have provided insights into the evolutionary relationships of this class of small RNAs among plants. However, miRNAs from barley, one of the most important cereal crops, remain unknown.

Results
We performed a large scale study of barley miRNAs through deep sequencing of small RNAs extracted from leaves of two barley cultivars. By using the presence of miRNA precursor sequences in related genomes as one of a number of supporting criteria, we identified up to 100 miRNAs in barley. Of these only 56 have orthologs in wheat, rice or Brachypodium that are known to be expressed, while up to 44 appear to be specifically expressed in barley.

Conclusions
Our study, the first large scale investigation of small RNAs in barley, has identified up to 100 miRNAs. We demonstrate that reliable identification of miRNAs via deep sequencing in a species whose genome has not been sequenced requires a more careful analysis of sequencing errors than is commonly performed. We devised a read filtering procedure for dealing with errors. In addition, we found that the use of a large dataset of almost 35 million reads permits the use of read abundance distributions along putative precursor sequences as a practical tool for isolating miRNAs in a large background of reads originating from other non-coding and coding RNAs. This study therefore provides a generic approach for discovering novel miRNAs where no genome sequence is available.