bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1377: Characterisation of mechanisms of resistance to sunitinib in a unique pre-clinical RCC model
Authors: Taylor Melissa , Barthélémy Amélie , Escudier Bernard , Farace Françoise 
Published: August 2012

Abstract
Background: Resistance to sunitinib, a broad spectrum tyrosine kinase inhibitor considered as first-line therapy for advanced clear cell renal carcinoma (ccRCC), is almost inevitable in patients. However, understanding the mechanisms underlying resistance to sunitinib remains incomplete. In order to decipher underlying drug-induced resistance mechanisms and identify potential targets to overcome sunitinib resistance in ccRCC, we developed a unique ccRCC xenograft model that mimicked clinical resistance to sunitinib. Methods: Untreated and sunitinib-treated Balb/C mice xenografted with RENCA cells were monitored for tumor growth. Sunitinib (40 mg/kg/day) administered 5 days/7 initially inhibited growth of xenografts, but tumors escaped after 6 weeks of continuous therapy. These sunitinib-induced resistant tumors were then removed and re-implanted to naïve Balb/C mice where re-implanted tumors exhibited immediately an aggressive phenotype. Re-implanted sunitinib-resistant tumors remained refractory to further treatment with sunitinib but responded to treatment with sorafenib and rapamycine, mimicking a strategy and tumor response that is often observed in the clinical setting. Transcriptomic and proteomic analyses of untreated, sunitinib-responsive and sunitinib-resistant tumors were performed, as well as evaluations of microvessel densities and host circulating angiogenic cells. Results: The aggressive phenotype of re-implanted sunitinib-resistant tumors suggested that the drug-induced acquired resistance was of intrinsic nature. However, transcriptomic analyses showed no differences in gene expression levels between untreated, sunitinib-responsive and sunitinib-resistant tumors. Proteomic analyses of tumors and serum samples are ongoing, as well as thorough analyses of the different angiogenic cellular compartments underlying host microenvironment responses. Conclusion: We have established a unique xenograft ccRCC model that mimicks clinical resistance to sunitinib. Our results show that while sunitinib-induced resistance is apparently intrinsic, tumor and host microenvironment are most likely critical mediators of resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1377. doi:1538-7445.AM2012-1377
Abstract 1406: A new ovarian cancer metastasis model using multicellular spheroids generated from human ovarian cancers tissues
Authors: Sun Guigin , Meng Fanliang , Zhong Mei , Yu Yanhong , Shan Weiwei , Anderson Matthew , Brewer Molly A. 
Published: August 2012

Abstract
Objective Most research aimed at dissecting the mechanism by which epithelial ovarian cancer (EOC) metastasizes has focused on the ability of individual cells to attach and create tumor implants. However, multicellular aggregates known as spheroids are frequently found in ovarian cancer ascites and these aggregates are increasingly thought to play an important role in metastasis not only for ovarian cancer but also other solid tumors where similar phenomena have been observed. We investigated characteristics of spheroids compared to cells grown in monolayer to further characterize these spheroids. Methods IRB approval was obtained for collection of human tissue. Fresh specimens of ovarian cancer were minced, enzymatically digested, rinsed and incubated either in DMEM to generate monolayer cultures or Mammosphere media to generate spheroids. Tumorigenicity was assessed by inoculating individual spheroids or an equal number of dissociated cells into the peritoneal cavity of SCID mice. Gene expression was examined using Western blot and quantitative real-time PCR. Results We found that cells from most ovarian cancers do generate spheroids and most of the spheroids generated are able to reliably induce peritoneal implants in SCID mice. At a molecular level, the spheroids were enriched for expression of specific markers including CD133, CD44, NANOG and OCT4, associated with populations of cancer initiating cells (CICs) as well as other stem cell markers. MiR-26b, characteristic of CICs, was significantly up regulated in spheroids compared to monolayer cells. Spheroids from CD133 positive cells induced ovarian and abdominal tumors in SCID mice, however, CD44 spheroids only generated localized tumor, suggesting that CD133 is important in metastasis of ovarian cancer. Conclusion Our results indicate that populations of cells from human EOC are capable of spontaneously generating multicellular aggregates that resemble the spheroids found in ovarian cancer ascites de novo. These spheroids are enriched for expression of markers including CD133, CD44, NANOG and OCT4, suggesting that spheroid formation enhances stem cell-like markers. CD133 might also serve as a necessary marker for metastasis of ovarian cancer. The increased expression of miR-26b in spheroids compared to monolayer culture is a novel finding that needs further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1406. doi:1538-7445.AM2012-1406
Abstract 162: Biomarker identification of residual triple negative breast cancer (TNBC) after standard neoadjuvant chemotherapy (NCT)
Authors: Sohn Joohyuk , Liu Shuyling , Chen Huiqin , Meng Xiaolong , Do Kim-Anh , Mills Gordon B. , Hortobagyi Gabriel N. , Meric-Bernstam Funda , Gonzalez-Angulo Ana M. 
Published: August 2012

Abstract
Backgrounds Residual TNBC after standard NCT has a poor prognosis. The aim of this study was to identify biomarkers that correlate with prognosis and can be used as novel therapeutic targets in this disease Methods 54 residual TNBC were identified. Protein was extracted and 76 antibiotics to proteins related to breast cancer signaling were measured by reverse phase protein arrays (RPPA). Univariable and multivariable Cox proportional hazard model ratios were fitted for each protein and simultaneously. Cross-validation was also performed. The coefficient in the multivariable Cox model were used to calculate a risk score (RS) for each sample. Results The unsupervised clustering analysis of the proteomic profiles for the 54 residual breast cancers and 76 proteins divided the tumors into two groups without significant survival difference. Multivariable analysis using the top 25 proteins from univariable analysis at a false discovery rate (FDR) of 0.3 showed that IGFPB2, LKB1, and S6 were significant predictors in relapse free survival (RFS). RS model calculated based on multivariable analysis was 0.3746*IGFPB2-0.8852*LKB1+0.6012*S6, AUC=0.807. Employing crossvalidation the model was found to be reproducible. Multivariable analysis suggested that RS was an independent predictor of RFS (HR: 2.705, 95% CI 1.549 to 4.723, P-value=0.0005). Conclusions We identified a RS of three biomarkers that predict outcome in patients with residual TNBC that could be studied as therapeutic targets for this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 162. doi:1538-7445.AM2012-162
Abstract 1621: Potent anti-cancer effect of crocin against hepatocellular carcinoma: A preclinical study
Authors: Amin Amr , Schneider-Stock Regine , Daoud Sayel 
Published: August 2012

Abstract
Background: This is a follow up of our study published in September issue of Hepatology and featured in October issue of Science News that documented the antic-cancer potential of saffron. Here, we show the chemopreventive actions and mechanisms of saffron-based bioactive ingredient; crocin, against diethylnitrosamine (DEN)-induced liver cancer in rats. Methods: Administration of crocin at two doses of 100 and 200 mg/kg body wt per day was started two weeks prior to the DEN injection and was continued for 22 weeks. Result: Crocin decreased the number and the area of placental glutathione-S-transferase positive foci in livers of DEN-treated rats. Furthermore, crocin counteracted DEN-induced oxidative stress in rats as assessed by restoration of superoxide dismutase, catalase, and glutathione-S-transferase levels and diminishing of myeloperoxidase activity, malondialdehyde and protein carbonyl formation in liver. The results of immunohistochemical staining of rat liver showed that crocin inhibited the DEN-mediated elevations in numbers of cells positive for Ki-67, cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa Bp-65 and the phosphorylated tumor necrosis factor receptor. Crocin also blocked the depletion in the number of cells positive for TUNEL and M30 CytoDeath in liver tissues of DEN-treated rats. In vitro experiments carried out using HepG2 cells also confirmed these findings and showed inhibition of NFkB activation, increased cleavage of caspase-3, as well as DNA damage and cell cycle arrest upon saffron treatment. Conclusion: The present study provides evidence that crocin exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis. This report also shows some evidence that crocin protects rat liver from cancer via modulating oxidative damage and suppressing inflammatory response. This study is funded by Emirates Foundation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1621. doi:1538-7445.AM2012-1621
Abstract 1638: Aspirin acetylates multiple cellular proteins in HCT-116 cells: Identification of novel targets
Authors: Gunaje Jayarama B. , Marimuthu Srinivasan , Chivukula Raghavender S.V. , Moridani Majid , Hagen Fred K. , Alfonso Lloyd F. 
Published: August 2012

Abstract
Aspirin, a non-steroidal anti-inflammatory drug has been consistently associated with a reduced risk of colon cancer; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate, and post-transnationally modify cellular proteins in HCT-116 human cancer cells to understand the potential mechanisms by which it may exert anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immune-affinity purification, mass spectrometry and immunoblotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeletal proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde 3 phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiments showed that aspirin also acetylated glucose 6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6-phosphate dehydrogenase activity. Selective inhibition of glucose 6-phosphate dehydrogenase and other key proteins through acetylation may represent important mechanisms by which aspirin may exert its anti-cancer effects.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1638. doi:1538-7445.AM2012-1638
Abstract 1650: Overview of the clinical ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) Consortium (CEC)
Authors: Goh Chee L. , Schumacher Fredrick , Kote-Jarai Zsofia , Kraft Peter , Easton Douglas , Henderson Brian , Eeles Rosalind 
Published: August 2012

Abstract
Background The inherited link of prostate cancer (PrCa) has led to large scale Genome Wide Association Studies (GWASs), which aim to identify susceptibility loci associated with PrCa. Currently, these Single Nucleotide Polymorphisms (SNPs) have only been evaluated against overall PrCa risk and several disease parameters. The challenge now is to translate these genetic risk algorithms into the clinical setting. This has led to NIH (National Institute of Health) funded post-GWAS initiatives in PrCa and the establishment of the Clinical ELLIPSE Consortium (CEC) to harmonise genetic, clinical and epidemiological data from existing consortia around the world. This will provide the necessary guidance in developing useful and powerful risk prediction models for PrCa risk, including screening outcome and treatment effects. These risk prediction models may have an immediate public health impact by providing clinicians with the necessary tools to improve clinical decision making. Methods Several projects are currently underway including the analysis of Active Surveillance outcomes against these SNPs, and the analysis of the PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome) consortium cohort, looking at the association of these SNPs with disease parameters. Collaborations have been established with ERSPC (European Randomized Study of Screening for Prostate Cancer), STAMPEDE (Systemic Therapy in Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy) and RAPPER (radiogenomic) consortia, to analyse these SNPs’ role in screening and treatment outcomes. Results An inventory collected across the consortium showed that there are 59688 cases and 191698 controls with clinical data. There were also large numbers of tumour (11982 samples) and blood (43624 samples) available. These figures are very encouraging and discussions are currently underway to access and combine data across the groups for analyses. Conclusion The CEC provides the necessary framework needed to foster successful collaborations and begin the transition from ‘bench-side’ research to ‘bed-side’ care. Acknowledgments This project is supported by The NIH grant: No. 1 U19 CA 148537-01 and Cancer Research UK.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1650. doi:1538-7445.AM2012-1650
Abstract 1663: Mapping genes that predict treatment outcome in admixed populations
Authors: Baye Tesfaye Mersha , Wilke Russell A. 
Published: August 2012

Abstract
There is great interest in characterizing the genetic architecture underlying drug response. For many drugs, gene-based dosing models explain a considerable amount of the overall variation in treatment outcome. As such, prescription drug labels are increasingly being modified to contain pharmacogenetic information. Genetic data must, however, be interpreted within the context of relevant clinical covariates. Even the most predictive models improve with the addition of data related to biogeographical ancestry in admixed population. Admixture influences populations in a manner different from geographic race or cultural ethnicity. When two genetically distinct populations interbreed, a set of unique relationships are created among sets of variants across the genome. This phenomenon results in the formation of long segments of DNA with distinguishable ancestral origins. Risk alleles carried within these segments can influence treatment outcome in a variety of contexts. As the scientific community moves toward characterization of outcome in diverse cohorts with DNA biobanks linked to comprehensive electronic medical records, a great need exists for the development of flexible, robust analytical strategies that leverage admixture to optimize the study of pharmacogenomics. We presented analytical strategies to develop ancestry informative marker (AIM) that leverage population structure to more fully characterize genetic determinants of outcome in large clinical practice-based admixed cohorts. Keywords: Admixture, ancestry, Ancestry Informative Markers, AIMs, admixture mapping, ancestry, biobank, database, pharmacogenetics
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1663. doi:1538-7445.AM2012-1663
Abstract 1668: Understanding cancer associated SNPs in the TERT-CLPTM1L locus through population genetics
Authors: Mirabello Lisa , Chung Charles , Yeager Meredith M. , Savage Sharon A. 
Published: August 2012

Abstract
Telomeres form the ends of eukaryotic chromosomes and are vital in maintaining genetic integrity. TERT encodes the telomerase reverse transcriptase, which is responsible for maintaining telomere ends by addition of (TTAGGG)n nucleotide repeats at the telomere. Recent genome-wide association studies have found common genetic variants at theTERT-CLPTM1L locus (5p15.33) associated with increased risk of several cancers, including glioma, basal cell carcinoma, testicular, pancreatic, breast and lung cancers, and possibly overall cancer risk. Our prior studies of common single nucleotide polymorphisms (SNPs) in the TERT gene region found low differentiation among populations and higher than expected levels of haplotype diversity in data from the Human Genome Diversity Panel (HGDP) and the International HapMap Project. In the current study we significantly expanded the population genetic analyses by utilizing data from the 1000 Genomes Project (2011 October release). Genetic variation from a total of 1092 individuals from 14 populations with European, East Asian, West African or American ancestry was evaluated. Data were acquired for 3468 variants in a 206kb region on 5p15.33, which included the TERT-CLPTM1L gene and flanking regions. The GLU genetics’ ld.tagzilla module was used for the tag analysis with a linkage disequilibrium (LD) pairwise r2 threshold of 0.8. Arlequin (3.5) and Genepop (4.1) packages were used to estimate diversity, LD, heterozygosity, and differentiation (FST) among populations. Pairwise LD was analyzed separately for the 4 ancestral groups (European, East Asian, West African and American) and used to select tag SNPs for each region. The 4 ancestral groups had differing LD patterns with the lowest level of LD occurring in individuals from Africa, as expected. These data were used to create the appropriate haplotype-tagging SNPs for the TERT-CLPTM1L region in each population; we present recommended tagging SNPs by ancestral group. The TERT-CLPTM1L gene region had low nucleotide diversity (mean 2 x 10−4) and differentiation among ancestral groups (90% of loci in this region had FST &lt;0.10). The limited diversity in this region may be due to its critical role in telomere maintenance and chromosomal stability. The recently identified cancer associated SNPs in this region had differing genotype frequencies among ancestral groups. Variation in cancer associated alleles among ancestral groups may correlate to varying disease risks.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1668. doi:1538-7445.AM2012-1668
Abstract 1688: Relevance of mTOR pathway in prognosis of patients with urothelial carcinoma of the bladder
Authors: Fahmy Mona , Mansure Jose Joao , Brimo Fadi , Yafi Faysal , Segal Robert , Althunayan Abdulaziz , Netto George , Meeker Alan , Hicks Jessica , Kassouf Wassim 
Published: August 2012

Abstract
Purpose. To investigate the role of mTOR signalling pathway on stage and outcome of patients with high grade and/or invasive bladder cancer. Methods. Tissue microarrays were built from archival of high grade and mostly superficial bladder tumour specimens (n=143 with complete clinical data collected). Immunohistochemical staining was performed for Phosphatase and tensin homolog (Pten), phosphorylated (phos) Akt, phos-mTOR, phos-S6, phos-4EBP1 and p27. The markers were evaluated for pattern, percentage and intensity of staining (H-score), and results correlated with clinicopathological characteristics and outcome. Results. The median age at diagnosis of the patient cohort was 71 years (range: 38-96 years). The TNM stage group was distributed as pTa (44%), pT1(49%) and pT2 (6%). After a median follow-up of 34 months, the disease recurrence, disease progression and overall death rates were 44%, 13%, and 11% respectively. The expression of p27 was significantly lower among pT2 compared to pTa and pT1 patients (p &lt; 0.03). The H-score of phos-mTOR was significantly correlated with p27 (p &lt;0.003), pS6 (p &lt; 0.004) and 4EBP1 (p &lt;0.001). In multivariate analysis, which included age, number of tumors, tumor size and stage, phos-S6 was an independent predictor of shorter recurrence-free (Hazard Ratio [HR]: 2.75, 95% Confidence Interval [CI]: 1.16-6.51). The expression of p27 was inversely correlated with recurrence-free survival (HR:0.37, 95% CI:0.18-0.88). None of the markers showed correlation with progression free survival and overall survival. Conclusion. Our results demonstrate that activation of mTOR pathway, as assessed by phosS6 might be used to provide prognostic information particularly as predictor of recurrence among patients with high-risk non-muscle invasive bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1688. doi:1538-7445.AM2012-1688