bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-24: Molecular subtypes of pancreatic adenocarcinoma with different biological characteristics and therapeutical responses
Authors: Sadanandam Anguraj , Collisson Eric A. , Olson Peter , Gibb William J. , Truitt Morgan , Olshen Adam , Tempero Margaret A. , Spellman Paul T. , Hanahan Douglas , Gray Joe W. 
Published: June 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an invariably lethal disease. Due to its late clinical presentation, surgical cure is attempted in only a minority, and resected patients usually recur quickly with incurable, metastatic disease. These attributes may reflect the variable and often disappointing responses seen when deploying the standard treatment, gemicitabine alone or in combination with other chemotherapeutic agents in unselected PDAC populations. Studies in other solid tumors have shown that heterogeneity in therapeutic responses can be anticipated by molecular differences between tumors, and targeting drugs specific to tumor subtypes in which they are predicted to be selectively effective can indeed improve treatment. Seeking to extend this new paradigm of personalized medicine to PDAC, we performed an integrative analysis of transcriptional profiles of human primary PDAC tumors (n = 143) and cell lines (n = 35). We have defined 62 gene (PDAssigner) signature that classifies the human PDAC tumors into three subtypes (classical, QM-PDAC and exocrine-like tumors) and present evidence that two (classical and QM-PDAC) of these three are present in human and mouse PDAC cell lines. Interestingly, we found that PDAC subtype classification is an independent predictor of overall survival, and patients with classical PDAC subtype tumors have significantly better survival than those with QM-PDA tumors. In addition, the expression of GATA6 (a transcriptional factor involved in the embryonic pancreas development) and KRAS (mutated in majority of PDACs) are functionally associated with classical PDAC subtype relative to QM-PDAC subtype. Intriguingly, treatment of PDAC cell lines with gemcitabine or erlotinib shows significantly differential and opposing responses between classical and QM-PDAC subtypes. Overall, we describe here a broadly integrative approach to PDAC subtype discovery and analysis that identifies gene expression signature with prognostic significance in primary patient samples and couples them with biological information and subtype specific drug responses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-24. doi:10.1158/1538-7445.AM2011-LB-24
Abstract LB-245: Loss of function of the TGFβRI receptor leads to the spontaneously regressing squamous carcinoma condition, multiple self-healing squamous epithelioma (Ferguson-Smith disease)
Authors: Goudie David R. , D'Alessandro Mariella , Merriman Barry , Lee Hane , Szeverényi Ildiko , Avery Stuart , O'Connor Brian D. , Nelson Stanley F. , Coats Stephanie E. , Stewart Arlene A. , Christie Lesley , Pichert Gabriella , Friedel Jean , Hayes Ian , Burrows Nigel , Whittaker Sean , Gerdes Anne-Marie , Broesby-Olsen Sigurd , Ferguson-Smith Malcolm A. , Verma Chandra , Lunny Declan P. , Reversade Bruno , Lane E. Birgitte 
Published: June 2012

Abstract
A re-examination has been carried out of the region on chromosome 9 containing the locus responsible for Ferguson-Smith disease, or multiple self-healing squamous epithelioma (MSSE/FSD); this is a rare autosomal dominant inherited condition first identified in the west of Scotland, that presents with multiple squamous cell skin carcinomas which grow, invade locally and then spontaneously regress.
Approach: A 4Mb locus on chromosome 9 was earlier identified by genetic mapping in a cluster of families. In this study a wider region encompassing 24Mb around this earlier identified locus was examined using high-throughput sequencing with exon capture, followed by Sanger sequencing.
Result: This effort identified mutations in the TGFBR1 gene in 18 out of 22 families diagnosed as affected by MSSE/FSD. These include 11 different mutations. The tumours occur in sun-exposed areas of the skin, and loss-of-heterozygosity in tumours is frequently seen. The sequence variants disturb the function of the TGFβRI receptor such that although heterozygous carriers are asymptomatic during development, loss of the second (wild-type) allele ablates the receptor function and leads to local cancer susceptibility.
Conclusions: The nature of the mutations sets the mechanism apart from that involved in Marfan syndrome-related disorders, in which developmental defects in vasculature are also caused by mutations in this gene. The involvement of TGFβ receptors in this condition is intriguing as TGFβ pathway effects are known to be biphasic and opposing at different stages of cancer development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2011-LB-245
Abstract LB-246: Recurrent inactivating mutations in SPOP define a molecular subset of prostate cancer
Authors: Barbieri Christopher E. , Demichelis Francesca , Grasso Catherine , Vuong Terry , MacDonald Theresa , Boysen Gunther , Banerjee Samprit , Kitabayashi Naoki , Berger Michael F. , Tewari Ashutosh K. , Garraway Levi A. , Chinnaiyan Arul M. , Rubin Mark A. 
Published: June 2012

Abstract
Considerable evidence exists that prostate cancer is driven by cardinal genetic alterations that activate oncogenes and inactivate tumor suppressors. Recently, recurrent fusions involving members of the ETS transcription factor family have been implicated in the majority of prostate cancer. In addition, several studies have shown that prostate cancers can be classified by genome-wide analysis of somatic copy-number aberration, or transcriptome-wide analysis of gene expression profiles. These discoveries raise the possibility that prostate cancer may soon transition from a poorly understood, clinically heterogeneous disease to a collection of homogenous subtypes identifiable by molecular criteria. However, the limited number of known driver alterations in prostate cancer currently limits this effort.
Here, we report the presence of recurrent mutations in human prostate cancer in SPOP, the substrate-recognition component of an E3-ubiquitin ligase. Recurrent missense mutations in SPOP were discovered by whole genome DNA sequencing (DNA-seq) and whole transcription RNA sequencing (RNA-seq). SPOP mutations were found in approximately 10% of prostate cancers in multiple independent patient cohorts. All mutations were heterozygous, and were found exclusively in the structurally-defined substrate-binding cleft of SPOP. Structural analysis suggests that these mutations inactivate SPOP function by disrupting SPOP-substrate interaction, and loss of SPOP function in prostate cell lines resulted in increased invasion. Prostate cancers harboring SPOP mutations displayed characteristic somatic genomic aberrations. However, all tumors with SPOP mutations lacked both ERG rearrangement and deletion of PTEN, two of the most common genetic alterations in human prostate cancer. We conclude from these results that recurrent mutations in SPOP define a distinct molecular subclass of prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-246. doi:10.1158/1538-7445.AM2011-LB-246
Abstract LB-256: S6K1 mediates glycolysis and apoptosis resistance in Pten deficient cells
Authors: Tandon Preeti , Gallo Catherine A. , Khatri Shikha , Plas David R. 
Published: June 2012

Abstract
Pten loss and subsequent Akt activation promotes cell survival in human cancer cells through activation of glycolytic metabolism and repression of pro-apoptotic factors. Because sustained glycolysis is required for Akt dependent apoptosis resistance, we investigated the downstream signaling components that mediate Akt dependent increases in glycolysis in Pten-deficient cells. Loss of the ribosomal protein S6K1 in Pten-deficient cells prevented Akt-induced glycolysis and triggered Bax translocation and commitment to apoptosis.
Inactivation of S6K1 was associated with decreased expression of the pro-glycolytic HIF1α transcription factor. Restoring HIF1α expression was sufficient to restore both glycolysis and cell survival in S6K1-deficient cells. Conversely, inhibiting HIF1α expression in Pten deficient cells resulted in decreased glycolysis and cell survival, mimicking the loss of S6K1. In vivo, S6K1 deficiency delayed the development of lethal disease in the Pten fl/fl Mx-1 Cre+ model of leukemia. Thus, together the data suggest that S6K1 is a useful target for counteracting the metabolic program that supports apoptosis resistance in Pten-deficient cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-256. doi:10.1158/1538-7445.AM2011-LB-256
Abstract LB-268: Tumor classification and prediction using the WG-DASL HT Assay in archived sectioned FFPE (AS-FFPE) material
Authors: April Craig , Hoshida Yujin , Fan Jian-Bing 
Published: June 2012

Abstract
Formalin-fixed archival tissues represent an invaluable resource for cancer research, since they are widely available and afford correlations of historical clinical data with gene expression signatures thereby facilitating better disease classification and prediction. While FFPE tissue is commonly available in block form, it is also standard practice to archive sectioned slices (AS-FFPE), often at room temperature, which further degrades genetic material due to oxidation. Because of these limitations, gene expression studies using FFPE material are usually performed on material derived from freshly cut blocks and not AS-FFPE samples. Previous mRNA data generated on freshly cut FFPE blocks for two independent liver cancer sample sets yielded gene expression signatures which classified hepatocellular carcinoma (HCC) samples into three subclasses (Cancer Res 2009, 69: 7385) and cirrhotic liver (CL) samples into two (good and poor survival) groups (N Engl J Med 2008, 359:1995). Here, using the WG-DASL HT assay (29K probes), we report on our efforts to use RNA derived from 5-year old AS-FFPE samples that were obtained from a subset of the previously assayed liver cancer sample sets, to generate clinically informative gene expression profiles. With a passing quality control filter of &gt;80% probes detected (p &lt; 0.01) we were able to obtain good quality data for 64/83 (77%) and 37/48 (77%) of the HCC and CL samples, respectively. On average, for the two sample sets, the sample reproducibility across all 29K probe intensities was R2 ∼ 0.85. We next performed prediction analysis using a nearest template prediction method and compared the results with that originally predicted for each of the two sample set. With a confidence threshold of p &lt; 0.05, 38/64 (59%) of the passing HCC samples yielded a prediction with an accuracy of 95% and an error rate of 5%. At the same confidence threshold (p &lt; 0.05), 13/37 (35%) of the passing LC samples yielded a prediction with an accuracy of 69% and an error rate of 31%. Together our results suggest that, despite degradative events such as oxidation and hydrolysis that further fragment archived FFPE sections, gene expression signatures derived from AS-FFPE samples can accurately classify disease states and provide clinically relevant prognoses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-268. doi:10.1158/1538-7445.AM2011-LB-268
Abstract LB-279: Cancer cDNA resequencing with an exon-capture system
Authors: Ueno Toshihide , Yamashita Yoshihiro , Soda Manabu , Mano Hiroyuki 
Published: June 2012

Abstract
While cancer is a genetic- and/or epigenetic-disorder, “driver” mutations in the cancer genome/epigenome are yet to be revealed for many cancer subtypes. A whole-genome resequencing should provide us with important information on this issue, but resequencing of multiple samples is still a demanding task. A recent introduction of the exon-capture systems has significantly facilitated the comprehensive resequencing of exonic regions that only occupy ∼1.5% of the human genome. However, such exon resequencing of cancer genome likely fails to identify fusion genes, since gene fusion usually takes place at introns. To efficiently discover gene fusions in addition to point mutations and indels, we here tried to resequence cDNAs of a given gene set by using a custom SureSelect system (Agilent Technologies). First we confirmed, by using the SureSelect X chromosome-purification kit, that capturing efficiency of cDNA is no worse than that of genomic DNA. Then we constructed a custom SureSelect system to capture cDNAs of cancer-related genes (n = 913 corresponding to ∼3.77 Mbp). Such cDNA capture system was then applied to a total of five cell lines of chronic myeloid leukemia. Deep sequencing of the purified cDNA fragments with Illumina Genome Analyzer IIx yielded the nucleotide information for an average of 54 million reads (= ∼4.1 Gbp) per sample. While BCR is not included in our custom SureSelect system, we could successfully isolate 38∼50 reads in each cell line encompassing the fusion points of the BCR-ABL1 cDNA, confirming the ability to detect gene fusions by our cDNA-capture system. A comparison of the read numbers in our data to the expression level defined by DNA microarray analyses has revealed a high concordance between the two data sets (Pearson's correlation coefficient = 0.73, P &lt;2.2 × 10–16). Computational analyses of the read data that passed our quality filtering revealed a total of 199 non-synonymous point mutations on 155 independent genes. Further, we discovered a total of 15 (3 in-frame) independent insertions and 19 (6 in-frame) deletions. Among such mutation profiles, we could readily confirm the G-to-C substitution corresponding to the G266R amino acid change of TP53, one C insertion at nt position 604 of TP53, and one three-base deletion (nt = 894∼896) of TP53. These data confirm that a coupling of a sequence-based cDNA capture system to a next generation sequencer is a feasible approach to discover point mutations and fusions of target genes in the cancer genome.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2011-LB-279
Abstract LB-73: Patient/Public Involvement in Cancer Research in the United Kingdom
Authors: Haswell Thomas 
Published: June 2012

Abstract
Academic cancer research in the UK is structured around key organizations. The National Cancer Research Institute (NCRI) is a ‘virtual institute’ that brings together government and charitable funders to set priorities and co-ordinate funding of cancer research. NCRI Clinical Studies Groups (CSGs), which provide the site-specific leadership to develop studies, will be adopted into the national portfolio of cancer studies as part of the National Institute for Health Research (NIHR) if the funding is available. The NIHR National Cancer Research Network leads the delivery of research through research networks throughout the UK. Related groups and initiatives facilitate or carry out specific tasks in research development, management and monitoring.
Patients have input at all levels and their voice has, throughout the history of NCRI & NCRN, been considered critically important in developing research. The key principles from researchers and clinicians include working together with consumers as partners in the research effort, involving consumers in developing strategy as well as specific initiatives and studies, listening to the consumer voice on research needs and the experience of participating in research, and learning from experience to develop and increase the impact of the consumer role in cancer research.
The NCRI Consumer Liaison Group brings together patient and caregiver members to support research development at all levels from the NCRI Board through CSGs to membership of individual Trial and Study Management groups. Impact has been captured in many narratives from researchers, clinicians and patients. Working together in a robust partnership is a particular strength of UK Cancer Research and forms the ideal platform to truly achieve research intended for patient betterment. This is recognized in the recent White Paper: ‘Equity and excellence: Liberating the NHS’. The organization's first decade of patient and public involvement is captured in the NCRI report: Patient, Carer & Public Involvement in Cancer Research.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-73. doi:10.1158/1538-7445.AM2011-LB-73
Abstract LB-74: NECCS- The Voice of Cancer Survivorship
Authors: Jeames Sanford 
Published: June 2012

Abstract
The disease of cancer extends its impact far beyond the clutches it holds over those diagnosed with cancer. The latest statistics from the American Cancer Society (ACS) estimate that over 500,000 Americans will be diagnosed with cancer in 2011, and these figures do not take into account the thousands of individuals under the age of 18 who are also diagnosed with cancer. A diagnosis of cancer not only affects patients, but also family members, caregivers, employers_all components of life.
The New England Coalition of Cancer Survivorship (NECCS) is an organization dedicated to advocating for the wider audience of those affected by cancer. The mission of NECCS is to educate and provide resources about issues related to cancer and cancer survivorship. Other significant aspects of NECCS's mission are to advocate on behalf of those impacted by cancer, and to empower cancer survivors, family members, friends and caregivers by creating strong communities, providing an information network, and providing access to resources, programs and events.
To achieve and reach its main goal of acting as the voice to the concerns of cancer survivorship, NECCS has initiated a variety of programs and activities to inform the public of its resources. NECCS is a collaborative partner with many organizations to better facilitate its effectiveness and outreach. NECCS board members serve on the survivorship workgroup of the Massachusetts Comp Cancer Coalition, the Leukemia/Lymphoma Society of New England and the New England Division of the American Cancer Society. NECCS programs include the Speakers' Bureau and Caregiver Program, which provides NECCS members to various community groups to share their experiences with cancer. NECCS provides printed materials through in the form of tip sheets, which highlight cancer survivors, caregivers and advocates, as well as providing information about the latest research. The NECCS website has links to state, regional and national organizations that address the concerns of cancer survivorship. A recent online campaign resulted in over 100 new members joining NECCS via its Facebook and Twitter accounts. NECCS also participated in the Boston Health Fair and was featured at a recent Boston Red Sox baseball game for its contributions to the Greater Boston area and surrounding communities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-74. doi:10.1158/1538-7445.AM2011-LB-74
Abstract SY16-02: microRNA regulation of the tumor angiogenic switch
Authors: Cheresh David A. , Anand Sud 
Published: June 2012

Abstract
Endothelial cells (EC) in the adult mammal are among the least proliferative cell types, with about 1 in 10,000 cells entering the cell cycle at any given time. Such a degree of quiescence is rapidly reversed in response to growth factors during pathological neovascularization, particularly during tumorigenesis. This robust proliferative switch of the quiescent endothelium is a complex process governed by intricate checks and balances. Recently, small 22-nt RNAs termed microRNAs (miR) have been identified as important regulators of several physiological processes including angiogenesis. To identify microRNAs that activate might regulate the tumor angiogenic switch, we profiled miRs in both human umbilical vein endothelial cells (HUVECs) treated with angiogenic growth factors VEGF or FGF and in a human embryonic stem (hES) cell vasculogenesis model in which hES cell derived embryoid bodies form well-defined, endothelial networks. We show here that microRNA miR-132 represents an angiogenic switch by targeting p120RasGAP in quiescent endothelium inducing neovascularization. miR-132 was highly expressed in the endothelium of human tumors and hemangiomas yet was undetectable in normal endothelium. Ectopic expression of miR-132 in endothelial cells increased their proliferation and tube-forming capacity while intraocular injection of anti-miR-132 blocked postnatal retinal vascular development in mice. Among its likely targets, miR-132 only impacted p120RasGAP expression, identified in normal but not tumor endothelium. Accordingly, endothelial expression of miR-132 suppressed p120RasGAP levels and increased Ras activity while a miR-resistant version of p120RasGAP reversed the miR-132-induced vascular response. Importantly, anti-miR-132 failed to inhibit angiogenesis in mice with an inducible deletion of p120RasGAP. Finally, vascular-targeted nanoparticle delivery miof anti-miR-132 restored p120RasGAP in the tumor endothelium, where it suppressed angiogenesis and inhibited breast cancer in mice. Therefore, miR-132 acts as an angiogenic switch by suppressing endothelial p120RasGAP expression leading to Ras activation and the induction of neovascularization, whereas the application of anti-miR-132 prevents this effect by maintaining vessels in the resting state.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY16-02. doi:10.1158/1538-7445.AM2011-SY16-02