bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-273: Preclinical assesment of a novel CDC7 inhibitor: Genomewide RNAi screening identifies unique synergetic and resistance genes
Authors: Liu-Sullivan Nancy , Bhinder Bhavneet , Shum David , Ramirez Christina , Radu Constantin , Djaballah Hakim , Frattini Mark G. 
Published: June 2012

Abstract
Despite extensive drug discovery efforts, drug-candidate failure and patients relapsing in the clinic remain as persistent problems. While insufficient drug-gene engagement leads to drug failure, de novo escape mutations give rise to patients relapsing, calling the need for systemic studies on how genes influence drug responsiveness. Towards this end, we have explored a functional short hairpin RNA (shRNA) based genomic screening platform aimed at interrogating drug-gene engagement and assessing its consequences on signaling pathways. We propose this concept as a novel way to evaluate drug candidates prior to clinical trials enabling liability assessment and predicting clinical outcome. We took advantage of the arrayed shRNA library produced in lentiviral particles and characterized by several obvious advantageous features including shRNA targeting one hairpin at a time and on the fly high content whole well microscopy imaging analysis. We carried out three parallel genomewide shRNA screens in the absence or presence of the novel CDC7 kinase inhibitor (MSK-777) at its IC20 and IC50 and have identified several gene candidates that influence MSK-777 sensitivity and resistance. These include synergizers that enhance MSK-777 sensitivity and rescuers that confer MSK-777 resistance. IPA analysis mapped clusters of these hits to multiple major pathways among them were the NF-kB pathway, the ubiquitin-proteasome pathway, DNA replication, and several epigenetic regulatory genes. We will present and discuss this concept together with the emerging pathways as a means to identify both key therapeutic targets and biomarkers of sensitivity and resistance. Thus, allowing for not only a broader applicability of assessing candidate genes that modulate specific drug agents, but also for the identification of a tailored and more efficacious therapeutic regimen to treat 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-273. doi:10.1158/1538-7445.AM2011-LB-273
Abstract LB-277: Dynamic functional analysis of the response of cancer cell lines to the drug UNBS1450
Authors: Bittner Michael L. , Smith Edward , Hua Jianping , Chao Sima , Cypert Milana , Gooden Gerald , Shack Sonsoles , Alla Lalitamba , Cerella Claudia , Diederich Marc , Weitman Steven 
Published: June 2012

Abstract
The analysis of the dynamics of cellular responses to drugs is currently bounded by inherent limitations of the methods most often used to assess levels of promoter activity and protein abundance or activation. The sensitivity of these assays is limited by the averaging of analyte over many cells, which can produce an average that is not accurately descriptive of the wide range of activities of members of the population examined. The ability of these assays to indicate the trajectory of the various responses is limited by a very infrequent sampling rate, frequently 2–4 time points spread over many hours. These limits are further exacerbated by populations of treated cells' inhomogeneity in the timing of their own response to the drugs. To improve the determination of the functional dynamics of cells' responses to drugs, PBS-Bio has developed technology that allows gathering data from living cells using fluorescent reporter technology. This technology allows measurements to be made serially on single populations of cells at the individual cell level, providing both high sensitivity in terms of when even a small fraction of the cells exhibit significant shifts of a particular activity, the rate of shift of cells in the population to this different activity and the ability to temporally order the timing of events relative to each other. Experimentation on two cell lines, A549 and PC3, using a variety of drugs that affect different cellular processes and a set of fluorescent reporters that provide information on a variety of cellular processes it was possible to show that the modified cardenolide drug, UNBS1450 (Unibioscreen), provoked a very early reduction in the expression of the MCL1 and MYC genes, followed by induction of a strong apoptotic response in both cell lines. As loss of MCL1 provoked by other means has been shown to be sufficient to induce apoptosis in both these lines, a very strong case can be made for UNBS1450's ability to provoke Mcl1 protein reduction as the drug's mode of apoptotic induction. This finding would also implicate Mcl1 as a useful biomarker of the possible efficacy of UNBS1450.
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-277. doi:10.1158/1538-7445.AM2011-LB-277
Abstract LB-69: Minnesota Ovarian Cancer Alliance
Authors: Gavin Kathleen A. 
Published: June 2012

Abstract
The Minnesota Ovarian Cancer Alliance (MOCA) is a nonprofit organization whose mission is to create awareness regarding early warning signs that may be indicative of ovarian cancer; to develop and promote resources for support, networking and education for women diagnosed with ovarian cancer and their families; to unite and educate individuals, the medical community and organizations to achieve earlier diagnosis, better treatment and a cure for ovarian cancer; and to advance ovarian cancer research toward earlier diagnosis, better treatment, and ultimately, a cure.
MOCA staff and members primarily serve as patient advocates and consumer reviewers to state and national gynecologic oncology research initiatives including the GOG, the Mayo Ovarian SPORE, the DOD, and others. MOCA funds ovarian cancer research, with the average grant award at around $70,000. To date, the organization has awarded $2.6 million to over 40 research projects in the last 10 years. MOCA also provides scholarships to support oncology nurses' attendance at national educational conferences.
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-69. doi:10.1158/1538-7445.AM2011-LB-69
Abstract LB-71: Poke, Tweet, Share, Tag: A New Generation of Cancer Advocacy
Authors: Hammersmith Leslie 
Published: June 2012

Abstract
After a diagnosis of cancer, a whole new, lasting identity imprints itself on you, especially if you're still young. Cancer in young adults brings a set of unique issues, including dealing with a delayed diagnosis, having access to clinical trials, finding age-appropriate peer support, feelings of isolation, and finding some kind of balance between survivorship and feeling cured. Encouraging, supporting and educating a generation of young advocates and survivors requires the attention of the medical community and mentoring from experienced advocates. Building credibility within the scientific community is crucial to establishing the influence of a community of survivors typically underrepresented.
Significant challenges exist for the medical community to be effective disseminators of cancer research information to generations 40 years and under. It also takes time for the young advocate to understand the many facets of engagement as a patient advocate. This poster will describe the experiences of a young breast cancer survivor, diagnosed at age 36, as she discovers how becoming an advocate for young women dealing with breast cancer in her community connected her to the science, politics, and ethics of the medical community. Generational expectations combined with professional and cultural differences between the young patient and medical community lead her to find ways to help educate her medical providers, cancer clinics, and fellow patients. The disappointment of finding that many research studies have not considered the issues unique to breast cancer in younger women and the revelation that awareness of breast cancer in women under 40 is minimal inspired her to seek out ways to increase her understanding of the science and improve her understanding of how the medical teams work. This poster will also discuss other opportunities for young advocates to add value to the science of cancer research and its impact on the patient. These opportunities include volunteering as a Patient Advocate with NCCTG through her local Cancer Center, serving as the patient advocate who reviews all research protocols being considered for deployment in her area, seeking out valuable professional development opportunities such as programs through Research Advocacy Network's Research Advocate Institute, and establishing a local affiliate of Young Survival Coalition to link communities of survivors with national resources and education. Through pokes, tweets, tagging, and sharing, she uses media to connect the experience of the young survivor to the science of accelerating progress against 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-71. doi:10.1158/1538-7445.AM2011-LB-71
Abstract LB-72: Advocacy in Action: A Research Advocacy Program with a Multilateral Approach at the Vanderbilt-Ingram Cancer Center
Authors: Hanson Caroline 
Published: June 2012

Abstract
The research advocacy program at Vanderbilt Ingram Cancer Center (VICC) is paving the way as a model for nationally-recognized research advocacy programs. As survivors and caregivers that come from a variety of backgrounds and perspectives, research advocates at VICC are well-equipped to collaborate substantially in the development, oversight and dissemination of cancer research. Our approach is to provide VICC researchers with the “patient perspective”_to help guide and refine research at our institution so it is meaningful and relevant to patients/participants and to improve the credibility of cancer research and clinical trials in the community. This multilateral approach does not discriminate cancer as limited to one organ site or one demographic. Research advocates at VICC participate in a wide variety of advocacy activities. Opportunities to provide the “patient perspective” include attendance at research seminars, research project meetings, conferences and advocate meetings. Advocates also develop and deliver research advocacy presentations and participate/collaborate with other VICC and community programs, as well as the National Cancer Institute to facilitate academic/advocacy partnerships. To help guide research at VICC to ensure it is meaningful and relevant to patient/participants, advocates review and provide input on research development, design, clinical trials and informed consent. Advocates also develop patient oriented resources and tools for clinical trials, as well as serve as grant reviewers. To improve the credibility of cancer research and clinical trials in our community, advocates collaborate with local, regional and national organizations to facilitate advocacy participation and develop educational programs for the community to promote awareness of cancer research in clinical trials. One example is a novel educational outreach program entitled, “Mythbusters: Cancer Research in Jeopardy,” that aims to dispel common myths associated with cancer research and clinical trials. The research advocacy program at VICC uses a strategy to educate the community using an interactive program significantly increases knowledge. This interactive approach, as well as more traditional methods, allows our research advocates to take an active role in the direction of cancer research and treatment, and to tackle the important task of bridging the gaps between cancer researchers, survivors, caregivers and the community.
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-72. doi:10.1158/1538-7445.AM2011-LB-72
Abstract SY16-03: Dose matters and angiogenesis
Authors: Hodivala-Dilke Kairbaan M. 
Published: June 2012

Abstract
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a fundamental role in integrin and growth factor mediated signaling and is an important player in cell migration and proliferation, processes vital for angiogenesis. However, the role of FAK in adult pathological angiogenesis is unknown. We have generated endothelial-specific tamoxifen-inducible FAK knockout mice by crossing FAK-floxed (FAKfl/fl) mice with the Pdgfb-iCreER mice. Tamoxifen-treatment of Pdgfb-iCreER;FAKfl/fl mice results in FAK deletion in adult endothelial cells (EC) without any adverse effects. Importantly however, endothelial FAK-deletion in adult mice inhibited tumor growth and reduced tumor angiogenesis. Furthermore, in in vivo angiogenic assays FAK-deletion impairs vascular endothelial growth factor (VEGF)-induced neovascularization. In addition, in vitro deletion of FAK in ECs resulted in reduced VEGF-stimulated AKT phosphorylation, and correlating reduced cellular proliferation and increased cell death. Our data suggest that FAK is required for adult pathological angiogenesis and validates FAK as a possible target for antiangiogenic therapies. In a follow up study we are testing the effects of reduced, as apposed to null, levels of FAK on tumor angiogenesis and will be reporting on that at the meeting.
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 SY16-03. doi:10.1158/1538-7445.AM2011-SY16-03
Abstract SY29-02: Pathway analysis of cancer GWAS data using ALIGATOR
Authors: Holmans Peter 
Published: June 2012

Abstract
Although genome-wide studies of complex traits have had some success, there have as yet been relatively few robustly replicated associations, and the effect sizes associated with individual genes tend to be small. One explanation for the small effect sizes observed in complex traits is allelic heterogeneity – that is, affected individuals may possess disease susceptibility alleles in different genes. If the susceptibility genes act together in a biological pathway, then a joint analysis of the set of genes in that pathway may increase power to detect association, and improve reproducibility across studies.
The statistical issues involved in pathway analyses of genome-wide association data will be discussed, including the selection of pathways to be analysed, multiple testing correction for multiple nonindependent pathways, allowing for variable gene size and correlated observations within and between genes. Often, individual genotype data is not available, so the performance of methods that use summary data, such as ALIGATOR (Holmans et al. 2009) is of interest. As a practical illustration of the utility of pathway analysis methods, ALIGATOR results from genome-wide association studies of a number of publicly available cancer datasets, including breast, prostate, and lung cancer, will be presented. These will be used to identify pathways common across different cancers, and those that differentiate between them.
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 SY29-02. doi:10.1158/1538-7445.AM2011-SY29-02
Abstract SY30-01: Metastasis mediated by lysyl oxidases
Authors: Erler Janine T. 
Published: June 2012

Abstract
Metastasis is responsible for over 90% of cancer patient deaths. Understanding the molecular processes that enable tumor cells to metastasize is key to understanding how best to prevent and treat metastases in cancer patients. Metastasis is a complex, multistep process driven by the tumor microenvironment. Two potent driving forces are hypoxia (low oxygen) and increased matrix stiffness. These are common features of aggressive solid tumors, and are clinically associated with metastasis and decreased survival of cancer patients. Both hypoxia and stiffness have been shown to greatly enhance the invasive and metastatic potential of cancer cells. We have identified two key mediator molecules, lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2). These are hypoxia-induced secreted enzymes that increase matrix stiffness through mediating the crosslinking of collagens and elastin in the extracellular matrix. We have investigated their role in metastasis using a variety of in vitro and in vivo models.
We showed that LOX expression is clinically correlated with hypoxia, metastasis and poor patient survival. Furthermore, inhibition of LOX through genetic, chemical or antibody means significantly reduces invasion and metastasis in several in vivo models of solid tumor metastasis. LOX enhances invasion through increasing matrix stiffness, thereby activating integrins, Src and FAK. LOX additionally enhances formation of distant metastases by playing a role in formation of premetastatic niches through recruitment of CD11b+ cells, which greatly enable metastatic colonization.
We have also investigated the role of LOXL2 in breast cancer metastasis and normal mammary tissue function. Like LOX, LOXL2 is clinically correlated with metastasis and poor patient survival. LOXL2 enhances invasion through regulation of matrix remodeling. Inhibition of LOXL2 through genetic, chemical or antibody means prevents invasion and metastatic dissemination in vivo. We further show that LOXL2 activity is highest during normal mammary gland involution, consistent with its role in matrix remodeling.
These findings provide insight into metastasis mediated by the tumor microenvironment and demonstrate preclinical effectiveness of anti-LOX/LOXL2 therapy, which may have important clinical implications.
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 SY30-01. doi:10.1158/1538-7445.AM2011-SY30-01
Abstract A25: CK 5/6 and EMT-markers as poor prognostic factors in breast cancer patients
Authors: Ahrends Tomasz , Markiewicz Aleksandra , Nowialis Paweł , ska Barbara Seroczy , Skokowski Jarosław , Szade Jolanta , kiewicz Marzena Wełnikca-Ja , aczek Anna 
Published: June 2012

Abstract
Introduction: Cytokeratins 5/6 are expressed in basal layer of breast epithelium and are considered as markers of poor prognosis in breast cancer patients. It was also shown that tumors expressing basal markers often present phenotypical changes connected with epithelial-to-mesenchymal transition (EMT), like vimentin expression and E-cadherin loss. The aim of this study was to evaluate the expression of master regulators of EMT - TWIST, SNAIL and SLUG in breast cancer samples and correlate it with expression of CK 5/6 and markers of EMT - E-cadherin and vimentin.
Materials and Methods: Fresh-frozen and FFPE tumor samples from 136 consecutive, stage l-III breast cancer patients were examined. Expression of TWIST, SNAIL and SLUG in frozen tissues was measured by RT-qPCR method using ΔΔCt approach. Expression of CK 5/6, E-cadherin and vimentin was analyzed in FFPE material with a use of immunohistochemical staining of tissue microarrays (TMA-IHC). Based on the median gene expression level or intensity of the IHC staining samples were classified as positive or negative for a particular marker. Results were correlated with clinicopathological data of the patients and their outcome.
Results: CK 5/6 staining was positive in 19 (11.3%) of the samples and correlated positively with presence of EMT phenotype (0.00027, χ2 test), with 58% and 19.5% of EMT-positive samples in CK5/6 positive and negative subgroup, respectively. Moreover, elevated expression of SNAIL mRNA was detected more often in CK 5/6 positive than in negative samples (89% vs. 51 %, p=0.032, Fisher's exact test). Elevated expression of TWIST (p=0.05, Fisher's exact test) and SNAIL (p=0.003, Fisher's exact test) genes was found in tumors with EMT phenotype. No correlation was found between TWIST, SNAIL, SLUG protein levels as well as SLUG gene expression and EMT phenotype. Expression of CK 5/6 was associated with decreased DFS (p = 0.00044, log-rank test) and OS (p = 0.00001, log-rank test), while occurrence of EMT phenotype with worse OS (p=0.01, log-rank test)
Conclusions: CK 5/6 was found to be a marker of poor prognosis in terms of DFS and OS in the whole studied group of patients. EMT phenotype and SNAIL gene overexpression were more frequent in CK 5/6-positive tumors, which suggests a link between basal phenotype of the tumors and their predisposition to undergo EMT process. As EMT is thought to confer aggressive behavior of the tumor, this correlation might explain the observed negative impact of CK5/6 positive tumors on patients' survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A25.
Abstract A50: Loss of pVHL inactivates p53 by permission of interaction between p14/ARF and progerin
Authors: Lee Su-Jin , Jung Youn-Sang , Lee Sun-Hye , Chung Ji-Yun , Park Bum-Joon 
Published: June 2012

Abstract
Renal cell carcinoma (RCC) is a common primary renal malignancy in adults. The typical feature is the nuclear irregularity which is a basis for grading. Moreover, resistance to chemotherapy and irradiation (IR) is also one of the characters of RCC. p53 inactivation without genetic mutation and pVHL mutation in early stage are shown in RCC. However, it is still remained the question about the mechanism of the nuclear deformation and chemotherapy resistance. Here we proposed that the effect of progerin on RCC. Progerin elevated in RCC and the elimination of progerin could ameliorate the nuclear morphology. Moreover, knockdown of progerin could recover DNA damage sensitivity and p53 activation in RCC. Loss of pVHL induces elevated progerin expression, which inhibit p14/ARF by direct interaction to suppress p53 activity. Moreover, forced enhancement of progerin is found in human leukemia sample. In this study, we provide that the novel mechanism for p53 suppression in RCC and the importance of progerin in cancer progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A50.