bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-362: The MEK inhibitor selumetinib (AZD6244 - ARRY-142886) prevents lung metastasis in a triple-negative breast cancer (TNBC) xenograft model
Authors: Bartholomeusz Chandra , Ali Dadbin , Saso Hitomi , Kondo Kimie , Smith Paul , Hortobagyi Gabriel N. , Ueno Naoto T. 
Published: August 2012

Abstract
Patients with TNBC are negative for estrogen receptor, progesterone receptor, and HER2 expression, and have a very poor prognoses because tumors often metastasize, leading to death. Preventing metastasis as well as inhibiting the tumor growth, is crucial to improving the prognosis of TNBC. We previously showed that patients with ERK2-overexpressing TNBC were at higher risk of death than those with low-ERK2-expressing tumors. Interestingly, when we treated the TNBC cells lines MDA-MB-231 and SUM-149 with the MEK1/2 ATP uncompetitive kinase inhibitor (selumetinib) at concentrations of 0.1 and 1.0 μM, it did not reduce cell viability in a two-dimensional (2D) cell culture. However, in a three-dimensional (3D) cell culture model, selumetinib changed the mesenchymal phenotype of TNBC to an epithelial phenotype. Cells undergoing epithelial-mesenchymal transition are well known to potentially contribute to the metastatic process and have increased ability to form mammospheres. Thus, we hypothesized that targeted inhibition of the MEK-ERK pathway by selumetinib may prevent lung metastasis in TNBC. In the present study, we observed that SUM-149 cells treated with selumetinib (0.1, 1.0 μM) exhibited cell-cycle arrest at G1 but did not exhibit apoptosis indicated by an increased proportion of cells at sub-G1 phase. Both SUM-149 and MDA-MB-231 cells treated with selumetinib exhibited significant inhibition of anchorage-independent growth, an indicator of in vivo tumorigenicity (P&lt;0.005). In addition, in SUM-149 cells and MDA-MB-231, treatment with selumetinib (0.01, 0.1,1.0 and 10μM) suppressed formation of mammospheres in a dose-dependent manner. Next, to determine the role of the MEK-ERK pathway in the prevention of TNBC metastasis, we used a metastatic TNBC animal model established with MDA-MB-231-LM2-4175 (lung metastatic subpopulation) cells transfected with a luciferase gene that were injected intravenously into the tail vein of mice. We observed that mice treated with selumetinib had significantly fewer lung metastases than did control mice injected with a vehicle (P&lt;0.05, 2-sided t test.) These findings support a crucial role for the MAPK pathway in metastasis and suggest that ERK pathway might provide clinical benefit by preventing metastasis. Targeted inhibition of the MEK-ERK pathway with selumetinib may be a novel approach to treatment of TNBC metastasis.
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 LB-362. doi:1538-7445.AM2012-LB-362
Abstract LB-37: Cancer patient navigators of Georgia (CPNG) advocate for cancer survivors
Authors: Patterson Angie 
Published: August 2012

Abstract
The Georgia Cancer Coalition (GCC) is a not-for-profit organization that seeks to unite government agencies, academic institutions, civic groups, healthcare organizations and survivors to reduce the number of cancer deaths in Georgia and to move Georgia to the top ranks of cancer care in the nation. The Georgia Society for Clinical Oncology (GASCO) partnered with the GCC and was awarded a grant from the American Society for Clinical Oncology (ASCO) to determine the interest in formulating a statewide multi-disciplinary organization for people who help cancer patients navigate the healthcare system. A survey was conducted and results from eighty navigators representing 25 cities demonstrated an organizational need. The Cancer Patient Navigators of Georgia (CPNG) was founded as a unique statewide organization of individuals who serve people with all types of cancer, at all stages, in all types of settings, with a diversity of education and training (from lay navigators to nurse navigators and social work navigators). CPNG's mission is to connect, educate and share best practices among patient navigators in Georgia, so that together we can successfully reduce barriers and increase access to services specifically related to cancer. The steering team developed a logo, by-laws, officers, working committees, electronic newsletters and a website, with a members-only section for social networking. Membership currently tops 230. A recent social networking survey had 100 respondents. We have conducted three annual meetings with attendance of each meeting exceeding 100. The GCC received a private gift of $250,000 to expand the patient navigation efforts in Georgia. One component of the gift is sponsoring the first Integrative Oncology conference to be held in Georgia on January 20, 2012 for the members of Cancer Patient Navigators of Georgia. In conclusion, the initial survey indicating an organizational need to create a statewide multi-disciplinary organization for people who help cancer patients navigate the healthcare system was the beginning of the Cancer Patient Navigators of Georgia (CPNG).
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 LB-37. doi:1538-7445.AM2012-LB-37
Abstract LB-377: Promoter methylation of the DAPK1 CLL predisposition gene is associated with chronic lymphocytic leukaemia risk
Authors: Candiloro Ida , Mikeska Thomas , Giles Graham , Severi Gianluca , Dobrovic Alexander 
Published: August 2012

Abstract
The pro-apoptotic gene DAPK1 has been identified as a hereditary cancer gene in some cases of chronic lymphocytic leukaemia (CLL). The causative mutation acts to increase the probability of methylation of the DAPK1 gene. Moreover, DAPK1 promoter methylation has been demonstrated to occur in nearly all cases of CLL, leading to down-regulation of the gene. We hypothesized that DAPK1 methylation thus underlies most cases of CLL and that predisposition to CLL might be associated with predisposition to methylate the DAPK1 gene. We thus accessed a large epidemiological cohort in which blood had been collected from participants who were then followed up indefinitely. This enabled us to compare methylation at the DAPK1 promoter in peripheral blood leukocyte DNA taken from individuals who developed CLL and control individuals who did not develop cancer. A quantitative MSP-based approach was used to analyse three regions within the 1.3kb promoter CpG island; (i) 5′ of exon 1 and at the 5′ end of the island. (ii) 3′ of exon 1 and in the centre of the island and (iii) 5′ of exon 2 and at the 3′ end of the island. No significant difference was found at the 5′ or the 3′ends of the island. However, when the central region (immediately after exon 1) was examined, the difference between the cases and controls was highly significant (p = 0.004). These results strongly support an important role for DAPK1 methylation in the early pathogenesis of CLL. Whilst methylation at the central part of the CpG island is not known to regulate any transcript, it may be an important first step in the CLL process as a seeding event. This hypothesis is supported by the fact that methylation at either end of the promoter was more likely if methylation was also present in the centre (p= 0.02 for controls and 0.006 for cases).
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 LB-377. doi:1538-7445.AM2012-LB-377
Abstract LB-39: Kidney cancer association fighting back togethe
Authors: Fahy Maria T. 
Published: August 2012

Abstract
The Kidney Cancer Association's (KCA) vision since its creation by founder Eugene P. Schonfeld, PhD has been The Elimination of Death and Suffering from Renal Cancers and to pursue A World Without Kidney Cancer. The Kidney Cancer Association has grown in the last 21 years to be an amazing organization that included over 55,000 people in more than 100 countries, The KCA is organization that pursues its worldwide vision through education, research and advocacy with a three person staff which is assisted by a dedicated group of professionals and other individuals who serve on a governing board, or a medical advisory board, or performs a host of other duties that allows the KCA to play an important role in the advances that have made in the diagnosis, treatment and follow up of renal cancers during the past two decades. As an independent advocate and daughter who lost her father to kidney cancer, Team Chema was born. With the help and support of KCA, Team Chema will be involved in bringing information about the latest research and best practices to the places that have cultural and language barriers that hinder cancer prevention and treatment. Team Chema is dedicated to supporting patients, organizing fundraising events and creating awareness.
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 LB-39. doi:1538-7445.AM2012-LB-39
Abstract LB-40: How patient advocacy can positively impact clinical research
Authors: Schroer Grace E. 
Published: August 2012

Abstract
The Bladder Cancer Advocacy Network (BCAN) was the first national patient advocacy group to focus on blader cancer. Since its establishment in 2005, BCAN has put forth a number of programs designed to advance the three goals of our mission; raising awareness of bladder cancer, providing education and support to the bladder cancer community and advancing bladder cancer research. As part of BCAN's mission to advance to advance research, they has sought to encourage collaboration among physicians and research who are dedicated to the study of bladder cancer and its prevention, diagnosis and treatment by hosting an annual scientific Think Tank meeting.
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 LB-40. doi:1538-7445.AM2012-LB-40
Abstract LB-406: Identification of functional enhancer SNPs in breast cancer models though ChIP-sequencing screening
Authors: Westerling Thomas , Tavera-Mendoza Luz , Brown Myles 
Published: August 2012

Abstract
The American Cancer Society estimates there were 288,130 new breast cancer diagnoses, and 39,520 breast cancer deaths nationwide in 2011. A number of life-style factors can influence breast cancer risk, however, it is apparent that both previously identified and still unknown genetic risk factors are contributing to the disease. Recent estimates place the unknown genetic component at around 70% of the total familial risk. Knowing the underlying genetic risk factors in these cases could greatly influence prevention and treatment strategies and outcome. The role of polymorphism and breast cancer and disease risk in various populations, and multiple genome-wide association (GWAS) studies have identified variants that confer risk for developing cancer or for disease progression. Importantly, the majority of these variants confer small increases in risk. Recent developments in genomics is rapidly increasing the amount of known genetic variants further confounding the discovery of risk alleles due to the need for extremely large cohorts in GWAS studies. Thus there is a clear and growing need to refine the static data with functional screening. Much of the genetic variation maps to non-coding gene deserts, leading to the popular idea that they affect cis-regulatory regions (distal enhancers) that serve as binding sites for long-range transcription factor (TF) activity, as recently demonstrated for a common variant that lies 350 kb upstream of the MYC oncogene. In order to identify functional variants that reside in and affect distal enhancer function we are employing high depth ChIP-sequencing of nuclear hormone receptors and their pioneer factors combined with SNP-array and whole genome sequencing data. Through this strategy we are building a bank of known functionally relevant SNPs that have direct association to a known DNA binding factor and its biological outcome in breast cancer models.
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 LB-406. doi:1538-7445.AM2012-LB-406
Abstract LB-412: TargetRich™ cancer gene panels: targeted next generation sequencing in cancer samples
Authors: Spayd Katherine J. , Vasenkova Irina , Shvetsova Tatiana , Bachmeyer Randall C. , Myers Richard M. , Moore D. Troy , Varley Katherine E. 
Published: August 2012

Abstract
Crucial to the adoption of next-generation sequencing within clinical cancer research is the ability to deeply sequence hundreds to thousands of targeted genomic regions across a large number of patient samples. Several targeting (PCR) and capture (hybridization) methods have been developed for next-generation sequencing, however these methods have limited utility with cancer patient specimens due to drawbacks such as large input DNA quantity requirements, wasted off-target sequencing, high cost of reagents, low sample throughput, specialized equipment, and inflexible content design. We developed TargetRich cancer gene panels employing Nested PatchPCR, which enables the targeted sequencing of hundreds of genomic regions in large numbers of patient samples to fully and efficiently utilize next-generation sequencers. Nested PatchPCR required only 250 ng genomic DNA, and was compatible with the fragmented DNA obtained from formalin fixed paraffin embedded samples (FFPE). No special equipment was needed, only a standard PCR machine. Patient samples were processed in parallel in a single 96-well plate. For each patient sample, we simultaneously amplified hundreds of exons from genes that are frequently mutated in cancer. We utilized standard library construction and barcoding methods to sequence targeted genes from 96 patient samples on a single Illumina GAIIx flowcell. The TargetRich cancer gene panels were highly specific; 95% of sequencing reads aligned to the targeted regions. The high percentage of on-target sequence data and focused content, allowed us to achieve high coverage across the loci (average of 400X read depth) for the sensitive detection of cancer mutations. We have created two cancer panels: CR (157 regions covering exons from 10 genes) and CS (760 regions covering exons from 62 genes) for use on the Illumina MiSeq, GAIIx & HiSeq platforms. Additionally, a CR panel for the Ion Torrent PGM has been developed with platform-specific primers added during the Nested PatchPCR reaction, allowing direct sequencing of products without time-consuming library construction.
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 LB-412. doi:1538-7445.AM2012-LB-412
Abstract LB-418: A live-cell miRNA reporter library for identifying non-genetic drug resistance networks at single-cell resolution
Authors: Leya Gregory , Albeck John , Brugge Joan 
Published: August 2012

Abstract
The effectiveness of targeted cancer therapies is limited by cellular resistance. Emerging research has demonstrated that a major source of drug resistance is non-genetic: pre-existing heterogeneity in protein expression levels, or induction of adaptive feedback loops, can protect cells from the effects of kinase inhibitors and other drugs. Traditional genomic or proteomic techniques may fail to identify key resistance pathways because they do not stem from changes in genetic sequences, are often transient in nature, and may operate in only a subset of cells within a population. To address this challenge, we have developed a library of over 80 live-cell reporters that, in combination with high-throughput automated microscopy, enable the identification of transiently active resistance pathways in drug-treated cells. These reporters are based on miRNA regulatory sequences since numerous miRNAs have been implicated in drug resistance and because miRNAs can act as surrogate indicators for the activation of signaling pathways in which they participate. We have developed and validated a novel ratiometric reporter design for optimal detection of miRNA expression changes at single-cell resolution and have constructed retroviral reporters for miRNAs involved in apoptosis, cell proliferation, cancer stem cells, metabolism, and stress response. Live imaging of mammary epithelial cells treated with inhibitors targeting EGFR, PI3-K, mTOR, and Bcl-2 identified a set of 20-30 miRNA reporters with significant expression level alterations in surviving cells that are consistent with miRNA expression changes characteristic of cancer cells. Bioinformatic analyses of these miRNAs revealed commonly regulated pathways and downstream targets, including Bcl-2 and Cyclin-D. Thus, the reporter library is capable of identifying, in living cells, pathways involved in the cellular response to targeted cancer therapies. By identifying components of the signaling networks controlling inhibitor resistance, we hope to discover new drug targets that can be used to sensitize tumor cells to existing targeted therapies. The reporter library can be easily expressed in most cell lines of interest and should have broad utility for identifying transiently regulated pathways.
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 LB-418. doi:1538-7445.AM2012-LB-418
Abstract LB-74: The estrogen receptor regulates the transcription of p53 target genes in breast cancer cells
Authors: Bailey Shannon T. , Shin Hyunjin , Liu X. Shirley , Brown Myles 
Published: August 2012

Abstract
Breast Cancer is a disease that affects thousands of women every year. A large subset of breast cancer is attributed to estrogen receptor (ER) dysregulation. Previously, our lab and others have determined the estradiol-stimulated ER cistrome in the MCF7 mammary epithelial cell line. To determine the relationship between ER and the apoptotic response, we compared our ER cistrome to a published p53 dataset. The p53 transcription factor is a tumor suppressor protein that is responsible for cell-cycle control and apoptosis. Our lab generated a doxorubicin-stimulated p53 cistrome in MCF7 cells, and we employed an integrative analysis approach examining the p53 and ER cistromes and gene expression microarray data to determine the genes coordinately regulated by both transcription factors. We identified a number of genes that are involved in the cell cycle, apoptosis, and DNA damage repair. By treating MCF7 cells with both stimuli, we found that the ER could inhibit the expression of a p53 target gene subset, thus diminishing the efficacy of the p53 program. These genes correlate with poor breast cancer clinical outcome. Moreover, we found that treatment of breast cancer cells with a combination of the anti-estrogen fulvestrant with p53 stimuli (i.e., doxorubicin and nutlin-3) leads to the synergistic enhancement of pro-apoptotic genes. Together, these data point to a set of genes essential for breast cell survival in ER-mediated breast cancer and suggest an improved paradigm for ER-positive breast cancer treatment i.e., the addition of fulvestrant with a p53 stabilizing drug.
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 LB-74. doi:1538-7445.AM2012-LB-74
Abstract LB-79: Synergistic anticancer effects of the 9.2.27PE immunotoxin and ABT-737 in melanoma involves silencing of the anti-apoptotic protein Mcl-1
Authors: Risberg Karianne , Fodstad Øystein , Andersson Yvonne 
Published: August 2012

Abstract
In cancer, combinations of drugs targeting different cellular functions is well accepted to improve tumor control. We studied the effects of a Pseudomonas exotoxin A (PE)-based immunotoxin, the 9.2.27PE, and the Bcl-2 family inhibitor ABT-737 in a panel of melanoma cell lines. ABT-737 inhibits the Bcl-2, Bcl-xl and the Bcl-w, but not Mcl-1 and A1 of the Bcl-2 family. The 9.2.27PE + ABT-737 drug combination resulted in synergistic cytotoxicity in the melanoma cells independent of BRAF mutation status. The cell death observed was associated with apoptosis, as activation of caspase-3, inactivation of Poly (ADP-ribose) polymerase (PARP) and increased DNA fragmentation could be prevented by pre-treatment with caspase and cathepsin inhibitors. In addition, ABT-737 caused endoplasmic reticulum (ER) stress with increased GRP78, phosphorylated eIF2α protein levels and increased intracellular calcium levels. The increased intracellular calcium levels were enhanced by silencing of Mcl-1 by short hairpin RNA or by treatment with the 9.2.27PE immunotoxin. These results suggests that Mcl-1 has an inhibitory effect on calcium release from the ER, and that strongly decreased Mcl-1 protein levels after treatment with 9.2.27PE or shRNA may be responsible for the increased intracellular calcium levels in ABT-737 treated melanoma cells. Calcium release has been shown to take place through the inositol 1,4,5-triphosphate receptor in the ER membrane, and the Bcl-2 family proteins Bcl-2, Bcl-xl and Mcl-1 have been shown to interact with the inositol 1,4,5-triphosphate receptor, supporting our results.1 Notably, the combination of 9.2.27PE and ABT-737 caused growth delay in a human melanoma xenograft mice model. 1. Eckenrode EF et. Al., J Biol Chem. 2010 Apr 30;285(18):13678-84
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 LB-79. doi:1538-7445.AM2012-LB-79