bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3011: Dietary fat, fatty acids, and ovarian cancer risk: Preliminary findings from the Shanghai Women’s Health Study
Authors: Akam Eftitan Y. , Murff Harvey J. , Xiang Yong-Bing , Khankari Nikhil K. , Cai Hui , Shu Xiao O. , Zheng Wei , Beeghly-Fadiel Alicia 
Published: July 2017

Abstract
Introduction: Dietary fat is an essential nutrient for human growth and development, but epidemiological studies have linked excess fat to the development of multiple malignancies. The few existing studies on ovarian cancer risk are inconsistent, possibly due to differences in sources and subtypes of fat. For example, omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are thought to be antineoplastic, while omega-6 (n-6) PUFAs may promote carcinogenesis.
Approach: We evaluated dietary fat in relation to ovarian cancer risk in the prospective Shanghai Women’s Health Study (SWHS). Intake levels were determined from food frequency questionnaires (FFQ) administered at baseline and during follow-up; specific nutrient components were based on the sum of specific foods multiplied by nutrient content from the Chinese Food Composition Table. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for dietary fat and fatty acid components categorized into quintiles. Minimal models included age and residual adjustment for total energy intake; fully adjusted models also included education, years of menstruation, years of oral contraceptive use, parity, years of breastfeeding, family history of ovarian cancer, smoking, drinking, NSAID use, BMI, and physical activity.
Results: Among 73,144 SWHS participants, we identified a total of 219 ovarian cancer cases in 1,114,828 person-years of follow-up. We found significant dose-response relationships between increasing total PUFA (P-trend=0.032) and n-6 PUFA (P-trend=0.022) intakes and decreased ovarian cancer risk. In both minimally and fully adjusted models, women with the highest quintile of total dietary PUFAs were approximately 35% less likely to develop ovarian cancer (RR=0.65, 95% CI: 0.43-1.00), and women with the highest n-6 PUFA intake had a nearly 40% lower risk (RR=0.61, 95% CI: 0.40-0.93). Total fat, monounsaturated fat, and n-3 PUFA intake were not significantly related to ovarian cancer risk.
Conclusions: Findings from our preliminary analysis of a large prospective cohort of Chinese women suggest that total PUFA intake may be protective of ovarian cancer, and that this association may be driven by n-6 rather than n-3 PUFAs. Further evaluation, including stratification, sensitivity analysis, and evaluation of source of dietary fatty acids, is currently underway.
Citation Format: Eftitan Y. Akam, Harvey J. Murff, Yong-Bing Xiang, Nikhil K. Khankari, Hui Cai, Xiao O. Shu, Wei Zheng, Alicia Beeghly-Fadiel. Dietary fat, fatty acids, and ovarian cancer risk: Preliminary findings from the Shanghai Women’s Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3011. doi:10.1158/1538-7445.AM2017-3011
Abstract 302: A novel epigenetic pathway in medulloblastoma
Authors: Ayad Nagi , Penas Clara 
Published: July 2017

Abstract
Medulloblastoma is the most common malignant pediatric brain tumor with variable prognosis due to its clinical and genomic heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from this disease. Therefore there is a need to develop novel therapies for patients. We recently reported that Casein kinase 1δ (CK1δ) may be an attractive therapeutic target for medulloblastoma. CK1δ is a serine/threonine kinase that controls cell cycle progression, signal transduction and neurogenesis. We found high levels of CK1δ protein in mouse models of medulloblastoma and human medulloblastoma samples. Furthermore, CK1δ inhibition dramatically reduced medulloblastoma tumor progression. We demonstrate here that CK1δ phosphorylates the epigenetic reader bromodomain-containing protein 4 (BRD4). BRD4 has been identified as a therapeutic target in several cancers, including medulloblastoma. We demonstrate that CK1δ phosphorylates BRD4 and that CK1δ is required for BRD4 binding to the Gli1 promoter in vitro and in vivo. Furthermore, combined CK1δ/BRD4 inhibition is a novel means of reducing medulloblastoma growth downstream of SUFU and SMO. These studies define a novel therapeutic means of inhibiting SMO inhibitor resistant medulloblastoma.
Citation Format: Nagi Ayad, Clara Penas. A novel epigenetic pathway in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 302. doi:10.1158/1538-7445.AM2017-302
Abstract 3022: Novel hydrocarbon stapled peptide inhibitors suppresses β-catenin dependent cancer growth and immunomodulates colorectal tumors
Authors: Zhu David , Jin Joy 
Published: July 2017

Abstract
Mutations in several components of the canonical Wnt pathway function as drivers in a range of common solid tumor cancers, including about 90% of sporadic colorectal cancers (CRCs), the third most common cancer in the US. In particular, activation of β-catenin (β-cat), a key Wnt signaling component, can initiate tumorigenesis in the intestine and promote cancer stem cell metastasis6,7. As such, targeting the Wnt pathway is an attractive approach to the development of cancer therapeutics. However, Wnt inhibitors tested to date, including those that disrupt β-cat activity, have either had limited efficacy or unacceptable side effect profiles1. Here, we developed a potent and robust, selective lead compound targeting oncogenic Wnt activity by disrupting the highly specific interaction of β-cat with its co-activators BCL9/B9L, which has been shown to abrogate transactivation. By using hydrocarbon stapled peptide technology and an acutely sensitive high throughput biochemical screening assay, we have identified several promising peptides that possess a strong pharmacokinetic profile. These peptides (i) exhibit robust activity in mouse models; (ii) inhibit cancer cell proliferation, metastasis, and stem cell progression; and (iii) modulate the immune microenvironment, demonstrating the feasibility of such peptide development and selection. Synergy is demonstrated between the stapled peptides and anti-PD1 antibodies, which has significant implications for combination therapy with commercial immune checkpoint blockers that have become standard of care for second-line melanoma treatment. These peptides represent a promising new potential therapeutic class for patients with CRC, for which traditional chemotherapy and targeted inhibitors have had limited therapeutic success.
Citation Format: David Zhu, Joy Jin. Novel hydrocarbon stapled peptide inhibitors suppresses β-catenin dependent cancer growth and immunomodulates colorectal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3022. doi:10.1158/1538-7445.AM2017-3022
Abstract 3028: Reactive oxygen species induced nuclear translocation of c-MET via INTERNET mechanism
Authors: Chen Mei-Kuang , Du Yi , Chu Yu-Yi , Hung Mien-Chie 
Published: July 2017

Abstract
c-MET is one of the receptor tyrosine kinases (RTKs) that are overexpressed in malignant cancer types including breast cancer. c-MET is traditionally known for its role in signaling transduction from the cell surface, our recent publication provided evidence that c-MET can be translocated into the nucleus and phosphorylate PARP1 in response to reactive oxygen species (ROS) stimulation (Du et al. Nat Med 2016). Oxidative stress is a common phenomenon in cancer cells due to alteration of metabolism, and constitutive oxidative stress related to ROS has been observed in breast cancer cells. In this study, we demonstrated that hepatocyte growth factor (HGF) as well as hydrogen peroxide (H2O2) can induce retrograde translocation of c-MET holoreceptor via a membrane-bound vesicle transport mechanism and translocate into the nucleus through INTERNET (integral trafficking from the ER to the nuclear envelope transport pathway) (Wang et al. J Biol Chem 2012) in breast cancer cells. While c-MET nuclear transportation increases dramatically under H2O2 treatment, our findings provide a putative mechanism by which breast cancer cells adapt to oxidative stress and suggest that INTERNET might be a general nuclear translocation mechanism shared among RTKs.
Citation Format: Mei-Kuang Chen, Yi Du, Yu-Yi Chu, Mien-Chie Hung. Reactive oxygen species induced nuclear translocation of c-MET via INTERNET mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3028. doi:10.1158/1538-7445.AM2017-3028
Abstract 3044: Rapid decay of engulfed extracellular miRNA by XRN1 exonuclease promotes transient epithelial-mesenchymal transition
Authors: Zangari Joséphine , Ilie Marius , Rouaud Florian , Signetti Laurie , Ohanna Mickaël , Didier Robin , Roméo Barnabé , Goldoni Dana , Nottet Nicolas , Staedel Cathy , Gal Jocelyn , Mari Bernard , Mograbi Baharia , Hofman Paul , Brest Patrick 
Published: July 2017

Abstract
Background: Extracellular vesicles (EVs) have been shown to play an important role in intercellular communication as carriers of DNA, RNA and proteins. While the intercellular transfer of miRNA thorough EVs has been widely studied, the stability of extracellular miRNA (ex-miRNA) once engulfed by recipient cell remains to be determined.
Materials and Methods: Lung cancer cells (A549 cell line) were incubated with neutrophils or their supernatant or isolated EVs from these supernatant. Kinetics of expression of miR-223-3p were followed by RT-qPCR. FOXO1 expression and EMT expression markers were used as endpoints to follow effective effect or miR-223-3p in recipient cells.
Results: We identified the ex-miRNA-directed phenotype to be transient due to the rapid decay of the ex-miRNA. We demonstrated that the ex-miR-223-3p transferred from neutrophils to cancer cells was functional as demonstrated by the decreased expression of its target, FOXO1, and the occurrence of epithelial-mesenchymal transition reprogramming. We showed that the engulfed ex-miRNA, unlike endogenous miRNA, was unstable, enabling dynamic regulation and a return to a non-invasive phenotype within less than 8 hours. This transient phenotype could be modulated by targeting XRN1/PACMAN exonuclease. Indeed, its silencing was associated with slower decay of ex-miR-223-3p and subsequently prolonged the invasive properties.
Conclusion: We showed that the “steady step” level of engulfed miRNA (ex-miR-223-3p) and its subsequent activity was dependent on the presence of a donor cell in the surroundings to constantly fuel the recipient cell with ex-miRNAs and of XRN1 exonuclease, which is involved in the decay of these imported miRNAs.
Citation Format: Joséphine Zangari, Marius Ilie, Florian Rouaud, Laurie Signetti, Mickaël Ohanna, Robin Didier, Barnabé Roméo, Dana Goldoni, Nicolas Nottet, Cathy Staedel, Jocelyn Gal, Bernard Mari, Baharia Mograbi, Paul Hofman, Patrick Brest. Rapid decay of engulfed extracellular miRNA by XRN1 exonuclease promotes transient epithelial-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3044. doi:10.1158/1538-7445.AM2017-3044
Abstract 3048: A noncoding function of TYRP1 mRNA promotes melanoma growth
Authors: Galibert Marie-Dominique , Gilot David , Migault Mélodie , Bachelot Laura , Journé Fabrice , Rogiers Aljosja , Donnou-Fournet Emmanuelle , Mogha Ariane , Mouchet Nicolas , Pinel-Marie Marie-Laure , Mari Bernard , Montier Tristan , Corre Sébastien , Gautron Arthur , Rambow Florian , Hajj Petra El , Jouira Rania Ben , Tartare-Deckert Sophie , Marine Jean-Christophe , Felden Brice , Ghanem Ghanem 
Published: July 2017

Abstract
RNAs competition to bind miRNA has been proposed to influence biological systems whether these RNAs are implicated in diseases onset is unclear. Here, we report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly governs cell proliferation by sequestering miR-16 on non-canonical miRNA response elements (MREs). Consequently, sequestered miR-16 is no longer able to repress its mRNA targets such as RAB17, which we show is involved in melanoma cell proliferation and invasion. Restoration of miR-16 tumor suppressor function can be achieved in vitro by silencing TYRP1 or increasing miR-16 expression levels. Importantly, TYRP1-dependent miR-16 sequestration can also be overcome in vivo using small oligonucleotides that mask miR-16 binding sites on TYRP1 mRNA. Together, our findings assign a pathogenic noncoding function to TYRP1 mRNA and underscore miRNA displacement as a new antimelanoma targeted therapeutic approach.
Citation Format: Marie-Dominique Galibert, David Gilot, Mélodie Migault, Laura Bachelot, Fabrice Journé, Aljosja Rogiers, Emmanuelle Donnou-Fournet, Ariane Mogha, Nicolas Mouchet, Marie-Laure Pinel-Marie, Bernard Mari, Tristan Montier, Sébastien Corre, Arthur Gautron, Florian Rambow, Petra El Hajj, Rania Ben Jouira, Sophie Tartare-Deckert, Jean-Christophe Marine, Brice Felden, Ghanem Ghanem. A noncoding function of TYRP1 mRNA promotes melanoma growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3048. doi:10.1158/1538-7445.AM2017-3048
Abstract 3049: Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing
Authors: Demeulemeester Jonas , Kumar Parveen , Møller Elen K. , Nord Silje , Wedge David C. , Peterson April , Mathiesen Randi R. , Fjelldal Renathe , Esteki Masoud Z. , Theunis Koen , Gallardo Elia F. , Grundstad Jason , Borgen Elin , Baumbusch Lars O. , Børresen-Dale Anne-Lise , White Kevin P. , Kristensen Vessela N. , Loo Peter Van , Voet Thierry , Naume Bjørn 
Published: July 2017

Abstract
Background. Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer.
Results. We sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells’ DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant ‘normal’ cells or ‘aberrant cells of unknown origin’ that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent, and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis.
Conclusions. Single-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.
Citation Format: Jonas Demeulemeester, Parveen Kumar, Elen K. Møller, Silje Nord, David C. Wedge, April Peterson, Randi R. Mathiesen, Renathe Fjelldal, Masoud Z. Esteki, Koen Theunis, Elia F. Gallardo, Jason Grundstad, Elin Borgen, Lars O. Baumbusch, Anne-Lise Børresen-Dale, Kevin P. White, Vessela N. Kristensen, Peter Van Loo, Thierry Voet, Bjørn Naume. Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3049. doi:10.1158/1538-7445.AM2017-3049
Abstract 3054: Tracing EMT with fluorescent biosensors (chromobodies) in living cancer cells
Authors: Maier Julia , Plaga Theresa , Egetemaier Stefanie , Traenkle Bjoern , Rothbauer Ulrich 
Published: July 2017

Abstract
Epithelial-mesenchymal transition (EMT) is a complex cellular program, involved in the progression of epithelial cancers to a metastatic stage. During this process characteristic epithelial marker proteins are repressed in favor of mesenchymal biomarkers, such as the intermediate filament protein vimentin. There is an ongoing need for reliable cell-based EMT model systems, which can be adapted to screening campaigns for novel anti-metastatic therapies. Imaging-based screening systems are restricted to endpoint immunofluorescence studies that provide only little information about the dynamics of the process, or to ectopic expression of EMT markers, fused to fluorescent proteins. However, overexpression of EMT marker proteins, particularly vimentin, have been shown to influence the EMT phenotype of the cells.
Here we introduce chromobodies as an innovative technology to monitor EMT in living non-small lung cancer cells. Chromobodies are fluorescently-labeled single-domain-antibodies that are functional within in living cells and directly target endogenous proteins. We generated chromobodies against the EMT biomarkers vimentin, actin and β-catenin and stably introduced them into the genome of A549 cells. Upon induction of EMT with transforming growth factor β (TGF- β), we could visualize the dynamic reorganization of endogenous vimentin, actin and β-catenin in the established EMT chromobody models in 2D as well as 3D cell culture. By means of these chromobody cell lines we further developed a 2D high content analysis system to visualize and quantify spatiotemporal changes of the endogenous biomarkers vimentin and actin during the EMT process. In a proof-of-principle screen, using known EMT-affecting reagents (e.g. TGF receptor I inhibitors LY364947 and SB505124) as well as EMT-unrelated agents, we were able to show that this high content analysis system can be applied to select compounds that inhibit TGF-β-induced EMT.
In summary, live cell imaging of EMT markers with chromobodies provides a novel versatile approach to study EMT in real time and allows the identification of EMT inhibitors as potential candidates for anti-metastatic therapies by high content screening.
Citation Format: Julia Maier, Theresa Plaga, Stefanie Egetemaier, Bjoern Traenkle, Ulrich Rothbauer. Tracing EMT with fluorescent biosensors (chromobodies) in living cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3054. doi:10.1158/1538-7445.AM2017-3054
Abstract 3059: UHRF1 deficiency exerts anti-tumor immune responses in non-small cell lung cancer
Authors: Xiang Handan , Chen Junying , Wang Xiao-Fan 
Published: July 2017

Abstract
Immune surveillance is essential for effective tumor clearance. However, the tumor microenvironment is typically impermissive for proper stimulation of both innate and adaptive immune populations. Epigenetic inhibitors have recently been shown to function as immune sensitizing reagents in the suppressive microenvironment. In our search for novel epigenetic regulators with immunomodulatory functions, we found ubiquitin-like with PHD and ring finger domain-containing protein 1 (UHRF1) being crucial for the suppression of immune activation. Loss of UHRF1 in cancer cells led to significant reduction of tumor masses in a syngeneic lung cancer model. The tumor shrinkage was due to increased infiltration of T cells with the enhanced ability to proliferate and produce IFN-gamma. Mechanistically, lung cancer cells deficient of UHRF1 had elevated expression of endogenous retrovirus genes due to DNA demethylation, which associated with enhanced type I interferon responses. Type I interferons are potent antitumor effector molecules by promoting immune cell infiltration into the tumor microenvironment, yet they can also dampen T cell activation by upregulating PD-L1 expression in tumor cells. Surprisingly, UHRF1 deficient cancer cells failed to upregulate PD-L1 even in the presence of excessive type I interferons, indicative of additional regulatory pathways for PD-L1. We further found that UHRF1 directly interacted with PD-L1 promoter regions and that UHRF1 promoted PD-L1 transcription. Therefore, the inhibition of UHRF1 augmented type I interferon responses while diminished PD-L1 expression, which synergistically contributed to the immune activation phenotype. Moreover, in non-small cell lung cancer (NSCLC) patients, UHRF1 expression was positively correlated with PD-L1 expression as well as poor prognosis. Together, our data suggested that UHRF1 represents a novel immuno-oncology target for NSCLC.
Citation Format: Handan Xiang, Junying Chen, Xiao-Fan Wang. UHRF1 deficiency exerts anti-tumor immune responses in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3059. doi:10.1158/1538-7445.AM2017-3059
Abstract 3070: Lenalidomide and SMAC mimetic LCL161 show combination activity in cells harboring loss of chromosome 5q
Authors: Hafeez Nafeeza , Gaither Alex , Porter Dale 
Published: July 2017

Abstract
LCL161 is a small molecule SMAC mimetic that binds to cIAP1, cIAP2, and XIAP and sensitizes cancer cells to TNF-alpha as well as other inducers of cell death. An siRNA screen was performed in the SK-OV-3 cancer cell line to identify genes that when knocked down prevent LCL161-mediated cell death. As expected, siRNAs targeting RIPK1 rescued cells from LCL161-induced death. Unexpectedly, siRNAs targeting GPR68 also rescued cells from LCL161-induced death. Since knockdown of GPR68 has been reported to rescue myelodysplastic syndrome (MDS)-derived cells harboring loss of chromosome 5q from lenalidomide treatment, we tested for combination activity with lenalidomide plus LCL161 in 7-day in vitro proliferation assays. Interestingly, combination activity was observed in the SET-2 cell line harboring cytogenetic features of MDS including loss of chromosome 5q. These data suggest that, in combination, LCL161 may improve responses to lenalidomide in subsets of MPN and MDS patients and potentially additional contexts where lenalidomide is active.
Citation Format: Nafeeza Hafeez, Alex Gaither, Dale Porter. Lenalidomide and SMAC mimetic LCL161 show combination activity in cells harboring loss of chromosome 5q [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3070. doi:10.1158/1538-7445.AM2017-3070