bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A39: Sall2 tumor suppressor protein is a novel Casein Kinase 2 target
Authors: Hermosilla Viviana , Rabalski Adam , Gyenis Laszlo , Litchfield David W. , Pincheira Roxana 
Published: May 2016

Abstract
Sall2 is a transcription factor with critical roles during development, including neurogenesis and eye formation. Importantly, Sall2 has also been associated with cancer, although its contribution to the disease remains controversial. Sall2 is down-regulated in several tumor types and its activity promotes cell cycle arrest and cell death. Despite its role as a tumor suppressor, little is known about its regulation.
In order to identify regulatory mechanisms of Sall2 protein, bioinformatic analysis were performed. Preliminary data lead to the identification of several putative phosphorylation sites within a potential and highly conserved PEST motif. All of these sites match the consensus sequence for Casein Kinase 2 (CK2)-mediated phosphorylation. CK2 is a ubiquitous and constitutively active kinase whose activity is increased in cancer cells. CK2 promotes both cell survival and proliferation by regulating stability, activity and/or subcellular localization of its target proteins, including tumor suppressors.
With the aim of determining whether Sall2 is regulated by CK2, several approaches such as pharmacological inhibition of CK2, mass spectrometry analysis, immunofluorescence, immunoprecipitation, in vitro kinase assays and site directed mutagenesis were used.
Our results indicate that Sall2 is a CK2 target in vitro. In cells, CK2 interacts with Sall2 and triggers the ubiquitination and subsequent degradation of Sall2 in a proteasome-mediated fashion. Moreover, phosphorylation of Sall2 at S763 and T778 was greatly reduced under CK2 inhibition, suggesting that these are the most important CK2-dependent phospho-sites in vivo.
In conclusion, we have identified Sall2 as a new CK2 target. Our results support a novel regulatory mechanism for Sall2 degradation and provide new insights into the means by which CK2 promotes cell survival and proliferation, two characteristic requirements of cancer cells.
FUNDING: FONDECYT1151031, CIHR
Citation Format: Viviana Hermosilla, Adam Rabalski, Laszlo Gyenis, David W. Litchfield, Roxana Pincheira. Sall2 tumor suppressor protein is a novel Casein Kinase 2 target. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A39.
Abstract A47: Expression of oncogenic alleles induces multiple blocks to HCMV infection
Authors: Xu Shihao , Schafer Xenia , Munger Joshua 
Published: May 2016

Abstract
Human cytomegalovirus (HCMV) poses serious threats to newborns and immune-compromised individuals. In contrast to most viruses studied, HCMV is unable to replicate in cancerous cells, but the mechanisms of this restriction are unclear. We explored these mechanisms by determining whether defined oncogenic alleles including the simian virus 40 (SV40) T antigens and oncogenic HRas G12V could inhibit HCMV replication. Our results show that the expression of SV40 T antigens blocks HCMV replication. In contrast, the replication of a related herpes virus, herpes simplex virus I, is not impacted by T antigen expression. The earliest restriction of HCMV infection involves a block of viral entry, as T antigen expression prevents viral tegument protein delivery. Subsequently we find that T antigen expression reduces the accumulation of platelet-derived growth factor receptor (PDGFR) alpha, a host protein that facilitates HCMV entry. Viral entry, gene expression and DNA replication could be partially rescued by PDGFR alpha over-expression. However, production of infectious viral progeny is not restored by PDGFR alpha over-expression in T antigen-expressing fibroblasts. Analysis of viral gene expression indicates that the accumulation of immediate early 2 (IE2), the major viral transcriptional activator, is inhibited by T antigen expression. Restoration of IE2 expression markedly increases downstream HCMV gene expression but not virion production, suggesting additional viral restrictions induced by T antigen. Similarly, PDGFR alpha over-expression in Hela cells markedly increases HCMV gene expression and DNA replication but not virion production. Combined, our results indicate that oncogenic alleles induce multiple restrictions to HCMV infection.
Citation Format: Shihao Xu, Xenia Schafer, Joshua Munger. Expression of oncogenic alleles induces multiple blocks to HCMV infection. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A47.
Abstract B13: In vitro animal cancer model for assessment of sulfated polysaccharides extract of Ulva lactuca as colon cancer therapeutic and chemopreventive agents
Authors: Abu-Serie Marwa , Demellawy Maha El , El-Sayed Mohamed , El-Rashidy Fatma 
Published: May 2016

Abstract
Purpose: Sulfated polysaccharides extract of Ulva lactuca (ULSP) was in vitro assessed as probable chemopreventive and therapeutic agents for colon cancer (CC) comparing with currently used chemotherapy (5-fluorouracil “5-FU” and mitomycin-C “MMC”) using our newly developed in vitro transformed cancerous rat colon epithelial cells.
Methods: The present study used an in vitro animal CC model as it resembles human multistage of chromosomal instability type of CC that is located mainly at distal colon. Hence, this model was used for evaluating ULSP by the detection of cytotoxicity against normal and cancerous colon cells and antimetastatic potency. Besides, ULSP efficacy as CC chemopreventive agent was assessed through the detection of CC progression markers; loss of heterozygosity of deleted in colorectal cancer (DCC) and p53, aldehyde dehydrogenase (ALDH) 1B1 expression, activities of ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2) and alkaline phosphatase (ALP), cellular redox state (Eh), doubling time, and mucin level.
Results: The apoptosis-dependent anticancer activity of ULSP (4.9 µg/ml) was revealed at all stages of cancerous distal colon epithelial cells by the formation of apoptotic bodies and DNA fragmentation (above 43%) without affecting normal colon epithelial cells. Also, its inhibitory effect on the invasion of cancerous epithelial and Caco-2 cells (above 49%) was stronger than that of 5-FU+MMC (about 11%). Cells were treated with ULSP before exposure to CC inducers and they showed normal tumor suppressor genes (DCC and p53), normal expression of ALDH1B1, and normal activity of ODC (0.03±0.0004 U/μg) and null activity of COX-2. In addition, their normal pattern of proliferations (doubling time 3 days and Eh 252.7±2.12 mV) and differentiation was confirmed by the maintenance of ALP activity (0.46±0.01 mU/μg) and the secretion of mucin (29.2±0.2 μg/ml) compared to normal and cancerous colon epithelial cells.
Conclusion: Our innovative in vitro model of colon cancer have proved that ULSP could have induced apoptosis at all stages of cancerous colon cells, inhibited cancerous cells to metastasize and blocked CC progression without effect on normal epithelial cells comparable to chemotherapy.
Citation Format: Marwa Abu-Serie, Maha El Demellawy, Mohamed El-Sayed, Fatma El-Rashidy. In vitro animal cancer model for assessment of sulfated polysaccharides extract of Ulva lactuca as colon cancer therapeutic and chemopreventive agents. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B13.
Abstract B27: Involvement of c-MET signaling in BCRP/ABCG2 activation and resistance to doxorubicin and photodynamic therapy
Authors: Choi Bo-hyun , Jung Kyeong-Ah , Kwak Mi-Kyoung 
Published: May 2016

Abstract
Overexpression of BCRP/ABCG2, a xenobiotic efflux transporter, is related to anticancer drug resistance in tumors. Proto-oncogene c-MET induces cancer cell proliferation, motility, and survival, and its aberrant activation was found to be a prognostic factor in advanced ovarian cancers. In this study, we demonstrate the potential cross-resistance of doxorubicin-resistant ovarian cancer cells to the pheophorbide a (Pba)-based photodynamic therapy (PDT) and suggest c-MET and BCRP/ABCG2 overexpression as an underlying molecular mechanism. The doxorubicin resistant A2780 cell line (A2780DR) showed enhanced resistance to PDT cytotoxicity with decreased level of reactive oxygen species generation and Pba accumulation than A2780. In microarray analysis, BCRP/ABCG2 is the sole drug transporter which was upregulated in A2780DR. The incubation with the BCRP/ABCG2 specific inhibitor reversed the both Pba-PDT and doxorubicin resistance in A2780DR. Importantly, we identified that the expression of c-Met, which is an oncogene activating PI3K signaling, was increased in A2780DR and the inhibition of PI3K/AKT or c-MET repressed resistance to doxorubicin and PDT. Finally, we showed that the pharmacological and genetic inhibition of c-MET diminished levels of BCRP/ABCG2 in A2780DR. Collectively, our results provide evidence that c-MET overexpression is linked to BCRP/ABCG2 activation and this mechanism leads to crossresistance to both chemotherapy and PDT.
Citation Format: Bo-hyun Choi, Kyeong-Ah Jung, Mi-Kyoung Kwak. Involvement of c-MET signaling in BCRP/ABCG2 activation and resistance to doxorubicin and photodynamic therapy. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B27.
Abstract B29: Characterization of the regulatory feedback program components after HER2 inhibition in breast cancer cells
Authors: Sakur Nareeza , Fink Marc 
Published: May 2016

Abstract
HER2 overexpression drives tumorigenesis in a subset of breast cancers and pharmacological inhibition of this receptor tyrosine kinase is currently used in the clinic for these patients. While all of the cancer cells within the tumor are dependent on HER2 signaling, treatment with HER2 inhibitors results in the establishment of two separate populations; cells that undergo apoptosis and cells that survive. The mechanisms underlying the decision-making processes are not well understood. A proposed mechanism for establishing resistance within a population involves induction of signaling components that may allow for bypass of HER2. Induction of these genes is dependent on AKT inhibition and subsequent activation of the FOXO family of transcription factors. The best-studied adaptive signaling components relevant to HER2-positive breast cancer are HER3, IGF1R, and IR. The involvement of these signaling components in acute adaptive resistance to HER2 inhibition was studied in the HER2-positive BT474 cell line. Lapatinib increased HER3 protein levels in a concentration dependent manner, however, at higher concentrations this effect was reversed. In contrast, inhibition of PI3K increased HER3 levels even at higher concentrations. Time course analysis of HER3 induction demonstrated strong regulation of protein levels at 8 hours post addition of inhibitor. Ongoing work is focused on determining whether these findings are generally applicable to the adaptive gene response. The results reported here provide a framework to model the effects of HER2 inhibition on apoptosis and survival in breast cancer cells.
Citation Format: Nareeza Sakur, Marc Fink. Characterization of the regulatory feedback program components after HER2 inhibition in breast cancer cells. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B29.
Abstract B36: Orally active low molecular weight heparin conjugates as a tumoral lymphangiogenesis inhibitor
Authors: Choi Jeong Uk , Byun Youngro 
Published: May 2016

Abstract
Heparin has been reported as not only an anticoagulant drug but also as a tumoral angiogenesis inhibitor by blocking tumor growth factors including VEGF, bFGF. Low molecular weight heparin conjugated with 4 pairs of deoxycholic acid (LHbisD4) was newly synthesized to enhance the oral absorption and efficacy. As the tumoral lymphangiogenesis is being considered to play the most important role in tumor metastasis, the purpose of this study is to evaluate whether LHbisD4 could suppress the tumoral lymphangiogenesis as well as the incidence of metastasis. To evaluate the inhibition effect of LHbisD4 on VEGF-C induced lymphangiogenesis, several in vitro experiments using human dermal lymphatic endothelial cell(HDLEC) was carried out. The inhibition effect of LHbisD4 on VEGF-C induced VEGFR-3 phosphorylation was evaluated by western blot. Proliferation assay, tubular formation assay, spheroid based sprouting assay were also done to evaluate the efficacy of LHbisD4 on suppressing lymphagiogenesis using HDLEC. For in vivo test, orthotopic breast cancer metastasis model was used and the incidence of metastasis to distant organs was evaluated. We found that VEGF-C induced phosphorylation of VEGFR3 which is the most important signaling cascade to initiate the lymphangiogenesis was highly inhibited in the presence of LHbisD4. Also through other in vitro experiment such as proliferation assay, tubular formation assay, spheroid based sprouting assay, LHbisD4 was proven to be effective enough to suppress VEGF-C induced lymphangiogenesis. In orthotopic model, 10mg/kg/day dose of LHbisD4 was administered orally and we found the incidence of metastasis is highly decreased compared with control group. Especially, weight and volume of the lymph node is highly decreased in case of drug treated group, which means the lymphatic metastasis is significantly suppressed. Through this study, we demonstrate that our novel heparin conjugate could be a good candidate for targeting VEGF-C induced lymphangiogenesis as well as an effective anti-metastatic agent.
Citation Format: Jeong Uk Choi, Youngro Byun. Orally active low molecular weight heparin conjugates as a tumoral lymphangiogenesis inhibitor. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B36.
Abstract B38: A novel (+)-dehydroabietylamine derivative shows activity against triple-negative breast cancer cells
Authors: Gautam Lekh Nath Sharma , Ling Taotao , Rivas Fatima 
Published: May 2016

Abstract
In both well developed and developing countries, breast cancer remains the leading cause of cancer-related death among women. Very few effective treatments are available to its subtype triple negative breast cancer (TNBC), being unresponsive to estrogen therapy. A phenotypic screening was performed on terrestrial natural products against the human breast carcinoma cell lines MDA-MB-231, MA11, and MCF-7 targeting new chemical scaffolds to TNBC. Further studies were focused on abietanes natural products that preferentially inhibited proliferation of triple-negative MDA-MB-231 cells over estrogen receptor–positive cells. The activity of the abietane carnosol prompted to generate a focus library from the readily available (+)-dehydroabietylamine. The lead compound (+)-pentafluoro sulfonamide derivative of dehydroabietylamine displayed a promising EC50 of 9.0 μM against MDA-MB-231 and our mechanistic studies indicate it induced apoptosis, which was associated with activation of caspase-9 and -3 and the cleavage of PARP. Current progress towards this promising therapeutic area will be discussed.
Citation Format: Lekh Nath Sharma Gautam, Taotao Ling, Fatima Rivas. A novel (+)-dehydroabietylamine derivative shows activity against triple-negative breast cancer cells. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B38.
Abstract IA11: Tumor dormancy and recurrence
Authors: Chodosh Lewis A. 
Published: May 2016

Abstract
For many types of human cancer, residual tumor cells remain following treatment that are not detected by conventional clinical testing. These cells have the ability to survive in a presumed dormant state within tissues for up to 20 years, either as solitary cells or as micrometastases. Ultimately, residual cells re-emerge from this latent state and resume growth, leading to cancer recurrence. Despite the unrivaled clinical importance of these aspects of breast cancer progression, the mechanisms underlying them are largely unknown. Since dormant residual tumor cells likely constitute the reservoir from which recurrent cancers arise, the lack of therapeutic approaches specifically targeted against these cells as well as our lack of understanding about their biology constitute major obstacles to the successful treatment of human cancers. As such, the development of targeted therapies designed to block pathways on which residual tumor cells depend for survival and growth would represent an attractive approach to preventing cancer recurrence. Consequently, elucidating the pathways that underlie dormant tumor cell survival and recurrence is a critical priority in cancer research.
Citation Format: Lewis A. Chodosh. Tumor dormancy and recurrence. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA11.
Abstract IA26: Long-term single cell quantification: New tools for old questions
Authors: Schroeder Timm 
Published: May 2016

Abstract
Stem cell systems are highly complex and dynamic, and consist of large numbers of different cells expressing many molecules. Despite intensive research, many long-standing questions in stem cell research remain disputed. One major reason is the fact that we usually only analyze populations of cells - rather than individual cells - at very few time points of an experiment. Tracking of individual cells would be an extremely powerful approach to improve our understanding of molecular cell fate control. We are therefore developing imaging systems to follow the fate of individual cells over many generations. We program new software to help recording and displaying the divisional history, position, properties, interaction, etc. of all individual cells over many generations. Our approaches also allow continuous long-term quantification of protein expression or activity in individual living cells. The resulting novel kind of continuous quantitative single cell data is used for the generation of improved models describing the molecular control of stem cell fates. I will discuss how we try to find answers for long standing questions in stem cell research.
Citation Format: Timm Schroeder. Long-term single cell quantification: New tools for old questions. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA26.
Abstract IA36: Signatures of mutational processes
Authors: Stratton Mike 
Published: May 2016

Abstract
All cancers are caused by somatic mutations. However, the processes underlying the genesis of somatic mutations in human cancer are remarkably poorly understood. Recent large-scale cancer genome sequencing initiatives have provided us with new insights into these mutational processes through the mutational signatures they leave on the cancer genome. In this talk I will review the mutational signatures found across cancer and consider the underlying mutational processes that have been operative.
Citation Format: Mike Stratton. Signatures of mutational processes. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA36.
Abstract A06: Characterization of a novel p53-regulated embryonic stem cell-specific lncRNA that safeguards pluripotency
Authors: Jain Abhinav K. , Akdemir Kadir C. , Xi Yuanxin , McCarthy Ryan L. , Allton Kendra , Aronow Bruce , Lin Chunru , Li Wei , Yang Liuqing , Barton Michelle C. 
Published: May 2016

Abstract
Recent work shows that long non-coding RNAs (lncRNAs), transcribed from 80% of our genomes, play important roles in gene regulation and are associated with disease pathogenesis. However, there is a broad gap in our knowledge regarding any contributions of lncRNAs in mediating p53 response or regulating stem cell state. Here, we report our discovery of lncRNAs that fine-tune p53's transcriptional outcomes in differentiating human embryonic stem cells (hESCs). By integrating RNA-Seq with p53 ChIP-Seq analyses along with active or repressive histone marks of hESCs undergoing differentiation, we defined a high-confidence set of 40 lncRNAs that are p53 transcriptional targets. We found that p53 directly regulates nuclear lncRNAs, which are either activated (HOTAIRM1) or repressed (lncPRESS-1) during hESC differentiation. Single-cell gene expression analysis during lineage-specific hESC differentiation revealed that lncPRESS-1 is a novel pluripotency-specific, p53-regulated transcript with expression tightly correlated with OCT4, NANOG and PRDM14. Loss-of-function of lncPRESS-1 results in diminished pluripotency and spontaneous differentiation of hESCs. In addition, mass cytometry-based multi-parametric analysis at a single cell level revealed that depletion of lncPRESS-1 results in overall loss of hESC pluripotency with marked induction of an ectoderm specific gene-signature. Further, we show that lncPRESS-1 physically interacts with SIRT6 and restrains its chromatin localization to maintain high levels of histone H3 Lys-56 (H3K56) and Lys-9 (H3K9) acetylation at promoters of pluripotency genes to sustain a chromatin architecture that favors pluripotency. In summary, we describe a novel pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity. Since lncPRESS-1 is repressed by p53, we believe that cancers that harbor mutant TP53 will have robust expression of this lncRNA. Further investigations are underway to determine the disease relevance of lncPRESS-1 and correlation with p53-mutations.
Citation Format: Abhinav K. Jain, Kadir C. Akdemir, Yuanxin Xi, Ryan L. McCarthy, Kendra Allton, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C. Barton. Characterization of a novel p53-regulated embryonic stem cell-specific lncRNA that safeguards pluripotency. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A06.