bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4723: Innovative cancer treatment of human lung cancer cells PC-9 with a synthetic retinoid Am80 and EGCG via inhibition of HDAC4 and HDAC5
Authors: Suganuma Masami , Oya Yukiko , Umsumarng Sonthaya , Iida Keisuke , Rawangkhan Anchalee , Sakai Ryo , Kagechika Hiroyuki , Shudo Koichi , Fujiki Hirota 
Published: July 2016

Abstract
A synthetic new retinoid Am80 (tamibarotene) is used for treatment of acute promyelocytic leukemia (APL) patients with resistance of all-trans-retinoic acid (ATRA). To potentiate efficacy of Am80, we challenged combination treatment of Am80 and EGCG on human lung cancer cell line PC-9. It is now well accepted that EGCG acts as synergist with numerous anticancer compounds, and that the average reduction of tumor volume for in vivo genograft mouse models implanted using various human cancer cell lines was 70.3% with combinations of 13 anticancer compounds and EGCG. We previously reported that combinations of NSAIDs (sulindac and celecoxib) or other retinoids (ATRA, 13-cis-RA and 9-cis-RA) and EGCG synergistically induced apoptosis of the cells along with strong expression of growth arrest and DNA-damage inducible gene 153 (GADD153) and death receptor (DR5) gene. Our objective was to investigate the mechanism of the synergistic induction for GADD153-DR5 apoptosis pathway. The proteomic analysis of lysine-acetylated proteins was conducted with a shotgun analysis using nanoLC-ESI-MS/MS in PC-9 cells. We found that the numbers of acetylated proteins were different: 551 acetylated proteins were found in non-treated cells, 331 proteins in cells treated with combination, and 59 proteins were common in both cases. Acetylation was mainly found in non-histone proteins, chaperons, transcription factors, and enzymes. The combination increased acetylated p53 (Lys382) about 3-fold compared with non-treated cells. In addition, combination significantly decreased the protein amounts of histone deacetylase (HDAC) 4 and HDAC 5 to 50% and 20%, respectively, but not HDAC6 among Class II HDACs. Class I HDACs (HDAC1, 2, and 3) were not decreased. All the results suggest that combination of Am80 and EGCG induces GADD153-DR5 apoptotic pathway, and reduces the amounts of HDAC4 and HDAC5 resulting in changing protein acetylation.
Citation Format: Masami Suganuma, Yukiko Oya, Sonthaya Umsumarng, Keisuke Iida, Anchalee Rawangkhan, Ryo Sakai, Hiroyuki Kagechika, Koichi Shudo, Hirota Fujiki. Innovative cancer treatment of human lung cancer cells PC-9 with a synthetic retinoid Am80 and EGCG via inhibition of HDAC4 and HDAC5. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4723.
Abstract 4738: The BET family bromodomain inhibitor ABBV-075 is a promising therapeutic agent for acute myeloid leukemia and myelodysplastic syndrome
Authors: Bui Mai H. , Lin Xiaoyu , Huang Xiaoli , Li Leiming , Sarthy Aparna , Albert Daniel , Magoc Terry , Lam Lloyd , Hessler Paul , Uziel Tamar , Elmore Steven , McDaniel Keith , Kati Warren , Shen Yu 
Published: July 2016

Abstract
Small molecule inhibitors of the bromodomain and extraterminal domain (BET) proteins exhibit interesting activities in preclinical models of various cancer indications, and several of these inhibitors are currently under clinical investigation. ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase 1 studies. Upon characterizing cellular responses to BET inhibitors across a large panel of cancer cell lines, we identified AML/MDS as one of the few cancer indications where BET inhibitors triggered robust apoptosis in cancer cell lines and in patient-derived cancer cells. The induction of apoptosis by BET inhibitors in AML/MDS cells may be partly attributed to their abilities to down regulate Bcl-XL and Bcl-2, and combining BET inhibitors with the Bcl-2 inhibitor venetoclax (ABT-199) resulted in robust cytotoxicity in AML/MDS cells. ABBV-075 exhibited significant antitumor efficacy as a monotherapy in flank xenograft models of AML and MDS. Furthermore, combining low doses of ABBV-075 with the standard of care agent azacitidine in the SKM1 model led to significant tumor regression, and the combination regimen was better tolerated than BETi monotherapy at doses that produced a similar degree of therapeutic benefit. Expression profiling of SKM1 tumors from mice treated with the ABBV-075/azacitidine combination or each of these agents as monotherapies revealed that ABBV-075 and azacitidine regulated a common set of biologic pathways. The combination of ABBV-075/azacitidine led to a more robust impact on these common pathways, which may partially contribute to the enhanced efficacy of the ABBV-075/azacitidine combination in the SKM-1 model.
Citation Format: Mai H. Bui, Xiaoyu Lin, Xiaoli Huang, Leiming Li, Aparna Sarthy, Daniel Albert, Terry Magoc, Lloyd Lam, Paul Hessler, Tamar Uziel, Steven Elmore, Keith McDaniel, Warren Kati, Yu Shen. The BET family bromodomain inhibitor ABBV-075 is a promising therapeutic agent for acute myeloid leukemia and myelodysplastic syndrome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4738.
Abstract 4741: Targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor
Authors: Pozo Karine , Zahler Stefan , Tan Chunfeng , Ishimatsu Keisuke , Takahashi Masaya , Bibb James 
Published: July 2016

Abstract
Neuroendocrine tumors are rare forms of cancers arising from hormone-producing cells that are scattered throughout the body. Medullary thyroid carcinoma (MTC) originates from the thyroid gland parafollicular cells. Treatment options for progressive, metastatic MTC patients are limited to the recently FDA-approved tyrosine kinase inhibitors (TKIs), Vandetanib and Cabozantinib, which target multiple receptor tyrosine kinases, including VEGFR2. However, the efficacy of TKIs is limited and development of TKI resistance is common.
Here we examined, the effect of a combinatorial drug therapy using the TKI, Nintedanib, and the histone deacetylase (HDAC) inhibitor, Romidepsin, on MTC growth in the NSE/p25-gfp bi-transgenic mouse line, an inducible MTC mouse model (see Pozo et al. 2013). The TKI- and HDAC inhibitors were administered intraperitoneally for 3 weeks and tumor growth progression was monitored using a T2 weighted magnetic resonance imaging on a 7 Tesla system. Tumor tissues were analyzed for oncogenic signaling pathways by immunoblotting and immunohistochemistry.
We find that co-administration of Nintedanib and Romidepsin stops tumor growth and increases the number of necrotic foci within the tumor tissue. Interestingly, Nintedanib treatment alone reduced tumor vascularization as shown by decreased density of the vascular marker, CD31, but did not stop parafollicular cell proliferation. Taken together, these results suggest that a combinatorial drug therapy with a TKI- and an HDAC inhibitor may be a more efficient strategy to target MTC progression and overcome recurrence.
Citation Format: Karine Pozo, Stefan Zahler, Chunfeng Tan, Keisuke Ishimatsu, Masaya Takahashi, James Bibb. Targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4741.
Abstract 4844: Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells
Authors: Chae In Gyeong , Chun Kyung-Soo 
Published: July 2016

Abstract
Thymoquinone (TQ), a compound isolated from black seed oil (nigella sativa), has been reported to possess anti-inflammatory and anticancer activities. However, the molecular mechanisms underlying the anticancer effects of TQ in renal cell carcinoma (RCC) remain poorly understood. This study revealed that treatment with TQ significantly reduced the cell viability and induced apoptosis in Caki cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression. TQ inhibited the constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) in Caki cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) kinases. Moreover, TQ attenuated the expression of STAT3 target gene products, such as survivin, cyclin D1, and D2. Since ROS is a universal entity mediating apoptosis, we examined whether TQ induced apoptosis via ROS formation. Treatment with TQ generated ROS in these renal cancer cells. Pretreatment of cells with ROS scavenger N-acetyl cysteine (NAC) abrogated the inhibitory effect of TQ on the JAK2/STAT3 signaling and rescued cells from TQ-induced apoptosis by blocking the induction of p53, and the cleavage of caspase-3, -9 and PARP in Caki cells. In conclusion, TQ induced apoptosis in Caki cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway.
Citation Format: In Gyeong Chae, Kyung-Soo Chun. Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4844.
Abstract 4863: PF-06840003: a highly selective IDO-1 inhibitor that shows good in vivo efficacy in combination with immune checkpoint inhibitors
Authors: Tumang Joseph , Gomes Bruno , Wythes Martin , Crosignani Stefano , Bingham Patrick , Bottemanne Pauline , Cannelle Hélène , Cauwenberghs Sandra , Chaplin Jenny , Dalvie Deepak , Denies Sofie , De Maeseneire Coraline , Folger Peter , Frederix Kim , Guo Jie , Hardwick James , Hook Ken , Jessen Katti , Kindt Erick , Letellier Marie-Claire , Liao Kai-Hsin , Li Wenlin , Maegley Karen , Marillier Reece , Miller Nichol , Murray Brion , Pirson Romain , Preillon Julie , Rabolli Virginie , Ray Chad , Scales Stephanie , Srirangam Jay , Solowiej Jim , Streiner Nicole , Torti Vince , Tsaparikos Konstantinos , Vicini Paolo , Driessens Gregory , Kraus Manfred 
Published: July 2016

Abstract
Tumors use tryptophan-catabolizing enzymes such as Indoleamine 2,3-dioxygenase-1 (IDO-1) to induce an immunosuppressive microenvironment. IDO-1 expression is upregulated in many cancers and described to be a resistance mechanism to immune checkpoint therapies. IDO-1 is induced in response to inflammatory stimuli such as IFN-ã and promotes immune tolerance through the catabolism of tryptophan and accumulation of tryptophan catabolites including kynurenine. IDO-1 activity leads to effector T-cell anergy and enhanced Treg function through upregulation of FoxP3. As such, IDO1 is a nexus for the induction of key immunosuppressive mechanisms and represents an important immunotherapeutic target in oncology. We have identified and characterized a new IDO-1 inhibitor. PF-06840003 is a highly selective orally bioavailable IDO-1 inhibitor. PF-06840003 reversed IDO-1-induced T-cell anergy in vitro. In vivo, PF-06840003 reduced intratumoral kynurenine levels in mice by &gt;80% and inhibited tumor growth in multiple preclinical syngeneic models in mice, in combination with immune checkpoint inhibitors. PF-0684003 has favorable predicted human pharmacokinetic properties, including a predicted t1/2 of 16-19 hours. These studies highlight the strong potential of PF-06840003 as a clinical candidate in Immuno-Oncology.
Citation Format: Joseph Tumang, Bruno Gomes, Martin Wythes, Stefano Crosignani, Patrick Bingham, Pauline Bottemanne, Hélène Cannelle, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, Peter Folger, Kim Frederix, Jie Guo, James Hardwick, Ken Hook, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Kai-Hsin Liao, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Stephanie Scales, Jay Srirangam, Jim Solowiej, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Paolo Vicini, Gregory Driessens, Manfred Kraus. PF-06840003: a highly selective IDO-1 inhibitor that shows good in vivo efficacy in combination with immune checkpoint inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4863.
Abstract 5004: APX005M, a humanized anti-CD40 antibody with strong immune-modulatory activities capable of tumor eradication in vivo
Authors: Björck Pia , Filbert Erin , Yang Xiaodong , Trifan Ovidiu C. 
Published: July 2016

Abstract
The success of immune checkpoint inhibitors validates the concept that immunotherapy is an effective approach for the treatment of solid tumors. In addition to reversing tumor-induced immune suppression, immune activating antibodies are being explored as the next generation of immuno-oncology therapeutics. CD40, which is expressed on antigen presenting cells such as dendritic and B cells initiates and regulates both innate and adaptive immunity and is essential for the activation of antigen-specific T cells. APX005M is a humanized IgG1 CD40 agonistic antibody developed using Apexigen's APXiMAB™ discovery platform. APX005M binds with high affinity to human (Kd = 0.12nM) and monkey (Kd = 0.37nM) CD40. It recognizes a unique epitope that overlaps with the CD40 ligand binding sites and thus blocks the binding of CD40 to CD40L. APX005M is a potent CD40 agonistic antibody capable of activating antigen presenting B cells (EC50 = 12pM) and dendritic cells (EC50 = 0.49nM). Its CD40 agonistic activity requires crosslinking by Fc-gamma receptors since F(ab)’2 fragment of APX005M loses the agonistic activity. Upon binding to CD40 expressing tumor cells APX005M induces antibody-dependent cellular phagocytosis (ADCP) and apoptosis. In vivo APX005M completely eradicates CD40+ lymphoma tumors and inhibits the growth of rituximab-resistant tumors. The data suggest that a CD40 agonistic mAb such as APX005M, that activates CD40 through binding to the CD40L binding site while being dependent on crosslinking via Fc-gamma receptors, may represent an ideal immune activating antibody drug candidate for stimulating effective immune responses against tumors. APX005M is currently being evaluated in clinical trials for the treatment of patients with solid tumors.
Citation Format: Pia Björck, Erin Filbert, Xiaodong Yang, Ovidiu C. Trifan. APX005M, a humanized anti-CD40 antibody with strong immune-modulatory activities capable of tumor eradication in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5004.
Abstract 5112: Galactose probes hit neuroblastoma cells through a specific galactose-galectin association
Authors: Simone Giuseppina , Ponzoni Mirco , Pastorino Fabio 
Published: July 2016

Abstract
Galectins are a family of proteins that decorate the cell membrane and form extracellular molecular associations with β-galactoside sugars.
In order to mimic multivalent molecular recognitions, galactoside moieties have been immobilized on microbeads and used in cytofluorimetric analysis and in microfluidic assay to study the molecular association between carbohydrates and proteins in neuroblastoma (NB) cells. The hypothesis behind this investigation was that the molecular mechanisms by which glycans modulate neural metastatic cells involve protein-carbohydrate association.
To evaluate the binding between microbeads and tumor cells, two human NB cell lines were used in cellular association experiments. GI-LI-N cells, derived from the peripheral blood of a bone marrow-infiltrated, high risk, stage IV NB patient, were chosen for metastatic characteristics; IMR-32 cells were chosen because derived from the primary tumor in the abdominal site of an unknown-stage NB patient.
In vitro experiments have revealed molecular binding preferences of the metastatic NB cells. This result underscores that the efficiency of the cellular association might be related to the differences in the expression of the galectins between the two cell lines (GI-LI-N cells &gt;&gt; IMR-32 cells) and that the formation of the molecular association galectin-galactose could discriminate the tumor stages.
Ex vivo investigations have supported in vitro results; indeed, galactose moieties mostly recognized GI-LI-N cells derived from orthotopic tumor-bearing mice respect to explanted IMR-32 cells. This molecular association was tumor cells specific because it discriminated healthy tissues.
The understanding of this mechanism of recognition, and of possible cellular discrimination, can be relevant for the diagnostic monitoring of metastatic NB cells, and for producing probes tailored to interfere with galectin activities associated with the malignant phenotype.
Citation Format: Giuseppina Simone, Mirco Ponzoni, Fabio Pastorino. Galactose probes hit neuroblastoma cells through a specific galactose-galectin association. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5112.
Abstract 5249: Crocin prevents early lesions of liver cancer:system biology approach
Authors: Amin Amr , Hamza Alaaeldin A. , Daoud Sayel , Khazanehdari Kamal , Al Hrout Ala’a , Baig Badriya , Chaiboonchoe Amphun , Adrian Thomas E. , Zaki Nazar , Salehi-Ashtiani Kourosh 
Published: July 2016

Abstract
The angiogenesis inhibitor, sorafenib, remains the only available therapy of the poorly diagnosed hepatocellular carcinoma (HCC). Only recently patents of VEGF receptors-3 inhibitors are developed.; hence,Thus, a novel approach against HCC is essential for a better therapeutic outcome. Saffron and its active constituents were reported to have anti-tumor properties. Objective: The aims of this study were to examine the chemopreventive action of saffron's main biomolecule, crocin, against chemically-induced liver cancer in rats, and to explore the mechanisms by which crocin employs its anti-tumor effects. Method: We investigated the anti-cancer effect of crocin on an experimental carcinogenesis model of liver cancer by studying the anti-oxidant, anti-inflammatory, anti-proliferation, pro-apoptotic activities of crocin in vivo. In addition, we provided a network analysis of differentially expressed genes in tissues of animals pre-treated with crocin in comparison to induced-HCC animals’ tissues. To further support our results, in vitro analysis was carried out. We assessed the effects of crocin on HepG2 cells viability by treating them with various concentrations of crocin; in addition, effects of crocin on cell cycle distribution of HepG2 cells were investigated. Results: Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in induced-HCC model. Crocin exhibited anti-inflammatory properties where NF-kB, among other inflammatory markers, was inhibited. In vitro analysis confirmed crocin's effect in HepG2 by arresting the cell cycle at G2/M phase, inducing apoptosis and down regulating inflammation. Network analysis identified NF-kB as a regulatory hub, and therefore, a candidate therapeutic drug target. Conclusion: Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC.
Citation Format: Amr Amin, Alaaeldin A. Hamza, Sayel Daoud, Kamal Khazanehdari, Ala’a Al Hrout, Badriya Baig, Amphun Chaiboonchoe, Thomas E. Adrian, Nazar Zaki, Kourosh Salehi-Ashtiani. Crocin prevents early lesions of liver cancer:system biology approach. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5249.
Abstract 5270: The UCSC Xena system for integrating and visualizing functional genomics
Authors: Goldman Mary , Craft Brian , Zhu Jingchun , Swatloski Teresa , Cline Melissa , Haussler David 
Published: July 2016

Abstract
UCSC Xena (http://xena.ucsc.edu/) is a bioinformatics tool to visualize functional genomics data from multiple sources simultaneously, including both public and private data. The Xena system consists of a set of federated data hubs and the Xena browser, which integrates across hubs, providing one location to analyze and visualize all data. The lightweight Xena data hubs are straightforward to install on Windows, Mac and Linux operating systems and easily allow hub administrators to authenticate users, ensuring that only authorized users have access to secure data. Loading data into a Xena hub is easy using either our application or command line interface. Hosting public data from major projects, such as TCGA, on public Xena hubs gives users access without having to download these large datasets. The Xena system makes it easy to aggregate across many hubs, allowing users to integrate public datasets and private secure data together or view them separately. This system of the browser and hubs helps researchers combine new or preliminary results from their laptops or internal servers, or even data from a new paper, securely with vetted data from the public sphere.
The largest public Xena hub, based at UCSC, currently hosts an expanding set of searchable data, including 806 public datasets from several large consortiums including TCGA (The Cancer Genome Atlas), ICGC (International Cancer Genome Consortium), Treehouse Childhood Cancer Project, CCLE (Cancer Cell Line Encyclopedia), and more. Xena hubs are flexible enough to handle most data types, including gene, exon, miRNA and protein expression, copy number, DNA methylation and somatic mutation data along with phenotypes, subtype classifications and genomic biomarkers. Dynamic Kaplan-Meier survival analysis helps investigators to assess survival stratification by any information while scatter plots and bar graphs offer new insights into the data. Integration with Galaxy gives users access to a myriad of bioinformatics tools for further analysis and hypothesis testing.
Citation Format: Mary Goldman, Brian Craft, Jingchun Zhu, Teresa Swatloski, Melissa Cline, David Haussler. The UCSC Xena system for integrating and visualizing functional genomics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5270.