tbuckley/cabot-search huggingface dataset:
Abstract 4654: Antitumorigenic activity of trans-chalcone in osteosarcoma
Authors: Gabriel da Silva, Mozart Marins, Ana Lúcia Fachin, Seung J. Baek
Journal: Cancer Research (2015)

Abstract Background and Aims: Osteosarcoma is the most common bone cancer, and it affects mostly teenagers and children. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Thus, there is a clear need to identify new anticancer therapies. Currently, much anticancer therapy uses drugs that affect molecular targets, such as up-regulation of p53 and down-regulation of Sp1. Building on this knowledge, our aims in this work were to evaluate the ability of trans-Chalcone to reduce viability, induce apoptosis, and to alter the levels of p53 and Sp1 in human osteosarcoma cell lines. Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Methods: Osteosarcoma cell viability and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The expression of p53 and sp1 was assessed by Western blotting. Transcriptional and post-translational regulation were measured by luciferase assay and proteasomal inhibitor experiments. Results: We identified that cell growth was inhibited by trans-Chalcone in a dose- and time-dependent manner, with a significant inhibition at 10 μM after 48 hours. After 24 hours of treatment with trans-Chalcone, apoptosis was induced in a dose-dependent manner-fold induction at 1.9 and 3.6 at 10 μM and 50 μM, respectively, compared to control. Western blot analysis indicated that trans-chalcone reduced Sp1 and induced p53 expression, compared to control cells. Further experiments suggest that trans-Chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. These results were confirmed by a luciferase assay of the MDM2 promoter and a proteasomal degradation assay using several inhibitors. Conclusions: Trans-Chalcone inhibits cell growth and induces apoptosis in osteosarcoma cells and targets p53 tumor suppressor and Sp1 oncogenic proteins in osteosarcoma. Thus, trans-chalcone could be the focus of future clinical trials to develop an anti-cancer drug for osteosarcoma patients. Support: The University of Tennessee Center of Excellence in Livestock Diseases and Human Health and a grant (No. process: BEX 3159/14-0) from the CAPES Foundation, an agency under the Ministry of Education of Brazil. Citation Format: Gabriel da Silva, Mozart Marins, Ana Lúcia Fachin, Seung J. Baek. Antitumorigenic activity of trans-chalcone in osteosarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4654. doi:10.1158/1538-7445.AM2015-4654
Abstract 4944: Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma
Authors: Ye Chen, Liang Xu, Masaharu Hazawa, Anand M. Thippeswamy, Henry Yang, Markus Müschen, De-Chen Lin, Phillip Koeffler
Journal: Cancer Research (2015)

Abstract Background Glioblastoma multiforme (GBM) is one of the most aggressive cancers in humans. Identification and characterization of the GBM-promoting factors is imperative for the development of novel and effective clinical interventions. We recently discovered that the expression of B-cell lymphoma 6 (BCL6), a gene involved in the development of B cell lymphoma, is up-regulated in GBM. This study aims to explore the functional implications of BCL6 in this disease. Methods We analysed the transcriptional level of BCL6 in primary glioma samples, and screened the protein expression in a panel of human GBM cell lines as well as primary GBM explants. cDNA microarray analysis was conducted to identify the potential downstream targets of BCL6 in GBM. Small-interfering RNA (siRNA), small hairpin RNA (shRNA), and CRISPR-mediated gene silencing strategies were applied to examine the biological function of BCL6. Finally, inhibitors targeting BCL6 were tested in glioma cells. Results In silico analysis revealed elevated BCL6 mRNA levels in both primary GBM samples and cell lines when compared with neural stem cell or non-tumor brain tissues. Western blot confirmed the prevalent expression of BCL6 in GBM cell lines as well as primary GBM explants. Functional studies showed that BCL6 played an important role in promoting cell growth. Depletion of endogenous BCL6 through siRNA, shRNA or CRISPR in GBM cells led to marked inhibition of cell proliferation both in vitro and in vivo. Transcriptome analysis showed that BCL6 is an important regulator of TP53 signaling pathway. Knockdown of BCL6 increased the expression of p53, p21CIP and p27KIP. CHIP-qPCR further confirmed that BCL6 interacted directly to the TP53 promoter and suppressed its expression. Moreover, BCL6 negatively regulated MEK-ERK activation in GBM cells. BCL6 depletion reduced the phosphorylation levels of both MEK1/2 and ERK1/2, but had little effect on AKT phosphorylation. Our further investigations uncovered that BCL6 modulated the expression of several key regulators of MEK-ERK pathway, such as SPRY1, SPRY2 and AXL. Finally, BCL6 inhibitor showed marked anti-proliferation activity in GBM cells, suggesting that targeting BCL6 may serve as a new strategy to treat GBM. Conclusion Our data suggest that BCL6 is involved in glioma tumorigenesis through regulating both the TP53 and MEK-ERK pathways, and that BCL6 is a potential therapeutic target for glioma treatment. Citation Format: Ye Chen, Liang Xu, Masaharu Hazawa, Anand M. Thippeswamy, Henry Yang, Markus Müschen, De-Chen Lin, Phillip Koeffler. Identification of B-cell lymphoma 6 as a novel therapeutic target in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4944. doi:10.1158/1538-7445.AM2015-4944
Population Pharmacokinetics of Fludarabine and Treosulfan in Patients with Thalassemia Undergoing Hematopoietic Stem Cell Transplantation
Authors: Ezhil Pavai Mohanan, John C Panetta, Shareen Stella Backia Royan, Ajay Abraham, Eunice Sindhuvi Edison, Kavitha M Lakshmi, Fouzia Nambiathayil Abubacker, Anu Korula, Aby Abraham, Auro Viswabandya, Biju George, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2015)
Hemostatic parameters do not predict restenosis after coronary angioplasty
Authors: R. Uebis, S.G. Thompson, M. Marzilli, R.M. Bertina, M. vom Dahl, C. Fechtrup, M. Casaccia, S. Pyke, F. Haverkate
Journal: Circulation (1995)

Abstracts From the 68th Scientific Sessions, Anaheim Convention Center Anaheim, California November 13-16, 1995
An Immunohistochemical Score Based On CD68 and FOXP3 Expression In the Tumour Microenvironment at Diagnosis Defines Prognostic Groups In Both Early and Advanced Stage Classical Hodgkin Lymphoma
Authors: Paul Greaves, Andrew James Clear, David Andrew Owen, Finlay Macdougall, Andrew Wilson, Andrew Lister, Maria Calaminici, John G. Gribben
Journal: Blood (2010)
Abstract LB-237: Vaccination increases the breadth and diversity of melanoma neoantigen-specific T cells in humans
Authors: Beatriz M. Carreno, Vincent Magrini, Michelle Becker-Hapak, Saghar Kaabinejadian, Jasreet Hundal, Allegra A. Petti, Amy Ly, Wen-Rong Lie, William H. Hildebrand, Elaine R. Mardis, Gerald P. Linette
Journal: Cancer Research (2015)

Abstract Melanoma genomes harbor somatic mutations that are caused by exposure to mutagens such as UV light. Tumor missense mutations (MM), translated into amino acid substitutions (AAS), may provide a form of non-self that elicits tumor specific T cell immunity. Indeed, T cell immunity directed against tumor encoded AAS has been reported in humans with cutaneous melanoma, thus implicating MM as a source of patient specific (private) neoantigens. However, a systematic evaluation of these putative neoantigens as validated targets is lacking and it is unknown whether the immune response directed against tumor encoded AAS can be augmented by vaccination. Here we show that vaccination against melanoma AAS-encoding peptides augments naturally occurring T cell immunity and reveals new HLA class I restricted private neoantigens in patients with advanced melanoma. Neoantigen specific T cells recognized naturally processed and presented antigen but failed to recognize wild type (non-mutated) antigen. The presentation of neoantigens by HLA-A*02:01 in human melanoma was confirmed by mass spectrometry. As determined by TCRβ CDR3 DNA sequencing, vaccination promotes a repertoire of neoantigen-specific T cells that is highly diverse in terms of both TCRβ usage and clonal composition. No evidence of autoimmunity was apparent after vaccination. Our results demonstrate that tumor MM can be targeted as neoantigens and vaccination directed at tumor AAS somatic mutations broadens the antigenic breadth and clonal diversity of anti-tumor immunity. These findings provide a new paradigm for private neoantigen identification in neoplasia and may form the basis of personalized cancer immunotherapies targeting somatic mutations. Citation Format: Beatriz M. Carreno, Vincent Magrini, Michelle Becker-Hapak, Saghar Kaabinejadian, Jasreet Hundal, Allegra A. Petti, Amy Ly, Wen-Rong Lie, William H. Hildebrand, Elaine R. Mardis, Gerald P. Linette. Vaccination increases the breadth and diversity of melanoma neoantigen-specific T cells in humans. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-237. doi:10.1158/1538-7445.AM2015-LB-237
OP06CHARACTERISING TISSUE ANISOTROPY OF THE PERI-TUMOURAL REGION IN GLIOBLASTOMA USING DIFFUSION TENSOR IMAGING
Authors: Jiun-Lin Yan, Natalie Boonzaier, Timothy Larkin, Stephen Price
Journal: Neuro-Oncology (2015)

INTRODUCTION: The invasiveness of glioblastoma can outreach beyond conventional T1 contrast imaging. Using DTI, white matter change, not shown in the conventional MR image, can be detected. This study analyzed tissue characteristics in areas of DTI anisotropic, outside the enhancing T1 contrast component, using MR spectroscopy. METHOD: Retrospectively reviewed 51 GBM patients who received underwent pre-treatment operative standard MR imaging as well as DTI and MRS. Diffusion tensor was further split into isotropic(p) and anisotropic(q) components. The q map was drawn around the visible abnormality. Region of interest was defined peri-tumoural q abnormality without contrast enhancement. This was compared to 1)peri-tumoural regions that appeared normal on q map, 2)T1 contrast enhanced area and 3)contralateral white mater. 1H MRS was used for tissue characterization. RESULTS: Among 51 patients, 28 had abnormal q component greater than T1 contrast area. The q abnormality area outside of T1 contrast enhanced area showed increase total choline compared to q normal area (p= 0.0175) and contralateral control area (p = 0.0028). Total NAA revealed no significant difference. The Choline/NAA ratio was higher in q abnormal area, than in q normal area (p= 0.0499) and control (p = 0.0451). The glutamate was found to be higher over peritumoural area with or without q abnormality. Additionally, compared to those who with q abnormality equal to or smaller than the T1 contrast, both overall survival and progression free survival were significantly higher in these 28 patients (p= 0.0055, p < 0.0001). CONCLUSION: Diffusion tensor MR imaging can provide more information about the peri-tumoural area with distinct tissue characterization.
The CD44‐Mediated Uptake of Hyaluronic Acid‐Based Carriers in Macrophages
Authors: Julio M. Rios de la Rosa, Annalisa Tirella, Arianna Gennari, Ian J. Stratford, Nicola Tirelli
Journal: Advanced Healthcare Materials (2016)

CD44 is a potentially rewarding target in cancer therapy, although its mechanisms of ligand binding and internalization are still poorly understood. In this study, we have established quantitative relationships between CD44 expression in differently polarized macrophages (M0, M1, and M2‐polarized THP‐1 human macrophages) and the uptake of hyaluronic acid (HA)‐based materials, which are potentially usable for CD44 targeting. We have validated a robust method for macrophage polarization, which sequentially uses differentiating and polarizing factors, and allows to show that CD44 expression depends on polarization (M1 &gt; M0 ≥ M2). It is noteworthy that THP‐1 M2 expressed CD44v6, suggesting their suitability as a model of tumor‐associated macrophages. In the uptake of HA, both as a soluble polymer and in the form of (siRNA‐loaded) nanoparticles, CD44 expression correlated positively with binding, but negatively with internalization. Counterintuitively, it appears that a higher presence of CD44 (in M1) allows a more efficient capture of HA materials, but a lower expression (in M2) is conducive to better internalization. Although possibly cell‐specific, this unexpected relationship indicates that the common paradigm “higher CD44 expression = better targetability” is too simplistic; mechanistic details of both receptor presentation and association still need to be elucidated for a predictable targeting behavior.
Abstract 1054: Aberrant TET1 methylation closely associated with CpG island methylator phenotype in colorectal cancer
Authors: Norihisa Ichimura, Keiko Shinjo, Fumiharu Ohka, Keisuke Katsushima, Akira Hatanaka, Masayuki Tojo, Yasuhiro Shimizu, Eiichiro Yamamoto, Hiromu Suzuki, Yutaka Kondo
Journal: Cancer Research (2015)

Abstract Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer (CRC). The relationship between TET inactivation and CIMP in CRCs is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) CRCs. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in CRCs, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of CRCs as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (24/55, 44%) than CIMP-N (3/113, 3%, P&amp;lt;0.0001) CRCs. This trend was also observed in colon polyps (CIMP-P, 18/40, 45%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P CRCs. CRCs with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and P = 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in CRC. Citation Format: Norihisa Ichimura, Keiko Shinjo, Fumiharu Ohka, Keisuke Katsushima, Akira Hatanaka, Masayuki Tojo, Yasuhiro Shimizu, Eiichiro Yamamoto, Hiromu Suzuki, Yutaka Kondo. Aberrant TET1 methylation closely associated with CpG island methylator phenotype in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1054. doi:10.1158/1538-7445.AM2015-1054
Ubiquitin Ligase Component Fbw7 Regulates the Quiescence of Hematopoietic Stem Cells.
Authors: Sahoko Matsuoka, Yuichi Oike, Ichiro Onoyama, Keiyo Takubo, Keisuke Ito, Fumio Arai, Yasuo Ikeda, Keiko Nakayama, Keiichi Nakayama, Toshio Suda
Journal: Blood (2006)
A Myeloid-Specific Gene-Dosage Regulator for CEBPA Expression in Myeloid Cells Is Commonly Targeted By Onco-Proteins in AML
Authors: Roberto Avellino, Stefan M Groschel, Harmen Van de Werken, Mathijs A. Sanders, Remco M. Hoogenboezem, Claudia Erpelinck, Marije Havermans, Eric Bindels, Ruud Delwel
Journal: Blood (2014)
Abstract 3102: AZD1152HQPA Accurin™ nanoparticles inhibit growth of diffuse large B-cell lymphomas and small cell lung cancer
Authors: Susan Ashton, Paula Taylor, Nicola Curtis, James Pilling, Thierry Dorval, Jeff Hrkach, Philip J. Jewsbury, Simon T. Barry
Journal: Cancer Research (2015)

Abstract Inhibitors of the Aurora Kinases have been developed to treat both liquid and solid tumours. The prodrug AZD1152 is an inhibitor of Aurora kinase B that is clinically active in acute myeloid leukaemia. Despite this clinical proof-of-concept, the broader clinical utility of AZD1152 is limited by the requirement for continuous IV infusion, and the mechanism-related dose-limiting toxicities seen with this class of inhibitors, in particular bone marrow toxicity. To address these challenges and maximise the clinical utility, an Accurin nanoparticle containing AZD1152HQPA, the active metabolite of AZD1152, has been developed. In preclinical models, the AZD1152HQPA Accurin shows increased efficacy without the bone marrow toxicity seen with the prodrug formulation. In preclinical studies, models of Diffuse Large B Cell Lymphoma (DLBCL) and Small Cell Lung Cancer (SCLC) show sensitivity to monotherapy Aurora B kinase inhibitors. Consistent with this, AZD1152 inhibits the growth of subsets of DLBCL and SCLC cells lines in vitro, while in vivo, AZD1152HQPA Accurin consistently reduces the growth of DLBCL and SCLC models. When given at 25mg/kg on days 1 and 3, AZD1152HQPA Accurin gave either equivalent or superior activity to AZD1152 delivered at 25mg/kg on days 1, 2, 3 and 4. When the dose-schedule was explored, increasing the dose intensity increases the anti-tumour effect, while modifying the timing and dose intensity of each dose cycle also influenced the anti-tumour activity. In a DLBCL model, low dose AZD1152HQPA Accurin (25mg/kg delivered as a fractionated dose on day 1 and 3) gave tumour stasis or partial regression, while a higher dose (50mg/kg delivered weekly) gave increased tumour response, which was durable on repeated dosing. The timing of AZD1152HQPA Accurin doses had significant impact on the shape of the tumour response, indicating that optimal scheduling is important to maximize the benefits of sustained release and enhanced tumour accumulation of Accurin nanoparticles. Collectively the preclinical data indicate that the AZD1152HQPA Accurin has the potential for activity in SCLC and DLBCL; is able to be used flexibly; and has an improved therapeutic index. Citation Format: Susan Ashton, Paula Taylor, Nicola Curtis, James Pilling, Thierry Dorval, Jeff Hrkach, Philip J. Jewsbury, Simon T. Barry. AZD1152HQPA Accurin™ nanoparticles inhibit growth of diffuse large B-cell lymphomas and small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3102. doi:10.1158/1538-7445.AM2015-3102
Circular RNAs in cancer: an emerging key player
Authors: Yeping Dong, Dan He, Zhenzi Peng, Wei Peng, Wenwen Shi, Jun Wang, Bin Li, Chunfang Zhang, Chaojun Duan
Journal: Journal of Hematology & Oncology (2017)

Circular RNAs (circRNAs) are a class of endogendous RNAs that form a covalently closed continuous loop and exist extensively in mammalian cells. Majority of circRNAs are conserved across species and often show tissue/developmental stage-specific expression. CircRNAs were first thought to be the result of splicing error; however, subsequent research shows that circRNAs can function as microRNA (miRNA) sponges and regulate splicing and transcription. Emerging evidence shows that circRNAs possess closely associated with human diseases, especially cancers, and may serve as better biomarkers. After miRNA and long noncoding RNA (lncRNA), circRNAs are becoming a new hotspot in the field of RNA of cancer. Here, we review biogenesis and metabolism of circRNAs, their functions, and potential roles in cancer.
Abstract POSTER-BIOL-1306: DNA methylation changes during epithelial-to-mesenchymal transition in ovarian cancer cells
Authors: Horacio Cardenas, Edyta Vieth, Jiyoon Lee, Yunlong Liu, Kenneth P. Nephew, Daniela Matei
Journal: Clinical Cancer Research (2015)

Abstract Epithelial-to-mesenchymal transition (EMT) is an important step in the process of metastasis and has been linked to cancer cell stemness. We hypothesize that aside from defined genetic changes associated with EMT, epigenetic mechanisms are involved and have not been fully elucidated. We determined DNA methylation in SKOV3 ovarian cancer (OC) cells during EMT induced by TGF-ß using the Infinium HumanMethylation450 array. Methylation levels of CpG sites were expressed as ß-values ranging from 0 (totally unmethylated) to 1 (totally methylated). Methylation of 468 and 390 sites changed (P&amp;lt;.01, ANOVA and FDR&amp;lt;0.05) after 48h and 120h of TGF-ß stimulation. The majority of changes (81%) reflected TGF-ß-induced increase in methylation. Methylation of 160 sites changed similarly at 48 and 120 h indicating that 34% of initial changes were sustained. The number of methylation changes decreased significantly after TGF-ß removal from the cell cultures, demonstrating that removal of TGF-ß stimulation reversed the methylation changes at most sites and restituted the baseline methylome. These results were consistent with those of the principal component and hierarchical clustering analyses. TGF-ß increased overall (average of all CpG sites) DNA methylation, total DNA methyltransferase activity, and amounts of DNMT1 protein and mRNA. The average methylation of CpG islands located in or near promoters increased in 193 genes at 24h and 494 at 120h, while no changes were observed after TGF-ß removal. Pathway analysis identified methylation changes in genes belonging to functional networks relevant to EMT and cancer progression, including: cellular movement, cell cycle, organ morphology, cellular development, and cell death and survival. Treatment of OC cells with the DNA methylation inhibitor SGI-110 prevented TGF-ß-induced EMT in association with an inhibition of the TGF-ß-induced downregulation of E-Cadherin. Results demonstrate that DNA methylation is a dynamic process involved in regulation of genes implicated in EMT and metastasis. Citation Format: Horacio Cardenas, Edyta Vieth, Jiyoon Lee, Yunlong Liu, Kenneth P. Nephew, Daniela Matei. DNA methylation changes during epithelial-to-mesenchymal transition in ovarian cancer cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1306.