tbuckley/cabot-search huggingface dataset:
Abstract 3038: G quadruplex stabilization induces mitophagy in S. cerevisiae
Authors: Jennifer Stundon
Journal: Cancer Research (2015)

Abstract G-quadruplex (G4) DNA structures are stable planar structures held together by multiple G-G base pairs. G4 structures are thought to affect transcription and other chromosomal processes but their presence in vivo is also expected to slow replication fork progression. Previous work from our lab demonstrates that the S. cerevisiae Pif1 5′ to 3′ DNA helicase is a particularly potent unwinder of G4 structures in vitro1. In addition, cells lacking the Pif1 helicase exhibit replication fork slowing and DNA breakage at G4 motifs, chromosomal sequences that form intra-molecular G4 structures in vitro1,2. In addition, treating yeast in vivo with the G4 stabilizing drug PhenDC3 increases G4-mediated genome instability3. We treated a collection of 4,783 S. cerevisiae strains that each contained a single gene deletion with PhenDC3 to search for genes that are sensitive or resistant to PhenDC3. We will discuss results showing that several yeast genes that affect maintenance of mitochondrial DNA and autophagy induction are hypersensitive to PhenDC3. Using fluorescent microscopy and immunoblotting, we further demonstrate that treatment of wild type S. cerevisiae cells with PhenDC3 induces autophagy, and more specifically, mitophagy. Moreover, cells lacking Pif1 are themselves activated for autophagy. Reference: 1 Paeschke, K. et al. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature 497, 458-+, doi:10.1038/nature12149 (2013). 2 Paeschke, K., Capra, J. A. &amp; Zakian, V. A. DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase. Cell 145, 678-691, doi:10.1016/j.cell.2011.04.015 (2011). 3 Piazza, A. et al. Genetic instability triggered by G-quadruplex interacting Phen-DC compounds in Saccharomyces cerevisiae. Nucleic Acids Res 38, 4337-4348, doi:10.1093/nar/gkq136 (2010). Citation Format: Jennifer Stundon. G quadruplex stabilization induces mitophagy in S. cerevisiae. [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 3038. doi:10.1158/1538-7445.AM2015-3038
Abstract 118: CTCF, a master epigenetic regulator, is a haploinsufficient tumor suppressor gene in multiple cell lineages
Authors: James M. Moore, Russell Moser, Leslie Smith, Kay Gurley, Denny Liggett, Galina Filippova, Christopher J. Kemp
Journal: Cancer Research (2012)

Abstract While changes in the epigenetic landscape are ubiquitous in cancer, the origin and causal effects of most of these changes on neoplastic progression are largely unknown. The DNA binding protein Ctcf, regulates a diverse array of epigenetic processes, including DNA methylation spreading, but is role in cancer is unclear. Here we show that Ctcf heterozygous knockout mice are remarkably susceptible to spontaneous, ionizing radiation, and chemically-induced neoplasia in a broad range of tissues. Analysis of lung tumors from Ctcf+/− mice establishes Ctcf as a haploinsufficient tumor suppressor gene whose loss cooperates with mutant Kras to accelerate tumor growth and malignant progression. Increased DNA methylation at Ctcf binding sites in normal tissues from Ctcf+/− mice indicates that reduction of Ctcf leads to epigenetic deregulation and this occurs prior to overt neoplastic transformation. This indicates epigenetic instability can predispose a broad range of tissues to neoplastic transformation. A mouse model of Ctcf regulated epigenetic stability provides a useful setting to dissect the mechanistic link between environmental exposure, and risk of cancer or other diseases with an epigenetic component. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 118. doi:1538-7445.AM2012-118
EXERCISE VENTILATORY POWER IN HEART FAILURE PATIENTS: FUNCTIONAL PHENOTYPES DEFINITION BY COMBINING CARDIOPULMONARY EXERCISE TESTING WITH STRESS ECHOCARDIOGRAPHY
Authors: Valentina Labate, Francesco Bandera, Greta Generati, Marta Pellegrino, Valeria Donghi, Eleonora Alfonzetti, Marco Guazzi
Journal: Journal of the American College of Cardiology (2015)
Abstract 5075: Targeting TSP1 and inhibiting angiogenesis in UV-induced skin cancer by apigenin.
Authors: Xin Tong, Bryan B. Bridgeman, Salida Mirzoeva, Susan E. Crawford, Olga V. Volpert, Jill C. Pelling
Journal: Cancer Research (2013)

Abstract Non-melanoma skin cancer (NMSC) is a major health problem in the United States, with over two million new cases diagnosed yearly. Among many genetic and environmental factors contributed to NMSC, ultraviolet B (UVB) radiation is the major carcinogen. As with all solid tumors, angiogenesis is a necessary prerequisite for the progression and metastasis of NMSC. Thrombospondin-1 (TSP1) is the first endogenous inhibitor of angiogenesis to be identified, and its expression is markedly downregulated in epidermis following UVB irradiation and throughout distinct steps of skin carcinogenesis. Apigenin (4’, 5, 7-trihydroxyflavone), a nonmutagenic plant flavonoid, inhibits UV-induced NMSC in mice. However, the molecular mechanisms of apigenin's chemopreventive function remain elusive. For the first time, we found that apigenin restores normal TSP1 levels in UVB-irradiated skin keratinocytes in vitro and in vivo. The regulation of TSP1 expression in UVB/apigenin-treated keratinocytes occurs post-transcriptionally and is mediated by RNA-binding protein Human antigen R (HuR). Importantly, HuR has recently been demonstrated to play an important role in translation of TSP1 mRNA, and we showed that apigenin promotes cytoplasmic localization of HuR, where polyribosomal translation of TSP1 occurs. In addition, knockdown of HuR by siRNA abrogates the ability of apigenin to maintain normal TSP1 levels in UVB-irradiated keratinocytes. Furthermore, apigenin inhibits microvascular density (MVD) in superficial dermis that occurs in response to UVB irradiation. Taken together, our results demonstrate that apigenin promotes TSP1 expression in UVB-irradiated epidermis via HuR leading to inhibition of angiogenesis. Identifying TSP1 as a key target of apigenin and demonstrating its important role in chemoprevention by apigenin will provide a compelling rationale to use apigenin for maintaining the expression of protective TSP1 in the skin as a novel strategy for NMSC prevention and treatment. Citation Format: Xin Tong, Bryan B. Bridgeman, Salida Mirzoeva, Susan E. Crawford, Olga V. Volpert, Jill C. Pelling. Targeting TSP1 and inhibiting angiogenesis in UV-induced skin cancer by apigenin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5075. doi:10.1158/1538-7445.AM2013-5075
Abstract 4102: Differing molecular mechanisms involved in the sensitization of human renal cancer cells to TRAIL-induced apoptosis
Authors: Alan D. Brooks, Candace R. Thompson, Richard J. Pompei, Nancy Booth, Kirk R. Gustafson, Curtis J. Henrich, James B. McMahon, Thomas J. Sayers
Journal: Cancer Research (2011)

Abstract We have previously shown that the proteasome inhibitor bortezomib (Velcade/PS-341) specifically sensitized certain human renal carcinoma (RCC) lines to apoptosis induced by the TNF family-member TRAIL. A high-throughput screen conducted by the Molecular Targets Laboratory identified several promising new TRAIL sensitizers. One of these novel TRAIL sensitizers was the natural product withanolide E. Withanolide E, in contrast to bortezomib, had no activity as a proteasome inhibitor. Also withanolide E could sensitize some human RCC to TRAIL that were resistant to the effects of bortezomib. Furthermore sensitizing concentrations of bortezomib were also cytostatic to the RCC, whereas those of withanolide E were not. Bortezomib treatment of RCC resulted in the appearance of various proteins associated with a stress response, yet these proteins were not elevated by withanolide E treatment. By contrast the antioxidant n-acetyl cysteine completely blocked the TRAIL-sensitizing effects of withanolide E but not those of bortezomib. This suggests that changes in cellular redox are important for the sensitizing effects of withanolide E but not those of bortezomib. In order to study the molecular basis for increased TRAIL-mediated apoptosis, we investigated proximal apoptosis signaling events at the death-inducing signaling complex (DISC). Both bortezomib and withanolide E treatments resulted in an enhanced activation of the apoptosis signaling enzyme caspase-8 following exposure of the RCC to TRAIL. However, immunoprecipitation of the DISC revealed that bortezomib treatment resulted in a 4-5 fold increase in the amount of DISC formed. By contrast withanolide E treatment did not significantly alter the amount of the DISC, but reduced levels of the antiapoptotic DISC component c-FLIP. Therefore, both compounds amplified the apoptotic signal from the DISC via distinct molecular mechanisms of action. Funded in part by HHSN261200800001E Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4102. doi:10.1158/1538-7445.AM2011-4102
Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms
Authors: Anouk Emadali, Neda Hoghoughi, Samuel Duley, Azadeh Hajmirza, Els Verhoeyen, Francois-Loic Cosset, Philippe Bertrand, Christophe Roumier, Anne Roggy, Céline Suchaud-Martin, Martine Chauvet, Sarah Bertrand, Sieme Hamaidia, Sophie Rousseaux, Véronique Josserand, Julie Charles, Isabelle Templier, Takahiro Maeda, Juliana Bruder-Costa, Laurence Chaperot, Joel Plumas, Marie-Christine Jacob, Thierry Bonnefoix, Sophie Park, Remy Gressin, Cornelis P. Tensen, Cristina Mecucci, Elizabeth Macintyre, Dominique Leroux, Elisabeth Brambilla, Florence Nguyen-Khac, Isabelle Luquet, Dominique Penther, Christian Bastard, Fabrice Jardin, Christine Lefebvre, Francine Garnache, Mary B. Callanan
Journal: Blood (2016)
Abstract SY14-03: Inferring causality for oncology drug discovery and development
Authors: Iya Khalil
Journal: Cancer Research (2011)

Abstract Decisions in drug development are made based upon determinations of cause and effect from experimental observations that span all development phases. Despite major advances in our powers of observation due to the advent of multi-omic technologies, the ability to determine disease mechanisms, biomarkers, and effective combination therapies from large-scale and diverse data sets in the context of ill-defined and complex biological systems continues to be a major bottleneck in the drug development process. Current methods of statistical analysis do not allow for causal inferences, leaving this impossible task to the human mind. This major bottleneck can only be overcome by utilizing automated computational learning methods that identify from compound data the circuits and connections between drug-affected molecular constituents and physiological observables. We will present several case studies in oncology drug development where we employ massively parallel machines to reverse engineer populations of models that predict the ‘gearing’ between drug, genetic, and genomic molecular components with respect to oncology phenotypic outcomes. Since a single topology or model cannot capture the reality of a biological system under investigation, Monte Carlo simulation strategies over the population of models reveal how the drug, genetic, gene expression and clinical variables work together to impact phenotypic outcomes. We will show how the marriage of multi-omic technologies within the network inference approach is helping to fill in the missing insights needed to improve drug development success rates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY14-03. doi:10.1158/1538-7445.AM2011-SY14-03
BICUSPID VALVE AND ANEURYSM PHENOTYPES: CLINICAL AND PATHOLOGIC ASSOCIATIONS
Authors: Charles M. Wojnarski, Eric Roselli, Jahanzaib Idrees, Yuanjia Zhu, Patrick Collier, Brian Griffin, Theresa Carnes, Ashley Lowry, John Ehrlinger, Lars Svensson, Eugene Blackstone, Bruce Lytle
Journal: Journal of the American College of Cardiology (2015)
The Medicare End-Stage Renal Disease Program
Authors: Norman G. Levinsky, Richard A. Rettig
Journal: New England Journal of Medicine (1991)

DURING the 1960s it became increasingly clear that patients with permanent kidney failure, previously certain to die, could be kept alive and in at least reasonably good health by long-term dialysis. At the same time, kidney transplantation was becoming increasingly successful as a result of improved programs of immunosuppression. Because of the high cost of these forms of therapy, especially long-term dialysis, and limited and fragmentary sources for payment of these costs, many patients were unable to obtain medically appropriate treatment for lack of funds. In 1972, Congress amended the Social Security Act to provide an entitlement to Medicare for . . .
Abstract 3709: Synthesis of chlorin-based fatty acid conjugate as photosensitizer for photodynamic therapy
Authors: Battogtokh Gantumur, Sook Hee Kim, Sumi Bae, Su Jin Bae, Uk Kang, Ahn Woong Shick
Journal: Cancer Research (2010)

Abstract Photodynamic therapy (PDT) is promising an approach to cancer treatment that requires the combination of photosensitizer (PS), tissue oxygen, and light. Many PSs have been developed for the PDT; however, very few have made in clinical trials because improved drugs that are more selective and that can be used conveniently and without sustained skin photosensitivity are needed. Tumor targeting drug delivery is another attractive strategy in cancer treatment. In this study, our purpose is to improve their selectivity on tumor cell as conjugating of chlorin-based PSs with unsaturated fatty acids (UFAs) that are taken up rapidly by tumors from the arterial blood, presumably for use as biochemical precursors and energy sources. We have selected methyl pyropheophorbide-d-OH (MPPd) and pyropheophorbide-a-173-N-hexanol (PPa-N-He) that possess reactive hydroxyl groups for the molecule as developing photosensitizers, which were conjugated with docosahaxaenoic acid (DHA) and oleic acid (OA) by esterification reaction DCC-mediated, respectively, and gave in enough yield. Our selected PSs were obtained according to Tamiaki et al.1 and Smith et al.2 reported. Novel MPPd-DHA, MPPd-OA, PPa-N-He-DHA, and PPa-N-He-OA were prepared and structure of them was confirmed by spectroscopy's methods (1D and 2D NMR, UV-vis, and MS). The spectrum data of the compounds was clear and easy to characterize. Our synthesized chlorin-based fatty acid conjugates that could be present a synergistic effect for PDT through a more accumulation of the conjugates on tumor cells due to both of those produce a reactive oxygen substrate (ROS). The conjugates have a high lipophilicity because the UFAs were linked to the PSs and the lipophilicity of PS has proven to be an important factor because it influences the biodistribution and clearance and thus the bioactivity of drugs. References 1. Tamiaki, H.; Miyata, S.; Kureishi, Y.; Tanikaga, R. Tetraheddron. 1996, 52, 12421-12432. 2. Smith, K. M.; Goff, D. A.; Simpson, D. J. J. Am. Chem. Soc. 1985, 107, 4946-4954. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3709.
Intrathecal Dacarbazine Treatment of Leptomeningeal Malignant Melanoma
Authors: M A Champagne, H K Silver
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Intrathecal Dacarbazine Treatment of Leptomeningeal Malignant Melanoma Get access Martin A. Champagne, Martin A. Champagne Search for other works by this author on: Oxford Academic PubMed Google Scholar Hulbert K. B. Silver Hulbert K. B. Silver Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 15, 5 August 1992, Pages 1203–1204, https://doi.org/10.1093/jnci/84.15.1203 Published: 05 August 1992 Article history Received: 20 April 1992 Accepted: 27 April 1992 Revision received: 15 May 1992 Published: 05 August 1992
Abstract 4801: p90/CIP2A may play a role in regulating the phosphorylation of CREB1 in cancer
Authors: Bo Peng, Ningjing Lei, Xuanxian Peng, Wei Qian, Eng M. Tan, Jianying Zhang
Journal: Cancer Research (2012)

Abstract Cancerous inhibitor of PP2A (CIP2A) is a tumor-associated autoantigen migrating in SDS-PAGE as a protein of 90kD (also called p90). This protein was shown to be expressed in the mouse embryonic stage but inactivated in adult tissues. It has been shown to inhibit PP2A function thus stabilizing the oncogene c-myc in human malignancies. In the present study, we used two-dimensional electrophoresis-based approach and identified 47 differentially expressed proteins upon the loss of p90/CIP2A in H1299 lung cancer cell line. Among these 47 proteins, 30 proteins have been well documented to be associated with cancer, of which 12 proteins are up-regulated and 18 proteins are down-regulated after knock-down of p90/CIP2A via shRNA. To investigate whether these proteins are associated with any known cancer-related pathway, differentially expressed proteins were analyzed using Pathway Studio bioinformatics software. The resulting data indicated that four possible transcription factors (c-myc, ESR-1, ETS-1 and CREB) may involve in the regulation of the differentially expressed proteins. Further studies showed that down-regulation of p90/CIP2A may affect CREB phosphorylation: treatment with serum induced less phosphorylation of CREB in cells transduced with p90/CIP2A shRNA than the cells tranduced with control shRNA. However, other treatments like KCl and forskolin did not show significant difference between these two groups. We also found that the phosphorylation of the CREB upstream kinase, AKT, was also down-regulated while other kinases p38 and p90RSK was unaffected. These preliminary data imply that p90/CIP2A may target AKT-CREB pathway to promote cell proliferation in a c-myc independent manner. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4801. doi:1538-7445.AM2012-4801
Abstract 1283: Chromosome 19 amplification and the consequent NOTCH and VEGF pathways over-activation are associated with malignant glioma poor outcome
Authors: Mahfoud Assem, Zita Sibenaller, Supreet Agarwal, Maha Al-Keilani, Mohammad Alqudah, Joyce Marner, Timothy C. Ryken
Journal: Cancer Research (2010)

Abstract Malignant gliomas are the most frequent type of primitive brain tumors. Their outcome did not improve despite new therapeutics, resulting mainly from their genetic heterogeneity and complexity. By using genome-wide explorations we have recently identified, for the first time, that chr.19 amplification correlates with a grim therapeutic outcome. The aim of our current study is to investigate the significance of the chromosome 19 genetic signature. To narrow the search for specific genes or pathways that may be responsible for this adverse outcome, we selected genes located on chromosome 19 and focused on those that were statistically significantly deregulated between tumors and non tumor tissues. We identified 41 genes which mapped to chromosome 19. The most significant genes are NOTCH3 and HIF3α. These genes belong to NOTCH and VEGF pathways and play important roles in angiogenesis. Using quantitative real time PCR, RT-PCR and immunobloting, we further analyzed the level of gene expression of critical elements of these pathways and confirmed that NOTCH3 was amplified in primary glioma cell lines that harbor gains of chr.19. This increase has been shown at both the mRNA and protein levels. Moreover, NOTCH ligand, and other constituents of the pathways (DLL3, SHC3, NOTCH4) were also activated in these particular cell lines. Further, HIF3α was also activated in our conditions whereas HIF1α, the other player of HIF transcriptional pathway, was down regulated. These over-expressions were accompanied by a parallel VEGF activation in these cell lines. This novel genetic signature may lead to critical insights into diagnosis, classification, prognosis, and prediction in improving therapeutic strategies and outcome based on the genetic makeup of the tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1283.