5 results on '"Ria Kidner"'
Search Results
2. Supplementary Tables S1-S2 from EWS-FLI1–regulated Serine Synthesis and Exogenous Serine are Necessary for Ewing Sarcoma Cellular Proliferation and Tumor Growth
- Author
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Lee J. Helman, Ralph J. DeBerardinis, Craig J. Thomas, Matthew B. Boxer, Jason M. Rohde, Christine M. Heske, Damien Y. Duveau, Tracy I. Rosales, Ria Kidner, Arnulfo Mendoza, and Sameer H. Issaq
- Abstract
Supplementary Table S1. Evaluation of drug combinations in TC32 and TC71 Ewing sarcoma cells; Supplementary Table S2. Evaluation of drug combinations in EW8 Ewing sarcoma cells.
- Published
- 2023
3. EWS-FLI1-regulated Serine Synthesis and Exogenous Serine are Necessary for Ewing Sarcoma Cellular Proliferation and Tumor Growth
- Author
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Lee J. Helman, Arnulfo Mendoza, Damien Y. Duveau, Tracy I. Rosales, Craig J. Thomas, Jason M. Rohde, Sameer H. Issaq, Ralph J. DeBerardinis, Ria Kidner, Christine M. Heske, and Matthew B. Boxer
- Subjects
0301 basic medicine ,Cancer Research ,Oncogene Proteins, Fusion ,Nicotinamide phosphoribosyltransferase ,Apoptosis ,Bone Neoplasms ,Mice, SCID ,Sarcoma, Ewing ,Biology ,medicine.disease_cause ,Article ,Serine ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Phosphoglycerate dehydrogenase ,Transcription factor ,Phosphoglycerate Dehydrogenase ,Cell Proliferation ,Gene knockdown ,Cell growth ,Proto-Oncogene Protein c-fli-1 ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Sarcoma ,RNA-Binding Protein EWS ,Carcinogenesis - Abstract
Despite a growing body of knowledge about the genomic landscape of Ewing sarcoma, translation of basic discoveries into targeted therapies and significant clinical gains has remained elusive. Recent insights have revealed that the oncogenic transcription factor EWS-FLI1 can impact Ewing sarcoma cellular metabolism, regulating expression of 3-phosphoglycerate dehydrogenase (PHGDH), the first enzyme in de novo serine synthesis. Here, we have examined the importance of serine metabolism in Ewing sarcoma tumorigenesis and evaluated the therapeutic potential of targeting serine metabolism in preclinical models of Ewing sarcoma. We show that PHGDH knockdown resulted in decreased Ewing sarcoma cell proliferation, especially under serine limitation, and significantly inhibited xenograft tumorigenesis in preclinical orthotopic models of Ewing sarcoma. In addition, the PHGDH inhibitor NCT-503 caused a dose-dependent decrease in cellular proliferation. Moreover, we report a novel drug combination in which nicotinamide phosphoribosyltransferase (NAMPT) inhibition, which blocks production of the PHGDH substrate NAD+, synergized with NCT-503 to abolish Ewing sarcoma cell proliferation and tumor growth. Furthermore, we show that serine deprivation inhibited Ewing sarcoma cell proliferation and tumorigenesis, indicating that Ewing sarcoma cells depend on exogenous serine in addition to de novo serine synthesis. Our findings suggest that serine metabolism is critical for Ewing sarcoma tumorigenesis, and that targeting metabolic dependencies should be further investigated as a potential therapeutic strategy for Ewing sarcoma. In addition, the combination strategy presented herein may have broader clinical applications in other PHGDH-overexpressing cancers as well.
- Published
- 2019
4. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells
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S. Henry, Robert Kiss, Antonio Evidente, Ramesh Dasari, Snezna Rogelj, Ria Kidner, Florence Lefranc, Véronique Mathieu, Liliya V. Frolova, Mary R. Reisenauer, Xiaojie Yu, Andrew Brenner, Alexander Pertsemlidis, Alexander V. Aksenov, Xiuye Ma, Igor V. Magedov, Alexander Kornienko, Jerry Pelletier, David Cavazos, Regina Cencic, Henry, Sean, Kidner, Ria, Reisenauer, Mary R, Magedov, Igor V, Kiss, Robert, Mathieu, Véronique, Lefranc, Florence, Dasari, Ramesh, Evidente, Antonio, Yu, Xiaojie, Ma, Xiuye, Pertsemlidis, Alexander, Cencic, Regina, Pelletier, Jerry, Cavazos, David A, Brenner, Andrew J, Aksenov, Alexander V, Rogelj, Snezna, Kornienko, Alexander, and Frolova, Liliya V.
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0301 basic medicine ,Haemanthamine ,Amaryllidaceae Alkaloid ,medicine.medical_treatment ,Antineoplastic Agents ,Drug resistance ,Pharmacology ,Pharmacologie ,Multidrug resistance ,Lycorine ,Article ,Plant Extract ,Antineoplastic Agent ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,medicine ,Tumor Cells, Cultured ,Humans ,Amaryllidaceae Alkaloids ,Chemotherapy ,Translation inhibition ,Bicyclic molecule ,Chemistry ,Plant Extracts ,Melanoma ,Organic Chemistry ,Amaryllidaceae ,General Medicine ,medicine.disease ,3. Good health ,Multiple drug resistance ,Chimie organique ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer cell ,Apoptosis resistance ,Glioblastoma ,Human - Abstract
Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2016
5. Abstract 434: Characterizing the role of serine metabolism in pediatric sarcomas
- Author
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Sameer H. Issaq, Jason M. Rohde, Matthew B. Boxer, Ria Kidner, and Lee J. Helman
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Cancer Research ,Gene knockdown ,Cancer ,Biology ,medicine.disease ,Serine ,Oncology ,Biochemistry ,Cell culture ,Cancer cell ,medicine ,Cancer research ,Sarcoma ,Phosphoglycerate dehydrogenase ,Rhabdomyosarcoma - Abstract
Sarcomas represent a diverse group of malignancies with unique molecular and pathological characteristics. In order to improve sarcoma treatment, a better understanding of the alterations associated with specific sarcoma subtypes is critically important. Renewed interest in the altered metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a novel therapeutic strategy. Metabolism of the amino acid serine is frequently altered in cancer, supporting a number of critical biological processes, including protein, lipid, and nucleotide synthesis, and redox balance. The first, rate-limiting step in the serine synthesis pathway is catalyzed by the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which is overexpressed in several cancers. Previous work has shown that PHGDH loss or inhibition is selectively toxic to cancer cells with high PHGDH expression or increased flux through the serine synthesis pathway. In this study, we have characterized the dependency of pediatric sarcomas on serine metabolism by examining expression of PHGDH in Ewing sarcoma and rhabdomyosarcoma cell lines, and evaluating the effects of PHGDH inhibition and serine deprivation on cellular proliferation and bioenergetic properties. We show that PHGDH is highly expressed in pediatric sarcoma cell lines, and that PHGDH knockdown resulted in decreased proliferation, especially under conditions of serine limitation. Moreover, pharmacological inhibition of PHGDH resulted in a dose-dependent decrease in proliferation and mitochondrial bioenergetic function. Furthermore, individual sarcoma cell lines were differentially sensitive to serine deprivation, indicating that some sarcoma cells may depend on extracellular serine in addition to de novo serine synthesis. Our findings suggest that the dependency of pediatric sarcomas on serine metabolism should be further investigated in order to identify vulnerabilities that could be targeted for potential therapeutic benefit. Citation Format: Sameer Issaq, Ria Kidner, Jason Rohde, Matthew Boxer, Lee Helman. Characterizing the role of serine metabolism in pediatric sarcomas [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 434. doi:10.1158/1538-7445.AM2017-434
- Published
- 2017
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